key: cord- -m hmv c authors: zhang, ya-zhou; cao, xu-yang; li, xi-cheng; chen, jia; zhao, yue-yuan; tian, zhi; zheng, wang title: accuracy of mri diagnosis of early osteonecrosis of the femoral head: a meta-analysis and systematic review date: - - journal: j orthop surg res doi: . /s - - - sha: doc_id: cord_uid: m hmv c objective: to evaluate the overall diagnostic value related to magnetic resonance imaging (mri) in patients with early osteonecrosis of the femoral head. methods: by searching multiple databases and sources, including pubmed, cochrane, and embase database, by the index words updated in december , qualified studies were identified and relevant literature sources were also searched. the qualified studies included prospective cohort studies and cross-sectional studies. heterogeneity of the included studies were reviewed to select proper effect model for pooled weighted sensitivity, specificity, and diagnostic odds ratio (dor). summary receiver operating characteristic (sroc) analyses were performed for meniscal tears. results: forty-three studies related to diagnostic accuracy of mri to detect early osteonecrosis of the femoral head were involved in the meta-analysis. the global sensitivity and specificity of mri in early osteonecrosis of the femoral head were . % ( % ci . – . %) and . % ( % ci . %– . %), respectively. the global positive likelihood ratio and global negative likelihood ratio of mri in early osteonecrosis of the femoral head were . ( % ci . – . ) and . ( % ci . – . ), respectively. the global dor was . ( % ci . – . ), and the area under the sroc was . % ( % ci . %– . %). conclusions: this review provides a systematic review and meta-analysis to evaluate the diagnostic accuracy of mri in early osteonecrosis of the femoral head. moderate to strong evidence indicated that mri appears to be significantly associated with higher diagnostic accuracy for early osteonecrosis of the femoral head. avascular necrosis of femur head (anfh), or osteonecrosis of the femoral head, is a pathologic process, which was first seen in the weight-bearing area of the femur. the stress can lead to bone trabecular structure injury (microfracture) and influence the repair process of the femur, and if not managed timely, it leads to the collapse and deformation of the femur. with many etiological factors, anfh results from interruption of blood supply to the bone and then leads to ischemic necrosis. anfh can be divided in traumatic anfh and non-traumatic anfh with the non-traumatic anfh further dividing into steroid-induced and alcoholic non-traumatic anfh and so on. the timely treatment of early anfh could promote the recovery the disease. however, in the late stage, it results in femur collapse, loss of hip function, and a very poor outcome that affects the quality of life. therefore, the early diagnosis of anfh is of great significance [ ] [ ] [ ] . several methods for early diagnosis of anfh have been proposed, including mri, spect, ct, x-ray, dsa, and laser doppler with different characteristics. mri has been characterized as being non-invasive, rapid and high sensitive, and commonly used by many clinicians [ ] [ ] [ ] . furthermore, mri has been used in many studies in the diagnosis of early anfh. therefore, in this paper, a systematic review and meta-analysis of all qualified studies were performed to explore the diagnosis accuracy of mri in early anfh. the following electronic databases were searched from their inception to december : the cochrane, pubmed, embase database, for all the qualified trails that analyze the diagnostic accuracy of mri of early osteonecrosis of the femoral head. other related articles and reference materials were also identified for additional available studies. the literatures were searched independently by two investigators, and a third investigator was involved to reach an agreement. the studies that met the following criteria were included in our review: ( ) prospective cohort study or cross-sectional study; ( ) the research objects are patients suspected with early osteonecrosis of the femoral head without other serious diseases; ( ) the studies provided the data of true positive (tp), false positive (fp), false negative (fn), and true negative (tn); and ( ) the publications were only available in english and chinese. the studies that met the following criteria were excluded in our review: ( ) repeat publications, or shared content and results; ( ) case report, theoretical research, conference report, systematic review, meta-analysis, expert comment, and economic analysis; ( ) the outcomes were not relevant; and ( ) two or more results of the tp, fp, fn, and tn were zero. two independent investigators extracted the following data based on predefined criteria. differences were settled by discussion with a third reviewer. the analyses data were extracted from all the included studies and consisted of two parts: basic information and main outcomes. the first part was about the basic information: the author name, the sample size, the percentage of male, and the age. the second part was the clinical outcomes. a × contingency table was constructed for each selected study; the results corresponding to the gold standard and mri were selected as positive or negative. the data included true positive (tp), false positive (fp), false negative (fn), and true negative (tn). in studies in which one single cell in the × contingency table had a value of , . were added to all of the cells for calculation. sensitivity, specificity, and likelihood ratio were calculated respectively, and the diagnostic odds ratio (dor) was used as the measure of diagnostic accuracy. a dor value of indicates a test without discriminatory power, and the higher the dor value is, the greater the degree of relevance of the assessed diagnostic test. the studies were performed by two reviewers independently. any arising difference was resolved by discussion. all statistical analyses were performed in the stata . (tx, usa). chi-squared and i tests were used to assess the heterogeneity of clinical trial results and determine the analysis model (fixed-effects model or random-effects model). when the chi-squared test p value was ≤ . and i test value was > %, it was defined as high heterogeneity and assessed by random-effects model. when the chi-squared test p value was > . and i tests value was ≤ %, it was defined as acceptable heterogeneity data and assessed by fixed-effects model. for further assessment of heterogeneity, diagnostic threshold analysis was performed based on the correlation (spearman's) between the logit of sensitivity and the logit of [ -specificity] . when a threshold effect occurs, the sensitivity and specificity of the investigated study exhibits negative correlation (or a positive correlation between sensitivity and [ -specificity]). therefore, a strong positive correlation between sensitivity and [ -specificity] suggests the presence of a threshold effect. when heterogeneity caused by threshold effect was observed, a summary receiver operating characteristic (sroc) curve was plotted. this method was appropriate given that the global sensitivity and specificity values were overestimated. in such cases, analysis of the roc panel points, as well as analysis of the sroc curve, was recommended. deeks' funnel asymmetry plot was used to identify the publication bias. a total of articles were searched by the indexes. after screening the titles and abstracts, articles were excluded, leaving articles for further selection. during full-text screening, articles were excluded due to the following criteria: unqualified outcomes [ ] , theoretical research or review [ ] , and has non clinical outcome [ ] . at last, studies with hips were involved in the final meta-analysis. the selection process was presented in fig. . the main characteristics of the included studies were summarized in table . the basic information included number of hips, age, and gender. all the included studies reported the results of the accuracy of mri of early osteonecrosis of the femoral head. based on the correlation (spearman's r = − . , p = . ) between the logit of sensitivity and the logit of [ -specificity], there was no threshold effect. based on the chi-squared test (q = . , p = . ) and i tests (i = . %), heterogeneity was high, so we chose the random-effects model to analyze the sensitivity. the global sensitivity was . % ( % ci . - . %, fig. ). based on the chi-squared test (q = . , p = . ) and i tests (i = . %), heterogeneity was high. therefore, we chose the random-effects model to analyze the specificity, and the global specificity was . % ( %ci . - . %, fig. ) . based on the chi-squared test (q = . , p = . ) and i tests (i = . %), heterogeneity was high, so we chose random-effects model to analyze the positive likelihood ratio, and the global positive likelihood ratio was . ( % ci . - . , fig. ). therefore, a positive mri result was increased by . -fold in the odds of an accurate diagnosis of patients who actually had early osteonecrosis of the femoral head. based on the chi-squared test (q = . , p = . ) and i tests (i = . %), with low heterogeneity, we chose the fixed-effects model to analyze the negative likelihood ration. the global negative likelihood ratio was . ( % ci . - . , fig. ), indicating the use of mri, which was close to zero. specifically, the odds of a false-positive result were increased by only a factor of . . based on the chi-squared test (q = . , p = . ) and i tests (i = . %), heterogeneity was low, so we chose the fixed-effects model to analyze the dor, with the global dor being . ( % ci . - . , fig. ). and the odds of a positive mri result were . -fold higher among individuals with early osteonecrosis of the femoral head compared to those without the disease. the area under the sroc was . % (auc = . %; % ci . %- . %, fig. ) , indicating high accuracy. several systematic reviews and meta-analysis have been published concerning the diagnostic accuracy of mri of early osteonecrosis of the femoral head. li et al. [ ] found that the sensitivity and specificity of mri were %( % ci - %) and %( % ci - %), respectively. moreover, the dor was . %( % ci . - . %), and the auc under the sroc was . . mri was associated with high diagnostic accuracy in the patients with suspected early anfh. song et al. [ ] , who included articles, reported that mri was more effective than ct in diagnosing anfh. significant statistical difference was identified between them (or, . ; % ci . - . ). su et al. [ ] , who included studies of patients, found the anfh positive rate between ct and mri was statistically significant (or, . ; % ci . - . ), so as the early stage positive rate (or, . ; % ci . - . ). therefore, mri appears to be a promising diagnostic tool for avascular necrosis of the femoral head. however, there were several limitations in this analysis: ( ) differences in the inclusion and exclusion criteria for fig. forest plot showing the diagnostic odds ratio of mri of early osteonecrosis of the femoral head patients, ( ) different patients with previous disease and treatments were unavailable, ( ) all the included studies were from english and chinese articles, which may be the source of bias, ( ) the fluency of technicians between different studies varied, and ( ) pooled data were used for analysis, and individual patients' data were unavailable, which limited a more comprehensive analysis. in summary, in this systematic review and meta-analysis, mri as a diagnostic method is associated with higher accuracy for detecting anfh. more studies and randomized controlled trails with high-quality and large samples are warranted for further evaluation. ethics approval and consent to participate not applicable. nontraumatic necrosis of bone (osteonecrosis) core decompression and conservative treatment for avascular necrosis of the femoral head: a meta-analysis comparison of core decompression and conservative treatment for avascular necrosis of femoral head at early stage: a meta-analysis early magnetic resonance imaging and histologic findings in a model of femoral head necrosis idiopathic bone necrosis of the femoral head. early diagnosis and treatment in brief: ficat classification: avascular necrosis of the femoral head comparative analysis of ct and mri in diagnosis of femoral head necrosis comparative study of ct and mri in diagnosis of cases of femoral head necrosis the value of contrast mri and ct in the early diagnosis of femoral head necrosis the 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analysis of ct and mri in diagnosis of avascular necrosis of femoral head comparison of ct and magnetic resonance imaging in diagnosis and treatment of femoral head necrosis effect of ct and mri in diagnosing femoral head necrosis diagnostic value of two methods of mri and ct in avascular necrosis of femoral head mri combined with ct in the diagnosis of avascular necrosis of the femoral head observation on the mri diagnosis on ischemic bone necrosis and surgical treatment the value of ct and mri examination in the early diagnosis of adult femoral head necrosis low field strength mri diagnosis of avascular necrosis of femoral head diagnostic value of multislice spiral ct and mill on femoral head necrosis evaluation of the value of multislice spiral ct and mri in the diagnosis of femoral head necrosis early diagnosis of avascular necrosis of femoral head in adults early osteonecrosis of the femoral head: detection in high-risk patients with mr imaging evaluation of magnetic resonance imaging in the diagnosis of osteonecrosis of the femoral head. accuracy compared with radiographs, core biopsy, and intraosseous pressure measurements the diagnostic value of magnetic resonance imaging in non-traumatic osteonecrosis of the femoral head the value of magnetic resonance imaging in the early diagnosis of noninvasive avascular necrosis of femoral head bone spect is more sensitive than mri in the detection of early osteonecrosis of the femoral head after renal transplantation comparative study of radionuclide scanning and mri in diagnosis of avascular necrosis of femoral head in early adults avascular necrosis in severe acute respiratory syndrome: mr imaging with radionuclide correlation diagnostic value of ct and mri in the early stage of adult femoral head necrosis meta-analysis of mri diagnosis of early avascular necrosis of femoral head meta-analysis of ct and mri diagnosis of avascular necrosis of femoral head meta-analysis of ct and mri diagnosis of avascular necrosis of femoral head the authors declare that they have no competing interests. key: cord- -e bn ui authors: nan title: ecr book of abstracts - a - postgraduate educational programme date: - - journal: insights imaging doi: . /s - - - sha: doc_id: cord_uid: e bn ui nan for pet-ct, the ct exam is generally performed as standard whole-body exam from the base of the skull to the upper thighs. standard parameters are non-ionic iodinated intravenous contrast material at . g/kg bodyweight with a venous delay of seconds after injection and - mm thick continuous axial reconstructions with medium soft convolution kernels. ct images frequently contain important diagnostic information beyond mere 'anatomic landmarking', so generally a diagnostic, contrast enhanced normal-dose ct should be performed except if a recent diagnostic ct scan is available for fusion. then, a low-dose ct is sufficient for attenuation correction. a difference from routine ct protocols is the expiratory position to match the respiratory position of pet acquisition. also, negative oral contrast material should be applied and the whole body should be included in the field of view to allow effective attenuation correction of pet images. diagnostic reading has to include lung, soft tissue and bone windows. optimally, the assessment should be performed by one reader evaluating ct and pet images simultaneously on multiplanar reformats. learning objectives: . to get acquainted with standard ct examination parameters for oncological imaging including the requirements for an effective attenuation correction. . to see the diagnostic value of ct beyond 'anatomical landmarking'. . to learn effective ways to interpret pet-ct examinations. nuclear medicine perspective t. beyer; zurich/ch combined pet/ct images were first proposed as early . since pet/ ct became available for broader clinical testing. since its commercial introduction in more than ' pet/ct systems were installed worldwide. pet/ct is a logical and technical consequence of early, manual or semi-automatic efforts to align functional and anatomical images for easier and improved diagnosis. pet, or positron emission tomography, is an emission tomographic imaging method based on the application of radioactively labelled biomolecules in order to measure and quantitate signalling or metabolic pathways. ct, computed tomography, on the other hand, uses an external ionising radiation transmission source to generate projection data of the transmitted radiation, thus helping to generate high spatial resolution images of the anatomy of the subject. both sets of information can be combined easily in a pet/ct, whereby both the pet and ct components can be operated in close spatial proximity within a single gantry without cross-talk effects. through the combination of ct and pet overall examination times of oncology pet studies are reduced by %. in addition, pet instrumentation has been advanced to include time-of-flight measurements for improved signal-to-noise ratio, extended axial field-of-view-coverage for higher sensitivity and novel image reconstruction for improved contrast. today, high-quality one-stop shop staging with pet/ct is possible in min, or less. learning objectives: . to illustrate the origin of combined pet/ct imaging. . to motivate the strength of pet: high spatial sensitivity, quantification and functional information. . to appreciate the difference between "contrast" and "tracer" imaging. . to highlight novel developments in pet imaging: time of flight (tof), extended axial field-of-view. computed tomography is the main contribution to diagnostic medial radiation exposure to the public. in the year , ct accounted for only % of all radiationassociated examinations; however, at the same time it accounted for % of the total radiation exposure. since the beginning of this century numerous international surveys had been performed with the aim to define diagnostic reference levels in european countries. radiation exposure by ct has increased particularly by cardiac ct examination, what has caused awareness to utilise all strategies for radiation protection in ct. modern ct scanners are equipped with automated anatomical or organ sparing exposure control. it is the ct investigators responsibility to check the clinical indication, limit the scan range and decide for the appropriate scan protocol with the least radiation exposure. newer technical developments in ct scanner hard and software will enable to further reduce the dose from ct. all these strategies are essentially necessary since the number of ct investigations and the scope of clinical indications are expanding with advancing medical progress. learning objectives: . to understand the meaning of diagnostic reference values. . to become aware of dose intense ct protocols. . to learn about strategies for radiation protection in ct. nuclear medicine perspective s.p. mueller; essen/de different radiopharmaceuticals labelled with positron emitting radioisotopes are used to study a multitude of molecular processes using a positron-emissiontomography (pet) scanner which nowadays is typically integrated with a ct scanner (pet/ct). this lecture will enable the attendee to comprehend that the radiation exposure from pet depends on the biodistribution and kinetics of the radiopharmaceutical, the physical half-life of the positron emitting radioisotope used for labelling, and the injected activity, leading to an understanding that there is no generic "radiation exposure from pet or pet/ct". learning objectives: . to learn that the comparison of doses for different radiopharmaceuticals is based on the concept of the effective dose which expresses the total stochastic risk from the non-uniform radiation exposure to individual radiosensitive organs in terms of a uniform whole body radiation dose. . to understand that the effective dose from certain radiopharmaceuticals may be reduced by simple means, e.g. if it is renally eliminated by frequently voiding the bladder, and that the effective doses for the most prevalent radiopharmaceuticals lie within the typical range of other diagnostic nuclear medicine tests and compare favourably to the radiation exposure from the ct portion of a whole-body pet/ct scan. pet and pet/ct are non-invasive, -dimensional imaging modalities which have become standard of care in patients with malignant lymphomas. these modalities have been extensively studied for staging, restaging, monitoring response to therapy, surveillance after definite treatment, and assessment of transformation. more recently, pet tracers have been suggested as surrogate markers for cancer drug development. learning objectives: . to understand in which clinical scenarios pet and pet/ct imaging are superior to standard imaging modalities or other diagnostic tests. . to learn the diagnostic accuracy and predictive potential of pet and pet/ct for staging/restaging hodgkin's disease and non-hodgkin's lymphoma. of the examination. therefore, for oncologic applications, pet-ct has already gained widespread acceptance for the initial staging of cancer, the management of recurrent cancer, and for monitoring the response to therapy. the development of a large variety of radiotracers is an evolving procedure. the most frequent used radiotracer in clinical practice, f fdg, is based on the identification of the fundamental aspects of tumour glucose metabolism. new radiotracers, with promising potential for pet-ct, are also currently available to visualise specific cellular and molecular tumour pathway and more being developed. learning objectives: . to appreciate the advantage of a combined pet-ct technique. . to consolidate our knowledge of optimal examination protocols and to be aware of the pitfalls that may be encountered using this technique. . to understand the indications for pet-ct in the diagnosis, staging, and therapy monitoring of a large variety of gi tumours. . to become familiar with the different radiotracers to obtain a tailored and personalized diagnosis for the large variety of gi tumours. a- integrated positron emission tomography (pet)/ct provides combined metabolic and anatomic information of malignancies. the addition of ct to pet for urogenital purposes is very useful. ct should be performed with oral and intravenous contrast agent administration as a full diagnostic technique. if performed under these conditions, this technique can help to avoid pet pitfalls including focal retained activity in ureters and urinary bladder, and increased uptake in physiologic and benign pelvic processes such as endometrial uptake in the menstrual phase, leiomyomatosis, endometriosis or infection. we will describe the use of pet/ct in the characterisation, staging and surveillance of urogenital malignancies including kidney, prostate, bladder, uterine cervix, endometrium and ovaries. pet/ct is internationally accepted as the most useful surveillance imaging tool in patients with ovarian cancer, and its use as a problem-solving modality has also rapidly grown in the rest of urogenital malignancies. learning objectives: . to learn the appropriate protocols and settings of a diagnostic ct in pet/ct for urogenital purposes. computed tomography remains the workhorse of clinical cross sectional imaging due to its good availability, enormous speed, high spatial resolution and sufficient tissue contrast to evaluate most diseases based on morphology. compared to pet and spect, room for improvement remains in sensitivity and specificity for certain diseases and, compared to ultrasound and mri, in dynamic imaging. however, already today there are new ct techniques which can provide diagnostically equivalent information as spect or pet but with higher spatial resolution, in shorter acquisition time and without radioactive tracers. one of these techniques is ct perfusion imaging with repeated low-dose acquisitions of the same organ. with this method, a detailed evaluation of brain perfusion is feasible e.g, for stroke assessment, or of tumour perfusion, e.g. to assess early therapy response. another option is dual energy ct which does not require additional dose but can provide additional important diagnostic information similar to pet or spect. examples are the evaluation of lung ventilation und perfusion with xenon gas and iodine contrast. for oncological imaging, the evaluation of tumour perfusion based on spectral identification of iodine is an attractive option to increase specificity without additional dose or radioactivity. similarly, it is feasible to assess myocardial perfusion along with coronary ct angiography. for some diseases, even the molecular substrate can be identified with this technique, e.g. uric acid in gout patients. these new techniques provide significant advantages in oncological imaging and may further add to disease characterisation if combined in pet-ct. learning objectives: . to understand the strengths of current ct technology in oncological imaging based on morphology. . to learn about the diagnostic value of ct beyond anatomical referencing. energy ct as options to improve disease characterisation. tracers beyond fdg in daily routine m. beheshti; linz/at the ability of positron emission tomography (pet) to study different biological processes opens up new windows for both researches and daily clinical use. addition of computed tomography (ct) to pet improves detection efficiency and results in better localization of the lesions. the aim of this review is to consolidate knowledge of oncological applications of pet tracers other than [( )f]fluoro- -deoxy-d -glucose] (fdg) in the daily clinical practice. fdg, as a non -specific tracer, has limited value in the assessment of different cancers such as prostate cancer, neuroendocrine tumours (net), brain tumours, hepatocellular carcinoma (hcc), and some types of breast cancers. hence, due to high sensitivity of pet in performing non-invasive functional studies, further investigations and developments are warranted for defining specific pet radiotracers and theirs clinical applications regarding different tumour entities. oncological non-fdg pet tracers can be generally categorized into groups: those labeled with f- , c- and other non-fdg tracers. fluorine- and c- are labeled with different amino acids, substrates involved in fatty acid synthesis, protein synthesis, amino acid transport substrate and tracers linked to nucleic acid synthesis. these tracers are also labeled with specific ligands for receptor imaging. the other non-fdg a- with the increasing use of abdominal cross-sectional imaging, incidental adrenal masses are being detected more often. the important clinical question is whether these lesions are benign adenomas or malignant primary or secondary masses. benign adrenal masses such as lipid-rich adenomas, phaeochromocytomas, myelolipomas, adrenal cysts and adrenal haemorrhage have pathognomonic cross-sectional imaging appearances. however, there remains a significant overlap between imaging features of some lipid-poor adenomas and malignant lesions. the nature of incidentally detected adrenal masses can be determined with a high degree of accuracy using computed tomography and magnetic resonance imaging alone. positron emission tomography is also increasingly used in clinical practice in characterising incidentally detected lesions in patients with cancer. the performance of the established and new techniques in ct, mri and to a lesser extent pet, that can be used to distinguish benign adenomas and malignant lesions of the adrenal gland will be reviewed. with the increasing use of imaging, incidentally detected renal masses are very common. while masses detected by ct or mr usually can be properly classified, renal masses detected by ultrasound frequently require further workup. the following considerations determine the diagnostic workup: simple cysts are very common but may present atypically. renal cell carcinomas may be cystic but usually display at least a small solid component. renal cell carcinomas have a bad prognosis when metastasized but metastases hardly every develop before the tumour has reached cm in diameter. differentiation between solid tumours by imaging alone is exceedingly difficult, save for the identification of angiomyolipomas in adults. this course will discuss suitable diagnostic algorithms based on the initial presentation of the mass. typical imaging findings of various benign and malignant renal masses will be presented. the role of the bosniak classification will be illustrated. newer developments such as a waitand-see approach or primary biopsy for small solid renal masses will be discussed. learning objectives: . to learn how to detect and characterise a renal mass. . to understand how to apply adequate protocols according to the clinical situation. the wrist and hand are characterised by variability of bones, fibrocartilage, ligaments, muscles and neurovascular structures. coalitions (most commonly lunotriquetral, prevalence of . %), ulnar impaction positive variance of the ulna, carpe bossu and an accessory medial lunate facet associated with osteoarthritis are typical variants of bone. the triangular fibrocartilage complex (tfcc) and the interosseous ligaments often present with small defects. radial tfcc defects are present in % of symptomatic but also in % asymptomatic wrists. in addition, their prevalence increases with age, apparently without increasing symptoms. accessory muscles are common and may clinically mimick a neoplasm. disease may also be mimicked by imaging artifacts. magic angle effects cause increased tendon signal and may thus lead to the incorrect diagnosis of tendinopathy. the lunate appears to be more dorsally tilted on sagittal mr images than on standard radiographs (radiolunate angle ~ ° larger on mr images). this value increases to ~ ° if the wrist is positioned in ulnar deviated as is commonly the case when the wrist is examined in the "superman position", with the arm above the head. magic angle artefacts are commonly encountered in the wrist. the extensor and flexor pollicis longus are especially prone to such artefacts, due to their oblique course approaching the critical ° with regard to the b field. in conclusion, variability is rather the rule than the exception in the hand and wrist. only part of the findings have clinical meaning. technical aspects add another dimension of variability. learning objectives: . to become familiar with the normal anatomy. . to be able to identify normal variants. . to appreciate the range of pitfalls that may simulate pathology. the imaging of the trauma stratifies the severity and the treatment strategy. the leading modalities in low-energy trauma are x-ray and ultrasound. the different approach has to be used in high-energy trauma -the silent life-threatening injury must be actively searched. although the first examination on the site of the accident could estimate whether the severe trauma is present, the imaging must confirm or exclude it. besides fast transport to the trauma centre has the extraordinary impact on survival the diagnostic algorithm. the installation of ct, ultrasound and x-ray directly within the emergency department is extremely important for the trauma management. if the focused assessment sonography for trauma (fast) is replaced by whole body ct, the life-threatening injury is detected at fastest. protocol includes imaging of non-enhanced ct head and cervical spine followed by the contrast-enhanced ct of the entire thorax, abdomen and pelvis, in cases of lower extremities trauma covering whole body. ct could be performed also under resuscitation, because whole imaging takes about three to five minutes. following findings listed recently according to their impact on survival must be confirmed or excluded: intracranial injury, cervical spine trauma, aortic injury, overpressure pneumothorax, severe bleeding in the abdominal cavity, organs injury, peripheral vascular trauma, bone trauma; the trauma team including anaesthesiologist, surgeon and radiologist discusses the findings and plans of the treatment. over the last two decades, spiral-ct has become a highly reliable imaging modality to diagnose haemorrhage in trauma, while the role of catheter angiography has changed from a diagnostic to a therapeutic modality. traumatic injuries of the heart and aorta lead to sudden death occurring at the accident site, whereas uncontrollable haemorrhage from larger arteries and parenchymal organs is the most frequent cause of mortality during the first h following severe trauma. in patients with ruptured aorta or major arteries, stenting and temporary balloon occlusion may contribute to saving lives, while transcatheter embolisation may prevent exsanguination in haemorrhage from visceral organs, arteriovenous fistulas, and secondary onset haemorrhage. however, a haemodynamically stable patient is a prerequisite for all angiographic interventions. definite haemostasis using the above-mentioned techniques can be obtained in - % (major and periphery arteries) and - % (visceral organs), respectively. possible complications following angiographic haemostatic interventions depend very much on the treated vessel bed but are, in general, as low as %. learning objectives: . to understand potential treatment options and when to treat and when not to treat. a s c b d e f g h to current best practice, restriction of opinions to one's own expertise, expression of opinions that take into consideration all of the material facts, and the readiness to change that opinion if additional information becomes available. any unusual, contradictory or inconsistent features of the case should be highlighted. the expert should highlight whether a proposition is a hypothesis (in particular a controversial hypothesis) or an opinion deduced in accordance with peer-reviewed technique, research and experience accepted as a consensus in the scientific community. he/she should indicate whether the opinion is provisional (or qualified), stating the qualification and the reason for it, and identify what further information is required to give an opinion without qualification. when there is a range of opinion on any question to be answered by the expert, (a) the range of opinion should be summarised, (b) highlight whether that range of opinion includes an 'unknown cause' (because of limited facts of the case or limited research/peer-reviewed publications), and (c) give reasons for the opinion expressed. reprints of scientific publications will assist the court, but will also enable the attorneys to undertake a more robust cross examination! learning objectives: . to learn about imaging findings in relation to whether or not abuse has occurred. . to understand in which cases the diagnosis of child abuse should be raised in the radiology report. . to become familiar with the terms that should be used when highly specific imaging indicators are identified in an otherwise normal infant. the radiologist at the eye of the storm : imaging plays a central role in the diagnosis of child abuse. is there any risk of the radiologist having a detrimental impact on either the welfare of the patient or the judicial process by either under-diagnosing or over-diagnosing child abuse? ovarian cancer continues to be a challenge to radiologists and clinicians, as it is one of the most lethal female tumours. this is mainly due to its diagnosis in an advanced stage in the majority of patients. however, new developments can be observed: new insights in tumour biology, advances in imaging and new concepts of ovarian cancer treatment and surveillance. furthermore, a multidisciplinary expert team approach has also substantially changed the management of patients with suspected ovarian cancer. the findings of radiology are becoming pivotal in a more individualised patient care. the role of radiology includes (a) characterisation of sonographically indeterminate adnexal masses, (b) staging as guidance for surgery and treatment planning (including identification of sites of non optimal resectabilty) in suspected ovarian cancer, (c) assessment of recurrent disease, and (d) in selected cases image-guided biopsy. in this session we provide an update on the aetiology and current concepts of treatment of ovarian cancer and on the contribution of radiology in characterisation and staging in patients with the working diagnosis of ovarian cancer. the panel discussion will focus on the role of radiology in multidisciplinary conferences in suspected ovarian cancer. session objectives: . to learn about new concepts in etiology and treatment of ovarian cancer. . to become familiar with optimised imaging protocols to diagnose ovarian cancer. . to learn about the value of ct and pet/ct as a basis for treatment planning in ovarian cancer. . to appreciate the role of the radiologist in multidisciplinary consensus conferences. session objectives: . to learn about current imaging practices in the evaluation of suspected child abuse. . to learn about imaging changes which permit a firm diagnosis of child abuse. . to become familiar how to construct a comprehensive report providing evidence of child abuse. how to image and detect patterns of skeletal injury indicating child abuse p.k. kleinman; boston, ma/us (paul. kleinman@childrens.harvard.edu) in infants, skeletal injury may form the basis for the diagnosis of abuse. the first step is the acquisition of a skeletal survey utilising meticulous technique adhering to a rigorous imaging protocol. a proper interpretation is ensured when the radiologist is familiar with the various patterns of skeletal injury, their specificity for abuse and those entities which may simulate inflicted injury. appreciation of the lesion morphology, the fundamental pathologic alterations and mechanism of injury are essential in assessing the significance of the findings and placing them in the clinical context. dating fractures poses a significant challenge, but in most cases, injuries can be placed in a certain time frame, especially if a follow-up skeletal survey is obtained. although radiography forms the basis of skeletal imaging, ultrasound, ct, scintigraphy and mri may clarify findings and optimise diagnosis and management. the radiology report must be constructed with care and the language should be crafted with the expectation that the radiologist may be called to testify in court, a daunting challenge in an often highly adversarial environment. learning objectives: . to learn about the appropriate imaging protocols and quality for skeletal survey in suspected child abuse. . to learn about patterns of skeletal injury typical of child abuse. . to become familiar with findings that point to alternative diagnoses. imaging strategies to fully determine intracranial injury resulting from child abuse c. adamsbaum, c. rey-salmon; paris/fr (c.adamsbaum@svp.ap-hop-paris.fr) radiologists play a key role in the early diagnosis of abusive head trauma (aht). symptoms are various and may range from coma to asymptomatic children. changing elements of the history provided previous injuries, bruising in non-ambulatory children and delay in seeking care raise a high index of suspicion. the most common finding in aht is of multifocal subdural haematomas over the cerebral hemispheres, the convexity, the posterior interhemispheric fissure and the posterior fossa. the haematomas are often associated with hypoxic-ischaemic injury and retinal haemorrhages. ct is the first diagnostic examination to be used for patients with acute injury. it can reveal intracranial haemorrhage, fracture and soft tissue swelling with a high degree of sensitivity. ct should be repeated after a time interval if the findings are doubtful or if there is a discrepancy with the neurological picture. mri (including t , t , t *, diffusion sequences and cervical spine examination) is required to fully determine intracranial injury as it can exquisitely demonstrate hypoxic-ischaemic injuries by showing areas of cytotoxic oedema. it is impossible to date precisely a haematoma whose pattern is influenced by numerous factors. however, the main point is to determine the presence of 'age-different' lesions. this not only provides a strong argument for the diagnosis but also suggest repetitive violence and thereby, a high risk for further injury unless protective action is undertaken. brain imaging must be performed in all siblings younger than years, living in the same conditions as the index case. learning objectives: . to learn about imaging protocols designed to: a) detect acute treatable conditions b) depict fully and determine the timing of all injuries. . to become familiar with imaging findings that are highly suggestive of child abuse. . to learn about head trauma that may simulate child abuse. what is the information required by any court and how the radiological reports should be phrased s. chapman; birmingham/uk (stevechapman@doctors.org.uk) this presentation will describe the role of a paediatric radiologist as an expert witness (as opposed to a witness to fact). the expert has an overriding duty to the court that takes precedence over any obligation from whom the expert has received instructions or by whom the expert is paid. particular duties include advice that conforms a- : ovarian cancer: update and role of radiology j.a. spencer; leeds/uk (johnaspencer @hotmail.com) ovarian cancer is known as the 'silent killer'. it is usually diagnosed late and most women have disease disseminated to the peritoneum (and/or pleura) at presentation. standard treatment comprises cytoreductive surgery followed by platinumbased chemotherapy. an alternative is neoadjuvant chemotherapy followed by interval debulking surgery (ids) then completion chemotherapy. data from the eortc trial show this to be as effective as the standard of care. there are strong genetic predispositions to ovarian, fallopian tube and primary peritoneal cancers. there is linkage with breast cancer in women with brca gene mutations and with colon cancer with the hnpcc gene. ongoing trials are screening women in the general population and at high risk of the disease. these use the serum tumour marker ca followed by us as screening tools. mr imaging is an effective tool to assess sonographically indeterminate adnexal masses and offers an earlier diagnosis of cancer than interval reassessment with us. ct is the most commonly used modality for assessment of disease extent prior to surgery. image-guided biopsy is necessary prior to starting neoadjuvant chemotherapy. the eortc and mrc (uk) ov trials of women with treated ovarian cancer have shown no outcome advantage for women treated early at 'ca relapse' of disease versus later with clinical or ct evidence of relapse. this questions the role of ca in follow-up and argues against investigation of the 'ca +ve, ct -ve' woman with more expensive and scarce imaging resources such as ct-pet and dcemr. learning objectives: . to become familiar with clinical features of ovarian cancer. . to learn about the etiology of ovarian cancer, including genetic predisposition and the current research into screening. . to become familiar with new concepts of treatment ovarian cancer and surveillance of the treated patient and their impact for the use and choice of imaging modalities. imaging of adnexal masses: is it feasible to diagnose ovarian cancer? i. thomassin-naggara; paris/fr (isabelle.thomassin@tnn.aphp.fr) adnexal masses can be depicted by many imaging modalities (us, ct, mr and pet-fdg). however, the characterisation of adnexal tumours is mainly based on two techniques: us and mri. for complex adnexal masses, mr imaging add to conventional criteria of malignancy common to all imaging modalities (bilaterality, tumour diameter larger than cm, predominantly solid mass, cystic tumour with vegetations, and secondary malignant features, such as ascites, peritoneal involvement, and enlarged lymph nodes) specific features based on the characterisation of the solid tissue (including vegetation, thickened irregular septa, and solid portion) of the adnexal tumour. signal intensity of solid tissue on t sequence (fibrous tissue), perfusion (neoangiogenesis), and diffusion (cellularity) are combined to make a decision tree analysis. low t signal, absence of high b signal, and time intensity curve type are predictive of benignity whereas high t signal and time intensity curve type are predictive of malignancy. combining common classical features and specific mr features for predicting malignancy, mr imaging has a high degree of accuracy ( %) for characterising complex adnexal tumours. this high diagnostic confidence rate may help young women wishing to preserve childbearing potential to opt for conservative surgery and avoid the systematic removal of benign complex adnexal masses in menopausal women. learning objectives: . to understand the role of ultrasonography in assessing and managing complex adnexal lesions. . to learn how to optimise the mri protocol and how to improve the characterisation of indeterminate complex adnexal masses. . to understand the added value of functional sequences (dce mri and dwi) in diagnosing adnexal masses. the european and american guidelines include breast ultrasound in a restricted diagnostic scenario for breast cancer diagnosis. the fourth edition of the european guidelines ( ) reviewed in refers to us in only twice. acr in its acr practice guideline reduces breast ultrasound examination to seven situations. evaluation of the axilla and ultrasound as a screening tool on high risk women is considered an area of research. the progression of us makes guidelines become obsolete very fast. its application still remains pending on the results of clinical trials. image smoothing on sono-ct or multiple frequency transducers will produce images, eventually with more diagnostic information. second tissue harmonics will produce sharper and more clear images. cad systems, doppler and contrast doppler will help in diagnosis. d with the new software and automatic probes constitute a very promising work in progress. they will make a dramatic change in our workload. the radiologist will be released of performing the exam, to review the images in the workstation. sonoelastography has evolved from the manual to the actual automatic shearwave. this system measures the transversal transmission of sound in biologic tissues. it is a new and promising technology, probably more objective and non-operator dependant, that is able to differentiate benign from malignant conditions. all of these systems will be reviewed and evaluated for its actual situation. the problem now is how to introduce new terms, new descriptors, and new technologies in the bi-rads system, once clinical evidence is demonstrated. diffusion-weighted mri (dwi) is a promising technique in oncology. it can be used for in vivo quantification of the combined effects of capillary perfusion and diffusion. using echoplanar imaging (epi), dwi is possible with fast imaging times minimising the effect of gross physiologic motion from respiration and cardiac movement. in this lecture, we will discuss the acquisition, post-processing and quantification methods and results of dwi in abdominal and pelvis tumours. we will also review the mechanisms associated with diffusion changes in tumours. mri-pathologic correlation will be shown. finally, limitations and future directions of the technique will be reviewed. diagnostic potentials -as well as limitations -associated with morphological cross-sectional imaging on the one hand and functional imaging on the other are increasingly well understood. it has become obvious that in many cases both kinds of imaging complement one another. hence, hybrid pet/ct imaging must be considered one of the most promising new developments in medical imaging. however, some questions have to be raised and challenges have to be met to avoid overrating pet/ct in oncology. pet/ct with [ f]- -fluoro- -deoxy-d-glucose (fdg) as a radioactive tracer has been reported to be more accurate than either imaging modality alone and sometimes even more accurate than ct and pet read side by side. however, the clinically important question should rather be the following: does this higher accuracy have an impact on patient management? furthermore, some tumours do not have an increased glucose metabolism making them fdg-pet negative. the most recently launched line of pet/ct scanners combines high-definition pet with high-end multislice ct. these imaging systems not only provide a higher diagnostic accuracy based on detection of smaller lesions with ct and pet, but also offer integration of complex ct protocols into the pet/ct scan. these protocols include ct perfusion, three-dimensional ct image reconstruction or virtual fly-through. the aim of this talk is to give an overview concerning pet/ct in oncology. the mechanism of radionuclide uptake, different tracers, the indications of pet/ct in oncology and its accuracy will be addressed. learning objectives: . to understand why uptake of the tracer provides information on the viability of solid tumours. . to learn whether pet/ct is able to give reliable quantitative information. . to know whether pet/ct is a valuable tool for tumour response to treatment. to gain additional functional information. functional imaging techniques such as diffusion tensor imaging and tractography as well as fmri are increasingly used and relied on in clinical practice. with diffusion tensor imaging and tractography the location, course and integrity of the major white matter tracts can be depicted, while with fmri the brain's cortical function is visualised. despite major technical advances, these techniques are still time consuming, labour intensive and have several limitations. they therefore need to be used and interpreted with care. the purpose of this lecture is to review the functional anatomy of the brain in a clinically relevant context and to illustrate when additional functional imaging techniques may be indicated. the most important eloquent brain areas are addressed and include the motor, visual and language systems. routine clinical cardiac mri requires speed and efficiency as a result of physical motion. consequently, the challenges and benefits of rapid mri are nowhere more apparent than in the field of cardiovascular mr imaging. to meet these challenges, one must balance the competing constraints of signal-to-noise ratio (snr), contrastto-noise ratio (cnr), spatial resolution, temporal resolution, scan time, and image quality. one of the main determinants of snr is the static magnetic field strength. hence, cardiovascular mri at . t or more holds the promise to overcome some of the snr limitations and to extend the capabilities of cardiac mri. all studies in cardiac mri at higher field strength have proven the feasibility of cardiac mri for the comprehensive assessment of cardiac morphology and function. the studies demonstrated a significant snr increase, but also outlined image-quality problems associated with b -field inhomogeneities and specific absorption rate (sar) constraints. with regard to acquisition speed, parallel imaging mri capabilities form an important enabling factor, especially if enough snr is available. therefore, the combination of higher field strength and parallel imaging strategies may help to overcome several of the present limitations in cardiac mri like cardiac perfusion and coronary artery imaging. the present indications, advantages and limitations of cardiac mri at . t will be discussed. the risks associated with the exposure of ionising radiation has raised increasing concerns in the radiological community. the recent years have shown an overall increase in the use of ct for the imaging of the heart and the coronary arteries. the downside of this increased use of cardiac ct is the increase in the collective radiation dose with cardiac ct which have been reported to be associated with an effective radiation dose of msv or more. increased awareness of the radiation dose with cardiac ct led to the development of several effective radiation dose reduction strategies including prospective ecg gating technique, anatomy and ecg-based tube current modulation, high pitch acquisition, and adaptation of the ct scanning parameters to the body habitus. however, the dose reduction strategies should be selected carefully on an individual patient basis in order to avoid serious image quality impairment by noise and artefacts. the lecture outlines the different radiation dose saving techniques currently used in clinical practice, the anatomy of the brain is often perceived as being complicated. especially the cortex is seen as an irregular arrangement of variable structures, which are difficult to differentiate and to identify. we will review the overall subdivision of the brain into lobes and describe their boundaries and their major gyri and sulci. we will then describe the location of specific functions. . primary sensorimotor cortex: motor is located in the precentral gyrus, sensory in the postcentral gyrus around the central sulcus (cs), hence the importance of always correctly identifying the cs. we will present interlocked methods to identify the cs in the axial plane (a) knob, (b) lateral axial, (c) medial axial, (d) gyral/cortical thickness and to identify it in the sagittal plane (a) lateral sagittal, (b) hook, (c) medial sagittal. . primary auditory cortex (a ): centred at the postero-medial part of heschl's gyrus (hg), we will present simple landmarks in each of the planes: (a) axial: adhaesio interthalamica, (b) sagittal: omega/heart shape of hg, (c) coronal: omega shape of hg. . primary visual cortex (v ): centred on the calcarine sulcus, we will discuss the characteristic shape that allows the identification of this structure in all planes. at the end of this lecture, you will know the subdivision of the cortex; the methods and landmarks necessary to identify the primary sensorimotor, speech, auditory, and visual areas. magnetic resonance imaging (mri) has undergone a rapid development in the last decade with numerous new techniques. nevertheless, pattern recognition of brain lesions based on signal intensities on conventional mr sequences (t -and t -weighted, flair) is the first step in diagnostic "work up". good examples for pattern recognition are lesions with t -shortening ("bright" on t wi) such as: fat containing lesions (lipoma), melanoma, lesions with colloid content, calcifications, and haemorrhagic metastatic lesions. t -shortening ("dark" on t wi) in enhancing lesions is suggestive of lymphoma and certain infections (tuberculosis, fungal abscesses). flow void (absence of signal) reflects high velocity flowing blood or csf, and will help in diagnosing vessel abnormalities and related pathologies. the purpose of this lecture is to refresh knowledge on patterns and normal variants useful for clinical practice. a simplified "pipeline" consisting of easy consecutive steps will be introduced. learning objectives: . to learn important normal variants of different structures and lesions in the brain. . to learn about recognition patterns that might be helpful in suggesting the most likely etiology of common brain lesions. . to consolidate the key imaging findings in different types of lesions and normal variants. a- : c. clinical symptoms correlated to brain anatomy m. smits; rotterdam/nl (marion.smits@erasmusmc.nl) diagnostic neuro-imaging heavily depends on a thorough understanding of brain anatomy in relation to the brain's function. clinical neurological symptoms and deficits not only give us an indication of the brain area(s) involved but may also direct us towards the use of specific imaging techniques, such as diffusion tensor imaging and tractography, as well as functional magnetic resonance imaging (fmri). specific imaging findings, on the other hand, may direct clinical management in a neurologically intact patient, such as the decision to resect a brain tumour in or near an eloquent brain area. again, specific imaging techniques may be used evaluation of response to treatment allows an early assessment of tumour response typically after - cycles of chemotherapy. this evaluation is most commonly performed with pet/ct during therapy for high grade non-hodgkin's lymphoma. this review presentation looks at the potential roles that ct, regional mri and whole body mri do and could play in response evaluation from a radiology perspective. the presenter is a radiologist who is clinical director of a medium volume pet/ ct centre. the talk focuses on discrepancies between ct and pet findings in tumour response and on tumours or situations where ct is the primary modality to determine tumour response. potential roles for whole body mri in response evaluation and assessment of solid tumours by mri are examined. at a general level, the role of the radiologist as part of the multidisciplinary oncology meeting (mdm), including when and where to use image-guided biopsy in response evaluation and the use of recist versus precist criteria is discussed. the aim of the presentation is to outline the role of ct in tumour response evaluation in the era of pet/ct and to explore potential roles particularly for whole body mri in tumour assessment. the presenter hopes to encourage radiologists to get fully involved in mdm discussions regarding ct, mri and pet/ct evaluation. learning objectives: . to learn the standard method (tumour measurements) for the evaluation of tumour response to treatment. . to understand the limits of international standard. . to become familiar with methods that provide functional or structural information, like perfusion ctmr or dw-mri. evaluation of tumour response to therapy: the role of nuclear medicine a. chiti; milan/it (arturo.chiti@humanitas.it) the high costs and possible side effects of chemotherapy and radiation therapy treatments favour the use of effective ways to monitor the treatment efficacy in oncology. molecular imaging demonstrated to be effective in evaluating the response after and during the course of therapy, in order to assess chemo-sensitivity and chemo-resistance of a particular neoplasm. the use of pet-ct in this setting can vary from very sophisticated and complex quantitative evaluation to simple qualitative analyses. in malignant lymphoma, international criteria for monitoring response to therapy have recently been revised, and fdg now plays a central role in defining tumour response. in a variety of solid tumours, studies have indicated that fdg pet-ct may provide early and accurate assessment of tumour response, suggesting that it could play a significant role in personalising the treatment of malignant tumours. performed during and after therapy for hl and aggressive nhl, fdg pet results have a high prognostic value and correlate with survival. fdg pet has been incorporated into revised response criteria for aggressive lymphomas, and several ongoing trials are under way to investigate the value of treatment adaptation based on early fdg pet results for hl and aggressive nhl. many technical aspects must be taken in consideration to avoid critical errors in evaluating response. from patient preparation to image acquisition a series of possible pitfalls must be avoided. in the clinical practice, the most widely used parameter is the suv, which can improve the accuracy of qualitative image assessment in many clinical settings. learning objectives: . to understand why pet-ct can be used to assess tumour viability. . to become familiar with the principles of signal quantification and to discuss its advantages and limits. . to learn about the incoming tracers that might enhance the role of pet-ct in the evaluation of tumour response. alzheimer's disease: the role of radiology j. alvarez-linera; madrid/es (jalinera@ruberinternacional.es) neurobiological changes in alzheimer's disease (ad) occur in an stereotypical pattern that begins in the medial temporal lobe (mtl) years before the clinical manifestation (brain reserve). brain atrophy is a marker of neurodegeneration that reflects the neurobiological disorder and is correlated with the neuropsychological changes at all stages of the disease. other imaging markers may reflect changes in microstructural (diffusion), functional (perfusion) or metabolic (mrs) domains that would provide additional information but are awaiting wider validation. in the early stages of ad, the most effective mri markers are those that reveal atrophy in mtl, particularly the measures of the hippocampus. the mtl atrophy mea-the required conditions in whom they may be successfully used, and how these techniques could be implemented in the daily clinical practice. proper linking of the data acquisition to the patients ecg is among the crucial prerequisites for successful cardiac imaging. while cardiac ct data acquisition itself does not impose any effect on the patients' ecg, inherent physical effects in the mr environment does show impact on the ecg trace and may hamper proper r-peak delineation. in addition, patient-related factors such as arrhythmia might affect image quality (iq). dose saving strategies in cardiac ct limit the possibilities of retrospective iq optimisation and as such more emphasis is recommended prior to data acquisition which is mainly related to patient selection/heart rate control. in cardiac mr a high amplitude ecg without influence of magnetic or scanning effects is of outmost importance. arrhythmia also remains a challenge that might be overcome by arrhythmia-rejection algorithms or real-time imaging. suboptimal contrast enhancement ought to be avoided by proper planning and timing as the majority of post-processing algorithms is based on signal behaviour. in the unfortunate situation of suboptimal contrast enhancement often only the use of standard post-processing tools is possible while semi-automated tools for cardiac post-processing may fail or necessitate substantial user interaction. the use of straight forward visualisation techniques is recommended for diagnosis while complex visualisation tools may add on confidentiality but are mainly suited for case presentations. coronary evaluation is typically performed using centerline tools allowing for the easy assessment of cad. while these tools potentially allow for estimation of the degree of diameter and area stenosis, accuracy though may still be limited. this is the second session between esr and eanm at each society's annual congress. few would argue but that patient's interests are best served by crossfertilisation and open communication between specialties. this is particularly true for radiology and nuclear medicine. this session elaborates on clinical scenarios where cross-fertilisation between both specialties is particularly important. the session will elaborate the radiologist and nuclear medicine perspectives on two common clinical scenarios, i.e. tumour response to therapy and evaluation of alzheimers disease. session objectives: . to appreciate how nuclear medicine and radiology provide complementary information. . to learn how each method can enhance the mutual performance of the radiologist and nuclear medicine physician. . to learn about recent advances in the field of tumour evaluation and early detection of alzheimer's disease. shown on mdct-images in the axial, coronal, and sagittal plane. variants of the normal anatomy, which are important to describe and to know are also shown. some of these variants are also delineated on mr images. in the second part of the lecture, the different expressions of congenital malformations of the external and middle ear will be explained. the different findings of the severity of the malformations will be shown and their importance for further clinical-therapeutical procedures will be explained. imaging investigation of cholesteatoma is required before surgery. if no surgery has been performed previously, ct will provide information about the location of the lesion (epi, pro, meso, retro, hypotympanum), the partial or total destruction of the ossicles, and possible extension to the inner ear. if there is no doubt about any of these factors ct is sufficient. in doubtful cases an mri examination is performed to confirm or refute the presence of cholesteatoma using t sequences without iv contrast medium, and diffusion weighted imaging with or without high resolution t , depending on the age of the patient. in postoperative recurrent cholesteatoma, mri is becoming the modality of first choice for detecting cholesteatomas, appearing : low in signal on t sequences, high in signal on diffusion weighted imaging. however, care is required since performing diffusion weighted imaging without t may lead to false positives. a granuloma with a slightly or markedly increased t signal is often associated with a high signal on diffusion. measurement of adc is useful for detecting cholesteatomas, infected cholesteatomas or abscess. finally whilst mri is the first examination in the follow-up of postoperative patients, the use of contrast medium is not necessary in most of the cases. a- : c. implants and postoperative findings in the middle ear b. verbist; leiden and nijmegen/nl many conditions which affect the function of the middle ear may require surgical intervention. postoperative imaging will be requested either to evaluate complete removal of diseases (eg in cholesteatoma) or because of new, persisting or recurrent complaints of the patient (e.g. vertigo after stapes replacement). in this presentation, different surgical procedures will be reviewed including the indications for a certain surgical approach as well as the different types of prosthesis. the normal postoperative imaging appearance of the most common surgical techniques will be shown. it will be discussed whether ct or mri should be performed to answer the clinical questions. an overview of possible failures and complications will be given. the management of patients with vascular malformations is often suboptimal. the reasons for this are many but include confusion regarding classification, uncertainty about the most appropriate imaging of the various forms of malformation and a sures are helping to propose new diagnostic criteria for ad, allowing a diagnosis of probable ad in predementia stages, when memory loss criteria are attached to imaging criteria (mri or pet) or measures of amyloid/tau in csf. the use of atrophy markers (global or mtl) increases the effectiveness in clinical trials (both by reducing the size of the sample and increasing the statistical power) and is therefore contributing significantly to the development of new treatments. the association of multiple markers of structural and functional imaging (mri and pet) and the use of advanced computational analysis techniques will allow better management of ad but it needs a broader validation and know the most efficient combination of biomarkers at each stage of the disease, including the preclinical period. scientists, researchers and clinicians all benefit from molecular imaging in dementia providing exciting new insights into their basic biology and pathophysiology. targeting specific aspects of neurotransmission, metabolism, inflammation or plaque formation -just to mention some of the current molecular approaches -increasingly gains impact on establishing the correct diagnosis, following the course of dementia or developing cns drugs. this talk will highlight the molecular targets and major pet and spect tracers for application in dementia, and will update on the results of the clinical imaging studies published in recent years. typical imaging patterns of alzheimer's disease (ad) will be discussed, including also the diagnostic discrimination from other types of neurodegenerative dementias such as frontotemporal dementias, lewy body dementia, and others. assessment of mci patients and the probability of transition in manifest dementia (predominantly ad) will be addressed together with its prognostic relevance. furthermore, recent advances in analysing tools which further improved the high diagnostic accuracy already reached by visual assessments will be presented. even though in competition with other modalities, ‚standard fdg' pet has shown to be a robust and both, sensitive and specific marker in the diagnostic work-up of dementia. fdg information will be markedly extended in clinical practice by specific amyloid imaging in the near future when these tracers are approved and thus generally available. learning objectives: . to become familiar with the nuclear medicine method that enables detection and evaluation of alzheimer's disease. . to learn about the potential development of functional studies using nuclear medicine. . to understand how nuclear medicine and radiology can provide complementary information. symptoms may require explanation and reassurance only. lesions with a mainly cutaneous element may be treated with laser. deeper lesions are usually treated with several episodes of sclerotherapy. agents such as alcohol, polidocanol and std will be discussed and the relative advantages and issues explained. informed consent is vital, and the approach to this will be outlined. high flow lesions are frequently associated with severe cosmetic changes, invasion of surrounding tissues, haemorrhage, and high output cardiac failure. lesions may be life threatening. in the extremities peripheral ischaemia and ulceration due to steal of blood by the arteriovenous malformation is common. informed consent will again be discussed, as potential for major complications is high. key to endovascular management of these lesions is an understanding of the nidus, arterial inflow and venous outflow. the role of liquid and solid embolic agents and specifics of transarterial, venous and direct approaches will be discussed. avms pose a major problem regarding classification and treatment. a case report discussed by the panellists demonstrates how these patients should be approached. the importance of establishing an interdisciplinary outpatient clinic is also presented. the most important organisational steps for providing an efficient clinical service are given. in addition, the most common pitfalls and complications of treatment are illustrated. computer-aided detection/diagnosis (cad) is recognised as a workstation or a system developed in order to assist the radiologists (clinicians) in performing their daily diagnostic tasks. clinically implemented cads are available at workstations and (if dicom compliant) may serve as a plug-in to pacs. the three-layer cad system includes: ( ) image analysis procedures whose development requires a medical and technical knowledge, ( ) a database module that is managed by experienced radiologists and it professionals, and ( ) graphical user interface (gui) that enables a user-friendly access to the data, the processing tools, and the results. a modern cad development involves a multidisciplinary team whose members are experts in medical and technical fields. a close collaboration of all experts is required at all stages of system life-cycle. at each stage the physicians knowledge and experience are indispensable. it includes medical analysis of the diagnostic problem, data collection, image analysis evaluation, and clinical verification. design, testing, and evaluation have to be successful in order to ensure cad implementation in a daily clinical routine. in this session three experts will share their experiences in the area of the overall cad architecture, its evaluation, validation and acceptance by clinicians, advantages and restrictions of solutions and clinical implementation in lung, breast and colon cancer. reading paradigm (primary, concurrent, second) in oncology as well as results of cad clinical implementation will be presented. perspectives in clinical cad implementation in diagnosis and treatment will be discussed. patients presenting with vascular malformations mostly are nomadic and hopeless individuals looking for help. finally having reached a "multidisciplinary specialistgroup" after a sometimes long and misleading trip throughout the ocean of "singleplayers" of different specialities these patients do not ask for any more diagnostics -they strongly claim for therapy. vascular malformations are congenital lesions, although merely seen at birth they become evident throughout the individuals growth. these developmental errors can affect all components of the vascular tree in any area of the body. the therapeutic goal must be defined rather as "control" than "cure" of this disease. to make this point understandable for both patients and collegues a fundamental understanding of the pathogenesis and natural course must be created. in special cases of complex vascular malformations the precise diagnosis and the information about all potential side-effects as well as risk-factors of progression enables these patients to manage their daily life. therefore, indications for treatment vary depending on the specific type of slow flow or high flow lesion, location, pain, functional and cosmetic impairments and general side-effects of each particular lesion, since no single specialist has enough knowledge to diagnose or treat vascular anomalies beyond the border of his distinct speciality multidisciplinary working-groups emerged at these interdisciplinary interfaces. their common language in classifying and their overall understanding of pathogenesis, prognosis offer these mostly hopeless patients a custom-fit treatment addressing their symptoms. imaging of vascular malformations should be directed by clinical assessment of the type of malformation to be expected, clinical symptoms and need for treatment. in order to make the proper decision of the required imaging modality or treatment, it is essential that the (interventional) radiologist is a member of a dedicated vascular malformation team. imaging needs to be tailored to the individual patient although general rules can be applied. duplex ultrasound together with a clinical assessment is often sufficient to make a proper diagnosis. this is especially true for the paediatric population. if more information about the extent of the lesion is needed, mr is often used in case of low flow lesions (venous/lymphatic), and mra or cta in case of high flow lesions. angiography is mandatory if an avm is diagnosed and treatment is planned. high frame rate imaging and selective injections are the only options for a proper evaluation of the nidus architecture of the avm. there are exceptions that warrant deviating from the above general rules. in this lecture, both the general rules and the exceptions will be discussed. at the onset of the st century humankind is focusing its attention on a very small molecule, as controlling co in the atmosphere is becoming a major goal, economically, socially and politically. yet, there is another small molecule which is going to play a more prominent role in the near future. h o, especially in its liquid form, the 'blue gold', is just indispensable to our lives. water makes to % of the human body weight and is crucial to the working of the biological machinery. still, how such a tiny molecule with its ° 'magic' angle could have been at the origin of life remains largely a mystery. different organisms have adopted different strategies in the way they get the most out of water, depending on their environment, and water contributes to the biodiversity. faulty mechanisms in the use of water by tissues may lead to severe diseases or death. clearly, water deserves to be seen as the prime 'biological molecule', and radiologists have long recognised its importance from the days of 'dry' (bone and air) radiology to the advent of ct which allowed contrast from 'wet' tissues to be explored. with mri one went one step further, as magnetisation of water is the sole source of contrast. life has led to intelligence, and recent mri studies have suggested that water may also actively contribute to the mechanisms underlying brain function. could the 'molecule of life' also be the 'molecule of the mind'? clearly, water must be radiologists' best friend. learning objectives: . to comprehend how the structure of the water molecule makes it important to life. . to understand the importance of water in biological and cellular processes. . to become familiar with the different ways water is responsible for image contrast in radiology. a. the role of cad in modern-day imaging a. todd-pokropek; london/uk (a.todd@ucl.ac.uk) the use of cad in medicine is an important and growing area of research. firstly good data must be acquired including not just images but associated information. the first step in that of preprocessing, notably (but not only) noise reduction. the data are then passed onto the segmentation step. often this step is semi-automatic requiring some manual intervention. conventional edge detection methods are not often of value, but active shape and appearance models, the use of markov random fields etc are commonly used. the next step is that of feature extraction both of shape and texture. these data are then submitted to one of several classifiers such as artificial neural networks (including mtanns) support vector machines (svm) and data reduction using principle and independent component analysis, and multiple voting techniques such as adaboost are also of value. the output may simply be returned to the observer (clinician) or as further input for a decision support system. examples considered will be in breast imaging (mammography), lung nodule detection, virtual colonoscopy and lumber spine. the use of the cad system as a simultaneous assistant or as a second reader is important. the use of cad in therapy is of increasing important. the assessment of such cad system (evaluation and validation) is still controversial. the difficulty of bringing systems both instrumentation and software for use in clinical practice in often underestimated and there have been some notable failures. some example of 'failures' will be given. ct colonography has evolved rapidly and disseminated widely over the last decade. the ability to provide an accurate whole colon examination with near perfect completion rates, use of reduced laxative bowel preparations and extra-colonic organ review has attracted very considerable interest amongst the wider radiological and gastroenterological community. inclusion of ct colonography in several core radiological training programmes confirms its evolution from super-specialist technique (performed in only a few centres) to mainstream. however, evidence supports highly variable performance, which is perhaps unsurprising given the complexity of both technique and interpretation methods -both which require specific training. notably, attendance at a training workshop generally represents the beginning of a radiologist's experience of ct colonography. indeed, most delegates rapidly progress from unconscious to conscious incompetence, acknowledging the need for a planned implementation strategy prior to offering ct colonography in their routine clinical practice. thankfully a decade of intensive research and large volume clinical experience has equipped the radiological community with knowledge and experience to inform successful ct colonography implementation strategies. by combining this experience with training and accreditation practices developed for colonoscopy, the prospect of a robust quality assurance framework is realistic and necessary to reassure both service commissioners and the general public alike. step one: the publication of international ct colonography standards, co-authored by eminent radiologists from across europe and beyond has been achieved. this talk will review the likely next steps. computer-assisted detection (cad) for ct colonography is now widely available in europe from a number of different vendors. this presentation will detail factors that potential users will need to know in order to properly evaluate cad systems, use them in clinical practice, and evaluate their likely impact. the different ways in which the performance of cad systems can be assessed will be discussed and the difference between weak methodologies (e.g. internal validation) and more valid assessments (e.g. external validation) will be explained. now that the diagnostic performance of ct colonography has been well-established, this state-of-the-art symposium will deal with issues related to the implementation ct colonography in day to day clinical practice. the lecturers will deal with the diagnostic performance of ct colonography, the technical requirements necessary to obtain high quality diagnostic data, the factors that underpin a high-quality service (including reader training), how implementation differs across different countries, and the possible impact of new developments, including computer-assisted detection (cad). two decades ago spiral ct technology initiated a new era in diagnostic imaging with virtual colonoscopy or ct colonography (ctc) as a major innovation. introduced by david vining in , ctc was rapidly endorsed as a potential tool for colorectal cancer screening. after an initial pioneering period defining the basic ctc principles, the advent of multi-slice ct significantly improved spatial and temporal resolution, allowing for isotropic image reconstruction with detailed d rendering of the colonic wall and very short acquisition times, reducing motion artefacts. furthermore, application and refinement of (ultra-) low dose technique almost completely tackled the issue of radiation dose. these improvements have resulted in the perfect optical colonoscopy imitator with reliable fly through of the colon in a timely manner. consecutively, the primary d reading paradigm with d problem-solving is getting more and more adepts, although in experienced hands primary d-read with d-problem solving is a solid contender. to improve depiction of the colonic wall new d visualisation methods were developed. these technical improvements with the application of state-of-the-art ctc technique have resulted in a very good performance of polyp detection. in three multi-centre studies, totalising patients, sensitivity ranged between - % and - % and specificity between - % and - % for lesions > mm and > mm, respectively. finally, it may be expected that further refinements of cad, laxative-free ctc with electronic cleansing and dual energy ct will bring ctc to the next level and will enhance it as the reliable and cost-effective tool for colorectal cancer screening. learning objectives: . to review the evolution of ct colonography since its introduction, with a focus on data acquisition and methods of data visualisation and interpretation. . to review the currently achievable test characteristics of ctc (sensitivity, specificity, accuracy) via reference to current trial data. . to become familiar with imminent developments that may further enhance ctc test characteristics. astinitis and extension of infection from adjacent spaces (neck, pharynx, pleura or retroperitoneum). typical cases including the role of radiologic findings with respect to sensitivity and specificity, and important differential diagnosis will be discussed. the distinction between a parapneumonic pleural effusion and an empyema based on radiologic findings is often impossible. features suggesting a "complicated" course requiring interventional or even surgical treatment at some point will be discussed. features of empyema and lung abscess at ct will be illustrated as well as ct indices of severity of empyema and its effect on the underlying lung that allow some prediction of functional outcome after surgical decortication. an empyema necessitatis describes a chronic empyema that attempts to decompress through the chest wall. infectious agents include tuberculosis, actinomyces, staphylococcus and various types of fungi. it has to be differentiated from other mostly neoplastic diseases that cross fascial planes such as lymphoma or pancoast tumour. most lymphomas arise in lymph nodes or other lymphatic tissues. extranodal lymphomas arise in tissues normally devoid of lymphoid tissue. involvement of so-called extranodal organs is a common finding after staging investigation, however, and a substantial part of nhl even arises in these sites. the latter form is often referred to as primary extranodal nhl. splenic lymphoma is common in both hodgkin disease and non-hodgkin lymphomas but it may be difficult to detect by imaging techniques because lymphoma nodules in the spleen are often smaller than cm. splenic enlargement alone is not a good indicator of lymphomatous involvement. primary hepatic lymphoma is rare compared with disseminated diseases at both nodal and extranodal sites. several forms of hepatic involvement can be seen including mass lesions/nodules, diffuse infiltrative form and extrahepatic involvement of the hepatic ligament. lymphomatous involvement of liver hilum nodes often infiltrates along the hepatic artery and portal vein toward the head of the pancreas and produces an infiltrative bulky mass that involves the liver, pancreas and duodenum. primary pancreatic lymphoma is very rare and can be difficult to differentiate from pancreatic adenocarcinoma. definitive pathological diagnosis of lymphomas is often obtained using image-guided biopsy. this noninvasive procedure is important as the prognosis and management of lymphomas differ greatly from that of adenocarcinoma or metastatic diseases. staging (ann arbor classification or modifications) and response to therapy is primarily by ct. community acquired pneumonia (cap) is a major health care problem because of their high morbidity and mortality rates. patients exposed to non-hospital risks who develop pneumonia have been traditionally categorised as having communityacquired pneumonia (cap). healthcare-associated pneumonia (hcap) is a new designation for pneumonias affecting individuals residing in non-hospital health care facilities, patients undergoing outpatient procedures or therapies, and patients who have been recently discharged from the hospital setting. when the diagnosis of cap or hcap is suspected, imaging studies are mandatory for the evaluation of affected patients. a nosocomial pneumonia is defined as one not acquired in a hospital or a long-term care facility. it occurs most commonly among icu patients, predominately in individuals requiring mechanical ventilation. pulmonary infection is a major cause of morbidity and mortality in patients with impaired immune function. increasing numbers of patients are becoming immunosuppressed, because of solid organ and hematopoietic stem cell transplantation, the use of immunosuppressive agents for treating a host of inflammatory diseases, or congenital and acquired diseases such as acquired immune deficiency syndrome (aids). mildy impaired host immunity as it occurs in chronic debilitating illness, diabetes mellitus, malnutrition, alcoholism, advanced age, prolonged corticosteroid administration and chronic obstructive lung disease have also been regarded as predisposing factors of pulmonary infections. the rapid diagnosis and treatment of pulmonary infections are essential. combination of pattern recognition with knowledge of the clinical setting is the best approach to pulmonary infectious processes. acute mediastinitis is a potentially life threatening but fortunately rare condition that requires prompt diagnosis and treatment. spontaneous or iatrogenic oesophageal rupture is the by far most common cause. other causes include post-surgical medi-ask the patient for those information. at the time of mr imaging plain films and/ or results of an ultrasound exam of the shoulder, if possible, should be available. however, only such prerequisites allow to run a tailored examination protocol and to support the orthopaedic colleague with the needed answers for further adequate therapy. the patient has to be placed in the magnet in a pleasant situation to avoid artefacts due to patients movement, which usually cause motion artefacts. it is very important to explain to patients to keep quiet during the whole examination, because artefacts may need repetitions of sequences, and lead so to prolongation of total examination time. furthermore, they make diagnosis more difficult and eventually more or less inaccurate. lastly, sequence repetitions decrease patient throughput and therefore cost effectiveness. imaging in three orientations (axial, paracoronalparallel to the supraspinatus tendon, and parasagittal -parallel to the glenoid cavity) using t w (pdw) and/or t w sequences have to be performed. in case of specific questions regarding lesions of the labrum intraarticular administration of contrast agent (mr arthrography) should be considered, which is sometimes (different from country to country) possible after discussion with referring orthopaedic surgeon only. mr imaging (mri) and mr arthrography are the primary diagnostic imaging modalities applied to patients with degenerative, traumatic and sports-related shoulder lesions. in this categorical course the characteristic mr imaging and mr arthrographic features of articular pathologies of the shoulder, in particular, instability-associated injuries, rotator cuff tears and biceps tendon lesions are discussed. beside lesion detection the radiological analysis comprises the understanding of the underlying pathomechanism and recognition of possible interrelations between different type of lesions (for example, secondary impingement and associated lesions of the posterosuperior labrum). the use of classification systems for specific lesions is introduced in order to improve the radiological report. a reasonable structure for written reports is discussed comprising a brief and clear description of pathological findings with subsequent interpretation and categorisation of findings with a view of therapeutic decision making. tissue changes in the treated neck by surgery and/or radiotherapy (rt) make the detection of residual or recurrent tumour more difficult. clinical evaluation of the neck is also hampered by these changes. therefore, any (non-invasive) method helping in the detection of recurrence is welcome. in order to evaluate the treated neck, radiologists should be familiar with expected post-rt findings. histological changes post-rt will be discussed in combination with imaging examples. this knowledge will enable radiologists to recognise non-expected findings post-rt. non-expected post-rt findings can be caused either by tumour recurrence, or by complications of treatment (e.g. chondro-radionecrosis). imaging examples will be shown. especially after surgery, including various types of neck dissection, lymphatic drainage patterns of the head and neck are altered. it is important that radiologists are aware of these changes. imaging examples will be shown. ct and/or mr-findings in the treated neck may be inconclusive. in these cases, there may be an additional role for metabolic (pet) imaging. at present, the position of metabolic imaging in the imaging protocol for the treated neck is unclear. information from the recent literature will be discussed. also, examples from daily practice will be shown, with emphasis on the importance of base-line imaging after treatment and the timing of such base-line scans. this knowledge will help in understanding the current indications and limitations of post-treatment metabolic (pet) imaging of the head and neck. an increasing number of functional and metabolic imaging options reflecting relevant aspects of tumour biology have rapidly been incorporated into clinical trials and, progressively, into clinical practice. while tumour staging according to the tnm system still rules most decisions regarding treatment choice in head and neck cancer, biological information from the tumour and its microenvironment has proven to have important predictive and prognostic value heading for a tailored and individualised patient's management. ct, mr and pet are the mainstay imaging modalities to access tumour extent, both of the primary tumour, lymphatic and distant metastases and for early depiction of recurrence during patient's follow-up. hypoxia and angiogenesis, the major driving forces for tumour aggressiveness, long linked to chemo and irradiation treatment failure, can now be imaged both by pet ( f-miso or cu atsm) or mri (bold and pwi, respectively). this information is being used to define biological tumour volumes, to tailor conformational and intensity modulated radiation treatments and to select patients for specific treatments such as radiosensitizers, hypoxia selective cytotoxic and antiangiogenic drugs. overexpression/amplification of egfr (epidermal growth factor receptor) are common genetic abnormalities in scc linked to increased cell proliferation and worse prognosis. imaging techniques reflecting cell proliferation/ density ( f-flt -desoxyfluorothymidine-and diffusion-weighted mri) can be used to select patients for treatment with egfr inhibitors. this special focus session will review the use of these imaging modalities both prior, during and after treatment of head and neck cancer focusing on their specific advantages and accuracies in these different settings. contrast-enhanced ct and mri are routinely used in order to determine the precise localisation, size and anatomic extent of the primary lesion. on the other hand, positron emission tomography (pet) is the most sensitive and specific technique for in vivo imaging of metabolic pathways and receptor-ligand interactions in the tissues. a common question is which of these techniques should be used in a particular patient. the most widely used technique is ct, as it has a number of important advantages over mri, like wide availability, relative low cost and short examination time. however, ct also has a number of disadvantages compared to mri: relative low soft tissue contrast resolution, severe image quality degradation by dental fillings or other metallic foreign objects, and radiation exposure. pet in combination with ct and/or mri has a good sensitivity and specificity for the detection of primary tumour and for nodal staging as well as for detection in a single examination distant metastases, occult tumours, second synchronous tumours, and for radiotherapy planning. by combining pet with ct and mri studies, either sequentially or synchronous performed, the diagnostic accuracy is significantly higher. in those situations, it has been proven that magnetic resonance (mr) imaging is a valuable adjunct to delineate the pathology. in non-pregnant woman the radiological evaluation is less difficult. still, a multimodality approach may be needed in certain cases. in this lecture, radiological features of non-gynaecologic emergencies such as acute appendicitis, diverticulitis, renal calculi and pyelonephritis will be discussed. the purpose is to discuss the role of imaging and the potential of different methods applicable in childhood uti -with a focus on us. the imaging task in uti has changed, and new questions arouse for radiology. in addition, growing economical demands pressurise radiology to restrict imaging to those conditions where an evident benefit has been demonstrated. this efficacy-oriented approach is difficult in children due to the lack of evidence-based data. thus, controversies exist on if, when and how to investigate childhood uti, trying to minimise procedures and reduce burden on children and health budgets without missing important conditions that may pose a threat to the kidney. furthermore, modern imaging with new methods, applications and potential (e.g. contrast-enhanced voiding urosonography = ce-vus) may influence the imaging algorithm. the in utero and post-natal follow-up of foetuses with urinary tract dilatation has provided lots of information about the proper management of urinary tract malformations. nowadays, affected neonates are evaluated following standardised charts panel discussion: the three musketeers were actually four : ct, mr and pet: how to choose between modalities in head and neck cancer patients. an increasing number of imaging modalities reflecting functional and metabolic aspects of tumours have rapidly been incorporated into clinical practice. these modalities provide additional information on tumour vascularisation/ angiogenesis (ct and mr perfusion); on tumour metabolism, hypoxia and proliferation (pet using different radioactively labelled substances) and on tumour architecture and cellular density (dwi). hybrid imaging, pet-ct and, in the near future pet-mr, can provide morphologic, metabolic and functional information in a one-stop-shop examination. the choice of the best modality (ies) to answer specific questions in the diagnosis, follow-up and in the prediction of response to treatment and prognosis will be addressed. acute abdominal and pelvic pain in pregnant women may be the manifestation of various gynaecological and non-gynaecological conditions. the correct diagnosis of the causes of acute pain during pregnancy is critical to minimise maternal-foetal morbidity and mortality. although ultrasound (us) is the primary imaging investigation in the diagnostic evaluation of the pregnant patient, the role of magnetic resonance (mr) imaging in the evaluation of foetal and maternal diseases in pregnant patients continues to expand. mr imaging offers different potential advantages in comparison to us for evaluating acute abdominal and pelvic pain; these include multiplanar imaging capabilities, a higher soft tissue contrast and the ability to detect and distinguish blood from other fluid collections. when us is equivocal or nondiagnostic, mr imaging is a valuable complement to determine the exact aetiology of acute abdominal pain. the intrinsic safety and the accuracy of mri in diagnosing abdominal and pelvic disease make it an excellent choice for triage of pregnant patients with acute abdominal and pelvic pain. mr imaging provides important information that influences patient management, and it is important for the radiologist to recognise the mr imaging appearance of the common causes of acute abdominal and pelvic pain during pregnancy. this lecture will discuss the use of mr imaging for maternal diseases that cause acute abdominal and pelvic pain during pregnancy. moreover, this lecture will discuss the different mr imaging techniques to use, and will show how to detect and to differentiate the gynaecologic and non-gynaecologic causes of pain during pregnancy. in this lecture, the role of imaging in the evaluation of gynaecologic emergencies will be presented. a combined approach using both clinical findings and imaging features is necessary. accurate evaluation is important as failure to make a diagnosis may lead to serious consequences. presenting symptoms, such as pelvic pain or vaginal bleeding or discharge, may overlap with pregnancy-related emergencies and with non-gynaecologic abdominal emergencies. the range of conditions to be considered include ovarian cyst emergencies (cyst rupture, haemorrhage or torsion), infective conditions (bartholins' or vulval abscess, pelvic inflammatory disease or tubo-ovarian abcess) and acute bleeding (from inflammation, neoplasm, or trauma). pain may be related to the menstrual cycle, as in endometriosis or ruptured corpus luteum, or may be unrelated, such as in fibroid or ovarian torsion or pelvic inflammatory disease. the imaging features of these acute abnormalities will be reviewed and discussed in the context of the differential diagnoses. the major functional imaging tools for tumour management are obtained with dynamic contrast-enhanced imaging, diffusion-weighted mr imaging, and mr elastography. these acquisitions allow understanding of tumour angiogenesis and perfusion, and tumour architecture. dynamic contrast material-enhanced imaging allows assessment of perfusion parameters. diffusion-weighted mr imaging provides information that reflects tissue cellularity and the integrity of cellular membranes. mr elastography evaluates the mechanical properties of tissue such as stiffness and viscosity. to date, tumour detection is mainly based on morphologic features. however, changes in perfusion parameters have been shown as early parameters of liver metastases detection in patient with colorectal carcinoma or breast carcinoma. tumour characterisation is usually based on morphologic features. yet, perfusion parameters have been shown to correlate with microvascular density and tumour differentiation helping tumour characterisation. furthermore, apparent coefficient diffusion (diffusion-weighted mr imaging) and stiffness and viscosity (mr elastography) are significantly different in benign and malignant tumours. despite these differences, these last parameters usually do not allow definitive subtyping. functional imaging starts playing a major role in non-surgical treatment follow-up especially with targeted cancer therapy. changes in perfusion parameters, apparent coefficient diffusion, and stiffness and viscosity are observed in responders. interestingly, these changes appear promptly after treatment initiation. these functional variables are not included in recist . but might be part of response criteria in the next future. many examples of functional imaging for tumour management will be provided. learning objectives: . to understand the potential of functional imaging in tumour detection. . to understand the potential of functional imaging in tumour characterisation. . to learn about the future use of functional imaging in treatment planning and follow-up. (among others, thanks to the esur-espr working group). at birth, a confirmatory ultrasound is performed in order to evaluate the type and degree of the malformation. urinary tract dilatation are separated into mild, moderate and marked. mild and moderate dilatation will be followed by us. voiding cystogram and functional studies will be performed only if the dilatation is significant or persists. the prognosis is usually good. patients with marked dilatation would be managed more "aggressively". their work-up would be initiated as soon as diagnosed in order to diagnose cases that need therapeutic manoeuvre. for them voiding cystogram, anatomical and functional studies cannot be skipped and are important for the prognosis. long-term follow-up are needed to prevent further damage. learning objectives: . to learn which infants with antenatal diagnosis of urinary tract dilatation require imaging and when. . to become familiar with the most important differential diagnosis. . to learn about the imaging strategies in these infants. c. renal and pararenal masses: basic rules p. tomà; rome/it (paolo.toma@opbg.net) the differential diagnosis of renal and pararenal masses firstly depends on the age of the child. wilms tumour (nephroblastoma) is the most common abdominal tumour in - years old ( % of cases in children less than years old -peak age . years). renal non-wilms tumours represent a significant proportion of renal tumours in children, especially in children aged less than months or greater than years. neuroblastoma most commonly arises from the adrenal gland but can arise anywhere along sympathetic chain; it is the most common tumour in children under years of age ( % of cases in children less than years -mean age < years). adrenal adenomas and carcinomas also occur in childhood. us is the initial imaging modality to investigate an abdominal mass in children. ct or mri is used to confirm the us findings and not uncommonly add new, valuable information. concerning wilms tumour there is a very diverse approach to treatment according to geographical location. this variation in therapeutic attitude has consequences for the choice of imaging modality at diagnosis. neuroblastoma staging includes also i-mibg, and laboratory investigations (bilateral bone marrow aspirates with histochemical tests and urine catecholamine level measurements). we focus on the points under discussion: revision to the staging of neuroblastoma, the problems inherent in distinguishing nephrogenic rests from wilms tumour and the approach regarding small lung nodules in children with wilms tumour. the principle of bi-rads imaging finding should be that of "quasi-benign" type, i.e. with a very low associated risk of malignancy (< %), opening the possibility of a short-term imaging follow-up as an alternative to imaging-guided needle biopsy. however, a number of issues should be regarded as relevant to radiologists and patients. ) radiologists' differences in classification. . when needle biopsy is optioned, vacuum-assisted biopsy under stereotactical guidance for mammographic only findings (typically, microcalcifications) and core-biopsy for sonographic findings should be used; fine needle aspiration cytology should be avoided due to the high probability of benign lesions which need larger tissue samples. . when short-term follow-up (typically, months) is optioned, the same technique on which the bi-rads lesions was initially detected should be used. . in the screening setting, short-term follow-up option is commonly not considered and the reader is forced to give a dichotomic reading (recall/not recall). . the choice between the two options should be clearly discussed with the patient, including the psychological cost of waiting six months to get a conclusive report, and a really informed consent should be obtained. . till now, there is insufficient evidence for using tomosynthesis or mri for evaluating mammographic or sonographic bi-rads findings. the premise behind the bi-rads classification is to identify a group of low risk lesions that can be safely placed on follow-up rather than biopsy. in practice this can be very difficult and is anachronistic to the principles of the european population screening programmes where the radiology objective is to diagnose or discharge. the panel will discuss these dilemmas. starting in the late s an american college of radiologists task force developed the concept of guidelines to standardise mammography reporting: breast imaging reporting and data system (bi-rads). there is evidence that over time there have been improvements in consistency of use, sensitivity, specificity and positive predictive value. however, bi-rads 'probably benign; short interval follow-up recommended; less than % risk of malignancy' has always been the most difficult and controversial, with the highest levels of discordance between classification and recommendation, wide variation in both intra-and inter-observer agreement and a literature review demonstrating ppv for malignancy of between and %. management of breast disease has moved on a great deal since the s. in the main driven by increasing specialisation associated with population screening programmes. nowadays a specialist breast radiologist works with a wide variety of needle options at his hip to such an extent that the breast multi-disciplinary team increasingly feels that failure to obtain a non-operative diagnosis of discrete lesions is unacceptable. in this setting, and mindful of the medico legal consequences of 'delayed diagnosis', is there still room to allow a patient to leave the one stop clinic without a definitive diagnosis? as the leaders of the diagnostic team we also have to take account of the emotional and psycho-social consequences for our patients as well as the financial costs to patient and the healthcare economy. breast imaging reporting and data system (bi-rads) was developed for standardising reporting and include mammography, ultrasound, and mri. bi-rads category "probably benign finding -short-interval follow-up suggested" should have less than % risk of malignancy. category has been subgrouped into a, b, and c, and this influence the classification of bi-rads . mammographic bi-rads : three nonpalpable findings in this category include clusters of punctate microcalcifications, well-circumscribed and noncalcified solitary masses, and benign-appearing asymmetric density. digital mammography will increase detection of amorphous microcalcifications and the number of bi-rads (or a) lesions. intramammary lymph nodes and calcified fibroadenomas are bi-rads lesions. ultrasonographic bi-rads : a most important bi-rads lesion is a solid oval mass ("tumour") with gently lobulations, circumscribed margins, and parallel orientation. using strict criteria, the negative predictive value is approaching %. two other lesions are nonpalpable "complicated cyst" and clustered microcysts. the "complex" cyst, i.e., a mass with cystic and solid components, should be classified as bi-rads . mri bi-rads : there is lack of evidence which mri findings should be categorised bi-rads . nonmass-like enhancement (nmle) and enhancement kinetics are unique to mri. lesions less than mm ("foci") need no assessment. a challenge is mri-detected tumours < mm as morphologic analysis is of limited value. benign kinetic curves may justify short-term follow-up. in high-risk women, mri-guided vacuum-assisted biopsy should be considered. in conclusion, bi-rads is justified in diagnostic settings but should be avoided or kept at a minimum in screening. what will be the standard machine and field of the future? l. darrasse; orsay/fr (luc.darrasse@u-psud.fr) improving the sensitivity has still been an essential issue in mri, because the signal from nuclear spins relies on extremely weak magnetic interactions dominated by thermal fluctuation. to push the signal-to-noise ratio upward, the basic routes have been (i) to increase the field strength, (ii) to improve the signal detection with radiofrequency coils and (iii) to enhance the signal dynamically with contrast agents or alternative preparation techniques. the first route is the most obvious one, driven by the trends in analytical mr spectroscopy and small-animal mri. going up to or even above t represents a considerable challenge, both technically and in view to renew the mr equipment market. however, this way is limited by safety issues, radiofrequency penetration concerns and susceptibility artefacts. alternatively, improving the radiofrequency system relies on a complex electrodynamics background, where tissue conductivity and different sources of noise have to be considered. during the last half-period of mri development, radiofrequency coil arrays have appeared as a powerful mean to improve the signalto-noise and to accelerate the spatial encoding process, even able to overcome some pitfalls with high-field mri. finally, the topics of an optimal field strength has always been highly controversial because the contrast mechanisms, on which the diagnostic information is mainly founded, are essentially field-dependent. basically, the contrast mechanisms tend to be dominated, respectively, by macromolecular cross-relaxation at low field, and by susceptibility-weighted diffusion at high field. an emerging question is then to address different pathologies or organs with either general-purpose or dedicated mri systems. learning objectives: . to learn about the possibilities of gaining a jump in signal. . to understand the respective strategies of field increase and coil improvements. . to consider the probable system in . will new technologies allow a jump in sensitivity? j. hennig; freiburg/de (juergen.hennig@uniklinik-freiburg.de) imaging technologies have made breathtaking progress for several decades and in all aspects of medical imaging -mr, ct, us and pet. amongst the current developments in mri there are several areas which hold promise to redefine the boundaries of sensitivity. ultrahighfield mri with field strengths of t and more starts to reveal insights into tissue microstructure so far inaccessible to mr (or any other technique). this is still under intense technological development with some key issues to resolve notably safety issues related to the high radiofrequency power. the unique contrast and resolution does hold promise for highly relevant applications such as neurodegenerative disease, small vessel disease, ms and others -although definite clinical studies for a ‚killer application' are still lacking. c-hyperpolarisation of metabolites such as pyruvate, succinate, bicarbonate, etc. lead to an increase in detection sensitivity by factors of - , . finally, the development of targeted probes is progressing extremely rapidly and for all imaging modalities. most of this work is aimed at preclinical research, but the tremendous impact of the new insight in translational research promises to be of high impact for clinical application. will these technologies allow a jump in sensitivity? yes and no. image quality, contrast and sensitivity will grow significantly. the biggest impact will, however, lie in the combination of the new possibilities with other data -imaging as well as non-imaging. a true change in paradigm will only be achieved if the current parcellated knowledge about various aspects of the disease is unified into a comprehensive picture. learning objectives: . to review the recent developments in rf-coils and gradients. . to learn about the new measurements technologies. . to envision how these new tools will allow a huge gain in sensitivity. will new mr contrast probes compete with pet? s. aime; turin/it (silvio.aime@unito.it) purpose: molecular imaging is a new science that will have a tremendous impact in the development of innovative diagnostic tools. in the first stage of its enrolment, it has relied massively on pet/spect and optical imaging technologies because of the superior sensitivity of their probes. in the long-term, mri/mrs approaches may recover a central role, provided that further sensitivity improvements will be attained. high sensitivity mri probes have been designed and tested for molecular imaging applications. in the case of paramagnetic based systems they rely on improved design of the coordination cage as well as on the encapsulation/incorporation in proper nanocarriers. for multiple detection studies, cest as well hyperpolarized c- containing molecules have been considered. results: as molecular imaging is the evolution of biologists' in vitro work that has revolutionized the way living cells and intact tissues were investigated, mri multiplex-visualization of biological processes appears to be a key task for the forthcoming years for an efficient translation of such outstanding achievements. the search for frequency-encoding mri contrast agents represented by cestand hyperpolarized c- containing molecules have opened the interesting perspective of detecting more than one agent in the same anatomical region. this task is largely precluded to nuclear probes. moreover merging mri and nanotechnology allows the attainment of high sensitivity systems also with the classical relaxation agents. conclusion: recent achievements in amplification procedures allow to tackle the intrinsic insensitivity of mri probes to make them more competitive in the arena of molecular imaging applications. the use of imaging to monitor response to treatment has become central in the care of patients with cancer. it is crucial therefore that radiologists involved in the management of patients with cancer understand the place of imaging within the clinical context of the management of patients with cancer; that they are aware of the criteria of the accepted current criteria for assessing response and are familiar not only with new developments in imaging that act as a surrogate end-point for evaluating the success of treatment but are also aware of how imaging is used to predict the likely response early in the patient's pathway. this session will concentrate on all these aspects on the use of cancer imaging in monitoring response to treatment in patients with cancer. we are in the era of targeted cancer therapy, whether by small molecules derived from knowledge of the molecular pathogenesis of tumours, or from biological therapies emerging from our understanding of immunology and cell biology. these approaches convey new challenges for the monitoring of response. small molecule therapeutics often stabilise tumours for significant periods without producing clear reduction of masses, and for these the assessment of surrogate endpoints takes on increasing importance. the measurement of pharmacodynamics is central to early phase trials in which confirmation of on-target effects is required to determine the biologically effective dose, and in many cases this is best done by functional imaging. biological therapeutics such as monoclonal antibodies and cellular immunotherapy also need novel approaches for the determination of their actions in vivo, particularly as they are frequently tested in the setting of low level disease. randomised trials are underway to assess the contribution of functional imaging, in particular ct-pet as a means to guide therapy. the emerging data suggest that there are broad variations in accuracy, both according to the disease in question and the context in which studies are performed, even before factors such as imaging quality control and standardised reporting are included. for the future, standardisation of techniques and common quality control will play a vital part in advancing our understanding in this rapidly evolving field. tas. there is regression of portions of these arches, but several remnants normally persist. any failure in this process can result in congenital anomalies of the aorta or pulmonary vessels. these anomalies can be categorised into aortopulmonary anomalies, systemic arterial anomalies, and pulmonary artery anomalies. the aortopulmonary anomalies comprise truncus arteriosus, hemitruncus arteriosus, aorticopulmonary window, patent ductus arteriosus, and transposition of the great arteries. the systemic arterial anomalies include the anomalies of the aortic arch, of which the most common is a left aortic arch with aberrant right subclavian artery. double aortic arch is the most common cause of a vascular ring and is characterised by left and right aortic arches arising from the ascending aorta and encircling the trachea and oesophagus. a right aortic arch can have three "subtypes": aberrant left subclavian artery, mirror image branching, or isolated subclavian artery. the first type is the most common one and is the second most common cause of vascular ring. aortic coarctation, pseudocoarctation and interruption of the aortic arch are other systemic arterial anomalies. the most important pulmonary artery anomalies are idiopathic dilatation of the pulmonary trunk, absence or proximal interruption of a pulmonary artery, pulmonary arterial stenosis, and pulmonary sling. cardiovascular magnetic resonance (cmr) imaging has become integrated into the assessment pathways for congenital heart disease in both paediatric and adult patients. cmr provides a powerful tool, giving anatomical and haemodynamic information that echocardiography and catheterisation alone do not provide. extracardiac anatomy, including the great arteries, systemic and pulmonary veins, can be delineated with high spatial resolution. vascular and valvular flow can be assessed, shunts can be quantified, and myocardial function can be measured accurately and with high reproducibility, regardless of ventricular morphology. finally, cmr surpasses both catheterisation and echocardiography in providing high resolution, isotropic, three-dimensional ( d) datasets. this allows for reconstruction of data in any anatomical imaging plane, giving complete visualisation of complex congenital cardiac anomalies, without the use of ionising radiation. in the congenital heart disease, cmr can be justified for any patient in whom clinical or echocardiographic data are insufficient for monitoring, decision-making or surgical planning. due to the complexity of both the anatomy and physiology of congenital heart disease, it is essential to have a systematic approach for cmr when assessing these patients. with the development of novel ct scanners, especially the dual source ct, novel strategies of examining congenital heart disease became possible. especially newborns and infants younger years of age are difficult to examine, since compliance cannot be expected. also young children are especially susceptible to ionizing radiation and should be exposed as little as possible. in a first step the course will illustrate the underlying technical principle how to examine children in < sec with sub msv exposure. also the course will teach how to avoid sedation in children of any age. in a second step the course will show how to apply contrast media in children of all ages and what strategy to use. in a third step the course will show how to appropriately choose scanning parameters for the ct scan since the size and weight varies considerable in children as there are small to date newborns with < kg body weight up to adolescents with a body weight > kg. since little comprehensive data is available how to examine with an optimal compromise between sufficient image quality and unnecessary radiation overexposure the data of the erlangen study will be presented and discussed. in a forth part typical indications for the exam are shown and how to interpret the exam. also limits for the exams are shown. in a final step a comparison with mri is shown which method is used for which pathology. in this session contrast-induced nephropathy and nephrogenic systemic fibrosis will be discussed. measures to reduce the incidence these adverse effects will also be presented. the pathophysiology of cin is complex and not well understood. basically, a misbalance between vasodilatation and vasoconstriction takes place inside the kidney after intra-arterial or intravenous cm administration. furthermore, increased oxygen demand of tubular cells due to increased reabsorbtion of sodium and water is a second mechanism, leading to transient medullar ischaemia. identifying the patient at risk is the first step in prevention. knowledge of the patient's medical record and a recent basic kidney function are mandatory. high-risk patients should receive prevention. two major topics in cin prevention are the questions whether iso-osmolar cm cause significantly less cin than low-osmolar cm and whether hydration schedules with nahco give significantly less cin than hydration schedules with nacl . %. currently up to % of all mri examinations worldwide are performed using contrast agents, either an extracellular agent or an organ-specific agent. the extracellular mri contrast agents are chelates that contain the paramagnetic ion gadolinium which strongly affects the relaxation properties of water protons, leading to changes in tissue contrast. gd-dtpa was the first extracellular agent to be introduced in clinical practice. since the introduction of gd-dtpa in , various gadolinium chelates with different chemical properties became available for clinical use. for many years, it was believed that gadolinium-based contrast agents (gbca) a s c b d e f g principles in the use of conventional/anatomic imaging for response assessment l. schwartz; new york, ny/us (lschwartz@columbia.edu) the standard way to assess a patient's response to chemotherapy is to use computed tomography (ct) to measure tumour size using uni-dimensional (recist) or bi-dimensional (who) criteria. this methodology has changed little in the past years despite the emergence of new therapies and advances in imaging technology. measuring the changes in the size of tumours in one or two dimensions does not always capture the effects of novel therapies on primary tumours and metastases. radiographic changes in the size of tumours treated, for instance, with epidermal growth factor receptor tyrosine kinase inhibitors such as gefitinib or erlotinib or inhibitors of angiogenesis such as bevacizumab do not necessarily occur at the same magnitude or speed as observed in those individuals treated with standard cytotoxic therapies. with these newer agents, tumours respond by undergoing cystic change, central necrosis, and density changes that may not be captured by conventional measurements of the largest lesion diameter. learning objectives: . to understand and appreciate the use of conventional/anatomic imaging for response assessment in clinical practice as well as in clinical trials. . to understand general and disease-specific challenges associated with response assessment at imaging. . to recognise potential improvement in imaging and image post-processing for response assessment. pet in monitoring response w. weber; freiburg/de pet imaging and specifically pet/ct with the glucose analogue fluorodeoxyglucose (fdg) has been evaluated in a significant number of studies to monitor tumour response in patients undergoing chemotherapy, radiotherapy or targeted therapies. the clinical value of for differentiation of residual or recurrent viable tumour and therapy-induced fibrosis or scar tissue has been established for malignant lymphomas and various solid tumours. furthermore, there are now several reports suggesting that quantitative assessment of therapy-induced changes in tumour fdg-uptake may allow prediction of tumour response to chemotherapy and targeted drugs very early in the course of therapy. in non-responding patients treatment may be adjusted according to the individual phenotype of the tumour tissue. current studies investigate whether fdg-pet can be used to "personalise" treatment and to reduce the side effects and costs of ineffective therapy. in addition to fdg, several other imaging probes are in clinical studies to monitor tumour response to therapy. these include among others [ f]fluorothymidine (flt) for imaging of cellular proliferation, [ f]fluoromisonidazole for assessment of tumour hypoxia and radio-labelled rgd-peptides for angiogenesis imaging. preclinical and early clinical trials with these imaging probes are encouraging, but need to be confirmed in larger clinical trials. learning objectives: . to understand how image acquisition and reconstruction influence visual and quantitative analysis of pet studies. . to describe current criteria for assessing tumour response in lymphoma and solid tumours and recognise the limitations of these criteria. . to understand how differences between scanner models can influence response assessment by pet. panel discussion: why does the radiologist need to understand the importance of monitoring response and how it is done? : monitoring the response to treatment has become a critical part of the management of patients with cancer. the markedly improved diagnostic performance of crosssectional imaging in delineating the extent of malignancy has meant that imaging has become increasingly important as a surrogate end-point. these two factors have resulted in an increasing need for a standardisation of the criteria of response both in therapeutic trials and in clinical practice. it is vital that all radiologists imaging patients with cancer are familiar with the limitations, pitfalls and strengths of these changing criteria and also are aware of the possibility of using imaging to evaluate the changing molecular make-up of the cancer. stent-grafts is steadily increasing. therefore, knowledge of this treatment option is fundamental to provide basis for procedure planning and a meaningful radiological reporting. imaging plays a crucial role in the assessment of patients with aortic aneurysms. eligibility for endovascular treatment depends very much on detailed anatomical knowledge of the aorta, its branches and vascular access through the iliac arteries. we will review the role of imaging modalities: us, ct, mr for detection and evaluation of anatomy of thoracic and abdominal aneurysms. the strength and weakness of each modality will be reviewed and inclusion criteria for endovascular aortic aneurysm repair will be presented. the precise sizing of the stentgraft obtained from the images is certainly one of the most critical points of the endovascular procedure and a condition of its success. although it is a minimally invasive treatment it is associated with complications. there is a strong need for general radiologists to know about the most prevalent normal and abnormal findings of the post-treatment aorta. the session will end with discussion addressing the central role of imaging in pre-and post-treatment evaluation of the patients with aortic aneurysms. indications for and experience with placement of endovascular stent grafts in the thoracic aorta are still evolving. recent advances in imaging technologies have drastically boosted the role of pre-procedural imaging. the accepted diagnostic gold standard, digital subtraction angiography, is now being challenged by the state-ofthe-art computed tomography angiography (cta), magnetic resonance angiography (mra) and trans-oesophageal echocardiography (tee). among these, technological advancements of multidetector computed tomography (mdct) have propelled it to being the default modality used, optimising the balance between spatial and temporal resolutions and invasiveness. mdct angiography allows the comprehensive evaluation of thoracic lesions in terms of morphological features and extent, presence of thrombus, relationship with adjacent structures and branches as well as signs of impending or acute rupture, and is routinely used in these settings. in this presentation, we review the current state-of-the-art radiological imaging for thoracic endovascular aneurysm repair (tevar), especially focusing on the role of mdct angiography. after analysing the technical aspects for optimised imaging protocols for thoracic aortic diseases, we will discuss pre-procedural determinants of candidacy, and how to formulate interventional plans based on cross-sectional imaging. the purpose is to present the essential principles of endovascular repair of abdominal aortic aneurysms (evar). abdominal aortic aneurysms (aaa) larger than . cm should be treated. inclusion criteria for evar include satisfactory aneurysm neck morphology and suitable access vessels. preprocedural imaging involves cta from the diaphragm to the femoral arteries. several devices may be used to cover a wide range of anatomy. evar procedures are generally performed as combined procedures by teams of vasculr surgeons and interventional radiologists. patients are followed up indefinitely by cta (or ultrasound) and plain radiography. the periprocedural mortality is three times lower compared with surgery. late mortality rates are similar between surgery and evar. quality of life issues favour evar in the short and medium term. early published series reported high complication and reintervention rates for evar, although these have reduced with increased experience and improved device technology. gene-reporter imaging has been used to monitor cell-based therapies in neurology. one of the most promising applications of molecular imaging principles is the targeting of amyloid deposition in the patients with alzheimer's disease. it is hoped that early diagnosis of the neurodegeneration may lead to better therapies. the advent of hybrid-imaging will be associated with the need for multimodal contrast agents exploiting the imaging characteristics of the involved instrumentation for more differentiated visualisation of structure, physiology, and biology. learning objectives: . to understand the working mechanism and radiation of current clinical tracers. . to become familiar with the potential clinical indications and applications. . to learn about potential new tracers. panel discussion: what specific precautions are mandatory in order to guarantee contrast media safety to patients and healthcare professionals? : current contrast agents are safer than previous products. however there are still safety aspects to consider, including patient's kidney function, thyroid metabolism, allergy, radiation exposure, or specific medical history, and there is no such thing as total or complete safety. while these simple precautions may appear obsolete in the era of sophisticated technical approaches, these issues are still quite complex and crucial in maintaining a high safety level. the discussion will give guidelines and tips for achieving a high level of safety when using contrast agents. room q the abc of evar magnetic resonance imaging (mri) is the best tool to explore white matter disorders (wmd), including the most common demyelinating disease: multiple sclerosis (ms). the formation of demyelinating lesions is related to an "inflammatory attack". new techniques as diffusion tensor imaging (dti), perfusion weighted imaging and uspio enhancing can explore earlier and more specifically lesions formation. acute demyelinating lesions may resolve (remyelination) or persist as "chronic black holes". chronic demyelinating lesions lead to axonal injury and wallerian degeneration. a diffuse neurodegenerative process leading to cerebral atrophy is actually a major landmark in ms. conventional mri sequences allows visualisation of white matter lesions (seen as hyper t /flair lesions, low signal t lesions and possible gadolinium contrast enhancement), presently the basis of ms diagnosis. ms follow-up is usually clinic but imaging could provide prognosis and therapeutic parameters ("surrogate markers") even if disease progression and axonal loss are independent from "lesion load". mr spectroscopy, dti or magnetization transfer imaging (mti) provide measurement of diffuse tissue damage in clinical research, and may correlate to disease progression, as well as brain volume measurement. after exclusion of alternative diagnosis (mri "red flags" as other wmd), mri lesions dissemination in space and time criteria are the main points in ms diagnosis. the widely used revised mcdonald criteria may be replaced by more simple and efficient magnims criteria. such criteria could allow starting "modifying disease treatments" as soon as the first "clinical isolated syndrome". since blood oxygenation level-dependent (bold) signal changes have been observed using mri and modulated using neuronal stimuli, functional mri (fmri) has quickly become the most popular non-invasive functional neuroimaging technique in clinical practice and cognitive neuroscience. indeed, high-field mr scanners and bold-sensitive sequences are now widely accessible in both clinical and research settings. bold signal that relies on deoxyhaemoglin concentration is detectable without injection of external contrast media. the colourful activation maps combined with three-dimensional brain anatomy may have also made this imaging method as much attractive as controversial. numerous applications of fmri have been suggested in medicine. after a -year long history in clinical practice and thousands of scientific papers even in prestigious journals, the role of fmri remains mostly dedicated to map eloquent cortex before a neurosurgical procedure. in fact, bold fmri is challenging because the relationship between the neuronal response to a stimulus and the activation blobs relies on neurovascular coupling, haemodynamic response, mr signal detection, and complex time-series analyses. besides an obvious and partially elucidated complexity, and several concerns on the interpretation of experimental paradigms in cognitive neuroscience, fmri is based on a robust physiological and physical framework. bold signal is reproducible across subjects and mr scanners. fmri requires a rigorous methodology to acquire and analyse data, an advanced knowledge in sulcogyral and functional neuroanatomy to estimate spatial displacement and reorganisation in patient with focal lesion, and a solid experience in bold imaging to distinguish artefacts and potential confounds from appropriate results. learning objectives: . to know the key points of quality in fmri. . to know the main pitfalls in fmri interpretation. . to learn more about advances in fmri of brain perfusion. a- : the role of imaging in follow-up k.a. hausegger; klagenfurt/at (klaus.hausegger@lkh-klu.at) the goal of surveillance after evar is to prevent late rupture eurysm. high pressure els (type i and type iii el) are risk factors for late rupture therefore have to be treated. type-ii, iv and type v (endotension) els are low pressure els with a low rupture risk. thus, it is essential not only to detect els but also to classify els correctly. until recently stent graft surveillance has been performed with contrast enhanced multislice ct (msct), typically , , and months after evar and thereafter in yearly intervals. however, although msct proved to be a very effective in fu cumulative radiation exposure, repetitive contrast medium load and increasing work load have to be seen critically. therefore, alternative surveillance protocols especially including ultrasound have been evaluated. several studies have shown that a risk-adjusted follow-up regime might be most efficient. patients with low risk of aneurysm-related mortality after evar have a normal -and -month msct scan and sack shrinkage at months. in these patients regular contrast enhanced us in yearly intervals have been proven to be safe for further fu. a one yearly non-enhanced low-dose ct or a plain film may be recommended to detect distortion or migration of the stent-graft. patients with a persistent type ii el after one year need to be followed more closely and imaging modality is chosen depending on the character of the el. in most cases el classification can be made correctly by msct or us; however, sometimes dsa may be needed. panel discussion: the key role of imaging in endovascular aortic aneurysm repair : many patients with aortic aneurysms are currently treated endovascularly. therefore the number of patients imaged pre and post-procedurally is increasing. radiologists evaluating aortic aneurysms with different modalities should know the key imaging features to look for in pre-treatment as well as follow-up examinations. j.-p. pruvo; lille/fr (jppruvo@chru-lille.fr) neuroimaging is one of the fields of radiology with the most exciting recent advances. moreover, these advances show dramatically important clinical applications. some are useful for the specialised neuroradiologist, but most are critical for the general radiologist as well. in this session, we will try to address some of the most relevant issues: white matter disorders are common diseases. expertise of the radiologist is important in detecting the disease, and in the evaluation of the activity after treatment. with this respect, standardisation of criteria is desirable for appropriate medical decisions. functional imaging is a fascinating insight into the human brain. it opens new horizons and has found many applications in the evaluation of psychiatric diseases, and in the planning before treatment of brain lesions, among other potential applications. although it is obvious that we ignore much more than we know, this field is already one of the most exciting topics in neuroradiology. although these methods are still in the field of specialists, everybody should be aware of the possibilities of functional imaging of the brain and its recent developments. stroke is by excellence a clinically relevant problem. because it is an emergency situation, time really matters, and we have more than one imaging tool to explore these patients, it is mandatory to provide strong recommendations and guidelines for the radiologist, in accordance with the clinical situation and with the treatment options. at the end of this session, the attendees will be aware of important advances in the domain of neuroradiology, and will take home very important landmarks for their own clinical practice. jaundice is rare in children but imaging has a major role to establish the cause which differs according to age. in the neonatal period the leading cause is biliary atresia (ba) which consists of the obliteration of the extrahaepatic bile duct (bd) without dilatation of intrahaepatic bd and requires urgent surgical treatment to reduce the need for liver transplantation. ba must be considered when there are persistent white acholic stools and firm hepatomegaly. us shows the absence of dilated bd and in a few cases a cyst at the porta hepatis or findings of the splenic malformation syndrome, but often it is not conclusive. mrcp has not yet proved to be reliable for the diagnosis of ba. other neonatal cholestases include medical intrahepatic causes which can be identified by biological tests or histological findings and rare causes of extrahepatic obstruction with dilated bd such as lithiasis, choledochal cyst or spontaneous perforation of bd. in childhood, us easily identifies all causes of extrahepatic obstruction by showing dilated bd; the main causes include choledochal cyst (the most frequent congenital malformation, defined by an abnormally long common bilio-pancreatic channel), cholelithiasis, tumoural compression, sclerosing cholangitis, portal vein obstruction, postsurgical or posttraumatic stenosis… in all these cases, in our experience, mrcp has become the modality of choice and has replaced invasive procedures which are nowadays reserved for treatment. mdct may be useful in rare instances, for example, to differentiate calculi and aerobilia after surgery. imaging protocols and illustrative cases will be presented. neonatal bowel obstruction generally presents within hours of birth. the diagnosis of bowel obstruction is clinical but imaging is vital to determine the cause. the plain radiograph will distinguish upper from lower intestinal obstruction. the radiograph alone is diagnostic in duodenal atresia and jejunal atresia and the baby may be taken directly to surgery. if the radiograph shows multiple dilated loops of bowel, more than loops, then the obstruction is distal ileal or colonic. the radiograph may give some clues as to the possible cause, such as a large fluid level in the dilated loop proximal to an atresia. contrast enema, usually with low osmolar water soluble contrast, is used in most cases, however, to determine the cause of lower intestinal obstruction because the management of this is different for different causes of obstruction. meconium ileus and ileal atresia are the commonest ileal causes of obstruction and hirschprung's disease and meconium plug syndrome are the commonest colonic causes of obstruction. colonic atresia is rare and imperforate anus is a clinical diagnosis. radiologically guided reduction is used to treat meconium ileus. intestinal obstruction in the older neonate may be due to volvulous, pyloric stenosis, duodenal stenosis or omphalomesenteric band. in the baby born prematurely, obstruction may be caused by stricture secondary to necrotising enterocolitis. radiographs and contrast studies are also used to evaluate these conditions. learning objectives: . to learn about the most common causes of neonatal obstruction. . to understand the role of plain radiography in establishing the diagnosis. . to know when upper and lower gi contrast studies are indicated and the contrast medium used. stroke around the clock: will the challenger (ct perfusion) beat the champion (diffusion mri)? in patients admitted for a suspected stroke, time management is the most important criterion for therapeutic decisions. less than four hours and a half, all patients admitted in emergency for an acute neurological deficit without impairment of consciousness (nih < ) and presented with a brain ischaemia of less than one third of the territory of the middle cerebral artery should receive iv thrombolysis. brain imaging must exclude bleeding and quantify the extent of ischaemic damages. between . and hours after onset of symptoms, intravenous thrombolysis and/ or intraarterial mechanical or chemical thrombolysis may be indicated in selected cases. the assessment of ischaemic penumbra and vessel permeability is particularly important for the therapeutic decision. this may be evaluated either by mri or ct. mri is the technique of choice that should be used whenever possible because of the absence of irradiation and iodine-related side effects, the optimal anatomical coverage, the detection of lacunar infarct and its sensitivity for evaluating ischaemic brain damages of the posterior fossa. imaging protocol should include flair (fluid attenuated inversion recovery), t *, diffusion/perfusion and mr angiographic sequences. in case of unstable patient or if mri is not available, a non-contrast ct scan must be performed and completed by perfusion ct and ct angiography. the main advantages of this technique are the short time of data acquisition and the absolute quantification of perfusion due to the linear relation between attenuation and concentration. pneumonia is a common cause of attendance to hospital. chest infections in children are usually viral and self limiting, but sometimes chest infections can be prolonged or repeated. there are many underlying causes for this, for example, congenital anatomical causes, underlying patient susceptibility, inhaled foreign bodies and unusual organisms. one of the more common causes seen in hospital is when pneumonia has become complicated by empyema. very rarely other conditions such as kawasaki's disease or tumours can masquerade as pneumonia. this session will review these conditions together with the benefits and limitations of plain radiography. it will also consider times when other imaging modalities such as ct and ultrasound can help to guide diagnosis and treatment. in children, congenital heart disease (chd) is more frequent than acquired heart disease. diagnosis and subsequent management of patients with chd relies heavily on different and often multiple complementary imaging modalities. serial assessment of the morphology and function of the heart and thoracic vessels is needed at various stages of care. although chest radiography is frequently used for monitoring the cardiorespiratory status and complications that may arise during clinical care or intervention, it rarely provides a complete diagnosis. echocardiography, as first line imaging modality, often provides all information required for diagnosis and follow-up, especially in small children with good acoustic windows. contrastenhanced computed tomography (ct) and magnetic resonance (mr) imaging are valuable for detailed three-dimensional evaluation of the extracardiac vasculature and cardiac anatomy. in addition to being radiation free, mr has the advantage to provide both morphologic and functional information with the use of different techniques including ecg gated gradient-echo cine imaging, gadolinium-enhanced angiography and velocity-encoded phase-contrast imaging. a comprehensive mr evaluation including quantitative measurements of ventricular volumes and function as well as blood flow in vessels and across valves can give important information on long-term sequelae of the underlying cardiac defect, the significance of residual lesions, and potential complications of surgery. it is also valuable for planning and timing of future interventions. today, ct and mr have become the next line of investigation when echocardiography does not provide sufficient information, while catheter angiography is reserved for the assessment of coronary arteries, measurements of pulmonary vascular resistance and interventional procedures. over the past years, diagnostic imaging has witnessed a veritable explosion in the modalities available for studying patients. when applied to the study of the thorax, they contribute to earlier detection of abnormalities and greater diagnostic accuracy. yet, the conventional radiographic examination of the chest continues to be the most commonly performed imaging study and, when properly interpreted, continues to demonstrate a wealth of information. for a correct interpretation of the chest radiograph, several premises should be met by the radiologist: a proper knowledge of the anatomy and semiology of the thorax, stressing the need for a lateral projection, understand the importance of reviewing previous studies and try to avoid unnecessary cross-sectional studies. this lecture will address the radiological approach to imaging children of all age groups presenting with cough. this is a common symptom with very diverse causes, from acute viral infection to complex vascular and intrinsic congenital tracheal anomalies and can be the presenting symptom of acute (rapidly fatal if not managed adequately) and chronic effects of foreign body aspiration. the various causes of cough vary with age and whether cough is acute, sub-acute or chronic. this has effects on radiological investigations deployed, and thence on subsequent clinical management. we will present a pragmatic approach to radiological investigations in this diverse set of patients, using simple algorithms and illustrate the more important (and often rarer) causes of cough with discussion around deployment of examinations that are fit for purpose using alara principles. guidance on imaging algorithms and ct technique will be given to children with this important presenting symptom of myriad diverse pathological processes. the attendee will learn the value and optimal use of imaging with tips on optimising ct technique as fit for purpose. learning objectives: . to learn about the differential diagnoses in the very young child and in older children. . to learn which imaging modalities best help to determine the final diagnosis in the various age groups. . to understand radiation protection requirements in chest ct examinations. clinical examples of dual energy ct l.s. guimarães; viseu/pt (luis.s.guimaraes@gmail.com) dual energy (de) computed tomography (ct) allows the discrimination of different materials, which has several clinical applications. the ability to differentiate calcium from uric acid renal stones allows the identification of patients that will benefit from drugs that alkalinise urine. a musculoskeletal application of the same technique is in tophaceous gout, where the crystals can be differentiated from bone. postprocessing of ct angiography images can be facilitated using de techniques to identify and remove the calcium signal. such an approach removes both bones and calcified plaques. "virtual non-contrast" images can be obtained by identifying and removing the iodine-containing voxels of contrast-enhanced ct images, simulating non-contrast images and potentially eliminating the need for some non-contrast acquisitions, but it should be realised that small misclassifications could result in missing tiny caliceal tip stones, for example. dect also allows the utilisation of low energies without the prejudice of unacceptable noise. since iodine signal is significantly higher at low energies, disease conspicuity can be improved. this is particularly beneficial in the liver (for hepatocellular carcinoma identification), in the pancreas (for visualisation of hypo-and hypervascular lesions), and in enterography (to increase the identification of hyperenhancement). the approach for displaying the enhanced iodine signal may be one of blending information from the two energies (into a single grey-scale image), or via an iodine-only view. further validation of dual energy techniques and their limitations is needed to understand the patient populations in which such techniques can be utilised and where conclusions based on dual energy data can be trusted. ct perfusion imaging is a quantitative technique that employs rapid sequences of ct images after bolus administration of intravenous contrast material to measure a range of physiological processes related to the microvasculature of tissues. ct perfusion parameters can provide surrogates for tissue hypoxia as well as the physiological processes such as vasodilatation that represent vascular responses to hypoxia. although the basic techniques for dce-ct have been available for decades, more recently a range of technological advances have contributed to the greater applicability of perfusion ct in the clinical environment including wider ct detectors, shorter gantry rotation times, 'table-toggling', radiation dose reduction and software corrections for image mis-registration due to respiratory or other patient motion. consensus guidelines are now available for the acquisition and processing of ct perfusion studies for the brain and body. to date, the main applications of ct perfusion imaging in stroke have been the confirmation of stroke diagnosis and extent, identification of penumbra and selection of patients for thrombolysis. the main applications in oncology have been in lesion characterisation, risk-stratification and assessment of treatment response. computed tomography (ct) systems have provided three-dimensional (x, y, z) data since their clinical introduction in the s. this session will address the extension of ct imaging into the fourth and fifth dimensions. the rapid acquisition capabilities of modern ct scanners open the door to the fourth dimension -time -where a time-course ct scan can provide clinical information about blood flow, perfusion and other physiological measures regarding organ function. the door to the fifth dimension -energy -is opened by dual energy image acquisition techniques, which are made possible by dual source ct scanners or rapidly switching x-ray source ct scanners. dual energy ct images can be manipulated to provide quantitative information with regard to the elemental composition of tissues, which, in turn, can be used to differentiate between bone and iodine contrast, with many other applications possible as well. modern ct scanners now provide multidimensional data sets characterised as i (x, y, z, t, e), and the additional information provided by these five-dimensional data sets provide genuinely useful clinical information which add to the diagnostic potential of computed tomography. x-ray computed tomography (ct) usually measures the attenuation of the patient or object cross-section in question at a fixed chosen voltage value; the result is presented as the linear attenuation coefficient µ expressed in hounsfield units (hu). dual energy ct (dect) acquires data at two different mean energies and evaluates the differences in attenuation. dual energy ct imaging has been a topic since the s. the acquisition modes have changed over the years from two separate scans at different voltages to single scans with rapid kv-switching, and dual source ct operating with different voltages and pre-filtrations. these concepts will be explained in detail including future options of energy-discriminating detectors. the basic physics principles remain the same for all acquisition schemes. the two independent measurements allow separating two tissue characteristics contributing to attenuation. for example, low and high effective atomic number material densities can be determined in the so-called basis material decomposition. arbitrary combinations such as monoenergetic or electron density and effective atomic number images can then be provided. these will be illustrated and explained by examples such as differentiation between plaque and contrast agent or virtual unenhanced abdominal organ imaging. dect meanwhile offers quite a number of accepted clinical applications which will be covered in a separate talk. ous lesions (adenomas) and curable early-stage cancer, screening for crc has high potential for reducing incidence and mortality of the disease. nevertheless, the benefit of population-based crc screening needs to be weighed against potential risks, psychological distress and required resources since only a minority of the population develops the disease and may thus benefit from screening. several industrialised countries offer faecal occult blood testing as a primary screening tool, with positive test results being followed up by colonoscopy. some countries, such as the united states and germany, also offer colonoscopy as a primary screening tool. while the results of randomised controlled trials regarding screening colonoscopy are still outstanding, there is evidence from observational studies that support its effectiveness in population-based crc screening. recent evidence suggests that colonoscopy, when performed in the community setting, is more effective in protecting from neoplasms in the left colon and rectum than in the right colon. decision-analytic models support the (cost)-effectiveness of screening colonoscopy but results vary, among others, according to compliance, (country-specific) cost estimates and screening schedules. learning objectives: . to learn about the incidence and prevalence of colorectal cancer and its precursors in the target population of screening. . to understand the rationale for colorectal cancer screening. . to become familiar with estimated (cost) effectiveness of colorectal cancer screening when using optical colonoscopy as a primary screening tool. facts from the statistician (true for once?): how accurate is ct colonography the issue of diagnostic accuracy of ctc for crc and polyps has been debated for a long time, because of the conflicting results published in the literature. those results led researchers to design three important studies: two large, multicenter trials testing the performance of ctc in comparison with cc in asymptomatic individuals (acrin and impact) and one randomised, double-arm trial (siggar) conducted on symptomatic patients with the aim to detect crc. both the acrin and impact reported per-patient sensitivity of % for polyps > mm and - % for polyps larger than mm; per-patient specificity was extremely high, over %, independent of lesion size. the major drawback of the acrin was represented by the poor positive predictive value (ppv) ( % for polyps ≥ mm); a definitely better ppv was documented in the impact trial ( % for lesions larger than mm) as well as in studies obtained in high-experienced centers. however, the negative predictive value in both the acrin and the impact was rather high, approaching %; this is extremely important in order to reassure negative patients about the significance of the examination. excellent results were also obtained in the munich colorectal cancer prevention trial, a single-center study where around asymptomatic subjects underwent low-dose ctc in comparison with other screening tests (cc, sigmoidoscopy and fobt). despite the good results there are still some open issues: the significance of diminutive (< mm) polyps, the management of intermediate ( - mm) lesions and the detection rate for non-polypoid, flat lesions. colonoscopy is a very useful and important method to examine the colon. in recent years virtual colonoscopy has become a popular alternative to optical colonoscopy. disorder of the colon includes colorectal cancer, which is one of the most common cancers worldwide and presents a threat to life since the mortality is almost %. colorectal cancer screening has been shown to be an efficient method to find early forms of colorectal cancer and also to reduce mortality in this disease. in this session we will discuss the various methods used to examine the colon, how useful they are and the economy behind using them. facts from the epidemiologist: incidence, prevalence, rationale for screening, standard results of optical colonoscopy. colorectal cancer (crc) is the third most common cancer in the world, with about million new cases and more than . deaths per year. incidence of crc strongly increases by age and is higher in men than in women. the lifetime risk differs between countries and is about % in the united states. because most cases of crc develop from removable precancer-stabilisation complex system a dual echo t /dp sequence could be performed in a sagittal-oblique plane drawing an imaginary line which on an axial image used as reference plane, is done perpendicular to popliteous tendon. gradient echo (ge) sequences are useful in cartilage and traumatic pathology. t -weighted sequences understimate cartilage thickness since cortex and cartilage have the same signal. pd sequences may have the similar signal for cartilage and adjacent joint fluid, obscuring defects; fat suppression solves this. if available, acquisitions performed in orthostatism could give further information in the assessment of meniscal and patello-femural pathology. learning objectives: . to understand the influences of patient positioning, scan parameters and magnet/coil technology on image quality. . to learn how to optimise scan protocols to maximise patient throughput without compromising diagnostic quality. . to recognise how and when to modify scan protocols to answer specific clinical questions. this talk will review appearances of normal anatomic variants identified at mri of the knee including discoid meniscus, transverse meniscal ligaments meniscal flounce, ossicles, and pseudotears. subsequently the talk will focus on diagnostic pitfalls reflecting both imaging technique and variations in anatomy such as the effect of motion, imaging plane and anatomic variations in patella shape. mri of the knee is one of the most frequent performed investigations, thus indicating that common abnormalities need to be familiar to the general radiologist. a simple and straightforward method of enabling assessment of clinically relevant anatomical entities is based upon a (pre)structured radiology report. use of speech recognition facilitates implementation of pre-structured reporting in a kiss manner. since one now is enabled to structure the report, using digital tools, terminology used should be discussed between the reporting radiology department and the clinical partners. it is mandatory that the important message, the clinical relevance of the information that radiologists put in their report, is understood by the referring clinician in the same manner as it was meant to be. we should consider the background of our referring physician, and tailor our report, both in chosen terminology as well as detailed information. when working in a centre in which both specialised orthopaedic surgeons as well as general practitioners (gps) or sports physicians are referring for mri, each of the three needs a tailored report, especially considering advise for secondary referral: gps and sports physicians will need different approach, compared to medical specialists. also, the knowledge of terminology used should be considered. the presentation focuses on common encountered pathologies, considering common abnormalities. emphasis is given to common abnormalities, and pitfalls that should be dealt with. some sports specific entities are discussed. implication of clinical correlation is stressed. the presentation will include casebased clinical illustrations. learning objectives: . to review the imaging appearances of common abnormalities. . to understand the use of terminology to describe pathological findings. . to learn how to structure a radiological report to ensure clarity and brevity. of view and the "third eye" colonoscope are under investigation. at the moment, however, the combination of both, exact diagnostic and sufficient therapeutic action at the same time, is the reason why optical beats virtual in this particular indication. since its evolution ct colonography has been advocated as a safe well tolerated alternative to colonoscopy, particularly in the context of colorectal cancer screening. notably perforation rates are lower than those of colonoscopy and cardiovascular effects are less. however, patient preference studies have produced mixed results and it is not clear if standard ctc will increase compliance with screening. furthermore, issues over apparent inferior sensitivity for polyp detection compared to colonoscopy, need for prolonged radiologist education and radiation dose exposure have been cited as barriers to widespread implementation in a screening context. technical developments in recent years are beginning to address these issues. use of reduced laxative regimes supplemented with faecal tagging have shown good results with superior patient acceptability. software developments have also speeded up dataset analysis -notably panoramic or "virtual pathology" d views reducing or eliminating hidden areas within the colon. furthermore, computer-aided detection software is increasingly fit for purpose and good data show a positive effect on radiologist performance both in the research setting and day to day clinical practice. this presentation will review the data on patient preference and safety and highlight developments in those areas in which ctc holds advantages over conventional endoscopic techniques. discussion will focus not only on colon cancer screening but also the on data supporting ctc in older symptomatic patients who are at higher risk of adverse events during colonoscopy. learning objectives: . to review the patient safety of ct colonography and conventional colonoscopy. . to review advanced computer techniques for maximising visualisation of the colon during ct colongraphy including d visualisation methods and computer aided detection. . to review the data on ct performance with particular emphasis on patientfriendly reduced laxative regimens. . to consider patient preference data. osteoporosis, osteomalacia, hyperparathyroidism and paget's disease have conventionally been considered the disease entities that comprise metabolic bone disease. the lecture will follow this convention and discuss the imaging characteristics that suggest osteoporosis in the elderly or anorexia nervosa in younger patients by the distribution of fractures and marrow changes as well as the role of bone mineral density evaluations in osteoporosis. oncogenic osteomalacia will be discussed in the context of appropriate imaging for detecting the tumour and emphasise the basic biochemical abnormality that most radiologists should be familiar with that leads to the diagnosis. radiologists most frequently encounter hyperparathyroidism in renal osteodystrophy with over a million patients worldwide kept alive by dialysis. dialysis-induced imaging changes such as amyloid and the spectrum of findings from long-term dialysis will be shown and demonstrated. paget's disease is on the decline. its distinctive mri signal characteristics in uncomplicated cases, in contrary to most bone lesions encountered in clinical practice, will be explained. learning objectives: . to get an overview of the entities that are considered in the realm of metabolic bone disease. . to understand common, less common and rare findings. . to learn about some imaging findings that occur as a consequence of treatment. osteoporosis is of great socioeconomic impact, as approximately % of all postmenopausal women have osteoporosis in developed countries. ageing of populations worldwide will be responsible for a major increase of the incidence of osteoporosis in postmenopausal women. in , the who working group defined osteoporosis according to measurements of bone mineral density (bmd) using dual energy x-ray absorptiometry (dxa) as a bone density t score at or below . standard deviations (t score) below normal peak values for young adults. the relative risk of a fracture is between . and . for each unit decline in spine or total hip t score. due to limitations of the t-score concept a -year risk calculating tool has been developed by the who to determine intervention thresholds. fragility fractures are, however, not only related to bone mineral density (bmd). trabecular bone microarchitecture is a significant determinant of the bone's mechanical properties and is thus of major clinical relevance in predicting fracture risk. trabecular bone structure analysis can be based on images from multidetector computed tomography, high-resolution peripheral computed tomography, highresolution mri and projection radiography. advantages and disadvantages of the different methods depend on radiation, costs, availability and a reasonable time for in vivo scanning. the purpose of this refresher course is to demonstrate bone ablation. the main aim of thermal tumour ablation is to destroy the tumour using ionic movement to kill the malignant cells without damaging adjacent vital structures. multiple sources of energy have been used to induce cell death. rf energy is an electromagnetic one. radio waves emanate from the non-insulated distal portion of the electrode. heat is produced by resistive forces (i.e., ionic agitation) surrounding the electrode as the radio waves attempt to find their ground. other type of ablations (using different wave lengths) include microwave, electoporosis, laser and radiofrequency ablation is still seeking its place among bone interventional techniques. this presentation is an overview, in an area of non-vascular interventions in the spine and the appendicular skeleton. it will explain the patient selection, indication and possible approaches to a bone lesion. available material will be discussed, as well as possible combinations of them in order to yield maximum results, while reducing possible drawbacks. over the last two decades, open nephron sparing surgery has become the preferred surgical alternative to nephrectomy for treatment of patients with a single, small (< cm) localised renal mass and a normal contralateral kidney. because - % of newly diagnosed small renal masses are identified incidentally on crosssectional imaging, often in elderly patients, less invasive surgical nephron sparing alternatives have been advocated, including laproscopic partial nephrectomy and laproscopic cryoablation, for select tumours in an effort to reduce surgical mortality and morbidity while preserving renal function. percutaneous image-guided ablation offers potential advantages over surgical methods including the minimally invasive nature of the procedure, less mortality and morbidity than surgery, shorter hospital stay, and quicker recovery. local tumour control rates of up to % have been reported for small tumours. central tumours and tumours greater than cm in diameter are more difficult to successfully treat with local tumour progression occurring % of central tumours. tumours larger than cm in diameter typically require overlapping ablations and incomplete treatment can result from residual tumour at the ablation interfaces. while in some reports, local tumour progression occurred in up to % of tumours larger than cm, in contrast, others have shown that all exophytic tumours, despite their size, can successfully be treated using multiple overlapping ablations and complete treatment may require more than one ablation session. the most clinically relevant and potentially avoidable complication is ureteral injury with resultant obstruction of the intrarenal collecting system. percutaneous image-guided radiofrequency ablation (rfa) represents as a safe and effective minimally invasive procedure in selected patients with unresectable or medically inoperable lung malignancies. when adequately performed, in selected patients, the procedure is associated with over % immediate technical success rate and relatively low incidence of major ( - %) and minor complications ( - %). pneumothorax represents the most frequent complication (up to %) but presentation, the worse the outcome in adulthood. avn is a significant complication. ct/mr assists orthopaedic planning. imaging strategy: plain radiographs. small children localise pain poorly. whole limb radiographs may be needed. us detects hip effusions but cannot differentiate pus from effusion. nuclear medicine may need sedation for scanning phase. a full bladder may obscure the pelvis. mr is sensitive for soft tissue pathology and marrow disease included in the area imaged. radiographs are needed before mr, which is insensitive for bone detail. other causes: spinal problems -discitis, avulsions of muscle origins, trauma -toddler's fracture, diffuse bone disease, localised bone disease; blind areas: spine, pelvis/sacroiliac joints. learning objectives: . to learn about the imaging approach to the child with suspected developmental hip dysplasia. . to become familiar with the differential diagnosis in the older child with a limp. . to learn which imaging modalities best help to arrive at a diagnosis. skeletal injuries are the most common findings noted on imaging studies in cases of child abuse. in infants, certain lesions, such as the classic metaphyseal lesion and posteromedial rib fractures are sufficiently characteristic to point strongly to the diagnosis of inflicted trauma. other fractures are less specific for abuse, but when correlated with other imaging findings and clinical information, their presence may add strong support for the diagnosis. many of the most specific injuries produce subtle radiographic alterations, and meticulous technique, adhering to a strict imaging protocol, is vital in providing optimal detection of the fractures. in recent years, increasing attention has been given to those conditions that may simulate inflicted injury. a variety of normal variants, naturally occurring diseases and accidental injuries may be confused with the findings of child abuse. other conditions, real or hypothetical, may be suggested by consultants in medico-legal proceedings. to be credible, a witness must be prepared to counter reckless and irresponsible testimony given by uninformed or biased medical "experts". to ensure that investigators and finders of fact are provided with testimony that is clear, concise and accurate, the radiologist must be fully informed and prepared to address the radiologic alterations and their significance to a reasonable medical certainty. learning objectives: . to learn in detail the investigation of a child with suspected non-accidental injury. . to learn about the typical skeletal injuries seen on plain radiography and the differential diagnosis. . to understand when further imaging is required and which imaging modality is best. acute osteomyelitis and septic arthritis are diagnostic and therapeutic emergency in children. diagnosis remains challenging because of their variable expression (acute, subacute, chronic stages, causative agents and hosts). imaging strategy relies on a multimodality approach including radiographs and ultrasonography as first line examinations with a complementary role for bone scintigraphy and mri. mri is especially useful for misleading challenging presentations (such as axial skeleton, pelvis and calcaneus osteomyelitis) and for detection of reversible osteocartilaginous ischaemia requiring urgent surgical drainage. juvenile idiopathic arthritis (jia) is an heterogeneous group of chronic inflammatory disorders that are classified on their mode of onset (systematic, pauci and polyarticular diseases). it is a diagnosis of exclusion and imaging plays a major role in the differential diagnosis. radiographic scoring systems of jia are different from adult scoring systems with less emphasis on joint space narrowing. doppler-ultrasonography and mri play an increasing role in a the assessment of disease activity and response to treatment. learning objectives: . to learn about the imaging approach to a child with suspected osteomyelitis and septic arthritis and to outline the classical features. . to learn how best to investigate a child with suspected arthropathy and the specific findings. . to understand the differential diagnoses of bone and joint infections. semiquantitative scoring method. vertebral morphometry is based on radiographs or scans from dxa-machines calculating ratios of vertebral heights with normal values to identify vertebral fractures. great need for early, accurate and reliable imaging indicators of tumour response to anti-angiogenic drugs which is ultimately defined by overall survival rate, but is mostly based on changes in number and size of measurable tumour "targets", i.e. blood vessels. thanks to its characteristics of high temporal and spatial resolution in limited fields and lack of ionising radiation and side effects (i.e. easy repeatability), contrast-enhanced us (ceus) is currently the simplest and also most reliable imaging modality for detection, analysis and quantification of intratumoural macro-and microvascularity (up to μm in diameter). even minimal changes can be easily detected and quantified with ceus during anti-angiogenic treatments: early disappearance (or severe reduction) of tumoural vascularisation is highly predictive of complete (or significant) response even before tumour volume decreases. initial clinical studies were conducted on hypervascular hepatic metastases (e.g. metastases from gists), but recently also hypovascular hepatic metastases and primary cancers of different organs are being assessed. for the quantitative analysis of tumour vascularity changes several parameters (peak intensity, time-to-peak intensity, area under the curve, etc). are currently being investigated and specific perfusion software connected to working stations are being developed and clinically tested. the clinical application of mr-mammography (mrm) in the last years has shown that this imaging tool has had significant diagnostic advantages in the field of breast diagnosis, e.g. the proof of small breast cancers, the differentiation between scar and recurrent tumours, the detection of multifocality/multicentricity, the search for primary tumours, the delineation of implants, etc. the clinical use of mr-mammography is steadily increasing. however, many still describe a "high sensitivity but a low specificity", which is wrong. achieving a high quality is not an easy task; a lot of teachers have to be learned and considered. this refresher course is focussing on high quality concerning technical and diagnostic aspects, especially focussing the question of improving specificity. dynamic contrast enhanced computed tomography (dce-ct) is a noninvasive method showing haemodynamic changes in living tissue in various oncologic and non-oncologic applications. recently, it has gained an increased popularity for studying malignant tumour blood supply and formation of new vessels, also known as angiogenesis, that plays a critical role in the growth of cancer. technical remarks: repeated rapid ct scans are acquired at the same location to allow determination of time-attenuation curves (tac). several quantitative parameters are assessed: tumour blood flow (tbf) (ml/min/ g), tumour blood volume (tbv) (ml/ g), permeability surface product (psp) (ml/min/ g) and mean transit time (mtt) (s) are calculated using dedicated perfusion software. indication: perfusion ct may be used by the distinction of benign from malignant lesions when conventional methods are unreliable, may improve staging by demonstrating occult hepatic metastases, may guide biopsy to the tumour region most likely to be of highest grade. several tumours with higher perfusion are more sensitive to the chemoradiation than that with lower perfusion. findings at dce-ct images after chemoradiotherapy are a significant predictor of early tumour response and overall survival. its applications have been stimulated by the development of anti-angiogenesis therapy for monitoring the effects of therapy and additionally may be used as a noninvasive tool in detection of hepatic toxicity of chemotherapy. in the future, new prognostic information could impact clinical management. studying the response of cancers by measuring changes in their blood flow may provide useful information on oncologic patients for managing cancers in the future. advanced imaging is now widely utilised in the research and clinical settings. in the clinical setting, qualitative, semi-quantitative and quantitative approaches such as review of colour-coded maps to roi analysis and analysis of signal intensity curves are being applied in practice. we will also compare the relative advantages for t dce mri with t * dsc mri in the estimation of perfusion and permeability metrics in the clinic as well as some more automated histogram analysis methods. the role of advanced imaging in the characterisation of tumour biology and different pathologies will be reviewed. differentiating between recurrent tumour and therapeutic necrosis is often a challenge. we will review the role of advanced imaging and also the effects of anti-angiogenic therapies on tumour microvasculature/microenvironment resulting in changes in diffusion, perfusion and mrs. pseudophenomenon has made conventional imaging with gadolinium contrast agent almost obsolete necessitating mechanistic techniques to differentiate entities such as pseudoprogression which is seen more commonly as a result of therapy with temozolomide and radiation for high grade gliomas as well as pseudo-response and pseudo-pseudoprogression. lastly to combine and apply these different imaging techniques in a multi-parametric algorithmic fashion in the clinical setting can be shown to increase our diagnostic specificity and confidence. learning objectives: . to become familiar with different advanced mr techniques used in brain tumour imaging. . to learn the role of permeability, perfusion, diffusion imaging and mr spectroscopy in characterising brain tumour biology and differential diagnostics. . to become familiar with a complete imaging protocol, which can be implemented in a multi-parametric algorithm fashion in brain tumour diagnosis. monitoring and prediction of treatment response p.c. maly sundgren; lund/se (pia.sundgren@med.lu.se) high-grade gliomas have a poor survival rate despite improvements in surgery, radiation and chemotherapy. a contributing factor to the poor survival is the inability of currently available imaging techniques to accurately delineate the tumour which results that targeted focal treatment my not be effective. conventional imaging is not able to give an early assessment of the effectiveness of radiation and/or chemotherapy. early identification of patients with a poor treatment response or who suffer from tumour recurrence can be of great advantage: it provides the opportunity to adjust individual more rapidly, and sparing patients unnecessary morbidity, and breast mri has shown diagnostic sensitivities of - % for invasive breast cancer; however, specificities have been reported significantly lower with values between % and %. the specificity of breast mri is in a routine clinical setting based on the evaluation of morphologic features and relative "slow" dynamic characteristics of enhancing lesions. the only moderate specificity that is achieved using these characteristics can result in a significant number of false positive findings during, for instance, screening or pre-operative imaging. these findings will often require short-term follow-up, target ultrasound with biopsy or even mri-guided biopsy. fast dynamic imaging, spectroscopy and diffusion weighted imaging (dwi) have been described to have potential for improving the specificity of breast mri. the use of fast dynamic imaging sequences result in a more accurate evaluation of the initial enhancement of the lesion. in combination with pharmacokinetic modelling this can result in a more quantitative evaluation of enhancement. in proton-mr spectroscopy (mrs) the presence of a choline signal, a cell-membrane precursor, in breast lesions can be used to differentiate benign from malignant lesions. the specificity of mrs varies between and % in literature (average %). dwi has also shown potential in differentiating between benign an malignant lesions, but, like with other techniques, varying specificity values are reported ranging between % and %. in this presentation the value of these techniques for improving the performance of breast mri will be discussed. although bedside chest radiograph is one of the less elaborate imaging examinations in our diagnostic armamentarium, it remains the most frequent radiologic procedure performed in intensive care patients. despite its limitations chest imaging is an important tool in the management of the critically ill patient. though the advent of digital radiography has vastly contributed to improved image quality of the bedside radiographs, optimal positioning and technique remain a real challenge for the performing technologist. in addition, the interpretation of chest radiography in the critically ill patient poses a challenge for the radiologist, because findings are frequently unspecific and lung opacifications have similar appearances in a variety of different cardiopulmonary pathologies. clinical information and an interdisciplinary approach are therefore crucial for optimal interpretation of these chest radiographs. the american college of radiology has established expert recommendations for the use of bedside chest radiography. current recommendations suggest that routine daily chest radiographs should be reserved for patients with acute cardiopulmonary problems and in patients receiving mechanical ventilation. acquisition of a portable chest radiograph is recommended after insertion of endotracheal tubes, central venous catheters, pulmonary artery catheters, chest tubes, and nasogastric tubes. therefore, knowledge of correct positioning of catheters, tubes, and monitoring devices and of various malpositions and associated complications is essential for the interpreting radiologist. chest ultrasonography (chus) is a useful imaging tool in patients at intensive care units, because of its simplicity and reproducibility. however, there are some limitations such as low specificity of some crucial sonographic signs and limited searching area (soft tissues, pleural cavity and lung consolidations). the icu patient can be examined in supine or sometimes in lateral or partly lateral position using intercostal spaces as an acoustic window. supine analysis of the anterior chest wall rules out pneumothorax, while lateral approach detects clinically relevant pleural effusion and parenchymal consolidations. chus is a method of choice in detection as well as in characterisation and volume estimation of free and/or loculated pleural fluid. with chus we can explore and characterise lung consolidations from the moment they reach the visceral pleura. they can be in contact with pleural line or can be observed through an effusion. however, in case of subcutaneous emphysema and/or diffuse oedema of soft tissues the lung parenchyma can not be reliably assessed. also, in the question of pulmonary embolisms in critically ill patient, chus could be contributive. sometimes small pleural effusion can be visible with some peripheral lung tissue consolidations indicating minute pulmonary infarction. typical pulmonary infarction is triangular tissue consolidation with air bronchogram and absence of doppler blood flow signals within consolidated lungs but cect for confirmation is mandatory. chus exploration of the diaphragm can reliably evaluate respiratory movements since pleural effusion even substantial does not affect the amplitude of diaphragmatic excursion. learning objectives: . to understand the advantages and limitations of bedside thoracic ultrasonography. . to learn about the us findings of pleural and parenchymal diseases suitable for bedside ultrasonography. . to review current guidelines for estimation of pleural effusion volume. delay in initiation of other maybe more effective treatment. in recent years, different functional imaging approaches such as dynamic contrast-enhanced (dce) and dynamic susceptibility-weighted contrast (dsc) mri, diffusion-weighted imaging and spectroscopy have been complementary used for diagnosis and treatment response. in this lecture different advance mr and ct imaging methods as well as the traditional way of monitoring to assess treatment response will be discussed. in addition, a novel recently published promising technique will be described -the parametric response mapping (prm), a novel voxel-wise analytical method of monitoring physiological and environmental changes in a tumour volume during treatment will be presented and compared to the traditional methods used. finally, the aim of the lecture is to consolidate the present knowledge and novel ideas in brain tumour imaging for future monitoring of treatment response and the possibility and limitations for future individualisation of cancer therapy. learning objectives: . to gain an understanding of the present traditional model for the treatment cycle for brain tumours and how they are monitored. . to learn about different imaging biomarkers for early assessment of brain tumour treatment response that might result in individualisation of cancer therapy. . to consolidate present knowledge and ideas in brain tumour imaging for future brain tumour therapy and monitoring of response. radiation necrosis and pseudo-progression vs recurrent tumour pseudophenomenon has made conventional imaging with gadolinium contrast agent almost obsolete necessitating mechanistic techniques to differentiate entities such as pseudoprogression which is seen more commonly as a result of advanced multimodal therapeutic concepts. advanced, non-enhanced and contrast enhanced mr imaging techniques include mr-spectroscopy, perfusion mr imaging, dynamic contrast enhanced mri and diffusion tensor mr. in the presentation we will analyse the application of those techniques in brain tumour assessment with focus on the post-therapeutic brain to differentiate therapy induced from tumourinduced changes. the results of the available studies in literature, all with relatively limited patient numbers, indicate that the combination of functional mri proved to be useful in the post-therapeutic workup of gliomas, lymphomas and metastatic disesease. the typical patterns of tumour recurrence and the different therapyinduced effects will be presented. in perfusion (dsc-mri) and dynamic contrast enhanced magnetic resonance imaging (dce-mri) the signal intensity measurements of the tumour reflect a composite of tumour perfusion, vessel permeability, and the extravascular-extracellular space. in contrast to conventional enhanced mri, which simply presents a snapshot of enhancement at one time point, both techniques permits a fuller depiction of the wash-in and wash-out contrast kinetics within tumours, and this provides insight into the nature of the bulk tissue properties on its microvascular level. with the strong demand in drug development the identification of biomarkers that can assess tumour microvascular properties noninvasive dynamic mri is the method of choice to assess tumour response and to identify atypical tumour response findings. indications and spectrum of pathological findings functional abnormalities of the pelvic floor represent a significant health-care problem, as they affect approximately % of older multiparous women. moreover, nearly . surgeries in united states are annually performed to correct those disorders. the success of medical and surgical therapies relies on the correct classification of dysfunction and identification of the pelvic compartments involved. clinical classifications of pelvic floor abnormalities are primarily topographic, rather than functional. however, as the pelvic floor muscles tend to act as a unique functional entity, their dysfunction usually leads to dysfunction of more than one organ system (genitourinary or gastrointestinal), resulting in a wide spectrum of symptoms variably associated, including dysuria, urinary incontinence, uterine prolapse, anal or pelvic pain, obstructed defaecation, rectal prolapse or faecal incontinence. because of the variability of symptoms and complexity of physio-pathological mechanisms, diagnosis of pelvic floor disorders is usually achieved by combining different diagnostic tools. dynamic mri of the pelvic floor has emerged as an alternative and effective modality for assessing and understanding of these disorders. it currently offers a complete morphological and functional evaluation of all three compartments at the same time. constipation and pelvic organ prolapse are the most common indications for a dynamic mri. the physio-pathological features of the main pelvic floor disorders and their mri findings will be shown in detail. mr images and movies, with particular regard to posterior pelvic floor abnormalities, such as rectocele, rectal invagination and prolapse, enterocele, descending perineal syndrome and spastic pelvic floor syndrome, will be illustrated and discussed. the ability to perform and interpret dynamic pelvic floor imaging is essential for the modern gastrointestinal (and indeed urogynaecological) radiologist. the other speakers in this session will be reviewing indications, pathologic findings, clinical relevance, and mr technique. although i will detail the mr and fluoroscopic techniques used at my institution, i will focus on the specific technical and diagnostic advantages and disadvantages of both dynamic pelvic mr and conventional fluoroscopic evacuation proctography (defecography). many practitioners wising to initiate this type of imaging will wish to know what modality to chose and existing practitioners using fluoroscopy will possibly be interested in migrating their practice to mr. i will illustrate what imaging findings are best imaged by each technique, continually referencing this to whether the finding is ultimately important to the referring clinician or not. using examples from our own research programme and clinical practice, i will illustrate why we have migrated our practice exclusively to dynamic mr. although dynamic pelvic mr imaging is increasingly used for imaging pelvic floor disorders, the crucial question is whether the technique can completely replace conventional techniques. although mr imaging provides excellent soft-tissue contrast which is a particular advantage when imaging the pelvis, it has to be acknowledged, that the examination is performed in supine position and not in physiological sitting position. this presentation will review the ultrasound appearances of pleural disease in ward and itu-based patients, and will discuss the indications for pleural procedures and the complications associated with them. the use of colour doppler to aid the diagnosis of effusions will be discussed, as will the identification of septations and the need for intrapleural fibrinolytic therapy. the advantages of guided versus blind drain insertion will be presented, and the benefits of large versus small bore drains will also be discussed. pelvic floor function and structure is complex. imaging has a key role in guiding the clinician in managing patients with incontinence, constipation, difficult rectal evacuation and pelvic organ prolapse. dynamic imaging is of particular interest for assessment of the pelvic floor since this kind of imaging gives a near physiological data set of what is happening and gives us a better understanding of the multifactorial causes of pelvic floor dysfunction. whereas conventional evacuation proctography was over years standard of reference for dynamic imaging of the pelvic floor, dynamic mr imaging of the pelvic floor is gaining increasing acceptance among radiologists and clinicians. however, dynamic mr imaging of the pelvic floor is (due to the architecture of most the clinically mr magnets) usually performed in supine position which does exclude the axial load on the pelvic floor. the lack of a physiological patient positioning during dynamic pelvic floor mr imaging is still brought into discussion if dynamic mr imaging of the pelvic floor can replace conventional techniques or not. the pelvic floor is a complex anatomic and functional unit. in clinical routine a simple anatomic concept of the female pelvic floor has gained acceptance. especially for treatment planning, the female pelvic floor may be separated into three functional compartments: the anterior compartment (bladder and urethra), the middle compartment (vagina, cervix, uterus, and adnexa), and the posterior compartment (anus and rectum). intact structure of the pelvic floor is a basic prerequisite for a normal mechanism of defecation and continence. over the last years, mr imaging has gained increasing acceptance as imaging modality for evaluation of the pelvic floor, which enables a global and integrated approach to the pelvic floor. using static t weighted sequences the morphology of the pelvic floor can be visualised in great detail. a rapid half-fourier t -weighted, balanced steady state free precession (bssfp), or gradient-recalled echo (gre) sequence are used to obtain sagittal images while the patient is at rest, during pelvic squeeze, during pelvic strain and to document the evacuation process. on these images the radiologist identifies the pubococcygeal line (pcl) (which represents the level of the pelvic floor). in normal findings, the base of the anterior and the middle compartment are above the pcl at rest, and the pelvic floor elevates during contraction. during straining, although most clinical diagnostic imaging studies employ anatomic techniques such as computed tomography (ct) and magnetic resonance (mr) imaging, much of radiology research currently focuses on adapting these conventional methods to physiologic imaging as well as on introducing new techniques and agents for studying processes at the cellular and molecular levels in vivo, i.e. molecular imaging. molecular imaging promises to provide new methods for the detection of minimal changes in diseased tissue and support for personalised therapy. although molecular imaging has been practiced for over years in the context of nuclear medicine, other imaging modalities have only recently been applied to the noninvasive assessment of physiology and molecular events. nevertheless, there has been sufficient experience with specifically targeted contrast agents and high-resolution techniques for mr imaging and other modalities that we must begin moving these new technologies from the laboratory to the clinic. several projects relevant to oncology will be discussed with emphasis on how they were/will be moved from the bench to the clinic. aortic dissection is increasingly managed by endovascular means. it is important for all radiologists to understand the benefits and disadvantages of varying imaging modalities in the differential diagnosis and the fundamental anatomical requirements for assessing suitability for endovascular repair. the causes, detection, classification and complications of aortic dissection will be discussed followed by a panel discussion of imaging strategies which give the best information for diagnostic work-up, endograft planning and monitoring of patients during and after treatment. with the introduction of targeted therapeutics and personalised therapy regimen there is increasing need to improve diagnosis of diseases in a way that insight into pathophysiological and molecular regulation is provided. in this context, molecular imaging can be of tremendous help in basic research, drug development and the clinics. many interesting approaches of molecular imaging have been tried in small animal models. new methods and tools have been identified, which are easy enough to handle, aceptable in its costs and, most importantly, reliable enough to be translated to clinical practice. unfortunatenly, as soon as they have entered the clinics they are often not classified as molecular imaging anymore. among those are mr-spectroscopy, spio/uspio enhanced liver and res imaging but also contrast agents like gd-eob-dtpa and most applications for pet/spect. other interesting applications such as targeted ultrasound imaging are already established tools in preclinical research and very close to first clinical use. near infrared optical imaging is another example of a rapidly developing technology and first clinical devices and dyes (e.g. to detect arthritic lesions) are availibe now. it can be expected that with the availability of targeted and activatable probes the acceptance and the use of optical imaging methods will further rise. most proably, this will initially happen in context with intraoperative diagnosis and endoscopy. in summary, it is the aim of this talk to give a realistic overview on the available molecular imaging tools and on their potential for preclinical research and patient use. cardiovascular diseases remain the number one cause of morbidity and mortality, both in the developed and developing countries, and in men and women alike. it is expected that these numbers will continue to increase in the coming decades due to escalating proportions of obesity and the aging population. atherosclerosis is the major cause for cardiovascular disease. since in about % of cases a stroke or acute myocardial infarction is the first symptom of atherosclerosis, it is of paramount importance to identify patient at high risk. a first step in the identification is the use of clinical risk profiling, such as the framingham risk score, which has an area under the curve (auc) of about . using roc analysis. however, clinical risk profiling alone is not sufficient to identify individual patients at imminent risk to develop a cardiovascular event in the near future. a next step in a more precise identification of the patient at risk is the development of serum biomarkers for atherosclerotic disease. however, so far serum biomarkers have failed to contribute substantially to improve the auc in the prediction of cardiovascular events using roc analysis. a major step forward in risk stratification is provided by the rapid development of cardiac computed tomography, which offers a rapid visual access to the coronary tree, at low radiation dose and in a patient friendly manner. however, for the identification of the vulnerable plaque we need to go beyond anatomical imaging, and use molecular imaging tools. in the lecture i will discuss the different targets for molecular imaging within the vulnerable plaque, such as inflammation, apoptosis and angionenesis. imaging of these substrates of plaque vulnerability may offer opportunities for a precise identification of the patient at risk, at the individual level. the aim of the lecture is to familiarise the audience with the specific paediatric conditions in trauma radiology. it will be described the major pathophysiologic differences in childhood and the consecutive altered injury pattern. the standard radiological imaging protocol for various involved body regions and different trauma settings/varying queries will be described, with suggestion for standardised diagnostic algorithams in some typical settings. special regard will be given to radiation protection and the potential of imaging modalities such as ultrasound, multi-detector ct as well as mri in paediatric trauma patients. the roll of the lecture is to provide some basic guidelines for young radiologists and general radiologists who less often have to deal with paediatric patients. learning objectives: . to become familiar with the major pathophysiologic differences in childhood trauma . to standardised diagnostic algorithm in some typical settings in field of pediatric trauma. basic principles in the interpretation of signal intensities on t -and t weighted images g. wilms; leuven/be (guido.wilms@uz.kuleuven.ac.be) the signal intensities of normal structures and pathological findings on conventional t -and t -weighted mr images depend on many factors. the amount of water, proton density, chemical structure and/or binding, presence or absence of flow (of blood or csf), calcification, fat, blood degradation products, melanin, mucine and even air are all factors that influence the signal characteristics. t -and t -lenghtening is the rule in most tumoural, vascular and infectious lesions and therefore is rather unspecific. t -and t -shortening can be due to the presence of fat (lipoma), melanin (melanoma and metastasis of melanoma), mucine (metastasis of sigmoid carcinoma), colloid material (colloid cyst, rathke cleft cyst) and even calcification (falx!). t -shortening with t -lengthening can be due to cholesterine (cholesterol granuloma, craniopharyngioma), high protein content (tumoural cysts), and methaemoglobin (late haemorrhage, thrombus). t -lengthening and t -shortening is almost exclusively due to deoxyhaemoglobin. acute haemorrhage and meningioma can be iso-intense on t -weighted images, while some meningiomas and micrometastases can be iso-intense on t -weighted images. absence of signal can be due to high-velocity flowing blood (aneurysm, avm, hypervascular tumours), high velocity flowing csf (normal pressure hydrocephalus, cortical bone or extensive calcification, air and a large amount of iron (coils, clips). it is concluded that the simple use of a combination of t -and t -signal intensities on conventional mr images can be used to arrive at the diagnosis and differential diagnosis of brain lesions. complications occurring after acute aortic dissections should be separated into those related to the disease per se and those related to post-treatment conditions. life-threatening complications related to the disease should be familiar as immediate consequences for treatment may ensue. most of these are either located in the aortic root or related to mal-perfusion syndromes. the aortic root with very thin walled structures of the sinus of valsalva is located within the pericardial sac. the structure is prone to rupture and may produce life-threatening pericardial tamponade or present clinically as sudden onset of severe aortic regurgitation. all imaging modalities suitable for diagnostic workup in such conditions have to be rapidly accessible and performable. this precludes lengthy mr imaging procedures and renders ultrasound and ct as the mostly used modalities. the condition that has to be recognised as the most important inductor of malperfusion syndromes in the descending aorta is the progression of dissection into aortic branches and the true lumen collapse. both conditions are easily discernible with ct imaging. complications related to treatment should be sub-classified into those after pure surgical treatment and those related to endograft repair. the acute surgical complication with most deleterious effects is related to spinal cord ischaemia. the condition also applies to endograft repair. it is therefore beneficial for the radiologist involved either in pre-surgical imaging or interventional treatment to acquire thorough knowledge of the spinal cord blood supply. endograft complications of interest encompass endoleak formations, stent migrations and endoluminal stent collapse. learning objectives: . to learn the most common complications. . to learn the most appropriate imaging strategy for diagnosis. . to understand the clinical significance of the most common complications. which imaging modality is best for endovascular management? : the various imaging modalities for establishing the diagnosis of acute non-traumatic dissections will be discussed. the panellists will present recommendations for diagnostic work-up with special respect to differential diagnosis such as acute myocardial infarction and acute pulmonary embolism. also, the problem of sizing the endograft and planning the procedure will be addressed. the panellists will discuss strategies for detection of complications and for monitoring patients following treatment. the quality of radiographs is determined by many parameters from both technical and clinical origin. during the presentation, we will make an overview of the particular features of x-ray tubes and plain films that affect the quality of the radiological image. the training session will start from very simple x-ray tubes and film, and gradually introduce more sophisticated, state-of-the-art technology. we will briefly explain concepts such as focal spot, heel effect, beam quality, filters, grid, film sensitivity, automatic exposure control, etc. from a practical point of view. the european commission and selected research groups have developed criteria to judge the quality of the images and we will show how they can be used to improve the daily practice. a more technical evaluation of quality is possible with images of test objects, some of which are very straightforward and interesting if problems have to be retrieved. x-ray quality should be at a high level every day. therefore quality control procedures have a role. one example evaluates the stability of the imaging chain by means of acquisitions of homogeneous blocks of pmma. we will illustrate typical findings with repercussions on the radiological practice, and show that the fight against artefacts is a never ending process. both with film and digital detectors, radiologists should be aware that quality management and quality control procedures are needed. quality has to be organized, and quality control procedures have to be automated and included in the routine practice. there are diverse underlying causes for "diagnostic mistakes". missed lesions due to inadequate technique, "satisfaction of search" or lack of perception have to be differentiated from interpretative mistakes of lesions that have well been seen but erroneously interpreted due to the lack of experience, misconception or overlap of findings that complicates the differential diagnosis. each of these underlying reasons require a different approach to avoid them or reduce their risk of occurrence. the first type of mistake arises more often when interpreting chest radiographs and refers to the detection of mostly small focal parenchymal densities but also to the interpretation of mediastinal and hilar contours. by analysing typical cases, visual "tricks", helpful display techniques and strategies for systematic review and analysis will be outlined that are thought to be helpful in reducing the risk of "missing" a lesion. the second type of mistake mostly represents a problem of interpreting parenchymal abnormalities seen on ct. since the lung has limited means to "react" against an injury, many radiologic findings are aspecific. interpretation of pathology of parenchymal changes is based on pattern analysis, the knowledge of disease distribution and additional findings of pleura and mediastinum. in many cases, an interdisciplinary approach of radiologists and clinicians is essential for correct interpretation. cases will be analysed to illustrate difficult differential diagnosis occuring in daily routine (e.g., infectious pneumonia versus organising pneumonia) and key features helping in going into the right interpretative direction will be outlined. emphasis will lie on focal lung disease rather on the interpretation of diffuse interstitial lung diseases. learning objectives: . to learn about visual tricks and strategies to overcome typical perception errors in chest radiography. . to become familiar with overlaps of morphologic findings of focal parenchymal lesions frequently occuring in daily routine when interpreting thoracic ct. . to recognise those additional findings that represent the "helpful clue" for correctly narrowing the differential diagnosis. panel discussion: what have we learned from our mistakes? : interpreting the results of imaging studies is more and more challenging and time consuming due to the large volume of data to evaluate, compare and post-process. moreover, errors in the interpretation of imaging studies can have significant effects on patient care, particularly in acute medicine and oncology. so the question is how to be aware of the potential pitfalls that may be encountered in the realisation and the interpretation of imaging studies and how to avoid them or to learn from them. acute pancreatitis remains a potentially life threatening condition with an overall mortality rate of %. its outcome is strongly related to a precise and timely diagnosis, a correct estimate of severity and subsequent appropriate treatment. radiologic imaging, particularly ct, plays a key role in staging the severity and therefore helps guiding therapeutic decisions. management of interstitial or edematous pancreatitis is supportive while severe or necrotising pancreatitis requires intense monitoring and specific therapies. the latter has a higher mortality and guarded prognosis, since it may lead to organ failure, infection, pseudocyst formation and extrapancreatic parenchymal and vascular complications. a number of severity indices have been established to determine the prognosis of acute pancreatitis, based both on clinical and imaging criteria. a ct-based severity index has become the main prognostic method to predict outcomes. this course reviews relevant imaging findings of various stages of acute pancreatitis and its complications by ct, including special conditions such as groove pancreatitis and autoimmune pancreatitis. currently established and modified severity indices are reviewed to learn how to estimate prognosis and guide therapy. interpreting the results of imaging studies is more and more challenging and time consuming due to the large volume of data to evaluate, compare and post-process. radiology errors are inevitable, affect all radiologists and may be defined as a mistake that has management implications for the patient. errors can be broadly classified into technical errors, active errors (errors in perception, judgment or knowledge) and errors of communication. the majority of errors are false-negative interpretations and occur during interpretation of ct examinations. good communication between the referring physician and the radiologist is essential. unfortunately, only a small minority of radiologists keep a personal record of their errors. patient safety should benefit from the repeat organisation of "error meetings" through the act of collective learning. radiologists and radiology departments must continue to improve the process of recording and addressing errors. a- : radiologists do make mistakes, diagnostic errors can be the cause of severe consequences to patients or, luckily, in many cases, they can be corrected. learning from mistakes is quite important since understanding why a mistake has been made help to avoid it in the future. during this lecture a series of mistakes made in the field of gu will be presented and causes which have lead to each of them will be analysed. dyspnoea is a common symptom in patients presenting to the emergency room. in almost two-thirds of all cases, dyspnoea is caused by either a pulmonary or a cardiovascular disorder. imaging in patients with dyspnoea depends mainly on the clinical presentation and the medical history of the patient. chest radiographs are a cost-effective and rapid test for the evaluation of patients with dyspnoea, with a fair sensitivity and specificity. for this reason, chest radiographs are usually performed early in the diagnostic evaluation of patients with acute and chronic dyspnoea. chest radiographs enable the diagnosis of frequent causes of dyspnoea of pulmonary origin, such as pneumonia, pneumothorax, pleural effusions, interstitial lung diseases, and emphysema. the diagnosis of cardiovascular disorders, such as pulmonary venous hypertension, cardiomyopathy, as well as valvular diseases, is also facilitated by chest radiographs. if chest radiographs, clinical studies, and laboratory tests, however, are non-diagnostic or equivocal, ct is indicated. ct offers high sensitivity and specificity for the evaluation of pulmonary embolism and for diseases of the pulmonary parenchyma and the airways. high-resolution ct represents the method of choice for the evaluation of suspected diffuse lung disease. additional expiratory scans are useful for the evaluation of mosaic perfusion and air-trapping. chronic pancreatitis (cp) is an inflammatory disease of the pancreas, with irreversible morphologic changes and fibrotic replacement of the gland, which progressively result in loss of exocrine and endocrine function. cp is morphologically characterised by irregular sclerosis associated with destruction and permanent loss of the exocrine parenchyma which may be either focal, segmental or diffuse. the primary symptoms of cp are abdominal pain and maldigestion, which may be physically and socially debilitating, although it is acknowledged that chronic pancreatitis can occasionally be painless. a classification based on the causes of cp is useful in order to better define the therapeutic interventions. however, morphological changes of the pancreatic ducts are the main rule of thumb for the classification in order to better compare the results of the treatment. imaging techniques have a role both on the diagnosis -especially in the early phases of the disease -and on the classification of cp, either for the grading of the disease, to explain the aetiology -even for rare forms -and to differentiate the focal mass from ductal adenocarcinoma. ct, mri and ercp have a specific role in the assessment of cp, due to the different capacity of the techniques to explore the pancreatic gland. however, thanks to heavily t w sequences, mri has a competitive role with ercp, which actually has more an interventional role in case of obstructive cp. finally, mri thanks to secretin test and dwi sequences is able to give a non-invasive assessment of pancreatic exocrine function. complications of pancreatitis may include fluid collections and pseudocysts, vascular complications such as arterial pseudoaneurysm or thrombosis of the portal venous system, and stenosis of common bile duct and pancreatic duct. inflammatory fluid collections in the context of acute pancreatitis often resolve spontaneously. drainage may become necessary in the presence of clinical complications such as abdominal pain, compression of adjacent organs by large pseudocysts, or if superinfection of a pseudocyst occurs. depending on clinical, morphologic, or technical factors, drainage may be accomplished with image-guided external catheter placement, by endoscopic internal (transgastric) drainage or by internal surgical drainage. arterial pseudoaneurysm carries the risk of acute intra-or extraperitoneal bleeding, and transarterial embolisation is usually indicated when pseudoaneurym is detected. strictures of the common bile duct secondary to chronic pancreatitis may require percutaneous or endoscopic retrograde intervention. learning objectives: . to review interventional techniques that are used to manage fluid collections in the setting of pancreatitis. . to compare the results with those obtained by surgical and/or endoscopic approach. . to learn about algorithms used for clinical decision making, and for treatment evaluation and follow-up. . to understand major shortcomings and complications and how to avoid them. discussion : ants include the presence of accessory muscles, a low-lying peroneus brevis muscle belly, pseudosubluxation of the peroneus brevis tendon, and a bifurcated or mildly crescentic peroneus brevis tendon. accessory muscles in the ankle area include in the lateral aspect the peroneal tertius and peroneal quartus, in the medial aspect the flexor digitorum accessorius longus, and posteriorly the peroneocalcaneus internus, tibiocalcaneus internus and accessory soleus. as variations are commonly seen in asymptomatic ankles, matching with clinical symptoms is important. pitfalls include pseudoloose bodies in the ankle joint, pseudolipomas, and artefacts such as the "magic angle" effect, chemical shift, susceptibility, motion, "ghost" and partial volume averaging. knowledge of normal anatomy, pitfalls and variants, aids radiologists in making the precise diagnosis of various disorders. the aetiology of dyspnoea is varied. it may be due to pulmonary or pleural disease, cardiac pathology or extrathoracic causes. imaging is an useful adjunct in the diagnosis of majority of cases of dyspnoea. in this lecture we will present selected cases which will demonstrate the usefulness of different imaging modalities, emphasising when cross-sectional imaging is indicated. learning objectives: . to review typical cases illustrating the role of imaging modalities in the differential diagnosis of dyspnea cases. . to motivate the audience by the use of voting pads to be involved in the diagnostic process. . to highlight the conclusion that may be drawn on the basis of the discussed cases. the term bone marrow oedema was introduced to describe ill-defined bone marrow hypointensity on t wi and hyperintensity on t wi and water sensitive sequences. bone marrow edema can be found in many similar unrelated disorders, such as bone contusions, osteonecrosis, inflammatory or degenerative disease, being a non-specific mri abnormality representing a diagnostic challenge for radiologist. recently has been demonstrated that bone marrow oedema might be a prognosis marker for oa (osteoarthritis) and inflammatory disease, and could be used as a powerful predictive tool for treatment options. therefore our role as radiologist is to try to increase specificity to help patient management and decrease progression. subchondral bone marrow lesions (bmls) are a hallmark of osteoarthritis (oa) on mri. radiologically, bmls in oa are understood as non-cystic subchondral areas of ill-defined hyperintensity on t w images and of hypointensity on t w images, but only water-sensitive fat-suppressed sequences depict the lesions to their maximum extent. bmls are observed regularly in conjunction with adjacent cartilage alterations. higher grades of cartilage loss are associated with higher prevalence and greater volume of concomitant bmls. as the disease progresses, an increase in bml volume is seen in the same region subchondrally in many patients, which is positively correlated with an increase in cartilage loss and radiographic joint space narrowing. cysts are strongly associated with bmls in the same subregion and develop within non-cystic bmls. the published data on the natural history of bmls are ambiguous but recent reports showed that the majority of subchondral bmls may regress or resolve completely. note that progression and regression of bmls may be observed within the same knee simultaneously. histologic correlation studies showed that the lesions consisted of a mixture of different tissue patterns with only little oedema. specific changes in bone mineralisation and remodelling in areas of bmls have been shown, and they appear sclerotic compared to unaffected regions from the same individual. differential diagnoses of oa-related bmls include traumatic bone contusions and fractures with or without disruption of the articular surface. osteonecrosis, inflammation, idiopathic bmls, red marrow and post-surgical alterations should also be considered. learning objectives: . to learn about the basic physiopathology of oa and its relation with bme. . to analyse the distribution and natural history of bme in oa. . to understand the differential diagnosis and relevance of bme in staging oa and as a marker of prognosis. b. bme and early inflammatory disease a.j. grainger; leeds/uk (andrew.grainger@leedsth.nhs.uk) marrow oedema is identified as a feature of many forms of inflammatory and mechanical arthritis, but has been most studied in the inflammatory arthritides and particular in rheumatoid arthritis. it was first reported as a feature of ra as far back as . work has been undertaken both using human specimens and specimens from animal models which suggest that marrow oedema seen on mri in ra corresponds to areas of inflammation been associated with invading pannus, lymphocytic aggregates and hypervascularity. there is also evidence that the marrow lesions seen on mri in ankylosing spondylitis correspond to histopathological inflammatory change. marrow oedema has been shown to be an important predictor the recent technological advances of ctu and mru have had an exceptional impact on the assessment of chronic/intermittent obstruction. imaging studies should help answer the clinical questions raised concerning the presence, level, and cause of obstruction. in this session, the recommended techniques of ctu and mru will be described and their relative merits and limitations reviewed. d ct images should be used as an adjunct to the transverse images, instead of a replacement, because volume-rendered images best depict the lumen and not the wall of the urinary tract. thin-section reformatted ct images likely are as sensitive as transverse images in the detection of urinary tract abnormalities. mru is being increasingly used because it provides excellent anatomic and functional imaging in a single setting. it has proved particularly valuable in pregnant women and children. the relative advantages of static-fluid mru and excretory mru will be discussed. the main aetiologies of chronic/intermittent obstruction will be illustrated, including intraluminal diseases (stones, clots, etc.), wall abnormalities (transitional cell carcinomas, tuberculosis, etc.) and extraluminal diseases (pelvic and retroperitoneal tumours, retroperitoneal fibrosis, gi tract diseases, etc.) upj syndrome is the most common site of urinary tract obstruction in children. vessels crossing a ureteropelvic junction obstruction contribute to the degree of hydronephrosis in up to % of these patients. demonstration of these vessels and their location anterior or posterior to the obstruction facilitates surgical planning. at the end of the lecture, attendees will become familiar with moderate or severe urinary obstruction and their various features and causes. . technological advances in both computed tomography (ct) and magnetic resonance (mr) imaging have improved the diagnostic imaging of the urinary tract, surpassing ultrasound and the intravenous urogram. multidetector computed tomography urography (ctu) is defined as ct examination of the kidneys, ureters and bladder with at least one imaging series acquired during the excretory phase of contrast enhancement. mr urography (mru) can be performed using heavily t -weighted sequences without contrast material or t spoiled gradient -recalled echo sequences during the excretory phase after administration of gadoliniumbased contrast material. in adults, ctu or mru is now the preferred examination. technical aspects of image acquisition and processing will be explored and technical tips relating to protocol design given. . the typical and atypical appearances of upper urinary tract urothelial tumours and bladder cancers will be demonstrated. a method of fluoroscopic biopsy of upper tract tumours is described for validation of the imaging diagnosis. . early and accurate diagnosis of urinary tract tumours helps optimise prognosis but conventional investigative pathways are complicated and lengthy, utilising multiple imaging tests and many diagnostic algorithms exist without rigorous evaluation. ctu offers a single imaging test of high diagnostic accuracy with the potential to replace multiple alternative imaging tests in the diagnostic pathway, improve patient experience, improve diagnostic performance and accelerate diagnosis. mru is a promising technique that may be used for the initial evaluation of patients at high risk for developing upper-tract urothelial carcinoma when ctu or intravenous urography is contraindicated. rhage and periventricular echodensities. the posterior fontanelle approach improves the detection of grade ii haemorrhage in % more cases than the anterior fontanelle, and the mastoid fontanelle approach is essential for diagnosing cerebellar haemorrhage. ventricular dilatation is the main complication of intraventricular haemorrhage and resolves spontaneously in approximately % of cases. the main challenge with periventricular echodensities is to differentiate them from classical periventricular leukomalacia. when cysts appear during follow-up, the diagnosis is straightforward. mri is considered to be more sensitive than us for evaluating white-matter damage. congenital brain malformations including ventricular dilatation of diverse aetiologies, corpus callosus agenesis and posterior fossa malformations are usually diagnosed prenatally. mri complements us for this purpose. acquired abnormalities arise mainly from infections and hypoxic-ischaemic injury. although mr is considered the gold standard, us still plays an important role in the study of hypoxic-ischaemic lesions when used to its full capacity. depending on the duration and severity of the hypoxic insult, patterns different from those seen in premature infants may be observed. brain malformations are conditions where the brain has not formed properly during pregnancy. these problems in brain structure are almost often (with some exceptions) associated with neurological and developmental problems. often, brain malformations are part of syndromic complexes that require a multidisciplinary approach. malformations may be caused by inherited genetic defects, spontaneous mutations within the genes of the embryo, or effects on the embryo due to the mother's infection, trauma, or drug use. classification schemes are currently shifting from a morphological to a genetic approach. the most frequent congenital brain abnormalities may be categorised into anomalies of the corpus callosum and telencephalic commissures, holoprosencephalies and related entities, malformations of the cerebral cortex, and malformations of the cerebellum. these congenital brain defects are diagnosed either from direct physical examination or from imaging studies including ct and mri. prenatal mri offers a viable method to improve detection and characterisation of these entities in utero. learning objectives: . to learn about the common supra-and infratentorial congenital abnormalities. . to learn when mri is required and the appropriate imaging protocol. . to learn if and when ct is still useful in the investigation of congenital anomalies. in addition to predicting bone destruction for erosion, marrow oedema is independently predictive of joint space loss and therefore cartilage destruction. it also correlates well with other measures of disease activity. we have applied dynamic contrast enhancement techniques to show that treatment with anti-tnf therapy brings about a reduction in contrast uptake in areas of marrow oedema in patients with ra. in the seronegative arthritides marrow oedema in the spine in ankylosing spondylitis has been shown to be predictive of future changes and of response to treatment. diffusion weighted imaging of marrow lesions in ankylosing spondylitis can also be used to show a treatment response, seen as a change in the apparent diffusion coefficient. bone marrow oedema, also referred as bone contusion or bone bruise, is frequently identified at magnetic resonance imaging after an injury to the musculoskeletal system. it may result from a direct blow to the bone, compressive forces from adjacent bones impacting one another, or from traction forces that occur during an avulsion injury. its location reflects the mechanism of injury, which allows for a focused search for predictable patterns of associated internal derangements. it is seen in any joint but are particularly common in the knee reflecting mechanisms such as pivot shift, hyperextension, contrecoup or dashboard injuries, as well as lateral patellar dislocation. in a context of trauma, bone marrow oedema, identified at mr imaging as areas of poorly marginated signal intensity alteration (best seen on fat-suppressed sequences) in the cancellous bone and marrow, represents areas of oedema and haemorrhage secondary to trabecular injury. it can be seen as soon as one hour after trauma and usually resolves in the following six to eight months, except in case of subsequent chondral lesion. learning objectives: . to learn about bhe physiopathology in trauma scenario, direct and indirect mechanism. . to recognise bme as a footprint that allows other soft tissue injuries to be ruled out. . to analyse whether bme can be a value tool for follow-up. can we still use the term bme or should we be more specific? : the term bone marrow oedema was introduced to describe ill-defined bone marrow hyperintensity on t weighted images. since then many studies have demonstrated that it can be found in many similar unrelated disorders, such as bone contusions, osteonecrosis, inflammatory or degenerative disease, and that it is a non-specific mri abnormality. it has been demonstrated that bone marrow oedema might be a prognosis marker for oa (osteoarthritis) and inflammatory disease, and could be used as a powerful predictive tool for treatment options. therefore our role is to increase specificity to help patient management and decrease progression. room e sonography is an essential tool for studying the neonatal brain. brain scans are usually performed via the anterior fontanelle; however, a more complete assessment of the brain can be achieved using the posterior and mastoid fontanelles, high-resolution linear array transducers and colour or power doppler. the most common lesions in premature infants are intraventricular/periventricular haemor- at initiation, tumours in a pre-vascular phase are supplied by oxygen and nutrients that diffuse from pre-existing normal vessels. when the tumour reaches a critical size of approximately - mm diameter, the resultant ischaemia leads to secretion of angiogenic factors. these factors, such as vascular endothelial growth factor (vegf), recruit and maintain tumour vessels. "new" vessels (neovasculature) exhibit increased blood volume and permeability compared with normal vessels. various new specific therapies in oncology target tumour vasculature or tumour neoangiogenesis. it is not uncommon that these targeted therapies have pronounced cytostatic and not predominantly cytotoxic effects. this limits the usefulness of size-based morphological tumour response assessments. of newer magnetic resonance imaging (mri) modalities, perfusion mri has emerged as a valid marker of tumour-induced blood vessels and their function. mri perfusion measures the vascularity within a tumour, as well as its component heterogeneous parts. of parameters which can be measured to date, blood volume and permeability are commonly applied in patient studies. blood volume measures the aggregate size of the vascular space, while the permeability function informs about the integrity of vessels and their ‚leakiness' to contrast agents. we will describe the use of mr perfusion to monitor such new therapies and discuss its specific advantages and limitations in comparison to ct perfusion protocols. pet-based strategies for targeted treatment-monitoring in oncology will be briefly mentioned, with prospect on the significance of combined vascular and metabolic imaging for further optimising non-invasive response assessment in specific anticancer therapies. after a brief review of physical and technical principles of diffusion-weighted mr imaging and pet-ct, the lecture describes the ability of these techniques in evaluating functional parameters in tumour tissue. diffusion-weighted sequences have been used in an attempt to further increase the diagnostic capability of baseline and dynamic mr study by providing functional information. diffusion-weighted mr imaging is based on the random microscopic movement of molecules that can be quantified by means of apparent diffusion coefficient (adc). in the early post-treatment period after loco-regional therapies, tumours may not change in size. recent studies demonstrated that water diffusion can be used to differentiate viable and cellular regions from necrotic area in the tumour, regardless morphologic or dimensional changes. moreover, new classes of antitumour therapy have been developed that have an antiproliferative effect, inducing a delay in tumour shrinkage. diffusion mr imaging can be promising in this clinical setting as a biomarker to predict early response to systemic chemotherapy. on the other hand, pet/ct, combining the functional and the structural imaging approach, was shown to be superior regarding conventional imaging modalities in the identification of intrahepatic and extrahepatic metastases. less experience and less publications are available for pet-ct in monitoring tumour response after interventional therapies, but the ability of pet-ct to measure early metabolic changes could make this technique useful in the development of novel anticancer drugs. until now, in oncology, only the recist criteria based on anatomical measurement of the tumour size are used for drug trials or in clinical practice because this is a standardised way to assess the tumour response that allows the calculation of the progression-free survival (pfs) or the time to progression (ttp) that are usually accepted as surrogate end point for overall survival. however, tumour follow-up evaluation using only morphology is usually delayed and with the emergence of new numerous and very expensive targeted therapies there is now a need to move beyond morphology to find new ways to assess tumour responses or progression not only for clinical trials but also in clinical practice to maintain or to change quickly a treatment. this is the aim of the functional imaging using ultrasound, ct, mri or pet. the ultimate goal of these technique is to find biomarkers able to predict the likely course of disease, irrespective of treatment (prognostic biomarkers) or able to forecast the likely response to treatment (predictive biomarkers); before (baseline values of a parameter) or during the treatment (dynamic variation of the parameter during the follow-up). during this session the presenters will discuss the technical issues and the results obtained today using ultrasound with share-waves or microbubbles, functional ct, dynamic contrast enhanced mri, diffusion weighted mri and pet-ct. the candidate biomarkers will be presented as well as the limits and the problems that are still to be overcome. a. us and ceus m. claudon; vandoeuvre-les-nancy/fr (m.claudon@chu-nancy.fr) for tumour evaluation, the main advantages of ultrasound (us) associate a high frame rate and a large range of data and parameters potentially extracted from the signal backscattered from tissues. beyond morphology, elastography is a first modality, based on in vivo estimation of the mechanical properties of tissues. data on displacement or strain of tissues and lesions can be obtained by manual external compression, but shear wave generation techniques allow for a quantitative and more precise estimation of their visco-elastic properties. in oncology, clinical evaluation included first breast. contrast-enhanced us (ceus) is obtained after intravenous administration of microbubbles which are pure blood pool contrast agents. ceus is capable for detection, characterisation and follow-up of tumour lesions, based on enhancement profiles during bolus, destruction-replenishment, or contrast burst depletion imaging. quantification of perfusion in normal tissues and lesions may be obtained by extracting various blood flow and blood volumerelated parameters from time-intensity curves. protocols have entered validation processes to improve reproducibility. as a predictive technique, ceus is a promising tool for monitoring changes of haemodynamic parameters and evaluating the early response during chemotherapy or antiangiogenic treatment. it is helpful in the guidance and follow-up of lesions treated by radiofrequency or cryoablation. recent advances of us and ceus include d/ d real-time imaging with matrix technology, and the evaluation of targeted agents, to be released on site after bubble destruction by the us beam. interventional radiology (ir) is the part of clinical radiology based on the percutaneous or endoluminal treatment of widespread conditions. the procedures performed by the interventional radiologists require a deep level of knowledge of clinical imaging and specific training in patient management and care. technical skills are also needed because complex devices and materials are used in some procedures. therefore, specific training programmes are required to address the training needs for the interventional radiologist. a multidisciplinary approach is required (based on team work) with defined levels in patient care. ir procedures have become the treatment of choice for many conditions as an alternative for some surgical procedures. even for some conditions without a defined treatment are now being treated by ir. thus, it is a discipline with a great deal of interaction with other clinical specialities that requires a clear definition. ir specialists have to receive recognition in the patient care process and their activity has to be known by the medical community. the recognition of ir as a subspecialty of clinical radiology by the uems will contribute to the development of specific training programmes in the european community and will promote training centres with certified specialists. interventional radiology (ir) procedures are complex and require specific training to ensure good results. in the uk, a curriculum for subspecialty training was established in specifying the required knowledge, training and core procedures expected of trainees. this curriculum has undergone several reforms since that time. however, training is not uniform throughout europe and this stimulated the development of a europe wide ir training document to ensure similar training in all countries as a way of ensuring good medical practice. radiology training is based on years of common radiology training and years of subspecialty training with an option for further specialist training in the th year. regular appraisals and assessments of trainees' performance should guide progress at local training institutions with the aim that competence is assessed formally at the end of training by a european board examination. this qualification will be recognised thoughout europe and ensures that the required proficiency in ir procedures has been attained. competence in the core skills for ir occurs during the first years of training. in the next years, trainees undertake modular training depending on their areas of interest and ultimate goals. the majority of this training is practical, supervised training in interventional suites and theatres, with clinical exposure. simulators play a role alongside the more traditional training methods and allow early training in a more forgiving environment away from the patient. development and validation of such simulation models is progressing. discrimination of individual x-ray quanta, i.e. the detectors can 'see' the colour of the x-rays. different materials attenuate the energy spectrum in their own characteristic way. by comparing the measured spectra with the spectrum emitted from the x-ray tube the penetrated material can be characterised. colour x-ray imaging can be used in breast imaging to detect, for example the uptake of an iodinated contrast agent to show the vasculature of a tumour while reducing the impact of the structures from the surrounding tissue. it can also be used to estimate the breast density and as a material decomposition technique to separate the digital mammogram into compositional images, showing different material types separately. colour x-ray imaging can, for example be realised with pulse height discrimination in a photon counting detector, multiple exposures with different x-ray tube settings or filtering the x-ray beam before or after the object. the most simple form of colour x-ray is dual energy where two images are acquired at different x-ray energies. lung cancer staging is based on imaging techniques in combination with tissue diagnosis and surgical exploration. the tnm staging system describes the local tumour extent (t -t ), presence or absence of lymph node metastases (n -n ) and distant metastases (m /m ). different combinations of t-, n-and m-factors translate into tumour stages (stages ia-iv). therapeutic decisions and assessment of prognosis are based on these tumour stages. recently, the tnm system has been modified: tumour size is now used more precisely for t staging: tumours <= cm: t a, > - cm: t b, > - cm: t a, > - cm: t b, > cm: t . satellite tumour nodules in the same lobe are now classified as t (previously t ) and in a different lobe of the ipsilateral lung as t (previously m ). satellite nodules in the contralateral lung (previously m ) and pleural or pericardial metastases (previously t ) are now classified as m a, whereas distant metastases outside the chest are classified as m b (previously m ). also, the tnm staging system should now be applied not only to non-small cell lung cancer (nsclc) but also to small cell lung cancer (sclc). during this refresher course the different t-, n-and m-stages will be presented including the recent changes and examples will be presented and discussed with the audience. therapeutic strategies in different tumour stages will be described and key decisions highlighted. the accuracy of different imaging procedures and findings will be presented and the role of biopsy in specific clinical scenarios will be discussed. x-ray computed tomography (ct) has been proposed and evaluated recently as a potential alternative method for breast imaging. efforts so far showed success with respect to contrast-enhanced dynamic imaging, but suffered from limited spatial resolution. respective efforts and clinical results will be reviewed. the new concept presented here builds upon micro-ct scanning approaches and aims at providing both high spatial resolution at around µm for micro-calcification imaging and advanced dynamic scan capabilities with continuous acquisition and scan times of about seconds for differential diagnosis of lesions. to achieve this, spiral scan modes, slipring technology, high-resolution detectors and high-power micro-focus x-ray tubes are demanded. the concept has been evaluated and confirmed by simulations and basic experiments; feasibility studies are expected by the end of . colour x-ray imaging can best be described as the x-ray analogy to optical colour imaging. in optical imaging the wavelength -the energy -of the light gives the different colours that we see. emerging x-ray detector technologies enable energy maintenance of confidentiality of patient information. in contrast, more hierarchical cultures often defer to elders for decision-making whereas communal cultures may involve community leaders in a shared decision-making process. gender and religious issues can also affect the provision of high-quality procedures with same gender care being a requirement within some cultural groups and gowning procedures that maintain cultural values frequently being an expectation. in addition, in many countries in the developing world, radiation still has mystique and fear associated with it, affecting participation in screening programs and recruitment to medical radiation technology educational programs. this presentation will present findings from a variety of countries and cultures that will help to contextualise these issues through a cross-cultural imaging lens. first line image interpretation is now commonly used in the united kingdom. for many years radiographers have used a system commonly known as "red dot" in order to identify to the referring clinician that an abnormality has been recognised on a radiographic image. this has more recently evolved into radiographer comment where the radiographers' experience in recognising abnormalities can help referring clinicians. junior doctors are often inexperienced at image interpretation, thus this system can assist in ensuring that a higher percentage of fractures and injuries are observed and the appropriate treatment obtained. this presentation will demonstrate the fundamentals of basic image interpretation of the cervical, thoracic and lumbar spine in a trauma situation. it will include basic anatomy, mechanism of injury, common fractures and soft tissue signs. using these principles this will encourage radiographers to use the comment system, both developing the radiographer's role and helping to improve patient care. two fasciae cross the suprahyoid neck: the superficial cervical fascia (scf) and the deep cervical fascia (dcf). the latter can be divided into three parts and these layers define different fascial spaces or compartments. the descriptions of these compartiments in the literature vary almost as much as those of the fasciae themselves. in addition, the names of the formed compartiments vary within the literature. despite these controversies, the knowledge of these compartiments is inestimable for correct differential diagnosis of pathologies that arise in the suprahyoid neck. with the utilisation of cross-sectional imaging, it has been noticed that growth of some tumours appears restricted by fasciae and knowledge of the anatomy of these fasciae allows not only prediction of growth patterns. by allocation of a tumour to a certain compartiment the number of differential diagnosis drop dramatically due to the fact that in different compartiments different types of tissue occur. in addition, the exact localisation of infectious disease of the suprahyoid neck may predict further intracranial or mediastinal spread. even though the number management of cancer patients, imaging pitfalls must be recognised to avoid both false-positive and false-negative interpretation. the principles and good practices of pet/ct will be explained. normal distribution of fdg, pitfalls and normal variants will be presented. specific examples will be discussed to demonstrate how the combined information of images of human anatomy upon which biological information within body structures is added improves delineation of disease, can guide surgical and radiation planning and biopsy. advances in technology result in new training requirements for radiologists who should promote close collaboration with nuclear medicine specialists. the metabolic syndrome refers to the clustering of cardiovascular risk factors including diabetes, obesity, dyslipidaemia and hypertension. the association between metabolic syndrome and cardiovascular diseases raises important questions about the underlying pathological processes. insulin resistance and visceral obesity have been recognised as the most important pathogenic factors. metabolic syndrome generally precedes and is often associated with type diabetes. cardiovascular risk reduction in individuals with metabolic syndrome should include ( ) control of obesity, diet and physical activity and ( ) control of the individual components of metabolic syndrome, especially atherogenic dyslipidaemia, hypertension, hyperglycaemia and prothrombotic state. appropriate management of metabolic syndrome should be able to prevent the progression from impaired glucose tolerance to frank diabetes and thus to prevent the increasing prevalence of type diabetes and vascular diseases. each % increase in hba c is associated with a % increase in risk of incident pad. diabetes is also highly associated with progression of pad and especially with the development of critical limb ischemia. rigorous control of blood glucose prevents the microvascular complications of diabetes, although similar benefits on the macrocirculation have not been ascertained. patients with diabetes and pad should have an aggressive control of blood glucose levels with a hba c goal of < . % or as close to % as possible. in the new tasc paper this recommendation is graded as c, meaning that it is based on evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities, while there are no applicable studies of good quality. peripheral arterial disease (pad) is a common cardiovascular complication in patients with diabetes. in contrast to non-diabetic pad, it is more prevalent and, because of the distal territory of vessel involvement and its association with peripheral neuropathy, it is more commonly asymptomatic. diabetic pad thus may present later with more severe disease and have a greater risk of amputation. the pervasive influence of diabetes on the atherothrombotic milieu of the peripheral vasculature is unique. the abnormal metabolic state accompanying diabetes results in changes in the arterial structure and function. the proatherogenic changes include increases in vascular inflammation and derangements in the vascular cellular components, alterations in blood cells and haemostatic factors. these changes are associated with an increased risk for accelerated atherogenesis as well as poor outcomes. in contrast to the focal and proximal atherosclerotic lesions of non-diabetic pad, in diabetic patients the lesions are more likely to be more heavily calcified, diffuse, and distal, sparing the proximal vessels and mainly affecting the more distal arteries in the calf and, in a later stage, the foot. by identifying a patient with subclinical disease and instituting preventative measures, it may be possible to avoid acute, limb-threatening ischaemia. the primary imaging modality to be used should be duplex ultrasound, due to its non-invasive nature, lower risks and costs. ct-angiography and mr-angiography are now replacing dsa as standard imaging methods, providing a non-invasive assessment of the localisation and extension of a vascular lesion and allowing an accurate planning of endovascular and/or surgical treatment. of spaces in the literature varies from seven to fourteen, the use of seven spaces or compartiments seems to be helpful for a sufficient diagnostic approach using cross-sectional imaging. anatomic landmarks and the radiologic appearance in a non-pathologic suprahyoid neck and a pathologic involvement of the suprahyoid compartiments will be reviewed extensively in a coherent manner. the anatomy of the suprahyoid neck is complex and the spectrum of diseases is wide. to improve studies of the neck, radiologists should become increasingly more familiar with the anatomy and expected pathology in the various spaces. this familiarity provides crucial information required for the selection of treatment options and therapeutic planning. in addition, radiologists should be aware of situations when diagnostic inaccuracies may lead to serious consequences and complications. for example, surgical approach to a deep lobe parotid tumour as though it is a parapharyngeal lesion will in all likelihood result in facial nerve injury. mri artefacts such as complex flow-induced increase in signals may be mistaken as a lesion prompting an unnecessary operation. an awareness of such pitfalls helps to improve the quality of imaging studies. this presentation highlights some pertinent anatomical knowledge that may help to improve the diagnostic accuracy of neck studies and at the same time explain the existence of pitfalls that may ruin imaging studies. three layers of the deep cervical fascia define the suprahyoid neck compartments, which include: prevertebral, retropharyngeal, carotid, masticator, parapharyngeal and pharyngeal mucosal space. knowledge of the structures inherent to these spaces will provide the radiologist with an accurate basis for differential diagnosis. also, expanding lesions will distort or displace adjacent structures and fascia in predictable fashion, which is crucial in defining the site of origin. both mri and ct are frequently used in the imaging of suprahyoid neck lesions. the introduction of functional imaging has also given some benefits. primary and secondary, benign and malignant processes occupying major suprahyoid neck spaces will be discussed, with regard to crucial findings necessary for appropriate treatment selection and treatment planning. since correct diagnosis requires close collaboration with ent surgeons, clinical findings will also be discussed, together with practical information needed for surgery. in vivo proton mr spectroscopy is a non-invasive mr technique that is routinely used to assess a number of paediatric neurologic conditions. it is based on the fact that protons belonging to different metabolites resonate at slightly different frequencies (chemical shift). using water suppression and volume localisation techniques we can obtain a spectrum (single voxel) or spectra (si) containing metabolite peaks corresponding to predetermined anatomical site(s). in paediatrics the majority of spectroscopy is performed in the brain and the metabolites detected usually are: n-acetyl aspartate, n-acetyl aspartyl glutamate, creatine and phosphocreatine, choline containing compounds (free choline, acetylcholine, phosphocholine, cytidine diphosphate choline and glycerophosphocholine), myoinositol, myoinositol monophosphate and glycine, aminoacids (glutamine, glutamate and gaba), lactate, lipids and macromolecules. these metabolites participate in fundamental metabolic pathways and their levels are being disturbed by various pathologies. thus, mr spectroscopy has a vast field of application including paediatric tumours, infarction, hypoxia, ischaemia, infection, inflammation, metabolic disorders neurological disorders and trauma. in many cases, it can redirect or narrow differential diagnoses; in selected instances, it may provide the key finding that points to a final diagnosis. however, mr spectroscopy alone is usually not specific, but can be very helpful especially in combination with other clinical, diagnostic and other mr methods. finally, particular caution is needed in data evaluation because spectral appearance and concentrations of the most prominent metabolites are affected by (a) experimental and preprocessing factors and (b) brain development. stroke in children is most often of ischaemic origin and thrombophlebitis is the second cause of stroke in children. stroke is considered as rare compared to the adult population. however, numerous aetiologies impose to look for a cause through series biological investigations. the goal of brain imaging is to confirm the diagnosis of stroke, to evaluate the extension of ischaemia and mostly to participate in the search of a cause for the stroke. prognostic is mostly related to the aetiology. a lot of cases are performed under general anaesthesia leading to limited indications of mra in the acute phase compared to adult. the role of cta at the acute phase is mostly to confirm thrombophlebitis and is the primary method to assess intracranial vessels at the acute phase of haemorrhage of arterial or venous origin. it is also the primary method to assess arterial vessels at the neck level (especially when dissection is suspected). cta permits to confirm or rule out arterial lesion that was suspected on mr: indeed, cases with pitfalls are numerous with mr angiography. the role of mra, also always performed in the acute phase or follow-up of vascular diseases, is not as clear as cta role because of artefacts especially in young children. the role of angiography (dsa) is finally limited to prove vasculitis when the other methods are not contributive and in cases of arterial or arterio-venous malformation to plan the treatment (endovascular procedure versus surgery or radiosurgery). diffusion tensor imaging (dti) studies demonstrate progressive apparent diffusion coefficient (adc) decrease within grey and white matter areas starting from foetal life as sign of brain maturation; meanwhile, fractional anisotropy (fa) increases in some white matter structures. changes in fa and adc, together with radial and axial diffusivity values, during cell proliferation-migration and during myelination, well correlate with modifications known from developmental histologic studies. acute adc decrease (i.e. ischaemia) can be detected already in foetal stroke and its measure is pivotal in monitoring neonatal hypoxic-ischaemic encephalopathy. adc calculation allows also to assess acute osmotic and metabolic anomalies in neonate (i.e. hypernatremia, hypoglycaemia, etc.). early fa decrease, with radial and axial diffusivity changes, is observed in white matter areas as sign or early wallerian degeneration after acute brain damage. chronic regional white matter fa reduction is detectable in sequelae of periventricular leukomalacia or adjacent to malformative cortex. also, in children with neurodevelopmental delay (autism, adhd, dyslexia, etc.). fa reduction and radial or axial diffusivity changes have been demonstrated, but in these conditions not on a single case basis rather in cohort quantitative studies. finally, building fiber tracking and colour coded (rgb) maps from dti data may help in better characterising suspected structural anomalies on a single case basis (i.e. corpus callosum, hippocampal fornix, optic radiation, cerebellar peduncles malformations, etc.). however, the potentials of fiber tracking applications still need to be fully exploited, especially in view of future higher spatial resolution image acquisitions. learning objectives: . to understand the relationship of adc-fa values with the structural characteristics of the normal developing brain. . to understand adc-fa value changes in paediatric cns diseases. . to learn about the potential impact of fibre tracking in clinical paediatric neuroradiological practice. congenital pulmonary malformations may involve the lung parenchyma, bronchi, arterial supply, and venous drainage. the pulmonary developmental abnormalities that most commonly result in clinically significant complications in neonates and children are hypogenetic lung syndrome, bronchopulmonary sequestration (bps), congenital lobar emphysema (cle), bronchial atresia, congenital cystic adenomatoid malformation (ccam), and bronchopulmonary foregut cysts. it should be noted that there is often considerable overlap between these conditions and that multiple lesions may be identified in the same patient either separately or as hybrid lesions. the aim of this presentation is to illustrate the characteristic imaging manifestations of the most important congenital lung diseases and their main differential diagnosis. emphasis will be given to pre-natal diagnosis using ultrasound or magnetic resonance imaging (mri) and post-natal diagnosis using mri or low dose ct in multidetector scanners. ultrasonography (us) is the primary screening modality in prenatal imaging. its diagnostic accuracy is usually very high so that the indications for foetal mri should be very rare. in some countries, because us is considered of secondary importance and is not exploited as much as it could be, there is a progressive shift from us to mri as a prenatal imaging modality. consequently, there are many discrepancies regarding the relative contributions of foetal us and mri in the prenatal literature. the main indications for foetal mri will be discussed, with emphasis on the central nervous system, which remains the main field of application. in daily practice, the technique of foetal mri has not changed during the last decade and most diagnoses can be assessed using t , t and t * sequences. the basic technique and patient preparation will be described. new techniques, based on a functional or a metabolic approach, have been developing during the past few years but their impact on daily practice is still very limited. many studies have underlined the high diagnostic contribution of foetal mri compared with us. however, the diagnostic accuracy of mri has not been studied in large series. comparison between pre-and postnatal data or between foetal mri and pathological findings make it possible to define the main limits of foetal mri. regarding the brain, migration or cortical development disorders are often overlooked or underdiagnosed. a tight collaboration between colleagues practicing prenatal us and mri should increase diagnostic accuracy, both modalities being complementary. founded on september , , the brazilian college of radiology comprises regional societies and ten thousand associates. the college is a branch of the brazilian medical association (amb) acting as its scientific department of radiology, imaging diagnosis and radiotherapy. it collects, under the same umbrella medical professionals and legal entities in the field of diagnosis and treatment using imaging methods and/or ionising radiation. session objectives: . to get an introduction to the practice of radiology in brazil. . to understand the importance of radiology as a method for diagnosing diseases in brazil. granulomatous interstitial lung disease: hrct path correlation c.i.s. silva; salvador/br (c.isabela.silva@gmail.com) granulomatous interstitial lung diseases are a group of lung diseases in which granulomas are an important component of the histologic findings. the most common conditions are hypersensitivity pneumonitis and sarcoidosis. hypersensitivity pneumonitis is very common in brazil because of the warm and humid climate in most regions and a large number of birds. the prevalence of sarcoidosis in brazil seems to be lower than that in north america and europe. other ubiquitous causes of granulomatous interstitial lung disease include intravenous talcosis, drug reactions, and some forms of vasculitis (e.g. churg-strauss syndrome). the aim of this presentation is to illustrate the characteristic high-resolution ct and histologic manifestations of the most common granulomatous interstitial lung diseases and to summarise the main differential diagnosis based on the pattern and distribution of abnormalities seen on high-resolution ct. learning objectives: . to become familiar with the characteristic high-resolution ct and histologic findings of the most common granulomatous interstitial lung diseases (hypersensitivity pneumonitis and sarcoidosis). . to learn about the most helpful features in distinguishing the granulomatous interstitial diseases from other parenchymal lung diseases. a- : the most common granulomatous lung diseases are fungal infections and tuberculosis. these infections are particularly prevalent in brazil, the most common fungal infection being paracoccidioidomycosis (south american blastomycosis). histoplasmosis and coccidioidomycosis may occur but they are uncommon. paracoccidioidomycosis is the most frequent endemic systemic mycosis in latin america, being seen particularly in brazil, argentina, colombia, and venezuela. the lungs are the main target organ of p. brasiliensis organisms, and infection of the lungs is the leading cause of morbidity and mortality in these patients. fungal infections need to be considered not only in patients living in endemic regions but also in patients who have travelled to these areas. although the prevalence of pulmonary tuberculosis has decreased in brazil in recent years it remains one of the most important causes of pulmonary morbidity and mortality. the aim of this presentation is to discuss the radiologic manifestations of the granulomatous pulmonary infections with emphasis in paracoccidioidomycosis and tuberculosis and to summarise the main differential diagnosis. magnetic resonance imaging (mri) is a highly sensitive technique that provides complementary information to conventional breast imaging (i.e. mammography and ultrasonography) for the detection of multinodular disease and for the assessment of primary tumour extent. the use of mr breast imaging has increased considerably in the past decade. although its use is well established for some indications, e.g. detection of unknown primary and assessment of uncertain disease extent, breast mri is still under investigation for other applications such as preoperative assessment in patients eligible for breast conserving therapy on the basis of conventional imaging and clinical examination. despite its superior ability to visualise disease spread, recent studies have shown increased rates of mastectomy without reduction in positive surgical margins or local recurrence rates. nonetheless, a shift in paradigm is occurring, focusing on the use of breast mri to reduce involvement of healthy tissue in breast-conserving therapy. this paradigm involves new methodology to optimise the transfer of information to the surgeons and radiation oncologists. new technological developments, such as diffusion-weighted imaging (dwi) and magnetic resonance spectroscopy (mrs) provide new insights to establish a link with underlying biology of the tumour. contrast-enhanced mri, dwi and mrs are examined for their ability to extract prognostically relevant information to individualise therapy to individual patients and tumours. this overview aims to summarise the current status of breast mr imaging and new developments geared towards providing therapists with patient-tailored information for treatment decision, treatment guidance and therapy response. this talk will review the current literature and clinical use of foetal mri in cases with ventriculomegaly. the initial part will discuss antenatal ultrasound in the detection, categorisation and diagnosis at the -week anomaly scan. the role of foetal mri will be discussed including which cases may benefit most from foetal mri when the resource is limited. the timing of the foetal mr with relation to gestational age and the value of further foetal mr scans at a later gestational age will also be discussed. this is still a controversial and debated area especially when the resource is limited or there are financial constraints. the current literature will be discussed on the issues around foetal mri in cases with ventriculomegaly both isolated ventriculomegaly and ventriculomegaly associated with other abnormalities. finally, this section will conclude by looking at the common associated abnormalities seen in cases referred with ventriculomegaly. the final section will discuss the role of foetal mr in imaging the posterior fossa, an area often difficult with ultrasound especially in the later stages of pregnancy. again the current literature will be discussed and the use of foetal mr in clinical practice. the concluding time will be used to summarise the referral pathway used by local centre in the uk. this will differ with other uk centres and centres worldwide. hopefully, time will allow an open discussion on this at the end of the session. learning objectives: . to learn about the differential diagnoses of ventriculomegaly identified on foetal ultrasonography. . to learn when mr should be performed and its value when compared to ultrasonography. . to understand the value of mri in assessing posterior fossa abnormalities. prenatal diagnosis involves obtaining genetic, anatomic, biochemical and physiological information about the foetus and analysing whether there are any alterations that might have repercussions during the foetal period or after birth. magnetic resonance imaging (mri) has been useful in the diagnosis of foetal anomalies for many years. thoracic abnormalities play an important role in infant morbidity and mortality. survival after birth depends largely on adequate lung development during gestation, and various pulmonary problems can affect foetuses. heart defects are present in of live births, and up to % of these are associated with other malformations. other thoracic anomalies (tracheoesophageal malformations, chest wall defects, and tumours, amongst others) can also cause morbimortality. congenital abdominal anomalies can affect many organs. it is essential to determine the location and morphological characteristics of the lesion to ensure an accurate diagnosis. mri's excellent contrast resolution between tissues is very useful in the diagnosis of these conditions. prenatal diagnosis also makes it possible to detect anomalies that can be difficult to recognise clinically in newborns but require early treatment to minimise possible complications.this presentation stresses the importance of diagnosing chest and abdominal problems before birth and analyses the usefulness of mri in this context. learning objectives: . to learn about the mr protocol when investigating the foetal chest. . to recognise the situations in which mri is helpful in assessing chest abnormalities. . to understand the value of mri when compared to ultrasonography in assessing congenital renal and gastrointestinal abnormalities. a s c b d e f g h structured reporting: improving the quality of radiology reports c.e. kahn; milwaukee, wi/us (kahn@mcw.edu) the radiology report communicates the results of an imaging procedure and provides the enduring legal record of the procedure. structured reporting uses standardised language and predefined formats to create reports. structured reports can integrate information collected during the imaging procedure, such as clinical data, technical parameters, measurements, annotations, and key images. in this presentation, well defined structured reporting describes its advantages and disadvantages, and identifies the motivations for its adoption. this session will discuss how structured reporting can make it easier to retrieve reported information, evaluate the appropriateness of exams, and aggregate data across health care enterprises. structured reporting can support radiology quality improvement, research, and education, and has the potential to improve the quality of communication between radiologists and their referring colleagues. beyond air-space disease is secondary to occupation of the acini and alveoli by oedema, exudates or malignant cells. it presents in the chest radiograph as ill-defined densities which tend to coalesce. the presence of an air bronchogram is pathognomonic. when the disease is widespread it shows the typical "butterfly" appearance. air- the pixel data set of modern imaging is transformed into a life altering insight for the individual patient through the radiologic report. a good report is patient and service centred, and forms the basis of the reciprocal relationship between radiologist and referring clinician. it is a creative process with serious scientific purpose and becomes part of the permanent record in a person's life. its primary role is communication of diagnostic and procedure-related imaging information but it has many vital adjunct roles in quality service delivery. in current practice of multidisciplinary care the report content must be of value to all the stakeholders beyond radiology. structured reports must have uniformity where possible to permit data-mining and audit whilst preserving the individual radiologist practice and style and the individual nature of each patient's health. report design has a particular role in modern alerting and safety-net systems when unexpected or critical imaging findings are discovered. the properly written report can be vital in medico-legal defence to reflect good practice. ultimately guidelines and standards on reporting must be meaningful to the users and appropriate to local resources, systems and needs. learning objectives: . to comprehend the role of the modern radiological report. . to understand the role of the report in communication and patient safety. . to become familiar with structured report formulations. structured reporting: european perspective r. silverio; grosseto/it (rsilverio@sirm.org) in the last decade, we observe an increasing interest in structured report (sr). this is a part of the dicom standard, where the technical and clinical information are organised in a standard format so that it can be retrieved and reused for clinical, statistical and research scopes. structured reports have three important features: a "structured" format, with fixed paragraphs, heading and subheading in which to describe technical data and clinical findings, impressions and conclusions; a consistent, "itemised" organisation, leading to a better way of reporting, even with automated speech recognition systems; and the possibility, or rather the need, of a common, shared language. when defined terms from a standard lexicon are associated with imaging reports, the information in the report becomes more accessible and reusable. moreover, sr allows the interoperability between the dicom world and the complex sphere of the e-health (electronic patient record, patient care, etc). it is possible to convert a radiological report created as sr in a cda (clinical document architecture) document. this clinical document will be used in every computerised healthcare application, as well in the several regional e-health projects (epsos, elga, calliope, renewing health, etc). promoted by european community. integrating the healthcare enterprise (ihe) initiative is as a key partner in fostering the adoption of structured report. in short, question of whether sr will be adopted by radiologists is now a question of "when", not "if." learning objectives: . to become familiar with structured report. . to keep up to date on the developments of e-health projects in europe. acute mesenteric insufficiency (ami) is due to arterial or venous occlusion. arterial ami is an emergency. the typical patient is elderly, may have atrial fibrillation and has recent onset intense visceral pain disproportionate to clinical signs. ct is the mainstay of diagnosis and may be supplemented by ct angiography (cta). waste no time if arterial ami is suspected. average mortality rates of % ( - %) have been reported and symptom duration before therapy is an independent predictor of mortality. age > years, metabolic acidosis and renal failure are other danger signs. interrupt routine ct lists; ensure that these patients are scanned as soon as possible -neutral oral contrast and high-dose iv contrast are essential. ct appearances should be correlated with serum lactate as acute arterial occlusion without reperfusion may produce falsely 'normal' bowel wall thickness. early diagnosis and aggressive surgical intervention combining bowel resection with revascularisation offer the best prognosis. venous ami may present with a more chronic, intermittent course of pain, fever, abdominal tenderness and ascites. therapy is bowel resection and anticoagulation. ischaemic colitis occurs in elderly patients with atherosclerosis spontaneously or after aortic aneurysm repair. this invited lecture explores the groundbreaking use of ct for studying antiquities and artworks from a wide range of cultures, irrespective of their age or material. dr. marc ghysels, a former interventional radiologist, comes from a family of artists and collectors. about ten years ago he set up a private radiology practice in brussels where he analyses antiquities and artworks. over the years he has built an international reputation among collectors and art dealers as well as museum curators and experts working in auction rooms. art specialists call on his radiological skills and knowledge to authenticate antiquities, and more specifically to show: what methods were used to make the works, what damage they have suffered over the years, how much restoration has been done, and to expose the many tricks used by forgers to deceive not only the discerning eye of the collector but also the methods of scientific analysis more commonly used than ct scans. his presentation will highlight the prominent role of ct as a nondestructive test to explore selected artworks made in wood, terracotta, stone, and ivory. acute abdominal organ ischaemia may be caused by hypovolaemic shock, spasm (ergotism), embolisation and aortic dissection. embolisation is the most common cause. it occurs typically in elderly patients with atrial fibrillation, after myocardial infarction or due to a thoracic aortic aneurysm (taa). the primary diagnosis is made by ct with contrast enhancement which can also demonstrate cardiac thrombi or a taa. interventional treatment can be performed with a thrombectomy device or fibrinolysis with recombinant tissue plasminogen activator (rt-pa; mg loading dose, mg/hr infusion dose). acute aortic dissection may cause dynamic compression of the true lumen with occlusion of the ostium of the visceral arteries (floating visceral sign). the primary diagnosis is made by ct. occlusion of the primary entry tear with a thoracic aortic stentgraft may decompress the false lumen followed by reexpansion of the true aortic lumen followed by reperfusion of the visceral arteries. chronic abdominal ischaemia in younger patients may be due to fibromuscular dysplasia, takayasu arteritis or neurofibromatosis. in the elderly it is usually caused by arteriosclerosis. the patient may have post-prandial abdominal pain (angina abdominalis), diarrhoea and/or weight loss. due to the collateral circulation, symptoms usually occur only if more than one of the major arteries (celiac trunk, superior and inferior mesenteric artery) is narrowed. the diagnosis can be made by color doppler ultrasound (cdus), ct and mr with contrast enhancement. endovascular treatment is done by pta and stent placement. to learn what to include in the report of cns infections for the treatment planning. . to learn how to report follow-ups and treatment monitoring of cns infections. finding of a palpable mass in the abdomen always raises the possibility of an important clinical problem. a potentially life-threatening process, especially malignancy is the major concern. the list of differential diagnosis of "abdominal mass" is a very long one. in the process of differential diagnosis the most common approach is to evaluate the patient according to the gender, age, patient history and co-existing clinical and laboratory findings. the accompanying symptoms and signs and the location of the abdominal mass are the key indicators in the clinician's way of thinking in the process of differential diagnosis. for instance, a palpable mass with acute abdomen or intestinal obstruction will be assessed differently than a mass found incidentally. imaging is commonly required to confirm or ascertain the diagnosis. cross-sectional imaging is required to accurately evaluate a palpable abdominal mass in most situations. ultrasound and computed tomography have each been used successfully in evaluating patients with palpable abdominal mass. although each modality is appropriate in most situations, the advantages and disadvantages of each modality in certain situations will be addressed and the appropriateness criteria will be reviewed in this lecture. knowledge of a detailed clinical history is as important to the radiologist as to the clinician. its impact on the diagnostic accuracy in the interpretation of the images will also be addressed. a palpable abdominal mass has a long list of benign and malignant differential diagnoses. these diagnoses may be as different as a hydatid cyst of the liver, a volvolus, an aneurysm, or a giant renal cell carcinoma. the diagnostic approach is based on two major steps: first, the affected organ must be indentified. second, the differential diagnosis must be established based on imaging characteristics. the choice of ultrasound, ct or mri should be based on location and size of the mass. despite the fact that ultrasound is frequently used as a first step, the overview and anatomic orientation in large masses may be hampered, making ultrasound a better technique for image-guided biopsy than for primary diagnosis. in the vast majority of cases, multidetector ct is the first technique of choice. a thin-section protocol should be used to allow for high-quality multiplanar imaging. a pre-contrast scan is usually not required but can be helpful in suspected hemorrhage. for most upper and middle abdominal masses, biphasic imaging in the arterial and portal phase is recommended in order to establish the relation of the mass to the vasculature and to assess vascularity. in the small pelvis, mr is the superior imaging technique. otherwise, mri is mainly used for problem-solving. this course will discuss how to use the various imaging tool efficiently to narrow the differential diagnosis, decide about the need for biopsy and establish a suitable therapy. the most common viral infection of the brain is herpes encephalitis (hsv ). it is a necrotising encephalitis with a a mortality of more than %. on imaging studies lesions will be seen in the "limbic system", i.e. the temporal lobes, hippocampi, insular cortex and cingulate gyrus. they appear as hypodensity on ct, t -and flair hyperintensity on mri, possibly with haemorrhagic transformation. diffusion is restricted in the early phase. enhancement occurs at a later stage. human immunodeficiency virus (hiv) infection is a multifocal giant-cell encephalitis eventually leading to a progressive leuco-encephalopathy. on mr atypical focal or diffuse symmetrical signal abnormalities are seen neither with mass-effect nor with enhancement and typically sparing the u-fibers. spectroscopy can show an increase of myo-inositol. progressive multifocal leuco-encephalopathy (pml) is due to reactivation of the jc polyomavirus in immunocompromised patients, % of which are hiv positive. on mri "scalloped" multifocal asymmetrical lesions are seen with minimal mass-effect and without enhancement. new treatments of hiv, especially highly active antiretroviral therapy (haart) can lead to a paradoxical worsening of patients due to the immune reconstitution inflammatory syndrome (iris). on mri mass lesions are seen with diffuse patchy enhancement. cerebral toxoplamosis appears as multiple enhancing lesions with marked perilesional oedema. calcification is possible. prion diseases are caused by a proteinaceous infectious particle leading to creutzfeld-jacob disease in humans. diffusion weighted mr-images show high signal intensities in the cortex and the basal ganglia. abnormalities on t -weighted images and flair occur at a later stage where atrophy is mostly prominent. to learn how to assist clinicians for the diagnosis and differential diagnosis of bacterial and parasitic cns infections. susceptibility effects, increased radiofrequency (rf) field inhomogeneity and more pronounced magnetic shielding effects. in the mean time, many investigators have proposed strategies to optimise imaging protocols and to decrease sar levels and to reduce artefacts including optimised coil and hardware design, in combination with parallel imaging and modulation of refocusing flip angles. many clinical applications in neurology and angiography for high field mri that were recently being investigated showed benefits over . t. however, as of to date, virtually no prospective comparative studies have been performed and published that could help to estimate whether or not there would be any clinical benefit of . t msk over . t. although many authors described the improved snr of msk imaging at . t allowing for higher spatial resolution this has not been prospectively investigated with comparison to . t. further studies have to show whether the improvement in speed and resolution will also translate into increased patient throughput and earlier depiction of disease in msk applications at . t. ultrasound is the best imaging modality for evaluation of acute scrotal conditions. mri is used only rarely, when us findings are equivocal and in cases of suspected infarction. ct is used exceptionally, for example, to detect air in the scrotal wall. high-frequency transducers with modern software like compound imaging and native harmonic, and very good colour sensitivity for low flow in small vessels provide excellent insight into testicular morphology and vascularisation. it is very important to distinguish testicular torsion from the acute inflammation, as it has important therapeutic and even medicolegal consequences. in testicular torsion rapid diagnosis is vital, and salvage rate is directly related to timely operation. torsion is more common in younger patients and orchiepididymitis is more common in adults. infection usually starts at the epididymis and then spreads to testis the patient presenting with an abdominal mass represents a common clinical problem. clearly, the differential diagnosis is large and obviously will depend on the age and sex of the patient as well as location of the mass. of course history and clinical examination are mandatory, but formal diagnosis will usually rest on radiological interpretation. contrast examinations have now been replaced by cross-sectional imaging and endoscopy and it behoves the clinical radiologist to be aware of the advantages and limitations of these methods in order to reach a diagnosis. particular difficulty may be encountered when the mass is so large that it is difficult to determine the organ of origin. the purpose of this interactive case discussion is to explore the relative merits of ultrasound, ct, mr and endoscopy in establishing a diagnosis in two different cases. the cases concerned are: . a -year-old man who presents with a right iliac fossa mass, but is otherwise asymptomatic. . a -year-old woman who presents with anaemia and a large upper abdominal mass. active audience participation will be encouraged by means of key pads in order to respond to issues raised during the debate. the most straightforward expectation from t mri scanners is a gain in snr that could be translated in improving spatial resolution and/or reducing imaging time at an at least constant cnr. together with field strength, susceptibility effects, chemical shift and t increase and t and t * decrease. also, relaxation properties of contrast agents are modulated. rf power deposition is higher at t and is often a limiting factor in sequence parameter optimisation. hence, the need to optimise mri sequence protocol parameters at t. for cartilage, muscle, synovial fluid and fat, t increases by between % and %, t decreases by between % and % and r of gd chelates decrease by % to % when b increases from . t to t. in most applications reduced t and increased t work synergistically towards a reduced snr. since the change in relaxation times is not linear for the different tissues, cnr varies with field strength, too. a relatively straight forward approach is to lengthen tr in order to compensate for longer t and to shorten te to compensate for shorter t (*). in non-fat-sat images bandwidth needs to be increased to control chemical shift effects. because of the better fat and water peak separation, t often helps improve frequency-based fat saturation but may also be greatly impaired by field inhomogeneities in the presence of metallic materials. field strength (b ) and appropriate dedicated multi-element coils are the hardware prerequisites to bring high resolution (hr) isotropic imaging into clinical routine. depending on the age of the child, hip symptoms may predict a variety of diseases. in the infant, developmental dysplasia and infection should be considered. after the age of , irritable hip most commonly due to transient synovitis is the commonest disease but infection is the more worrying condition. perthes disease affects some and this condition overlaps into those over who may have a slipped upper femoral epiphysis. fractures and rare cases of osteonecrosis and chondrolysis are a concern in the adolescent. in the young and indeed in most cases, ultrasound provides a useful first line test. aspiration of effusion may be both diagnostic and therapeutic. in the older child and, especially when sufe is a risk, conventional radiographs with an external rotated "frog leg" view is very important. despite the logistics problems in children, there is an important role for mri especially in cases where the initial imaging does not explain the symptoms. i will review the imaging pathways and provide examples of common diseases. i will also discuss how to manage the difficult case and show recent audit data on detection rates and clinical management. fai refers to a conflict between the proximal femur and the acetabulum. both an abnormal shape of the proximal femur (fai of the "cam-type": aspheric femoral head with a laterally increasing radius and/or a waist deficiency of the femoral neck) and the acetabulum (fai of the "pincer-type": acetabular retroversion or a deep acetabulum) or a combination of the two may be present. for a long period the fai may be asymptomatic and the only clinical finding will be an impaired internal rotation of the hip joint. later as the disease progresses, cartilage damage (outside-in abrasion of the acetabular cartilage/cartilage delamination) and labral tears occur. labral tears are most common in the anterosuperior aspect of the acetabulum. a typical labral tear is an incomplete detachment with a tear located at the base of the labrum. anatomic variants such as a sulcus may be present and should be distinguished from tears. a sulcus is common at the junction of the labrum with the transverse ligament and is generally located beyond the equator of the hip joint. insufficiency fractures about the hip commonly occur in the region of the femoral neck. another site vulnerable to overuse is the symphysis pubis. often, a bone marrow oedema pattern around the symphysis pubis is observed. a characteristic finding is the "secondary cleft sign", which reflects a partial tear of the adductor tendon aponeurosis at the symphysis pubis. understanding age-related changes is essential for interpretation of imaging studies. age is a risk factor strongly correlated with osteoarthritis (oa) which is the most common hip joint disease seen in adults. the diagnosis of oa is based on a combination of radiographic findings and characteristic subjective symptoms. the lack of a radiographic consensus definition has resulted in a variation of the that is painful and hypervascularised on colour doppler imaging. in cases of torsion b-mode findings are non-specific, while on colour doppler flow is absent in complete torsion, but may be present and diminished in incomplete torsion, or increased in intermittent torsion. in cases of trauma ultrasound is important to diagnose haematoma, haematocele to evaluate integrity of testis and assess whether the testicular fracture is present or if the surgery is needed in cases of testicular rupture. imaging is helpful in cases of rare causes of the acute scrotum, such as fournier gangrene, testicular appendage torsion, vasculitis, and also in evaluation non-scrotal causes of symptoms, like in cases of renal colic, abdominal inflammatory and traumatic conditions, etc. a scrotal mass is an important clinical problem and a source of anxiety to the patient. radiologists play an important role in the management of these cases, since imaging is required to provide information about precise anatomical location of the lesion, its size and extension and, possibly, to elucidate the nature of the disease. the us and mri findings of the many different scrotal tumours will be presented in this lecture. special attention will be given to two topics. the first are the possibilities offered by imaging to differentiate among the different pathologies, especially to differentiate between benign and malignant lesions. the second will be the problem of the small, non-palpable, indeterminate testicular mass. such lesions have been shown to be relatively frequent. prevalence of malignancy varies widely in the literature, and orchidectomy seems not justified in all cases. the use of contrast-enhanced mri and of advanced us techniques (contrast-enhanced us and elastography) may help to narrow the differential. furthermore, the use of intraoperative us to guide removal of non-palpable testicular nodules can help to perform conservative surgery in lesions with no malignant potential. learning objectives: . to understand the typical imaging appearance of benign and malignant scrotal tumours. . to review differential diagnosis of intra and extratesticular scrotal tumours and the impact of imaging. c. imaging of the penis m. bertolotto; trieste/it (bertolot@univ.trieste.it) ultrasonography (us) is the first-line imaging modality in patients with penile disease. using high-end equipment after pharmacologically induced erection penile anatomy is well defined and virtually all clinically significant penile vessels can be evaluated in normal and in impotent men. the superior soft-tissue contrast resolution afforded by mr imaging provides an opportunity to advance imaging evaluation of the penis in selected cases. in the clinical practice, erectile dysfunction is the most frequent penile abnormality which is investigated with doppler us. the clinical role of this evaluation, however, reduced after the introduction of oral medications for impotence. differentiation among different forms of erectile dysfunction is mainly based on evaluation of doppler waveform changes in the cavernosal arteries. peyronie's disease is the most frequent cause of penile induration. imaging is often required to evaluate the extension of the plaques, involvement of the penile septum, and relationship between the plaques and penile vasculature. in patients with penile traumas, imaging allows accurate evaluation of albugineal tears, extra-albugineal and cavernosal haematomas, vascular lesions producing high flow priapism and other pathological changes. compared with us, mr imaging has some advantages in identification of small albugineal tears, and is more accurate in identification of urethral or spongiosal involvement. other situations in which penile imaging can be required are circumscribed or diffuse cavernosal fibrosis, tumours, priapism, severe inflammation, and evaluation of postsurgical complications. most of these conditions are first investigated with us; mr imaging is optimal for tumour staging. endocrine tumours of the pancreas are derived form the apud cell system. they often show early clinical sign related to the hormones produced by these tumours. the usually very specific symptoms raise the suspicion of an endocrine tumour of the gastro-entero-pancreactic tract and initiate imaging studies for tumour detection. in this setting usually the pancreas is among the most frequent tumour sites. since endocrine active tumours of the pancreas usually show a strong vascularisation, they can be differentiated from other solid tumours of the pancreas -including adenocarcinoma of the pancreas. metastases in the pancreas are very rare -however, they represent a potential differential diagnosis either for non-functioning neuroendocrine tumours or for adenocarcinoma of the pancreas. since the evaluation of the whole pancreas is crucial, transabdominal ultrasound plays an only limited role for the detection of endocrine pancreatic tumours. usually mri and ct -alone or in combination with specific nuclear medicine tracers in pet -are needed for accurate diagnosis and staging of these tumours. published incidences and prevalence of oa. the progression of oa traditionally has been measured using radiographic joint space width (jsw). weight-bearing radiographs centered on the hip are the most reproducible and reliable ones. the sequence of degeneration includes the following radiographic findings: joint space narrowing, osteophyte formation, subchondral sclerosis, and cyst formation. current definitions of radiological oa based on reduced jsw and osteophytes display predictive validity for clinical hip oa. radiographs are also useful for assessing developmental dysplasia and other congenital disorders which may lead to early oa. there are cases though, that radiographs show minor changes and the clinical suspicion of early disease can be confirmed with more sophisticated imaging methods, such as ct and mri. ct is helpful for additional measurements such as femoral and acetabular abnormal version which might lead to oa. femoroacetabular impingement has been shown to cause labral and chondral lesions and leads to oa. prompt recognition of abnormal head-neck junction on radiographs enables proper conservative or surgical treatment planning. mr arthrography is the method of choice for assessing the labra whereas ct arthrography might be used as an alternative for articular cartilage assessment. cystic tumours of the pancreas include a variety of masses which can be classified into cystic tumours of the exocrine pancreas, cystic tumours of the endocrine pancreas, cystic tumour-like lesions of the exocrine pancreas. in order to simplify the approach only the relatively common cystic tumours -the intrapapillary mucinous tumours (ipmt), the serous cystoadenoma (sc) and the mucinous cystoadenoma (mc) -will be considered. ipmt are characterised by ductal dilatation. imaging characteristics of ipmt are best displayed at mr-cholangiopancreatography. on the basis of the extent, these tumours can be divided into ipmt of the main duct (or central), ipmt of the secondary ducts (or peripheral) and mixed ipmt. central and mixed ipmt have a malignant behaviour and therefore need to be treated surgically, while peripheral ipmt have a benign behaviour and, in general, need only follow-up. sc are characterised by a microcystic architecture in most cases. imaging features are typical in cases of microcystic appearance and consist of small amounts of fluids interspersed within multiple septae of a "sponge like" mass. the differential diagnosis with a mucinous cystoadenoma is difficult in cases with a oligo-macrocystic appearance. mc appears as a uni-oligolocular cystic mass, with a simil-ovaric stroma in the tail of the pancreas. imaging features include a cystic mass with a definite wall and inner septae. when calcifications and enhancing nodules are present, a mucinous cystoadenocarcinoma has to be suspected. therefore, a careful evaluation of imaging features of pancreatic cystic tumours is needed to differentiate benign form malignant masses. learning objectives: . to understand the classification and management of cystic pancreatic tumours using rad/path correlation. . to learn how to provide a differential diagnosis and how, when and why imaging techniques should be used. . to review pathological and imaging findings of intra-ductal cystic tumours. . to learn how to deal with the incidental pancreatic cyst. a s c b d e f g the evolving role of the radiologist p. brader; vienna/at (peter@brader.md) in the past two decades, enormous strides have been made in medical imaging and many new technologies and agents are now available for breast cancer research, clinical trials and patient care. advances in experimental and clinical breast imaging are likely to improve our knowledge of how breast cancer arises at the cellular level, which will help not only to identify and locate tumours but also to assess the activity of biological processes within these tumours. this recent and concomitant progress, in imaging in general, and in breast imaging in particular, has been facilitated by the convergence of molecular cell biology, pathology, chemistry, physics and engineering in a multimodality and multidisciplinary way. the challenge for radiology is to begin thinking at the molecular level. it is, therefore, important that the next generation of radiologists become more involved in multidisciplinary research and clinical work, and that younger radiologists receive special training in diagnostic imaging and nuclear medicine, as well as a solid understanding of physics, radiochemistry, pathology and biology. applying this approach to breast cancer patients should allow earlier detection, stratification of patients for treatment, and objective evaluation of new therapies. the outcome will be considerably better management and care of those with breast cancer. breast cancer is the leading cause of cancer death among women worldwide. imaging plays a key role in the early detection of breast cancer. mammography is an accepted screening modality with some limitations such as over-treatment. to overcome these limitations research is going on to characterise breast cancer more accurately. currently researchers are working on different strategies spanning the spectrum from tomography-based systems to mri and even molecular imaging. this panel discussion will focus on these different strategies. the auditorium will learn if in imaging still plays a major role in breast cancer detection or whether a simple blood test will eventually solve the problem. breast cancer is the leading cause of cancer death among women world wide. imaging plays a key role in the early detection of breast cancer. mammography is an accepted screening modality with some limitations such as over treatment. to overcome this limitations, research is going on to characterise breast cancer more accurately. currently researchers are working on different strategies spanning the spectrum from tomography-based systems to mri and even more molecular imaging. this panel discussion will focus on these different strategies. the auditorium will learn if in imaging still plays a major role in breast cancer detection or a simple blood test will eventually solve the problem. is mammography still an accepted modality for breast cancer imaging in ? m.j. yaffe; toronto, on/ca (martin.yaffe@sunnybrook.ca) x-ray mammography is currently the only imaging modality that when used in routine screening has been demonstrated to contribute to reduced mortality in women in the age range - . but, the accuracy of mammography is limited with respect to both sensitivity and specificity. digital mammography has provided increased sensitivity in women with dense breasts and three-dimensional methods such as digital breast tomosynthesis or dedicated breast ct promise to yield further improvement. however, these techniques are dependent on detecting rather gross physical changes as masses, microcalcifications or architectural distortions develop and, therefore, their ultimate potential is limited. it is likely that before , detection tools that are more specifically targeted to molecular characteristics or early functional changes associated with cancer will be clinically available. these may be either in the form of an imaging test, based on a specific biomarker for the cancer or possibly an innocuous test designed to sense a circulating biomarker in the blood or urine. in the latter case, a positive test would be followed by an imaging study to provide localisation for therapy. such tests could not only detect the presence of disease but would also provide prognostic information to guide the type and aggressiveness of therapy so that overtreatment could be avoided. promising imaging techniques based on targeted imaging with ultrasound, x-ray contrast agents, mr and radio-labelled agents are already under investigation. by exploiting new molecular or functional signals one of these is almost certain to replace mammography before . can we assess cell density of tumours with imaging techniques? d.-m. koh; sutton/uk imaging is increasingly used to define endpoints of clinical trials in oncology. tumour cellular density may be inferred by diffusion-weighted mr imaging (dw-mri) and measurement of the t relaxation time. dw-mri is unique as the mechanism of contrast is based on differences in the mobility of water between tissues, which can be quantified by the apparent diffusion co-efficient (adc). tumours are frequently more cellular compared with their tissue of origin which impedes water diffusion, resulting in increased conspicuity on dw-mri and lower adc values. studies have shown negative correlations between histopathologically determined cell density and adc in several tumour types, including prostate cancer, soft tissue sarcomas and cerebral tumours. dw-mri is sensitive for tumour detection, especially for disseminated peritoneal disease, liver and bone metastases. whole body dw-mri with background suppression (dwibs) is an emerging technique that has shown substantial promising for staging of lung cancer, prostate cancer, lymphoma and multiple myeloma. effective treatment results in reduction in cell density due to cell lysis, apoptosis and necrosis, leading to a rise in adc value. adc increase has been observed within days of anti-tumour treatment (including chemotherapy and radiotherapy); and as early as one to two weeks after treatment. quantitative adc measurements may also be prognostic as tumours with higher pre-treatment adc have been shown to respond poorer to chemotherapy and radiotherapy. nevertheless, a number of challenges still have to be overcome to qualify adc as a response and prognostic biomarkers in a multi-centre setting across different imaging platforms. angiogenesis is an essential process whereby tumours derive vascular supply from adjacent tissue, to sustain tumour growth and metastatic spread. newer targeted antiangiogenic therapies differ significantly from current cytotoxic therapies for cancer. the methods of dose selection are either invasive, such as biopsy and histology, or time consuming, such as tumour shrinkage and time to disease progression, both of which take months to assess and fraught with other limitations. moreover, cancer is a very variable disease, which means that some patients will respond to a particular therapy while others will not. there is, therefore, a great need to establish surrogate markers for drug response that are both rapid and reliable, not only for clinical trials of new drugs but also to aid in the selection of optimal treatment for individual patients. multiparametric imaging techniques provide a non-invasive insight into tumour cell density, vascularisation, and biochemistry. imaging data have the potential to provide information on disease profiling pertaining to diagnosis, prognosis, selection of therapy, monitoring of response to therapy, and pharmacokinetic information of drugs. undoubtedly, these methods hold great promise, but how can we standardise these techniques, in terms of acquisition parameters and image analysis (post-processing), and validate imaging parameters as biomarkers in multicenter international cancer trials. beginning with a review of the frequently used response evaluation criteria in solid tumours (recist), the development and optimisation of new imaging parameters as biomarkers of treatment response and optimised monitoring of tumour therapy in multicenter eortc clinical trials will be presented. dw-mri is sensitive for tumour detection; adc is affected by the different cellular density of a tumour. still, a number of challenges need to be overcome to qualify adc as a response and prognostic biomarker in a multicenter setting. the large variety in primary tumours and imaging methods, as well as the large variety and continual evolution of imaging equipment, point towards the need for a concerted design of imaging protocols in order to assure that these protocols are applicable to multicenter trials. furthermore, reliable evaluation of imaging data requires imagers experienced in the area of the definite cancer targeted in this trial and in the use of imaging tools for lesion quantification. from this session, a roadmap for future collaboration between eortc and esr combining different imaging modalities will emerge. session objectives: . to prove that advanced multiparametric imaging techniques play a crucial role in the diagnosis, staging, treatment monitoring and follow-up of oncological patients. . to explore avenues for future collaboration between eortc and ecr. . to suggest input of radiologists in the design and implementation of multicenter trials. the eortc imaging group: vision and strategy on cancer imaging s. stroobants; antwerp/be (sigrid.stroobants@ua.ac.be) response to cancer treatment is evaluated by subsequent assessments of target lesions and is defined as a significant decrease in measurable tumour dimensions (who, recist). the new targeted therapeutics which cause cytostasis rather than cytotoxicity have challenged volume-based response criteria and tumour regression is increasingly recognised as an unreliable end point. new imaging modalities looking at tumour biology, like positron emission tomography (pet) or diffusion weighted (dw) and dynamic contrast enhanced (dce) magnetic resonance imaging (mri) or increasingly used to identify subpopulation of patients most likely to respond. recently, new response criteria were introduced that incorporate fdg-pet (recist . for solid tumours and new cheson criteria for lymphomas). since imaging is becoming increasingly important in novel trial design, the eortc decided to invest in an imaging platform. eortc has established a medical imaging exchange infrastructure allowing to store imaging data linked to the clinical databases. a functional imaging expert group is set up to review protocols, organise central review and develop specific initiatives for imaging biomarker validation. eortc is part of the quicconcept consortium that within the eu innovative medicine initiative (imi) will try to validate the use of novel pet probes and dw-mri as biomarkers for apoptosis and proliferation. functional imaging techniques can only evolve successfully into biomarkers that are clinically valuable and important for drug development, when there is agreement on the standards for measurement and analysis and working groups are set up in collaboration with the different professional organisations (esr, eibir, eanm) to set up imaging guidelines. conditions such as ttts in twin pregnancies and foetal demise. the living foetus can also suffer from abnormal blood supply to the cns, and thus showing small or even large hemispheric infarcts. other diffusion technique, dti is also used to demonstrate the white matter formation of the foetal brain. mrs is also used in the evaluation of the foetal brain. the values of the naa, choline and the existence of lactate are different than the values in the paediatric and adult brain. learning objectives: . to explore the new imaging techniques for the study of the foetal brain. . to understand the use of diffusion-weighted imaging in the foetal brain. . to become familiar with the accurate use of t -weighted sequences in the foetal brain. . to understand the possibilities of tractography in the fetal brain. the paediatric central nervous system is a complex structure undergoing rapid development. as such, there is a rapid, continuous modification of what is "normal" in relation with age and the stage of development. knowledge of the normal patterns of brain development in the clinically relevant ages from to years is necessary to interpret neuroimaging findings correctly. knowledge of embryology and normal variants is also greatly helpful. mr imaging equipment and parameters need to be adjusted and optimisation for paediatric studies. pitfalls often occur from the misunderstanding of normal conditions that are perceived as abnormal based on a comparison with the appearance of the normal brain in adults. this includes, for instance, the evaluation of the brain in the first - years of life during the course of the process of myelination. a summary of the most frequent conditions that may lead to misinterpretation of findings will be provided here. learning objectives: . to understand a different approach to neuroimaging in the developing paediatric brain and spine. . to appreciate that, despite the wide and potentially complex spectrum of diseases seen in neuropaediatrics, most interpretations can be made through the thoughtful application of basic neuroradiological analytical techniques. . to be aware of certain areas where common pitfalls, myths and misunderstandings occur. the ability to develop more aggressive treatments of acute neurological disorders in children is nowadays improving; however, infants and children are often uncooperative, clinical signs are not always easily localised, and diagnosis and therapy may be both delayed. effective imaging of the central nervous system assumes an increasingly important role in the evaluation of these critically ill children. this lecture will review the main indications to perform a neuroimaging procedure in children with a neurological emergency. with didactic purposes, acute conditions will be classified in traumatic and non-traumatic (ischaemic and haemorrhagic stroke, infection and acute metabolic disorders). differential diagnosis will be discussed based on representative cases selected from the daily routine in a paediatric tertiary hospital. the varied neurological complications that can occur in the child admitted at the intensive care unit will also be presented in a didactic manner, including pres (posterior reversible encephalopathy syndrome), acute liver failure, osmotic demyelination syndrome, hypoglycaemic encephalopathy or induced neurotoxicity. eventually, some peculiarities in oncologic and immunosupressed children, particularly opportunistic infections, will be highlighted. practical algorithms with the preferential use of either ct or mri will be developed for each section. ct continues being the primary modality for trauma, although it should be better used in cases of non-available mri in the other acute conditions to save radiation in children. mr imaging is nowadays better for imaging these children owing to the new techniques that can be used, such as diffusion imaging (di), spectroscopy, arterial spin labelling (asl) or susceptibility-weighted imaging (swi). learning objectives: . to learn the characteristic neuroimaging findings that may be useful in establishing differential diagnoses. . to understand the various neurological complications that can occur in the intensive care unit and to become familiar with their most typical imaging patterns. . to consolidate knowledge of the best neuroimaging protocols for the acutely ill child and establish the main indications for the use of mr imaging, particularly diffusion and spectroscopy. challenges for morphologic imaging in oncology trials: reproducibility and reading f.e. lecouvet; brussels/be (frederic.lecouvet@uclouvain.be) beside clinical endpoints and biological or molecular parameters, beside emerging perfusion or diffusion imaging techniques, morphologic imaging remains the cornerstone of the evaluation of treatment response in the majority of primary or metastatic tumours. the large variety in cancers and imaging methods, as well as the large variety and permanent evolution in imaging equipments, raises the need for a concerted design of imaging protocols to guarantee transposability of these protocols to multiple centers. the reliable evaluation of imaging studies obtained in trials requires readers experienced in the area of the definite cancer targeted in this trial, and in the use of imaging tools for lesion quantification. the imaging group of the eortc targets this optimisation of imaging protocols. first, the different "organ groups" of the eortc will benefit from the availability of expert radiologists in the different fields of oncology, involved in the choice and tuning of adequate and generalisable imaging tools from the beginning of trials design. the design of ct or mri studies should target acquisition parameters transposable in a large number of centers; there is no need for "cutting edge" protocols for a reliable assessment of response in a majority of cancer patients. second, the central review of imaging studies will be possible based on the involvement of expert radiologists, and on a robust imaging platform that guarantees availability, quality control, and "side by side" evaluation of baseline and follow-up examinations. principles and limits of response evaluation by morphologic imaging in oncology will be illustrated. a practical approach to hrct of the chest for diagnosis of diffuse lung diseases includes: recognition of the abnormalities, definition of their distribution within the secondary lobule or the lung, identification of associated findings. when combined with the patient clinical history, these steps allow to shorten the list of differential diagnoses and may sometimes lead to a specific diagnosis. a reticular pattern consists of multiple lines as the result of interlobular septal thickening, intralobular lines or cystic walls of honeycombing. when present as a predominant abnormality, thickening of interlobular septa has a limited differential diagnosis which includes pulmonary oedema/haemorrhage, lymphangitic spread of cancer, sarcoidosis and alveolar proteinosis. honeycombing represents destroyed and fibrotic lung tissue containing numerous cystic airspaces with fibrous walls and is considered a ct feature of established pulmonary fibrosis. when honeycombing is present, uip is likely the histologic pattern and ipf is the most likely diagnosis, in the absence of a known disease. a nodular pattern consists of multiple rounded opacities - mm in size. the distribution of nodules is the most important factor in making an accurate diagnosis. a centrilobular predominance of nodules that typically spare pleural surfaces is a frequent sign of bronchiolitis and airway disease. a perilymphatic distribution is most frequently seen in patients with sarcoidosis, silicosis and lymphangitic spread of cancer. a random distribution with nodules diffusely and uniformly distributed can be the result of infection, haematogenous metastases and other rare diseases such as langerhans cell histiocytosis. the diffuse interstitial lung diseases (dilds) are a heterogeneous group of disorders which principally affect the lung parenchyma. basic hrct patterns are common to many disease processes and are usually non-specific. however, their distribution and their temporal evolution are often characteristic enough for diagnostic purposes. increased lung opacity: air-space consolidation, by definition, occurs when alveolar air is replaced by fluid, cells, or other material. on hrct, consolidation results in an increase in lung opacity associated with obscuration of underlying vessels. conversely, ground-glass opacity is defined as: "... hazy increased attenuation of lung with preservation of bronchial and vascular margins". the significance of ground-glass opacity depends on the clinical scenario. cysts and decreased lung opacity: a cyst appears as a round parenchymal lucency or low-attenuating area with a well-defined interface with normal lung. lung diseases characterised by cysts include langerhan´s cell histiocytosis, lymphangioleiomyomatosis, lip, postinfectious pneumatoceles, and amyloidosis. recently, lung cysts have been reported in association with extrinsic allergic alveolitis. honeycombing is a process characterised by the presence of cystic spaces.the determination of the presence or absence of honeycombing on hrct in patients with idiopathic interstitial pneumonia is of great importance. honeycombing may have an atypical distribution particularly in asbestosis, sarcoidosis, non-specific interstitial pneumonia (nsip), drug-related fibrosis and hypersensitivity pneumonitis. hrct is now an integral component of the clinical investigation of patients with suspected and established interstitial lung disease. a knowledge of the close relationship between histopathological changes and ct appearances. learning objectives: . to understand the different patterns on hrct scans of the chest. . to learn about a systematic approach to differential diagnosis of diffuse lung diseases. . to review key imaging findings. how do we report ct of the chest? : the radiology report is often the primary method of communicating imaging findings to the referring physician. practical guidelines on how to report ct scans of the chest for diffuse infiltrative lung diseases will be provided by the panel. emphasis will be placed on both report content and style in order to provide the clinician a tool for good patient care. with the advent of volumetric data acquisition and with increasing knowledge of patho-radiological correlations, hrct has further matured over the last decade and provides the radiologist with an excellent tool for accurately demonstrating gross lung anatomy and precisely analysing abnormal findings. the radiologic diagnosis of many pulmonary abnormalities is based on an assessment of their pattern and distribution. while the pathologist has the advantage of being able to evaluate specimens microscopically, the radiologist is confined to the assessment of more gross disease. however, the radiologist is able to examine the entire lung providing him with information about the distribution of disease and about additional diagnostic clues in mediastinum and pleura. both together, characterisation of the gross findings and knowledge of their distribution represent the key features for arriving at a confident diagnosis. session objectives: . to become familiar with the standardized and internationally accepted terminology for describing and analysing hrct findings. . to learn how a structured analysis of the predominant pattern and its distribution represent the key for making a specific diagnosis in the best case scenario or to understand how it helps to narrow the differential diagnosis. . to promote the understanding how the variability of manifestations of some diseases can cause an overlap of findings being responsible for difficulties the radiologist encounters when categorizing diffuse diseases of the lung parenchyma. a. most radiological reports consist of a ‚descriptive part' in which the radiologist describes the findings and a short ‚conclusion part' containing the interpretation of what is seen. both parts are filled with ‚jargon'. some terms are typical radiological ‚language' while others refer to terminology also used by clinicians and pathologists. some terms are purely descriptive but others may contain already some interpretation of what is seen and hence narrow the differential diagnosis. the meaning of a term may also change over time. it is very important that both radiologists and the readers of their reports speak the same language and know and understand the meaning and full content of each term. this is especially important when radiological findings in patients with diffuse lung diseases are described and interpreted. diagnosis of diffuse lung disease is indeed largely based on the recognition and description of the appearance pattern of the disease because this often allows developing an appropriate list of differential diagnosis. members of the fleischner society have introduced a glossary of terms for thoracic imaging. this presentation will emphasise on the importance of such a glossary for both describing and interpreting chest images. special attention will be given to the terms used to describe the different patterns in diffuse lung diseases: ( ) reticular and short linear opacities, ( ) nodular opacities, ( ) increased lung opacity and ( ) cysts and decreased lung opacity. a s c b d e f g h the purpose is to describe ethical dilemmas related to the use of radiation in finnish radiographer's work in diagnostic imaging. the data were collected during the spring and summer of , and it consisted of thematic interviews of diagnostic radiographers (n= ) whose working experience varied from to years. the data were analysed by the method of data-oriented qualitative inductive content analysis. ethical dilemmas related to the use of radiation were found to concern justification and optimisation principles, which were found to be inadequately implemented by radiographers. the background factors of these dilemmas were found to be both dependent on and independent of the employee, resulting in worsened well-being at work and in seeking for change. the current processing methods of dilemmas were found to be insufficient, and suggestions for better processing methods were made. the results suggest that there may be shortcomings in radiographers' knowledge of radiation usage. attitudinal problems within the work community seem to maintain ethical shortcomings. instead of ethically inadequate routines and passing the baton to other professionals, radiographers should be encouraged in committing themselves into responsibility and safety culture. respondents repeatedly described powerlessness and inability to intervene in ethical problems. the common cold is one of the most frequent illnesses in europe and the united states. although most cold are mild and resolve within a short time period, colds cost billions of dollars per year, mostly due to lost time at work and school. the common cold is a group of symptoms caused by one of a large number of viruses. rhinoviruses cause the greatest number of colds; there are more than different varieties of rhinovirus. the average adult experiences two to three colds per year, while children average - colds per year. in most cases, colds do not cause serious illness. most colds last for - days, although many people continue to have symptoms (coughing, sneezing and congestion) for up to weeks. some viruses that cause the common cold can also depress the immune system or cause swelling in the lining of the nose or airways; this can lead to bacterial infection. one of the more common complications is sinusitis, which is usually caused by viruses and rarely (about % of the time) by bacteria. however, it can be difficult to distinguish bacterial sinusitis from sinusitis caused by a cold because the signs and symptoms can be similar. however, due to the fact that a runny nose can also result from inflammation, trauma, foreign body and other abnormal processes, including tumours, an excellent diagnostic workup is necessary. the purpose is to examine the relationship between man and technology within radiography without considering man and technology as separate entities. the study is designed as an observational study which took place in a danish radiological department. it involved examinations followed up by three semi-structured interviews. through emergent narratives radiographers construct a practice in which the relationship between man and technology is marked by a struggle of domination of one over the other. the struggle expresses itself through two competing plots: a diagnostic plot with a prevailing, but not merely chronological structure mostly composed of events tied to pathology. the life story, in opposition, plots the examination as a significant experience in the patient's life, transforming it into events stretching towards a future yet unknown. most often the radiographers contributed to the domination of man over technology through active engagement of their narrative alertness. errors and failure to keep the time schedule can, however, lead the radiographers to a change of perspective that makes them displace man from the scene of radiography by playing on the premises of technology. in several stories technology can be labelled ‚setting' while the patient plays the main role. the radiographers act with the patient as point of origin, but they reason with technological arguments. hence, the human aspects of radiography constitutes an underground practice, which is not explicitly articulated valuable. this creates a field of tension between man and technology, with risk of technological dominance. the private life of everyone of us as well as the everyday practice of our profession is deeply embedded in ethical/deontological aspects which play a critical role into: our profession, the relationship with our patients, with our colleagues, with the health care team we work with, and with ourselves. the radiographer's everyday practice has to take this aspects into account. ethics finds its origins in the fusion of three different sources, as if it were a compromise between: the species we belong to, the society we live in, and ourselves. yet, we are not obliged to abide to these three elements. it is through our actions that we decide how to behave in certain situations. and this is the reason why every single action towards the others gathers importance, the simple rites when individuals meet play a pivotal role in the creation of a relationship with the others. shaking hands, greeting and using polite forms of speech, all these actions are ethically important, they allow us to catch the benevolence of our interlocutor and to discourage any possible hostility. what would happen if our professional identity were perceived and acknowledged through the way we can interact and relate to others? in this case, the work no longer ennobles the man, but it is the man, through his actions, who ennobles his profession. behaving ethically towards one's own profession, towards the others and towards ourselves, is it, or could this be the common ground of european professional ethics? whenever a diagnostic x-ray examination of a pregnant patient is considered to be necessary, conceptus dose estimation is an important step in assessing the risks to the unborn child. accurate estimation of conceptus dose is also needed after inadvertent irradiation of a pregnant patient from a diagnostic x-ray procedure. several methods have been developed to estimate conceptus dose from radiologic examinations. when the uterus is remote from the directly exposed tissues, the conceptus is exposed to scattered radiation and its dose is negligible (< mgy). examinations involving the abdomen-pelvis may deliver higher dose to the child. variations in maternal body size and uterus position should be taken into account to obtain accurate conceptus dose estimation. multidetector ct (mdct) scanners have replaced conventional ct technology. conceptus doses from abdominal mdct range from about to about mgy during the first post-conception weeks for a scan acquired at kvp, mas with a pitch of . , depending on maternal body size and uterine position. multi-phase abdominal ct examinations may deliver relatively high doses to the unborn child. doses to the conceptus below mgy should not be considered a reason for termination of pregnancy. the risk to the embryo/foetus for stochastic effects is assessed on the basis of dose using appropriate risk factors. although these risks from a single diagnostic procedure are low for the majority of diagnostic x-ray examinations, it is important to ensure that doses are kept as low as reasonably achievable. learning objectives: . to learn how to manage and counsel pregnant patients in case of (a) intentional and (b) accidental exposure. . to learn how to estimate conceptus radiation dose from diagnostic x-ray examinations. . to learn how to assess the radiogenic risks to the embryo/foetus from diagnostic x-ray examinations. epithelial cells. the mucociliary transport drains each sinus in a specific pattern through its ostium to the nasal cavity and ensures a constant flow of mucus containing bacteria and particulate matter. functional endoscopic sinus surgery (fess) aims to enlarge the preformed ostia to allow physiologic drainage. preoperatively, anatomic variants have to be ruled out or shown by ct to avoid injury. special emphasis lies on the ostiomeatal unit, a complex anatomic region at crossroads of mucociliary drainage from frontal, anterior ethmoid and maxillary sinuses (uncinate process, haller, agger and frontoethmoidal cells, inverse turbinate). description of the level of the cribriforme plate in relation to the roof of the ethmoid is another key element in a report to avoid skull base injury (keros i-iii). preoperative identification of variations in the location of the optic nerve and the cavernous portion of the internal carotid artery is also mandatory. furthermore, the close proximity of the sinuses to neighbouring structures and their thin bony walls predispose to certain pathways of spread. runny and stuffy noses may be due to a long list of pathologic conditions, which require distinct imaging strategies and treatment options. acute rhinosinusitis, for example, is normally managed by gps without any imaging study. occasionally, signs and symptoms suggest orbital or intracranial complications: in such cases msct allows a prompt diagnosis and is preferred to mri for wider availability and faster acquisition. persistence of signs/symptoms for longer than weeks classifies rhinosinusitis as chronic (crs); the condition may or may not be associated with the presence of nasal polyps. in patients affected by crs cross-sectional imaging aims at precisely depicting bone structures and air conduits. in detail, imaging shows the anatomic arrangement of sinus drainage pathways and their patency, maps anatomic variants that may facilitate crs or increase surgical risk, depicts bone changes induced by crs or by the mechanical pressure exerted by polyps. these tasks are better accomplished by ct, even more so after the advent of multislice technology allowed multiplanar reconstructions along oblique planes. after surgery, imaging is required when signs/symptoms recur -to asses presence and extension of crs or nasal polyps -or when late complications are suspected -such as mucosal synechiae impairing mucus drainage or mucocele. mri plays a limited role in sinusitis because it fails to demonstrate thin bone structures; nonetheless, its use is advocated in aggressive inflammatory diseases (such as invasive mycoses and wegener's granulomatosis) to demonstrate the involvement of deep spaces of the face and of the skull base. sinonasal tumours are rare and comprise only % of all malignancies. the clinical and radiological challenge is to differentiate malignancy from benign or inflammatory changes. most malignant tumours present at advanced stages. malignant tumours are most common in the th - th decades and have a male preponderance. squamous cell carcinomas are the most prevalent ( %) followed by adenocarcinomas. squamous cell carcinomas are most common in the maxillary sinus, next the nasal cavity and ethmoid sinuses, while adenocarcinomas are most often seen in the ethmoid sinuses, and commonly caused by occupational exposures, e.g. nickel and hardwood workers. inverting papilloma is one of the most common benign tumours and have been associated with human papillomavirus. ct should be the first modality in paranasal sinus imaging, while complementary mri before and after gadolinium i.v. is mandatory to differentiate tumour from inflammatory disease. a general rule is that tumours more often have unilateral extension and that malignant tumours usually erode the bone. however, malignancy may mimic benign tumours with thickening or remodelling of the adjacent bone. while ct is superior to demonstrate changes in the bone, mri can differentiate tumour from inflammatory changes and demonstrate tumour invasion and perineural spread. malignant tumours are: squamous cell carcinoma, adenocarcinoma, adenoid a s c b d e f g h b. x-ray imaging and pregnancy: justification and optimisation of exposure p. vock; berne/ch (peter.vock@insel.ch) as outside pregnancy, justification and optimisation are the main steps to be done when an imaging examination using ionising radiation is considered during pregnancy. however, the risk concerns the embryo/foetus in addition to the mother which means that justification has to be more critical whenever the uterine dose is not neglectable. the practical approach to an examination in any woman of child-bearing age starts by ruling out pregnancy, whether by taking history or by a laboratory test. when pregnancy cannot be ruled out, further steps will depend on the type of examination needed and the urgency of diagnostic clarification. ultrasound is the alternative to be preferred when it can answer the clinical question. but even among x-ray examinations, the uterine dose is varying widely which asks for a careful selection, optimisation and, maybe, for postponing the test. once pregnancy is confirmed, the major question is whether the specific type of diagnostic examination will include the uterus in the primary radiation field. examinations not involving the uterus by direct radiation -despite a potentially significant exposure by scattered radiation -can usually be performed without a relevant risk to the embryo/ foetus. the situation is more critical when the uterus is within the examination field and when therapeutic interventions are considered. the presentation will discuss the practical approach to these different situations, the influence of the stage of pregnancy, optimisation methods and the choice between alternative methods in some frequent clinical situations. this paper explores the risks to the foetus when magnetic resonance imaging (mri) is used. mri uses three main components to produce images from inside the body: a static magnetic field; a pulsed radio-frequency (rf) fields and time-varying gradient electromagnetic fields. the exact frequencies of these fields depend on the mri system purchased, for example; a . t scanner uses mhz rf, a . t system uses mhz and a t system uses mhz rf. there is also a wide range of options for gradient strengths and slew rates to be considered as well. the overall exposure for the foetus depends ultimately on the imaging sequence used and the area being scanned. this paper will discuss particular hazards that need to be addressed for pregnant women including biological effects of the static and time-varying magnetic fields, heating effects of the rf pulses and acoustic noise generated by the spatial encoding gradients. the circumstances for foetal exposure in mri will also be discussed including the following situations: the patient may not be aware that she is pregnant, likely to be in the first trimester; the mother is referred for direct foetal imaging after ultrasound (normally second or third trimester); the expectant mother may need diagnosis; research on pregnant volunteers. the exposure for pregnant staff working in mri is also an essential consideration. finally, how to minimise the exposure for the foetus during mr imaging will be discussed. a b c d e f g h in terms of cerebral perfusion (rcbf, rcbv, mtt and ttp) and cell metabolism (cytotoxic versus vasogenic oedema, diffusion restriction). the fundamental goals of stroke imaging in the acute phase are: . to rule out intracranial haemorrhage, and other non-stroke causes of the patient's symptoms; . to show occlusion of a major blood vessel, e.g. by ct or mr angiography; . to demonstrate ischaemic brain tissue (cytotoxic oedema), e.g. by diffusion-weighted mri; . to reveal tissue blood flow and to identify areas of salvageable brain tissue ("penumbra"), e.g. by perfusion ct or mri; . to select candidates for thrombolytic therapy within the critical to hour time window. the purpose of this presentation is to review how new developments in neuroimaging improve our understanding of the pathophysiology of acute stroke and to demonstrate that multiparametric techniques now play a crucial role in the rapid diagnosis, clinical management, therapy and outcome prediction of patients with an acute stroke. organisation is crucial to the practice of dethrombosis. the first step is to grasp the fact that ischaemic stroke is an emergency. stroke victims require an organisation similar to that provided for heart attack patients. patients must be taken to hospital in an ambulance manned by a specifically trained crew. ideally equipped with a mini ct scanner recently made available. this device provides an immediate morphological scan and ct angiogram to be sent by satellite to the reference hospital so that the problem will be clear and the medical team ready on the patient's arrival. clinical and neurological assessment of the patient must be undertaken immediately along the lines of uk practice implementing a simple, clear and rapid procedure. if the clinical, ct and ct angiography findings indicate intra-arterial treatment, responsibility shifts to the neuroradiology team, organised to work a hour shift, at the hospital or at least on call. dedicated imaging systems must be available: a multi-layer ct device (ct angiography and perfusion studies). dedicated angiography suite is essential. a flat panel system would be ideal. there is growing evidence supporting the availability of an mr system. this device would certainly enhance the possibilities of a stroke unit but it is not essential in the initial stages. a stroke unit should be based on a dedicated facility, with emergency access separate from the general emergency room, dedicated equipment, dedicated ambulances and appropriate links including a dedicated ward and a rehabilitation unit essential to the success of the project. learning objectives: . to learn about the benefits and risks in stroke intervention. . to consolidate knowledge of different methods of intervention in stroke therapy. . to learn about the different imaging methods used to decide on and perform stroke intervention. where do we stand in stroke therapy today? : stroke is a common health problem with high socio-economic costs. in recent years much effort has been focused on finding ways to ensure early intervention as well as new methods not only for early detection but for early treatment. the discussion will focus on where we stand today and whether we think stroke imaging and treatment will advance further. during the last decade imaging of stroke has developed from a minor field dealing with a barely treatable disease to one of the most dynamic parts of neuroradiology. the routinely treatment with intra-venous thrombolysis within the . hour time window and the continuously expanding treatment of severe strokes with intra-arterial thrombectomy have lead to increasing requests from clinicians and interventional neuroradiologists to provide imaging information for treatment guidance. all radiologists involved in the management of stroke are facing mainly three demands: first, to have good knowledge of the causes and the pathophysiology of ischaemic stroke and a proper understanding of the current models for infarct development, as a prerequisite for rational decision making and efficient communication with the clinicians. second, to be able to choose and to use appropriate imaging modalities for the acute work up of patients with stroke and to be aware of the benefits and drawbacks of ct and mri. finally, is good knowledge about the therapy options mandatory in order to be able to support the clinicians in the time critical treatment decision. this session will try to cover these three demands in order to give an overview on the current status and the opportunity to discus future perspectives. a. aetiology and pathophysiology of stroke r. von kummer; dresden/de (ruediger.vonkummer@uniklinikum-dresden.de) "stroke" is the commonly used diagnosis for disturbances of brain blood supply due to ischaemia, haemorrhage, or venous obstruction. it is evident that "disturbances of blood supply" in stroke patients do not represent a useful concept in order to develop effective treatment. it is the radiologist's task to describe the acute brain pathology, its conditions (pathophysiology), and its aetiology to give directions for specific treatment and prophylaxis. the approach is vascular and brain tissue imaging. brain ischaemia is the cause of stroke in about % of patients, intracranial haemorrhage in % of patients. arterial obstruction causing brain ischaemia is thrombotic or embolic. it can as well be caused by arterial wall dissection or inflammation. arterial wall diseases and heart diseases including a patent foramen ovale are sources for brain embolism. the obstruction of a brain supplying artery causes brain tissue ischaemia of various degrees depending on the capacity of collaterals supplying the same arterial territory. the chances for collateral compensation depend on the site of obstruction and the development of collateral vessels. neurons cannot tolerate low cerebral blood flow (cbf) below ml/ g x min for more than minutes and develop first cellular then irreversible ionic oedema. they survive, but do not function with low cbf between and ml/ g x min. enhancement of cbf in such regions, e.g. by arterial recanalisation can mean functional recovery. the imaging diagnosis of damaged brain is therefore the first aim in acute ischaemic stroke patients. focal liver lesions are part of our everyday practice because radiologists performing various types of examinations may encounter them without being aware of any clinical condition rising the suspicion of these changes. in a situation like this several important decisions are to be made by the radiologists, like: is the lesion clinically significant, is the lesion benign or malignant, are additional imaging examinations necessary, does it require medical, surgical or interventional radiological action, should it be, and if yes, how frequently followed up, etc. for providing a well-established answer to these questions the reporting radiologist has to be familiar with medical history and results of former examinations (physical, laboratory, imaging, etc.); consider the age, gender, physical condition, eating and drinking habits, potential drug abuse of the patient; bearing in mind the prevalence and statistical probabilities of different pathologic conditions. with all this information at hand the thorough analysis of images obtained by different modalities will allow a rather reliable differential diagnosis and a well-established planning of therapy of the incidentally detected lesions. learning objectives: to learn more about the clinical conditions that may result in the appearance of focal liver lesions. . to be informed about the clinician's way of thinking in the process of differential diagnosis. the spectrum of differential diagnoses is broad in the liver. therefore, incidentally discovered liver lesions represent a challenging clinical situation. fortunately, there are specific imaging features for the most common benign and malignant liver lesions (such as, e.g. hemangioma, fnh, cysts, vascular pseudolesions, hcc and metastases) so that a minimal-invasive diagnosis with a biopsy is not needed in a lot of cases. in ultrasound, the echogenity and recently also the contrast agent behaviour are used for liver lesions characterisation. in ct, attenuation and also contrast agent behaviour are used for characterisation. mr imaging offers several options including t -and t -weighted images, use of chemical shift imaging, gre sequences with long echos and diffusion weighted images, so that tissue components such as fat, water, glycogen, iron, etc. can be evaluated already in the pre-contrast examination. beside the evaluation of dynamic signal characteristics in the early dynamic phase after contrast agent application, mr can utilize also tissue-specific contrast agents dedicated to the res or to the hepatocytes. other modalities such as angiography, pet or other nuclear medicine methods usually only play a minor role nowadays in the evaluation of incidental liver lesions in nononcological patients. in oncological patients the clinical consequences and also the range of diagnoses and pre-test probabilities are different from the non-oncological group; therefore, the demands to imaging are even higher. in case of atypical presentation of otherwise benign liver lesions such as sclerosed hemangioma close follow-up or even biopsy can be necessary in such a setting. thyroid nodules are common. in - % of adults nodules can be palpated and at ultrasonographic examination nodules are seen in - %. most nodules are benign, the eventual diagnosis in patients with a palpable nodule is carcinoma in only % of cases. the incidence of thyroid carcinoma is low. papillary carcinoma is the most common type and is found in - % of thyroid cancer. lymph node metastases in thyroid carcinoma are primary to the paratracheal and prelaryngeal nodes (level vi), and the upper (level iii) and lower (level iv) jugular nodes. malignancy should be suspected when there is rapid growth, a firm or fixated mass, when enlarged lymph nodes are present or in case of vocal cord paralysis. in patients with multiple thyroid nodules the cancer risk per patient is not altered. ultrasound is the primary imaging technique in patients with a palpable thyroid nodule. it is best performed with the patient supine, the neck slightly extended and using a high frequency linear-array transducer. several ultrasonographic features are more often associated with benign or malignant nodules. however, while some ultrasonographic features may strongly suggest malignancy it may be very difficult to rule out malignancy by means of these features alone. ultrasound-guided fine needle biopsy can be performed in an attempt to differentiate between benign and malignant nodules. unfortunately, even with ultrasound guidance, an important number of cytological examinations will be non-diagnostic. in addition, in follicular lesions it is usually impossible to differentiate cytologically between benign and malignant follicular nodules. learning objectives: . to learn about the optimal settings for us examination of the thyroid. the neck is host to a large variety of benign and malignant diseases ranging from simple cysts to acute inflammation with complications to highly malignant sarcomas and imaging plays an important role to assess the nature and the extention of disease. patient history and clinical findings will decide which imaging technique is best suited to resolve the diagnostic dilemma. ultrasound is recommended to differentiate between a cystic or solid lesion, to guide fna, being quick and accurate. pathologic flow within or around a lesion can be assessed adding doppler technique. in acute illnesses with anticipated complications, such as a deep neck abscess, contrast-enhanced ct is required to evaluate local extention and demonstrate spread from the neck deep to the mediastinum. mri is indicated to assess non-inflammatory, subacute or chronic diseases, such as vascular malformations, branchial cleft cysts, benign and malignant soft tissue tumours, brachial plexus pathology and neurologic diseases. vascular malformations are easily depicted with mri using t sequences in different image planes. persistent fistulas of the branchial system can also be depicted by mri running from the anterior border of the sternocleidomastoid muscle to the lateral pharyngeal wall. assessing the origin of a soft tissue tumour has major implications for surgery. staging a malignant soft tissue tumour must comprise the skull base and upper mediastinum including local extention, pathologic neck nodes and perineural spread. follow-up during chemotherapy and postoperative monitoring of malignant disease are important indications for (mr) imaging, the more so in young patients, diminishing ionising radiation. learning objectives: . to identify different compartments in the neck. . to be able to choose the optimal imaging technique relating to request. . to become familiar with the most common pathology in adults and children. . to be able to address a short list of differential diagnoses. patients ( %) and by ultrasound in patients ( %). the activity of the disease was assessed correctly in % patients by ultrasound, compared to % patients by enteroclysis. there was no statistically significant difference. bowel us is a useful investigation for the diagnosis and follow-up of patients with crohn´s disease. learning objectives: . to learn about us techniques used in the assessment of patients with inflammatory bowel disease. . to learn tips for interpretation of us in the diagnosis and follow-up of patients with inflammatory bowel disease. . to understand the pros and cons of using us, including ceus, in the diagnosis and follow-up of patients with inflammatory bowel disease, including assessment of disease activity. . to appreciate the accuracy, reproducibility and usefulness of us compared with other imaging techniques in assessing patients with inflammatory bowel disease. a- : the use of computed tomography (ct) in the diagnostic imaging of patients affected by inflammatory bowel disease (ibd) has a long standing history. ct techniques such as ct-enteroclysis and ct-enterography have been reported as efficient tools for a radiological assessment of disease. the state-of-the art methods will be reported and their potentialities in diagnostic accuracy discussed in different clinical type of ibd. the acute setting of unknown ibd could be demanded as well to ct examination performed in emergency without endoluminal contrast medium administration. the ct appearance of the intestinal wall of the segments involved by an active disease could be not correctly interpreted if the knowledge of basic and classic typical findings of ibd is not combined to consider different pathologic entities that could affect the intestine, offering similar but not even equal signs. the entire abdominal background needs to be evaluated according to the clinical symptoms, signs, laboratory parameters and history of the patient. ct examination could be an efficient tool to determine the degree of disease activity in patient with known ibd as well as to assess the presence of an acute inflammatory disease of the intestine in patients with unknown ibd affection. the actual role of ct in the early diagnosis of ibd, in disease staging and detection of complications as well as monitoring therapy in follow-up will also be considered and discussed. learning objectives: . to learn about state-of-the-art ct techniques for the assessment of patients with inflammatory bowel disease. . to learn tips for interpretation in terms of diagnosis and differential diagnosis of inflammatory bowel disease. . to discuss the value of ct in determining disease activity and monitoring therapy. the aim of this lecture is to give an overview of the techniques and typical findings for imaging crohn's disease (cd) with either multidetector row computed tomography (mdct) or with magnetic resonance imaging (mri) and compare the two different modalities. optimal imaging of cd begins with the preparation phase. the small bowel has to be distended for a concise examination. this can be done either invasively, i.e. enteroclysis or orally, which is named enterography. there is much debate on which of these two preparation methods is better. for the administered intraluminal contrast, best is water with some additives, which are neutral in ct and biphasic in mr. imaging in mdct is done sec and sec after iv administration of iodinated contrast with a thin collimation. all image data are reconstructed in axial, coronal and sagittal planes. the aim of imaging in cd should be to establish the following: ( ) presence, severity, and extent of the disease; ( ) its activity; and ) extra-intestinal complications. both modalities have proven to be a good tool to evaluate the extent, the activity of the disease and the presence of extraluminal complications. both are also able to identify the type of the disease, being either the active/inflammatory, the fistulising/perforating, the fibrostenosing or the reparative/regenerative type. the challenge for mri is mostly the in-plane resolution of the image data whereas radiation dose is for ct. incidental lesions are frequently discovered during routine radiographic evaluations. correlation with clinical history and additional confirmatory imaging is essential to the development of an accurate, focused differential diagnosis and for appropriate management. the objective of this presentation is to describe the imaging findings associated with incidentally found liver lesions and to review those clinical and radiologic features, which should be considered in development of an ordered and accurate differential diagnosis. learning objectives: . to introduce typical cases illustrating the role of imaging modalities in the differential diagnosis of unexpected liver lesion cases. . to motivate the audience by the use of voting pads to be involved in the diagnostic process. . to highlight the conclusion that may be drawn on the basis of the discussed cases. the diagnosis of ibd is based on complex evaluation of clinical signs, endoscopic appearance, radiological imaging, laboratory tests and histology. besides crohn's disease (cd) and ulcerative colitis (uc) the modern classification advises to use the term ibdu (ibd unclassified) colitis to those % of cases, where the distinction between cd and uc is impossible based on the results of multiple exams. these cases are usually clinically more severe, with humbler therapeutic results. the new classification of cd types includes besides the phenotype (b : inflammatory non stenosing non penetrating, b : stenosing, b : penetrating) the age (a : ≤ y, a : - y, a : > y) the location (l : ileum, l : colon, l : ileocolic, l : upper gi tract) and p perianal involvement. in uc the most important clinical factors are extent, type and severity. the classification includes length and clinical types as acute, relapse-remission and chronic continuum. the radiological imaging in cd is needed for lesions not reachable by the endoscope, for categorising, for follow-up and detecting complications. different modalities fit best for these different tasks. the goal of imaging in uc is rather to help differential diagnosis and detection of complications. while in uc there are good correlation between laboratory and endoscopic signs of activity and severity so there is not much need for radiological activity indices, in cd the clinical activity does not correlate with the histological changes. although cdai is widely used for clinical studies, it includes several subjective factors, thus radiological activity indices may be of help. crohn's disease is more likely a systemic disease governed by a shift in the immune response, thus affecting the whole malt system. bowel ultrasound is a quick, simple and effective investigation. the method is simple and requires no bowel preparation. we use both -convex (c - -overview, anatomical orientation) as well as linear transducer (l - -preferred, incl. ceus, l - -children and very slim patients, l - -tdps, deep structures). we examine patients in supine position, first small bowel, than mesentery and large bowel. finally, we examine the terminal ileum and cecum or the areas of anastomoses. we assess folds, hastrum, wall thickness, vascularity, echogenity of the surrounding fat, the presence of nodes and peristalsis. in some cases we use intravenous contrast (ceus). at least four studies have prospectively compared the diagnostic accuracy of us with radiological studies, endoscopy or surgery in those with suspected crohn's disease. in these studies, the sensitivity of us ranged between % and % and its specificity reached % and %. in our prospective study we investigated patients by ultrasound and enteroclysis. we established the diagnosis by enteroclysis in the central venous vasculature and particularly the upper venous system may be obstructed by either benign or malignant lesions. malignant central venous obstructions are mainly due to bronchial carcinoma, mediastinal metastasis, mesothelioma or lymphoma. the most common cause for benign central venous obstruction is haemodialysis related; other benign reasons are rather uncommon but increasing due to the omnipresent use of permanent central venous access catheters as well as implantable cardiac rhythm management devices. the incidence of haemodialysis-related central venous obstruction resulting in angioplasty is described to be more than times higher compared to, for example, pace-makerinduced stenosis. in any case, early detection and treatment of complications are essential to provide adequate care. contrast venography for many years has been the standard of reference; yet this procedure has its shortcomings. sonography is not consistently reliable for detection of central pathologies, owing to difficult access to these vessels. today contrast enhanced ct is employed to define the site of the obstruction and the presence of possible thrombosis and reveal surrounding soft tissue alterations. mri is of comparative or even higher sensitivity and specificity in evaluating the patency of the central veins. the efficacy and safety of stent placement in central venous occlusion of benign and malignant origin lead to rapid relief. stenting provides fast symptomatic help. repetitive percutaneous intervention can prolong the cumulative patency. thrombolysis may be required to improve the final result, should, however, not be employed as a sole means for revascularisation. us and mr are excellent imaging techniques for studying tendons and muscles. during this integrated session we will review the advantages and disadvantages of us and mr for the diagnosis and follow-up of sports injuries. tricks of both techniques will be addressed, together with some useful guidelines for specific sports injuries. ultrasound is being used at the pitch side and in sports medicine practice as an adjunct to clinical practice. with this in mind there are a number of questions that will be answered in these talks. . when us and mri are the primary imaging and when they are complimentary. . what advances have there been in us and mri imaging to help advance our use of these techniques in tendon and muscle injury. . should we be aspirating haematomas and using autologous blood injections or prp to treat tendon or muscle disease. . can we predict the athletes return to sport? a- : muscle imaging is inherently complex and presents unique morphologic challenges and continuing integration of dynamic, physiologic and functional capabilities. in sports medicine, ultrasound (us) has proved to be an excellent tool to evaluate muscle strain and contusion injuries in athletes providing good correlation with clinical findings. in the acute phase, us has nearly equal sensitivity to mr imaging to diagnose muscle strains, except in the first few hours after the injury, when fresh haemorrhage and oedema have similar echogenicity to normal muscle and strains may go unnoticed. later in the process, us has been shown to be a useful tool in assessing the sequential stages of muscle repair, showing progressive resolution of blood fluid products, decrease in oedema and formation of scar tissue, thus aiding rehabilitation planning. dynamic us during muscle contraction can be valu- . to compare the diagnostic accuracy of ct versus mri in crohn's disease. . to learn about a strategy for the use of ct and mri in the radiological workup of patients with inflammatory bowel disease. five good reasons for the radiologist to be at the forefront : the chairman and speakers will debate the optimum imaging paradigms according to ( ) the clinical indication, ( ) assessment of those with suspected but as-yetundiagnosed disease, ( ) staging of the small bowel in those with newly diagnosed crohn disease, ( ) evaluation of response to therapy and ( ) assessment of those with long standing disease. the optimum approach to assessing and monitoring disease activity will be discussed. deep vein thrombosis (dvt) is a common condition which can lead to possible lifethreatening pulmonary embolism (pe). the primary imaging modality nowadays is duplex ultrasound. in cases where the pelvic veins and/or the vena cava is involved, a venous-phase ct is helpful to determine the exact extend of the clot burden. standard therapy for dvt is anticoagulation. however, if there is a contraindication or a complication (bleeding) to anticoagulation a vena cava filter is a good option to prevent pe. a filter should also be considered if a catheter directed thrombolysis is performed. with the new optional filters the filtration can be terminated either by removing the filter or by converting the filter into a stent. one problem which was observed with these optional filters is that (too) many of them are left in place. despite a low complication rate of filters, a filter may cause an increased risk of further dvt, or a caval occlusion and in rare cases even a migration or penetration is possible. therefore, patients with optional filters should be followed and filters should be retrieved when clinically no longer needed. varicose veins are an early manifestation of venous insufficiency of the lower limbs which can also lead to skin changes including extensive ulceration. it is a very common problem affecting up to % of adults in europe. patients presenting with venous insufficiency must first be assessed by a history and clinical examination to determine the presence and extent of the disease. a duplex ultrasound examination is essential to determine the cause from which an appropriate treatment plan can be decided. depending on the patients wishes and their funding options it is perfectly reasonable to treat all stages of the disease even if just cosmetic. treatment aims to eliminate the reflux in all contributing veins starting proximally and moving distally. surgery used to be the commonest treatment offered to patients but this has been largely superceded by endovenous methods which have significant advantages including: no general anaesthesia, outpatient based, no cuts, no scars, low recurrence, rapid convalesence. there are several endovenous methods using laser, rf, foam sclerotherapy and most recently steam heating and a combined mechanical/sclerosant system (clarivein (r)). laser and rf give almost identical results and % permanent truncal vein closure is to be expected. foam sclerotherapy is cheaper and quicker but long-term results are poorer and patients often have to return for repeat procedures. having ablated the main truncal veins using laser or rf at least % of patients require additional treatments for residual varicosities, e.g. microavulsions or foam sclerotherapy. adenocarcinoma is the most common pancreatic malignancy, affecting the head in - %. mdct is very effective in detection and staging of adenocarcinoma, with a sensitivity of up to % for detection and accuracy of - % for staging, but it has limitations (detection of small cancers, characterisation). mri is a problem-solving tool in equivocal ct to depict small cancers. mri with mrcp helps to differentiate between adenocarcinoma and focal pancreatitis. the "duct penetrating sign" at mrcp is indicative of an inflammatory mass. examination protocols for mdct include oral administration of - . l of water ("hydro-ct"), iv contrast administration of ml/kg b.w. (app. - ml), a flow rate of - ml/s, and a biphasic scan in parenchyma and venous phases. mri protocol should include non-fatsat and fat-sat t w gre, t w tse, dwi, mrcp, and contrast-enhanced sequences. gadoliniumenhanced t w d-gre are helpful for assessment of vessel infiltration and cystic tumours, whereas mangafodipir-enhanced sequences improve delineation of small tumours. in patients with locally advanced tumours, neoadjuvant chemoradiation may be used for tumour downsizing to make it amenable to radical surgery. however, pancreatic cancer often does not shrink after tumour response, which renders mdct or mri unreliable for tumour assessment in this setting. pet/ct may play a role in this indication. in conclusion, ce hydro-mdct is an excellent and robust tool for pancreatic cancer detection and staging. mdct in combination with mri or eus provides high accuracy for characterisation of tumours. further improvement is needed to assess tumour response after neoadjuvant chemoradiation. ct is the established imaging technique for evaluation of pancreatic adenocarcinoma. mri, however, can play a major role in this disease. technical advances of mri including parallel imaging techniques, multichannel receive coils of the abdomen, dynamic gadolinium-enhanced t -weighted fat sat d gre sequences, d mrcp sequences, mangafodipir-enhanced mri and diffusion weighted imaging (dwi) have greatly improved the results of mri in the assessment of pancreatic tumours. standard imaging sequences include t -weighted gre with fat saturation, in-phase and opposed phased t -weighted, axial single-shot turbo spin-echo (tse) and coronal/oblique d and/or d mr cholangio-pancreatography (mrcp) pulse sequences, post-gadolinium-enhanced d t -weighted fat sat sequence and dwi with multiple b values. mr imaging may be useful as subsequent examination for: ( ) detection of small non-contour-deforming tumours with isoattenuated appearance at ct, ( ) evaluation of local extension and vascular encasement, ( ) detection of the presence of lymph node and peritoneal metastases, and ( ) detection and characterisation of associated liver lesions and liver metastases. diffusion-weighted imaging may be helpful as a complementary imaging method in the differentiation between mass-forming focal pancreatitis and pancreatic adenocarcinoma. due to its superior soft-tissue contrast compared with ct, mri ap-able to monitor the healing process. local complications, such as vein thrombosis, irritation of adjacent neurovascular bundles, chronic haematoma and myositic ossificans can be demonstrated with this technique as well. however, us tends to underestimate the extent of injury and the abnormalities seen disappear more quickly when compared with mr imaging. at least in elite athletes, mr imaging seems, therefore, to play a more significant role in management of muscle injury, particularly when decisions regarding the time at which the patient can return to play are needed. by contrast, us is more accessible, and cheaper than mr imaging. in most clinical settings, us should be regarded as the first-line imaging choice for assessing skeletal muscle injury. learning objectives: . to understand the mechanism of injury of muscles in athletes. sports activity can affect tendons due to chronic overuse or acute injury. both can result in complete tendon rupture. us is helpful in precise assessment of rupture severity and extend, but enables alsofor assessment of tendon degeneration, where rupture of individual collagen fibres stimulates a chronic cycle of reparative response caused due to repetitive microtrauma. in chronic tendinopathy histopathological changes, such as hypoxic, mucoid, calcifying, or lipoid degenerations are present. us enables for differentiation of partial tears, tendinosis, tenosynovitis or paratendinosis, because of active and passive dynamic examination possibilities, and high-resolution capability when using high frequency probes. us developments as power doppler us, sonoelastography and contrast enhanced us allow further for new insights into tendinopathy. with the use of us, tendon changes can be diagnosed before they become symptomatic and a reduction of tendon load and initiation of treatment before the condition becomes chronic seem to gain important place in therapeutic regimes. furthermore, us-guided therapies are advisable over blinded-guided injections to minimise side effects and to allow an accurate targeted therapeutic approach. although diagnosis of acute muscle injuries in athletes is usually clinical, magnetic resonance imaging (mri) is a very helpful adjunct tool in this setting, showing the location, extent and severity of the injury and thereby streamlining the management of the patient. portability of ultrasonography (us) on the playfield in the acute setting is not matched by mri, which nevertheless has distinct patterns of grade - muscle strains; however, it is usually with nonacute and deeper injuries of the muscles that mri is especially helpful. presence of bone contusion, stress reaction, or stress fracture is readily displayed by mri and this is practically beyond the limits of us. evolving haematomas, fibrosis, scarring, and myositis ossificans are sequelae of direct or indirect muscle injury which are usually outlined in a single field of view by mri. delayed onset muscle soreness and chronic exertional compartment syndrome, as well as acute and chronic stages of muscle denervation changes, are readily diagnosed with mri. by providing an understanding of distinct muscular denervation changes, mri may actually noninvasively point to the entrapped or involved nerve and guide medical or surgical intervention. foci of mucoid degeneration within the muscle, myotendinous junction, or tendon itself are readily shown by mri, which thereby displays potential sites of failure during sport activities. diffusion tensor imaging may have a role in displaying the subtle architectural disruptions of directly or indirectly injured muscles. learning objectives: . to understand the specific role of mri in the evaluation of muscle and tendon injuries in athletes. . to recognise imaging patterns of tendon abnormalities in athletes: acute and over-use injuries. . to review different mechanisms of muscle injuries: direct and indirect. . to understand how mri might be used in the management of athletes. when a defect occurs in the bowel wall, air will appear within the peritoneal cavity, most frequently due to perforated peptic ulcer and perforated sigmoid diverticulitis. in most perforating gastrointestinal conditions however, the -imminent-perforation is walled-off by neighbouring bowel loops, mesentery and especially by the omentum, nick-named "policeman of the belly". if this walling-off process occurs timely and effectively, no or only minimal free air will appear. the most important causes of walled-off gastrointestinal perforation are appendicitis, peptic ulcer disease, sigmoid diverticulitis, bowel malignancy, crohn disease and -often underdiagnosed-accidently ingested sharp foreign bodies, as toothpicks, fish bones, chicken bones, etc. the extent to which the perforation is walled-off, determines the eventual course of the disease. the us hallmark of -imminent-perforation is inflamed fat around the involved bowel structure. inflamed fat on us corresponds to what is often called "dirty fat" on ct scan: hypodense fat is interspersed with hyperdense streaks. this represents oedema or cellular infiltration of the fatty mesentery and omentum, which have migrated towards the site of the imminent perforation in an attempt to seal it off. on us inflamed fat is recognised as hyperechoic, non-compressible fatty tissue often interspersed with hypoechoic streaks. if fluid collections occur within the inflamed fat, this implies abscess formation. inflamed fat is an important and valuable sign in perforating gastrointestinal conditions. if found in the absence of bowel pathology, the diagnosis is usually epiploic appendagitis or omental infarction. mdct is an extremely powerful tool when the search for a gi perforation is required. the high spatial and contrast resolutions make mdct the most accurate imaging method to identify even small amount of free intraperitoneal air. there is general consensus about the acquisition of a contrast-enhanced scan acquired during the portal venous phase of enhancement (delay of around - sec). controversies are still present in the literature about the utility of a pre-contrast scan as well as the need for a preliminary administration of an oral soluble iodinated cm or for an enema or gaseous distention of the distal gi tract. image reviewing needs the use of a workstation because multiplanar reformations have been demonstrated to improve the detection of small amount of free air. an appropriate window setting is mandatory and it makes mdct % accurate for identification of free air and almost % accurate in the identification of the precise site of perforation. the aim of the examination is not only to assess the presence of free air but also to detect the site of perforation: this is an extremely useful clinical information especially if surgeons decide to perform a laparoscopic repair. several ct signs have been described, able to guide the diagnosis and to differentiate between a perforation originating in the upper gi tract (stomach and duodenum), in the small bowel or in the colon. evidence-based radiology' (ebr) is based on best current evidence, traditionally acquired radiological expertise, the alara principle and the values of referring doctors and patients. any appropriately trained radiologist can formulate an answerable question, search the literature, appraise the retrieved evidence, apply their findings to local practice and evaluate the results. this presentation will describe and illustrate the 'ebr' process. patients with chronic pancreatitis (cp) may present with features resembling pancreatic carcinoma, for which cp is a risk factor with an incidence of . % after yrs. ebr methods were applied to the problem of differentiating mass-forming cp from pancreatic adenocarcinoma. a focused question and literature search found no secondary literature or imaging guidelines. primary literature searching found relevant papers, comprised current best evidence. for ct, time-attenuation curve characteristics had a sensitivity of % and a specificity of % for carcinoma. for mr, dynamic time intensity curve characteristics were only reported in a descriptive study but the duct penetrating sign (mrcp) had a sensitivity of % and a specificity of %. for pet/ct, f-fdg had a sensitivity for carcinoma between % and % with specificity of %- %. for eus/fna, the sensitivity for carcinoma in pre-existing cp was consistently low ( - %), but the specificity was %. simple bayesian analysis was used to establish the best order in which to apply these studies in practice. an algorithmic approach will be presented. the presentation will also consider other 'grey areas' in the field of pancreatic adenocarcinoma imaging using ebr methods. learning objectives: . to learn about evidence-based methods of literature searching and appraisal. . to understand how these methods can be used to produce diagnostic algorithms using the differentiation of pancreatic adenocarcinoma from mass-forming chronic pancreatitis as an example. . to learn about diagnostic algorithms based on different clinical scenarios (local and distant staging, advance versus early disease) involving multiple imaging techniques. : - : room f the hole in the guts in recent years, continuing trends in radiology have diminished the importance of plain films of the abdomen significantly. ultrasonography and mdct are applied with enormous success to the investigation of many abdominal conditions in the emergency setting. in the eyes of the radiologist, plain films, therefore, seem irrelevant in the presence of such powerful imaging procedures. surprisingly, referring physicians, mostly surgeons, gastroenterologists and urologists, still request plain films although the potential of mdct is obvious to them as well. in their perception, the plain film is either a definitive examination before initiation of treatment (e.g. stone at the ureteropelvic junction in us proven hydronephrosis) or a preliminary study prior to mdct or surgery (exclusion of pneumoperitoneum or ileus). in the present climate of cost and radiation consciousness this trend may continue. moreover, many surgeons, gastroenterologists, urologists, etc. have greater skills in reading plain films than in understanding mdct. therefore, the radiologist should poration. all these techniques remain investigational at this time for the treatment of breast cancer. the limitations of and challenges associated with each ablation technique and the issues raised by early pilot studies, which have so far prevented these techniques from replacing standard surgical techniques, will be discussed. in the elderly the co-existence of several diseases, the prevalence of involutional and degenerative aspects, together with physical and cognitive problems represent 'the norm'. it is therefore important to know how to distinguish the healthy elderly from those in need of treatment to avoid overdiagnosis and overtreatment. so the question is how to be aware of the potential and limits of diagnostic imaging and its applications in geriatric patients. brain development occurs rapidly during the last trimester of pregnancy and continues at a rapid pace in the first two years of life. more subtle maturation, for example in the white mater, occurs well into the third decade of life, as evidenced by diffusion tensor imaging (dti). evidence of brain degeneration is occurring soon afterwards and includes mild brain volume los, reductions in white mater integrity on dti, widening of virchow-robin spaces and accumulation of incidental white matter lesions (wml). severe wml and incidental cerebral microbleeds (mbs) are associated with know cardiovascular risk factors and while the concurrent impact may be subtle in terms of cognition, they carry a poor prognosis in the long run. the same is true for silent cerebral infarcts, which increase the risk of dementia. neurodegenerative (general brain volume loss, ventricular dilatation and hippocampal atrophy) changes also occur well before the onset of clinical signs of dementia. in genetically predisposed subjects (e.g. apoe carriers) abnormal (compensatory) brain activity on functional mri and increased (compensatory) cerebral metabolism on fdg-pet have been observed that predict subsequent cognitive decline. more recently, pet studies employing amyloid tracers have shown abnormal binding in a significant proportion of cognitively elderly, suggesting that these subjects are at risk to develop alzheimer's disease -the pace of which is currently undetermined. the objective of percutaneous needle biopsy of the breast is to obtain an accurate preoperative diagnosis with a low upgrade rate post-surgery. indications arise in both symptomatic and screen-detected lesions. a range of biopsy needle designs are available and their selection depends on being aware of the range of needle design types, their advantages and limitations. cutting needles, guns, vacuum systems and mr compatible devices will be discussed. guidance technique for ultrasound, x-ray stereotaxis and mr-guided procedures is extremely important, beginning with patient positioning and anaesthesia prior to commencing the procedure. accurate needle placement under direct vision using high frequency ultrasound probes, x-ray stereotaxis with digital systems and mr guided -with the option of using a cad system for distance calculation -will be presented. typical imaging signs and potential pitfalls of each technique, both anatomical and technical, will be highlighted. methods to increase accuracy including the use of meticulous technique, adequate sampling and correlation of specimen pathology with imaging findings at multidisciplinary meetings are essential. there is always the possibility of a false negative biopsy results in any type of percutaneous image-guided needle biopsy (fnac, core biopsy, vacuum-assisted biopsy). the risk depends upon the quality of the harvested cytologic or histologic material. the quality is closely related to the amount of material collected and the accurate targeting of a lesion. some lesions are at a higher risk of underestimation (sizes < mm, architectural distortions, microcalcifications, stellate lesions) than others (i.e. focal lesions). the false-negative rates for microcalfications using vacuum-assisted biopsy were reported to be . %, for mass lesions . %. using ultrasound-guided g-core needle biopsy the false-negative rates were reported to be in the range of . %. radiologic-histologic correlation plays a key role in the definite and correct judgement of the diagnostic result. in case of imaging-histologic discordance re-biopsy, possibly using larger needle diameters, or even open biopsy should be considered. the european guidelines for quality assurance of breast cancer screening and diagnosis define outcome parameter for breast biopsies. guidelines from the european society of breast imaging published in define the standards and skills necessary to perform these procedures. documentation standards should be used (b -b ) to allow continuous yearly evaluation of the individual institution results and quality improvement. the aim of any needle biopsy is to get as much, i.e. representative material as possible. nevertheless, a certain amount of underestimation, caused by lesion type (adh, dcis, lin, papilloma, for example) will remain and has to be reflected. the presentation will discuss the role of large vessel arteritis within the spectrum of thoracic vascular diseases. it will detail the pathological entities and their morphological, functional, and clinical characteristics. it will present typical ct and mri findings and discuss key elements to the differential diagnosis. it will finally discuss the clinical relevance of this diseases, with a special emphasis on overall evolving importance of thoracic vascular disorders. severe haemoptysis can occur in about % of patients. it is associated with high mortality due to asphyxiation, if not treated, and needs urgent and comprehensive evaluation of the lung parenchyma, airways, and thoracic vasculature. multidetector row ct angiography is a very useful noninvasive imaging modality for initial assessment of haemoptysis in stable patients. it can accurately identify the source and the most common predisposing causes of haemoptysis (bronchiectasis, chronic bronchitis, lung malignancy, tuberculosis and fungal infection) and the effects of haemorrhage on the lungs and airways. moreover, the combined use of thin-section axial and complex reformatted images allows clear depiction of the origins and trajectories of abnormally dilated systemic arteries that may be responsible for the bleeding in over % of cases requiring intervention with arterial embolisation or surgery. nonbronchial arteries may also represent an important cause of haemoptysis. the road maps of dilated bronchial and nonbronchial arteries provided by ct angiography represent a useful guide for endovascular treatment. ct angiography is a quick and noninvasive tool that is helpful in the diagnosis and management of haemoptysis. disorders that affect the elderly population. some misleading radiological presentations typically occurring in this population will be also presented. in the elderly the coexistence of several diseases, the prevalence of involutional and degenerative aspects, together with physical and cognitive problems represent 'the norm'. it is therefore important to know how to distinguish the healthy elderly from those in need of treatment to avoid overdiagnosis and overtreatment. so the question is how to be aware of the potential and limits of diagnostic imaging and its applications in geriatric patients. fast development in the area of imagining modalities demands a lot of work in dose and image quality optimisation and management. deterministic harms have been reported both in interventional and diagnostic radiology. there are also some special groups (e.g. children) which need a lot of attention and especially tight indications for x-ray examinations. radiation dose and image quality optimisation can be applied with small steps in everyday clinical work as a part of self assessment, if the safety culture is agreed by all professionals. the vendors put the settings high in order to reach the best image quality. after installation the settings must be re-evaluated before starting clinical use of the equipment. also, the sensitivity of aec (automatic exposure control) must be turned according the detector. using the air gap ( cm) instead of grid, e.g. in hip axio-lateral project or scoliosis, dose decrease can be even two thirds. the role of radiographer is expanding to new areas. quality assurance and dose and image optimisation could be parts of the expanded role. the new technical solutions in imaging offer a lot of possibilities for dose reduction, if we want, but there is also danger of dose creeping if the doses are not followed up frequently. the management and legislation offer the basics but the work must be done among those who are working in radiological departments. commitment to the safety culture on all levels in medical radiation offers better care and procedures with lower doses to the patients. radiological procedures are performed because of medical benefits to patients, but they also cause some harm because of the dose. if medical benefit overweighs detriment the procedure is justified. the purpose of the optimisation is then to adjust the procedure in a way to maximise the ratio of benefit over harm. question is who is responsible to do it and how it can be done. who should participate: we believe there is a major role of radiographer as she/he is present at each and every radiological procedure performed. but it is absolutely mandatory for them to understand benefits of the procedure and understand harm (dose). radiographer's position is the connection between radiologist, medical physicist and vendor's engineers. radiologists usually do not have in depth knowledge of technology and dose and physicists and engineers on the other hand do not understand in depth the medical aspects of procedure. radiographers must also understand operational possibilities of every x-ray machine. to get to know them they should be there at the acceptance of the x-ray machine and talk to service engineers and applicators. they should also talk to physicist when he/she is doing tests. and finally simulation of procedure(s) using different phantoms is the best way to understand how machine parameters are affecting image quality and dose. in presentation, some examples for different modalities will be given. learning objectives: to gain knowledge about how to start with optimisation of radiological procedures. . to understand the basics of quality control (qa) for radiographic modalities and how to use experience acquired from qa in daily work. . to become familiar with guidelines and applications for good radiological practice and how to implement them in the optimisation process. . to consolidate knowledge of technology of radiographic modalities and the use of materials in daily practice according to guidelines, and to be familiar with the radiographers responsibility in the field of radiation protection. the availability of magnetic resonance (mr) scanners operating at t and above has already proved beneficial for mr imaging and spectroscopy of the human brain and promises similar benefits in the human body. these advantages result from the increases with the magnetic field of the intrinsic signal-to-noise ratio, blood oxygenation level dependent (bold) contrast, which forms the basis of the vast majority of functional mr imaging (mri) experiments, and chemical shift dispersion. these gains can be exploited in improving the spatial and/or temporal resolution of anatomical and functional mri experiments and in increasing the spectral resolution in volume selective spectroscopy or chemical shift imaging. operation at the increased magnetic field also offers easier access to t * -contrast and improved implementation of susceptibility-weighted imaging (swi) in which the phase of gradient echo images provides information about local variation of magnetic susceptibility. in the brain, such variation appears to be dominated by differences in iron concentration and myelin content, so that high-field swi may provide useful information about the progression of neurodegenerative disease. the elevated t relaxation times at t also offer benefits for arterial spin labelling and time of flight angiography. current and potential future applications of high-field mri in clinical and pre-clinical studies in a number of areas and will be discussed in this presentation, along with the barriers to wider usage of t systems for clinical studies. the purpose is to present and discuss the role of imaging in non-traumatic acute abdomen, with particular focus on ultrasound (us). the neonatal gi tract emergencies, associated with specific disorders and imaging strategies, are excluded. acute abdomen in children refers to a wide variety of conditions ranging from benign disorders, such as gastroenteritis, to threatening disease, such as midgut volvulus or intussusception. the recognition of a surgical emergency requires usually, after a competent clinical evaluation, an imaging investigation in order to avoid negative or unnecessary surgery. abdominal plain film is known as poorly sensitive in most situations, except bowel occlusion. ultrasound requires experience and a thorough examination but has demonstrated a high sensitivity and specificity for diagnosing bowel obstruction, midgut volvulus, intussusception, acute appendicitis, over the recent years the clinical mri field strengths have gradually been increased to tesla; however, whole body mri systems with higher fields of up to . tesla have become available in experimental settings. compared to clinical field strengths, mri at very high magnetic fields has several advantages but also some unique challenges. with increasing field strength the signal-to-noise ratio increases, which can be used to either increase the spatial resolution in the images, or to acquire the images more rapidly. unfortunately, the energy deposited in the human body via the rf excitation scales quadratically with the field strength. thus, the specific absorption rate (sar) is a critical factor in all rapid imaging protocols, and requires the design of rf pulses with low sar, (e.g. verse pulses). inhomogeneities of the rf field which are induced by standing wave phenomena have to be compensated, and make the design of efficient spin echo pulse sequences very difficult. at higher field also the field inhomogeneities become larger and stronger imaging gradients are required to overcome the susceptibility-induced image distortion. stronger gradient systems are difficult to manufacture, and the usable gradient slew rate is limited by peripheral nerve stimulation thresholds. furthermore, stronger and faster gradients become very loud at high fields, and special measures for sound protection are required. despite these limitations, high-field mri offers image with very high resolution, it provides unique contrasts, a better spectral separation of the resonance lines and high signal for non-proton applications. clinical mri usually aims to depict anatomic regions of interest with uniform coverage and contrast behaviour. to this end it is essential to use suitably homogeneous radiofrequency (rf) magnetic fields for spin excitation, refocusing, and saturation. traditionally, such uniform transmit fields are generated by volume resonators based on quasi-stationary electrodynamics, which, however, gradually cease to apply as clinical mri explores high field strengths of t and beyond. the concomitant increase in operating frequency entails shorter rf wavelength and increasing tissue interactions, which render the tailoring of rf fields substantially more complex and patient-dependent. one promising response to this challenge is to depart from volume resonators and perform rf transmission by multiple, individually fed transmitter elements. with such transmit arrays the effective rf field can be tailored on a per-patient and per-scan basis by adjusting the relative magnitude and phase of driving the elements (rf shimming). in advanced imple- : - : room z neural stem cells are in the process of finding their translation into the clinic. however, it is well-known that the cells by themselves do not regrow lost tissue. to this end, neural stem cells need further support and guidance. tissue engineering is using biomaterials to provide a structural support for cells, but can also incorporate the release of factors that guide the fate of transplanted cells. ideally, an in vivo imaging approach would encompass all these processes. we here demonstratethe use of a f mri contrast agent to detect clinical-grade human neural stem cells non-invasively over days within a tissue cavity formed by stroke. to provide structural support for these transplanted cells within the tissue cavity, cells were mixed with an engineered de-cellularisedextracellular matrix (ecm). using diffusion mri, we were able to detect the presence of the ecm within the stroke cavity. this approach hence provides a novel approach as to how we can study transplanted cells and tissue regeneration in vivo by mri. our lab has been among the first to exploit dendritic cell (dc) therapy to treat melanoma patients. over the past years, immunological responses are increasingly reported and clinical responses have consistently been observed. moreover, dc therapy often has much milder side effects than standard chemotherapy. a key hurdle in the development of the dc therapy is accurate delivery of the cells to lymph nodes (lns), or their successful migration from the site of injection to lns. in particular, tools for measuring cell migration in vivo are necessary. ideally, we would be able to quantify the number of dcs at the relevant site, with high resolution anatomical context to allow differentiation of lns and the possibility of longitudinal data acquisition. furthermore, functional data on the ensuing immune response is also required. towards these ends, we have been working on developing imaging techniques to study dcs in vivo, for example with scintigraphy on in-labeled dcs, and magnetic resonance imaging (mri) on iron-labelled dcs. scintigraphy is quantitative, but it is restricted to the relatively short half-life of the radioisotope and is unable to resolve individual lns. mri allows high resolution anatomic localisation, but the use of contrast agents such as iron oxide is not quantitative. our recent work has focused on imaging the functionality of these dcs using positron emission tomography (pet) to study ln activation. finally, we have also developed in vitro assays that closely mimic in vivo dc migration in d scaffolds imaged using quantitative f mri, as a substitute for in vivo optimization. we plan on applying f mri to the tracking of dcs in vivo, as the technique allows both quantification and high-resolution anatomic detail. hypertrophic pyloric stenosis, etc. it enables some differential diagnosis such as infectious ileocolitis, ischaemic colitis, henoch schonlein purpura, complicated meckel diverticulum or duplication, etc. or even pyelonephritis. it can provide some findings suggesting mesenteric adenolymphitis, viral gastroenteritis, etc. the us findings will be described as well as the potentialities and limitations of us in each of these conditions. the accurate knowledge of the clinical findings together with the results of us will guide the need for another imaging modality: enhanced ct in case of suspected appendicitis with inconclusive us, upper gi series in an infant with bilious vomiting and impossibility to display the mesenteric vessels, etc. at last, some aspects of pancreatic and biliary tract emergencies will be shown. the purpose is to discuss the role of emergency imaging in acute paediatric gu conditions, with particular focus on the potential of ultrasound (us). besides gu tract trauma conditions such as urosepsis, renal failure, renal colics, ovarian or testicular torsion with all the respective relevant differential diagnoses have to be considered and urgently addressed adequately. particularly with respect to radiation protection (alara-principle) and due to the superb us potential in childhood, us is often used as the primary imaging tool. in many conditions us will reveal all treatment relevant information and no additional imaging is necessary in the acute setting. however, in other conditions such as severe (multiple) trauma ct remains the best primary imaging tool, however, only by using age-adapted ct protocols. the work-up and follow-up may also require imaging, usually achievable by us and partially by mri, scintigraphy and/or cystography. all these lead to imaging algorithms that differ from adults. the most important conditions, their imaging appearance, the potential pitfalls and some important methodical details will be presented, also discussing the recommended dedicated paediatric imaging algorithms. in most paediatric acute gu conditions us is adequate as the first and often sufficient imaging modality. rarely other imaging is necessary particularly in the acute setting -except for ct in severe (multiple) trauma. all imaging should be indicated with respect to therapeutic consequences and the alara principle, and proper paediatric protocols as well as methododical skills (e.g., dedicated paediatric us) should be provided hours throughout the year. learning objectives: . to learn about the diagnostic imaging approach in acute urinary tract disease. computed tomography (ct) is the imaging method of choice in the evaluation of abdominal injury after blunt trauma in haemodynamically stable children. an unstable patient needs to be stabilised prior to ct or to proceed directly to surgery. evaluation with ct allows for accurate detection and quantification of injury to solid and hollow viscera, and can also identifies an active haemorrhage. ct can help prioritise optimal management by diagnosing the major or most life-threatening site of haemorrhage or injury. ct can also demonstrate associated bony injury to ribs, spine, and pelvis. a normal ct examination may prevent other unnecessary explorations. the decision for operative intervention in the small percentage of children who require surgical haemostasis is primary made based on clinical criteria and not on ct findings. interventional techniques deeply changed approach to treatment of diseases. in each country, interventional radiology practice establishment varies according to local factors, but following a standard strategy seems better to set up this facility. according to above-mentioned points, i decided to establish this specialty in our hospital since as the pioneer center in interventional radiology iran. at first the procedures included percutaneous laser disc decompensation (pldd), and vertebroplasty followed by vascular procedures such as uae in later years. now, we are performing all interventional procedures in our country including aortic stent and all neurointervention procedures. the following items will be discussed: . prepare step by step strategies for establishing intervention. . solving issues regarding interventions procedures. . modified techniques for lowering costs to cover interventions in poor people. . setting of fellowship courses. . co-operation with dedicated and pioneer international centers such as using neocrylate for treatment of brain aneurysms in conjunction with ucsd for the first time on human. when presenting our experience we want to review how we should start interventional radiology in developing countries. fibroids are the most common benign tumours of the uterus during female reproductive age. uterine artery embolisation (uae) is a procedure in which using embolic particles (pva, gelfoam, etc.) we block blood supply to uterine fibroids. it has been reported as a relatively safe, effective, and durable nonsurgical alternative method diminishing fibroid-related symptoms. uae is typically performed in both uterine arteries by an experienced interventional radiologist. after uae, reduction in menorrhagia has been reported as - % and the mean decrease in fibroid size varies from % to % in the literature. complications including amenorrhoea are frequency ranging from % to % in the literature. uae may be followed by menopause in % of the cases. nevertheless, it is usually encountered in women in their late s. it seems that the future of uae depends on optimal selection of patients based on the prediction of volume-shrinkage, the outcome of fertility, and the long-term efficacy. although pregnancy is possible after embolisation, neither fertility preservation nor its improvement can be definitely guaranteed. women who desire to become pregnant should definitely be cautioned about potential complications during pregnancy. in this presentation we are going to review the position of uae in iran and to present our experience about the efficacy, and safety of uae. besides, we will discuss some methods of dose reduction during uae and the effects of uae on fertility and pregnancy outcome. purpose: labelling pancreatic islets (pi) with superparamagnetic markers enables their detection as hypointense spots on magnetic resonance (mr) images. we tracked pi transplanted into the liver and quantified their signal loss in liver tissue using mr imaging over a six-month period. methods and materials: pi were labelled with ferucarbotran μl/ml for - hours and transplanted into the portal vein in c-peptide negative recipients ( infusions). the liver was examined prior to transplantation and subsequently day and , , and weeks after transplantation using a t mr scanner. results: in all recipients significant c-peptide levels and near-normal hba c values were achieved with - % insulin dose reduction. no side-effects related to the labelling procedure were documented. a significant decrease in the number of islet spots was detected at week post-transplantation (on average %) with a subsequent only slight decrease for up to weeks. in two subjects with a labelling period of less than and hours respectively only a few islet spots were detected corresponding to poor islet visualization in phantoms labelled for the same period of time. conclusion: pi visualization was successful in all recipients but was less efficient if the labelling period was less than hours. a significant decrease in islet spots occurred at week post-transplantation suggesting early islet destruction or impaired engraftment. then, the decrease in islet spot numbers slowed and islets were still detected at weeks post-transplantation. data shows that mr detection of ferucarbotran-labelled islets correlates with sustained c-peptide production. areolar complex), the presence of other imaging findings (extension to the skin, inflammatory cancers) and the status of regional lymph nodes. this information influences the type of treatment given to the patient and it is very important to gather as much information as possible in order to obtain a one-step surgical excision with free margins at pathology. on the basis of this information and on discussions held in multidisciplinary meetings, markers will be placed wherever needed in order to locate the exact distribution of the tumour(s). the different parts of a structured report (clinical data relevant to the report, technical description of the diagnostic or the interventional modality, pitfalls during the exam, description of breast composition, description of lesions, categories and overall assessment) should always be included in order to guarantee that all the important information is there. breast imaging, like other subspecialties in radiology, is a multimodality area of knowledge where it is vital to integrate the information obtained through diagnostic and interventional procedures in order to supply the clinician with a body of data that is useful and straightforward. liver metastases are of the most difficult therapeutic challenges in oncologic managements. surgery is frequently impossible due to disease extent and systemic chemotherapy usually fails. in other body parts, the combination of radiotherapy and systemic chemotherapy is used for several types of malignancies. we successfully adopted a novel image-guided form of this combination for such masses referred to as radiochemoembolisation, which substantially intensifies the treatment locally. patients underwent transarterial radiochemoembolisation with chemotherapy protocol of mitomycin, doxorubicin, and cisplatin and embolisation with radioisotope particles of p. the effectiveness of method was determined by comparing contrast-enhanced ct images, pre-and post-intervention. treatment response was evaluated using recist criteria. we also used some arbitrary criteria such as tumoural mean density and enhancement pattern. for stable and partial-response cases, the procedure was repeated. we did not repeat the treatment for progressive diseases. complete-response cases were only followed. after completing treatment sessions, regardless of the tumour source, considerable amount of patients showed substantial response. in terms of recist criteria, a significant portion of patients gained at least a "partial response". but the decrease in tumour density and the appearance of non-enhancing tissues were more promising. radiochemoembolisation is an effective method for the treatment of patients with unresectable hepatic metastases. although this study lacks a control group, it shows the effectiveness of the treatment. literature review showed the response to treatment with regard to recist criteria had been better in our study comparing with studies only used chemoembolisation or radioembolisation. , which showed the superiority of digital mammography for younger and perimenopausal women, as well as those with dense breasts; the national ct colonography trial (nctct), demonstrating the equivalence of ctc with colonoscopy; and the national lung screening trial (nlst) which has preliminarily reported a % decrease in lung cancer-specific mortality associated with annual ct screening. acrin's current focuses include the assessment of emerging imaging biomarkers for the prediction of and monitoring of response to treatment and the extension of its activities to disease processes beyond cancer. according to the second approach, termed as ‚dark lumen mrc', dense barium or tapped water is used to distend the colon in conjunction with post-gadolinium d gradient echo with fat-saturation sequences. the colonic wall and the corresponding polyps exhibit high signal intensity as a result of gadolinium uptake while the colonic lumen presents with low signal intensity. mr imaging of the pancreas and bile ducts relies upon a combination of t -w and t -w strategies in order to safely acquire anatomic, cross-sectional and functional information. tissue-imaging strategies include free breathing t -w imaging (obtained with echo-train spin-echo sequences with or without fat saturation) and breath-hold d-gradient echo t -w imaging (obtained with fat saturation) without gadolinium and in the capillary phase and in the interstitial phase post-gadolinium. this combination is valuable in the assessment of the full spectrum of pancreatic diseases and malignant bile duct obstruction. hardware improvements (gradients) and the advent of more sophisticated phased-array coils and parallel imaging capabilities in modern mr scanners allowed to increase the spatial and temporal resolution of "conventional" t -w and t -w sequences. furthermore, it provided the possibility of adding high-b-value diffusion weighted imaging (dwi) to our routine protocol in order to increase the sensitivity of mri in detecting malignant and inflammatory diseases. to obtain conventional mrcp imaging thick-slab heavily t -w tse sequences or d heavily t -w tse sequences may be used. advantages and limitations of both sequences will be underlined. functional bile duct imaging is obtained imaging modality or technique for this problem. increasing technological capabilities and knowledge of how to optimise ct/mr contrast utilisation provides better ways to characterise tumours than ever before such that key clinical specialties outside of radiology now recommend nonbiopsy imaging diagnosis of hcc to triage patient treatment. radiologists must work extra diligently to learn the clinical issues, triage points and implications that are associated with specific clinical presentations and imaging findings. the perfect test that does not require cognitive interpretation of the constellation of imaging findings with integration of the patient clinical presentation to optimise patient care is not in our near future. this lecture emphasises historical advances in liver imaging and how data in the literature impacted patient care decisions in ways that may be different than expected from radiologists. an emphasis on pathologic-imaging correlation will be used to put apparent disparate published results in proper perspective to allow radiologists to meaningfully interact with clinical colleagues in determining optimal patient treatment. liver mri is undertaken to assess the liver parenchyma, vasculature, and biliary system. it is necessary to use a variety of unenhanced and contrast-enhanced mr pulse sequences to achieve lesion detection and characterisation. a set of t -, t -w and dwi sequences is now standard for lesion delineation and assessment of liver fat and iron content. in-phase and opposed-phase t -w gre images show focal or diffuse fatty infiltration and focal sparing. a fat-suppressed t -w tse sequence is robust and provides high tumour contrast, with . t units now allowing acquisition of isotropic d-tse sequences. the quite popular t -w half-fourier single-shot tse (e.g., haste) pulse sequences show anatomic detail (including bile ducts), but lack lesion contrast. in case of suspected iron overload (i.e., haemosiderosis and haemochromatosis) an additional t *-w gre is recommended. acquisition of dwi patient transport into the radiology department, contact to other potentially infectious persons, and things such as breath-holding are reasonable burdens and dangers to immunocompromised patients. when searching the focus of fever, imaging should help to identify an affected organ system in order to eventually guide invasive procedures to identify underlying micro-organism or non-infectious disease. equally relevant is the exclusion of its involvement with a reasonable specificity. depending on local epidemiology, organ system, and the clinical signs and symptoms, suspected differential diagnosis can be derived from image patterns. some of these diagnoses might be exclusion diagnosis, others might require invasive procedures including time consuming and costly analysis to be verified. invasive procedures, however, require adequate hemostasis, which is usually not available for a substantial duration due to pancytopenia in patients who underwent chemotherapy. if imaging fails to derive the underlying disease confident and conclusively in a fast way, clinicians might need to treat on an empirical basis. empirical treatment plays a major role in immunocompromised or severely ill patients at risk, because mortality rises within hours of untreated disease. on the other hand, empiric treatment causes relevant toxicity and substantial costs, while imaging might become cost-effective. using contrast agents that are taken up by hepatocytes and excreted through the biliary system in combination with volumetric t -w sequences. we use this technique in postoperative complications and to elucidate complex biliary anatomy. functional imaging of the pancreas is obtained by combining mrcp along with hormonal stimulation with secretin. in addition, secretin improves anatomic delineation and allows mri quantification of fluid production by the exocrine pancreas. despite the advance of cross-sectional techniques, the chest radiograph remains a basic tool for the initial approach to heart diseases. in this lecture we will present our current approach to evaluate cardiac pathology in conventional radiography illustrating it with selected cases. the basic approach consists of seven steps, evaluating the size and shape of the cardiac silhouette, cardiac calcifications, pulmonary circulation and lung changes, great vessels and implanted devices, all of them correlated with the clinical findings. looking at the heart on a chest film may be considered at a first glance as wasting time since, today, many other techniques are available today to offer an impressive luxury details of the morphological and functional evaluation of heart. nevertheless, the chest film remains often the first modality performed in many situations in which symptoms can be both from pulmonary or cardiac origin and then, careful analysis of heart may avoid rough mistakes in patient management. acquired and congenital pericardial or cardiac abnormalities may be responsible for a deformity of the cardiac silhouette and lead to explore the patient by a chest ct. ct with fast scanning capabilities can acquire images of the thorax with reduced cardiac motion artefacts, improving the evaluation of the heart in the course of a thoracic ct. unexpected findings of cardiac structures on both unenhanced and enhanced acquisition can dramatically influence the patient's clinical management. in many situations, a chest ct is performed without cardiac gating and it may be necessary to complement the initial examination by a gated acquisition to provide a more dedicated analysis. the normal appearance of cardiac structures and the most common cardiac abnormalities should be known by all the radiologists. various conditions such as idiopathic and acquired cardiomyopathy, ischaemic heart disease, valvular dysfunction can be identified even on non-gated scans. pulmonary diseases may also involve pericardium and cardiac structures and this should be clearly identified. learning objectives: . to learn how to detect and characterise cardiac abnormalities in the chest radiograph. . to learn how to detect and characterise cardiac abnormalities on chest ct. . to learn the limitations of the interpretation of cardiac abnormalities on ungated chest ct. . to learn when further evaluation is required. nal in discs and vertebrae to the adult shape and signal pattern will be reviewed. the normal pattern of unfused bony segments and apophyses in the child and fusion to the mature adult form will be reviewed. normal variants such as persistent segmentation/non-union leading to limbus vertebrae and dysraphism will be reviewed. intervertebral discs, vertebral body endplates, posterior elements and bone marrow show a wide degree of variation and the borderland of normal variant versus pathological abnormality is often difficult to navigate. common borderland findings such as schmorl's nodes versus scheuermann's disease will be discussed. transitional vertebrae as such are normal but incomplete transitional changes are associated with clinical symptoms. even without associated pathological changes the terminology of transitional vertebrae is a common pitfall. simple coping strategies will be reviewed. various imaging artefacts can have an influence on image interpretation though lumbar spine mr imaging is more resistant to these than imaging of the cervical and thoracic spine. this talk will review an approach to imaging complications of total hip replacements. the talk will briefly review surgical techniques and types of prostheses. the talk will subsequently review early and late complications of prostheses and focus on the integrated use of all modalities including radiographs, aspiration arthrography, scintigraphy and mri in achieving a diagnosis. there are many surgical techniques to repair meniscal tear, focal cartilage defect, cruciate ligament tear, malalignment, fracture, osteoarthrosis, etc. conventional radiography, ct-scan, ct-arthrography and mri play an important role in evaluation of the knee after surgery or arthroscopy. indications for postoperative imaging are infection, persistent pain and dysfunction. every radiologist should be familiar with "normal" imaging findings after arthroscopy, osteosynthesis, ligament reconstruction, osteotomy, knee prosthesis and meniscal or (osteo)chondral repair, but also recognise the main complications after knee surgery or arthroscopy. orthopaedic hardware is usually evaluated on plain radiography or ct, and only a relative contraindication for mri. microscopic metal artefacts and fibrotic scarring are frequently seen along the course of the instrumentation tract. after partial meniscectomy, an obtuse angle at the apex of the meniscus and increased signal intensity of the remnant part of the meniscus are normal findings, whereas fibrillation and recurrent tear may explain the complaints of the patient. various intra-and extra-articular reconstructive procedures exist for anterior and posterior cruciate ligament reconstruction. besides the neoligament, an osseous tunnel, screws and metal artefacts are also visible. postoperative findings of the extensor apparatus include a thickened patellar tendon, focal myxoid degeneration, fibrosis and focal defects, e.g. after harvesting tendon tissue for acl reconstruction or after release of the lateral patellar retinaculum for 'unstable' patella. accelerated osteoarthritis may be a late postoperative finding. mri very well depicts incorporation and alignment of osteochondral auto-or allografts, and the position, morphology and integrity of the meniscus after repair or transplantation. to evaluate postsurgical patients it is important to know the primary clinical diagnosis, the surgical treatment, the interval since surgery, and patients' current clinical symptoms. radiography is the most common imaging modality to evaluate the postoperative ankle, particularly in traumatic cases; after reduction and fixation of a fracture or dislocation it is generally carried out as routine. ultrasonography is highly sensitive and specific in postoperative tendon assessment, thanks to the superb resolution, and the opportunity for dynamic evaluation of tendon integrity. chest drains ( - fr) with underwater seals achieved decompression of pleural fluid collections. recent literature suggests small bore drains may be adequate, with image guidance playing an important role. pleural space anatomy, including fissural locations will be revised. aetiology of transudates, exudates and empyemas, along with typical clinical presenting features are outlined. various examples of plain film, ultrasound, multi-detector computed tomography and mri appearances of pleural collections and their aetiologies are presented. selection of patients, image guidance methods, catheter size, insertion technique, pitfalls and procedure complications are discussed. importance of physician-radiologist liaison with respect to catheter management and catheter dwell times is emphasised. pleural space fluid collections are common clinical entities that radiologists can accurately diagnose as well as successfully treat. overview of aetiology, radiological appearances and method of image-guided drainage of infected pleural fluid collections is provided. pelvic abscess drainage may employ more difficult access routes due to anatomic restrictions. the procedure may carry a higher risk of complications compared to simple abdominal drainage. to optimise patient preparation, correction of coagulation deficits, optimisation of antibiotic treatment, and sedation or anesthesia may be needed. the usual access routes for deep pelvic abscesses are the anterolateral and the posterior transgluteal approach. in selected cases, a transvaginal or transrectal approach may be the safer and more efficient option. depending on the viscosity of the drained fluid, the presence of necrotic solid tissue and gas, different sizes of drainage material may be needed. do not hesitate to employ large drainage catheters if indicated. an overview of the available material will be given. intestinal laceration is a major complication which can be managed percutaneously in selected circumstances. often, the weakest part of percutaneous drainage is the postinterventional management. it is advocated that the management is actively guided by the interventionalist who ensures that the drainage is properly handled, rinsed, and cleaned, that follow-up imaging is performed at the right intervals, and who is also responsible for indicating drain removal. chest ct and mri are commonly performed to evaluate patients with acute chest pain. a number of imaging techniques are available that may cover the entire chest, including the cardiovascular system. the radiologist will encounter more and more cardiovascular disease that was not visible with ungated ct and mri techniques. the differential diagnosis of acute chest pain may include over possible diagnoses, a substantial number related to cardiovascular disease. it is important to recognise chronic and acute coronary disease, myocardial infarction and its complications, left ventricular function, pericardial disease, atrial disease and large vessel disease. case material will be presented and discussed using both ct and mri techniques to illustrate the spectrum of usual and more unusual cardiovascular pathology that should be considered in the differential diagnosis of unexplained chest pain. pulmonary hypertension (pht) remains a disease difficult to diagnose because the clinical findings are nonspecific, often leading to a delayed diagnosis. once recognised, it is necessary to determine the underlying cause and to estimate the severity of pulmonary hypertension. among the noninvasive methods of assessment of pht, ct angiography (cta) now plays an important role in the diagnosis and post-therapeutic management of pht. numerous recent technological advances of multidetector-row ct technology (mdct) have reinforced the clinical impact of this technology by introducing new tools for the morphological evaluation of small-sized pulmonary arteries and pulmonary capillaries, the latter being accessible with dual energy ct and often referred to as pulmonary "perfusion". the role of ct now also includes the possibility to investigate the presence of pht on the basis of functional parameters, such as the distensibility of the pulmonary arterial wall, and to integrate cardiac functional information, with great interest towards right ventricular function. the major clinical impact of these new scanning modes is that morphology and function can be obtained from the same data set, with no restriction on the diagnostic performance of high-resolution ct angiographic images. the purpose of this lecture is to review these new trends in imaging of pht and estimating right ventricular function through practical clinical situations, including the most common causes of pht. ct scans of the chest are usually performed and reported as if the lungs were the only organs in the thoracic cage. however, the heart and pulmonary arteries can show significant abnormalities either as associated findings of the parenchymal disease or as incidental findings. so the recommendation is: do not forget the heart and pulmonary vessels when reporting a ct scan of the chest. mri has rapidly become important in post-operative assessment of the ankle, because it provides high soft-tissue contrast, multiplanar capability and osseous structures visualisation. it shows signal changes of ligaments and tendons, hypointense subchondral sclerosis, subchondral bone marrow oedema, joint effusion, capsular thickening, fibrosis, and synovitis. mri has also an important role in the evaluation of post-surgery ankle pain due to impingement syndrome and in the hindfoot chronic instability related to postoperated sinus tarsi syndrome; it demonstrates the anatomy of sinus tarsi, chronic synovitis and nonspecific inflammatory changes, synovial cysts, fibrosis and subtalar joint effusion. it is important also in the follow-up of tumours and tumour-like conditions of bone and soft tissues after surgery. computed tomography is the most valuable method to define the osseous anatomy of the postoperative ankle, so it is important in the follow-up of the operated osteochondral lesions of the talus. ct allows the evaluation of irregularities or degenerative changes, and progressive degenerative arthritis; however, ct usually fails to evaluate soft tissue's ankle lesion. the development of subsecond mdct scanners with high temporal and spatial resolution has significantly reduced scanning times and now it is possible to have very good quality images of the heart during routine chest ct examinations. therefore, the importance of looking at the heart and pulmonary vessels on a ct scan performed for non-cardiac reasons will be emphasised. anatomic cardiac details that every radiologist should know will be discussed in the first talk; the presentation is aimed mainly at the non-cardiac radiologist. it will review normal cardiac anatomic details, as routinely encountered on modern multi-detector ct studies. it is now possible to delineate much of the intracardiac anatomy on a contrast enhanced study and significant pathology may also be evident on non-enhanced ct examinations. important incidental findings and their clinical relevance will be discussed in the second talk. unexpectedly, cardiac abnormalities may be diagnosed when lung disease is clinically suspected and vice versa; the focus of this presentation will be the comprehensive evaluation of lung and heart/large vessels diseases.the strong correlation existing between pressure in the pulmonary artery system and dilatation of the pulmonary trunk and central branches will be discussed in the last talk. ct is considered more useful than echocardiography because it can depict the cardiac structures in all patients including those with extensive parenchymal abnormalities. at the end of the presentations we should try to answer the question about the routine reporting of cardiovascular findings on ct scan of the chest. a. anatomic cardiac details that every radiologist should know s.p.g. padley; london/uk (s.padley@ic.ac.uk) this presentation is aimed at the non-cardiac radiologist. it will review normal cardiac anatomic detail, as routinely encountered on modern multi-detector ct studies. it is now possible to delineate much of the intracardiac anatomy on a contrast enhanced study, and significant pathology may also be evident on non-enhanced ct examinations. this study will primarily review normal cardiac anatomy, including cardiac chambers, valves and coronary vessels. the typical radiological appearances of innocent incidental intra-pericardial abnormalities will then be reviewed. important incidental pathology will be discussed in the next talk. liver fat, inflammation, and fibrosis are important pathological features in patients with diffuse liver disease. the clinical gold standard for assessing these features is liver biopsy. due to its invasiveness and sampling variability, however, liver biopsy is suboptimal for screening, monitoring, and clinical research. there is, therefore, a need to develop biomarkers to assess liver fat, inflammation, and fibrosis non-invasively. in recent years, many quantitative imaging techniques have been developed, refined, tested, and made available. the question becomes: are these techniques ready for routine clinical use or are they most appropriate for research? in this special focus question, we will begin with a brief overview of diffuse liver disease and discuss basic concepts of biomarker validation and qualification. dr. reeder then will discuss conventional and state-of-the-art imaging-based biomarkers of liver fat. dr. cobbold will discuss the current status of non-invasive biomarkers for liver inflammation. dr. van beers will discuss ultrasound-and mr-based biomarkers of liver fibrosis, with emphasis on techniques such as transient elastography and mr elastography that measure visco-elastic properties of liver tissue. we will conclude with a panel discussion asking the question: are the repeatability, reproducibility, and robustness of the non-invasive biomarkers presented in this session adequate for routine clinical implementation? session objectives: . to review the clinical importance of diffuse liver disease. . to understand that key features of diffuse liver disease include fat accumulation, inflammation, and fibrosis. . to understand the need for non-invasive biomarkers to assess fat, inflammation, and fibrosis. . to review basic concepts in biomarker validation and qualification. quantification of liver fat s.b. reeder; madison, wi/us (sreeder@wisc.edu) intracellular deposition of fat within hepatocytes (steatosis) is a common condition of the liver. fat is the histological hallmark of non-alcoholic fatty liver disease (nafld) but also may occur with alcohol abuse, viral hepatitis, hiv and genetic lipodystrophies, and chemotherapy. nafld alone afflicts an estimated - million in the us and is a rapidly growing condition in other western societies, paralleling the expanding epidemics of obesity and diabetes type ii. this talk will review the clinical, pathogenic and histological features of liver fat, including an overview of fatty liver disease and diseases where fat is an important disease feature. next, it will review the current use and limitations of non-targeted biopsy in diffuse liver disease, and why quantitative non-invasive biomarkers of liver fat and iron would be beneficial. currently available conventional magnetic resonance imaging techniques that attempt to detect and quantify liver fat will then be discussed, as well as known confounding factors that corrupt the ability of conventional methods to quantify fat. this lecture will then describe emerging quantitative imaging methods for accurate and precise quantification of liver fat, and the advantages offered by these methods address in comparison with conventional methods. finally, remaining challenges and unsolved problems for quantifying liver fat will be discussed. conventional mri techniques, such as t w and gadolinium-enhanced t w sequences, which are highly sensitive for detecting demyelinating plaques, are recognised as the most important paraclinical tool for diagnosing multiple sclerosis (ms). however, the changes seen on mri in patients with ms are not diseasespecific, as focal white matter t hyperintense lesions (thl) are also commonly observed not only in the elderly but also in middle age and young patients, and in a large list of different disorders such as hypoxic-ischaemic vasculopathies (atherosclerotic and hypertensive small vessel disease, cadasil, fabry's disease and susac's syndrome), cns vasculitis, sarcoidosis, adult forms of leucoencephalopathies, trauma and radio chemotherapy, and acquired metabolic conditions (hepatic encephalopathy, alcoholism), among others. while it is recognised that a combination of findings from clinical history, physical examination and laboratory tests is commonly required to correctly establish a firm and clear aetiological diagnosis of thls, a detailed analysis of different mri features should also be considered essential, e.g. lesions shape, size, and distribution; contrast-uptake; and associated structural lesions (microbleeds, infarcts, spinal cord, brainstem and cerebellar involvement, …). in addition to these conventional mri-based features, non-conventional mr techniques (diffusion, mrs and perfusion) may also provide in some cases useful diagnostic information. knowledge of these features will assist the diagnostic work-up of patients presenting with thls, and should be considered a first step to take full advantage of the potential of mri, and in doing so should result in a reduced chance of misdiagnoses and facilitate the correct diagnosis of sometimes treatable disorders. learning objectives: . to be aware of the limited specificity of brain multifocal t abnormalities. . to learn about recognition patterns that might be helpful in suggesting the most likely etiology of brain multifocal t lesions. . to learn about the role of spinal cord imaging and advanced neuroimaging techniques for the differential diagnosis of brain t hyperintense lesions. . to be able to establish a neuroimaging diagnostic strategy in patients with multiple brain t lesions of unknown origin. breast imaging reporting and data system (bi-rads) was developed by american college of radiology in order to set standards for mammography reporting, common terminology and data collection. bi-rads is being used widely for over a decade and many studies have assessed the validity of the system. an important component of bi-rads is the lexicon which gives descriptors of specific imaging features that facilitate image interpretation and unify the reports. two main titles for these descriptors are about masses and calcifications. an asymmetry is called a mass when it is seen in two projections. a mass is defined with its shape, margin and density. definition of a mass with these three modifiers would help the radiologist to determine the type of the mass and probability of its malignancy. calcifications are divided into three categories by their shapes and another descriptor is defined for their distribution. the first category is for typically benign calcifications. the other two are for probably malign calcifications where biopsy should be suggested. the distribution modifiers for calcifications can also play an important role in assessing the probability of malignancy. bi-rads defines assessment categories from to for the final report that facilitate data management for yearly audits. category is the transition zone between malignant and benign lesions where the suspicion for malignancy should be less than % and requires short-term follow-up. bi-rads morphology and distribution descriptors are effective in assessing the risk of malignancy with a reasonable positive predictive value. the breast imaging reporting and data system (bi-rads ® ) for ultrasound (us) was developed by the american college of radiology (acr) and published in . although this lexicon was created to achieve a consensus among radiologists when describing breast abnormalities, clinical practice shows substantial intraobserver agreement but only moderate interobserver agreement. most problems are reported for descriptors related to shape (when trying to classify abnormalities containing lobulations and/or elliptical with not-parallel orientation), echo pattern and margin. especially mass margin is a critical feature for determining whether a lesion should be biopsied or not. other problems are related to the final assessment, including difficulties in applying the subcategories and the relatively high percentage of false negative cases for lesions interpreted as category . many computer-aided diagnosis software have shown the potential to improve performance amongst less experienced readers and decrease interobserver variability; still they do not solve all the problems. the bi-rads ® lexicon is actually under advanced revision by an international panel and ellen b. mendelson chairs the us subcommittee. revision is reviewing both descriptors and categories; it will include also new parameters linked to the evolution of us technology as colour flow mapping and elastography. troubles. characterisation of aml is possible, based on identification of its fatty content mainly using ct. when microscopic, this component may be missed and biopsy is required with immunostaining. mr imaging may be helpful using chemicalshift sequences but thresholds, to rule-out clear cell carcinoma, have to be better defined. presence of necrosis or calcifications rules-out diagnosis of aml. amls must be treated if haemorrhagic, painful or if diameter exceeds cm. embolisation is the main nonsurgical method, using microparticles, alcohol and/or coils but postembolisation syndrome must be prevented. volume regression may require all agents whereas aneurysm occlusion requires coiling. the effect on volume and on haemorrhagic risk is substantial making surgery as an alternative method for nephron sparing purposes. secondary surgery is required in less than % of embolisation. rf ablation is also possible but its efficacy is still under evaluation. the number of small renal tumours is increasing due to the large amount of imaging examinations of the kidneys performed with various modalities and the true increasing incidence of renal cancer. conservative therapy of small renal tumours is now widely recognised as the reference technique for the treatment of these small lesions. the increasing rate of chronic renal failure in the elderly and the efficacy of conservative therapy to treat cancer as demonstrated by the urologists performing partial nephrectomy and tumourectomy emphasise the role of percutanaeous minimally invasive ablative procedures, particularly in patients with surgical contraindications. radiofrequency ablation and cryotherapy are the two most developed techniques, but new technical approaches are under development such as microwave ablation, electroporation, etc. the evaluation of the success of the procedure relies on imaging techniques showing the lack of enhancement within the lesion and the size and shape of the necrotic covering the entire tumour area. the techniques, indications, results, and complications of both radiofrequency ablation and cryotherapy will be discussed. a variety of diseases including neoplasms, but also infectious, inflammatory, vascular and traumatic processes, may present as focal intracranial mass lesions. modern neuroimaging, primarily with mri, enables differentiation of these entities allowing for accurate diagnosis in almost all cases. the requirements are appropriate image acquisition and detailed analysis of imaging findings, while pertinent clinical information may be very helpful in certain cases. the distinction is frequently broad, between different disease processes, such as with tumefactive demyelination versus neoplasm, which is often sufficient for clinical decision making and patient management; at times this may be more specific, approaching histological diagnosis, such as with pilocytic astrocytoma versus medulloblastoma. this presentation will go briefly over the imaging techniques and various disease processes, while heavily concentrating on the differentiating features of intraaxial primarily non-haemorrhagic mass lesions. the emphasis will be on the key distinguishing imaging features, such as presence or absence of mass effect or vasogenic oedema, signal intensity characteristics, presence and pattern of contrast enhancement, as well as diffusion and perfusion features. decision making process will be discussed. a number of cases with intracranial masses will then be reviewed and analysed, using a step by step approach, accentuating the most reliable distinguishing findings. the role of mr imaging in adult gliomas consists of many steps. ( ) is there a lesion in the brain? ( ) is the lesion a tumour? ( ) is the tumour a glioma? ( ) is it a high-or low-grade glioma? ( ) if there is a suspicion and a biopsy is planned, which part of the tumour should be targeted at biopsy. ( ) how the surgery should be performed to avoid injury to functional areas of the brain (e.g. motor cortex). ( ) if there is need for adjunctive radiotherapy, how the extent of the tumour should be defined? ( ) after radiotherapy, if a new enhancing lesion occurs, is it a recurrent neoplasm or radiation necrosis? conventional anatomical mr imaging is not always powerful enough to answer these questions. however, with advanced mr imaging techniques such as diffusion mr (including tractography), perfusion mr, mr spectroscopy and functional mri (fmri) we can answer the above questions reliably in most cases. the purpose is to gain numerical information of accuracy in the treatment of localised prostate cancer and calculate the necessary size of the safety margin around the clinical target volume (ctv-ptv). in addition, the purpose was to evaluate the accuracy in treatment set up with patients with high bmi to find out whether patients with high bmi need a larger safety margin. portal imaging was used to measure off-line random set-up error from bony structure. the sample size was , i.e. all the patients who received radiation treatment for localised prostate cancer in landspítali -university hospital (lsh) . a total of portal images were acquired. in , the task was repeated for patients having gold fiducial markers in the prostate. the calculated -d imrt safety margins in lsh was to be . mm. correlation is with high bmi and set-up errors in medio lateralis (m-l) direction (r= . ). this indicates that a patient with an increased pelvic circumference has a tendency to have more set-up errors. reformed procedural workflow resulted in more acceptable calculated margins in . when corrected on line times per week the margin is to be . mm and . mm if corrected times per week. in conclusion, for delivery of - gy to the prostate with imrt and spare surrounding healthy tissue effort is needed to secure the accuracy in the overall procedure of treatment planning and delivery. learning objectives: . to gain knowledge on how to improve the target accuracy in treating prostate cancer with radiation therapy using electronic portal imaging. . to understand the importance of gaining numerical information of accuracy in the treatment of clinically localised prostate cancer and how to use the information to calculate the necessary size of the safety margin around the clinical target volume. . to become familiar with the preparation needed before starting treatment with imrt and be aware that there is a need to look at all the treatment elements including the technical side, quality, education, staff and patients. . to consolidate knowledge of radiation therapy for prostate cancer and the meaning of giving high dose to the target while minimising radiation dose to healthy tissue. b. image-guided radiation therapy: when imaging meets therapy a. sarchosoglou; athens/gr (anastasia @hotmail.com) the aim of this presentation is: to understand the necessity of imaging in the delivery of external radiotherapy; to be familiar with the technology of image-guided radiation therapy and to to gain knowledge about the implementation of d igrt. the aim of radiotherapy is to deliver high dose to target volume while minimising the dose to surrounding healthy tissues. however, during treatment delivery many uncertainties may arise that can result in higher toxicity and poor local control. thus, it is crucial to monitor and adjust if necessary, the actual treatment. image-guided radiation therapy is the process where images are taken immediately prior or during a course of radiation treatment, to assess and improve the accuracy of therapy. manufactures have developed a number of systems to perform igrt providing the options of ionising radiation images/non-ionising imaging technology and gantry mounted/room mounted equipment. d igrt can be performed by acquiring computed tomography images on the treatment unit. these images are matched with reference images from planning ct and potential discrepancies are recognised, calculated and corrected by couch shifts giving optimal results. such advanced technologies require quality assurance systems to be in place and high trained personnel. when properly implemented, igrt meets the aim of radiation therapy. imaging provides confidence to radiation therapy to be aggressive, to fight cancer. imaging promises radiation therapy a great future with improvements in clinical outcomes and patient survival! multicentre trials have shown that ct colonography is ready for widespread clinical use. however, these studies have also highlighted the inconsistent performances of ct colonography, with divergent results being recorded in different centres and between readers. inter-observer and inter-centre variability may be related to reader experience but it is also affected by how ct colonography is performed. while faecal tagging has been accepted universally as the proper way to prepare patients for ct colonography, there is no consensus on which tagging agent is better, on the timing of contrast agent administration and on whether laxatives should be administered and in what dosage. in a similar way it is not yet clear which is the best way to obtain colon distension, whether by administering spasmolytic agents routinely or by changing patient's decubitus. standardising bowel preparation and technique is one of the most important goals that need to be achieved for ct colonography to be universally accepted and this presentation will attempt to deal with the issue using an evidence-based approach. the evaluation of ct colonography (ctc) studies is based on detection, interpretation and reporting of colonic findings. it is performed on a computer workstation equipped with dedicated ctc software by a primary d or a primary d approach. in either case, the alternative viewing technique must be available for rapid correlation and characterisation of suspicious findings. primary d evaluation is based on "lumen tracking" by interactively scrolling through the axial slices and multiplanar reformatted images, focusing only on the air-distended colonic lumen from one end to the other one. primary d evaluation provides information about the attenuation of findings during the search process and is time-efficient. primary d evaluation is based on d virtual endoscopy in an antegrade and retrograde fashion and increases both, the conspicuity, especially of small and medium-sized polyps, and the duration of visualisation. the use of advanced d displays like virtual dissection or unfolding techniques may reduce the interpretation time for primary d evaluation. computer-aided detection (cad) algorithms used as a nd reader were shown to reduce the number of perceptual errors by pointing out possible abnormalities that might otherwise be missed. colonic findings are characterised by their morphology, their attenuation characteristics, and by their mobility. knowledge of ctc imaging features of common colonic lesions and artefacts is necessary for characterisation of findings and differentiation between definite colonic lesions and pseudo-lesions. standardisation of ctc reporting facilitates classification and communication of findings and the comparison with previous studies, thereby better assisting physicians in making appropriate management decisions. the revolutionary development in multidetector ct (mdct) technology during the past decade has contributed to a substantial increase in its diagnostic applications and accuracy in children. a major drawback of mdct is the use of ionising radiation with the risks of radiation-induced side effects, of which the induction of secondary cancer is the most important. therefore, justification and optimisation of paediatric mdct is of great importance in order to reduce these risks as much as possible (‚as low as reasonably achievable' principle). optimisation of paediatric mdct starts with a solid understanding of all technical aspects of ct, including the most relevant scan parameters, dose reduction techniques and technique of iv contrast material administration. furthermore, due to the smaller size and lack of visceral fat in young children the interaction and absorption of radiation will be different which will influence the choice of the various technique and scan parameters. although all these issues are pivotal for a successful ct examination, it may become worthless if the importance of pre-scan issues such as justification and patient preparation are ignored. after a short overview concerning the current knowledge on radiationrelated risks in children, this lecture will focus on several aspects relevant for mdct optimisation in children. issues such as justification, patient preparation, technique and scan parameters will be addressed. finally, some guidelines for radiation dose level-based ct protocols will be given. the purpose is to present an overview of the safety hazards and safety protocols related to infants undergoing mri examinations. mri infrastructure-dependent safety hazards originating from: (a) static and fringe magnetic fields, (b) gradient subsystems, (c) radiofrequency subsystems and (d) acoustic noise sound pressure will be reviewed and discussed. safety hazards related to upcoming technological issues and future trends concerning mri will be presented. the current status of the organisations responsible to the problems of mr safety will be reviewed. which authority is responsible and where the responsibility is addressed to (directives, legislation policies, etc). an optimised protocol related to a variety of clinical mr sequences in reference to temperature measurements, emf measurements, sar and acoustic noise figures using basic commercially available infrastructure will be presented. d/ d tse sequences with different etl's, d/ d gre, d/ d ssfp and se/gre epi sequences with multi-(b) diffusion gradients and d tof mr angiography sequences will be examined. in vitro measurements of snr, spatial resolution and scan times will be performed for each clinical mr sequence. a comprehensive mri equipment operational policy (optima: (etl, tr, te, b-value, epi factor etc).) for a safety protocol for infants undergoing mri is proposed. recommendations for safe infant mri examinations will be summarised and presented. conclusion: mri equipment can operate safely for infant imaging but require policies and procedures beyond those required for standard diagnostic mri examinations. learning objectives: . to get an overview of the three basic safety hazards related to infants undergoing mri examinations. . to become familiar with safety hazards related to upcoming technological issues and future trends. . to learn about a safety protocol that could be applied in mri examinations for infants. a s c b d e f g h perfusion imaging. new possibilities arise in mri almost every day. imaging algorithms are to provide the correct diagnosis in the shortest time with the lowest expenses and harm to the patient. mri is the first method of choice in neurological diseases with two exceptions: acute stroke and acute trauma, ct providing the necessary information, more available and with easier patient care. adequate imaging protocols optimally visualise the anatomical region of interest and pathological processes, optimise the comparison between serial examinations and provide the information in reasonable examination time. appropriate and well understood clinical information is indispensable (neuroradiology means good clinical knowledge combined with expertise in imaging methods and their evaluation). complicated protocols are superfluous without competent clinical background but adequate information must be provided to experienced clinicians. basic protocols help to gather important information but do not exclude additional necessary methods. examples to be demonstrated are mri protocol for the pituitary, epilepsy, multiple sclerosis and spine. the up-to-date concepts of image evaluation and interpretation will be demonstrated for brain ct, brain mri and spinal mri, including the importance of follow-up. the body and conclusion part of the structured neuroradiological report will be discussed. consultation with other neuroradiologists and with clinicians is the final tool to reach the goal: to help in recovering the patients' health. ten authentic and original typical clinical cases illustrating the importance of imaging modalities in the differential diagnosis of focal neurological symptoms from headache to epilepsy will be presented while respecting the privacy of the patient. the spectrum of pathologies includes vascular, inflammation, metabolic, degenerative diseases, congenital malformations and neoplasms of the central nervous system. each case story will be described shortly in a standard form followed by demonstration of typical ct and/or mri images. in some cases, conventional mri will be supplemented by multi-voxel mr spectroscopy, dti, mr tractography images, and morphological pictures. follow-up images will be presented where appropriate. several diagnostic options will be offered for attendants. the audience will be asked to participate in the diagnostic process by the use of voting pads. after highlighting of final diagnosis the basic differential diagnostic considerations will be briefly summarised and emphasised from the clinical and imaging point of view for each presented case. learning objectives: . to introduce typical cases illustrating the role of imaging modalities in the differential diagnosis of focal neurological symptoms. . to motivate the audience by the use of voting pads to be involved in the diagnostic process. . to highlight the conclusion that may be drawn on the basis of the discussed cases. diagnostic quality mri of soft tissue masses can be performed using a variety of magnetic equipments and a variety of field strengths. regardless of system design, efforts should be made to maximise signal-to-noise ratios (snr) using the most appropriate coil to include the lesion and associated oedema. fov should be tailored to the size of the patient and the size of the mass. it is important to obtain images in at least two planes through the lesion. slice thickness vary depending on the size of the lesion and interslice should be not more than one-half of the slice width. imaging matrix should be balanced to in-plane spatial resolution. parallel while ctc has achieved excellent results in average risk individuals with regard to detection of clinically relevant polyps, it has not yet been implemented on a large scale in colorectal cancer (crc) screening programmes. this is mainly due to the fact that it uses ionising radiation. there is uncertainty about adequate screening strategies and the risk of radiation-induced malignancy. this presentation will summarise recent results of ctc in a screening setting, will look at the dose associated with ctc, and summarise calculations of radiation-associated risk of malignancy. the key question is whether low doses from ctc will cause relevant negative effects in the screening population. the lecture will also feature a comparison between ct and mr colonography, an imaging test that might be able to provide high sensitivity crc screening without ionising radiation. from headache to epilepsy… or from "normal", physiological "headache" to life threatening pathological conditions. when do we need "neuroimaging" and what is the optimal diagnostic work-up? the radiologist must and should remain first of all a medical doctor: he/she should keep close contact with the clinical world and always keep an active dialogue with the referring clinician. indeed, medical imaging has become more and more sophisticated but also more expensive. imaging is not a "screening procedure" in brain pathology but should be performed in order to confirm a clinical, suspected diagnosis keeping still in mind that differential diagnosis must be considered as well. imaging plays also a unique role in lesion evaluation and treatment monitoring. the radiologist must answer precise questions about the patient's suspected pathological condition and if necessary, discuss the imaging findings with the clinician in order to narrow the differential diagnosis. each mri or ct must be performed with a clear knowledge of the clinical question and the suspected pathology. therefore, the radiologist will make the proper choices of imaging techniques especially with mri where imaging sequences have become numerous. headaches and seizures are symptoms only and may be present in multiple and very diverse pathological conditions as infectious, neoplastic, haemorrhagic, vascular diseases: by knowing the clinical history a good "clinically conscious" radiologist will undoubtedly be of greater "added value"! learning objectives: . to learn more about the clinical conditions causing focal neurological symptoms. . to be informed about the clinician's way of thinking in the process of differential diagnosis. neuroradiology has a continuously changing and developing array of modalities. conventional radiography has lost its importance. angiographic practice has shifted from diagnostics to therapy. ms-md ct scanners provide high-quality ct angiography and a s c b d e f g h t w-mri to localise pz-zone pca. in the t-zone, stromal nodules commonly have a low adc value simulating pca. significant differences in tumour adc values existed between patients with low-risk, and those with higher risk localised p-zone pca. with s-mri, the best accuracy for diagnosing pca is obtained by combining a positive t w-mri and a choline+creatine/citrate ratio > . . in the t-zone, s-mri has the same limitations than dce and dw-mri. multiparametric functional mri accuracy of mri to detect pca can be improved by combining different functional sequences. at the moment, it seems that the most widespread used protocol is a combination of dw and dce-mri for detection of p-zone tumours. performance of functional mri to detect t-zone pca is less well established. multiparametric mri can now be used to perform stereotaxic trus-guided biopsies after trus-mri image fusion. the role of imaging in patients with increased psa level after radical prostatectomy or radiation therapy is to aid in differentiating locally recurrent disease which can be managed with local therapy from distant metastatic disease requiring systemic therapy. although the majority of local recurrences in post-surgical patients can be detected by mri in the perianastomotic region which can also be evaluated with trus and trus-guided biopsy, some recurrences can occur at pelvic sites that are beyond the range of trus; mri has a role of labelling these sites for trusguided biopsy. the combination of an external phased-array coil and endorectal coil is recommended for detecting local recurrent cancer. current protocols involve t -weighted mri combined with functional techniques such as dynamic contrastenhanced mri (dce-mri), magnetic resonance spectroscopy and diffusionweighted mri. in the post-prostatectomy bed, recurrences present as lobulated masses having low to intermediate signal intensity on t -weighted images and showing early, nodular enhancement with early washout of gadolinium on dce-mri. the predominant finding after radiotherapy is a diffusely low signal intensity with an indistinct zonal anatomy where the contrast between a hypointense recurrence and benign irradiated tissue decreases. on dce-mri, peripheral zone enhancement is lower after radiotherapy and any focal enhancement should be regarded as suspicious. the overall diagnostic efficacy of dce-mri for detecting recurrent prostate cancer is better than t -weighted mri alone. on mri, bone metastases have low and high signal intensity on t -and t -weighted images, respectively, and enhance after intravenous gadolinium administration. learning objectives: . to understand the role of mri in the follow-up of the patients with prostate cancer after radical prostatectomy or radiotherapy. in this presentation new techniques with potential clinical value will be described with a focus on prostate cancer multi-modality mr imaging. techniques such as t w, dwi, dce and mrsi will be addressed, and their role in screening, determination of tumour aggression and localisation, mr-guided biopsy, mr-guided minimal invasive focal therapy (laser, cryo, hifu), and mr-guided radiotherapy will be discussed. examples will be shown. the major area of debate is how to approach patients with increased psa levels. the discussion has two parts: one is the patient who has not had a prior cancer diagnosis and the other one is the patient who has already been treated for prostate cancer. what is the role of mr (as well as mrs, dw mr and dynamic mr) in precluding the need for multiple biopsies? when should we stop in cases with high or increasing levels of psa despite consecutive negative biopsy outcomes? a s c b d e f g h and that radiation therapy and systemic treatments play a major role for curing minimal residual disease. for evaluating and predicting response to neo-adjuvant treatments, the major question is the debate between morphology (size and volume) and function (perfusion, spectroscopy and diffusion). for follow-up after treatment, considering the number of women concerned, cost benefit analyses are mandatory to offer the most efficient imaging strategies based not only on defined subgroups (risk factors of local relapse) but also over time. one of the first take home messages of this course is the multidisciplinary approach of this disease or in another way: we do not treat images but patients! a. evaluation of residual disease after excisional biopsy c. boetes; maastricht/nl (c.boetes@mumc.nl) mammography can have an additional value in evaluating if microcalcifications are left behind in the case of dcis and irradical operation. ultrasonography has proven to have no additional value in evaluating the postoperative breast, because of haematoma and scar tissue. mr imaging of the breast can of all imaging techniques predict residual disease in the most accurate way. however, false positive results can exist because of enhancing scar tissue. also, false-negative results exist, especially owing to residual low and intermediate grade dcis. it is recommended to perform postoperative breast mri in premenopausal women in the right time of the menstrual cycle, that means between the th and th day after the start of the menstrual cycle. unclear is how soon after the operation one should perform breast mri. if a large mass of residual disease is suspected, mri is an excellent tool to confirm this fact. but, if a mastectomy is considered, pathological confirmation before the re-operation is recommended. another imaging technique is tc- m-mibi scintimammography. this seems a promising technique with a high sensitivity and specificity. neoadjuvant chemotherapy is regularly used for downstaging of locally advanced breast cancer. while it is equivalent to adjuvant therapy regarding overall survival and occurrence of distant metastasis, more patients are eligible for surgical treatment by less aggressive breast conservative therapy. neoplastic growth depends on blood supply with nutrients and oxygen. hypoxia-induced angiogenesis is an early step in tumour progression. mri is the imaging modality providing highest sensitivity for detection of breast cancer, highlighting tumour vascularisation by injection of t -shortening contrast agents. characteristic differences between benign and malignant lesions are cause. ultrasound (us) and computed tomography (ct) are readily available and widely used imaging techniques for this work up. us comprises an examination of the abdomen with the graded compression technique. a transducer should be used optimised for the visualisation of the bowel. the ct protocol includes the use of intravenous contrast medium, while oral contrast medium will not be routine in many institutions. findings are bowel wall thickening (or enlarged appendiceal diameter), fat infiltration, free air and fluid collections. the present evidence on the role of imaging in appendicitis and diverticulitis is substantial and has been summarised in systematic reviews. although us is accurate in diagnosing appendicitis and diverticulitis, ct is more accurate than us. further advantages of ct are better identification of alternative diagnoses and better comparison between consecutive examinations. thereby, ct is more helpful in communicating the diagnosis to the referring physician. cost effectiveness of ct in acute appendicitis has been demonstrated as well as the positive impact on management. for colitis, the evidence is more limited and imaging has more limitations here. drawback of ct is ionising radiation exposure. an imaging strategy with initial us and ct only in inconclusive of negative us cases results in the highest sensitivity, reduces ionising radiation exposure and is cost effective. accurate and rapid diagnostic imaging is essential for the appropriate management of acute biliary tract disorders. ultrasonography (us) continues to be the first and often the only test needed to confirm suspected diagnoses affecting the ducts and gallbladder. however, there has been an increase in the overall use of computed tomography (ct) in the emergency room setting, mostly because for its widespread availability and the relative speed, ease and uniformity with which evaluations can be performed. thus, ct may be the first imaging examination performed on patients presenting with signs and symptoms that are less specific for biliary diseases. magnetic resonance (mr) imaging has similarly robust potential as ct, although its integration into the acute care setting requires greater technical and logistical effort. improved mr imaging sequences, advances in coil technology, streamlined imaging protocols, and increased technical and professional familiarity with the modality make it an increasingly attractive option when there is concern about patient radiation exposure or allergy to iodinated contrast material, as in pregnant patients with acute abdominal symptoms. mr can also be used as a problem-solving modality. in this presentation, the common and uncommon imaging appearances on us, ct and mr of acute diseases of the biliary tract and gallbladder will be reviewed. potential pitfalls to be avoided with the three modalities are also illustrated. learning objectives: . to learn the etiology and clinical presentation of acute inflammatory liver diseases. . to understand imaging strategies using us, ct and mri. . to know typical findings and the spectrum of differential diagnoses. pancreatitis is an abdominal condition potentially life threatening. imaging plays a key role not only in the diagnosis but also in the staging and patient management of acute and chronic pancreatitis. pancreatic inflammation and necrosis can be easily identified by imaging methods and has prognostic implications. the clinical prognostic criteria in acute pancreatitis are currently coupled with imaging criteria. ct plays a central role in the evaluation of patients with known or suspected pancreatitis. a ct-based severity index is the main prognostic method to predict outcomes. in addition, mri and mrcp play increasingly important roles in pancreatitis evaluation. integrity of the pancreatic duct can be easily evaluated by this last method, particularly if enhanced with the use of secretin. imaging appropriateness criteria determine the value of distinct imaging modalities with regard to the stage of disease. we review the modern imaging criteria for the diagnoses, staging and patient management in acute and chronic pancreatitis. we also discuss current severity indices and imaging appropriateness criteria. advancements in ct and mri technology have lead to an increasing use of these modalities in the non-invasive assessment of coronary arteries, myocardial perfusion, and cardiac function. while their role in detecting coronary artery disease and functional disorders has been widely accepted, it is still unclear whether they could be adopted in triaging patients for the best therapeutic approach. large studies have already suggested that indication for surgery and percutaneous interventions cannot be solely based on the demonstration of morphologic alterations and that such "cosmetic" interventions are not always leading to the expected outcomes. therefore, non-invasive imaging techniques have to offer more then just the detection of grades of coronary artery stenosis, of areas of infarcted myocardium, or of valvular alterations. adjustment of imaging protocols for additional evaluation of coronary flow reserve, of myocardial perfusion and contractility and of valve size, position and damage with subsequent quantification of degree of stenosis and/ or regurgitation are necessary in order to allow to choose the most appropriate therapeutic approach and thus become the "gold standard" for prognosis and pretherapeutic diagnosis of cardiac diseases. a. can ct predict the outcome of percutaneous intervention? c. loewe; vienna/at (christian.loewe@meduniwien.ac.at) the outcome of coronary revascularisation is not only defined by primary technical success but also by improvement of symptoms and quality of life. thus, despite the individual comorbidities, the outcome and thus the potential benefit of coronary revascularisation depends on many different factors, including morphology, distribution and severity of coronary lesions, myocardial viability, and ventricular function. consequently, the detection of coronary stenosis is not sufficient for planning an optimised treatment. it should be evaluated if the myocardial territory supported by the diseased artery is still vital. in addition, lesions at risk for plaque rupture (culprit lesions) should be identified and treated to avoid major coronary events. cardiac ct allows for the exact assessment of coronary morphology including length, calcification and severity of lesions. based on this morphological information, success of a percutaneous revascularisation procedure can be anticipated with high prognostic accuracy. in addition, the possibility of identification of culprit lesion by means of coronary ct has been described recently. by this, dedicated treatment of only the relevant stenosis should become possible avoiding multiple, potentially unneeded, stents. finally, even the assessment of myocardial viability by means of ct becomes possible. using all the possibilities of cardiac ct optimised treatment plan can be established, and outcome can be estimated. radiological interpretation always incurs some degree of error due to the nature of disease presentation coupled with the difficulty in diagnosis, especially where early signs of disease need to be identified such as in medical screening. early research studies of radiologists' performance concentrated upon the chest radiograph but more recent work has studied breast screening extensively, as well as mri and ct. as radiology is now almost fully digital then research has also examined observer behaviour with a range of digital images, viewing conditions, and image display presentations. it is possible that radiological interpretation will never be accomplished without some errors occurring; however, it is important that steps are taken to minimise any causes of errors as far as possible. the reported error rates found in numerous investigations across different radiological domains will be reviewed and the reasons for these will be elucidated. appropriate reporting conditions will be highlighted for different image viewing scenarios. a theoretical framework for understanding error causation, especially where abnormalities are missed will be detailed. furthermore, the underlying visual, perceptual and cognitive processes which lead to errors will be detailed and approaches to minimise error occurrence will then be proposed. the relationship between human perceptual and cognitive skills and computer imaging processing will be discussed and the usefulness of cad systems outlined as how they can best aid the radiologist from the human performance viewpoint. learning objectives: . to review the basic principles of perception, detection and detectability. . to learn about specifics of perception in medical imaging. . to learn how image processing can help us with the perception process. ing using graf's method led to higher treatment and follow-up rates than that based on nhi alone, i.e. - % vs. . - . % and - % vs. - %, respectively. however, improved examination techniques and a better understanding of the findings have led to a more tailored approach, and an extensive meta-analysis performed in , including papers, could not find any differences in treatment rates due to different ultrasound techniques. in this lecture i will present a crude status for us techniques used and also give recommendations for a worth while screening strategy based on present knowledge, and on work performed within the espr's ddh task force group. with technological advances in recent years, paediatric whole body imaging is now a clinically feasible and increasingly accessible technique. the two principle modalities available are pet, with or without co-registered ct images, and whole body mri (wb-mri), both of which can be utilised to evaluate widespread disease states efficiently. the main application of these techniques has hitherto been oncological; however, as these techniques become more accepted, their use is becoming more varied. pet provides functional assessment, utilising a radiotracer, most commonly fdg- , to assess metabolic activity within tissues, with areas of greater metabolic activity depicted as increased tracer uptake. the use of combined ct-pet enables accurate specific uptake values (suv) to be determined, via attenuation correction, and anatomical co-registration which reduces perceptual errors. wb-mri primarily provides an anatomical assessment, using tissue contrast to identify pathology. this typically uses water sensitive sequences to provide high sensitivity. "physiologic" mri sequences, such as diffusion weighted imaging (dwi) can also be employed to obtain functional mri data, either qualitatively or quantitatively. there are advantages and disadvantages to both techniques, including ionising radiation exposure, acquisition times, movement and other artefacts, and reproducibility, which all need to be considered when choosing a particular technique for whole body assessment in any given paediatric patient, with the disease process being investigated also influencing the technique used. the relative merits, clinical applications and evidence base for the use of pet/ct and wb-mri in paediatrics will be discussed. near future developments, such as pet-mri will be touched upon. the practice of medical image diagnosis is currently undergoing a fast transformation. vast amounts of data can be generated in standard examinations and focus is shifting from improving the collection of relevant data for diagnosis to development of effective methods to analyse, visualise, navigate and interact with medical information. it is now becoming generally accepted in the medical community that one of the most important keys to manage the increasing information work load is the use of d and d applications. this talk will take its starting point in state-ofthe-art medical visualisation and then discuss the need for a research agenda that focuses on the development of the next generation of medical visualisation tools, emphasising the fact that these tools must be based on medical user requirement and work flow studies as well as on new technical developments. childhood osteomyelitis is a relatively rare finding in childhood with an estimated annual incidence of per and is predominantly seen in young children (< years). it can be caused by via haematogenous spread, contiguously from local areas of infection or from penetrating trauma or surgery. usually it is caused by bacterial infections, but occasionally fungi, viruses or parasites are causative agents. clinical findings can range from mild to severe and depends on many factors such as age, site of infection, acute versus chronic osteomyelitis, and causative agent. the crp and sedimentation rate are usually elevated; however, this is not always the case. given the variability in clinical presentation radiology plays a crucial role in the detection of osteomyelitis. although conventional radiography (cr) has a limited sensitivity and specificity for the diagnosis of osteomyelitis, its wide availability makes it the first diagnostic technique of choice in children. for further analysis both mri and radionuclide bone scintigraphy (rbs) have shown to have a high sensitivity for the detection of osteomyelitis. the advantages and disadvantages of both the techniques will be addressed. ct mostly plays a role in the diagnosis of chronic osteomyelitis or in the pre-surgical work-up. the use of radiology also allows for a differential diagnosis of osteomyelitis, based on clinical cases, an overview of this differential diagnosis will be given. the aim of this lecture is to present an evidence-based diagnostic strategy for childhood osteomyelitis. developmental dysplasia of the hip (ddh) is the most common musculoskeletal disorder in childhood, with a reported prevalence of - % according to method of ascertainment and definitions used. ultrasound has enabled a detailed view of both neonatal hip stability (nhi) and morphology, and two different schools have developed; one arguing that nhi alone is the major pathology warranting splinting, the other including acetabular dysplasia as an important feature. both static (graf, morin) and dynamic (harcke) ultrasound techniques, as well as a combination of the two (modified graf (rosendahl)), have been described and are currently used. in europe, graf's ultrasound technique or a modification of this is commonly used within the german speaking countries and areas, in parts of scandinavia, the uk, italy, france, hungary and the netherlands. others use a modified morin's method while harcke's method is used only occasionally. initially, universal ultrasound screen-(helium or xenon), oxygen-enhancement or other technologies. all of these might also provide quantitative read-outs for disease and/or therapy monitoring. learning objectives: . to learn how ct and other imaging methods can be used to examine the structure-function relationship in sad. . to review the state-of-the-art imaging methods that can provide information about disease extent, disease activity and global and regional lung function in patients with sad. . to become familiar with the current use and the future developments of these techniques. panel discussion: signs of small airways disease can be seen on ct but when and why do they really matter? : signs of small airways disease are a frequent finding on ct especially when expiratory scans are performed in addition to inspiratory scans. when should we report these changes? are they always important, do they perhaps predict the development of more severe disease, or are there cases where they have little influence on diagnosis and therapy? when should an expiratory scan be performed? careful preoperative staging and preoperative using high-resolution mri together with preoperative multidisciplinary team discussion has been shown to reduce margin involvement by tumour from % to < % by identification of patients that require more radical preoperative therapy and surgery. the detailed demonstration of preoperative prognostic factors also recognises patients on imaging that are not at risk of local recurrence and therefore the avoidance of unnecessary preoperative therapy in a proportion of patients. the use of eus can help in the assessment of early stage flat lesions suitable for local excision and is a powerful complementary tool. pet-ct is crucial for the preoperative work up of patients undergoing radical procedures such as metastatectomy. follow-up for colorectal cancer patients at high risk for developing recurrent disease is now well established, and the emergence of specialised multidisciplinary teams, combined with a range of treatment options for recurrent disease has improved curative resection rates following metastatectomy and pelvic recurrence surgery. radiologists with a solid understanding of not only the pathological manifestations of primary and recurrent rectal cancer but also the treatment options available play a key role in enabling the appropriate selection of patients -increasing overall cure rates and reducing treatment-related morbidity. this refresher course aims to provide radiologists with an understanding of local staging of rectal cancer, the assessment of recurrent disease, and assessing response to treatment. the course will highlight how imaging underpins the key preoperative decisions for surgical and oncological treatment planning in rectal cancer. a. staging with us and ct a. maier; vienna/at (andrea.maier@meduniwien.ac.at) for rectal cancer surgery a variety of alternative operations are currently possible. furthermore, there is an increasing trend towards treating patients with radiotherapy before surgery. the choice of operation and the decision whether to employ radiotherapy is based on preoperative staging. in patients with primary rectal cancer accurate assessment of tumour extent and the presence or absence of lymph node invasion are factors for determining prognosis and risk of tumour recurrence. endorectal ultrasound (eus) is effective for t-staging. it has been recommended as the investigation of choice in the selection of potentially curative local excision. lymph node staging by this method is less precise than tumour staging. initial reports of the use of ct for tumour staging were encouraging. studies which compare ct with eus staging consistently show the latter to be more accurate for both tumour stage and lymph node stage. thus, the usefulness by the speakers at the end of the session. at the other end of the clinical and imaging spectrum to obliterative bronchiolitis is exudative small airways disease, typified by (japanese) diffuse panbronchiolitis. the exudative bronchiolitides are characterised by direct signs on hrct, notably a tree-in-bud pattern. while this is a readily appreciated and specific sign, other diseases that mimic this hrct finding will be discussed. bronchiectasis of variable severity is a usual accompaniment to both obliterative and exudative bronchiolitis and the relationship between large and small airways disease will be explored. the instances in which hrct findings of obliterative and exudative bronchiolitis co-exist are relatively few, and the differential diagnosis for this situation will be considered. in practice, hrct will often show signs of bronchiolitis (whether obliterative or exudative) limited to a segment or even subsegment, and the interpretation of the clinical significance of such a chance finding is sometimes a difficult judgement. learning objectives: . to become familiar with the direct and indirect signs of small airway involvement on ct. . to know how to correlate these signs with the pathological changes. . to understand the differential diagnosis with other diseases that can show similar ct findings. from pattern to diagnosis c. beigelman; paris/fr various schemes of classification of sad have been proposed according to clinical, pathologic or imaging criteria that are confusing. an optimal approach, mainly based on ct analysis of direct and indirect features, usually allows the recognition of the two main types of sad, namely inflammatory/exudative and fibrotic/constrictive/ obliterative bronchiolitis. a miscellaneous group that corresponds to bronchiolar involvement in diverse diffuse lung diseases may also be individualised. direct signs of sad that refer to direct visualisation of diseased bronchioles strongly suggest inflammatory bronchiolitis. they mainly consist in centrilobular nodules with tree in bud appearance. conversely, indirect signs mainly represented by mosaic attenuation, air trapping, bronchial wall thickening and dilation characterise fibrotic bronchiolitis. volumetric acquisition, performed a dose reaching that obtained with classical hrct protocols, may be of interest in several ways. particularly, maximum intensity projection tool may facilitate the recognition of the tree in bud pattern. the minimum intensity projection mode may optimise the recognition of the mosaic attenuation pattern requiring an appropriate contrast resolution, as well as the analysis of proximal airways. expiratory ct, optimally performed on a dynamic mode, may be useful in some conditions at a dose equivalent to around chest x-rays. a combination of post-processing tools from a volumetric acquisition performed with carefully chosen parameters might therefore appear useful in the evaluation of sad. furthermore, additional co-existing findings such as ground glass opacity or other features of interstitial pneumonias may be detected. their analysis may help to recognise the cause of sad in addition to clinical data. structural changes associated with sad are difficult to depict directly on ct. indirect signs of sad, such as mosaic attenuation on an inspiratory scan and/or air trapping on an expiratory scan, are common findings. they nicely illustrate the structure-function relationship between obstruction or expiratory collapse of the small airways and the subsequent effects on ventilation (local hyperinflation) and perfusion (hypoxic vasoconstriction). these "functional" signs are thought to be more sensitive than the direct visualisation of the underlying structural changes. careful interpretation and software tools help to generate data about disease extent as well as global and regional lung function. beyond paired inspiratory-expiratory ct scanning, dynamic expiratory cine as well as perfusion and ventilation imaging on the basis of both, ct and mri, can be applied to increase sensitivity, specificity and accuracy of the diagnosis of sad. some of them are ready for routine clinical use, such as dynamic expiratory cine ct, cine mri during continuous breathing as well as gadolinium-enhanced perfusion mri. future developments in the fields of ct and mri will provide novel technical approaches for functional imaging of sad. these will include novel applications of dual energy/spectral ct using iodine-enhancement for perfusion and xenon-enhancement for ventilation enhancement as well as ventilation mri using hyperpolarised gases to understand the advantages and limitations of bi-rads in clinical practice to appreciate the potential of an automated analysis of the descriptors to trace continuous modifications required by technological advancements. . to review bi-rads categorisation with case illustrations a. how i do it p. richards; stoke-on-trent/uk (paula.richards@uhns.nhs.uk) . always report in the same logical manner for each examination, which imprints normal pathology 'jumps out at one'. . evaluate all images before looking at the clinical information to prevent bias and satisfaction of search. . review every scout image. scoliosis transitional vertebrae and pseudoarthrosis become more obvious on coronals. single kidneys, hydronephrosis and renal tumours may explain 'back pain', especially if there are mets. . review any x-rays or old ivus, remembering that abdominal x-rays show the spine. . indications; summarise the reason for the scan. think of the differential diagnosis to exclude. . technique; allows one to check the levels scanned. be sure there has been no area missed between studies. . report vertebral alignment and disc height. . mri just like an x-ray, i.e. there is normal alignment from d to s . . start at the far sagittals and look at the nerve roots in the 'key hole', the pars and facets. . determine the worst abnormality on the axials and report the most significant findings first. check the facets at each level. . have a checklist of normals at the end; 'the bone marrow, cord and csf return normal signal. the conus ends normally with no pars or metastasis'. .opinion: explain what you think is causing the patient's symptoms. assume this is the only part read, so if there is only one kidney reiterate here. the lecture will illustrate additional information on scout images and benefits of coronal images. learning objectives: . to understand the influences of patient positioning, scan parameters and magnet/coil technology on image quality. . to learn how to optimise scan protocols to maximise patient throughput without compromising diagnostic quality. . to recognise how and when to modify scan protocols to answer specific clinical questions.a- the lumbar spine undergoes morphological changes with age. normal appearances and relevant normal variants will be discussed. in particular, the morphological change from an almost round intervertebral disc in newborns with high water sig-postgraduate.educational.programme s a b c d e f g h radiotherapy is an area with a rapidly improving development of new techniques and improved possibilities for accuracy. this lecture aims to illustrate and discuss points of contact and the need for collaboration between radiotherapy and radiography. european educational programmes and working fields for radiotherapy nurses and radiotherapy technicians are compared. radiotherapy nurses and radiotherapy technicians are responsible for the administration of radiotherapy to cancer patients and for the clinical care related to the treatment. apart from prevention and treatment of side effects and psychosocial support during the treatment, it encompasses preparations, delivery and verification of the radiation dose. educational programmes differ in terms of academical level and target groups, whether it is nurses or technicians in radiology or radiotherapy exclusively. areas in the radiotherapy process where competences from radiography are needed are discussed, considering both technical development and research progresses. learning objectives: . to gain knowledge about the differences and similarities between the areas of education and profession in radiography and radiotherapy from a historical perspective. the demand from the public for greater accountability and standards has increased the importance of audit and accreditation in modern healthcare delivery. specifically radiology departments participate in audit and accreditation by a number of entities. these include: . national bodies concerned with improving radiation safety particularly originating from eu / directives. . hospital wide accreditation surveys from state and private accrediting organisations. . auditing of standards from within professional bodies. . following from investigation of specific incidents such as misdiagnosis or radiation concerns. . modality-specific standards.although the specific requirements of the accrediting or auditing body may differ, the processes and practical aspects in demonstrating compliance with standards and quality improvement are generally similar. mechanisms such as outcomes, quality cycles, and performance indicators are critical in the success of any accreditation or audit program. in addition to fulfilling basic regulatory requirements, the medical physicist is playing an increasing role in developing performance indices particularly in radiation safety, clinical image quality and equipment management. the increasing role of the medical physicist in audit underpins the requirement for inclusion of audit and accreditation as part of their education. recent experience of setting up and participating in eu / directive-based clinical audit in ireland highlighted the critical need for clarity of roles and ownerships of processes to be communicated to those who are carrying out audit and those who are being audited in hospitals and dental practices. performing imaging studies in a child requires basic knowledge. the first point is to reassure and to avoid stressful/painful procedure. training of radiographer and radiologist is fundamental. explanations, presence of a parent (if not pregnant…), are preferable. specific devices may be useful for immobilisation and to avoid repeated exposures. antalgic drugs (traumatic circumstances) or sedative nitrous oxide inhalation (mcug) may be useful. x-rays exposition in relation with conventional radiology is lower than the one encountered with ct. but dose depends on type of examination and also on imaging equipment. new devices, such digital fluoroscopy with x-rays pulsed emission, flat-panel detector, slot-scanning x-ray imager need less ionising radiation than conventional screen-films devices or even photostimulable phosphor imaging plates. the scale between the higher and the lower dose for the same examination can be from ten to one. common principles of protection that apply to all x-ray imaging procedures, known as alara concept (as low as reasonably achievable), have to be used daily. act in accordance of the medical justification of the examination, without any non-ionising alternative method, remains the first step. the second one is the optimisation of each procedure, the limitation of expositions, with control of the x-ray beam adjusted to optimise the critical balance between image quality and exposure to the child. measure of the dose is mandatory to demonstrate appropriate levels on child exposure and to be sure in the future that very low radiation doses received during conventional imaging procedures will not produce adverse effects. the council directive / /euratom introduced the concept of clinical audit to medical radiological (diagnostic radiology, nuclear medicine and radiotherapy) procedures. clinical audit is a systematic review of the procedures in order to improve the quality and the outcome of patient care. according to the directive, clinical audits shall be implemented in accordance with national procedures. the review of its implementation in europe has revealed a high variation of approaches and many practical problems. therefore, the european commission has published further guidelines on clinical audits in its report radiation protection no. ( ). the purpose is to improve the implementation of clinical audits and to enable the member states to adopt the model of clinical audit with respect to their national legislation and administrative provisions. the guideline points out the importance of both internal and external assessments for clinical audit. it deals with all types and levels of clinical audit and gives practical guidance for application. it defines the list of topics which should be covered, while the actual criteria of good practice are discussed on generic levels only. the borderline between clinical audit and other quality assessments (accreditations, certifications, peer reviews) and regulatory inspections is also discussed. the guideline is addressed to all professional groups, hospital management, auditing organisations and regulatory bodies. it is important to recognise that the guideline is not a legal requirement. this refresher course lecture will give a summary of the ec guidelines and discuss briefly the implementation of clinical audits in europe.learning objectives: . to understand the purpose and essential contents of the european commission guideline on clinical audit. b. national perspective: clinical audit inspections s. ebdon-jackson; didcot/uk (steve.ebdon-jackson@hpa.org.uk) european council directive / /euratom requires under article ( ) that "clinical audits are carried out in accordance with national procedures". implementation of this requirement across europe has been varied. this paper will reflect on the experience in the uk and will consider examples of the various initiatives undertaken in the uk by professional bodies and organisations. this will be contrasted with the role of the regulator and the aims of the inspection process with regard to compliance with the specific regulation addressing clinical audit and the remaining regulations addressing justification, optimisation, etc. examples will be provided of the type of audits undertaken within uk hospitals. a uk perspective of ec and iaea initiatives in clinical audit will be provided. percutaneous radiofrequency ablation (rfa) is a safe and effective treatment for well selected patient with hepatic tumours such as hepatocellular carcinoma (hcc) and liver colorectal metastases (lcm). an appropriate selection is crucial. it is based on clinical and technical arguments. clinically, surgical resection of the haepatic tumours remains the gold standard. indeed, survival data following rfa are not as good as surgical resection. the only exception seems to be the rfa of the very early hcc (≤ . cm) in cirrhosis that is not candidate for liver transplantation. most often, the rfa offers an alternative for patients with medical comorbidities, poor liver function or prior hepatectomy. technically, there are three decisive points for complete ablation. the first point is the good visualisation of the tumour either under ultrasound or un-enhanced computed-tomography (ct) examination. metallic coil placement, lipiodol tattoo and virtual ct sonography with magnetic navigation are technical tricks that allow the rf ablation of "invisible" tumour. the second point is the tumour size: in most series, a diameter less than - mm is commonly admitted as a prognostic factor. this is probably because the maximal ablation diameter is slightly larger than mm with the electrode needles available now. micro-waves ablation might improve the local control by increasing the ablation diameter. the last point is the "heat-sink effect" that requires a temporary occlusion of a large vessel close to the tumour. the quality of follow-up imaging is a key factor for evaluation of tumour destruction. partial hepatectomy for liver metastases or primary liver tumours can only be performed when the future remnant liver volume (frlv) is considered large enough to avoid the risk of post-operative liver failure. in normal livers a frlv of - % is considered safe whereas in compromised livers a frlv of at least % is required. in patients whom the flrv is considered to small, pve may be performed pre-operatively to increase the frlv. pve involves percutaneous selective embolisation of the portal venous (pv) system, usually of the right liver lobe, which leads to atrophy of the embolised lobe. this, in turn, leads to hypertrophy of the frlv. because of the dual vascular supply to the liver (arterial and portal venous), necrosis of the embolised lobe does not occur. this compensatory hypertrophy of the left lobe facilitates resection in patients in whom the frlv would otherwise have been to small to allow resection. pve is most often performed percutaneously under conscious sedation and local anaesthesia through an ipsilateral approach, using a combination of particles, such as polyvinyl-alcohol (pva) and embolisation coils. potential complications of pve include thrombosis of the contralateral pv, liver abscess formation or cholangitis and are rare. most of the hypertrophy occurs in the first - weeks after pve and increase in volume of the frlv averages % after this time period. ct-volumetry should be performed both before pve and after - weeks to measure increase in frlv. accurate identification and reporting on soft tissue extremity masses is essential for correct diagnosis and optimal treatment planning. this lecture focuses on the mri signs to stage and grade-characterise soft tissue mass lesions. these two objectives are the major structural components of the mri report and fit the request of the referring clinician. this implies an accurate description of these signs with appropriate terminology in the report. local staging is essential for the preoperative work up. important staging parameters are size, compartmental location, skip lesions and relationship to neurovascular structures and joints, as well as distance to the nearest joint space. grading and characterisation is complex and multifactorial and classifies the lesions as "certainly benign" (no biopsy needed) and "possibly " or "certainly malignant" (biopsy needed). grading parameters are homogeneity, (changing) signal intensities in multiple acquisition techniques and static and dynamic gadolinium enhancement pattern. these are used to define the composition of the lesion, i.e. fat, met-hb, hemosiderin, myxoid tissue, collagen, viable, cystic or necrotic components. other important grading and parameters are lesion margin, shape, perilesional invasion or destruction, multiplicity, specific location and associated findings but also age and gender of the patient. image guidance and imaging fusion techniques represent an integral element in oncologic interventions and liver surgery. in addition, several liver planning techniques such as the virtual liver surgery planer enhance simulation of a proposed liver resection. using roboter-assistance or navigational guidance combined with thermal ablation techniques such as radiofrequency ablation, significantly enhances accuracy of ablation probe placement and efficacy of ablation necrosis. furthermore, the local recurrence rate can be considerably reduced, and the amount of complete tumour ablation is significantly more likely. integrating magnetic resonance imaging, and focused ultrasound to deliver and activate nano-capsules carrying anti-cancer drugs to effectively target tumours will be another task. this will involve drugs being injected into the body in the form of tiny capsules, which are harmless until they are activated by a concentrated focused ultrasound `blast'.the mri scanner will then be used to track the passage of the drugs, visualise the target and monitor the delivery of the drug treatment. the risks associated with radiation exposure in ct is of concern to radiologists, medical physicists, government regulators, and the media. thoracic ct is a technically robust, non-invasive imaging technique for the evaluation of several traumatic and non-traumatic thoracic emergencies. technical advances in the past years have resulted in improvements in image acquisition speed, spatial resolution, and the temporal resolution. consequently, thoracic ct can now be performed rapidly in emergency conditions without substantial delay in treatment. state-of-the-art ct systems are now capable of imaging the entire thorax within a few seconds. however, radiation exposure associated with thoracic ct have been increased with the advantages of modern ct systems particularly in the evaluation of chest pain syndrome. thoracic aortic ct angiography with cardiac gating may now be considered the preferred technique for the evaluation of chest pain syndrome in selected patients but is associated with a substantial higher radiation dose than routine non-gated thoracic ct. several effective strategies have been developed to limit the radiation exposure in cardiac gated thoracic ct including prospective ecg gating techniques, anatomy and ecg-based tube current modulation, high pitch acquisition, and adaptation of the ct scanning parameters to the body habitus. in addition, several techniques are available to reduce the radiation exposure in nongated thoracic ct depending on the patient's body habitus and the clinical indication. because of advancing technical developments and increasing diagnostic utility of mdct in emergency care, its use has expanded significantly and has changed patient care, especially in chest emergencies. however, mdct has important drawbacks in cost and radiation exposure. the first presentation will discuss mdct in acute chest pain (acp). scan techniques in different scanners will be addressed. the reasons why cta/ctca can be a viable application for acp and the current evidence for cta in acp will be discussed followed by an update on indications. the next presentation will address mdct in chest trauma. its significance, the utility of this imaging method and its advantage compared to other modalities will be discussed. the examination protocol and the role of post-processing methods will be addressed. the interpretation of mdct, findings, benefits, limitations and pitfalls will be shown. the utility of chest x-ray and ultrasound as primary examinations and the indication for mdct, routine or selective, will be discussed. our last speaker will familiarise us with procedures to measure radiation dose in thoracic mdct, followed by an update of radiation exposure associated with the protocols for the different clinical indications. finally, available techniques for radiation dose reduction in ecg-gated and non-gated mdct and their effectiveness in radiation dose reduction will be demonstrated. however, the best way to reduce radiation is to perform mdct only when there is an appropriate indication and this will be the focus of the concluding panel discussion of this session. chest trauma is, particularly in younger population, a significant cause of morbidity and mortality. it is directly responsible for - % of trauma-related deaths and in other % of deaths it is an important contributing factor. imaging methods play the key role in management of this group of patients. introduction of mdct in the last decade of the th century markedly changed the diagnostic approach to the thoracic trauma. fast data acquisition and increased resolution in the z-axis enabled reliable assessment of all chest anatomical components (often together with other parts of the body) in one examination. compared to x-ray mdct defines more accurately the extent and severity of traumatic changes and may detect serious in % of nontraumatic cases, subarachnoid haemorrhage (sah) is the result of aneurysmal rupture. other causes of sah include perimesencephalic sah ( %) and other disorders ( %) such as arteriovenous malformation (avm), vertebrobasilar artery dissection, dural av-fistula, cortical vein thrombosis, amyloid angiopathy, … sah represents an emergency situation and diagnosis should be established asap.plane computed tomography (ct) is the initial diagnostic test of choice (wide availability, easy accessibility, high sensitivity and specificity). if ct is negative, lumbar puncture and/or mri of the brain (including flair images) and spine should be performed. d tof mr angiography (mra) sequences have high sensitivity and specificity in detecting cerebral aneurysms; but because of their lower spatial resolution are insufficient to analyse in detail aneurysm morphology. this in contrast with cta. both cta and mra may be proposed as a first-choice, noninvasive examination, but the negative predictive value is poor, and therefore digital subtraction angiography (dsa) is mandatory for all sah cases with negative cta or mra. catheter angiography remains the golden standard in the detection and evaluation of cerebral aneurysms (size, relationship between neck and adjacent vessels, etc). increased attenuation (ct) and hyperintense signal (flair) within the basal cisterns and sulci are a characteristic finding of sah; however, it is aspecific. pattern and location of the blood may help to locate the ruptured aneurysm; sometimes helpful when multiple aneurysms are found. pseudo-sah may be a potential imaging pitfall because it may be observed in other acute neurological conditions (cerebral edema, bacterial meningitis, etc). recurrent disease following treatment for primary breast cancer can occur in the same breast following conservation surgery, ipsilateral breast tumour recurrence (ibtr) or in the contralateral breast, metachronous contralateral breast cancer (mcbc). estimations for the rate of recurrence are between and . % each year. the rate of recurrence is higher than breast cancer incidence in the general population. risk factors for recurrence are young age (< ), high grade disease, incomplete tumour excision and no radiotherapy. due to the large numbers of women who develop and survive breast cancer the cost and resource required to follow-up these women is considerable. there are variable guidelines in europe for the surveillance of women but most regimes include clinical follow-up and mammography. variations concern the frequency of mammography, the length of follow-up required, and whether clinical examination is required. the clinical effectiveness and cost-effectiveness of different surveillance mammography regimens after the treatment of primary breast cancer will be reviewed together with the results of systematic reviews. modelling of two data registries was undertaken to ascertain the survival benefit. alternative methods of surveillance will be considered such as mri with the diagnostic accuracy of the various imaging techniques considered. a summary of the economic evaluation will be presented to demonstrate the assumptions that require to be made in this complex area where there is a paucity of evidence.learning objectives: . to understand the risk of recurrent disease and second primary following the treatment of breast cancer. . to review literature on surveillance mammography and other imaging methods for detection. . to appreciate the range of recommendations for surveillance mammography and clinical follow-up with cost benefit analysis. the new challenge in breast cancer: evaluation of response : evaluation of the treated breast is one of the major challenges in breast imaging.there is especially much debate on the evaluation of response to therapy. the best imaging modality, the best imaging criteria, timing, accuracy and limitations of imaging are currently being investigated. whether it is time to reach conclusions regarding these aspects is the issue of this panel discussion. intracranial aneurysms are abnormal dilatations of the arteries, and will be found in % to % in general population. in % cerebral aneurysms are saccular and develop from the arteries of the circle of willis or its major branches. aneurysms typically become symptomatic between the age of and years, with subarachnoid haemorrhage (sah) or intracerebral haematomas. less common are giant aneurysms usually found in middle-aged women presenting with signs more indicative of a mass lesion. ct angiography (cta) has been proven to be an excellent tool to visualise intracranial arteries. the average sensitivity of cta for the detection of intracranial aneurysms reaches %. post-processing allows assessment of the aneurysm with maximum intensity projections (mip) and surface-rendered d projections in multiple plains. mr angiography (mra) is a practical and noninvasive tool for screening of high-risk individuals for aneurysms. dsa is diagnostic method of choice for assessment of intracranial aneurysms and was considered to be a 'gold standard' for evaluation of cerebral vessels. a clear shift from invasive to noninvasive imaging of cerebral vessels has been noticed in the last decade. this lecture will discuss advantages and disadvantages of cta, mra and dsa in detection, assessment, and post-treatment evaluation of intracranial aneurysms. intracranial aneurysms have a multifactorial origin. a heterogeneous and complex group of pathogenic mechanisms including luminal, mural and extramural factors interact for the development and growth of aneurysms. there are several types of intracranial aneurysms, being the saccular the most common type. the aneurismal treatment is dependent on its type and needs a multidisciplinary approach including endovascular and microsurgical teams. endovascular treatment is recognised as the first-line treatment for most of the ruptured saccular intracranial aneurysms. there has been an enormous improvement in the endovascular technology and techniques offering a wide spectrum of treatment possibilities that broadened the variety of aneurysms that can be treated. the treatment options include the use of coils with/without the help of balloon-remodelling and/or stenting. other options include the use of covered stents, of "flow-diverter" stents, of liquid embolics, or the parent vessel occlusion. the multislice computer tomography angiography (mscta) is a reliable method for pretreatment evaluation of intracranial aneurysms. for the posttreatment evaluation, magnetic resonance angiography (mra) can be used for the follow-up of embolised aneurysms; and mscta may be used for the follow-up of surgically treated aneurysms. there are several challenges remaining in aneurysm management. in the diagnostic field, improvement of the non-invasive techniques for the diagnosis, for the morphological and haemodynamic characterisation and for the posttreatment follow-up of aneurysms is expected. in the endovascular field, technological breakthroughs to improve the occlusion rate, to increase the treatment durability, and to promote the vessel wall healing are desired. learning objectives: . to learn about present treatment of brain aneurysms. . to understand the strategies for multimodal ct and mr aneurysm imaging pre and post-treatment. . to present the challenges for neuroimaging in the field in the near future. where do we stand in brain aneurysm treatment today? : there is a significant difference in the management of patients with ruptured versus un-ruptured brain aneurysms. this panel discussion will focus on the management of patients with brain aneurysms and will with simple case presentations show the management in ruptured and un-ruptured aneurysms and discuss the involvement of the neurosurgeon in more complex cases.cone beam ct (cbct) is a method for obtaining ct-like images using a c-arm system. our aim was to investigate the accuracy of these images compared with multi-detector ct (mdct) as a gold standard in radiological imaging of abdominal aortic aneurysms (aaa). patients with aaa referred for elective evar were included in a pre-therapy protocol ( patients) and in a post-therapy protocol ( patients). all were exposed to standard mdct and one additional cbct. image data were evaluated by two radiologists and statistically compared using a linear mixed model. first, predefined arterial measurements were performed, then predefined anatomical areas were assessed and scored for visibility on a scale from to . all measurements were chosen to be relevant for evaluating of aaa before and after evar. for the arterial measurements no significant differences were found between mdct and cbct. visibility for the anatomical areas was significantly better for mdct; however, most of the cbct readings were above lowest acceptable level. visualisation of the iliac arteries was suboptimal. we think that our results support the start of clinical trials that scientifically can test the outcome without the use of mdct immediately before and after evar. the problem with poor visualisation of the distal iliac arteries might be solved with newer technology. in conclusion, the result indicates that cbct in the operation room gives sufficient image-based information to support evar in a pre-and post-therapy setting. undertaking theatre radiography can appear a daunting task for the radiographers lacking in confidence in their ability but others (like all expert practitioners) make it look easy and uncomplicated. theatre radiography requires all the knowledge, skills and abilities of a competent radiographer together with assertiveness, reflection and the ability to modify your technique at a moment's notice. there are a multitude of 'traits' which distinguish the expert from the novice. these include production of optimum images, effective use of the equipment, radiation protection, infection control, effective communication and teamworking. there is also a clear depth of knowledge together with a multitude of skills and abilities. the key to a stress-free experience is preparation. it is essential that there is a mechanism for theatre staff and the radiology department to communicate effectively and give the radiographer prior notice of all cases requiring their attendance. it is also desirable to be in the theatre when the patient arrives for their examination to enable you to check the patient's identity, pregnancy status and ensure the patient is positioned correctly to facilitate screening. there are few excuses to give the surgeon if you cannot screen the area of interest because of poor positioning of the patient and equipment. this paper will discuss the knowledge, skills and abilities required to undertake theatre radiography in a safe and proficient manner without feeling threatened by the experience. learning objectives: . to understand the key skills required to undertake radiographic procedures in the operating theatre. . to gain an insight into the interpersonal skill required for effective radiographic practice in the operating theatre. prediction of coronary revascularisation outcome represents a major clinical question because a large number of medical and surgical options have become available for ischaemic cardiomyopathy with need to identify more rigorous criteria for patient's selection. the combination in a single examination of function, stress-perfusion and tissue characterisation with t -weighted 'oedema-sensitive' and late-gadolinium enhancement (lge) techniques supported the role of cardiac mr (cmr) as an important technique for the evaluation of patients candidates to revascularisation. besides more "traditional" indicators such as ejection fraction, end-diastolic wall thickness or endsystolic volumes, extent and distribution of myocardial scar depicted with lge has been identified as one of the most important predictors of post-revascularisation outcome with direct influence on functional recovery and on major adverse cardiovascular events (mace) due to the potential induction of arrhythmias from the scar.lge technique has been shown to be superior to nuclear medicine for the assessment of myocardial viability due to the higher spatial resolution (up to -fold greater than spect) and an intrinsic high contrast resolution. a further technique that could be adopted before revascularisation is stress imaging. myocardial ischaemia detected by either cmr adenosine first-pass perfusion or dobutamine-induced wall motion abnormalities has been shown to predict subsequent cardiac death whereas normal stress perfusion showed a high negative predictive value for mace. in conclusions, although as a relatively new diagnostic modality prognostic evidence is predominantly derived from singlecenter studies, cmr is increasingly becoming an important tool for risk stratification of patients before revascularisation, offering indications about outcome and mortality. cardiac valve diseases are an important public health problem, strongly linked to the general increasing age of the western population. the most frequent valve disease is aortic stenosis, for which percutaneous aortic valve replacement (pavr) is currently evolving to a feasible alternative therapy for the classical surgical approach in high-risk patients. nevertheless, careful evaluation of all aspects of this new approach is still required to avoid uncontrolled diffusion. imaging plays a key role in selecting patients who may be eligible for pavr, focusing on the evaluation of leaflet anatomy, severity of valve dysfunction, haemodynamic consequences and potential problems in the access route. while echocardiography is commonly used for both the anatomical and functional evaluation, multidetector ct (mdct) has important intrinsic advantages providing state-of-the-art d imaging with a high spatial resolution over a large anatomic coverage. during this course, we will discuss the advantages and disadvantages of mdct compared to other imaging modalities. the relevant anatomy of the aortic valve and annulus will be reviewed, with emphasis on correct alignment of the imaging planes, and its implications for correct reporting of the necessary measurements targeted at the clinicians need. furthermore, mdct scan protocol design will be reviewed, focusing not only on optimal implementation of common scan parameters but also on the need of ecg-triggering and its consequences. finally, we will present the current status of evidence on using mdct in pavr procedures, and discuss future challenges and perspectives. learning objectives: . to understand how to optimise the imaging protocol for aortic valve imaging. . to learn how to report the findings and what to include in the report. . to understand the impact of this approach on patient management. the need for quantitative image analysis in radiology is universal: computer-aided detection, segmentation for d volume visualisation, image enhancement, pattern recognition, etc. all need effective, robust and preferably generic (not 'ad hoc') algorithms for the computer. how to design such algorithms? a good inspiration source is the functionality of the visual system, the best investigated brain structure today. in this talk we will explain how we think the brain calculates features in images, why the retina measures at a wide range of resolutions and how we can exploit this. the visual system is strongly adaptive and self-learning. new optical recording techniques have given new insight in how the cells in the visual cortex are functioning. we will go through these functionalities step-by-step. what we discover is quite amazing. we recognise huge amounts of filter banks in the first stages of vision: many filters analyse each pixel of the incoming image at a range of scales, orientations, derivative order, for each colour, and also as a function of time. extensive feedback loops take care of optimal settings locally. we programmed these filters into the computer, and were able to build many interesting applications for computer-aided diagnosis: detection of catheters at seriously reduced levels of x-ray radiation dose, automatic polyp detection, quantitative analysis of ischaemic heart ventricle deformation, breast cancer cad, pulmonary emboli cad and analysis of in vivo microscopy images now so abundant in modern life-sciences research. postgraduate.educational.programmethe gi tract are leading causes but any tumour involving the abdominal cavity or haematological malignancy may be implicated. during treatment with chemotherapy or radiotherapy acute abdominal symptoms are common as a consequence of direct toxicity. imaging must be used as an adjunct to clinical assessment. patterns of abdominal involvement are often modified in the later phases of disease. gi tract obstruction may be due to progression or the mechanical consequences of prior surgery and is more commonly at multiple levels. perforation or fistulation may occur with either progressive disease or tumour lysis in response to therapy. cancer does not protect against the common inflammatory conditions but poor host response and the use of steroids may mask signs leading to extensive abnormality at diagnosis. bone marrow suppression increases susceptibility to infection including neutropenic enterocolitis and haemorrhage. bone marrow transplantation and consequent graft versus host disease is a potent cause of acute abdominal symptoms. ct is the major imaging technique although mr has an increasing role particularly in the assessment of the female pelvis. major determinants when considering the differential diagnosis include; the nature and initial stage of the primary, any prior anatomical modification (surgery), the nature and relationship to current treatment and the bone marrow status. this workshop will begin by describing the current limitations of mri in evaluating prostate cancer patients and will show how to overcome these with advanced imaging techniques including diffusion weighted mri (dw-mri), mr spectroscopic imaging ( h-mrsi) and dynamic contrast enhanced mri (dce-mri). the emphasis will be on the use of processing tools that are readily available for clinical practice. we will describe how to analyse images and provide a scheme for reporting findings back to surgeons/oncologists. we will show that using more than one mri tool improves imaging performance and that the relative importance of each technique remains unresolved. we will demonstrate new indications for advanced mri in prostate cancer patients. abdominal hernias are common in daily practice and can be divided into: external or abdominal wall hernias, internal hernias and diaphragmatic hernias. external hernias typically involve protrusion of abdominal contents through a defect in the abdominal wall. internal hernias involve protrusion of viscera through congenital or acquired defects in the mesentery or the peritoneum. diaphragmatic hernias involve protrusion of abdominal contents into the chest. among these conditions, the diagnosis of internal hernia is the most challenging. bariatric surgery and liver transplantation with biliary-enteric anastomosis, with the roux-en-y loop placed in a retrocolic position, are recognised predisposing factors for internal hernia development. symptoms of hernia are nonspecific and vague, and clinical and radiologic diagnosis can sometimes be challenging. immediate diagnosis is mandatory because misdiagnosis can be complicated by bowel obstruction, volvulus, strangulation, incarceration, or trauma. mdct with its multiplanar capabilities is widely believed to facilitate this diagnosis, because it is able to delineate hernia type, location, size, and shape and is particularly useful to diagnose unsuspected hernias. it also allows distinguishing hernias from masses of the abdominal wall, such as tumours, haematomas and abscesses. as a result, knowledge of the ct findings of abdominal hernias may allow early and more accurate diagnosis, with a resultant decrease in the mortality rate. the title of this talk limits the discussion of torsion to the mesentery and omentum. it has to be mentioned, however, that an abnormal twist (torsion) can involve any peritoneal reflection of those suspending and fixating hollow viscera, (e.g. stomach, small bowel, cecum, sigmoid and gallbladder), solid organs, (e.g. spleen, ovaries), or even extraperitonel (extraabdominal) organs such as the testicles, leading to the pathologic entity of volvulus or torsion of the corresponding viscous with its associated (different) imaging findings, prognosis and treatment. moreover, twisting of the mesentery and volvulus can occur secondary to a variety of conditions including congenital anomalies of intestinal rotation with variable prognosis. finally, torsion of the omentum can be either primary or secondary, also associated with different pathology, imaging findings and treatment. consequently, a broad spectrum of abnormalities ensues related to the pathophysiology of torsion which requires a detailed classification, an accurate description and the use of correct terminology making it impossible to be covered within the time limits of a presentation. therefore, focusing the discussion on to abnormal twist of small bowel mesentery and omentum will simplify the approach to avoid overlaps and confusion. this case-based lecture will present typical clinical cases of pelvic pain as well as some unusual but important causes. cases of acute and of chronic pelvic pain, and benign as well as malignant disease will be included. the audience will have the opportunity to participate in case discussion by the use of interactive voting pads. the selection of imaging modality for each clinical presentation and the importance of knowing the clinical findings at the time of the radiological interpretation will be discussed. for each case, the key radiological features will be illustrated. the essential elements of the radiology report and the key information required by the clinician will be discussed. in each case, the differential diagnosis and the need for follow-up imaging will be considered. the key teaching points for each diagnosis will be reviewed. this lecture provides a practical approach to the fundamentals of normal cross-sectional anatomy of the hip. basic knowledge necessary to identify the different portions and contents of the joint anatomy is provided. a special emphasis is on cartilaginous structures, the acetabular fossa, and capsular fibers and ligaments. functional anatomy of muscles and tendons about the hip is reviewed. the location of bursae and their association with adjacent structures is discussed. in the second part of the lecture attendees will learn how to avoid commonly seen pitfalls about the hip. a special focus on anatomic variants of the acetabular labrum simulating disease is given. osseous variants including acetabular ossicles and the superior acetabular notch will be explained and explored. debates about the role of herniation pits referred to as a normal variant are reviewed. the lecture offers an overview of muscular and tendinous variations around the hip joint. pelvic pain is an important part of clinical practice for any clinician who provides health care for women. pelvic pain may be acute, recurrent or chronic. acute pelvic pain (app) rarely lasts more than one month without crisis, resolution, or cure. pain of more than or or months of duration is considered as chronic pelvic pain (cpp) and in many settings may be considered and treated as an illness itself. women who present with app frequently exhibit nonspecific signs and symptoms. diagnostic considerations encompass multiple organ systems, including obstetric, gynaecologic, urologic, gastrointestinal, and vascular aetiologies. as the first priority, urgent life-threatening conditions (e.g. ectopic pregnancy, appendicitis and ruptured ovarian cyst) and fertility-threatening conditions (e.g. pelvic inflammatory disease and ovarian torsion) must be considered. adolescents and pregnant and postpartum women require unique considerations. ccp is a common and significant disorder of women, with a prevalence of . - %. many disorders of the reproductive tract, gastrointestinal system, urological organs, musculoskeletal system, and psychoneurological system may be associated with ccp, the most common being endometriosis, adhesions, irritable bowel syndrome and interstitial cystitis. ultrasonography should be the initial imaging test because of its sensitivities across most aetiologies and its lack of radiation exposure. computed tomography (ct) serves an important role in patients with nonlocalizing symptoms, an indeterminate us evaluation, or in patients who require a wider search beyond the field of view available with us. magnetic resonance imaging is an extremely useful second-line modality for problem solving after us or ct. fat-suppression sequences help to establish fat-containing lesions and increase the conspicuity of inflammatory lesions. different sequences will be discussed. mr is rated below us and ct for evaluation of acute pelvic conditions, but is excellent alternative when administration of iodinated contrast media or radiation exposure is undesirable, especially in young or pregnant patients. long imaging times, limited access and cost are major drawbacks of mri. imaging findings of various gynaecologic and nongynaecologic conditions causing female pelvic pain will be presented. an overview of the interventional radiology management of painful osseus metastases will be presented. consideration will be given to patient, lesion and treatment modality selection (including radiofrequency ablation, cryoablation, microwave ablation, laser ablation, ethanol ablation, mr focused ultrasound ablation, cement osteoplasty, transarterial embolisation and combinations therein, e.g. combined radiofrequency ablation and cement osteoplasty). the evidence supporting these techniques and patient outcomes will be reviewed. molecular imaging -defined as the non-invasive assessment of biological mechanisms at molecular and cellular level -will play a major role in future disease diagnosis and treatment planning. in this context, the aim of this session is to introduce in simple terms several major research areas in molecular imaging and to discuss their future potential for clinical radiology. the differential diagnosis of hip pain is broad and includes intra-articular pathology, extra-articular pathology including referred pain from the spine, and mimickers including groin pain and pain from the joints of the pelvic ring. the diagnosis of all causes of hip pain/pathology has improved with greater use of magnetic resonance imaging (mri) to complement traditional investigations. in this session pathology involving the hip and groin will be reviewed in a systematic way which will outline an approach to the hip that will allow the reader to maximise their diagnostic ability. the review will include evaluation of bone marrow disorders such as avascular necrosis and transient osteoporosis and intra-articular pathology including labral tears and femoroacetabular impingement (arthritis and traumatic fractures will not be reviewed). extra-articular diagnoses such as bursitis, groin pain (osteitis pubis and adductor/ gracilis dysfunction) and common muscle and tendon injuries will then be reviewed. today, many procedures of bone and joint are performed under imaging control. minimally invasive procedures require less resources, time, recovery, and cost, and often offer reduced morbidity and mortality, compared to other modalities. many percutaneous techniques are available. some aim to treat pain and consolidate bone (cementoplasty). others ablate or reduce the tumour (chemical and thermal ablation techniques). the interventional radiologist with an efficient imaging-guided technique (flat panel fluoroscopy, ct, and mri) can increase the precision of the above-described procedures allowing an improvement of the results and reduction of the complications. furthermore, the presented interventions are carried out either on an outpatient basis or with hours hospitalisation which contributes to the reduction of overall costs and presents a major advantage for patients of working age. some of these minimally invasive procedures can be considered as alternatives to surgery without excluding further surgical options if necessary. back pain is one of the most common complaints, it is estimated that almost % of working adults will experience it in any given year. diseases of peripheral skeleton may produce painful symptomatology as well. some of the algogenic structures of the spine and peripheral skeleton are lumbar intervertebral discs, facet joints and atlanto-axial/occipital joints, sacroiliac joints, nerve root dura, periosteum, ligaments, fascia. among several aetiologies which can involve these structures, spine degenerative pathology plays the leading role. nowadays, several different interventional techniques are available, each one with its specific target of action. with the right indication each of them has been proved to be effective as painkilling modality. herein, we present an up to date comprehensive overview on the interventional techniques available with their own indications. small airways and small airways diseases (sad) have attracted a lot of interest that has resulted in a large number of publications since the early s. despite the several histopathological and clinical subtypes that have been described diagnosis is not always obvious. the introduction of thin section ct and the fact that this ct technique is able to depict signs of sad has not only renewed interest but has also improved insights in these disorders. in this session the direct and indirect ct signs of sad will be presented and the ct techniques that can improve their detection will be explained. correlations between pathological findings and the presence of these ct signs will be made and diseases that can mimic these ct findings will be discussed. schemes of classification of sad based on clinical and pathological findings will be discussed briefly, but most attention will be given to the radiological classification, which is based on the recognition of the direct and indirect signs of sad. algorithms that help to identify the cause of sad will be presented. finally, the use of ct and also of mr as a tool to examine the structure-function relationship in sad will be discussed. it will be shown how careful interpretation and software tools can help to generate data about disease extent and global and regional lung function. the ability to recognise direct and indirect signs of small airways disease on hrct has led to renewed interest in these elusive disorders. the "purest" of these diseases is constrictive obliterative bronchiolitis which is manifested on hrct by the indirect sign of a mosaic attenuation pattern; the differential diagnosis for mosaicism and an algorithm that helps to identify the correct cause of small airways disease will be presented. the necessity for routine expiratory hrct to make the diagnosis of obliterative bronchiolitis is controversial and will be discussed jointly whole body fluorescent imaging and bioluminescent imaging are now widely applied in small animals to study all kinds of biological and molecular processes like i.e. gene expression, tumour progression and metastasis, apoptosis, inflammation, angiogenesis, proteolysis and to follow trafficking, differentiation and fate of cells (i.e. stem-, immune-and tumour cells). this has been done mainly by using gene reporters expressing fluorescent proteins or luciferases. recently new mutated red shifted fluorescent proteins (with better light penetration and less absorption and autofluorescence) and codon optimized and mutated luciferases have been developed making optical imaging more sensitive and offering the possibility to use dual gene reporters. apart from new "smart gene reporters" there has also been a great development in injectable near infrared fluorescent (nirf) probes, especially for tumour detection. these nirf probes can either be targeted or enzyme-cleavable. these new developments has opened up the possibility to apply nirf imaging in the clinic especially to image tumour tissue and to identify sentinel lymph nodes during operation. the assessment of the tumour-free margin during cancer surgery is critical to completely remove the tumour and improve the prognosis of the patient. by injecting a tumour specific nirf probe, tumour tissue and local metastases can be visualised in real-time during operation using a dedicated nirf camera system. we now already use nirf imaging in the clinic to detect the sentinel lymph node (sln) in several types of cancers. in the current presentation preclinical and clinical applications of nirf imaging in image-guided surgery will be discussed. targeted ultrasound contrast agents have opened up the door for molecular imaging with sonography. these contrast agents, which consist of encapsulated gas microbubbles, are coated with antibodies or specific ligands. injected into the circulation, microbubbles are retained in diseased tissue where they can be detected and quantified by different approaches such as "semiquantitative -d" or "quantitative -d" imaging techniques. due to their size, microbubbles behave similar to red blood cells and remain within the intravascular space. therefore, the disease process must be characterised by specific molecular changes on the surface of the endothelial cells to be assessable by ultrasound. several angiogenic markers such as vegfr , α v β -integrins, icam- and vcam are known to be overexpressed by the endothelium in neoplastic, inflammatory and vascular diseases. thus, molecular ultrasound imaging seems perfectly suited to detect these markers and monitor changes which might occur during treatment response or disease progression. today, targeted ultrasound contrast agents are becoming a routinely used preclinical tool and the first application of specific microbubbles in a clinical scenario is expected for the near future. this talk will introduce into the principles of molecular imaging with ultrasound. based on recent studies, basics of tumour biology, potential endovascular targets, synthesis of molecular probes and different imaging approaches for a preclinical and clinical application of molecular ultrasound will be discussed. in this rc, a general insight of imaging in epilepsy, including indications, protocols, and the most common neuroradiological conditions to be identified, will be covered. particular interest will be given to tumours as a cause of epilepsy, and to their more relevant neuroradiological aspects. finally, the contributions of different imaging techniques in the specific context of epilepsy surgery will be reviewed. brain tumours are a common cause of epilepsy more often in adults, less in children.tumours detected in patients with chronic epilepsy are predominantly located in the brain cortex area, affecting the temporal lobe most often. any benign or malignant brain tumour can be responsible for seizures, but some are more frequently associated with epileptic symptoms. low-grade astrocytomas, oligodendrogliomas, gangliomas, dysembryoplastic neuroepithelial tumours (dnets) and glioblastomas multiforme are the tumours significantly often presenting with seizures in adult population. brain tumour-related epileptogenesis in not fully understood yet, but one can list a number of factors playing an important role in this process, including: disruption of physiological neuronal structure, tumour affection on the release of neurotransmitters and abnormal electrical activity of the brain. different imaging techniques are widely used for evaluation for neoplasms in epileptic patients. ct is reserved for acute conditions, one must remember to exclude other possible aetiologies of seizures like haemorrhage, trauma or inherited malformations. mri remains the gold standard in imaging investigation of patients with epilepsy. conventional pre-and post-contrast se sequences are mandatory to perform in every subject. newer and more sophisticated techniques such as diffusion-weighted imaging (dwi), functional studies (fmri), spectroscopy (mrs) and pet are helpful in qualification for surgery and preoperative functional mapping. mri has become established as the modality of choice for preoperative local staging of rectal cancer. the most important general advantages of mri compared to other crosssectional imaging modalities are the soft tissue contrast resolution between the propria muscle layer of the rectum and the perirectal fat, the ability to visualise the different pelvic compartments including the visceral pelvic (mesorectal) fascia and the surrounding tissues in the pelvis. high resolution t -weighted sequences sagittal, transaxial and perpendicular to the tumour is the basic standard for morphological evaluation of the tumour, the distance of the tumour to the anal verge and for evaluation of extramural extension and the distance to the circumferential resection margin. presence of other adverse features such as extramural venous invasion and local lymph node metastases is also noted. the mr-images are ideally demonstrated by the radiologist in a local multidisciplinary conference to make sure that the information is used to select the best possible treatment for the patient. when neo-adjuvant treatment is administered, mri is usually performed both before and after treatment to assess treatment response. when planning surgery, both the pre-as well as the post-treatment images should be available for surgical planning. finally in this lecture, the potential benefits of t compared to . t for pre-operative imaging of rectal cancer as well as the present role of additional techniques, such as diffusion-weighted imaging (dwi) and specific contrast agents that have been evaluated for assessment of rectal cancer will be addressed. locally recurrent rectal cancer is the main concern after rectal cancer surgery and has long been regarded as a rarely curable disease. patients were treated palliatively, and subsequent median survival was months and the -year survival rate was %. however, during the past - years, more patients were considered candidates for curative treatment due to better treatment options. patients with distant recurrences from colorectal cancer, especially those in the liver or lung, have improved chances for cure with better imaging, better surgery and alternative minimal invasive treatment. in the follow-up after colorectal cancer surgery it is thus important to detect recurrences at an early stage. besides cea, imaging is often used as a surveillance tool. it is still unclear which is the most cost-efficient (imaging) tool for monitoring distant and local recurrences. this lecture aims at providing the evidence for surveillance by imaging and reviewing the guidelines for the detection of recurrences after colorectal cancer surgery. it will also discuss the role of mri for establishing resectability of locally recurrent rectal cancer and the imaging patterns and features of recurrent disease. its strength comprises a high sensitivity in detecting coronary stenosis > % and an excellent negative predictive value. the stringent limitation of cta lies in its confinement to anatomic grading of coronary stenosis and a lack of information regarding whether a stenosis causes reversible myocardial ischaemia indicating the need for coronary revascularisation. recently published data in animals and humans indicate that myocardial computed tomography perfusion (ctp) imaging is feasible, promising and accurate. the advantage of cta is the comprehensive evaluation of coronary arteries and myocardial perfusion defects from the same datasets, which permits both visualisation of coronary anatomy and physiology.further, ct provides information about regional and global myocardial function. the aim of this course is to understand basic principles of ct perfusion and functional imaging, to learn "how-to" perform ctp and comprehensive cta/ctp scans, to review current scientific evidence and to discuss potential clinical applications. nuclear medicine tests (spect and pet), mri and more recently mdct have been involved in myocardial perfusion imaging. in clinical practice, perfusion analysis is routinely performed with qualitative or semiquantitative assessment, both based on relative evaluation of uptake or enhancement of myocardium, considering a remote region as normal. however, the assumption of part of myocardium as normal can be wrong and cause false negatives. absolute quantification has been introduced mostly with pet perfusion imaging (water, ammonia and rubidium), but its incremental value for the clinical decision making has not been widely investigated. more recently, mr perfusion imaging has been used for quantitative analysis with different technical approach. there are some clinical scenarios where quantification can change the clinical interpretation: . multivessel coronary artery disease (cad), . balanced multivessel cad, . exclusion of cad in symptomatic patients, . microvascular disease, . revascularised patients. however, there are still some limitations in the use of absolute quantification: first, the setting of cutoff value for normal or abnormal perfusion; second, some clinical situations, such as heart failure patients, where perfusion is reduced and heterogeneous. finally, studies concerning the prognostic value and the cost-effectiveness are needed. epilepsy is a common disorder with a prevalence of up to % in the general population. epilepsies are broadly classified into generalized and focal. though most generalised seizures are controlled pharmaceutically, % of focal seizures are medically intractable. in this subset of patients, the overall sensitivity of mri in identifying responsible substrates is approximately %. the purpose of neuroimaging in epilepsy patients is to identify underlying structural abnormalities that require specific treatment (usually surgical) and to aid in formulating a syndromic or aetiologic diagnosis. in this presentation imaging findings of the most common non-neoplastic lesions responsible for focal epilepsy, namely: a. hippocampal sclerosis, b. malformations of cortical development, c. vascular abnormalities and e. gliosis, will be discussed along with their differential diagnosis and pertinent imaging pitfalls. since routine mr imaging is suboptimal in identifying epileptogenic substrates, imaging should be tailored accordingly. hippocampal sclerosis, the most common cause of mesial temporal lobe epilepsy, is best demonstrated when the temporal lobes are imaged with thin sections in coronal plane perpendicular to the longitudinal axis of the hippocampus. inversion recovery sequences best demonstrate morphology and volume loss in the hippocampus, mammilary body and fornix. t and flair images best demonstrate the increased signal due to gliosis. for malformations of cortical development flair is useful in assessing hyperintense signal. t gradient volume sequences can demonstrate subtle developmental malformations. finally, because many epileptogenic lesions are subtle and easily overlooked, a systematic diagnostic approach to mri interpretation in the clinical setting of epilepsy is helpful and will be discussed. epilepsy surgery is an effective and safe therapy for selected patients with intractable localisation-related epilepsy. when morphological mri fails to reveal focal, structural pathology (e.g. tumour, dysplasia, etc). as the putative aetiology for the seizures, other modalities may be taken into account. in the absence of structural pathology it is essential to identify the epileptogenic zone as exactly as possible in order to (a) increase the chance of a good outcome (reduction or termination of seizures) and (b) limit post-surgical sequelae. this lecture will cover some modalities that may add valuable information in this process. the need to individualise the pre-surgical evaluation and the concept of a multimodality epilepsy protocol will be discussed. the main focus will be on spect (single-photon-emission computed tomography), functional mri, pet (positron-emission tomography) and the added value of co-registration on morphological mri (e.g. siscom). briefly, ictal spect may help to identify focal areas of hyperperfusion (ictal zones). functional mri is used for several reasons. one is to determine language laterality (dominant hemisphere); another is to localise eloquent cortical structures to aid the planning of the surgical approach. pet may detect hypometabolic areas corresponding to areas involved in epilepsy. mrs (magnetic resonance spectroscopy), meg (magnetoencephalography) and intradural eeg-registration and stimulation will be mentioned. the term epilepsy covers a wide spectrum of symptoms and underlying etiologies. an essential part of the work-up of patients with epilepsy includes the radiological examination. in recent years more sophisticated methods radiological methods have emerged and the discussion will focus on how these new advanced techniques may help finding underlying causes and be of help in the pre-surgical work-up. excellence in teleradiology: key issues in workflow management j. schillebeeckx; bonheiden/be (jan.schillebeeckx@imelda.be)the healthcare market is undergoing significant change. the market is evolving from a provider centric to a patient centric model, requiring relevant data to converge at patient level in a timely and structured fashion. the push towards setting up collaborative networks for radiology is strong in most european countries. the most important challenge for teleradiology is to ensure that it develops in a manner that benefits patient care and ensures overall patient safety, and does not in any way reduce the quality of radiology services provided to the citizen. therefore, these collaborative networks require more than just it infrastructure with it support. but as important is case management, workflow management and the administrative and management support that provides all the stakeholders with operational, analytical and statistical qa reports. through a centrally operated hub, the radiology workflow is optimised to ensure throughput of cases, involving radiologists in the network, with the difference that only the services are provided by the hub to the network, not the medical acts, which remain in the hands of the radiologists. learning objectives: . to learn about the technical needs of a teleradiology infrastructure adapted to a distributed environment. . to understand that teleradiology involves much more than just technology.optimising the workflow and time management are also important. . to appreciate how creating collaborative networks can improve the efficiency of radiology procedures and bring improved work/life balance to radiologists. to make teleradiology an integrated part of clinical radiology, it must change from being a provider of radiology reports into a close collaboration with the client radiology department. there are many different aspects on workflow in a clinical setting and the teleradiology service should adapt to these specific needs in order to make a seamless collaboration. however, there are advantages with the global aspects of teleradiology that could improve diagnostic accuracy and efficiency in the clinical setting that should be woven into the collaboration. teleradiology services have developed substantially over the last few years from limited use between hospitals and tertiary care centres for second opinions and patient transfer to the international provision of reporting services. there is no doubt that teleradiology provides a valuable service in some circumstances, but it also has a number of inherent limitations regarding the proper provision of imaging services to the patient and therefore may increase risks for the patient. we will highlight the problems that have arisen and reiterate key parts of the guidelines which were developed for the benefit of patient care. this lecture will demonstrate a multimodality approach to the imaging of salivary colic. the relevant us and mri salivary anatomy will be highlighted and the ultrasound, computed tomography and magnetic resonance appearances of salivary grafts. respectively. graft sclerosis develops in % of nonoccluded venous bypass vessels after years and in % after years. this sclerosis causes more than % luminal narrowing in approximately half of the affected vessels. non-invasive imaging of coronary bypass grafts by md-ct require information about the operative procedure. with the increasing implementation of slice ct scanners and beyond, it is possible to scan the heart and the full anatomic extent of grafts with sub-millimeter slice-thickness within a single breath-hold. when analysing the grafts, three graft segments should be assessed: the origin or proximal anastomosis, the body of the graft and the cardiac anastomosis, either single or sequential. recent studies have shown that graft patency and the presence of significant graft stenosis can be assessed with an accuracy of % using most recent md-ct technology ( / slice ct or dual source ct). the assessment of native coronaries with respect to the progression of cad may still be problematic in cases with severe calcifications of the native coronary arteries. in these cases, mr perfusion imaging in combination with cine and late gadolinium enhancement (lge) imaging may be helpful in detecting newly developed, stress-induced myocardial ischaemia. teleradiology services have developed substantially over the last few years from limited use between hospitals and tertiary care centres for second opinions and patient transfer to the international provision of reporting services there is no doubt that teleradiology provides a valuable service in some circumstances, but it also has a number of inherent limitations regarding the proper provision of imaging services to the patient and therefore may increase risks for the patient. we will highlight the problems that have arisen and to reiterate key parts of the guidelines which were developed for the benefit of patient care. it is now well understood that teleradiology cannot be considered just as 'telereporting', i.e. the simple interpretations of images remotely acquired and sent as a message in the bottle. teleradiology procedures, being medical acts, must ensure the full involvement of the interpreting radiologist in all phases of the well established practice of diagnostic imaging: appropriateness check, personalised acquisition protocols, access to clinical history and prior imaging examinations, communication with referring physician and patient. any obstacle that teleradiology causes to these activities may put our patients at risk (and therefore may expose us at liability suits). the presentation will describe the organisational as well as technological remedies for reducing such risk. for several decades, monte carlo simulation has been recognised as a powerful technique to simulate the transport of radiation in media, as well as to provide solutions for calculations too complex for classical approaches. several general purpose codes and databases providing particle interaction cross-sections have been developed, and with the increase in computing power, simulation has become more and more popular within the field of medical imaging. using monte carlo simulation methods, the different steps involved in the formation of a medical image can be analysed in detail, and the whole system optimised. a topic that has deserved particular attention in the past is the simulation of x-ray tubes and x-ray spectra, which is the first step in the simulation of a medical imaging system. when simulating an x-ray tube, various complex phenomena need to be taken into account, such as the electron multiple scattering, bremsstrahlung interactions, characteristic x-rays emitted from the k-shell and auger electrons emitted during a photon interaction. together with the simulation of the target material and the filtration of the x-ray beam through permanent (e.g. a be window) and added filtration (e.g. al, mo, rh, ag, etc)., this technique can lead to a good estimation of the emitted x-ray spectrum, a task which is hard to achieve with experimental methods. this review will provide an overview of the basic knowledge necessary to start the simulation of an x-ray tube as well as of how to accelerate the calculations. emphasis will be given to mammographic x-ray tubes. breast cancer screening and diagnostic imaging, as all clinical imaging, are increasingly multimodality. a number of new imaging modalities have been developed, including digital breast tomosynthesis and dedicated breast ct. they have shown promise in early studies; however, their technological complexity present obstacle for optimisation. the ultimate technology tests are clinical trials, which are, however, challenging, particularly for breast cancer screening, as large studies are needed due to the small number of detected lesions. clinical trials are costly, long, and they involve repeated exposure of women to radiation. as an alternative, we have been developing virtual clinical trials, based upon our virtual breast phantoms and simulation of phantom images. this talk will describe the development of anthropomorphic computer breast phantoms, and illustrate their use in the analysis of phantom digital mammography and digital breast tomosynthesis images. different currently used phantom designs will be compared in terms of their flexibility and realism. specific phantom requirements related to different imaging modalities will be emphasised. the role of phantoms in tissue-specific analysis of the radiation dose during mammography will be discussed. in addition to the anthropomorphic phantoms for breast imaging, the use of virtual patients in various clinical imaging disciplines will also be illustrated. learning objectives: . to learn about requirements for anthropomorphic phantoms (virtual patients). . to understand the value of anthropomorphic phantoms for breast imaging. . to compare advantages and disadvantages of several types of anthropomorphic phantoms. . to learn how to estimate typical patient doses from simulations with virtual phantoms.colic will be shown and techniques for optimising the imaging of salivary colic given. the use of us, ct, mri, and both mri and conventional sialography in the imaging of salivary colic will be discussed. the role of interventional sialography and minimally invasive techniques in benign salivary gland obstruction will be demonstrated. trigeminal neuralgia is defined as recurrent episodes of lancinating pain most common in the second (v ) or third division (v ) of the trigeminal nerve. the pathogenesis is a neurovascular conflict by an artery or vein associated with focal demyelination of sensory fibers at the glia-schwann cell junction. apposition of demyelinated fibers induces abnormal generation and transmission of impulses. mr imaging is based on high-resolution d sequences: ciss/fiesta/ d t space with coronal and sagittal oblique mpr and a d tof intracranial sequence with axial and coronal thin mip reconstruction to delineate the course of vessels along the trigeminal nerve form the pons, and glia schwann cell junction to the gasserian ganglion. the brainstem and brain are assessed by t , flair and d isotropic gd-enhanced t sequences; the viscerocranium is examined by a noncontrast and coronal t gd fat suppressed sequence. analysis of images is focussed on recognition of displacement and distortion of the proximal trigeminal nerve by the sca, rarely by the aica, ba or petrosal, pontomesencephalic or peduncular vein. correlation of the circumferential site of distortion at the root entry zone with the somatopic representation of fibres increases the, in general, low specificity of the neurovascular contact. ruling our compressive tumours, neoplastic infiltration, inflammation or demyelination and delineating a neurovascular conflict stratifies patients for potential microvascular decompression in case of failure of medication. the purpose of this lecture is to provide an overview of the key imaging features of painful swallowing with or without associated mucosal pathology. in the presence of a mucosal lesion, painful swallowing is most often caused by infectious, neoplastic or traumatic lesions of the pharynx itself, whereas in the absence of mucosal alterations, painful swallowing is the result of functional disorders (dysfunction of the cricopharyngeus muscle), infectious, inflammatory or neoplastic diseases affecting adjacent neck spaces (retropharyngeal and paraphyrngeal space), neurologic impairment (glossopharyngeal neuralgia), carotidodynia and eagle's syndrome. the indications for ct, mri, us and videofluoroscopy will be reviewed and their respective role in the detection and precise description of the underlying cause. major emphasis will be put on how to report the findings in a comprehensive way. learning objectives: . to recognise the most common causes of painful swallowing in patients with a normal pharynx at clinical examination. . to review the role of different imaging techniques in the diagnosis and treatment of painful swallowing. . to review the key imaging techniques in the diagnosis and treatment of painful swallowing. . to review the key imaging features of the most common causes of painful swallowing as seen with the respective imaging techniques.the typical hrct features of interstitial lung disease are ground-glass opacity, consolidation, pulmonary nodules, tree-in but sign, bronchiolar wall thickening, mucoid impaction, air trapping, septal thickening, mosaic perfusion and honey combing. most frequent diseases in children to be dealt with are bronchiectasis, cystic fibrosis, asthma, constrictive bronchiolitis, bronchiolitis obliterans and extrinsic allergic alveolitis and they will be demonstrated with use of a systematic approach. during the lecture we will present and validate methods to simulate radiographic images with the monte carlo software mcnp/mcnpx in a time efficient way. we will start the lecture by introducing three image detector models that can be used in mcnp/mcnpx. the first detector model that will be presented is the standard semideterministic radiography tally, which has been used in previous image simulation studies. furthermore, we will present two alternative stochastic detector models: a perfect energy integrating detector and a detector based on the energy absorbed in the detector material. the image detector models will be validated by comparing calculated scatter-to-primary ratios (sprs) with published and experimentally acquired spr values. subsequently, we will introduce a method to modify the images, generated with the mcnp/mcnpx image detector models, for the physical characteristics of a computed radiography (cr) imaging systems. the method presented in this lecture takes into account the signal intensity variations due to the heel effect along the anode-cathode axis, the spatial resolution characteristics of the imaging system and the various sources of image noise. to demonstrate the accuracy of our model we will compare the threshold-contrast detectability in simulated and experimentally acquired images of a contrast-detail phantom. thoracic trauma in children is most commonly seen in a polytrauma context, and is associated with significant morbidity and mortality. blunt trauma accounts for the majority of cases, often resultant from motor vehicle accident and pedestrian crash. common thoracic injuries include pulmonary contusion, rib fractures, pneumothorax and haemothorax. diaphragmatic and mediastinal injuries, such as aortic rupture and tracheobrocheal tear, are rare but potentially life threatening. different patterns of injury are seen in children due to anatomical and physiological differences, and these should be recognised. chest radiography is the first and most important imaging modality. mdct allows accurate diagnosis for most traumatic injuries, and is usually performed for severe chest and/or polytrauma. adapted paediatric protocols are essential. foreign body inhalation is a common paediatric domestic accident, with potential serious or even fatal consequences. clinical history is the key for the diagnosis. with a definite history, bronchoscopy is the modality of choice for both diagnosis and treatment. however, in many cases the aspiration event is not witnessed and the diagnosis is often delayed or overlooked. the majority of aspirated foreign bodies are non-opaque and imaging findings largely result from complete or incomplete airway obstruction. chest radiography is the first imaging modality. expiratory films (or lateral decubitus or fluoroscopy) are very useful to demonstrate air-trapping. chest mdct offer excellent details of the tracheobronchial tree and pulmonary parenchyma, and is usually reserved for more complex cases and/or long-standing foreign bodies. high-resolution ct of the chest is the imaging technique of choice for the evaluation of most infiltrative diseases of the chest. in children dose-adapted protocols should be used and recommendations for suitable protocols will be given in the course. the mediastinum is a region of the thorax that separates both lungs and communicates with the neck and the abdomen. these two anatomic features are very important to understand the behaviour of some diseases and their radiological manifestations. most asymptomatic mediastinal masses are benign, while clinical symptoms might raise the possibility of a malignant lesion. imaging plays a very important role, especially ct and mri. in the presence of a mediastinal mass we must ask ourselves two questions: . where is the mass located? the classic divisions of the mediastinum in compartments remains very useful, because it narrows the differential diagnosis. . is the lesion cystic or solid? pure mediastinal cysts are benign and their characterisation depends on their location. thymic cyst (anterior mediastinum), bronchogenic and duplication cysts (middle mediastinum) and menyngoceles (posterior mediastinum). solid lesions may be benign or malignant while some lesions may have a cystic component. solid lesions of the anterior mediastinum are usually thymomas, germ cell tumours or lymphomas. in the middle mediastinum most masses are of lymphatic origin but we should also include aortic or oesophageal pathology. intrathoracic thyroid usually follows the trachea and thus is situated in the upper-middle mediastinum although posterior and anterior extensions may occur. in the posterior mediastinum most masses are of neural origin. there are some locations that will typically indicate specific diagnosis or a narrow differential. such is the case of the cardiophrenic angle masses, juxtadiaphragmatic lesions and thoracic inlet pathology. colorectal cancer is common. approximately , new cases occur each year in the million population of the states which comprise the eu. after lung, it is the second commonest cause of cancer death resulting in approximately , deaths per annum. these relatively high mortality figures are a reflection of the fact that the disease is often advanced at the time of presentation. efforts to reduce mortality, therefore centre on early detection as well as accurate staging. the latter is particularly important in rectal cancer-the commonest site for colonic cancer. detection depends on presentation, which is often protean or non-existent; hence, the introduction of screening programs. typical diagnostic tools include the barium oenema, optical colonoscopy and ct colonography. the limitations of the barium enema have been exposed by optical colonoscopy and it can no longer be advocated in this role. ct colonography, however, rivals optical colonoscopy in the detection of polyps and tumours, although of course has no therapeutic potential. major advances in the treatment of rectal cancer include total mesorectal excision (tme) of the rectum as well as neo-adjuvant therapies such as chemo-radiation. their use depends on highly accurate staging of the primary disease, which can only be achieved by mr examination, although of course ct or pet/ct is required for the assessment of more distant metastatic disease. finally, once treated, it is essential that these patients are followed-up; usually by a regime of colonoscopy and ct. these issues will be discussed in an interactive lecture. decreased opacity of the lung may be a bilateral or unilateral process. if unilateral, it may involve an entire lung, a lobe or a segment. faulty radiological technique must always be excluded. the most common cause of unilateral decreased opacity is a previous mastectomy. bilateral decreased opacity occurs in copd and asthma. it is also caused by decreased blood flow in the lung/s. expiratory films separate the true lung causes from all the others, by demonstrating air trapping. pulmonary nodules are spherical radiographic opacities (solid and subsolid) that measure up to mm in diameter. extremely common in clinical practice, pulmonary nodules, especially small ones under cm in diameter, are a challenge to manage. it is important to identify malignant nodules because they are potentially curable. the first step in assessing a pulmonary nodule on a chest radiograph is to determine that it is indeed a lung nodule rather than a pleural or chest wall abnormality. it is essential to review images from previous examinations, because a solid nodule that remains stable for at least years is probably benign. topics discussed in this talk include the importance of nodule size, growth rate, margin morphology, density (solid, ground-glass and part solid), calcifications or fatty components within the nodules, the significance of cavitations or bubble-like densities, enhancement patterns at dynamic contrast-enhanced ct, and findings on positron emission tomography (pet). the talk also covers the current guidelines for the management of incidentally detected nodules (solid and subsolid). this presentation has the purpose to familiarise radiologists with the spectrum of mesenteric and omental cystic masses, demonstrating the additional correlation with the underlying pathology. cystic masses of the mesentery or omentum are not common lesions; however, radiologists should be aware of these entities as well as with other cystic lesion of the abdomen. important tool for the diagnosis is to determine the organ from which the mass originates. common types of mesenteric and cystic masses include lymphangioma, enteric duplication cyst, enteric cyst, mesothelial cyst and non-pancreatic pseudocyst. other entities such as cystic mesothelioma, cystic spindle cell tumour and cystic teratoma could be located in the mesentery also. due to the overlap in the imaging features, not always the final diagnosis could be reached by imaging only and therefore histologic examination is necessary to establish the diagnosis. however, it is important for the radiologist to define the cystic nature of the mass and demonstrate the potential mesenteric or omental origin, targeting to the correct differential diagnosis of the cystic lesion. cancer cells from intraabdominal neoplasms, carried by peritoneal fluid throughout the abdominal cavity, result in widespread metastases in the form of implants, the socalled peritoneal carcinomatosis. the location of implants development is governed mostly by peritoneal fluid circulation and by specific anatomic pathways formed by peritoneal reflections. the most common sites where the peritoneal fluid may temporarily arrested facilitating implantation of cancer cells include cul-de-sac, distal small bowel mesentery, right paracolic gutter, posterior sub-hepatic space, greater omentum and sub-phrenic spaces. the role of imaging is to disclose the presence and extent of the disease -i.e. fundamental in candidates for cytoreductive surgery -to monitor response to treatment and to reveal recurrences. mdct with thin collimation and i.v. contrast material supplemented by multiplanar reconstructions is the primary imaging modality for the investigation of peritoneal carcinomatosis. ascitis, contrast enhanced smooth, nodular, or plaque-like peritoneal thickening, peritoneal nodules, plaques or masses, rounded, ill-defined soft-tissue or cystic mesenteric masses, mesenteric fixation with increased attenuation values and thickening, irregular soft-tissue permeation of omental fat or confluent solid omental masses are the most frequent ct findings of peritoneal carcinomatosis. ct has a sensitivity and specificity between and %, depending on the size/location of implants and examination protocol used. mr imaging employing a post-gadolinium-enhanced d flash sequence with fat saturation may alternatively be used and it is advantageous in cases of diffused layered type of peritoneal/mesenteric involvement. diffusion mri may be of value in post-treatment imaging evaluation. primary solid tumours of the peritoneum and mesentery occur much less frequently than metastatic disease in the same location. however, these rare primary neoplasms (peritoneal mesothelioma, primary peritoneal serous carcinoma, desmoplastic small round cell tumour, mesenchymal tumours, mesenteric fibromatosis or mesenteric desmoid tumour, mesenteric sarcoma, etc.) are often first detected at ct and should be considered in the absence of a known primary organ-based malignancy. ct appearance combined with patient's relevant clinical and demographic data can help narrow the differential diagnosis for a primary peritoneal or mesenteric tumour in many cases; diffuse sheetlike thickening of the peritoneum and stellate appearance of the mesentery at ct or mri are suggestive of primary malignant mesothelioma in older men with high level of asbestos exposure. absence of an ovarian mass is mandatory in suggesting the diagnosis of primary peritoneal serous carcinoma in a post-menopausal woman. desmoplastic small round cell tumour occurs in young men and often presents with a large primary peritoneal mass with calcification. a solid mesenteric mass at ct or mri, regardless of its pre-and post-contrast appearance, occurring in a patient with familial postgraduate.educational.programme embolisation of hcc with drug eluting beads k. malagari; athens/gr (kmalag@otenet.gr)drug eluting beads have proved predictable pharmacokinetics and achievement of higher doses of the chemotherapeutic, prolonged contact time with cancer cells.in addition, research data today have shown response, and tolerance benefit of drug eluting beads compared to conventional chemoembolisation for the more advanced subgroup of bclc -class b patients. for diameters larger than μm dc bead loaded with doxorubicin have proven to be more effective with respect to local response, recurrence rates and time to progression (ttp) compared to bland embolisation with similar diameters. in this session results of studies on dc bead loaded with doxorubicin for the treatment of hcc will be discussed, and guidelines for optimal clinical use will be presented. selective internal radiotherapy j.i. bilbao; pamplona/es (jibilbao@unav.es)selective internal radiotherapy, also called radioembolisation (re), consists in the delivery of beta-radiation to liver tumours using microspheres loaded with yttrium- (y ) that are injected into the hepatic artery or its branches. y is a pure beta-emitting radioisotope, with a limited tissue penetration (average: . mm and maximal: mm) and a half life of hours. y can be either incorporated or labelled into glass or resin microspheres ( µm). once the particles are infused into the hepatic artery, they travel to the distal tumoural arterioles, from where the beta-emissions from the isotope irradiate the tumour. with traditional external beam radiation, doses are limited to - gray (gy) due to the risk of radiation-induced liver disease that may occur with higher doses. with re, tumours can receive a higher dose of radiation due to their preferentially arterial vascularisation and a higher tolerance of the non-tumoural liver parenchyma to this form of radiation. re has shown an encouraging antitumoural activity with a good safety profile in patients with hepatocellular carcinoma, even in the presence of portal vein thrombosis or invasion. local tumour growth control is achieved in the majority of patients although response rates using volumetric criteria are achieved in only - % of patients. in liver-predominant unresectable metastases, there is promising evidence that re combined with systemic chemotherapy significantly extends the time to progression of liver metastases and increases objective response rates as well as enabling patients to receive systemic chemotherapy for a longer period of time. learning objectives: . to learn about the technique, legal and safety requirements in the cathlab. . to understand the diagnostic and interventional procedures before radioembolisation. combined therapies before and after ablation r. lencioni; pisa/it (lencioni@med.unipi.it) image-guided rfa is currently established as the standard of care for patients with early-stage hcc when transplantation or resection is precluded. however, histologic data from liver specimens of patients who underwent rfa as bridge treatment for transplantation showed that the rate of complete tumour eradication is highly dependent on the size and the presence of large abutting vessels. combined percutaneous-transcatheter approaches that aim at increasing the ablation volume by minimising heat loss due to perfusion-mediated tissue cooling have been developed, using either a balloon catheter occlusion of the tumour arterial supply at the time of the rfa or by performing a prior tace. experimental studies in animal tumour models have shown that lowering the temperature threshold at which cell death occurs by combining sublethal heating with cell exposure to trans-arterial chemoembolisation takes advantage of the largely portal vascularisation of liver tissue, while metastatic tissue is supplied almost exclusively by hepatic arteries. the benefit of intra-arterial application of chemotherapeutic drugs is proportional to the first pass extraction of the drug by the target tissue and inversely proportional to the body clearance of the drug. these figures vary greatly with different chemical properties of the drug. intratumoural drug concentration after transarterial application (compared to intravenous application) is approximately x for thp-adriamycine, x - x for fu, x - x for mitomycine, x for cisplatin or oxaliplatin, and x for doxorubicin. several trials support superiority of intraarterial fu over i.v. application in response rate, and partly with a moderate survival benefit. however, with the advent of novel chemotherapeutics (mainly oxalyplatin, irinotecan), response rates of i.v. chemotherapy approached the results after i.a. fu. more recently, i.a. oxaliplatin has shown a % response rate in a multicenter trial on non-responders to i.v. oxalyplatin. also, combinations of i.a. oxalyplatin and i.v. fu and cetuximab have achieved promising response rates as first line therapy. even though intraarterial chemoembolisation alone can achieve promising response rates, the actual survival benefits are limited to date. also, the beneficial effect of additional embolization (over conventional arterial injection) remains largely unproven for a large number of different embolisation agents in hepatic metastases. in an attempt to further increase tumour uptake, chemotherapeutic agents (anthracyclines and irinotecan) have been electrostatically coupled to microspheres. irinotecan-eluting microspheres have been untilized in the treatment of crc metastases in smaller case series. due to the high parenchymal drug uptake, appropriate medications to mitigate postembolization side effects need to be emphasised. while the initial response rates were over % (according to easl), tumour progression was observed within months in the majority of responders, suggesting potential stimulation of angiogenesis at the tumour boarders. potentially, adjuvant antiangiogenic treatment can provide an overadditive effect in these patients.primary bone tumours require both local staging and the identification of distant metastases to guide management. mr imaging is the modality of choice to determine local disease extent and allows excellent depiction of intra-and extraosseous disease. chest ct enables pulmonary metastases to be identified and bone scintigraphy allows evaluation of the presence of bone metastases. the roles of whole body mri and pet/ct in the staging of bone tumours will also be discussed. whilst imaging may allow a narrow differential diagnosis to be reached, histological confirmation of the nature of the lesion is required pre-operatively to plan appropriate treatment. image-guided biopsy may be performed using fluoroscopy, ct, mri and occasionally ultrasound guidance. the relative values of each of these techniques will be covered. percutaneous therapies are increasingly being utilised in the treatment of a number of primary bone tumours. radiofrequency ablation is the method of choice for osteoid osteoma and is now used in the treatment of chondroblastoma. alternatives include microwave therapy, cryotherapy and sclerotherapy. these percutaneous techniques may also be used for local disease control where disease recurrence is encountered. magnetic resonance imaging (mri) has evolved to become the most important diagnostic method for local staging of primary bone tumours and for detecting postoperative tumour relapse. it allows accurate preoperative staging of local tumour extent and helps to obtain adequate safety margins. mri is a noninvasive technique that can be used to obtain information regarding tumour vascularisation, metabolism, and pathophysiology, and allows early assessment of therapeutic effects of cancer drugs. one approach is dynamic contrast-enhanced (dce) mri, which measures tumour vascular characteristics after administration of a contrast medium. mri enhanced with small-molecular-weight contrast agents is extensively used in the clinic to differentiate benign from malignant lesions, as well as to monitor tumour microvascular characteristics during treatment. diffusion-weighted mri (dwi) is a more recent technique and it allows noninvasive characterisation of biologic tissues based on the random microscopic motion of water proton measurement. several studies have shown that dwi allows early detection of tumour response to chemotherapy. the use of water diffusion is a surrogate marker used to distinguish highly cellular regions of tumour from acellular and necrotic regions. whole body diffusion-weighted sequence (wb dwi) is a new promising technique feasible to evaluate multifocal disease. dwi has revealed great potential in the evaluation of patients with cancer or benign disease, as it supplies both quantitative and qualitative information of the whole body. this presentation will focus on the potential role of dwi in combination of dce mri in bone tumours as well as on the possibilities of wb dwi. in this integrated refresher course, the impact of basic and advanced imaging on the entire process, from diagnosis to treatment of bone tumours, will be addressed. diagnosis is based on understanding the imaging features from a histopathologic chemotherapeutic agents is an attractive alternate strategy to increase tumour necrosis. the efficacy of a combination therapy, including rfa plus the intraarterial administration of drug-eluting beads has been recently demonstrated, while the use of intravenously administered, thermally sensitive drug carriers is currently being explored. despite the advances in local treatment, the long-term outcome of treated patients remains unsatisfactory because new tumours emerge in about % of the cases within years. clinical trials evaluating the usefulness of adjuvant molecular targeted therapies with anti-angiogenic and anti-proliferative activity in preventing early recurrence after successful ablation are ongoing. in this integrated refresher course, the impact of basic and advanced imaging on the entire process from diagnosis to treatment of bone tumours will be addressed. diagnosis is based on understanding the imaging features from a histopathologic perspective. staging, biopsy and image-guided treatment require an integration of imaging findings with basic knowledge of surgical-oncological principles, as well as skills. can technically driven development of advanced mr techniques change how we diagnose, monitor therapy and determine prognosis. techniques and procedures that improve patient outcome in a cost-effective way will be identified based on presentations and a panel discussion. a. diagnosis: from radiographs to mri k. wörtler; munich/de (woertler@roe.med.tum.de)the diagnosis of a bone tumour is based on clinical findings, the age of the patient, the location of the lesion, its radiologic appearance, and, if imaging does not allow for a specific diagnosis, its histopathologic features. radiography remains the initial imaging modality for evaluation of the localisation of the lesion with respect to the longitudinal and axial planes of the involved bone, for the depiction of matrix mineralisations, and for estimation of biologic activity by analysing the patterns of bone destruction and periosteal response. ct can add "radiographic" information particularly in regions of complex skeletal anatomy such as the spine, pelvis and shoulder girdle. mr imaging has classically been used to determine the local extent of a bone tumour (local staging). in addition to radiography and/or ct, it can at times also be valuable in establishing the differential diagnosis, especially in cystic bone lesions and cartilaginous tumours. whole-body applications have recently gained importance in demonstrating the presence and extent of bone (marrow) involvement in benign and malignant systemic/polyostotic tumourous diseases. this course reviews the basic principles of diagnosing bone tumours in a multimodality approach (with an emphasis on conventional radiography). the different steps of morphologic analysis as well as the advantages and disadvantages of the individual imaging techniques are illustrated on the basis of pathologically confirmed cases. s a b c d e f g h review: ( ) the biological rationale for using perfusion imaging in brain tumours, ( ) methods available for the imaging of microvascular structure and function in brain tumours. we will discuss the relevant advantages and disadvantages of t versus t weighted acquisition strategies. early diagnosis and treatment of acute stroke is crucial for a favourable prognosis. while non-contrast mri is much more sensitive to ischaemia in comparison with non-contrast ct, perfusion studies make both techniques comparable. ultrafast ct scanners cover most of the brain with perfusion imaging; the scanning is faster and quality imaging results depend less on patient co-operation than in mri. however, mri enables diffusion imaging adding more specific information to the diagnostic process. because of the short time window to eventual vascular intervention, in many institutions ct is the technique of choice. besides depiction of hyperacute stroke by means of diffusion weighted imaging, mri has the advantage of performing a contrast agent-free perfusion study using a promising new technique called arterial spin labelling (asl). thus, an mri perfusion study can be performed even in patients with impaired renal functions where iodine and gadolinium-based contrast agents may be dangerous. perfusion imaging is an emerging non-invasive tool that enables evaluation of brain function via assessment of various hemodynamic measurements such as cerebral blood volume, cerebral blood flow, and mean transit time. these techniques have become important clinical tools in the diagnosis and treatment of patients with cns disorders via evaluation of brain tissue during cerebrovascular diseases, noninvasive histopathologic assessment of tumours, evaluation of neurodegenerative conditions and assessment of the effects of drugs. perfusion imaging is helpful to analyse and assist in judging the biological behaviour (especially haemodynamic features) of central nervous system diseases. qualitative and quantitative information can be obtained to evaluate pathoanatomical structures and pathophysiological changes of the lesions. cerebral blood flow (cbf), cerebral blood volume (cbv), mean transient time (mtt), permeability surface (ps), regional blood volume, microvascular permeability measurements and more information can be obtained for the diagnosis and differential diagnosis of the diseases. advantages and disadvantages of the ct perfusion imaging (ctp) and magnetic resonance perfusion imaging (mrp) in the different diseases will be evaluated in detail. hints and tips for the better applications and postprocessing will also be discussed. techniques for ct and mr, post-processing, radiation r.a. meuli; lausanne/ch (reto.meuli@chuv.ch)brain perfusion can be assessed by ct and mr. for ct, two major techniques are used. first, xenon ct is an equilibrium technique based on a freely diffusible tracer. first pass of iodinated contrast injected intravenously is a second method, more widely available. both methods are proven to be robust and quantitative, thanks to the linear relationship between contrast concentration and x-ray attenuation. for the ct methods, concern regarding x-ray doses delivered to the patients need to be addressed. mr is also able to assess brain perfusion using the first pass of gadolinium based contrast agent injected intravenously. this method has to be considered as a semi-quantitative because of the non linear relationship between contrast concentration and mr signal changes. arterial spin labeling is another mr method assessing brain perfusion without injection of contrast. in such case, the blood flow in the carotids is magnetically labelled by an external radiofrequency pulse and observed during its first pass through the brain. each of this various ct and mr techniques have advantages and limits that will be illustrated and summarised. learning objectives: . to understand and compare the different techniques for brain perfusion imaging. . to learn about the methods of acquisition and post-processing of brain perfusion by first pass of contrast agent for ct and mr. . to learn about non contrast mr methods (arterial spin labelling). brain tumours a. jackson; manchester/uk (alan.jackson@manchester.ac.uk) this presentation will discuss the current 'state of the art' in the use of perfusion imaging techniques in neuro-oncology. the term "perfusion imaging" is commonly used but is in fact a misnomer since perfusion and blood flow are not the only imaging biomarkers of microvascular structure and function in common use. indeed, in oncological applications measurements of proportional blood volume, endothelial capillary permeability or vessel size can be of equal or greater importance. we will reproduction is by spore formation which is prolific and therefore human respiratory tract exposure is almost constant. the spectrum of aspergillus infection includes aspergilloma (mycetoma), chronic pulmonary aspergillosis, chronic necrotising pulmonary aspergillosis (subacute invasive, chronic airway invasive), invasive pulmonary aspergillosis (angioinvasive, non-angioinvasive including acute tracheobronchitis, exudative bronchiolitis and bronchopneumonia), and allergic disease (allergic bronchopulmonary aspergillosis (abpa) and bronchocentric granulomatosis). immunocompromised individuals are particularly susceptible to invasive aspergillosis. the risk factors for invasive aspergillosis include: profound neutropenia, haematopoietic stem cell transplant recipients, solid organ transplantation, potent immunosupressive therapy, prolonged corticosteroid use and aids. invasive aspergillosis can be further subdivided into angioinvasive and non-angioinvasive forms. the imaging features of angioinvasive aspergillosis are characterised on ct by nodules with a 'halo' of surrounding ground glass opacity due to alveolar haemorrhage. in the context of neutrophil recovery, nodules may demonstrate cavitation. airway invasive aspergillosis may manifest as areas of consolidation (bronchopneumonia), nodular 'tree-in-bud' densities on ct (exudative bronchiolitis), or an acute tracheobronchitis with large airway thickening. falling rates are stabilising in europe. tuberculosis is developing new faces due to changes in host cellular immunity, such as hiv infection, immunosuppressive therapy, malignancy and due to multi-drug resistance. chest radiography plays a major role in screening, diagnosis, and response to treatment of patients with tb; however, radiographs may be normal or show only mild or nonspecific findings in active disease. ct and high-resolution ct (hrct) are more sensitive than chest radiography in the detection and characterisation of parenchymal disease, small foci of cavitation, mediastinal lymphadenopathy, and pleural complications. based on these findings, hrct is useful in determining disease activity and plays also an important role in the management of tb. radiological manifestations of primary tuberculosis are lymph node enlargement, airspace consolidation and pleural effusion. the most common findings of post-primary tuberculosis are centrilobular nodules, branching linear and nodular opacities, patchy or lobular areas of consolidation, and cavitation. miliary tuberculosis results from acute haematogenous dissemination of tb bacilli in lungs and other organs and ct-findings consist of innumerable small nodules randomly distributed throughout both lungs. airway tuberculosis is characterised by circumferential wall thickening and luminal narrowing, with involvement of a long segment of the bronchi.sensitive diagnostic tool. radiological semiotics are always useful and often very specific in addressing the diagnosis: some fundamental concepts include the peculiar pattern of vasogenic oedema, which, in opposition to what happens in the brain, tends to involve the central grey more than the peripheral white matter. distribution pattern of the lesion can also often address to aetiological diagnosis. in fact, lesions selectively involving posterior or lateral columns, asymmetrically, and sparing the central grey matter, are more typical expression of demyelinatinginflammatory diseases (multiple sclerosis, adem, devic's disease, les, behcet's disease), while selective and symmetrical involvement of both posterior columns, extended for more than myelomers, and possibly associated with involvement of lateral columns, is typical expression of combined sclerosis (b vitamin deficit). ischaemic lesions are also usually symmetrical, but they involve both grey and white matter, extending to the anterior two-third of the cord, or, sometimes, remain limited to the central grey matter. on the other hand, selective involvement of the anterior horns is typical of poliomyelitis. early stage head and neck cancer can be cured by surgery or radiotherapy. the choice depends on the functional and cosmetic result to be expected, tumour histology, patient's condition and preference, and institutional policy. in advanced lesions, nowadays concomitant chemoradiotherapy is offered, with surgery reserved for salvage. a relatively high locoregional control rate can be obtained, at the expense of acute and late toxic side effects, and a higher incidence of treatment complications. on post-therapeutic imaging studies, treatment-induced tissue changes are often visible; these changes should not be misinterpreted as evidence of persistent or recurrent tumour, or treatment complication. after radiotherapy, the visible changes depend on the radiation dose and rate, the irradiated tissue volume, and the time elapsed since the end of treatment. basically, thickening of the laryngeal and pharyngeal walls, increased attenuation of fat planes, postirradiation sialadenitis, lymphatic tissue atrophy, and retropharyngeal oedema will be seen. these irradiation-induced tissue changes usually appear symmetrical. the acute effects of radiotherapy occur during or immediately after treatment, and usually settle spontaneously. complications of radiotherapy are usually seen months to years after the end of treatment. there is no clear consensus regarding optimal time points for surveillance, but clinical assessments are more frequent in year and are performed over at least - years, during which time most locoregional failures and second primary tumours are detected. ideally for imaging surveillance at least one post-treatment baseline head and neck scan (mri/ct) should be performed at - months, and often closer surveillance is desirable. candidates for salvage surgery after (chemo) radiotherapy undergo a post-treatment scan at - weeks, followed by regular scans ( - months in year ; - months thereafter, the exact time period being tailored to the patient the most recent advances of radiotherapy techniques are characterised by the increased precision with which the radiation energy is released to the target, the reduced collateral damage to adjacent non-neoplastic tissues, and the synergic viral agents are part of the spectrum of organisms which cause community acquired pneumonias. furthermore, they are thought to function as a trigger for bacterial infections in the hospital or health care setting. in addition, viruses play a significant role as causative agents for infections in the immunocompromized host. within the last years, outbreaks of viral infections have challenged regional, national and even global health care systems, have effected thousands of individuals and have resulted in significant morbidity and mortality. most of the involved viral agents represented emerging organisms with an unpredictable impact on individual and society health. the radiologic community has learned several lessons from the documented outbreaks, and radiologists around the world have contributed to the early diagnosis of the disease, the monitoring of its course, and the documentation of complications as well as of response to therapy. thus, imaging plays an important role in the diagnosis and management of these patients. in this course, epidemiologic aspects, patho-physiology and clinical features of emerging viral infections will be presented. in addition, their radiologic features and the role of radiology in diagnosis and management will be discussed. attendees will learn how to understand, recognize, report and follow patients with emerging viral infections. major changes in the treatment of head and neck neoplasms encompass the advances of endoscopic-based surgical techniques, mainly for nasosinusal and laryngeal tumours, and the application of sophisticated radiation therapy techniques, combined with chemotherapy. as most tumours arise from the mucosa of the upper aero-digestive tract, clinical surveillance is necessary to detect superficial recurrences, while morphological and 'functional' imaging techniques are indispensable to detect subclinical extra-mucosal and nodal recurrences. how can imaging techniques discriminate recurrence, inflammation, necrosis or scar? key points include the knowledge of the normal appearance of tissues (morphology and signals) on ct, mri, and pet-ct after surgery and chemo-radiotherapy. specifically, when non-surgical treatment has been used, that means to become familiar with the expected changes both of tumour and adjacent tissues. morphology-based imaging techniques are often inadequate to discriminate small recurrences from vascularised scar tissue (enhancing). ct or mri do require to be integrated by information provided by functional-based imaging techniques, fdg-pet-ct being the most established. recently, a great interest among radiologists is focused on the application of dce-ct or dce-mri and dwi-mri in the follow-up of head and neck neoplasms. in fact, several studies have credited these techniques for providing functional information about tissues (perfusion, water exchange) that help to discriminate scar from recurrences. obviously, the horizon pursued is to combine morphology and functional data in a single examination. though clearly promising, these new techniques share significant limitations, like the reproducibility of ct and mr-based functional results, their introduction and feasibility in the day practice. today, ct angiography (cta) is considered as a safe, non-invasive and wellestablished procedure for vascular imaging. modern multi-slice ct technology allows for coverage of larger vascular territories -even the whole body -in just several seconds. further technical improvements such as wide detectors of up to cm width or moving table techniques are making new applications possible, such as perfusion imaging, or time-resolved ct angiography. especially with the moving table technique (the so-called "shuttle-mode"), vascular territories of up to cm can be covered in a dynamic fashion, which can be helpful in the diagnosis of aortic dissections or peripheral vascular occlusive disease. on the other side, radiation exposure has to be maintained within a reasonable range applying these repeated acquisition modes. another interesting field opening new options in cta is dual energy ct (dect). a number of technical setups may allow for spectral ct imaging, such as systems with two tubes (dual source ct), ct systems with switching kv modes or with special detectors. in vascular applications, dect is especially helpful for automated bone removal, plaque removal, and potentially for "perfusion" imaging (iodine mapping). in this course, the basics of modern ct angiography will be highlighted, with a special focus on new applications such as time-resolved cta and dual energy cta. angio- d with digital flat-panel detector has recently been adapted for use with c-arm systems and provides a higher detector quantum efficiency (dqe) than conventional detectors based on ii camera. this configuration represents the next generation of imaging technology available in the interventional radiology suite and is predicted to be the platform for many of the three-dimensional ( d) roadmapping and navigational tools that will emerge in parallel with its integration. it provides projection radiography, fluoroscopy, digital subtraction angiography, and volumetric computed tomography (ct) capabilities with the ability for immediate multiplanar post-treatment assessment in a single patient setup, within the interventional suite. such capabilities allow the interventionalist to perform intraprocedural volumetric imaging without the need for patient transportation. the clinical benefits of d angiography with these new systems have been assessed in the fields of cardiology and interventional radiology. these key features alone may translate to a reduction in the use of iodinated contrast media, a decrease in the radiation dose to the patient and operator, and an increase in the safety and performance of interventional procedures. proper use of this new technology requires an understanding of both its capabilities and limitations. this article provides an overview of the potential of this new technology. learning objectives: . to learn the basic principles of flat panel ct. . to review imaging protocols, results and radiation exposure aspects. . to become familiar with the most common applications.effect of chemo-radiotherapy. as the treatment planning becomes progressively 'tailored', strong predictive factors for the individual tumour arising in a specific patient have to be identified. these factors would ideally provide a quantitative assessment of the risks of both relapsing (in the primary, nodal or distant sites) and developing treatment-related (early or late) complications. predictors are related to tumour's characteristics (biology, metabolism, site, volume and spread) and to patient's overall clinical conditions. imaging-based predictive factors have been founded upon morphological findings ( d, volume) until the development of new techniques, which analyse 'functional' parameters like fdg-pet-ct, the most established, and perfusion-ct or dwi-mri. evidence of level a has been provided on the impact of negative predictive value of fdg-pet-ct in ruling out residual disease, whilst there is no clear data regarding the role of pre-treatment intensity of glucose metabolism (suv) in predicting the outcome after radiotherapy. this limitation can be addressed to the enrolment of tumours arising in various sites in the head and neck. a major disadvantage common not only in pet studies but also in most dce and dwi-mri studies. perfusion-ct and dwi-mr are promising techniques, as they provide information about neo-angiogenesis and water-flow in submicroscopic tissue compartments. however, these techniques still require randomised trials and confirmation studies about the reproducibility of their interesting results. in the follow-up after minimal invasive surgical techniques or chemo-radiation, a major limitation of standard morphological imaging is the differentiation of the highly vascularised scar tissue (enhancing, with mass effect) from persistent or recurrent neoplasm. is it time for integrating standard imaging with the functional information provided by dwi and/or ct or mr perfusion techniques? which evidence level are we at presently? is it now feasible in daily practice? three-tesla mri scanners offer an increased signal and contrast for mr-angiography (mra) compared to . -tesla machines. mra can be performed within a shorter time enabling the acquisition of temporally resolved three-dimensional datasets with high spatial resolution. due to high signal and contrast the dose of gadolinium may be reduced. furthermore, novel imaging protocols for mra at . -tesla with intravasal contrast agents and prolonged enhancement during high-spatial-resolution steady-state enable new possibilities for angiography of the upper and lower extremities including veins and vessels below the knee, spinal arteries, vascular malformations, and double-gated angiography of coronary arteries and bypass vessels to compensate for the complex cardiac motion pattern. a . -tesla mri system equipped with a matrix coil system allows for whole body mra with continuous table movement, which is an applicable technique for imaging peripheral vessels without the need for planning different steps and field of view positioning, thereby considerably reducing the examination time. phase contrast magnetic resonance angiography may develop into an important, noninvasive method for obtaining quantitative information on blood flow. in addition, non-enhanced three-dimensional mr angiography using turbo spin echo (tse) imaging with non-selective refocusing pulses may be a promising imaging technique for vascular imaging in patients with renal insufficiency. the advent of minimally invasive surgery has made even more important the place of preoperative imaging assessment of patients selected for this type of surgery. in fact, the loss of tactile feed-back and the bi-dimensional intraoperative vision have limited the capability of surgeons to assess extent and anatomic relationship of a given disease, particularly cancer. preoperative planning can be further enhanced by the use of d models of the target anatomy, derived from ct scan dataset. in addition, dedicated technology can be implemented to introduce mixed reality environments in the operative room. using d helmets with built-in microcameras, the surgeons' view of the operative field can be fused with the preoperative d anatomy of the patient. localiser should be used, either infrared based or electromagnetic. the last step would be intraoperative navigation. this offers special problems to be addressed, due to organ shifting and soft tissue in the setting of abdominal surgery. the appropriate use of information and communication technology (ict) and associated systems is considered by many experts as a significant contribution to improve workflow and quality of care in clinical settings. a conceptual design and prototypical implementation of such an infrastructure, i.e. a therapy imaging and model management system (timms) will be introduced as a solution to a patientspecific medicine. a timms is an information technology concept and framework for the collection, organisation, and utilisation of medical information from sources such as the electronic medical record, pacs, etc. timms was originally designed as a surgical assist system, but has many general medical uses as well, including all forms of model-guided medicine and may therefore be generalised to a medical information and model management system. the architectural framework and a number of individual ict components of a timms have been realised. these include standardised interfaces for communication of patient-specific and workflow models, thereby creating a unified environment for the input and output of data, including the representation and display of information and images, as well as the electromechanical control of interventional and navigational devices. in conclusion, the patient-specific model (psm) is the central construct for a patient within a personalised medicine environment in order to provide a clinician with a real-time representation of critical information about the patient. the required information concerning the patient for model-guided therapy is extracted by timms agents and assembled within the framework of an active psm and workflow management system. the introduction of picture archiving and communication systems (pacs), through a much more effective image sharing, has dramatically changed the role of radiology both within the hospital and on a geographic perspective. historically, the latter has become apparent first with the early implementation of teleradiology applications. physicians and the general public have understood that digital images can be read, processed, and stored independently on the site of production. therefore, teleconsultation and telereporting activities have been carried out among medical users, and generic users have learnt to include radiological images in their own on-line personal health records. only later the full potentialities of multidisciplinary image sharing within the hospital have been discovered, and now it is increasingly common to see advanced integration between radiologists and surgeons for planning and guiding surgical interventions. during this session, the lecturers -exceptionally expert in their respective fields -will give insights into image sharing: from the geographical applications (teleradiology) to the hospital-based applications, with specific reference to the support to surgeons (intraoperative guidance and model-guided surgery). medical imaging is part of a changing medical environment, a changing patient environment and consequently a new medical world. in the recent decennium one of the most important changes in radiology is the conversion from analogue to digital. in no time medical images have become interchangeable through the digital highway and could be post-processed in a different location. teleradiology has become a reality since then. we have seen the maturation of commercial international teleradiology companies offering a wide portfolio of services. another aspect is the availability of image data for all medical specialties beyond radiology and beyond the regular medical disciplines. an increasing number of surgical or oncological specialties and even pharmaceutical companies increasingly use image data to prepare a strategy for operative procedures, to choose the right therapy, to decide which prosthesis to the best to use, for follow-up or for post-processing purposes. they are supported by many new techniques and software. an increasing number of medical computer applications such as complex navigation and visualisation tools based upon digital images is already in clinical use or under development. another trend is the increasing interest in e-health and telemedicine in europe, also among european policy makers. now we see mobile health that brings care directly into the patient environment. the purpose of this presentation is to give a comprehensive overview of and insight into these new developments and to create awareness among radiologists of the increasing importance of integration of medical imaging in a multidisciplinary environment. key: cord- -due tloa authors: nan title: ecr , part a date: - - journal: insights imaging doi: . /s - - - sha: doc_id: cord_uid: due tloa nan percutaneous needle biopsy has been a mainstay of oncologic diagnosis for almost three decades, since the advent of ultrasound and ct. the basic principles of fine-needle aspiration and core needle biopsy can be applied to almost any site in the body, with subtle differences in technique depending on the organ being investigated and the imaging modality utilised. while excisional biopsy is still appropriate in certain cases, percutaneous needle biopsy has become the standard of care in the diagnosis of most tumors throughout the body and is also used to diagnose noncancerous conditions, such as infection. percutaneous biopsy is also beneficial in the staging of patients with cancer, particularly when another treatment method may be more appropriate than surgical resection. the advantages of percutaneous biopsy over surgical excisional biopsy include time and cost savings and reduction in morbidity. the aim of this course is to discuss the practical aspects of biopsy, needle selection, and guidance techniques and to show how to approach difficult lesions and avoid complications. imaging after treatment of breast cancer is for confirmation of lesion removal, identification of postprocedural fluid collections, detection of residual or recurrent cancer and screening for metachronous cancers. posttherapy changes -which include fluid collections, edema, skin thickening, architectural distortion, scarring and calcifications -are mainly due to surgery, axillary dissection and radiotherapy. the greatest treatment-related changes occur - months after therapy, and mammographic stability is achieved after two to three years. for mammography, pre-and all posttherapeutic images have to be compared. ultrasound is the method of choice for evaluation of fluid collections. mri is for problem solving (i.e. differentiation between scar and relapse) and should not be performed prior to months after therapy to avoid false-positive diagnoses. dystrophic calcifications may develop in areas of fat necrosis mimicking malignancy. fat necrosis predominantly occurs at the treated site; however, it can develop anywhere in the ipsilateral breast. its appearance may be indistinguishable from cancer at all imaging modalities. to differentiate between fat necrosis and other common post-treatment changes from relapse, it is important to know the timeline when these changes occur and schedule follow up imaging accordingly. mammography serves as the basis for postoperative surveillance. ultrasound is helpful in the early postoperative phase, whereas mri is the method of choice, especially for differentiation of scar and relapse in the later postoperative phases. breast radiologists need to be familiar with post-treatment imaging findings in patients with breast cancer, but often patients are also imaged after a diagnosis of benign entities which are treated surgically (fibroadenomas, radial scars, papillary lesions) or after a percutaneous diagnosis of a high-risk lesion which has undergone a surgical biopsy to avoid underestimation (atypical ductal hyperplasia, lobular neoplasia or flat epithelial atypia). these procedures will leave an imprint on the breast which can be a cause of concern due to the surgical scar. furthermore, imaging findings after plastic surgery for mastopexy, reduction mastoplasties, implants or auxiliary techniques (lipofilling, hyaluronic acid) are becoming frequent in our daily practice and have their peculiarities that can overshadow breast cancers. interventional percutaneous procedures can also be a cause of tissue distortion. there are advanced systems for biopsy (bles) and for percutaneous removal of benign lesions (fibroadenomas, papillomas), which use large-gauge needles and have to be accounted for due to their trace in the breast tissue. endoscopy is currently considered the reference standard for the evaluation of colonic disease activity in patients with inflammatory bowel disease (ibd). however, it only allows evaluation of the mucosal surface and is not always complete. it cannot, therefore, help to estimate the depth of involvement of transmural inflammation and extraluminal complications, both characteristics of ibd. an evolving role for cross-sectional imaging in the evaluation of patients with ibd is increasingly recognised, especially in the setting of crohn's disease (cd) since the cross-sectional imaging has been demonstrated to have a high diagnostic accuracy not only for assessing the presence and extension of luminal disease, but also for evaluating the cd-related acute or chronic complications. available evidence suggests that ultrasound, computed tomography and magnetic resonance have similarly high diagnostic accuracy in the detection of disease activity, location, severity and complications: in particular, the penetrating and stricturing lesions which are characteristic of cd. thus, the choice of the technique for assessing cd may be influenced by local availability or expertise. in the case of ulcerative colitis, cross-sectional imaging, although less evaluated, may also be helpful in certain circumstances. there is evidence indicating that cross-sectional imaging is an alternative problem-solving tool to endoscopy whenever tissue sampling is not required and can provide valuable guidance for performing medical and surgical treatment with maximised efficacy and safety. overall, findings from crosssectional imaging accurately reflect disease activity and provide reliable information for decision-making and patient care optimisation. learning objectives: . to learn about optimised examination protocols for ulcerative colitis and colonic crohn's disease in the acute, subacute and chronic disease setting. . to become familiar with the criteria for the assessment of disease activity through ct, mri and ultrasound. . to learn about an integrated approach to the use of cross-sectional imaging in colonic inflammatory bowel disease. liver transplantation is the accepted treatment of patients with irreversible liver cell failure and some metabolic disorders and in a selected group of patients with hepatocellular carcinomas. over the last decade, major transplant centres have reported improving survival rates, though during this period they have developed more complex surgical techniques, including split-liver, auxiliary and live-related transplantation, and have treated more marginal higher risk patients. this successful outcome has been dependent on appropriate recipient selection, robust surgical technique, improvements in immunosuppression and intensive care management and the prompt recognition and treatment of complications. diagnostic and interventional radiology have been core specialties in achieving the goals of improved graft and patient survival. improvement in surgical techniques has decreased the more common vascular and biliary complications, but the newer techniques present differing diagnostic and interventional challenges, particularly in paediatric recipients. developments in mr and mdct allow many of these vascular, biliary and infective complications to be diagnosed non-invasively. vascular techniques of angioplasty and stent placement may reverse the sequel of graft ischaemia or portal hypertension. mrc allows the diagnosis of biliary strictures that may be treated by dilatation or stent placement. imaging is also important in the diagnosis of recurrent disease and the acquired diseases of prolonged immunosuppression including atypical infections and the post-transplant lymphoproliferative disorders (ptld). this interactive session will present these appearances by case example and provide guidance of the appropriate diagnostic and treatment paradigm. learning objectives: . to understand the common imaging findings after liver transplantation. . to recognise significant complications following liver transplantation. a- : b. imaging of treated liver tumours i. bargellini; pisa/it (irenebargellini@hotmail.com) imaging findings after systemic and loco-regional treatments vary greatly depending on baseline features of the treated tumour and treatment modality. conventional uni-dimensional and bi-dimensional criteria (such as recist . and who criteria) have been extensively validated in metastatic lesions treated with conventional chemotherapy. however, their prognostic value is limited in patients treated with new molecular targeted therapies and after locoregional treatments. in the setting of hepatocellular carcinoma (hcc), specific response criteria (such as easl and mrecist) have been proposed that take into account variation in the size of the viable tumour. these criteria have been extensively validated, although their interpretation could be troublesome after some specific treatments, such as molecular targeted agents and y radioembolisation. on the other hand, there is no consensus regarding tumour response criteria for metastatic lesions after loco-regional treatments. the role of morphological criteria and several imaging biomarkers (such as those provided by diffusion and perfusion imaging, fdg activity, dual source ct) is under investigation, being able to provide additional information on tumour activity and biology. while new drugs with different mechanisms of action and new treatments are becoming available, the work of radiologists is changing and there is increasing evidence that tailored radiological response criteria are required for these new targeted and tailored treatments. learning objectives: . to understand the common imaging findings after chemotherapy for liver tumours. . to recognise common imaging findings after radiofrequency ablation of liver tumours. . to be aware of the common imaging findings following transarterial treatment of liver tumours. vessel size is practical, since it is related to the pathological changes as well as to the clinical and radiological presentation. the two main large vessel vasculitides are giant cell arteritis and takayasu arteritis. behcet disease may combine large and small vessel vasculitis. imaging plays an important role in primary vasculitis. chest radiographs are not especially useful in large vessel vasculitis. contrast ct and mri further detect and especially help in the characterisation of large vessel vasculitis. vessel wall changes are well detected with both techniques. contrast enhancement, distribution of vessel involvement and morphological vascular changes should be considered. today, pet/ct is the recommended imaging technique in the assessment of vessel wall inflammatory changes and in the evaluation of treatment response. although the clinical scenario differs usually between takayasu and giant cell arteritis, the radiologist should combine the imaging findings with clinical and laboratory data to suspect a specific vasculitis. therefore, this presentation will concentrate on the basic signs and associated findings in large vessel vasculitis, pathologic correlation, imaging protocols and the differential diagnosis. the term vasculitis refers to a variety of clinico-pathological entities. the most widely used chapel-hill classification divides the vasculitis syndromes into three groups based on the size of vessels primarily involved. small vessel vasculitis such as anca-associated granulomatous vasculitis (wegener's disease), churg-strauss granulomatosis and microscopic polyangitis are most often associated with pulmonary abnormalities. the spectrum of hrct findings is quite variable and differs by entity. the hrct findings will be discussed together with clinical and laboratory findings to be integrated into a multidisciplinary diagnostic approach. the typical findings in wegener's granulomatosis include solitary or multiple, often cavitary nodules or masses, or focal or diffuse consolidations, churg strauss is dominated by interlobular thickening or transient multifocal and nonsegmental consolidations frequently in subpleural distribution. all types of pulmonary vasculitis may present with focal or diffuse pulmonary haemorrhage that produces pulmonary ground glass or consolidations in various distributions. a number of collagen vascular diseases (e.g., lupus erythematosus) or other granulomatous diseases (e.g. sarcoidosis) may affect the small pulmonary vessels causing haemorrhage or pulmonary hypertension. per disease entity, the course will review typical and more rare hrct features and key features that allow for diagnosis and classification, discuss side-to-side overlapping of morphologic features important for differential diagnosis and illustrate the findings of other diseases that represent the most challenging differential diagnosis, e.g. oedema, infection or malignant diseases. learning objectives: . to learn when hrct is of value in investigating pulmonary vasculitis. . to appreciate the different appearances of pulmonary vasculitis on hrct. a- : d. inflammation and remodeling a.a. bankier; boston, ma/us (abankier@bidmc.harvard.edu) the presentation will lay out the pathological and pathophysiological basis for the complex processes of inflammation and remodelling. the implications of these processes for imaging will be discussed and illustrated by selected pathologies. finally, the presentation will indicate how the imaging reflections of these processes could be used in the future as imaging biomarkers for the diagnosis, follow-up, and outcome evaluation of disease. at (marcus.hacker@meduniwien.ac.at) appropriate diagnosis and therapy of coronary artery disease (cad) frequently require information about both the morphological and functional status of the coronary artery tree. thus, combined imaging consisting of invasive coronary angiography (ica) plus spect myocardial perfusion imaging (mpi) is practiced in clinical routine diagnostic of patients with stable angina since many years and can therefore be accepted as the reference standard in the diagnosis of hemodynamically relevant coronary artery stenoses. both morphological and functional information are mandatory for the decision of performing an interventional therapy or initiating/maintaining medical treatment in numerous symptomatic patients. the hemodynamically relevance of coronary artery lesions is a major condition to decide whether an interventional therapy should be performed or not. a non-invasive concept providing both information could provide accurate allocation of perfusion defects to their determining coronary lesion and specific morphological and functional classification of patients with coronary artery disease. in symptomatic patients, a normal stress mpi confers a very low short-term risk for cardiac death and/or acute myocardial infarction. however, a normal mpi does not exclude the presence of underlying coronary atherosclerosis, which may be extensive although not yet flow-limiting. in this regard, ct will unmask a sizeable subgroup of patients with coronary atherosclerosis who should receive more intensive antiatherosclerotic intervention than would have been indicated by mpi results alone. knowledge regarding the presence and extent of subclinical coronary atherosclerosis in patients who do not have ischemia by mpi can be of importance in patient management. learning objectives: . to appreciate the scope of information a spect/ct cardiac study can deliver. . to become familiar with protocols of spect/ct studies. . to learn a structured approach to performing and reporting a spect/ct study. a- : c. mr/pet: do we really need it? h.h. quick; erlangen/ de (harald.quick@imp.uni-erlangen.de) following pet/ct and spect/ct, mr/pet hybrid imaging is the most recent addition to the palette of hybrid imaging modalities. mr/pet synergistically combines the excellent soft tissue contrast and detailed image resolution of mr with metabolic information provided by pet. integrated mr/pet systems furthermore offer the ability to acquire hybrid imaging data simultaneously. this can be applied to mr-based motion correction of pet data. these features open up several cardiac applications, e.g. evaluation of cardiac function and viability, diagnosis of cardiac inflammatory diseases and tumorous diseases. to fully assess the diagnostic potential of mr/pet, however, several technical challenges have to be considered: attenuation correction (ac) of the patient tissues in mr/pet has to be based on mr-images and is currently hampered by a limited number of tissue classes and undercorrection of bone tissue. cardiac radiofrequency coils and ecg gating equipment are currently not considered in ac. consequently, quantification of pet data therefore might be biased. the clinical workflow is rather complex and needs to be tailored to cardiac examinations. few research groups currently explore this new hybrid imaging modality in selected cardiac applications. cardiac mr/pet: do we really need it? considering the sparse clinical experience that is available today, it is quite early to answer this question yet. however, once the remaining technical hurdles are overcome and the diagnostic potential can be fully exploited clinically, the answer is most likely positive. the majority of malignant bone tumours can be detected on plain radiography. the age of the patient, location of the tumour in a bone and history of a preexisting bone abnormality should be included in determining the likely diagnosis. careful analysis of the pattern of bone destruction, periosteal reaction and matrix mineralisation allow for characterisation of most cases of osteosarcoma, ewing's sarcoma, chondrosarcoma and adamantinoma. mri is the best imaging technique for staging by displaying . the extent of bone marrow involvement, including epiphyseal infiltration and skip lesions, . the presence and extent of extraosseous soft tissue mass, . involvement of the neurovascular bundle, muscle compartments and adjacent joint. this allows to find the best biopsy approach and establish the feasibility of limb salvage as opposed to amputation. longitudinal non-contrast t sequences are the most accurate for determining intraosseous extent. axial fat-suppressed pd or t sequences optimally demonstrate soft tissue extension, and dynamic contrastenhanced mri is useful for differentiation of extraosseous tumour from edema and for assessment of tumour response to chemotherapy. chest ct is the most sensitive modality for detection of pulmonary metastases, and technetium skeletal scintigraphy is still frequently used for detection of osseous metastases. the most valuable, readily available and easy-to-use techniques to assess response to radiation therapy and chemotherapy are dynamic contrast-enhanced mr imaging, diffusion mri and colour-doppler ultrasound. to evaluate local control of disease and for detection of local recurrence, mri is usually the best imaging technique. plain radiography may detect complications of prosthesis. learning objectives: . to consolidate knowledge on malignant primary bone tumors on plain radiography, ct and mri. . to understand the principles of tumour staging and monitoring chemotherapy. . to become familiar with imaging findings following chemotherapy and surgery. oncologic approach to malignant primary bone tumours c. dhooge; ghent/be (catharina.dhooge@ugent.be) the most common bone sarcomas are osteosarcoma (os) and ewing sarcoma. os occurs primarily in long bones, ewing sarcoma occurs also in the pelvis, spine or chest wall. localised disease confers a % cure rate, and initially metastatic disease %. a multidisciplinary approach which includes neo-adjuvant systemic chemotherapy and local control measures for primary and metastatic sites followed by adjuvant chemotherapy has become the standard of care. complete surgical excision is mandatory in os; in ewing, radiation can also be used. standard chemotherapy for os is based on a combination of cisplatin, doxorubicin and high-dose methotrexate. ifosfamide and etoposide will be further considered (euramos). systemic therapy for ewing includes vincristine, doxoribicin, cyclofosfamide, ifosfamide and etoposide. high-dose chemotherapy with autologous stem cell reinfusion is evaluated in intermediate prognosis and metastatic disease (euro-ewing). among the different prognostic factors, response to neo-adjuvant chemotherapy by measuring chemotherapy-induced necrosis is a powerful indicator of outcome in bone sarcomas. patients who achieve a good histological response to pre-operative chemotherapy, defined as < % viable tumour at the time of tumour resection, have a better survival than those who show poor response (>= % viable tumour). five-year survival for good responders is o- % compared to - % for poor responders. however, the outcome for malignant bone tumours has improved little in the last years. large international studies exploring new drugs such as biologic agents (interferon) or mechanisms conferring drug resistance (topoisomerase inhibitors) in randomised controlled trials will hopefully lead to therapeutic innovation. learning objectives: . to become familiar with the principles of chemotherapy in malignant primary bone tumours. . to understand what the oncologist expects from the radiologist. . to recognise the value and limits of chemotherapy in malignant primary bone tumours. thursday a- : surgical approach of malignant primary bone tumours g.m.l. sys; ghent/be (gwen.sys@ugent.be) in primary malignant bone tumours, three surgical procedures are necessary: biopsy, resection and reconstruction. whether a biopsy is performed in an open or a percutaneous way is a matter of preference, but in each case it should provide sufficient and representative material for pathological investigation without compromising the following treatment. the area of interest and the trajectory should be determined preoperatively in a multidisciplinary meeting. as the biopsy tract has to be removed during the resection surgery, it should be close to the planned approach for the subsequent resection. if a biopsy is performed improperly, the diagnosis may be wrong or the following resection may be impaired because of extensive contamination of compartments, resulting in a severe functional deficit. surgery planning is based on clear imaging and a multidisciplinary discussion of tumour extension, aiming for a wide resection of the tumour with clear margins. correct perioperative measurements are based on predefined fixed bony landmarks that should preferably be visible on the same image as the tumour. an amputation is performed if a surgical limb-salvage procedure is expected to result in a non-functional limb. nowadays, several reconstruction techniques for bones (bone grafts or prostheses), tendons (artificial or human ligaments) and skin (skin flaps or grafts) are available. invasion of the soft tissues such as the neurovascular structures, muscles and skin, will determine which reconstruction technique (s) are necessary to restore the patient's function. each reconstruction technique bears inherent complications requiring a regular follow-up. we outline the current opportunities and threats in diagnostic radiology: traditional diagnostic radiology has been rapidly replaced by clinical radiology and the role of the radiologist is changing from image interpreter to clinical manager of imaging data. to care for the patient`s medical problem and not only his images is important. this contains great opportunities for radiology to develop and for the radiologist to become a central player in patient management. however, this requires not only clinical knowledge and involvement, but also visibility and sometimes even / availability. the need for " only" image reporting is declining as clinical subspecialisation easily brings image interpretation into the domain of non-radiologists. to understand the importance of identity, visibility is very important. visibility can be achieved by being part of mdt s and also in many other ways. clinical radiology is an idea which, after all these years, has not been very well embedded in current radiology and radiology training. to understand the importance of certified training, maybe the most important action we have to undertake now is to capitalise on our radiological expertise. image interpretation in a clinical context can only be done or franchised (to non-radiologist) under conditions of certification and accreditation by radiology. we should never let the primate of education and certification slip to non-radiologists. radiology certification should be a quality standard, recognised by international and national medical bodies, such as medical chambers and specialist societies. the latter should have high priority. session objectives: . to learn about the current opportunities and threats in diagnostic radiology. . to understand the importance of identity. . to acknowledge the importance of certified training. where are the turf battles in diagnostic imaging? g.m. bongartz; basle/ch (georg.bongartz@usb.ch) turf battles in radiology are a foreseeable development for most imaging techniques which evolve push-button methods and readily interpretable imaging results. we as radiologists must learn to accept competition. turfs should rather be seen as challenge than as threat. predominantly, nonirradiating techniques like ultrasound and mri have become progressively easier to apply (us) or to understand (mri), where the final image in some standardised areas (eg joints) can readily be interpreted by medical specialists in this field. but also x-ray diagnostics in dental medicine or orthopedic imaging is largely applied outside the radiologic department. ct today seems still relatively excluded because of its complexity. but with increasing resolution, optimal d reconstruction and fast accessibility, it is only a question of time when the added value of the radiologist will be under question. radiology has changed. we must become experts with respect to patho-anatomy and radiological differential diagnosis. this requires profound education, both initial training and ongoing education. radiology must be advertised internally and externally. in radiological publications, outcome studies are still underrepresented. demonstration of our dedicated skills, fostering our special expertise and offering this as support to our medical colleagues will preserve radiology for the future. cooperation with partners seems the only way out of a turf battle -we need to search for alliances and integrate our partners to create a win-win situation. a- : beating threats in europe with radiological training a.k. dixon; cambridge/uk (akd @radiol.cam.ac.uk) by introducing radiology to medical students, it is hoped that they will begin to appreciate how difficult it is! likewise, when teaching residents, they must come to understand the basic anatomy and principles better than their clinical colleagues; this is very much the tenet of subspecialty training. they should also appreciate that patient care is optimal when there is close collaboration between clinicians and radiologists. passing of an examination (national or edir) offers some proof that a radiologist has attained a certain standard, but the principle of testing oneself formally or informally at regular intervals again provides a measure of continuing competence. such certification can be of value in the case of litigation. radiology is one of the fastest growing specialties and the techniques that we learn during training are quickly outdated; hence, the need for life-long learning and effective continuing professional development. learning objectives: . to understand how to teach radiology to undergraduate medical students. . to become familiar with the principles of self-assessment. . to appreciate the necessity for life-long learning. history of ultrasound in radiology: lessons learned l.e. derchi; genoa/ it (derchi@unige.it) the relationship between radiology and us has never been an easy love story, and still isn't. in the early s this new imaging field was not readily covered by radiologists and many other colleagues established us sections within their departments. then, important fields of us (cardiology, obstetrics, gynecology) became almost exclusive domain of non-radiologists. in the s, the increasing success of us initiated turf battles with other clinicians. nowadays, clinical specialists perform > % of us examinations wordwide. in europe, most in-hospital us examinations is still performed in radiology, but this is not the case in all countries. a strong practice in us is quite important since this is often the first approach to patients. if initial us referrals are kept, radiologists will continue to guide decisions in subsequent imaging workup. furthermore, us keeps close to patients; in europe the examination is usually done directly by radiologists or, if by sonographers, the radiologist usually checks the case with limited directed us imaging. this clearly shows our role as physicians. to maintain a key role in us radiologists need to: ) have the best specialists in us; attention must be given to us in residency programs. ) invest in us technology (as examples: ceus, elastography, d/ d). ) invest in us research. ) have high visibility in the us community, keeping close contact with all clinical colleagues. ) present higher visibility of us within radiology, with leaders supporting us within the radiological community and each radiologist promoting us in his/her environment. learning objectives: . to understand why ultrasound has moved out of the hands of radiology in some subspecialties. . to learn what this means for daily radiology practice and the quality of work. . to know about the threats and how we should deal with them. thursday a- : interdisciplinary cooperation without losing identity m.f. reiser; munich/de recently, major shifts in the paradigms of patient care took place: interdisciplinary counseling and including the patient in the decision making process for diagnostic and therapeutic measures. the new concept is that the patient no longer comes to the specialist, but the specialists come jointly to the patient. this is reinforced by the competition among health care providers, political decision makers and the public. in many hospitals this general trend has resulted in the establishment of various centers and boards such as the breast cancer centers, vascular centers and tumor boards for several cancer entities to name only few. at the university hospital of munich centers and boards have been implemented up to now. in almost all of them the participation of radiologists is required. this results in a major challenge in terms of personal resources. together with the regular clinical-radiological rounds the time necessary for these activities equals full-time radiologist posts. the participation of radiologists has many beneficial aspects: acknowledgement of radiology as an important clinical discipline and of the radiologist as a clinical consultant; participation in and influence on the creations of sops and (internal) guidelines; opportunity to advocate appropriate radiological methods for diagnosis and interventions; increase of knowledge in clinical medicine and new concepts of therapy; close personal links with our clinical partners. in order to prevent radiologists from losing their identity as radiologists it is mandatory that they remain firmly integrated in the radiology department and to strengthen the position of radiology as the central institution for providing cost-effective imaging and interventional services. moreover it must be taken care to offer attractive career options within the field of radiology. at (michael.fuchsjaeger@medunigraz.at) ultrasound (us) is the adjunct method of choice to mammography in breast imaging. over the past two decades, us technology has undergone profound advancements and refinements. us has, therefore, become an assessment tool with a defined field of indications as well as a unique set of diagnostic descriptors for breast lesion differentiation. the acrin study has demonstrated the special benefit of us in patients at risk with dense breast tissue. the bi-rads lexicon for ultrasound, in its second edition, expanded the role of breast us. further enhancement of image quality as well as the recent advent of automated breast us has even fueled scientific discussions on the potential role of us for breast cancer screening. automated breast us, which is based on computed generation of a d imaging data set obtained from many parallel d images, offers a different approach with a variety of benefits. images are obtained by the sonographer in standardised fashion, whole breast data sets can be reviewed at any time after the examination, reducing operator dependence, and image fusion with, i.e. mri is easily possible. the basic physical background, the significance as well as important aspects of practical use of handheld and automated breast us will be explained and illustrated by the respective imaging examples. emphasis will be laid on strengths and potential weaknesses of both us technologies with regard to breast imaging. the terms "complicated cyst" and "complex-cystic lesion" are based on breast ultrasound (us) terminology. the simple cyst is a fluid-filled, clearly defined, anechoic lesion without any suspicion of a solid intracystic mass. if a simple cyst is complicated by echogenic fluid, it is called complicated cyst. this echogenic fluid can be caused, e. g., by cell debris. thin echogenic septa are common in complicated cysts. vascularisation can never be found in these echogenic components. a complicated cyst has no solid component and no thickened wall or thickened septa. the expected probability of malignancy is %. the us criteria of a complex-cystic lesion following berg et al. categorise it into types: type , thick outer wall and thick internal septa (alone or in combination of both); type , one or more intracystic masses; type , mass of mixed cystic and solid components (at least % cystic); type , predominantly solid with eccentric cystic foci (at least % solid). complex means there is a suspicion of a tumour inside a cyst or a solid tumour with cystic components. a complicated cyst will usually be followed by us after months. a complexcystic lesion needs a correlation with mammography. us-guided large core needle biopsy in combination with a us and mammography visible marker placement is useful in type and in type complex-cystic lesions. in type and type complex-cystic lesions, a preoperative hook wire placement and excision surgery is the typical procedure. learning objectives: . to learn about the us appearance of complicated cysts and complex-cystic lesions. . to consolidate knowledge on differential diagnosis for these respective lesions. . to understand the diagnostic algorithm for a work-up of these lesions. renal colic is the most frequent non-obstetric cause for abdominal pain and subsequent hospitalisation during pregnancy. intervention is necessary in patients who do not respond to conservative treatment. ultrasound (us) is widely used as the first-line diagnostic test in pregnant women with nephrolithiasis, despite that it is highly nonspecific and may be unable to differentiate between ureteral obstruction secondary to calculi and physiologic hydronephrosis. magnetic resonance imaging (mri) should be considered as a second-line test, when us fails to establish a diagnosis and there are continued symptoms despite conservative management. moreover, mri is able to differentiate physiologic from pathologic dilatation. in fact in the cases of obstruction secondary to calculi, there is renal enlargement and perinephric oedema, not seen with physiological dilatation. in the latter, there is smooth tapering of the middle third of the ureter because of the mass effect between the uterus and adjacent retroperitoneal musculature. when the stone is lodged in the lower ureter, a standing column of dilated ureter is seen below this physiological constriction. mri is also helpful in demonstrating complications such as pyelonephritis. in the unresolved cases, computed tomography remains a reliable technique for depicting obstructing urinary tract calculi in pregnant women, but it involves ionising radiation. nephrolithiasis during pregnancy requires a collaboration between urologists, obstetricians, and radiologists. learning objectives: . to list the us, mr and ct imaging findings of urolithiasis and urinary tract infections. . to discuss the role and the appropriate uses of us, mr and ct for imaging these suspected conditions in pregnancy. . to discuss how imaging can influence the management of nephrolithiasis during pregnancy. oncology t.f. hany; zurich/ch (thomas.hany@gmail.com) in malignant tumours, pet/ct imaging using -fluoro-deoxyglucose (fdg) is widely used nowadays. fdg-uptake is an unspecific process and results in physiological as well as pathological malignant and non-malignant tissue uptake. to properly understand and interpret pet/ct imaging, knowledge of the mechanism and pathways of fdg in different tissue types like brain and the gastrointestinal tract is key. intrinsic as well as extrinsic factors influence uptake pattern not related to oncological disease like uptake in brown fat in patients exposed to cold ambient temperature and psychological stress or increased muscular uptake in nonfasting patient. typical treatment-related changes occur during and after treatment and must be recognised correctly so as not to overstage patient disease. a systematic analysis and knowledge of all these factors facilitate and improve the reading of oncological clinical cases. learning objectives: . to understand pattern of physiological fdg-uptake. . to learn about the pattern of non-pathological uptake in several tissue types. . to understand the influence of chemotherapy and other agents on fdguptake in the body. radiologists mostly prefer to use the comparative technique while evaluating radiological images, especially when the anatomy is identical for both sides. comparative analysis mostly works if the anatomic details are not complex or the right resembles the left. however, the complex anatomy and relatively high incidence of individual variations in head and neck may hinder this way of interpretation. variable pneumatisation of paranasal sinuses and temporal bone may cause difficulty. vascular system, especially venous structures may be sources for pseudolesions. for example, asymmetrically enlarged jugular vein or venous plexuses at any location may be misinterpreted as mass of any origin. veins may also become problematic on mr imaging due to entry slice phenomenon, in-plane flow, and flow turbulence effects and can have variable enhancement. normal anatomical structures such as facial nerve may enhance and can be mistaken to be pathologic on mri. technical issues can be considered as a group that may cause pseudolesions. images of the improperly positioned patient may become problematic while evaluating tiny structures. pet and pet-ct carry their own risks for pitfalls. normal structures may confound interpretation and result in false-positive findings. the situation may become much more complicated when there is asymmetry. similarly, atrophy and unilateral absence of a structure may be misread as a mass on the contralateral side. because of the complex anatomy and relatively high incidence of individual variations, head and neck imaging demands much more attention and careful analysis. the appropriate imaging technique and detailed knowledge of anatomy are essential to recognise pseudolesions. as a general rule, detailed knowledge of the patient's clinical history is essential before any imaging study is performed, to evaluate the appropriateness of the indication, tailor the acquisition protocol and correctly interpret the study. in head and neck imaging, this rule particularly fits in the emergency setting. in certain circumstances, the swelling and enhancement of soft tissues produced by infectious lesions may mimic a neoplasm. even more so, in patients already treated with surgery or chemoradiation. in these patients, the challenge is double: to identify any abnormality in the new anatomy produced by treatment and to discriminate between inflammation, complication and relapse. these can be very difficult without knowledge, for example, of the reconstructive procedure after surgery. previous images are extremely useful, not only because they help detect abnormalities, but also because through indirect information on the growth rate of the lesion they are crucial for correct interpretation of findings. tablets in radiology represent a novelty. since the introduction of the tablets on the market, the radiological field has been probably the first medical discipline to discover the many advantages of these devices. in fact, many applications for image management have been made available on the app stores (apple and android), and allow radiologists and non-radiologists to handle dicom images on the tablet, as part of the patient's record. however, the emerging applications are driving the process from the simple dicom image viewing to the full integration of the tablet with the pacs, allowing the handling of a patient's full record and presumably the possibility to report. in view of this rapid technological development, again radiology falls in the middle of a storm and is asked to find a solution to problem: are tablets suitable to read and report dicom images? and if so, which kinds of images (ct, mri, x-ray, etc) .? how can we manage the portability of patients' data (security issues, data loss, etc).? what will be the impact on teleradiology? these issues will be addressed by the panel of experts who will speak in the refresher course. session objectives: . to appreciate the current state of tablet technology and its practical use in radiology. . to understand the pros and cons of the use of tablets. . to learn about specific critical areas of utilisation (dicom images reading and teleradiology). a. tablet-computers: a technical overview j. fernandez-bayo; sabadell/es (jfernandezb@cspt.es) since their introduction in , tablet pcs have evolved extensively. they have become very popular, filling the gap between laptop computers and smart mobile phones. we will review technical aspects like the processors, storage space and memory, size and weight, connectivity and networking, software, autonomy, and battery life in different devices. special focus will be on the displays and different possible uses in radiology. for diagnostic purposes, different technical aspects must be taken into consideration, like the display size, resolution, pixel size (pixel pitch or pixels per inch), luminance, and contrast. displays in radiology normally have sizes between " and " and resolutions up to mpx, with luminance that ranges from cd/m to cd/m . by contrast, tablets have screen sizes between " and " and resolutions up to mpx, with luminance that ranges from cd/m to cd/m . due to their screen size, tablets score better in pixel pitch, with around ppi versus ppi in medical displays. the two systems have similar contrast ratios. other technical aspects of display that we should take into consideration are the number of distinguishable grays that can be represented, which in tablets correlates with the number of colours that can be displayed (color gamut) and colour accuracy (delta-e). additionally, we should take into consideration that displays should be calibrated for medical diagnostic purposes and tools to calibrate tablets have recently become available. learning objectives: . to learn about the pc evolution: from desktops, to laptops and tablets. . to appreciate the versatility features of a tablet. . to understand the hardware features with a specific focus on display. . to understand the hardware features with a specific focus on networking. a- : b. reading dicom images on the tablet o. ratib; geneva/ch touch screen tablets are becoming widely available, providing convenient mobile solutions for physicians and health-care providers. this is particularly attractive in medicine to "nomad" physicians, who need to be able to access relevant patient data and images anywhere-anytime in their daily practice where they are rarely at a single location. while they may not always be adequate for routine diagnostic tasks, they provide a convenient mobile solution for on-call and remote consultations. there are different types of software architecture that can be implemented for such tasks. two different major designs are: ( ) online web-based applications where the device serves as a "thin-client" to display images rendered and manipulated on a remote computer and ( ) local applications that reside on the mobile device and can run independently after images have been downloaded on the device. the first solution requires the user to be constantly connected to the network, while the second solution can continue to function after being disconnected from the network. most pacs vendors are starting to provide web access to their imaging solutions that can be accessed from mobile devices. web access can however be slow and dependent on reliable access to wireless network. we chose to develop a stand-alone companion application to our open source imaging platform osirix. with the increasing capacity and computing power of mobile devices, users will soon be able to perform most of the processing and image manipulation functions that are today only feasible on desktop or laptop computers. learning objectives: . to learn which dicom readers are available for tablets. . to appreciate the different approaches to dicom reading (local vs remote) and the pacs/tablets integration. . to understand the pros and cons of dicom image reading with the tablet in regards to image quality and displays. the optimisation of clinical breast cancer care comprises the prevention of over-diagnosis, reduction of over-treatment, and avoiding unsuccessful treatments. these goals are targeted in the vph-prism project by seven european and two us partner institutions. from the prospectively collected data, we will derive optimised imaging protocols that comprehensively take a woman's history and risk factors into account. the tight integration of radiological and histopathological images enables joint assessment of quantitative tissue parameters from microscopic and macroscopic imaging. more informed therapy decisions can be taken by such enhanced multidisciplinary data, backed by a powerful case database. the reduction of overtreatment, and highly individualised diagnosis and therapy decisions are closely related. we ultimately aim at deriving predictive parameters from the multi-modal and multi-disciplinary database to select the treatment option with the best chance of enduring recurrence-free survival. prospectively collected data, personal risk factors, and corresponding imaging data fed into the database from three large cohort studies are expected to provide insights into the individual preconditions and factors affecting disease progression. to optimise therapy, the decision between therapy options is key. this will be addressed by a decision support system using the project database. for surgical excision planning, vph-prism will aim at providing better estimates of tumour size, and with visual planning aids supporting radiologists and surgeons. for chemotherapy, quantitative lesion parameters, tracked over time during therapy, may help to detect success or failure of the treatment early on, such that a chemotherapy regime can for a non-responder be switched to a different regime in due time. quantitative imaging biomarkers in dementia; the fp vph-dare@it project w.j. niessen; rotterdam/nl (w.niessen@erasmusmc.nl) the number of individuals suffering from dementia today is roughly million. due to ageing societies, this number is predicted to increase to million by . worldwide annual costs are estimated to be € billion. in , the who declared dementia a global health priority, highlighting the urgent need for improvements in this area. vph-dare@it's aim is to enable more objective, earlier, predictive and individualised diagnoses and prognoses of dementias to cope with the challenge of an ageing european society. the expected impact of vph-dare@it will influence the scientific, clinical and industrial communities across europe and internationally to improve health care of dementia patients. in this presentation we will introduce the vph-dare@it project. we will then focus on the development, validation and implementation of quantitative imaging biomarkers for the early detection and differential diagnosis, which will take place as part of the project. author disclosure: w.j. niessen: advisory board; part-time detached to quantib bv as scientific director. shareholder; co-founder and shareholder of quantib bv. horizon : improving diagnosis and medical interventions and support to medical imaging j.-l. sanne; brussels/be (jean-luc.sanne@ec.europa.eu) research and innovation contribute to increasing europe's competitiveness. at the same time, research and innovation help make people's lives better by improving things like healthcare. in january the european union launches horizon , the biggest eu research and innovation programme ever, with a budget of € billion (current prices) over seven years ( ) ( ) ( ) ( ) ( ) ( ) ( ) . eu support for research and innovation helps drive international projects across the european union and beyond, and promotes the progress of knowledge and technology. one of the three key pillars of horizon will be tackling societal challenges (priority ) such "health, demographic change and well-being". one feature is the development of new and more effective diagnostics. relevant tools and technology innovations will be supported in view to improve disease outcomes through earlier, more accurate diagnosis and by allowing for more patient-adapted treatment. support will be provided through the work programme - of societal challenge "health, demographic change and wellbeing". additional opportunities are offered in the work programme - of priority (industrial leadership) "leit -information and communication technologies". practically, all imaging modalities have been used in space research since a long time ago. first of all, radiology is targeted in research activities, because by definition all cosmonauts and astronauts are healthy persons. the biggest volume of examinations had been performed on crew members for studies of organs and functions of the human body before and after long-term flights. health effects of zero gravity were of special interest. for example, multiple studies with involvement of both russian and international specialists were done on bone mineralisation (bone densitometry), muscle volume (mri) and metabolism (mr-spectroscopy) both in astronauts and healthy control subjects. first, ultrasound (us) examinations were conducted in space onboard russian orbital stations in . complex us studies were done by the author himself during his flight as a crew member of "salut- " orbital station in . the author had found some complex changes in blood and fluid dynamics under weightlessness. teleradiology was used for data transfer to medical specialists on the earth. today, we are continuing to use radiology for research on astronauts. for example, applications of sophisticated brain mri and fmri methods are of special interest for studies of subtle brain changes in space travellers. among our targets are flights to the moon, mars and large asteroids. to be better prepared for that task, we need better diagnostic tools. new versions of mobile us systems, miniature x-ray and ct machines suitable for use inside spaceships are under development. there are several mri pitfalls that should be recognised when imaging the female pelvis. mri appearances of uterus and ovaries are dependent on the phase of menstrual cycle/use of exogenous hormone therapy. normal postsurgical and post-radiation appearances of the pelvis can sometimes mimic tumour recurrence. it is important to become familiar with these appearances to avoid potential pitfalls. one very common pitfall is differentiation of transient myometrial contraction from adenomyosis. interrogation of all imaging planes over the duration of the entire mri examination can be useful to distinguish between the two, although myometrial contractions can last up to min. the choice of the correct imaging plane is crucial for the precise classification of uterine anomalies (coronal oblique) and accurate evaluation of parametrial invasion (axial oblique) in patients with cervical cancer. both dynamic contrast-enhanced mri and diffusion-weighted mri improve the accuracy of mri in the evaluation of malignant pelvic conditions. however, certain pitfalls related to each technique should be recognised to avoid misinterpretation. it is crucial to be familiar with the anatomy of the uterovesical (uv) ligament, as it is often the site of pelvic lymphoma (such as bladder or cervix lymphoma). however, some benign conditions such as endometriosis can involve the uv fold and invade both bladder and uterine wall. certain mri features can be helpful in making the correct diagnosis. learning objectives: . to become familiar with normal variations in mri appearances of female pelvis resulting from physiological conditions (e.g. different phases of menstrual cycle) and treatments (including exogenous hormone therapy, surgery and radiation) potentially mimicking disease. . to consolidate knowledge on the role of the correct mr imaging plane in avoiding potential mis-classification of uterine anomalies and parametrial invasion in patients with cervical cancer. . to learn about certain pitfalls related to dynamic contrast-enhanced mri and diffusion-weighted mri. a- : b. pitfalls in ultrasound k. kinkel; chêne-bougeries/ch (karen.kinkel-trugli@wanadoo.fr) pitfalls of sonographic findings in the pelvis can be related to technical issues, interpretation errors or to the patient's specific condition or pathology. common problems consist of insufficient bladder filling, misinterpretation of posterior enhancement or shadowing according to the anatomical structure and pathology of a size that goes beyond the field of view of the probe. organspecific problems will be illustrated in interactive questions, particularly for the uterus and the ovaries. identification of diseases can be difficult in many areas of abdominal imaging and therefore misses are easily made, also by the more experienced radiologist. it is difficult in the mesentery and peritoneum, covering a large area but being a very thin structure where abnormalities are easily missed. therefore, knowledge of the peritoneal anatomy and pathophysiology of peritoneal diseases is not widespread and differential diagnosis can be difficult. hence, special attention should be paid to prevent misses. another difficult area is diagnosing occult gastrointestinal bleeding. here, the choice of the proper imaging method is crucial as well as understanding the pros and cons of the method. the technique used should be optimised, as otherwise sometimes subtle signs of bleeding are missed. the presence of bowel dilatation itself is often correctly diagnosed, but the extent of the obstruction, the cause of the obstruction and especially complications (ischaemia) might be misdiagnosed. ct is the preferred technique for evaluation of bowel dilatation. care should be taken to scrutinise the examination for principal findings in patients with bowel obstruction. a. mesentery and peritoneum d. akata; ankara/tr (dakata@hacettepe.edu.tr) imaging findings of neoplastic or inflammatory diseases within the peritoneal cavity and the mesentery sometimes overlap and cause difficulties in interpretation. even disease processes in the peritoneum, mesentery or omentum may not be recognised on radiological examination, causing major difficulties in the management. peritoneal anatomy and physiopathology of peritoneal diseases must be well understood for better evaluation. ct is the best modality to assess the whole cavity. mr is equally sensitive with better contrast resolution; however, both modalities have advantages and limitations. ultrasound has a complementary role in evaluating the peritoneal fluid content. the presence of lacelike mobile thin septa is highly significant for tuberculosis. for better diagnosing the pathology, systematic approach is needed such as assessing the presence or absence of fluid in the peritoneal cavity, its character and location, accompanying soft tissue densities and their location. some inflammatory or infectious causes, such as acute pancreatitis and tuberculosis, involve typically parietal peritoneum and certain peritoneal reflections. peritoneal carcinomatosis involves typically both visceral and parietal peritoneum as well as subdiaphragmatic space. contrast enhancement patterns of the peritoneal membranes and the mesentery also have a complementary role in differentiating a variety of diseases. learning objectives: . to learn about the imaging characteristics of peritoneal and mesenteric masses and their differentials. . to appreciate the potential and limitations of imaging techniques in the detection of such lesions. . to understand the common pitfalls in diagnosis. a- : a. filippone; chieti/ it (a.filippone@rad.unich.it) patients with persistent, recurrent, or intermittent bleeding from the gastrointestinal tract for which no definite cause has been identified by initial oesophagogastroduodenoscopy, colonoscopy, or conventional radiologic evaluation are considered to have an occult gastrointestinal bleeding (ogib). the management of ogib is clinically challenging, since the causes of such a bleeding frequently arise in the small bowel (sb), until now considered as the ''dark continent''. conventional barium contrast studies allow only a limited evaluation of sb, whereas angiographic diagnosis is strictly related to active bleeding. the introduction of capsule endoscopy (ce) as well as of crosssectional imaging dedicated to the sb visualisation, such as multidetector-row computed tomography enteroclysis (cte) and magnetic resonance enteroclysis (mre), represents significant technological advances that have overcome the limitations of older diagnostic tests. although ce is recommended as a first-line investigation in ogib patients, cte or mre are alternative diagnostic tools when ce is contraindicated due to suspected/known obstruction or stricture. moreover, in patients in whom a tumour is suspected, cte or mre may be the preferred initial test. therefore, radiologists have to be familiar with cte and mre techniques, in terms of bowel distension, scanning parameter selection, contrast administration as well as with specific imaging findings. similarly, they have to be aware of the potential pitfalls such as suboptimal bowel distension, artefacts due to peristalsis or breathing, intraluminal food debris and previous surgery. learning objectives: . to understand the causes of gi bleeding and underlying pathophysiology. . to appreciate the strengths and limitations of the imaging techniques used in diagnosis. . to learn about common pitfalls in diagnosis. dilatation. presently, ct takes a major place in this setting with a reduced role for plain films. sonography is an alternative method when ct is not recommended. the questions of mondor in were pointed before the advent of cross-sectional imaging; these are still valid and have to be answered: ) is this a true occlusion (how to differentiate it from adynamic ileus)? ) does the obstruction concern the small bowel or the colon (impacting on the decision to operate or not)? ) what is the cause of the obstruction? ) are there signs of bowel ischaemia? the key points to avoid missing imaging diagnoses in bowel dilatation are to make the distinction between true mechanical obstruction and adynamic ileus (an early sign of mesenteric infarct) and to detect signs of strangulation leading to ischaemia (such imaging findings are present despite normal blood tests). in this setting, ct is the preferred technique; if it is not available, plain films and sonography can help in an optimal medical decision. the national lung screening trial (nlst) found a % reduction in lung cancer mortality with three annual screens using helical ct relative to chest xray. the us preventive services task force has issued draft recommendations to provide annual ct screening to high risk individuals defined by age and smoking criteria. questions remain regarding the implementation of ct screening: the determination of risk to identify those who should be screened, the frequency and duration of screening, definitions of screen positivity based on detected nodule characteristics, diagnostic algorithms for the follow-up of positive screens, overall societal costs of screening, and methods to adequately diffuse this technology across all socioeconomic groups at risk. answers to these questions are being addressed by several groups through ongoing research and secondary analyses of trial data. several models exist to identify individuals at highest risk of lung cancer (and lung cancer mortality), which may be enhanced if validated molecular markers are included. ongoing analyses of nodule features and likelihood of lung cancer will better inform screening interpretation guidelines and diagnostic algorithms. estimates from the nlst suggest that screening as performed in the nlst will be cost effective: the base case estimates $ , per quality adjusted life year gained (qaly). subset analyses suggest that screening is much more cost-effective in women than men, in higher versus lower risk groups, and in current versus prior smokers. while several variables influence cost-effectiveness, major drivers of cost are the cost of ct screening exams as well as the number of follow-up ct scans per positive screen ( . in nlst). while the national lung screening trial (nlst) had shown a significantly reduced lung cancer-specific mortality and all-cause mortality, the current results from the various european trials do not show such positive results. the dutch-belgian nelson trial, the german lusi trial and the british ukls have not yet published their results. so far, more cancers were detected in the screening arm of published danish and italian trials, but the positive effect on cancer mortality could not yet be shown. the italian mild trial even showed higher mortality in the yearly screening arm, and no difference between yearly screening and the control arm. this presentation discusses the implications of these findings and the consequences on implementation on screening in clinical practice. while limited in number of participants, european trials used advanced approaches that are most likely to be used if screening will ever be implemented. this presentation will discuss issues such as growth assessment and volumetry as critical factors for nodule assessment, handling of sub-solid lesions, computer aided detection and evaluation, and use of nonradiologists for reading and standardised follow-up. the goal is to provide an insight into how the european trials have affected our idea on practical implementation of lung cancer screening. the discussion will address the following issues: . are there sufficient data to support the implementation of individual lung cancer screening in clinical practice? . if yes, how to move from efficacy to effectiveness: what are the most optimised risk profiles for screening? what is the minimum level of infrastructure support and organisation required? how should subjects be informed about screening? what are the optimal follow-up duration and screening interval? what are the technical and positive screen management requirements? . what about the alternatives of waiting for additional data from ongoing trials or the validation of new biomarkers of lung cancer, permitting better selection of screened population before implementing individual lung cancer screening? attendees' opinions will be collected interactively. the speakers will be asked to comment and debate. treatment of prostate cancer depends strongly on the stage of the disease at the time of detection. however, treatment is controversial, even in prostate cancers found through early detection. this presentation will be based on a careful recent literature review. early detection of prostate cancer by use of psa testing leads to a significant reduction of at least % of disease-related mortality in screened men. this is however at the price of - % of overdiagnosis, usually resulting in overtreatment. diagnostic developments which reduce overdiagnosis and the proper identification of cases which may not require treatment are central issues of current research and will be addressed by referring to available evidence. active observation of potentially nonaggressive cancers is an option in the management of this disease until, preferably, the diagnosis of such cases can be avoided all together. radical prostatectomy and radiotherapy are the options for treating those cancers which are judged to be aggressive. treatment recommendations for prostate cancer continue to evolve and are affected by technological advances in surgery, new discoveries in tumour biology, and the development of predictive and prognostic biomarkers. with the increased complexity of treatment decision-making, the role of mri is also evolving. the more individualised and targeted the treatment approach, the greater is the role of imaging in treatment selection, planning and follow-up. mri is especially crucial for planning technologically sophisticated treatment approaches such as robotic surgery, igrt, or focal therapy and in assessing patients' eligibility for active surveillance. though needs for uniform interpretation and standardised reporting remain unresolved, the value of mri in pretreatment staging of prostate cancer, particularly for evaluating extracapsular extension and seminal vesicle invasion, has been documented. not only the tumour stage, but also its size, volume and grade (aggressiveness) are important factors that influence treatment selection. therefore, the introduction of functional mr is essential. when added to t weighted mri, diffusion-weighted mri, dynamic-contrast-enhanced mri, and mr spectroscopy, in addition to improving tumour detection, can provide an indication of tumour aggressiveness. mri performance on all sequences is dependent on lesion size/volume and grade, and this should be considered when applying mri results to treatment selection and planning. while it has been shown that multiparametric mri is generally more accurate and informative than anatomic mri alone, evidence-based guidelines specifying which combinations of sequences are essential for specific indications in patients with prostate cancer are yet to be developed and validated in welldesigned studies with robust outcome measures. in major trauma, it is essential to immediately recognise life-threatening conditions and to initiate early treatment. the majority of these patients succumb at the site of the injury to severe injuries of the central nervous system, heart and great vessels. however, there is another peak of early deaths within the first four hours after the injury. in the majority, these patients are at risk due to haemorrhage which is basically controllable by early minimally invasive treatment. consequently, this means that the vast majority of internal injuries can be survived as long as bleeding control is achieved within the first four hours after an injury. minimally invasive interventional techniques are already in use at a very early stage of the clinical decisionmaking process. particularly, we have witnessed a major paradigm shift in the treatment of blunt aortic injuries. endovascular repair has replaced open repair in many trauma centres. in appropriately selected patients, this adoption of endovascular stent grafts has resulted in a reduction in perioperative mortality, stroke and paraplegia, as compared to open repair. this entire session will provide knowledge about indications, requirements, standard procedures, and outcome of vascular emergencies, pardon me, urgencies. a. aortic emergencies m. cejna; feldkirch/ at (manfred.cejna@lkhf.at) aortic emergencies can be classified into several categories. "acute aortic syndrome": acute aortic syndrome is an entity of changes of the aortic wall. these include aortic dissection, intramural thrombus, and penetrating atherosclerotic aortic ulcer. besides coronary malperfusion and aortic valve insufficiency (type a dissection), emergency presentation is often due to visceral/limb ischaemia. sequelae of aortic syndromes are pseudoaneurysm formation and potentially aortic rupture. endovascular treatment has been established as the treatment option in at least type b dissections and penetrating aortic ulcers. aortic aneurysm rupture: with increasing diameter, aneurysms in the thoracic, thoraco-abdominal and abdominal aorta are prone to rupture. signs of impending aortic rupture are pain and imaging signs are sometimes subtle just like blurred contours of the aorta and (blister like) vascular wall deformation. endovascular treatment is an alternative to vascular surgery. aortic trauma: in severe thoracic trauma (mostly deceleration trauma), pseudoaneurysm formation and aortic rupture occur at the level of the aortic isthmus. endovascular treatment is considered the treatment of choice. inflammation, mycotic aneurysms and aorto-enteric fistulae: with acute and chronic inflammation, aneurysm and pseudoaneurysm formation and fistulae to enteric structures can occur. endovascular treatment is more often considered as bridging to vascular surgery instead of being a definitive cure. iatrogenic aortic injuries: besides accidental aortic injury during operations or interventional procedures, transaortic valve replacement and placement of aortic balloon pumps can result in iatrogenic trauma. endovascular treatment may be a minimally invasive approach. the focus will be on systematic presentation of aortic emergencies and the role of endovascular treatment. there are a number of vascular visceral emergencies that may be traumatic or nontraumatic in origin. the degree of urgency or potential for urgency varies with each condition and the subsequent management and intervention techniques will vary accordingly. an understanding of the natural history, pathophysiology, diagnostic tests and interventional techniques for these conditions will aid the diagnostic and interventional radiologist in identifying the pathology and knowing when to refer or initiate definitive treatment. i talk about embryonal development and anatomical differentiation of cardiovascular system, with special attention to the peripheral vascular system. the goal of this part of presentation would be to understand the anatomical structure and architecture of arteries and capillaries. we will discuss the casual classification of different kinds of peripheral arterial emegencies; e.g. congenital, posttrauma, arteriosclerotic and iatrogenic. the audience will learn about different therapy approaches, interventional and non-interventional, with accent on pad (classification, pathophysiology, risk factors, statistical facts and therapy). at the end, we will review different studies about combination therapy (conventional and interventional) with different possibilities and outcomes. modern cancer research and increasing therapy are mechanism based with the development of disease-modifying therapies that target the hallmarks of cancer. modern imaging tools enable the visualisation and quantitative assessment of the expression of molecular targets, of their interaction with potential ligands, as well as of the functional consequences of interactions at a molecular, cellular, metabolic, physiological, and morphological levels in a temporo-spatially resolved manner. the ability to gather such information from the intact organism renders imaging highly attractive for biomedical research and drug development. the determination of cell proliferation with radiolabelled thymidine is a wellestablished method in various life science branches where [ h]thymidine has been used for more than years and still represents the gold standard for the assessment of tumour cell proliferation. since non-invasive determination of this parameter is required in clinical studies, considerable efforts have been made in radiopharmaceutical research. the synthesis of a large series of proliferation markers resulted therefrom mostly focussing on pyrimidine nucleosides. the labels used were gamma as well as positron emitting radionuclides. here, [ f]flt ( '-deoxy- '-fluorothymidine) is examined and discussed with respect to its preclinical and clinical application. since apoptosis is an important mechanism of cell death in tumours responding to treatment, the non-invasive assessment of apoptosis with tracers for the detection of phosphytidyl-serine presentation and/or caspase activation could be used as surrogate marker for therapeutic efficacy. several approaches have been followed during the last years; their potential and limitations will be presented. angiogenesis is one of the hallmarks of cancer that is considerably easy to characterise with many different imaging modalities and methods. it is not only crucial for invasive and metastatic tumour growth, but is also a prerequisite for the accumulation of anticancer drugs and highly impacts the success of radiotherapy. this talk summarises our experiences in microstructural, functional, and molecular imaging of tumour angiogenesis. the microarchitecture of vessels can longitudinally be studied using high-resolution ( )ct. dce mri and hf-us are introduced as favourable tools to characterise perfusion, vessel permeability and vessel maturation during antiangiogenic treatments. using targeted probes, it is shown that "fluorescence molecular tomography (fmt)", mri and us are capable of estimating the expression of angiogenic marker molecules on tumour vessels and of matrix-associated enzymes in the interstitial space during vascular remodelling. additionally, examples are also given for epr-based nano-sized theranostics and it is shown how us can aid in better accumulating them at the target site by inducing vascular permeation. many of these novel imaging concepts and tools can relatively easily be translated into clinics. thus, one can expect them to play a major role in the clinical management of tumour treatments soon. mammography technique from the point of view of radiographic compression and positioning is no different from film screening and radiologists ignore this at our peril. we will discuss the danger areas at the edges and the back of the breast and help you to find lesions only seen on one view. with digital capture the technologist can view images immediately, but the temptation is for them to repeat exposures to obtain radiographic perfection on otherwise clinically acceptable images. however, the task of assessing quality cannot be left to them, as viewing conditions on the 'lower resolution' acquisition monitor in a bright x-ray room is not enough. there is now evidence from population screening programmes that poor image quality can reduce cancer detection from between % in france to % in ontario. 'quality' can be lost at keys points in the imaging chain: the x-ray beam and dose, the detector and finally display. in flanders, poor detector performance was compensated for by increasing the x-ray dose by % and by meticulous quality control. postprocessing is less well understood, but reader studies now show different algorithms will affect performance particularly for the detection and classification of micro-calcification. finally, it does not matter how good all the equipment is if we try and read the images with the lights on full. mammography is the most important breast imaging technique allowing the visualisation of masses and micro-calcifications. however, in conventional mammography the three-dimensional breast tissue is reduced to a twodimensional image. therefore, small lesions may be undetectable due to superimposed glandular tissue. digital breast tomosynthesis (dbt) has emerged as a new imaging modality to overcome this limitation. several lowdose mammographic projections are performed over a limited angle of up to degree using a standard mammography system. the average glandular dose of a tomosynthesis scan is somewhat higher compared to one-view mammography, but lower compared to a standard mammography in two projections. based on the low-dose projections, a stack of cross-sectional images covering the entire breast is reconstructed with an interslice distance of about mm. several studies have shown that tomosynthesis improves both tumour detection and the characterisation of focal masses. due to the crosssectional nature of dbt, the techniques allow on the one hand the reliable differentiation of true focal masses from summation artefacts. on the other hand, tomosynthesis improves the detailed analysis of the lesions' border to differentiate benign lesions and carcinomas. additionally, contrast-enhanced spectral tomosynthesis may allow analysing signal-intensity time curves. in conclusion, dbt adds important information to standard two-projection mammography and can replace spot compression and rolled views as problem solver for difficult cases. however, the impact of tomosynthesis on breast cancer screening has to be investigated in larger clinical trials. reading screening mammograms is not the same as reading diagnostic mammograms. the vast majority of women attending a screening programme are usually asymptomatic and do not have abnormalities associated with a malignancy. the task of a mammogram reader is to scan a mammogram and perceive any possible abnormalities that could be associated with a malignancy. in other words, we are talking about perception and not diagnosis of a finding. examples will be shown about this crucial step. in modern population-based screening programmes, we use computerised reading and recording systems. since the work flow is rather quick, we have to ensure basic steps such as identity control and see that both ris and pacs are synchronised so that decisions of screening readings are recorded in both the systems of one and the same patient. in computerised screening programmes, we use standard reports informing a woman that no signs of malignancy have been detected on her screening mammograms. in case of findings that need further assessment, there are several ways to deal with this situation. the most common way is via a phone call, but this can also be done with a letter. a screening report should be short and concise and should only inform whether we see signs of a possible abnormality that can be associated with a malignancy. extensive reports describing the contents of a breast or findings of no clinical relevance should not be part of a screening report. emergency radiology services are very much on the rise in the last decade. medical emergencies and trauma are of enormous importance and a leading cause of death in all age groups. the use of radiological imaging in emergency departments showed an exponential increase since the s. the annual growth rate in ct is - % per year depending on the institution. even for advanced level ° medical centres running an own emergency radiology unit, it is a challenge to integrate advanced radiology services in an interdisciplinary team treating patients with acute traumatic and non-traumatic emergencies. general principles: radiology and radiological imaging procedures should be integrated in an interdisciplinary team. imaging should be guided by interdisciplinary clinical algorithms or guidelines (e.g. nexus or canadian cspine rule). many clinical diagnoses relay today on a early and thorough initial radiological diagnostic workup -mostly based on mdct. emergency radiology (er) is still a relatively young subspecialty in european radiology -it deserves specific training. the lecture will cover: the development of emergency radiology and its future perspectives; the use of conventional radiography, ultrasound and mdct; logistics and management of the patient; clinical guidelines and mdct in the primary patient survey (e.g. using atls for trauma) and advanced scanning protocols for mdct. infants and children with abdominal emergencies present special diagnostic challenges because of similarities in clinical findings between various paediatric conditions. imaging is frequently a critical part of the diagnostic process, but the choice of the best imaging modality can be controversial. patient age and safety issues such as radiation exposure must be taken into consideration when planning imaging. because certain pathologies are more likely to occur in specific age groups, patient age is a primary determinant of the imaging approach. this presentation will illustrate the differences in pathology between several paediatric age groups and discuss effective imaging algorithms for congenital and developmental, inflammatory, and obstructive conditions. the optimal use of radiographs, ultrasound, ct, and mri will be discussed. pitfalls that should be avoided in ultrasound and ct will be emphasised. in diagnostic imaging, we tend to focus on radiation protection, justification and optimisation, as the primary opportunity for radiographers and radiologists to ensure the safety of patients, both adults and children; however, this ignores some other important issues. this session aims to raise awareness amongst medical imaging professionals of some key considerations in relation to a number of child protection issues. when imaging a child in case of suspected non-accidental injury, every detail of that examination from conversations with the child and their parents or guardians, technical aspects of the examination, observations during the examination and the language used following the examination need to be carefully considered. another area of medical imaging requiring attention is how we communicate any radiation risks associated with examinations or procedures with children and their parents. there is evidence that while consent processes for invasive procedures are usually in place, these often lack focus on the risks associated with a high exposure to ionising radiation. these two medico-legal areas, suspected non-accidental injury and risk communication, are commonly encountered by radiographers and radiologists and as such it is important to make sure that we operate at the highest possible professional standards and in keeping with both regulations and best practice including the production of witness statements/contemporaneous notes. on rare occasions, we may find ourselves involved in legal proceedings as a witness or expert witness and it is thus important that we are all aware of the key considerations in this regard. session objectives: . to appreciate the need for radiographers to focus on more than just the imaging procedure in paediatric examinations. . to understand the extremely vulnerable nature of paediatric patients and the need for all health professionals to pay particular attention to this. a. professional responsibilities: an international perspective m. davis; dublin/ie (michaela.davis@ucd.ie) radiographers play a vital role in imaging children with suspected nonaccidental injuries. this session will also explore the wider role that radiographers have in child protection. current legislation and its implications will be explored from a variety of countries including those outside europe. in addition, case studies will be presented focussing upon child protection issues that have arisen in the x-ray department during imaging procedures. several of the barriers to radiographers becoming involved in child protection will be explored. radiographers and their contribution to child protection will be discussed and practical examples given. learning objectives: . to become familiar with current legislation and guidelines which have particular relevance to radiographers from an international perspective. . to appreciate best practice in child protection and the need for all radiographers to be aware of this. . to learn about child protection case reports involving imaging, radiologists and radiographers. a- : b. risk communication in paediatric examinations j.l. portelli; msida/ mt (jonathan.portelli@um.edu.mt) medical imaging plays a vital role in the diagnosis and treatment of numerous medical conditions for millions of patients worldwide. however since most medical imaging examinations utilise ionising radiation, the associated risks of radiation exposure also need to be acknowledged, especially since high doses of radiation are known to cause adverse biological effects. medical imaging professionals should have a good understanding of the benefits and risks associated with the imaging examinations they perform, so as to ensure a high benefit-risk ratio for all patients undergoing diagnostic imaging procedures, and to be able to appropriately communicate such information to patients, their families and other healthcare professionals. this may be particularly more important when imaging paediatric patients, who are relatively more susceptible to the effects of radiation and receive a higher effective dose per unit of radiation when compared with adults undergoing the same medical imaging examination. indeed, following worldwide media attention about radiation incidents and their adverse effects, some parents/legal guardians may be concerned and reluctant to pursue important medical imaging examinations requested for their child, as they may have a misconception of the risks involved. in this regard, this lecture will seek to enhance awareness about the radiation doses associated with common paediatric imaging examinations; highlight the importance of medical imaging professionals having an appropriate understanding of benefits and risks associated with these examinations; and encourage such professionals to improve patient care by making use of this knowledge to have better discussions with referring clinicians, patients and their families. learning objectives: . to appreciate the frequency and radiation dose associated with certain paediatric imaging examinations. . to become familiar with the current status quo in the communication of radiation dose-related risks. . to understand best practice and potential considerations in providing accurate information to referring clinicians, patients and their families. c. what to do if you find yourself being called to give evidence m.d. viner; london/uk radiology is a powerful tool in the investigation of cases of suspected nonaccidental injury and suspicious death in children. the evidence obtained can be pivotal in bringing successful prosecutions against suspects and protecting the child and others from further harm. it is essential that evidence is obtained, recorded and presented in accordance with applicable rules of evidence in order to be admissible in court. it is thus important that those undertaking such examinations are appropriately trained, conversant with standards of evidence and maintain continuity of evidence throughout the investigation. this presentation will review rules of evidence for cases of suspected child abuse and their application to imaging examinations. it will examine the role of the radiographer and the importance of training and familiarity with legislation and guidelines that underpin forensic practice, highlighting the pitfalls that lawyers may exploit if procedures have not been followed. drawing on examples, it will discuss best practice from the radiographer's perspective, detailing the importance of continuity of evidence and maintenance of contemporaneous notes and witness statements. it will address key considerations for radiographers and others who provide evidence or act as an expert witness. imaging professionals play a pivotal role in the investigation of suspected child abuse. it is essential that this evidence is obtained, recorded and presented with regard to the applicable standards of evidence. for those called to give evidence, the importance of appropriate imaging protocols and procedures, detailed documentation and thorough preparation cannot be understated. learning objectives: . to understand the importance of contemporaneous notes and witness statements if involved in any forensic or suspected non-accidental injury examination. . to become familiar with the importance of continuity of evidence in forensic examinations. . to appreciate the key considerations if you are asked to provide evidence or act as an expert witness in court. brain tumours are the second most common neoplasms in children after leukaemia. as "paediatric brain is not just a small brain", paediatric brain tumours are not the same as tumours in adults. mri is a method of choice in their diagnosis in accordance with the principle alara in the paediatric population. by the age of approximately years, supratentorial tumours dominate; later ( - years of age), the majority of children show infratentorial neoplasms which are pilocytic astrocytomas, most often found in the hemispheres, and medulloblastomas or ependymomas -in the fourth ventricle. after the age of , both groups are diagnosed with equal frequency. cerebral hemispheric tumours include astrocytoma which is the most frequent, teratoma in neonates, and in older children atypical teratoid/rhabdoid tumour, ependymoma, pnet, ganglioglioma and dnet. in the midline, we deal with chiasmatic or hypothalamic glioma, craniopharyngioma and germ cell tumours of the pineal region. extraparenchymal tumours are uncommon in the paediatric population. apart from the location, imaging pattern in various sequences, and contrast enhancement of the tumour, advanced mri techniques are helpful in establishing the diagnosis. dwi helps to differentiate between tumours of high and low cellularity showing low adc values in case of medulloblastoma and high in astrocytoma. mrs, pwi and dti also add important information to the diagnosis. mri of the spinal canal is obligatory in case of these primary brain neoplasms that have a high propensity to metastasise to other parts of the central nervous system such as medulloblastomas, ependymomas, high-grade gliomas, cerebral neuroblastomas, and pineal region neoplasms. learning objectives: . to learn about the difference between paediatric and adult brain tumours. . to understand the imaging strategy for the paediatric population. . to become familiar with the most common paediatric brain tumours. pancreatic endocrine tumours (p-nets) include both pancreatic neuroendocrine tumours associated with a functional syndrome (functional p-nets) and those associated with no distinct clinical syndrome (non-functional p-nets). non-functional p-nets may show immunohistochemical positivity for hormones which may be produced, but not secreted, which are clinically inert and whose serum concentrations are insufficient to induce symptoms. among functional p-net, the most common are gastrinomas and insulinomas, whereas those secreting vasoactive intestinal peptide, glucagon, somatostatin and other hormones are considered together as a group called rare functional p-nets. non-functional p-nets are classified, according to the who classification, in well-differentiated neuroendocrine tumours and poorly differentiated neuroendocrine carcinomas (necs) of small or large cell type. well-differentiated neuroendocrine tumours are then divided according to a grading scheme based on mitotic count or ki index in nets-g (with a mitotic count < per high-power fields (hpf) and/or % ki index), and nets-g (with a mitotic count - per hpf and/or - % ki index). all poorly differentiated neuroendocrine carcinomas are graded g (with a mitotic count > per hpf and/or > % ki index). most pancreatic nonfunctional p-nets are well-differentiated tumours, whereas poorly differentiated neuroendocrine carcinomas are uncommon. pancreatic endocrine tumours (p-net) are divided into functional p-nets and non-functional p-nets. diagnostic imaging of these tumours includes detection, characterisation and staging. there are significant differences when dealing with functional p-nets and non-functional p-nets. in fact, in the first case the main aim of diagnostic imaging modalities is the detection of the tumour, while for non-functional p-nets the main aim is the characterisation and the differential diagnosis with other tumours of the pancreas, mainly with pancreatic adenocarcinoma. staging is also important for both tumours, but mainly for non-functional p-nets. a large number of imaging modalities are available, both "morphological" and "functional". we can arbitrarily divide the imaging modalities for the diagnosis of p-nets into three levels: the first level includes us (with contrast-enhanced us), mdct, mri and nuclear medicine techniques; the second, endoscopic us, angiography and venous sampling; the third, intra-operative us. functional p-nets are represented mainly by insulinomas and gastrinomas which are small in size in most cases. their detection is still difficult, but significant improvements have been made with us, mdct and mri, so that these tumours are detected in most cases if appropriate imaging techniques are performed. however, still, no single modality is % effective. non-functional p-nets can be differentiated from pancreatic adenocarcinoma, since they are hypervascular and usually large in size. since they are potentially malignant, they require accurate staging by imaging modalities, both morphological (mdct, mri) and functional (pet/ct) to plan surgery and chemotherapy. there is worldwide consensus about surgical treatment of resectable p-nets in the following clinical situations: proven malignancy, whenever it is possible to remove the primary tumour and at least % of liver metastases (debulking); p-nets associated with a clinical syndrome caused by hormonal hypersecretion (insulinomas and gastrinomas mainly); non-functional p-nets with a size larger than cm. vice versa, there are different expert opinions about the surgical treatment of functional and non-functional p-nets in men syndromes and in sporadic non-functional p-nets less than cm in size. in men all insulinomas should be resected, while for gastrinomas the extent of resection is patient tailored, deserving standard whipple for selected cases. in the most common sporadic small incidentalomas, where long-term prognosis is favourable, surgical treatment has to be weighted with co-morbidities and morbidities of the patient and the procedure planned. these tumours have a risk of node metastases at the time of diagnosis in less than % of patients. whenever possible, mini-invasive approach with pancreas-sparing operations should be recommended. in elderly patients, a first period of follow-up should be preferable and surgery should be offered only if the size of the tumour demonstrates increasing trends. the "acute aortic syndrome" includes three closely related emergency entities of the thoracic aorta: aortic dissection, intramural hematoma and penetrating atherosclerotic ulcer. as these conditions present with similar symptoms, cross-sectional aortic imaging is essential for diagnosis, triage and treatment planning. initial imaging features of these pathologies including typical early complications as well as their differential diagnosis will be reviewed. as nowadays several of these patients will undergo early endovascular thoracic aortic repair, an update on its indication, the different technical options and their clinical results will follow. finally, the focus will be on repair-related late complications and progression of aortic disease. imaging follow-up protocols, features of chronic complications and their interventional repair will be discussed. a. pre-therapeutic radiological evaluation j. ferda; plzen/cz (ferda@fnplzen.cz) the acute thoracic aorta syndrome covers patients suffering from acute chest pain and those injured during high-energy trauma. despite the similar symptoms, the aortic pathologies are heterogeneous, including acute aortic injury, intramural haematoma, aortic dissection, and ruptured thoracic aortic aneurysm and mycotic aneurysms. the diagnostic approaches could include the whole pallete of the imaging modalities: chest x-ray, transesopheageal echocardiography (tee), multidetector ct angiography (mdcta), mri and pet/ct. because of some disadvantages of tee, like problems with intubation in injured patients or problems of mri with seriously ill patient monitoring, mdcta has become the most used modality due to its ability of discrimination between aortic and non-aortic pathologies, and also due to its high sensitivity, specificity, availability and especially superior geometrical resolution and potential of d imaging. the proper pre-therapeutic mdcta protocol is using sub-millimeter isotropic resolution covering the entire aorta with pelvic arteries. when the pathology of thoracic aorta is found during the triple rule-out triage protocol, additional mdcta of the rest of the aorta and pelvic arteries has to be completed. ecg triggering could be an important advantage in the reduction of pulsation-derived artefact. the volume of applied contrast material used should be as small as possible to plan applications during endovascular treatment. d reconstruction of the thoracic aorta with its side branches and advanced vessel analysis have a crucial role in the measurement of the aortic diameter, diameter profile and lengths in the selection of proper stent graft type and size. they can be accommodated even in patients with small vessels and tortuous anatomy. calcified arteries can be no longer considered absolute exclusion criteria. some devices are designed to reduce the incidence of endoleaks, improving sealing capabilities by the use of a polymer to better adjust to the variable morphology of the proximal neck or to fill the aneurysmatic sac completely. more importantly, the introduction of fenestrated devices has resolved the problem of facing difficult anatomies when the aneurismatic pathology involves renal or visceral arteries. obviously, the use of these new devices requires a learning curve. beyond an increase of cost, they permit treating those patients who in the past were considered unfit candidates for evar. the evar new frontier requires performing the procedure in an outpatient fashion. a multicentre study was conducted on patients who were discharged / hours after uncomplicated stent-graft implantation. cases ( %) with access vessel complications required additional procedures and patients were hospitalised overnight. the -day readmission rate was % for access vessel stenosis or false aneurysm. from the time of the first evar procedure, significant improvements have been achieved but there is still room for further progress. the standard imaging modality after endovascular treatment for thoracic aortic pathology (tevr) is ct angiography (cta). cta enables the radiologist to assess for the patency of the endografts, the presence of any complications after tevr, and the development of any new pathology related not only to the aorta, but elsewhere above and below the diaphragm. the role of mr is reduced compared with cta, particularly in the presence of stainless steel endografts. however, good images can be obtained by mri and mra if nitinol endografts have been inserted. mr is a useful modality for follow-up in young patients who require lifelong follow-up and, therefore, limited exposure to ionising radiation. ultrasound has no practical role in the follow-up after tevr, and although plain thoracic radiographs are routinely performed by some centres post-tevr, in practice almost equivalent information can be obtained by ct. the main complications after tevr are endoleaks, type a dissection, paraplegia and stroke. the classification of endoleaks is similar to the classification for evar. type and type endoleaks require treatment by additional endograft coverage with or without supraaortic or visceral artery bypass. other treatment options include the use of branched, fenestrated endografts or the use of chimneys and snorkels. type endoleaks are less common than post-evar. similar to the evar population, intervention is mandated for an enlarging aortic diameter and involves embolisation in most cases. interventional oncology is a discipline that uses imaging-guided procedures in the treatment of cancer patients. when the malignant disease in not curable, interventional techniques such as biliary and oesophageal stenting can provide useful palliation and improve the patient's quality of life. in patients with potentially curable tumours, thermal ablation, cryotherapy and radioembolisation provide useful alternatives to radiotherapy and surgery in carefully selected patients. interventional radiologists who treat patients with cancer should practise as clinicians, participating in multidisciplinary meetings where treatment choices can be discussed with specialists from other oncological disciplines. they should involve themselves in all stages of clinical practice, including pre-treatment consultations, ward rounds and patient follow-up. radiation oncology and interventional oncology have much in common, including the potential for curing cancer using minimally invasive techniques. interventional oncologists can usefully adopt many of the principles and methods of practice in radiation oncology, including quality assurance and the collection of robust outcome measures. an alliance between these disciplines would be beneficial to clinical practice and research in both disciplines. session objectives: . to understand the contribution of interventional radiology to oncology. . to appreciate the areas of overlap between radiation oncology and interventional oncology. . to understand the need for a clinical pattern of practice in interventional radiology in oncology. the current scope and future challenges j.i. bilbao; pamplona/es (jibilbao@unav.es) together with chemotherapy, surgery and radiotherapy, interventional radiology (ir) is the fourth pillar in oncology. transcutaneous and endovascular procedures, guided by imaging, constitute a fundamental knowledge essential for the multidisciplinary management of oncologic patients. the range is wide and covers most of the needs in patient´s care. in short: obtaining samples for making an accurate diagnosis and also to know more about its specific biology (biomarkers); ir covers any possibility needed for vascular access; percutaneous needle ablation is the best alternative in selected patients; endovascular embolisation with "vehiculisation" of therapies is an outstanding method for selective treatment, and sometimes precise ablation, of different tumors; ir is a unique way to offer palliation in a wide range of tumoral complications, such as embolisation for bleeding, stenting for vein obstructions or drainage of fluid collections. there is an obvious need of continuous technical refinement. image-guided therapy is a continuous process that implies many disciplines and that includes every step, from staging through guidance of the procedure to the evaluation of the outcomes, both immediately, during and in the follow-up. future developments in ir may be focused towards the personalisation of therapies to each patient and to a better understanding of the biological mechanisms of tumour response or progression and their image expression. finally, radiologists must be actively involved in the whole process of clinical trials, from the creation of new lines to the performance of therapy until the evaluation and diffusion of the data. radiation treatment has a fundamental role in the multidisciplinary management of people with cancer. the evidence base for radiation therapy is robust and approximately % of people diagnosed with cancer will benefit from radiation treatment. most of this benefit comes from an increase in cure. the technical quality of delivery of radiation treatment is of great importance in avoiding a geographic miss and also in reducing the amount of normal tissue being irradiated unnecessarily. as well as the excellent technical delivery of any treatment offered, of paramount importance is the intelligent integration of care with attention to evidence base choices for both local and systemic treatment. multidisciplinary teams are in the best position to integrate surgery, radiation treatment, interventional oncology and systemic therapy in a planned and deliberate fashion. best practice: how to organise an interventional oncology unit a. gangi, j. garnon, g. tsoumakidou; strasbourg/fr (gangi@unistra.fr) interventional oncology is a fast growing field. interventional oncology is a clinical and technical speciality. solid clinical knowledge associated with the technical skills is mandatory for a successful practice. the technical skills should be associated to the clinical part. the knowledge of all treatment modalities and the participation of a multidisciplinary team is vital for the best practice. every single patient should be seen by the interventional oncologist and followed-up. the interventional oncologist is part of a multidisciplinary team, taking care of the patient. the team includes oncologists, radiotherapists, pain specialists, psychologists, surgeons, and anesthesiologists. the interventional oncology unit should include specialised nurses, technician, anesthesiologist, anesthesiologist nurses, and the interventional radiologist. the team should be able to take care of the patient's follow-up and eventual complications. to summarise, high-quality interventional oncology services are essential for safe and effective patient care. the technical skills of the interventional oncologist should be associated with an excellent clinical knowledge of the disease. a multidisciplinary team work is mandatory for a successful interventional team. harmonisation of training and appropriate credentialing is required for clinical services of the best quality. interventional radiologists continuously improving their skills and knowledge, patient access to safe and effective minimally invasive treatment options is increasing. whereas cardiac ct and mri are routine examinations for specialised radiologists, it has been necessary to wait for the introduction of fast scanning techniques to modify the behavior of nonspecialised radiologists regarding the interpretation of cardiac cavities. the objective of this session is twofold. first, cardiac radiologists will underline the role of these imaging modalities in the assessment of congenital heart disease but also in ischaemic and nonischaemic cardiomyopathies. in the second part of this session, chest radiologists will focus on the diagnostic information accessible at the level of the right ventricle, known to be the target of numerous respiratory disorders. two practical situations will illustrate this approach: pulmonary thromboembolic and chronic respiratory diseases. accurate assessment of the right ventricle (rv) is crucial for the management of congenital heart disease. echocardiography can provide some information, but as the rv sits directly behind the sternum and as many patients have undergone multiple operations, visualisation can be difficult. furthermore, for long-term follow-up and treatment planning, accurate measurement of ventricular size and mass, and valvular flow (tricuspid and pulmonary), and assessment of anatomy in d and d are vital. this presentation will outline the role of cross-sectional mri and ct for assessing the rv, and describing the indications, imaging protocols, technical pitfalls and relevant information for treatment planning. right heart failure in ischaemic and non-ischaemic cardiomyopathies m. grothoff; leipzig/de (matthias. grothoff@herzzentrum-leipzig.de) the role of the right ventricle (rv) has been underestimated for many years. today, we know that the rv is of importance for keeping up a sufficient circulation and that right heart failure in both ischemic and non-ischemic cardiomyopathies can result in hemodynamic compromise. rv ischemia has a higher in-hospital morbidity and mortality but post-infarction chronic right heart failure is a rare finding. as the rv has a different physiology from the left ventricle (lv), also the pathophysiology of ischemia is different here. using our standard cmr tools t weighted imaging for detection of edema and late gadolinium enhancement imaging for detection of necrosis/scar we can find that the rate of myocardial salvage is much higher in the rv than in the lv and that rv failure in the acute phase is basically caused by reversible ischemic effects. in non-ischemic cardiomyopathies like hcm and dcm changes in the rv myocardium mostly resemble changes of the lv. in arrhythmogenic right ventricular cardiomyopathy/dysplasia (arvc/d) however, there are specific findings in the rv and the role of imaging in diagnosing arvc has been strengthened by the revised task force criteria published in . cine imaging should be performed carefully for detection of rv akinesia, dyskinesia or small aneurysms as well as the planimetry of the rv. findings like the detection of fibrosis in lge imaging and the detection of fat in t imaging can provide additional information, but are not diagnostic for arvc. learning objectives: . to learn about the different ct and mri techniques for evaluating right heart morphology and function. . to understand the prognostic impact of right heart involvement in ischaemic heart disease. . to learn about the basic morphological and functional features of different non-ischaemic cardiomyopathies. right heart and chronic respiratory diseases: can ct be used as a onestop-shop? m. remy-jardin; lille/fr (martine.remy@chru-lille.fr) over the last decade, ct technology has evolved towards fast scanning capabilities and high temporal resolution, enabling improved evaluation of the heart and surrounding structures in the course of routine thoracic ct imaging. this has progressively modified the radiologist's implication in the interpretation of chest ct examinations. firstly, it is more and more common to integrate the physiological interactions between heart and lung when analysing the ct features depicted on a given examination. secondly, it is now possible to integrate cardiac functional information into a diagnostic ct examination of the chest, providing prognostic information in the management of patients with a wide variety of chronic respiratory disorders. the purpose of this presentation is to provide non-specialised radiologists with some practical guidelines in the choice of the scanning protocols and range of functional information that can be deducted from chest ct examinations. right ventricular dysfunction and levels of pressure within the pulmonary circulation are the key points of such approaches. learning objectives: . to appreciate the clinical impact of a cardiothoracic evaluation from the same ct examination. . to learn about the scanning protocols enabling such a combined analysis. . to understand its compatibility with other non-invasive modalities. rv and prognosis in pulmonary thromboembolic disease n.j. screaton; cambridge/uk (nicholas.screaton@papworth.nhs.uk) right ventricular failure is the most common cause of early death following acute pulmonary embolism and in patients with chronic thromboembolic pulmonary hypertension. echocardiography is sensitive in diagnosing and quantifying rv dysfunction. ct is the reference standard for the diagnosis of acute pe diagnosis and has the potential to provide comprehensive evaluation of the pulmonary arteries, heart and lung parenchyma. ct signs of right ventricular dysfunction which have shown predictive value for adverse outcome include: flattening of the inter-ventricular septum or bowing towards the left ventricle, reflux of contrast medium into the ivc, relative rv/lv diameter ratios on transverse and -chamber reconstructions, and ventricular volumetry as assessed both on routine non-gated ctpa and ecg-gated ct. in patients with cteph, mri permits imaging of the pulmonary vasculature and functional evaluation of the right ventricle and pulmonary circulation, enabling both morphological assessment and prognostic evaluation. learning objectives: . to learn about clinical and imaging factors associated with prognosis of thromboembolic disease. . to understand the benefits and weaknesses of different imaging modalities in predicting prognosis in thromboembolism. . to discuss the merits of comprehensive imaging evaluation in the routine diagnostic workup of suspected thromboembolic disease. multimodality imaging including ultrasound has within recent years been introduced in several anatomical regions. pet, ct and mri datasets can after an initial co-registration be fused and shown either side by side or using overlay on screen while doing real-time ultrasound; thus, the pet, ct or mri dataset is reformatted in a projection to fit the real-time ultrasound images. several methods of aligning the images are available and have been shown to have a high accuracy. image fusion involving ultrasound has been tested in phantoms, animals and in patient studies, mainly in abdominal imaging. by combining several imaging modalities, it is possible to benefit from the strengths of each modality. it is useful for characterisation of and intervention on liver lesions, abscesses containing air and lesions in areas with poor overview by ultrasound. also, the method is useful for characterisation and biopsy of pet-positive lesions, especially in patients with a history of cancer. the background of the method and clinical examples, mainly from abdominal applications, will be covered. also, perspectives and future research topics will be highlighted. contrast-enhanced ultrasound (ceus) has proved to improve the detection and characterisation of pathologies compared to conventional ultrasound, ct and mri in a number of indications. ultrasound contrast agents (uca), which are purely intravascular, do not show any interstitial diffusion or glomerular filtration like iodinated complexes or gadolinium chelates. dynamic contrastenhanced ultrasound (dce-us) allows to display the enhancement of a lesion with a high frame rate after bolus or infusion administration of uca, and to compare enhancement profiles between normal and abnormal tissue. quantification of dce-us is useful to quantify tumour enhancement and to limit intra-and interobserver variability. mathematical models with several perfusion parameters can be used. dce-us has shown to be of interest after antiangiogenic therapies as it allows an earlier evaluation of tumour response than usually done with ct and mri, which remain mainly based on the recist criteria. the common perception of d ultrasound (us) is of surface-rendered images, especially of the foetus. the same approach, enhanced by new transducer technology and software, can be used to take ultrasonography to another level in general body imaging, providing different image presentations and working practices similar to those of ct and mr. the technology involved in a us volume acquisition was represented initially by mechanical d transducers, and more recently by purely electronic, matrix probes. this latest technology allows bi-plane real-time acquisitions, fast switch to volume acquisition up to degrees, and d acquisitions with acceptable frame rates. protocols have been described for major abdominal and retroperitoneal organs, with fast optimisation of acquisition settings. the technology supports contrastenhanced ultrasound (ceus). after volume acquisition, interpretation for volume us datasets requires a post-treatment phase, including multi-planar reconstruction, multislice imaging, and volumetric analysis. virtual cystoscopy and volume ceus quantification are new options. the implementation of this new, efficient us modality in a radiology department supposes deep changes in the daily practice with delayed post-treatment reporting times. it should represent a more effective way for comparison between different examinations and a better communication tool with clinicians. the proven and potential benefits, in terms of clinical accuracy, training, workflow and overall efficiency, will be discussed. the purpose of this lecture is to emphasise some pitfalls in liver imaging. morphologic changes in the liver are usually attributed to chronic liver disease where liver cirrhosis represents the most important cause. however, noncirrhotic diseases may also induce atrophy-hypertrophic changes of the liver. the most common mechanisms are related to venous obstruction (either portal or hepatic venous) and biliary obstruction. multidetector ct and mr imaging are essential to highlight these abnormalities. when dealing with liver tumours, the most important question that has to be solved is tumour characterisation. yet, it is often difficult to assess whether a large tumour is intra-or extrahepatic. imaging findings that might be helpful will be shown. last, some liver lesions can mimic liver tumors. vascular disorders and focal fatty changes or focal fatty sparing are the most common causes. some other conditions can be also mimickers and such cases will be shown. the technique and the anatomy of the bile duct and pancreatic duct will be described. the anatomical variants of the biliary duct and the pancreatic duct system will be analysed and their possible role in generating diagnostic imaging pitfalls described. strategies to avoid pitfalls in diagnostic imaging of the bile duct and the pancreatic duct system will be illustrated, considering the possible source of pitfalls. diagnostic imaging findings of different diseases involving the biliary ducts and pancreatic duct system will be illustrated, as well as the diagnostic imaging criteria useful for the differential diagnosis. over the last two years, the number of ct and mri units has increased by %, and modern pet centers and leading centers for radiotherapy have been built. we can identify an approximately % increase in the number of radiological research projects--mainly ultrasound, ct, and mri investigations. during the last ten years the total number of vascular interventions and mr studies has increased by ten times, four times for ct, and the annual growth of us and x-ray investigations is about %. unfortunately, these technical innovations are not always accompanied with pacs and ris installations; this is a reason why all advantages of digital equipment are not achieved. we see rapid development of private medicine; new private hospitals and ambulances have grown by more than % and investment companies are looking for new projects in this field. however, the professional education of radiologists is not enough to work with new diagnostic equipment. this is a reason why in we will start a pilot project to create a new system of continuing medical education in clinical medicine, including diagnostic radiology. we hope, this pilot project will increase the efficiency of clinical practise. differential diagnosis (dd) including tumour and non-tumour brain pathologies is an integral part of neuroradiological diagnostics and in some cases is a challenge to experienced neuroradiologists. more than patients with different cns pathologies have been investigated in the department of neuroradiology, burdenko neurosurgical institute since . in the vast majority of the cases, there were tumours. we used deconvolution method for bv, bf, mtt and ps maps reconstruction on commercially available software (perfusion . . , . protocols, adw, ge). ct perfusion has demonstrated high level of information in determining the degree of malignancy in glial brain tumours. a strong correlation between bv and ps and tumour degree has been demonstrated. the use of ct-pwi makes it possible to successfully carry out dd between radiation necrosis and tumour progression. some histological types of brain lesions are characterised by unique haemodynamic properties which enable using this method as non-invasive "biopsy". ct-pwi has been especially useful in dd of the skull base region, bone and extracranial pathologies. the absence of artefacts created by the skull base bones makes this method especially valuable as compared to the mri t *-and asl-perfusions. ct-pwi makes it possible to successfully differentiate tumours and a number of non-tumour cns lesions including demyelinating diseases, infectious and non-infectious granulomas, etc. ct-pwi is a powerful method for differential diagnosis of brain pathology. t-pwi can provide unique functional information regarding tumour pathophysiology and haemodynamics, which are not available with routine ct and mri. learning objectives: . to become familiar with the technique of brain perfusion ct. . to understand the added diagnostic value of perfusion ct. . to learn about input of ct perfusion for assessment of treatment. interlude: development and use of web-based teleradiology in russia o.s. pianykh; newton highlands, ma/us (opiany@gmail.com) the largest territory in the world, russia, presents a perfect teleradiology use case of extremely unevenly distributed health care, concentrated in moscow and spread thin outside over an enormous area and sparse population. this unevenness deeply affects the quality and availability of radiological services, and cries out for efficient and practical teleradiology solutions. however, the same unevenness in medical expertise, financing and it infrastructure frequently acts against the advancement of teleradiology projects, blocking their natural progress. as a result, technical, financial, educational and clinical matters, interleaved into the nascent russian teleradiology ventures, require serious and predictable solutions, based on analysis and adaptation of already developed, internationally proven strategies. currently, russian teleradiology simply takes advantage of whatever is available to make its progress better, but needs to develop itself up to the tasks it faces. tuberculosis in russia: a challenge for a national radiological service i.e. tyurin; moscow/ ru (igortyurin@gmail.com) approximately, . billion people worldwide are infected with mycobacterium tuberculosis, of which million are active cases. the reasons for resurgence of tb infection include the hiv epidemic, a rise in reactivation disease in the elderly, a growing migrant population and spread of drug-resistant strains. the incidence of atypical tb infection is also on the rise, of which mycobacterium avium intracellulare is the most important human pathogen. the pathologic form of the pulmonary infection depends on the sensitivity of the infected host and is classified as primary or postprimary. primary tb pattern represents infection resulting from recent contact with the pathogen. postprimary tb pattern results from reactivation of a dormant focus within the lungs. thoracic tuberculosis produces a broad spectrum of radiographic abnormalities. the radiological patterns had been described as parenchymal, airway, vascular, mediastinal, pleural, and chest wall lesions. common causes of a missed diagnosis of thoracic tuberculosis are failure to recognise hilar and mediastinal lymphadenopathy as a manifestation of primary disease in adults, overlooking of minimal productive lesions or reporting them as inactive, and failure to recognise that an upper lobe or superior segment of lower lobe mass might be tuberculosis. in aids patients, the imaging features depend on the degree of immune suppression. a pattern of postprimary tb is also usually seen among patients with decreased immunity due to alcoholism, renal failure, diabetes mellitus, ageing, malignancy, and renal and cardiac transplantation. learning objectives: . to understand the scope of the problem with tuberculosis screening in the russian federation. . to learn about the changing imaging patterns of thoracic tuberculosis. . to appreciate the current role of imaging in the differential diagnosis and follow-up of this pathology. interlude: mystery of denisov's cave and paleoradiology m. mednikova; moscow/ ru (medma_pa@mail.ru) this study focuses on the anatomical identification of fossil bones from altai highland in southern siberia, their radiological description, and parallels among other hominin fossils. methods describe the small and isolated tubular bones. we used microct versaxrm- by xradia inc. and digital microfocus x-ray. denisova cave is the best studied paleolithic cave in north asia. archaeological data suggest that about thousand years before the present, a group of humans migrated to southern siberia from the west. their descendants had lived in the altai mountains in relative isolation for thousand years. the taxonomic status of the early inhabitants of southern siberia was clarified thanks to palaeogenetic studies. it was concluded that the altai hominin was genetically twice further from modern humans than were neanderthals. phylogenetic analysis suggests that this clade diverged from that ancestral to humans and neanderthals very early -about billion years ago. descendants of this clade apparently survived in the altai refugium until the period - thousand years ago. due to structural patterns of preserved pedal and manual phalanxes, humans from denisova cave could be expected to be the bearer of "archaic" traits. the extraordinarily thick walls of tubular bones in adults reflect a high level of occupational stress. radiological volumetric microscopy of the denisovan girl phalanx gave evidence for the histological estimation of the developmental age. radiological methods seem to be the perspective approach in the study of rare and fragmentary fossil human remains, differentiating between archaic and modern humans. advances in imaging of pancreatic masses g.g. karmazanovsky; moscow/ru (karmazanovsky@ixv.ru) modern diagnostic radiology allows not only to detect pancreatic tumours, but also to carry out their differential diagnosis with high accuracy. this is especially important because many benign tumours of the pancreas do not require immediate surgery. at the same time, many benign tumours may become malignant. the differential diagnosis of the pancreatic cystic lesions using endoscopic ultrasound and magnetic resonance pancreaticocholangiography has now become particularly accurate. contrast enhancement allows detecting signs of tumor invasion into the main blood vessels and adjacent organs. modern developments of radiology help to use extended operations for malignant tumours and sparing surgery with minimal removal of intact functioning pancreatic tissue in benign tumours. learning objectives: . to become familiar with major types of pancreatic masses and their radiological manifestations. . to understand approaches to the selection of diagnostic pathways in pancreatic tumours. . to become acquainted with new developments in diagnostic imaging of pancreatic tumours. interlude: an artistic view of ct a.l. yudin; moscow/ ru (prof_yudin@mail.ru) radiology is a specialty based largely on figurative perception of diagnostic imaging. the radiological picture of many symptoms reminds one of objects and environmental phenomena (for example, vanishing lung, draped aorta, geographic liver, porcelain gallbladder, dirty fat and others). training of creative mentation promotes lasting assimilation of educational material at the associative level. metaphorical thinking skills can also be improved by searching for amusing fragments in radiological images similar to the objects in everyday life; animals, cartoon characters, and others. the essential help in the study of the physical foundations of radiology and functional capabilities of workstations provide the execution and study of x-ray films, ct or mri of fruits and vegetables, flowers, various artifacts and other objects in the environment. eventually, it is just beautiful. ultrasound of the breast is an established imaging technique with several advantages. it has been used to differentiate solid from cystic breast lesions for a long time. it has also been increasingly used to visualise small lesions in mammographically dense breasts and is the initial imaging method of the breast in young women. the features of the lesions that need to be analysed are: shape, relation to anteroposterior to laterolateral diameter, margins, internal structure and absorption of sound (distal acoustic phenomena). color doppler enables the thorough assessment of flow within the breast lesions. elastography is established as a useful method to differentiate breast lesions on the basis of their stiffness, which can be quantified. the accurate staging of axillary disease is an important aspect in the management of patients with breast cancer. it is recognised, however, that underlying malignancy can be found in lymph nodes that appear morphologically normal. a variety of morphological features that may be seen in pathological nodes have been described (cortical thickness of > . mm and absence of a fatty hilum). the automated breast ultrasound technique has been known for a long time, but with recent improvements now may play an important role. the automated breast volume scanner (avbs) employs frequencies of - mhz. avbs has various major advantages, such as being independent of the experience of the operator as well as supplying consistent and reproducible results. additionally, for the first time it has become possible to obtain coronal images of the complete breast, which greatly assists in the planning of surgical interventions. to study the technical basics in breast ultrasound (us), a breast scanning phantom helps to understand different us settings of greyscale imaging. typically, breast us work has a linear array transducer with a minimum field of view of . cm and a high frequency of minimum mhz. a broadband transducer (e.g. - mhz) with different bands is preferred. in the central axillary area, a lower frequency band offers a deeper penetration depth. high frequencies improve the tissue contrast and optimise the axial and lateral resolution. the transmitter focus is adapted to the region of interest. highly sensitive color doppler detects slow flow rates ( cm/s and less). for frequencies and power settings used in diagnostic greyscale and color doppler studies, no safety limitations have to be considered. breast us is mainly used as a second-line imaging tool to mammography (mg). a correlation between both imaging modalities is crucial. skin markers and additional mgs may help to solve the correlation problem. in bi-rads or us lesions with unclear correlation in mg, a marker placement after us-guided large-core needle biopsy helps to clear the problem. the pathomorphological growth pattern of a lesion is the basis to understand different imaging aspects with different modalities. second-look us after mri is an important correlation of lesions, which were first visible with mri. understanding the complementary imaging criteria will help to reduce the number of false-positive results. a practical imaging approach to brain and neurovascular trauma will be reviewed, with an emphasis on understanding the correlation between pathophysiology and imaging signs. guidelines on when to order acute neurovascular studies will be presented. special technical considerations to help optimise ct and mr imaging protocols for suspected brain injury, cns haemorrhage, and arterial dissection will be discussed. neurological emergencies are often associated with high morbidity and mortality, and thus require prompt diagnostic and therapeutic action. nontraumatic emergencies may however have a subacute onset, and radiological signs may be subtle, which can lead to delay in diagnosis and treatment. since clinical features are often nonspecific, the radiologist may be the first to point the clinician in the direction of the correct diagnosis. it is therefore of great importance that the radiologist is aware of and familiar with the various imaging findings, on both computed tomography (ct) and magnetic resonance imaging (mri), of non-traumatic neurological emergencies. these include vascular, infectious and inflammatory diseases. commonly encountered emergencies are ischaemic and haemorrhage stroke, venous thrombosis, arterial dissection, abscess, acute disseminated encephalomyelitis (adem), and encephalitis. radiological findings in rarer diseases may mimic those in the more commonly occurring diseases, but need to be correctly interpreted as therapeutic strategies and prognosis may be entirely different. such entities include for instance posterior reversible encephalopathy syndrome (pres), reversible cerebral vasoconstriction syndrome, susac's syndrome, and status epilepticus. furthermore, initial findings of (impending) complications of brain disease, such as hydrocephalus and herniation of brain structures, may be subtle, while early recognition allows for prompt and adequate intervention. finally, diagnostic and therapeutic interventions performed in an emergency setting may interfere with the diagnosis and interpretation of clinical and imaging findings. associated limitations and pitfalls therefore need to be recognised to avoid false-negative or false-positive diagnosis, respectively. learning objectives: . to learn about the modalities (ct/mri) and protocols for non-traumatic neurological emergencies. . to learn how to diagnose the main non-traumatic neurological vascular and non-vascular emergencies. . to become aware of the pitfalls and limitations of clinical presentation and imaging findings in non-traumatic neurological emergencies. the current century has brought with it new challenges in radiation protection, many of which follow the development of mdct which greatly enhanced diagnostic capabilities and substantially reduced scanning time to just a single breath-hold for chest ct, making ct scanning both patient-friendly and the physician's preferred tool. ct has also been added to nuclear imaging systems to create hybrid scanners (pet/ct; spect/ct image gently years later: lessons learned in radiation protection for children. the alliance for radiation safety in pediatric imaging was founded in to promote radiation protection for children worldwide through awareness, education and advocacy. comprising over medical professional societies and agencies, the alliance seeks to change practice locally for improved paediatric patient safety in medical imaging. since its inception, the alliance has had campaigns in ct, diagnostic and interventional radiology, nuclear medicine, digital radiography and an outreach campaign to parents and educational summits. yet, there is still work to be done. there is a need for parents and patients to receive information about their imaging test prior to the performance of imaging procedures, particularly those involving ionising radiation. the paediatric medical imaging community should work tirelessly with the manufacturers of imaging equipment to tailor equipment for children to optimise the study and ensure that the users of the equipment are knowledgeable in its safe use in children. the routine display of size-specific dose estimate on ct scanners will better estimate patient dose for quality improvement within facilities and in dose registries. finally, there is a need for diagnostic reference levels in paediatric radiology. this presentation will update the audience in progress to date regarding these challenges. the image wisely programme continues to move forward, guided largely by its steering committee, composed of two representatives each from acr and rsna and one representative each from aapm and asrt. the image wisely website (www.imagewisely.org) has educational content for imaging professionals (radiologists, medical physicists, and technologists) and referring physicians. a patient tab features links to radiologyinfo.org and the image gently website. a tab for "my equipment" links visitors to radiation dose-related 'microsites' developed by ge, hitachi, philips, siemens and toshiba. as of august , , , individuals, facilities and associations have taken the image wisely pledge. to attract traffic to its website, image wisely has recently instituted 'news' and 'top reads' sections on the splash page highlighting recent articles and announcement, highlighting breaking news coverage and journal publications on relevant topics. in , content on nuclear medicine procedures was finalised, completing two of the three targeted foci of the initial action plan_ct and nuclear medicine. in october , a launch meeting will initiate the process of developing content for the third target area, fluoroscopy. in and , image wisely has concentrated on efforts to engage referring physician communities, with particular interest in paediatricians and emergency medicine physicians. progress has been slow, but has recently gained traction with emergency medicine in the form of radiologist participation in a symposium, diagnostic imaging in the emergency department: a research agenda to optimise utilisation, organised by the society of academic emergency medicine. learning objectives: . to learn about the image wisely campaign for radiation protection of adults. . to understand the lessons learnt while communicating messages. lessons from a national approach to patient safety in radiation protection p. cavanagh; taunton/uk (petecavanagh@gmail.com) in considering a european campaign on radiation awareness, it is useful to gain information from similar campaigns in health care. there have been a number of national patient safety campaigns based on the institute for healthcare improvement (ihi) , lives campaign initiated in the usa in . following the success of this, a similar campaign was launched in england. part of this process included an analysis of the success of the programme and the key interventions and drivers that were considered essential at both the national and local level. these included strong leadership, . bone (pseudo)-tumours: the majority of bone tumours can be detected on plain radiography. the age of the patient, location of the tumour in a bone and history of pre-existing bone abnormality should be included in determining the likely diagnosis. careful analysis of pattern of bone destruction, periosteal reaction and matrix mineralisation allow for characterisation of most bone tumours and differentiation from pseudotumours. ct may be useful for osteoid osteoma and mri is the best imaging technique for further diagnosis and staging by displaying tumour composition and extent of bone marrow involvement, including skip lesions, presence and extent of extraosseous soft tissue mass, and involvement of neurovascular bundle, muscle compartments and adjacent joint. this allows to find the best biopsy and surgical approach. to evaluate local control of disease and for detection of local recurrence, mri is usually the best imaging technique. . soft tissue (pseudo)-tumours: the majority of soft tissue tumours can be detected on ultrasound. except for cysts and subcutaneous lipoma, mr will be the next imaging technique for diagnosis, local staging, and eventually to find the best biopsy and surgical approach. the age of the patient, location of the tumour and careful analysis of the signal characteristics on mri allow for characterisation of many soft tissue tumours and differentiation from pseudotumours. plain radiography and ct may be useful for detection of calcifications and myositis ossificans. to evaluate local control of disease and for detection of local recurrence, ultrasound and mri are the best imaging techniques. in this honorary lecture, i will review a number of personal impressions that may contribute to the successful performance of research projects in cardiovascular radiology. also, issues and obstacles in performing successful research in the field of radiology will be considered. key factors for success include guidance by inspiring mentor, genuine interest and motivation, some creativity and serendipity. radiology has developed tremendously with many innovative modalities over the last years, providing ample opportunity to participate in clinical research. potential issues that should be addressed are subspecialisation, turf battles, competition from other clinicians/ imaging specialists and adequate training in radiology research. the field of imaging research includes traditionally more clinically oriented research by focussing on developing and testing of new modalities and applications, now becoming more basic by including molecular imaging, population imaging, outcome studies and alike. silicone-filled implants (single or double lumen) require a dedicated sequence where silicone exhibits a high signal intensity, whereas signals from fatty and fibro-glandular tissues are cancelled. diagnosis of intracapsular rupture relies on the detection of a linguine sign (direct sign) or multiple "key-hole" and/or " teardrop" images (indirect signs). extracapsular rupture is defined as the presence of silicone outside the capsule (breast, soft tissues, lymph nodes). breast reconstruction after mastectomy may involve autologous tissue flaps (skin, fatty tissue, muscle and fascia). the transferred muscle is inserted in front of the major pectoralis muscle and enhances after contrast medium injection. the most common benign findings seen in such reconstructed breasts and also after a breast-conserving treatment are oedema, seroma, haematoma, fat necrosis and fibrosis. diffuse thickening of the skin and trabeculae is usually observed the first year after completion of radiation therapy. small focal areas (less than mm) of non-mass-like enhancement and thin linear or rim enhancement at the lumpectomy site can all be expected findings. these benign findings decrease progressively, but residual enhancement may be observed in % of women at or more years. in patients who were switched from tamoxifen to aromatase inhibitors, a stronger or re-appearance of a background enhancement may be observed. before classifying such findings as benign or probably benign, clinical examination and standard imaging data must be taken into account. highly suspicious lesions in such patients are similar to bi-rads lesions in the nontreated breast. prevention strategies for women at high lifetime risk of breast cancer are usually adapted to the individual woman's risk of breast cancer. women at high risk (brca mutation carriers or women with a % likelihood of brca-heterzygosity) are offered primary prevention, which includes chemoprevention by tamoxifen or surgery (risk-reducing mastectomy and/or salpingooopherectomy, where the latter also helps reduce the risk of subsequent breast cancer by %). if women opt for secondary prevention (active surveillance/screening), this has to start at at the latest. mri is considered a compulsory component of all programs worldwide. due to the very limited added cancer yield of mammography in this subset of women, and because of the still unsettled issue of possibly increased radiosensitivity of brca-mutation carriers, mammographic screening is not recommended until the age of . there is broad agreement that (at least) an annual screening is important; especially for brca mutation carriers, screening every months may be more appropriate. we recommend interleaved screening, with annual mri and annual ultrasound (± mammography) phase-shifted by months. there are important differences between brca -and brca -associated cancers in terms of age distribution and incidence rates, histologic features, but also specific imaging features which must be known by radiologists. mri screening protocols must be adjusted to the specific needs of this (usually very young) screening population. this presentation will review the current evidence with respect to screening of women at high familial risk of breast cancer and will provide information on all aspects mentioned above. chest trauma is directly responsible for % of all trauma deaths and is a major contributor in another % of all trauma mortality. blunt trauma, accounting for % of chest injuries, is the third most common site of injury in polytrauma patients. plain radiographs still have a role in recognition of some acute thoracic pathology that requires immediate further management, either diagnostically and/or therapeutically, such as tension pneumothorax, major transdiaphragmatic herniation, large hemothorax or obvious mediastinal hematoma. mdct of the chest is now typically included in a whole body scan with iv contrast to facilitate rapid diagnosis on polytrauma cases using less radiation than selected segmental scans. mdct is the well-proven diagnostic gold standard for chest injury evaluation. the major advantages of mdct over other modalities include identification of active bleeding, direct signs of trachea or esophageal injury, direct evidence of major arterial vascular injury, such as pseudoanurysms, pneumo and hemopericardium, location and extent of lung contusion and laceration, and assessment for thoracic spine, shoulder girdle and rib fractures. diaphragm injuries are well depicted by mdct, especially on the left by identifying both the torn diaphragm edges, herniation and constriction of abdominal contents at the level of the torn diaphragm (collar sign), and direct contact of herniated structures with the posterior chest wall (dependent viscera). tracheal injuries are suggested by diffuse and progressive pneumomediastinum, dilated tracheostomy cuff, ectopic endotracheal tube, and direct connection of mediastinal air with the trachea lumen. ct-angiography eliminates the majority of indications for diagnostic catheter angiography. pulmonary symptoms such as chest pain, shortness of breath or wheezing are common non-traumatic symptoms prompting er visits. because clinical symptoms are very non-specific, imaging plays a major role in differentiating life-threatening from less severe diseases and forming a diagnosis. the chest radiograph remains the first imaging despite its limited sensitivity for certain diseases and being prone to inter-observer variability. comprehensive cardiothoracic ct examinations using most modern ct equipment are well evaluated in their diagnostic accuracy to determine the presence of vascular life-threatening events such as aortic dissection, acute coronary disease or pulmonary embolism. protocols and literature evidence will be discussed. the main focus of the course, however, will lie on the analysis of pulmonary ct findings and its contribution to the differential diagnosis of pulmonary emergencies (e.g. pneumonia, oedema, pneumothorax, exacerbation of fibrotic or obstructive lung diseases) and how to further integrate imaging findings, laboratory findings, patient history and clinical information to tackle the differential diagnosis. imaging findings will be discussed by clinical case studies, key findings and also overlapping morphological features of other differential diagnosis will be discussed side by side, illustrating the options and also limitations of imaging findings. mentor was first introduced in greek mythology, and in its modern usage first recorded by a french writer, françois fénelon, in . since then, this concept has been widely used in the development of mentoring, mentorship and more recently of mentees, with an overarching principle based on accompanying, sowing, catalysing, showing and harvesting. this concept remains today as a fundamental one in all teaching activities and implies generally a close contact between the mentor and the mentee. however, the development of internet with concomitant e-learning capabilities, which are hugely increasing, raises the very challenging necessity to re-think this concept and to adapt it to this new era. the esr is very concerned by this endeavour in the context of the striking development of esor, on one hand, and with the launching of its e-library, on the other. n. gourtsoyiannis; athens/gr (gournick@gmail.com) the presentation "esor in action" gives an overview on all esor activities in and . a detailed report on the esor courses and teaching programmes in is presented, containing statistics about the number of course participants and of scholarship and fellowship grants. additionally, all educational activities in , including dates, venues, topics and local organisers, are announced. evidence-based radiology: the basics evidence-based medicine (ebm) was derived from clinical epidemiology during the last century. it "is the conscientious, explicit, and judicious use of current best evidence in making decision about the care of individual patients" (dave l. sackett, ) . this means integrating ( ) individual clinical expertise with ( ) the best available external evidence from systematic research and ( ) patient's values and preferences. when considering evidence-based radiology (ebr), the needed expertise is not only clinical, but also technical, while ( ) radioprotection issues assume a relevant value according to the "as low as reasonably achievable" (alara) principle. ebm (and ebr) can be practised according to the "top-down" model, when using guidelines issued by governmental, professional, or academic bodies, or the "bottom-up" model, when local physicians ( ) formulate an answerable question, ( ) search for the best evidence; ( ) appraise critically; ( ) apply findings to practice; and ( ) evaluate the performance. a hierarchy of radiological studies has been established according to the investigated matter: . technical performance; . diagnostic performance; . diagnostic impact; . therapeutic impact; . patient outcome; . societal impact. different degrees of recommendations are based on different levels of evidence, with experts' opinion as the lowest level and meta-analyses of high-quality homogeneous studies and multicenter studies being the best level of evidence. to practise ebr, radiologists should be familiar at least with basic statistics and epidemiology as well as of methods for study design, thus recognising the principal types of bias which can limit the value of published studies. learning objectives: . to understand the historical development and general principles of evidence-based medicine (ebm) with its top-down and bottom-up approaches. . to learn how to apply ebm principles to radiology (evidence-based radiology, ebr) and to illustrate the main reasons for the relative delay in developing ebr, including the challenges of fast technological innovation in medical imaging. . to learn about the relationship between levels of evidence and the strength of recommendations for diagnostic imaging and interventional radiology. . to learn how radiologists could play a stronger role in building the evidence in favour of diagnostic imaging and interventional radiology, taking the patient's interest as the primary aim of clinical practice and science. education in research: action plan j. hodler; zurich/ch a survey regarding education in research has been commissioned by the esr and published in insights imaging ( ) : - . the results indicate that education in research, associated with career models, needs promotion. the research committee of the esr is working on possible future steps to promote research through education. several problems will have to be addressed, most notably inhomogeneity within europe, motivation issues, illdefined career paths as well as funding issues. several stakeholders will play an important role, including scientific societies, although this is the core business of academic radiology chairmen. most young professionals starting a career in academic institutions are eager to expand their professional and personal aptitudes. an effective way to support young professionals in this regard is by mentoring. mentorship is a relationship where the mentor supports a junior faculty member (mentee) in personal and professional development. the mentee benefits from early determination and initiation of career-relevant steps, greater productivity in research and publishing activity and developing techniques in networking and collaboration. moreover, the mentee gains perspectives on how his/her discipline operates academically, socially and politically, improves self-efficacy and deals more confidently with challenging intellectual work. the mentor, a knowledgeable, experienced and regarded person, benefits from fresh ideas, energy and curiosity of mentees, as well as through acceptance as a mentor an enhanced status in the department. it is a trusted relationship of dialogue, learning and challenges, based on mutual interests. however, the mentor is not automatically the best friend or the sole exclusive advisor of the mentee. more and more academic medical institutions offer facilitated mentoring programmes, which help the mentoring pairs to create an effective mentoring relationship to accomplish the desired skills. evaluation of faculty mentoring programmes in academic medical institutions demonstrates the importance of mentoring in research and academic development as well as in patient care. especially in radiology where over many years there have been challenges in recruiting and retaining talented young professionals, mentoring is considered as an essential way for preparing the next generation of scientific and intellectual leaders. pitfall: "a hidden or unexpected danger or difficulty". imaging methods can provide an extraordinary amount of useful data to specialists treating head and neck (cancer) patients. it is crucial that these data are used to full advantage of individual patients. the most important factor in this process is mutual cooperation between the physicians in charge of patient care and the diagnostic imaging specialist. pitfalls in the head and neck may present in various ways: normal variants may look like disease, incidental findings are frequently encountered and suboptimal technique may obscure important findings. moreover, many pitfalls are directly related to technical errors. the presentation aims to familiarise general radiologists, who have an interest in head and neck imaging, with common pitfalls encountered on ct and mr studies focussing on the neck. in an interactive setting, examples from daily practice will be discussed. imaging of the skull base and maxillofacial skeleton requires a meticulous imaging technique and a good knowledge of normal anatomy and possible anatomical variants. asymmetry in the pneumatisation of the paranasal sinuses, skull base or temporal bone is a common reason for misinterpretation. for example, hypoplasia of the maxillary sinus may be misinterpreted on conventional radiography as maxillary sinusitis or orbital blowout fracture, depending on the context; asymmetric pneumatisation of the petrous apex or mastoid bone may mimic, respectively, a cholesterol granuloma and fluid effusion in the non-pneumatised side on mri. vascular variants may also cause interpretation problems. for example, turbulent flow in a large jugular bulb may mimic a jugular foramen tumour on mri. variants in the vascular plexus surrounding the trigeminal or facial nerve may occur, and cause asymmetric findings on mri, possibly mimicking neuritis or perineural tumour spread. incomplete maturation or arrested development of skull base structures may also cause confusion. examples are the cochlear cleft, not to be confused with otosclerosis, or arrested pneumatisation of the sphenoid sinus, possibly mimicking a tumoural lesion in the central skull base. to avoid problems, one should keep in mind the existence of such variants, while correlating the imaging findings with the clinical problem; in some cases, an additional imaging study may be needed to exclude a pathological process more confidently. this short -min introduction by the session chairman will give an overview of the current state of cardiac computed tomography (ct) for diagnosis and prognosis. in addition, the introduction will provide the basis for the subsequent dedicated lectures covering low radiation dose, diagnostic accuracy, and incidental findings in cardiac ct. what are the protocols with the lowest radiation dose in clinical practice? j.-f. paul; le plessis robinson/fr (pauljf@ccml.fr) the radiation dose delivered for coronary ct angiography using retrospective gating is high, because only a small part of the total radiation delivered is used for the reconstruction of the image in the retrospective mode. on average, % of the radiation burden is used to reconstruct one phase of the cardiac cycle. ecg-triggered tube current modulation allows reducing the nominal dose by up to % in the systolic phase. another approach for reducing radiation exposure is to use prospective, sequential acquisition, with this approach being associated with % dose reduction compared to the spiral retrospective acquisition. exposure time may be also shortened by an increase of pitch, in particular on the dual-source ct. however, applicability to each dose-sparing technique depends on the heart rate and its regularity. dose-sparing strategies should be modified in case of high or irregular heart rate and radiation dose reduction may be less effective. for coronary ct angiography, individually weight-adapted protocols have been successfully applied, by adjusting mas to patient's weight. more recently, settings of kv and even kv have been successfully used for cardiac studies, especially in slim patients or children. reduction of exposure time and individual adaptation have an additive effect on dose reduction: it has thus been possible to scan down under msv in selected, slim patients, using this combined approach. in many cases, using the latest technology, radiation dose may be lower than the mean radiation dose associated with conventional angiography. learning objectives: . to understand various protocols to lower radiation dose in cardiac ct with regard to the clinical situation and the risk of image quality impairment. . to learn how to tailor the radiation dose level to each patient in terms of morphology. . to become familiar with modulating exposure windows in regards to a patient's ecg. how accurate and prognostically valid is coronary ct angiography? f. cademartiri, e. maffei; monastier di treviso/it (filippocademartiri@gmail.com) the role of cardiac computed tomography in cardiovascular diseases is becoming increasingly important. cct is a robust and reliable investigation for the detection and exclusion of significant coronary artery disease. in addition, cct provides reliable noninvasive information concerning coronary plaque burden (severity, distribution, type), morphology and function of left and right ventricle, valves, aorta, and so forth. in the past years, the prognostic role of cct has been established. the prognostic information that can be extrapolated from cct is very diverse and most of it is still under investigation. there are converging evidences that cct can stratify cardiovascular risk better than conventional clinical methods, especially in symptomatic patients. for asymptomatic individuals, the role is still controversial since coronary calcium score alone has a very important role already. several aspects of cct information seem to have importance for prognostic stratification: plaque presence, obstruction, plaque type and distribution. more recent studies have started showing the relationship between cct and pharmacological treatment. this is a very new and appealing topic, since the evidence is towards the fact that the most effective pharmacological treatment (e.g. statin) should be restricted to patients with at least some nonobstructive cad as detected by cct. this might become a revolutionary concept in cardiovascular medicine with several implications. learning objectives: . to learn about and integrate the prognostic information from coronary ct angiography into conventional methods. . to learn about coronary ct angiography and conventional methods. . to appreciate the prognostic impact of coronary ct angiography and conventional methods. incidental findings in cardiac ct: how to report and proceed s. leschka; st. gallen/ch (sebastian.leschka@kssg.ch) rapid advances in computed tomographic (ct) technology have facilitated the widespread use of ct for cardiac imaging worldwide, and can be considered nowadays an essential part of the clinical workup of patients with suspected coronary artery disease. albeit that the performed ct study is focussed on the cardiac structures and the coronary arteries, adjacent noncardiac structures are in the field of view whenever a patient undergoes cardiac ct to quantify coronary calcium or to perform a noninvasive coronary angiogram. in addition, the location of the heart near other anatomic regions, including the lungs, mediastinum, upper abdomen, and bones, necessitate that these structures are included when acquiring coronary ct angiographic images. several publications have demonstrated a high frequency of incidental findings on coronary ct angiography. the availability of this information is part of an ongoing clinical debate. while some radiologists believe that every image should be interpreted completely, others believe that examining noncardiac structures reveal too many incidental findings of uncertain clinical significance, which may harm because additional testing increases risk, cost, and patient anxiety. the aim of this lecture is to separate solid facts from opinions and beliefs. the diagnosis of pulmonary embolism (pe) is usually established by a combination of clinical assessment, d-dimer testing, and imaging with either pulmonary ventilation-perfusion (v/q) scintigraphy or pulmonary multidetector ct angiography (ctpa). v/q scintigraphy is a functional imaging method using isotopes for the visualisation of ventilation and perfusion distribution in the lungs. in recent years, the imaging techniques for diagnosing pe have improved. many nuclear medicine centres have adopted the single photon emission computed tomography (spect) technique as opposed to the planar technique when diagnosing pe. the introduction of -dimensional v/q spect technology instead of -dimensional planar v/q scintigraphy has resulted in fewer indeterminate results and a higher diagnostic value. the latest improvement is the addition and combination of a low-dose ct without contrast to the v/p spect (spect/ct) technique. the spect/ct in combination has been compared to ctpa, planar scintigraphy and spect alone, and one study has shown that spect/ct in combination had the highest diagnostic accuracy for pe diagnosis. spect in combination with low-dose ct without contrast enhancement is superior, especially for small subsegmental emboli; however, consensus is lacking regarding the clinical impact and treatment. spect and spect/ct may provide alternative diagnosis if pe is refuted and are feasible in almost all patients, because there are no definitive contraindications. in the present lecture, spect and spect in combination with low-dose ct are discussed in the context of diagnosing pe. over the last few years, emergency radiology (er) has been a subspeciality with growing interest. because of rapid developments in technology, ct has become the most useful tool in evaluating trauma and other emergency patients. in this lecture, the basics of planning and organising an er department are presented and discussed. besides optimising technical equipment and protocols for imaging, different logistic concepts have to be considered in planning and organising er departments. first of all, logistic concepts have to be considered for obtaining an optimal workflow: the radiology department has to be in close proximity to the emergency department and the admitting area, in particular. the whole workflow must be optimised for speed and accuracy. this also mandates having dedicated and standardised examination and viewing protocols for ct. in contrast to the usa where dedicated emergency radiology departments are well established, nonspecialised radiologists still frequently do the reading of emergency radiology cases in european countries. the radiologic staff involved has to be trained for interpretation of trauma and other emergent cases. this does not only account for residents, but also for consultants and attending radiologists. since a large number of cases will arrive during after hours and on weekends, staffing has to be adjusted to this fact, which includes attending radiologists to be available during these hours on call or, preferably, on-site. this lecture will give an overview of logistic concepts and organisation of an emergency department and will also discuss critical issues in polytrauma imaging. at least during the radiological training in hospitals, every radiologist will personally be confronted with the treatment of polytraumatised patients. it is a fact that standardised whole body mdct (wb-ct) as an independent predictor is able to save around % of patient lives. thus, wb-ct is the major diagnostic tool and should be performed as fast as possible. some institutions bypass the emergency room and directly start patient stabilisation in the ct cabinet. however, radiographs and focused ultrasound remain important in general settings as long as they are performed in a way which does not delay ct diagnostics. after scanning, specially trained radiologists support the whole interdisciplinary team with correct, appropriate and prioritised diagnoses. besides optimisation of parameters like logistics, patient positioning preferably 'feet first', reading and communication, 'choosing the right protocol' is a crucial factor for ideal radiological patient care. four types of protocols should be differentiated: there is a wide agreement that for patients with polytrauma, integrating whole body computed tomography (ct) scan into early trauma care significantly increases the probability of survival. therefore, ct is today considered the most important imaging technique in the diagnostic workup of polytrauma patients. the downside of whole body ct represents the relatively high radiation exposure. to overcome this handicap, the following measures can be taken: . positioning of the arms during whole body ct above the head results in reduction of radiation dose; . adaption of scan parameters, especially reduction of tube voltage to kv reduces radiation dose; . installation of recent technical improvements like iterative reconstruction algorithm reduces noise in the image, allowing a downward adjustment in radiation dose to obtain standard diagnostic quality images; . installation of dose control software enables optimisation and improved dose management over time. another disadvantage of high-resolution whole body ct is the amount of acquired data. to optimise the workflow in the evaluation of a couple of thousand submillimetre images it is necessary to connect the mdct scanner with a dedicated workstation for volume image reading, which offers the possibility of quick multiplanar online evaluation. in this introduction i will define the connectome (a comprehensive map of neural connections in the brain) and related concepts such as scaling, structural and functional connectivity as well as the integration-segregation paradigm. the development of mri-based techniques such as white matter tractography and segmentation of white and gray matter has played a crucial role in the emergence of connectomics by providing tools to map in vivo the entire human structural connectivity at a macroscopic scale. i will explain these methods and how from mr imaging a human connectome can be mapped and represented as a network (set of nodes and edges). finally, i will also review the validation work related to those techniques and mention the foreseen technical advancements in the field. session objectives: . to learn what the human connectome is and how it is affected by brain disease. . to understand how the human connectome can be imaged and characterised with mri. . to become familiar with the network formalism and its interpretation. . to understand the relationship between brain function and underlying structural connectivity. . to understand the conceptual ideas behind connectomics. . to learn about the general workflow, from diffusion imaging to mapping a structural brain network. . to become familiar with the robustness of the technique by reviewing validation studies and getting a glimpse of the technical challenges. the economics of brain networks e. bullmore; cambridge/ uk (etb @cam.ac.uk) we review the methods and recent results of network analysis of human neuroimaging data. human functional mri and structural mri data can be analysed using mathematical tools drawn from graph theory to quantify the complex (non-random) topological properties of brain networks. these results can be substantiated by meta-analysis of prior neuroimaging results and analysis of non-human nervous systems. brain networks consistently express complex topological features, such as small-worldness, hubs, modules and rich clubs. some of these features entail disproportionate biological cost, but may be "worth it" by supporting integrative information processing and adaptive behaviours. highly connected hub nodes are high cost/high value network components that likely also represent special points of vulnerability for diverse brain disorders. these economical principles of brain network organisation are expressed at the microscopic scale, e.g., in the nervous system of the nematode worm c. elegans, and may therefore provide a new axis for translation between macro and micro systems neuroscience. neuroimaging can be used to elucidate the economical principles of human brain network organisation in health and disease. connectomics in brain pathology m.p. van den heuvel; utrecht/nl (m.p.vandenheuvel@umcutrecht.nl) healthy brain function depends on efficient functional communication within a complex network of structural neural connections, a network known as the connectome. conversely, damage to the brain's network, disrupting local neuronal processes and/or global communication between remote functional systems may lead to brain dysfunction. in the last few years, emerging evidence from a wide variety of studies suggests that connectome abnormalities may indeed play an important role in the aetiology of several brain disorders. in my talk, i will discuss the results of recent studies suggesting an important role for affected connectome organisation in a number of neurological and psychiatric disorders. in particular, i will highlight the findings of affected functional and structural brain network in neurodegenerative disorders such as alzheimer's and als, as well as discuss how the application of network science and connectomics may aid our understanding of the biological basis of psychiatric disorders such as autism and schizophrenia. learning objectives: . to understand the role of connectome architecture in (cognitive) brain function and dysfunction using diffusion mri/functional mri. . to become familiar with connectomics as a tool for examining disease pathology in a wide range of neurological and psychiatric brain disorders. linking structure and function: the role of modeling in understanding the pathophysiology the interplay of the brain's intrinsic activity and the external world has seen a revival in the last decade, especially in neuroimaging. a long-held assumption in many of these studies has been that ongoing brain activity is sufficiently random that it averages out in statistical analysis. hence, imaging studies are termed 'activation' paradigms, where experimental manipulation results in the activation of cerebral circuits that are necessary for performing the task. nevertheless, a large amount of recent literature reports a body of observations that there are consistently distributed patterns of activity during rest. this fact has led to the suggestion that it might be possible to characterise network dynamics without needing an explicit task to drive brain activity. indeed, numerous neuroimaging experiments have evidenced the solid existence of spontaneous long-range correlations, i.e. functional connectivity (fc), by fmri, meg, and eeg techniques. the functional connectivity is defined as the statistical dependence between remote neurophysiological dynamics. the emergence of resting functional connectivity is intrinsically linked with the underlying anatomical connections between those areas, i.e. the structural connectivity. whole brain modeling can indeed establish a direct link between structure and function. furthermore, the modeling can shed light on the origin of pathological functional disfunction by making the link with the underlying anatomy explicit. we will show how, structural dti tractography, functional imaging and modelling studies can be combined for reaching this goal. traumas to the paediatric pelvis and hip include traumatic dislocations of the hip, fractures of the femoral neck, fractures of the pelvic ring, acetabular fractures and apophyseal avulsion fractures. traumatic dislocations of the hip, fractures of the femoral neck, fractures of the pelvic ring and acetabular fractures are rare in children (less than % of paediatric fractures), as compared to adults. these fractures are commonly the result of high-energy trauma. imaging is based on plain radiographs, but ct and mri are very useful to precisely assess bone (ct) and cartilage and soft tissue (mri) lesions. imaging enables accurate diagnosis, appropriate treatment and detection of potential complications (femoral head osteonecrosis, premature physeal closure …). in contrast with the previous injuries, apophyseal avulsion fractures of the hip and pelvis are common in children and adolescents, usually associated with athletic activities. in most cases, these fractures are of good prognosis and can be treated conservatively when minimally displaced. plain radiographs confirm avulsion injuries to ossified apophyses, but mri and ultrasound are the modalities of choice to demonstrate injuries to nonossified apophyses and to assess apophyseal displacement. the elbow is a very common site for fractures in a child. the challenge for the radiologist is to differentiate normal variants of growth from possible injury and this is usually achieved by having good-quality radiographs and an understanding of normal growth. it is important to recognise those fractures which require surgical intra-operative treatment. in a small number of cases when assessing for vascular integrity, intra-articular extent and injury to cartilaginous structures, ultrasound and mr imaging have a valuable role. this lecture will give an overview of the radiographic appearance of fractures, highlight the features which require orthopaedic intervention and illustrate the use of additional imaging modalities. learning objectives: . to become familiar with the types of injuries seen in the paediatric elbow. . to understand the strengths and weaknesses of different imaging modalities. a- : the diagnosis of c-spine injury is more complex in children than in adults. early diagnosis is crucial since delayed diagnosis results in high morbidity and mortality. leading mechanisms of pediatric c-spine trauma are motor vehicle accidents, sports and pedestrian injuries. due to their anatomy, children are prone to different types and locations of injuries. children < yeas of age are more likely to injure the spinal cord itself and are prone to dislocations and high (c -c ) bony injuries. children > years of age more often sustain c-spine fractures. in children under the age of years, radiographs are rarely helpful. ap and lateral radiographs are helpful in children aged between and years. in children aged > years, additional lateral and odontoid views are obtained. anatomical variants such as pseudosubluxation of c -c , widening of the atlantodental interval and ossification centres may appear to be of concern on imaging, but are normal. abnormal radiographic findings require additional imaging to differentiate them further with ct on the area of concern. mri is mandatory if signs of atlantorotary subluxation and spinal cord injury without radiologic abnormality (sciwora) are present. mri identifies injuries to the spinal cord that are not apparent with other modalities, and should be used when a child presents with a neurologic deficit but normal radiographs on ct scan. nowadays, ultrasound (us) has become the first choice for performing most breast biopsies. the main advantages of this technique are non-ionising radiation, full control of the needle position in real time and widespread use of us equipments at all centres. us allows access to difficult places (such as the axilla or near the nipple), multiple lesions can be safely biopsied in one single session, the breast is not compressed, there is excellent comfort for patients and radiologists, local anaesthesia and haematoma do not hide the lesion and it is a cost-effective technique. however, the main limitation is that the lesion must be visible on us. us-guided fine-needle cytology was widely used in the past, but today its use has decreased. us-guided core-needle biopsy has proven to be a reliable technique to perform a biopsy for breast lesions, showing a sensitivity value of about %. furthermore, it can be safely used for performing biopsies of axillary lymph nodes. vacuum-assisted devices can be used not only for diagnostic purposes, but also for therapeutic ones, because small palpable benign lesions (such as fibroadenomas), papillomas and radial scars can be completely removed. stereotactic breast biopsy is the performance of tissue sampling under mammographic guidance. as with any imaging technique, some lesions are only seen with mammography. when these lesions are suspicious (e.g. birads or higher), there are no imaging techniques that can downgrade this suspiciousness directly, although for birads lesions follow-up might be a viable alternative. in mammography, most lesions that are only visible on the mammogram consist of clusters of microcalcifications. these harbour a likelihood of around % being malignant and should thus be classified as birads . this implies that tissue sampling is mandatory. different from ultrasound-guided biopsy, it is not possible to perform a real-time biopsy under mammographic guidance. rather, stereotactic biopsy uses triangulation to assess the depth of a lesion within the breast, while the lesion location in the xand y-plane is assessed on a scout view. the needle is positioned using the coordinates thus obtained. since there is no real-time feedback of the accuracy of needle positioning, it is necessary to obtain substantially more tissue than under ultrasound guidance. therefore, vacuum-assisted systems are essential. in case of calcified lesions, the biopsy result is controlled by x-ray. calcifications should be present in the sample. biopsy complications that occur under stereotactic guidance are usually limited. most common is the formation of large haematomas. scarring may also occur. breast magnetic resonance (mr) imaging is the most sensitive modality available to evaluate the breast for cancer. it can detect lesions that are occult at mammography and ultrasound. it has a limited sensitivity and the positive predictive value ranges between and %. histopathological assessment of mr-detected lesions is therefore mandatory. some of these lesions will be visible at second-look ultrasound and can be biopsied sonographically. a significant number however will only be discernable on mr, and mr-guided biopsy is therefore the sampling technique of choice. mr biopsy has become an essential component of any breast imaging practice. several mr-biopsy techniques are available including the grid-localising, pillar and post and the freehand techniques. the technique for preparing and performing a mr-guided vacuum-assisted biopsy using the grid-localising technique is reviewed. potential complications, limitations of mr breast biopsy and actions to prevent failure are discussed. imaging-histologic correlation is essential to ensure accurate sampling. clip placement and follow-up imaging should be performed to ensure sampling, including ultrasound correlates. finally, new developments in mr-guided therapeutic interventions are discussed. abdominal injuries require a timely and reliable diagnosis to prevent potentially lethal outcomes. the armoury of clinical tools (physical examination, lab tests) does not fulfil these criteria, since they are either not fast or not reliable. imaging diagnostic modalities help the clinician to acquire the necessary amount of information to initiate focused and effective treatment. however, the selection of the appropriate imaging algorithm, modality and technique, as well as the precise detection and interpretation of essential imaging findings are frequently challenging, especially because the circumstances, under which these examinations are performed (open wounds, bandages, non-removable life-supporting equipment, lack of patient cooperation, etc)., are frequently less than optimal. knowledge of critical imaging signs, symptoms and the role they play in the evaluation of the patient's condition, as well as fast decision-making and ability to closely cooperate with the clinicians are skills of key importance for radiologist members of the trauma team. this presentation will describe the technique and important findings for ct stone studies as well as the accuracy of this study. an explanation of when iv contrast should be given to augment a ct stone study and findings of gu and non-gu diseases that can mimic symptoms of stone disease will be provided. examples and descriptions of acute mesenteric vascular abnormalities, bowel obstruction and infectious conditions will be included. ways to differentiate and categorise emphysematous infections for proper treatment will be described. lower tract emergencies will also be illustrated and described. a systematic approach to evaluating abdominal cts will be described to avoid mistakes. using cases and an audience response system, this segment of the course will go over the optimal imaging approach for patients presenting with acute abdominal pain and abdominal injuries. ct findings will be emphasised. key imaging findings of traumatic and nontraumatic causes of acute abdominal pain including gastrointestinal tract and urinary tract pathology will be explained. a systematic approach for the imaging evaluation of patients with abdominal emergencies will be illustrated and explained including proper scan protocols and analysis of imaging findings. imaging diagnosis of blunt and penetrating abdominal injuries, urinary tract obstruction, infection, bowel obstruction, and ischemia will be emphasised. transcatheter renal denervation represents a novel therapy for treating patients with treatment-resistant hypertension, leading to higher risk of major cardiovascular events. an overview of sympathetic nervous system anatomy, physiology and physiopathology will be followed by a description of the technical aspects of renal denervation. first, results in patients with therapyresistant hypertension look very promising. however, these data need to be confirmed. importantly, long-term efficacy and safety need to be assessed. as a consequence, the treatment cannot be considered, at the moment, standard therapy. future studies need to address other disease conditions characterised by sympathetic hyperactivity, including heart failure, chronic kidney failure and others. it is a general opinion that in the near future the treatment will also be applied to lesser severe hypertensive patients. future studies should also include formal cost-effectiveness analyses. renal denervation can be achieved by a number of different techniques that include radiofrequency ablation, intraluminal and high-intensity focussed ultrasound ablation, chemical ablation and radiation ablation. radiofrequency and ultrasound ablation are currently the most commonly used techniques. most of the evidence to date is derived from studies and trials based on devices that use radiofrequency ablation technology. there are a number of currently ce-marked devices available and each device differs in the catheter design, generator design and energy delivery. these device types include single-point ablation, multi-point ablation, balloon-mounted systems and irrigated technology. the indications for renal artery denervation have been formulated by various international and european societies based on the various clinical trials and studies. these indications include patients with true resistant hypertension, age - years, egfr > ml/min/ . m (mdrd formula), single renal arteries with diameter > - mm with a landing zone of - mm depending on the device, no significant renal artery stenosis > %, no renal artery aneurysm, no previous renal artery angioplasty or stenting and the absence of significant valvular heart disease where lowering blood pressure will be dangerous. renal denervation of the sympatic nerves around the renal arteries is a new catheter technique to treat patients with resistant hypertension. resistant hypertension is seen in about %- % of all patients with hypertension. the mechanism of sympatic nerve driven resistant hypertension will be explained. the available techniques for rdn will be discussed, focusing on the pros and cons of each technique. currently, rf ablation, hifu and cryo-ablation are the techniques under investigation. the technique and physics of renal denervation with radiofrequency ablation will be explained in more detail, focusing on available devices in the market. patient selection and nonresponders will be discussed. the current evidence from the available trials will be reviewed. the future of rdn and the role of radiology and the radiologist will be illuminated. the adrenal glands are composite endocrine organs consisting of the steroid hormone-producing cortex and the catecholamine-synthesising medulla. the increased use of imaging modalities has demonstrated the presence of varying sized mass lesions in up to % of individuals subjected to ct studies for reasons unrelated to adrenal dysfunction. most of these incidentally discovered lesions are non-functioning benign lesions of cortical origin. however, incidentalomas may also represent functioning lesions and malignant masses. clinical diagnostic and biochemical evaluation is used to further subdivide functional and non-functional adrenal lesions. f-dopa has been found to be of high sensitivity and specificity in pet imaging of pheochromocytoma. ct and mr imaging are first choice in characterisation of adrenal lesions. techniques of dual energy ct and histogram analysis may offer additional information. pet-ct has been shown to contribute to the diagnostic power, especially in oncologic patients. knowledge of the physiologic appearance of adrenal glands in -fdg pet is necessary to correctly identify pathologic processes. fdg-pet also has the ability to detect metastatic lesions in non-enlarged adrenal glands. in addition, fdg-pet has the advantage of simultaneously detecting metastases at other sites. the role of mr-dwi and mr-spectroscopy in characterising adrenal masses has to be defined by further studies. differentiating benign from malignant adrenal masses using non-invasive imaging methods can reduce the need for percutaneous adrenal biopsy in patients with underlying malignant disease and the follow-up imaging of incidentally detected adrenal adenomas. renal cell carcinoma (rcc) is the most common malignant tumour of the kidney. as response rates to radiation and nonantiangiogenic chemotherapy are low, surgical excision, i.e. radical nephrectomy has been the treatment of choice. however novel treatment options have emerged, so that imaging of rcc is of increasing interest. nephron sparing partial nephrectomy has become an accepted operative option and antiangiogenic agents such as inhibitors of tyrosine kinase (tk) and mammalian target of rapamycin (mtor) have been approved for treatment of advanced rcc. thus, it has become important to perform correct local staging and identify patients suitable for partial nephrectomy using standardised scoring systems such as renal or padua. furthermore, optimal imaging strategies for monitoring of advanced and metastatic rcc are discussed, as current antiangiogenic therapy evaluation in clinical routine is based only on morphological imaging information, but changes in tumour size may lag behind functional changes. finally, common side effects, i.e. pneumonitis, of vascular disruptive agents are addressed. characterisation of renal masses can be performed using three categories with respect to the lesion size and gross architecture: the indeterminate very small masses, the cystic, and solid renal masses. lesions with diameters below mm are usually difficult to classify due to partial volume effect that prevents accurate ct attenuation measurement. in the general population, these lesions are likely to be microcysts and do not require further workup. better characterisation remains needed in selected patient populations such as patients with hereditary renal tumour disease and previous history of renal carcinoma. in this case, mri combining t w, diffusion-weighted imaging and dynamic contrast enhanced sequences or contrast-enhanced us may help differentiate very small cysts from solid neoplasms. cystic renal mass characterisation still relies on bosniak's classification with categories: benign (i) and minimally complicated (ii) cysts, indeterminate cystic lesions (iif and iii) and malignant cystic masses (iv). some cystic masses remain unclassified at ct because of atypical attenuation characteristics or enhancement properties. us, contrast-enhanced us, and mri are now playing a key role by providing additional diagnostic information that help distinguish between atypical fluid filled masses and atypical solid neoplasms, especially poorly enhancing solid papillary rcc. the characterisation of small solid renal tumours starts at ct with the identification of macroscopic fat, a typical feature of angiomyolipoma. in the case of non-fatty indeterminate renal neoploasms, percutaneous-guided biopsy can be performed when accurate characterisation is needed before surgery or when renal metastases or lymphoma are suspected. drug development being a complex and costly process, there is an increasing need for imaging biomarkers to take go/no go decisions in the early clinical phases. the recist criteria based on tumour size measurements at ct are currently used for this purpose. however, additional functional and molecular biomarkers have been developed to assess the early biological effect of drugs on tumours. development of imaging biomarkers is a structured process in which new biomarkers are discovered, validated and qualified against biological processes and clinical end points. the validation not only concerns the determination of the sensitivity and specificity, but also the measurement of reproducibility. reproducibility assessments, standardisation of the acquisition and data analysis methods and quality control are crucial when imaging biomarkers are used in multi-centre trials. functional and molecular parameters obtained at perfusion imaging, diffusion-weighted mr imaging and pet are being developed and validated. the perspectives (earlier assessment of response to treatment) and limitations (limited validation and standardisation) of these imaging biomarkers in cancer drug development will be presented. more recently, pharmacodynamic imaging biomarkers such as fdg-suv and k trans have been introduced. drug developers are reluctant to use more exploratory unvalidated imaging biomarkers (i.e. cannot distinguish a true negative from a false negative). the extensive literature on biomarker validation mostly refers to biochemical biomarkers extracted as analytes from biospecimens and is unhelpful to radiologists. unlike biospecimen biomarkers, the quality and validity of imaging measurements as biomarkers depend crucially on the use of a diagnostic imaging device, in the presence of the patient, in a manner for which the device (a) was not designed, (b) has not received regulatory approval and (c) may be unfamiliar to the user in the trial site. technical validation and biological validation are orthogonal activities. ''technical validity'' is confidence that the imaging biomarker can be measured reliably anywhere in the world. ''biological validity'' is confidence that the biomarker correctly reports some underlying biology that is important to the patient's future clinical outcome. since the physician always has access to the patient's clinical status and history, the biomarker is only useful if it provides a better forecast than clinical data alone. (if the forecast is near perfect, the biomarker might be a surrogate end point). technical and biological validations are massive undertakings best achieved by consortia, and in particular publicprivate partnerships, of which the innovative medicines initiative in europe and the biomarkers the standard imaging assessment of tumour response relies on size measurements, which, with predominantly cytostatic targeted agents, may not reflect the drug effect. functional imaging biomarkers have the potential to quantify the biological characteristics of tumours and measure on-target and off-target effects that indicate early likelihood of response to a specific therapy, which can then be used to guide the optimal biological dose and drug schedule. serial, non-invasive assessments of whole tumour are possible. this is particularly important in the context of inter and intra-patient tumour heterogeneity, as different parts of the tumour and primary vs metastatic lesions may be biologically different and these characteristics may change with treatment. however, functional imaging end points suffer from variability, which can be very significant in a multicentre setting. strict quality assurance and quality control measures need to be implemented at the start of a trial and the variability across centres documented. data acquisition protocols need to take account of equipment variations. data analysis methodology needs standardisation of software, central review and preferably double reading of scans. automation may not always prove the most robust and reliable option. this presentation will focus on the factors that are crucial in determining the compatibility of data in multicentre trials with functional imaging end points. learning objectives: . to learn about the potential role of quantitative imaging in processes related to tumour growth such as cell metabolism, cell death, and vascular function in the assessment of tumour response. . to become familiar with the issues of accuracy, reproducibility and standardisation for using functional imaging biomarkers in drug development. quantitative nuclear medicine in drug development w. weber; new york, ny/us nuclear medicine techniques can detect and quantify very low concentrations of radiolabelled pharmaceuticals in the human body. this allows investigators to use nuclear imaging for various purposes during drug development. nuclear imaging can visualise drug targets that are only present in nanomolar concentrations and can thus identify patients most likely for therapies directed against these targets. a recent example is folate receptor spect imaging for the selection of patients for treatment with a folate-targeted drug conjugate. in addition, nuclear imaging and specifically pet can measure the concentration of pharmaceuticals within tumour and normal organs over time. nuclear imaging can also be used to monitor target inhibition, for example the blocking of oestrogen receptors by anti-oestrogens. finally, nuclear imaging can assess tumour response to therapy by measuring changes in tumour metabolism or proliferation, e.g. with fdg-and flt pet/ct. this allows an earlier and more sensitive detection of tumour response than morphologic techniques. since pet is a whole body imaging technology, pet imaging can also be used to study the heterogeneity of target expression, tissue pharmacokinetics, target inhibition and response. pet imaging is now widely available in many countries and has become internationally standardised. it is therefore a robust clinical technique that will increasingly be used during drug development. there are about . patients per year in europe who lose their leg. about % are due to diabetic ischaemic and ulcerative leg problems. in diabetic patients the prevalence of foot ulcerations is about % and the risk for developing foot ulcerations is increased four times. diabetic foot problems may be due to neuropathy and malperfusion or a combination of both. the neuropathic ulcer and the neuroischaemic ulcer are usually at the plantar pedis, have a punched-out appearance and are painless. bone deformities (charcot foot) may be associated. the arterial ulcer is usually at the toe, forefoot and ankle, with pale, cold skin and it may be painful. patients need a multimodality approach involving a diabetologist, vascular specialist (angiologist, vascular surgeon, interventional radiologist) and podiatrist. pain control, antibiotic and antithrombotic treatment and the treatment of cardiovascular risk factors and other co-morbid disease have to be done first. in case of ischaemic pain and ulceration imaging such as mra and cta is the next step. patients should be referred to a team of vascular specialist early in the course of their disease to plan for revascularisation options. revascularisation is the optimal treatment for patients with an ischaemic and neuroischaemic diabetic foot. a. pathophysiology of the diabetic foot v. bérczi; budapest/hu (berczi@hotmail.com) the incidence of diabetes mellitus, associated with both predisposing genetic and environmental factors, is increasing globally. several major clinical trials have proved that complications may occur many years following proper glycaemic control. besides peripheral arterial disease, sensory and motor neuropathy along with an altered response to infection is of crucial importance. recent studies have showed that microvascular occlusive arterial disease is not a major factor affecting the diabetic foot; infrapopliteal macrovascular disease and microvascular dysfunction (e.g. arteriovenous shunting, precapillary sphincter malfunction, capillary leakage, venous pooling) are major components of impaired perfusion of diabetic foot. there are no randomised controlled trials analysing the major outcome following endovacular or open bypass surgery. the major outcomes, however, were similar in the case series: -year limb salvage showed a median of % (interquartile range - %) and % (interquartile range . - . %) following open surgery and endovascular treatment, respectively. limb salvage rate, however, was considerably higher with either type of revascularisation compared to medical therapy. negative pressure wound therapy, hyperbaric oxygen therapy, effective off-loading or nonweight-bearing therapies (total contact casts rather than removable devices) have also shown promising results in recent publications. endovascular arterial revascularisation is today a solid option in the management of cli with low complication rates and limb salvage rates comparable with surgery. the restoration of adequate blood flow to the foot is crucial to facilitate wound healing, provide pain relief, and avoid whatever amputations. the angiosome concept was first introduced in by taylor and further developed by attinger for planning treatment of ischaemic lesions of the foot. they divided the foot into six distinct angiosomes, arising from tibial and peroneal arteries. planning the procedure on the basis of this concept will yield the best local results of wound healing, compared with the indirect intervention. a proper pre-procedure assessment through colour doppler us and dsa of lower limbs is mandatory for guiding the procedure through the vessels of the foot. several studies have evaluated the efficacy of pta in the btk and the reliability of the angiosome model, approaching % with a limb salvage rate of up to % at months. on the basis of these data, we can conclude that pta in diabetic patients with btk disease is a safe and effective technique. the first endovascular treatment option is related to the angiosome model, but when not feasible the indirect technique is also a valid and similarly effective procedure. to face technical failures, up to % in crural chronic total occlusion a decade ago, different approaches and dedicated devices and technologies have been developed in the last few years. furthermore, percutaneous revascularisations are gaining more interest, particularly in patients with critical limb ischaemia not only as first-line treatment, but also as the only possible treatment for complex lesions and high-risk patients. special techniques for crural endovascular revascularisations are by design techniques rarely used in routine practice, but could offer wide possibilities for the interventional radiologist to solve challenging situations and manage complex lesions. these techniques include options for arterial access (trans-popliteal, trans-tibial, trans-pedal), approaches for crossing chronic total occlusion (assisted endoluminal, lambda technique, re-entry technologies) and uncommon routes for angioplasty/recanalisation (trans-metatarsal loop technique, trans-collateral techniques). combined antegrade and retrograde approaches have also been developed as well as related methods for successful re-entry. deciding when the patient/lesion is a potential candidate for special techniques is also a crucial issue. the interventional radiologist should be able to convert at any time if necessary the strategy of treatment to another one. he should also be able to select the most appropriate technique for the patient in planning revascularisation. continuous medical education and training is however mandatory and for some techniques the learning curve is relatively long. pathology of the eye and orbit is rare in the radiologist's practice. however, differential diagnosis is not too difficult if the compartment model is applied. in the orbit, different anatomical structures like the optic nerve as part of the cns, muscles for moving the globe, vascular structures and glandular tissue are present in a very small space. each anatomical structure is found in a special compartment; each compartment may give rise to a different group of pathologies, and only to these pathologies: glioma in the optic nerve, rhabdomyosarcoma in the eye muscles, varix in the venous vessels (intraconal compartment) and pleomorphic adenoma in the lachrymal gland. understanding the compartments in the orbit is therefore the key to differentiating different pathological entities. this presentation explains the orbital anatomy, how the compartments are differentiated, and what changes in anatomy treatment may induce. orbital congenital lesions are uncommon. they can be diagnosed prenatally, at birth or later during childhood. several orbital components can be involved. we will focus on congenital globe lesions (such as staphyloma, coloboma, persistent hyperplastic primary vitreous, coats disease), the developmental cysts such as epidermoids and dermoids, and vascular malformations such as lymphangioma and vascular tumours, e.g. capillary haemangioma. orbital inflammatory and infectious lesions are on the other hand common. orbital pseudotumour can involve any area of orbit, being one of the great mimickers in the orbit. if located in the orbital apex and/or cavernous sinus, it will be called tolosa-hunt syndrome. other inflammatory processes in the orbit are sarcoidosis and wegener and sjogren syndrome. among infections the most common is the orbital cellulitis, mostly secondary to a sinusitis and frequent in the urgency setting. the role of the radiologist is to assess whether it is preseptal or already postseptal or complicated by a subperiosteal phlegmon or abscess. also of importance is to know and evaluate the possible intracranial complications. finally, we will focus on inflammatory and infectious lesions of some specific regions such as the globe and lachrymal gland and give some clues for their differentiation. as more than pathologies can be seen in the orbit, a systematic approach is very important to come to the right diagnosis. the main and most helpful criteria of differential diagnosis of any orbital pathology is the definition of the affected orbital compartment, as some tumours may only or preferentially involve specific orbital structures. the criteria of the most frequent masses of the globe, malignant melanoma and retinoblastoma are presented as well as those of cavernoma and lymphoma, the main representatives of intraconal tumours. there are numerous extraconal neoplasms, only few arising from the nasal sinuses, and only a little number of tumours of the optic nerve. the presentation will include the most frequent as well as rare, but important tumours. the routine practice of oncologic imaging requires standardisation, which means that we need to harmonise technical protocols and agree on the meaning of selected words for the radiological report. the words "response, "progression" and "stable disease" are precisely defined according to internationally accepted thresholds and criteria. although the rules are quite simple and rather easy to apply, they are very efficient in the classification of the response to treatment, and therefore for the medical decisions. however, the role of the radiologist is not limited to measurements and calculation. the detection of new lesions may be challenging and requires experience. the differential between cancer progression and complications of the treatment might be very difficult and requires an adequate communication with the referring clinician. overall, most of the decisions taken by the clinician will be related to imaging results, stressing the importance of adequate protocols and reports. in solid as well as non-solid tumours, pet/ct imaging using -fluorodeoxyglucose (fdg) has demonstrated the ability to a) correctly stage disease, b) demonstrate therapy response and c) predict therapy outcome. fdg uptake can be measured objectively; however several factors in the standardisation processes of tracer application, image acquisition and post-processing are needed for reproducibility. the term standard uptake value (suv) measurement is used for compensating the influence of injected dose, decay time and body mass and represents fdg uptake in any selected pixel of the image. for therapy assessment, drop in fdg uptake represents tumour cell kill, notably a negative pet scan does not exclude viable tumour cells but overall has a better outcome. pet response criteria in solid tumours (percist . ) have been introduced to refine previously established pet response criteria by eortc. major changes concern the use of lean body mass-based suv (sul), sulpeak measurement in a fixed roi, use of only a single target lesion and normalization to liver uptake. metric measurements in ct component of the pet/ct as an intrinsic asset like in recist . have not yet been introduced, but might be crucial in the future. the proposed percist . criteria are not yet standard, since several limitations hamper its general use but may improve metabolic tumour response assessment. malignant gliomas (who grade iii and iv) are the most common primary tumours of the brain. according to consensus guidelines, the standard of care of these tumours includes maximal safe surgical resection followed by combined treatment with chemoradiotherapy. radiological assessment is critical in the follow-up and should be performed at four different times: . within hours after surgery, an early post-operative mri must be done to evaluate residual tumour and to be used as baseline for follow-up. . two to six weeks after completing radiotherapy, a new mri examination is recommended to evaluate the response to treatment. four possibilities are envisaged according to the rano criteria: complete response, partial response, stable disease or progressive disease. the evaluation of this first mri examination after rt is challenging and the pseudoprogression phenomenon can appear. advanced mr techniques may be of help in this respect. . additional follow-up should then be performed by mri every to months to rule out clinically silent progression. . in any case, an mri examination must be completed when there is a clinical suspicion of progressive disease. several options for treatment can be offered when progressive disease is detected, including antiangiogenic drugs. evaluation of response to these drugs is challenging too, and the pseudoresponse phenomenon can then appear. due its complexity, it is recommended that the management of malignant gliomas be performed in the context of multidisciplinary teams and that the radiologists are strongly involved in these teams. we are facing complex times with no parallel in human history. the worldwide economic crisis, in combination with a non-regulated process of globalisation, is pressuring countries to change their social and political model. these changes are affecting academic institutions and the health-care sector. higher education was always more internationally open than most sectors because of its immersion in knowledge, which was never worried about country juridical boundaries. it is well recognised that it was the knowledge created by universities research that contributed to the development of societies. we, as european citizens, must be able to transmit the message that having more knowledge and being capable of understanding better the world we live in will make us stronger, more successful and more competitive. european academic institutions must be prepared for this shift of paradigm and understand that they are no longer educating only for their country but for the globalised world. it is also important to bear in mind that developed health-care systems are suffering several pressures and a call for a new inter-professional collaboration concept is needed, based on each one's roles and responsibilities, towards a better and more efficient health-care delivery for the patients. in this session, the invited speakers will give us an overview about the challenges that academic institutions will face in the near future and the way they must adapt to become more attractive and at the same time guarantee that radiographers and radiologists are educated and trained according to the highest professional standards. session objectives: . to appreciate the challenges that academic institutions must face in order to educate graduates with the ability to work internationally and to actively contribute to the healthcare sector of the future. . to explore innovative approaches in education and assessment. . to highlight the importance of inter-professional collaboration in order to ensure that graduates are ready to meet the demands of the modern healthcare sector. challenges in undergraduate education l.j.o.c. lanca; lisbon/pt (luis.lanca@estesl.ipl.pt) radiographers operate a wide range of sophisticated equipment and perform a range of techniques in several radiological procedures. they are responsible for the radiation delivered to the patient while assuring safety and image quality at an acceptable level for an accurate diagnosis. education and training in radiography, in line with the constant technological developments, is a requirement to be fulfilled by higher education institutions (hei). this is of major importance in undergraduate education where radiographers learn to play an effective role as healthcare providers in planning, preparing and performing accurate and safe radiological procedures within the diagnostic or therapeutic field. the european qualifications framework (eqf) for radiography, in terms of the development of knowledge, skills and competences, provides a european standard for the development of radiography learning outcomes at eqf level . this constitutes an opportunity to develop, tune, advance and promote standards of radiographic practice, education and research throughout europe. the eqf provides guidance to increase the educational and professional recognition of radiography in europe. at a european level, the cooperation between hei in undergraduate radiography education would be an opportunity to provide discussions of mutual concern, explore new perspectives and views of different cultures, and also share learning and teaching methods. international cooperation is an opportunity to improve and provide the harmonisation of education regarding a professional group that plays an effective role in healthcare in their field of competence and expertise. there is a vast amount of evidence available from the published literature that higher education institutions continue to explore innovation in both teaching and assessment practices. this is especially true of health professional programmes as evidenced by the abundance of literature relating to medicine, nursing, radiography and other allied health professions. such higher education, health professional programmes would appear to be more innovative than many other disciplines often as a direct attempt to mirror the dynamic clinical environment in which most graduates will work. there are, however, challenges associated with any such educational innovations and novel approaches to delivery and assessment. these specific challenges must be carefully considered in parallel with the larger challenges facing higher education institutions, both nationally and internationally, along with the professions which they contribute to. through a case study approach, supported by published peer-reviewed literature, institutional reports and research, this presentation will consider international best practice in education along with the value of collaborative, inter-professional approaches to teaching and assessment. haemodialysis accesses have become the most commonly performed type of vascular surgical procedure. however, only % of all haemodialysis accesses remain patent at years. autogenous fistulas have a higher rate of primary failure compared to prosthetic grafts ( % vs. %), but the long-term patency of fistulas is superior to that of grafts. autogenous fistulas fail after a median of to years, whereas prosthetic arteriovenous grafts fail after a median lifetime of only to months. the pathogenic stenoses causing access failure occur in various locations, but the most common site in prosthetic arteriovenous grafts is at the anastomosis between the graft and outflow vein, as identified in % ( , ) to % of cases, or in the outflow vein itself in autogenous arteriovenous fistulas. clinical assessment alone will detect a large number of failing fistulas. by assessment of the thrill, pulse character, palpation of the fistula itself, excessive bleeding and difficulty needling a fistula may all indicate a failing fistula. if the venous pressures during haemodialysis exceed mm hg, fistula flow falls to< ml/min, graft flow decreases to< ml/min, or access blood flow falls by more than %. a fistulogram is recommended if monitoring or surveillance suggests that thrombosis is either imminent or has already occurred. duplex can be used to assess the fistula, but cannot visualise the central veins. mr and ct venography has also been used in many patients successfully. treatment of symptomatic stenosis of vascular access is essential as it can lead to thrombosis and loss of vascular access. but treatment can lead to restenosis. the treatment of stenosis remains a challenge which requires a good knowledge of different materials (guidewire, catheters, balloons and stents). though the pathophysiological mechanism of stenosis is different for native fistulas, grafts or restenosis, the treatment technique remains the same. the basic principle is the use of high inflation pressure balloon angioplasty. whatever the material used, the key is to have no residual stenosis greater than %. so far, no study has demonstrated the superiority of the "new" tools (cutting balloon, drug-eluting balloon, cryotherapy) regarding restenosis. except perhaps for anastomotic grafts stenosis, stents should be reserved to treat complications or failure of balloon angioplasty. the stents indications are residual elastic stenosis, wall obstructive damage, acute rupture during angioplasty, aneurysm or restenosis. complications of stenosis treatment are rare, but can lead to the loss of vascular access. the main complications are thrombosis and acute rupture. as with any treatment, there have been contraindications: infection, distal ischaemia, high flow, newly created or surgically revised access (< weeks). when dealing with a vascular stenosis access, never compromise on the future, but think about the surgical alternative. so, the management of stenosis vascular access must also be multidisciplinary. percutaneous treatment of a thrombosed dialysis access can be extremely challenging. the major concern does not stem from the fact that the procedure can be complexly long, but arises rather from the management of its complications, which can be serious particularly when the access is branched onto the brachial artery. access infection is an absolute contraindication. temporary contraindications include fluid overload and severe hyperkalaemia. percutaneous thrombectomy of grafts is very well standardised and predictable: size of mm, well palpable wall which is easy to needle, small average clot burden, and an underlining stenosis almost always found at the venous anastomosis. thrombectomy of avfs is subject to variations in approach and technical difficulties depending on their anatomical particularities. all techniques employed follow rules: first, the removal of thrombi and, second, dilation of the stenosis responsible for the thrombosis. heparin and antibiotics must be injected. the basic principle is to place in the arterialized vein or graft introducer sheaths in opposite directions to work on both the venous outflow and arterial inflow. thrombus lysis or removal can be achieved by mechanical, pharmacological and pharmaco-mechanical methods. all techniques may work in grafts given that the modest amount of thrombus ( . ml on average) can be simply pushed into the lungs. prosthetic grafts are thus easier to declot than native fistulas, but they are much more prone to early rethrombosis. thrombi located at the arteriovenous anastomosis form a firm and rubbery plug, frequently and notoriously resistant to thrombolysis. drug-induced lung disease is an increasingly common cause of morbidity and mortality. the diagnosis is based on clinical history and consistent radiologic findings. lung biopsy is performed in a small percentage of cases. highresolution ct may demonstrate different parenchymal patterns including diffuse alveolar damage, acute or chronic alveolar haemorrhage, nonspecific interstitial pneumonia (nsip), hypersensitivity pneumonitis, organising pneumonia, and eosinophilic pneumonia. the imaging and histologic manifestations are often nonspecific. a systematic approach to the radiological evaluation of drug-related lung diseases is essential and includes not only chest imaging pattern recognition, but also integration of available clinical information. in this interactive session, we will present and discuss several cases illustrating thoracic changes after instrumental procedures in the thorax such as surgery, radiofrequency ablation, interventional endoscopy, and intensive care. radiologists have an important role in assessing the results of these procedures as well as in depicting the complications. however, knowledge of the normal appearance after those procedures has to be presented. the initial imaging workup of polytrauma patients remains challenging. besides hardware requirements, workflow issues continue to evolve, with the current focus on the introduction of whole body ct into the early resuscitation phase of severely injured patients as a standard and basic diagnostic imaging method. this session is aimed at a thorough discussion on the requirements for advanced imaging in the early clinical situation in emergency radiology. focus is directed on the issues of radiation dose as well as on ct and contrast media protocols. a. chest and abdomen m. scaglione; castel volturno/it (mscaglione@tiscali.it) thoraco-abdominal injuries are a significant cause of death in the polytraumatised patients. early recognition and communication of lifethreatening thoraco-abdominal injuries is the major task of the radiologists involved in the emergency room. although most of these patients reach the hospital prior to dying, lethality continues to remain high. heart, thoracic great vessels, trachea, bronchus, pleura, lung, diaphragm, abdominal/retroperitoneal, vascular and solid organ injuries are potential cause of death. any appropriate surgical/interventional management approach must be carried out "around the clock", before thoraco-abdominal injuries reach the level of clinical evidence. on the other hand, non-operative management has actually become the standard of care for the most serious thoraco-abdominal injuries. these goals become feasible if a correct contrast-enhanced mdct diagnosis, in a dedicated facility in which the trauma team works effectively h a day, days a week, is performed. thus, in this lecture, the most serious thoraco-abdominal injuries will be illustrated, with special emphasis on vascular/injuries as well as the value of post-processing techniques, protocols, pitfalls, tips and tricks. furthermore, the importance of a rational and integrated imaging approach will be pointed out and, finally, the role of the radiologist in the emergency room will be emphasised. spinal and musculoskeletal trauma account for significant morbidity in severely traumatised patients. traumatic injuries to the spine encompass a variety of frequently occurring disorders and primarily result in stable injury. although rare, unstable disorders comprise injuries to the bone, the discs, and the ligaments. in the majority of cases, spinal cord injuries result in devastating medical and social consequences. severe musculoskeletal disorders usually are the result of high-impact accidents, such as motor vehicle accidents and falls from a height. for instance, the injured pelvic ring causes one of the most life-threatening conditions that the trauma team must handle. pelvic injuries are often associated with severe arterial, venous, and/or osseous bleeding. radiography is no longer recommended as the primary screening modality in spinal and pelvic trauma for adults. despite the radiation dose burden of ct, patients with a high risk of spine injury receive mdct imaging, as it is the method of choice. mr imaging is indicated primarily when patients present with myelopathy, and to search for spinal cord pathology. interventional radiology plays a major role in the therapy of complex traumatic pelvic disorders. extremity injuries in patients after polytrauma can be complex and are initially often difficult to be fully diagnosed. emergency radiology diagnosis is today mostly based on a standardised whole body ct (wbct), which can be extended with cta and adapted to cover extremity injuries. extremity injuries comprise: fractures of ( ) long bones, ( ) articular joints, ( ) complex fractures of hands and feet, ( ) vascular, ( ) soft tissue, ( ) nerve and plexus injuries and ( ) amputations. imaging protocol: *mdct is indicated in all major and complex bony fractures and is carried out early or integrated with wbct. cta using mips and mprs enables a thorough workup. * the role of us and cr is limited. * the role of mr and mra (in stable patients only) is to evaluate unstable articular injuries, injuries of tendons or major ligaments and nerve and plexus injuries). * the role of dsa is mostly for intervention. clinical findings and findings from wbct determine how to proceed, "first things are done first" in a priority-oriented clinical algorithm. treatment of extremity injuries must therefore be priority oriented and carefully planned in the context of possible concurrent injuries and a possible risk of multi-organ failure (mof). systemic drugs can be used for the treatment of cns and non-cns diseases. both classes can affect the brain inadvertently. common general drugs that affect the brain in a bystander manner are steroids (~ % brain volume reduction), recreational drugs (alcohol, cocaine, heroin, xtc), metronidazole and anti-epileptic drugs (corpus callosum demyelination) and immunosuppressants like cyclosporine/tacrolimus (pres/rpls) and methotrexate. mechanisms of action include neurovascular compromise, fluid/metabolite shifts and toxic effects to myelin of other tissue components. among cns-targeted drugs, especially immunomodulating agents may cause specific side effects. cytokine-release syndromes may occur with broad-acting agents such as general t cell antibodies. specific side effects may occur in multiple sclerosis, where treatment with natalizmumab may cause reactivation of jc virus leading to progressive multifocal leukencephalopathy (pml). upon withdrawal of therapy, this may then evolve into an immune reconstitution inflammatory syndrome (iris). in alzheimer disease, novel antibodies or vaccinations against amyloid may cause amyloid related imaging abnormalities (aria), which may present with microhaemorrhage on t * images, or with edema and effusion on flair. the objective of this session will be to review the diagnostic value of conventional sequences as well as the use of contrast in the monitoring of brain tumours, with special attention to gliomas. also, we will address the advantages and limitations of advanced techniques: perfusion, diffusion, and spectroscopy. immediately after surgery, the main objective of neuroimaging is the detection of the remaining tumour. it may also be necessary to rule out complications such as haemorrhage, ischaemia or infection. the fundamental technique is mri with contrast in the first hours and also diffusion sequences. in late follow-up, the goal is to differentiate the changes secondary to treatment of those related to tumour progression or recurrence. in these cases, conventional sequences present important constraints and are useful studies of diffusion, perfusion and spectroscopy. during follow-up after chemoradiotherapy, the objective is to assess tumour response. the response according to the new rano criteria will be revised. the combination of chemotherapy and radiotherapy, as well as the use of anti-angiogenic drugs causes changes that complicate the assessment of the response to treatment, with cases of pseudoprogression and pseudoresponse. in these cases, perfusion techniques, diffusion and spectroscopy can provide relevant information, although it is necessary to standardise the quantification to make its wide use possible. the speakers in this course will update the audience on contrast media safety such as steps to be taken before contrast administration and present the newest safety guidelines. the first speaker will cover new concepts of non-renal reactions to contrast media explaining which hypersensitivity reactions are allergic and non-allergic. the audience may learn assessing symptoms according to the ring and messmer classification and understand the importance of tryptase sampling and skin testing in the follow-up. the second speaker will address nsf. the presentation will review the pathophysiology, risk factors, recent recommendations and prevention of nsf. patients with gfr less than ml/min/ . m have increased risk of developing nsf. lowstability gadolinium contrast media show the strongest association with nsf. following existing guidelines on the use of gadolinium contrast agents minimises the risk of nsf. potential long-term harm from gadolinium accumulation in the body and legal issues are discussed. the last speakers will cover contrast medium-induced nephropathy with more recently published guidelines related to that issue. the presentation will include the definition of cin and the choice of contrast medium and prophylactic measures. recent changes in esur guidelines will be explained. the risk of cin is considered significantly lower following iv. cm administration and patients referred for enhanced ct are genuinely at risk if they have an egfr < ml/min/ . m . volume expansion with isotonic saline or sodium bicarbonate may be used for preventing cin in at-risk patients. acute immediate hypersensitivity reactions occur within the hour following the administration of contrast media. they can be seen with iodinated and gadolinium-based contrast agents. over the last ten years, new concepts have emerged in the way of understanding, managing and exploring hypersensitivity reactions. the clinical appearance is best classified by the ring and messmer scoring, from grade (cutaneous and subcutaneous signs) to grade (cardiovascular arrest). the mechanisms involve either true ige-mediated hypersensitivity or non-allergic hypersensitivity. the differential diagnosis in favour of allergy is made on a triad: clinical signs (the more severe, the more are the chances to be allergic), elevated tryptase levels in the plasma (indicating mastocyte triggering) and positive skin tests performed one month after the reaction. these new concepts induce important consequences in managing hypersensitivity reactions: be prepared to treat the patient adequately, be prepared to draw blood after the reaction to dose tryptase levels, send the patient to a dedicated allergologist, and forget about the preventive role of premedication against severe reactions. the authorities have introduced several restrictions on the use of high-risk agents, which will be followed by every physician in the eu. the agents are contraindicated in ) patients with severely reduced renal function including dialysis, ) acute renal insufficiency, ) neonates and ) pregnant women. they may only be used with caution in patients with moderately reduced renal function and children less than year old. there must be at least days between injections in those patients. renal function must always be determined by laboratory methods before use of high-risk agents. women should stop lactation for hours. these agents should never be given at doses higher than . mmol/kg per examination in any patient. for the intermediate and low-risk agents, the restrictions are significantly less; they should only be used with caution in patients with severely reduced renal function including dialysis. if a physician does not follow these rules, he or she will have legal problems as they have been introduced into the spc by the authorities. the contrast media safety committee (cmsc) of the esur has updated its guidelines on contrast medium-induced nephropathy (cin). the acr recently updated its guidelines as well. new guidelines were produced by nephrological societies. the topics reviewed include the definition of cin, the choice of contrast medium, and the prophylactic measures used to reduce the incidence of cin. the cmsc considered it appropriate to keep the definition of cin that was agreed in . however, nephrologists have recently agreed on a new definition. in the previous guideline, a number of risk factors were listed (raised s-creatinine levels, particularly secondary to diabetic nephropathy, dehydration, congestive heart failure, age over years, concurrent administration of nephrotoxic drugs). the significance of these risk factors has been confirmed and new risk factors were added. the cmsc agreed that the risk of cin was significantly lower following intravenous cm administration and concluded that patients referred for enhanced ct were genuinely at risk if they had an egfr < ml/min/ . m . the previous cmsc guideline suggested the use of low or iso-osmolar cm in patients with risk factors for cin and the cmsc considered that this previous guideline should not be changed. the cmsc considered that there was enough evidence to recommend that either volume expansion with isotonic saline or sodium bicarbonate may be used for preventing cin in at-risk patients, while the efficacy of nac and other drugs in reducing the incidence of cin remained unproven. guidelines produced by other societies provide very similar suggestions, thus further validating these recommendations. jia is the most common rheumatic entity in childhood and includes a subset of childhood arthritis, all of which are characterised by chronic synovitis with a potential risk of progressive joint destruction. radiological investigations in jia should ideally be able to determine the presence and degree of active inflammation, precursors of bony destructions and established erosions. however, there are many pitfalls in the interpretation of joint pathology in children. ultrasonography is often the initial tool in the assessment of arthritis and can depict joint fluid and synovitis. erosions and cartilage destruction of small joints may also be seen. the major problems are standardising the imaging technique and the lack of normal standards of anatomy in us in children. radiographs can show bone erosions and may depict cartilage loss indirectly through joint space narrowing, but are insensitive to inflammation and early joint destruction. mri is the only imaging modality that can assess all relevant anatomical structures in joint inflammation and is sensitive to early inflammation and destruction. however, large variations in the amount of joint fluid, bone marrow oedema-like lesions and changes resembling erosions are seen in children and also in healthy individuals. the differentiation between true pathology and normal findings on mri in children remains a challenge, particularly in early disease. in this lecture, the role of radiographs, ultrasound and mri and the typical radiological findings in joint pathology in jia will be presented. current knowledge on validity and reliability of the different imaging techniques in jia will be discussed. brain mri plays an important role in those criteria, as it can demonstrate the classical dissemination in time and space and helps earlier diagnosis, which is of major importance since the present recommendation in children is to start immunomodulating treatments as soon as diagnosis is established. among paediatric ms, % begin before the age of years and % before the age of years, frequently with an adem presentation in young children as initial manifestation of ms. however, only % of the adem indicate ms onset and the most predictive factors should be known, i.e. periventricular, deep white matter, corpus callosum high t signal lesions and black holes on t sequences. mri evaluation is also instrumental in differential diagnoses such as nonrelapsing adem, vasculitis, immunogenetic diseases and occasionally leukodystrophies. finally, brain mri is useful to evaluate the risk of more severe ms. the obesity epidemic represents one of the most significant european and public health challenges in the st century with prevalence of the disease having tripled in many countries during the past years. this is resulting in an ever increasing cost to healthcare systems including hospital and in particular radiology services which face unique challenges when imaging this group of patients. obesity significantly increases the patient's risk of various comorbid diseases including the incidence of cancer, diabetes, and cardiovascular and liver pathology with a multidisciplinary team approach mandatory for optimal patient care. this multidisciplinary symposium will review the implications of the epidemic with cutting edge, in-depth lectures presented by european experts addressing the epidemiology, role of imaging in the bariatric surgical patient as well as the importance of abnormal fat deposition in the liver. session objectives: . to learn about the impact of the obesity epidemic on european healthcare. . to appreciate the value of imaging techniques in the management of the post-operative bariatric patient. . to understand the role of radiology in fatty liver disease and the importance of imaging during subsequent patient surveillance. obesity: causes and consequences to the patient r. batterham; london/uk (r.batterham@ucl.ac.uk) obesity is one of the greatest st century public health challenges. its prevalence has tripled in many european union (eu) countries since the s. currently, % of eu adult population is overweight and % obese, and the numbers of those affected continue to rise. overweight and obesity are risk factors for numerous health problems, including hypertension, diabetes, cardiovascular diseases, respiratory problems, musculoskeletal diseases and some forms of cancer. mortality also increases sharply once the overweight threshold is crossed. because obesity is associated with higher risks of chronic illnesses, it is linked to significant additional health care costs and is already responsible for - % of health costs. changes in our environment are the main driver for this increase in overweight/obese. however, a person's genetic make-up can either increase or decrease their chances of becoming overweight. the gastrointestinal tract is the body's largest endocrine organ producing hormones that regulate bodyweight. dietary modifications, such as caloric restriction, are the first-line obesity treatments. however, dieting produces only moderate weight-loss with poor weight-loss maintenance. compensatory gut hormone changes induced by dieting are thought to contribute to the failure of dieting. in contrast, bariatric surgery is an efficacious treatment modality for obesity, producing durable weight-loss, amelioration of obesity-associated co-morbidities and reduced mortality. consequently, the number of bariatric procedures undertaken within europe has doubled in the last years with , procedures undertaken in . there is increasing evidence that surgically-induced alterations in circulating gut hormones mediate the weight-loss and metabolic beneficial effects of bariatric surgery. learning objectives: . to understand the epidemiology of obesity and its impact on european healthcare provision. . to appreciate the aetiology of obesity and the scientific rational for surgical treatment. . to learn about the effects of obesity on health. imaging of modern surgical procedures and their complications m. rengo; latina/ it (marco.rengo@gmail.com) we will illustrate the common bariatric procedures, in particular their normal appearance on different diagnostic technique as well as their early and late complications. we will illustrate the correlation between conventional barium studies and advanced imaging with mdct and mr. we will explain how to optimise mdct and mr acquisition protocol according to the clinical indication. we will explain what to evaluate before redo surgery, in particular quantitative and functional analysis. we will illustrate the role of interventional radiology in the management of early postoperative complications, in particular in the management of patients subjected to gastric banding. non-alcoholic fatty liver disease comprises a variety of pathological disorders ranging from simple steatosis to steatohepatitis. this condition is common in the western population and is typically associated with obesity and the metabolic syndrome. its incidence increases dramatically. diagnosis of fatty liver and distinction between simple steatosis and steatohepatitis are keys because the latter can lead to extensive fibrosis and cirrhosis with an increased risk of hepatocellular carcinoma (hcc). imaging plays a crucial role in diagnosing fatty liver. the two most important imaging modalities are ultrasound and mr imaging. ultrasound can exclude major steatosis but lacks accuracy to precisely quantify fat, while mr is the most accurate for quantification. the technique of reference is mr spectroscopy, but sophisticated sequences based on chemical shift principle have been shown as accurate as mr spectroscopy. unfortunately, imaging has still limitations to assess the presence of fibrosis and inflammation which are associated with steatohepatitis and functional tools could be of interest. today, imaging is combined with clinical and biological biomarkers to evaluate the risk of steatohepatitis. due to the increased risk of hcc and cirrhosis-related complications in patients with steatohepatitis, patients at risk should be enrolled in the surveillance programme. learning objectives: . to understand the pathophysiology of fatty liver disease and its link to cirrhosis. . to become familiar with the role of imaging in the detection and quantification of fat in the liver. . to learn about the importance of imaging in the surveillance of patients with fatty liver disease. the concept of breast cancer units originates from the need for making available to all women in europe high-quality breast services where breast disease could be looked after by specialists working as teams. such teams have to provide all the services related to breast cancer, including genetics and prevention, treatment of the primary tumour, care of advanced disease, palliation and follow-up of previously treated women. the breast unit is made up of a group of dedicated breast cancer specialists including a radiologist, radiographer, surgeon, reconstructive surgeon, pathologist, medical oncologist, radiation oncologist and breast care nurse. the specialists involved in breast cancer units have access to all the facilities required for high-quality care and spend most of their working time dealing with breast cancer. in our hospital, we routinely work as a team and to make it possible we organise weekly meetings involving specialists from different disciplines to evaluate and plan patient care at any step of the diagnostic and therapeutic process. each year, we take care of about . newly diagnosed patients with primary breast cancer and of . patients in follow-up. about are patients who undergo rt. after a short introduction from our fellows from pathology, surgery, oncology and radiation therapy, who will discuss their role in the breast unit, we will try to give a practical demonstration of the everyday work of breast units with particular emphasis on the role of the radiologist. the european society of urogenital radiology (esur) published, in , the new clinical guidelines for evaluation of the multi-parametric mri of the prostate. this structured reporting/scoring system (pi-rads) is based on literary evidence and consensus of experts' opinions. the pi-rads scoring system is similar to that already employed by breast imaging (bi-rads) and reflects the probability of a prostatic lesion to be significant. each lesion can be scored in all sequences used in the multi-parametric prostate mri protocols (t -and diffusion weighted imaging, dynamic contrast enhanced imaging and mr spectroscopy) based on defined mri criteria, which are specific for each sequence. based on the scoring in the particular sequences a final pi-rads score for each lesion can be assessed. for each lesion a five-grade scoring systems was created where, for example, the score means that clinically significant disease is highly unlikely to be present and score clinically significant disease is highly likely to be present. this lecture elucidates the principles of this scoring system and its impact on the target definition for the invasive diagnostics and therapy. prostate cancer screening with psa and extended systematic biopsy protocols have led to the over-detection and over-treatment of small and well differentiated cancers, considered clinically insignificant. these cancers cover up to % of the overall prevalence and may not be of any threat. multiparametric (mp)-mri has shown recently its value in the detection, localisation and characterisation of prostatic tumour foci larger than . cm, and may be of value to address the issue of over-detection and over-treatment. an mri-targeted biopsy strategy alone, without any additional systematic biopsies, has been suggested to decrease the detection rate of insignificant tumours while increasing that of potentially aggressive tumours. in patients with no evidence of lesion on mp-mri, the biopsy may probably be deferred. in patients with localised prostate cancer, mp-mri may also become a cornerstone in the selection, guidance and surveillance of patients managed with focal therapy. the rational for this new modality of treatment is to decrease over-treatment by destroying exclusively the index lesion detected on mp-mri. the precision of such treatments may be increased with mritransrectal ultrasound image fusion, allowing for real time navigation during the procedure. the accuracy of multiparametric mri has greatly improved the ability of localising tumour foci of prostate cancer. this property can be used to perform a trus-mr image registration, a new technological advance, which allows for an overlay of an mri onto a trus image to target a prostate biopsy towards a suspicious area. three types of registrations have been developed: cognitivebased, sensor-based and organ-based registration. cognitive registration consists of aiming at a suspicious area during biopsy with the knowledge of the lesion location identified on multiparametric mri. sensor-based registration consists of tracking in real time the trus probe with a magnetic device, achieving a global positioning system which overlays in real time prostate image on both modalities. its main limitation is that it does not take into account prostate and patient motion during biopsy two systems (artemis and uronav) have been developed to partially circumvent this drawback. organbased registration (koelis) does not aim at tracking the trus probe, but the prostate itself to compute in a d acquisition the trus prostate shape, allowing for a registration with the corresponding d mri shape. this system is not limited by prostate/patient motion and allows for a deformation of the organ during registration. the pros and cons of each technique and the rationale for a targeted-biopsy only policy are discussed. radiotherapy of the prostate typically takes the form of either external beam radiotherapy or alternatively, brachytherapy using radioactive seed implants. in both cases, the use of ultrasound has been proven to be highly useful and this presentation will give an current state of the art overview of ultrasound in external beam and radioactive seed radiotherapy. in the case of external beam radiotherapy, accurate localisation of the prostate is essential to ensure adequate target coverage with minimal damage to normal tissue. dedicated ultrasound scanners are able to provide sub millimeter localisation of the prostate superior to the imaging traditionally obtained using ct scanners. this positional information can be obtained daily. in addition, ultrasound allows the imaging of patients with metal hip implants which are normally difficult to image using ct. apart from the benefits of the technique, some pitfalls will also be highlighted. in the case of prostate brachytherapy, the use of ultrasound in the -d volume imaging of the prostate both prior and during treatment will be discussed. in both cases, some time will be spend discussing the quality assurance requirements for ultrasound imaging systems. image-guided radiation therapy (igrt) with onboard kilovoltage cone-beam ct (cbct) allows image guidance during radiotherapy treatments for patient setup and dose replanning. all these items will be discussed in connection with other topics: organ dose and image quality. it is compulsory to convert cbctimage's pixels from arbitrary grey scale to hounsfield unit (hu). this conversion was obtained using a catphan phantom. the same phantom is used for image quality evaluation; standard ctdi head and body phantoms and a farmer chamber were used to measure the cbdi to estimate organ and effective doses by monte carlo software of different protocols of acquisition. ctdosimetry software (ver. . . -impact) and pcxmc . rotation software were used. to verify the dose replanning techniques by cbct, horizontal and vertical dose profiles were compared with the same obtained from ct. patient replanning was verified using cbct vs ct in terms of conformity index. image quality parameters of cbct (in comparison with ct images) are fine for spatial resolution, but are less useful for low contrast. cbdi of . mgy/ mas was measured; msv effective dose, mgy prostate dose and mgy bladder dose were evaluated and discussed during the presentation. replanning on cylindrical phantom shows a mean percentage difference for each profile % and a variation on d mean in all inserts < %. the mean percentage difference between parameters characterising ct and cbct-based plan values is less than %. the replanning showed a substantial agreement with doses evaluated on the reference ct-image; patient dose must be evaluated for all radiation sources. cranial nerves i-vi have an anteroposterior course and are best examined in the coronal plane. cranial nerves vii-xii run in an anterolateral direction and are therefore best examined in the axial plane. these two planes also allow left-right comparison which makes lesion detection easier. lesions involving the cranial nerve nuclei can be detected on axial proton-density/t /multi-echo-ge images and diffusion-weighted images can exclude acute infarction. the cisternal segment of the cranial nerves is best detected on heavily t -weighted images (drive/fiesta/ d-tse/ciss). at -tesla, d-sequences (e.g. b-ffe) can be used and it is often possible to cover the cisternal segments of all cranial nerves. in the cavernous sinus, the cranial nerves can only be evaluated on coronal gadolinium-enhanced high-resolution t -weighted images and similar axial images are needed to evaluate the nerves in the jugular foramen and hypoglossal canal. axial and coronal gd-enhanced highresolution t -weighted with or without fat suppression are used to image the extracranial course of the cranial nerves. today, the tse-dixon sequences provide non-fatsat and fatsat images simultaneously, making cranial nerve imaging faster and easier. time-of-flight images can be used to study neurovascular conflicts, although these can also be detected on submillimetric gd-enhanced t images. of course, it is important to know the major anatomy of the cranial nerves and the most frequently occurring lesions. the abovementioned imaging techniques, the most important anatomy and the most frequently occurring lesions will be demonstrated and discussed in this lecture. mri study of the lower neck space includes the study of anatomy and pathologies of the thoracic outlet, or cervicothoracobrachial junction, extending from the cervical spine and the mediastinum to the lower border of the pectoralis minor muscle, the brachial plexus and the supraaortic vessels (carotid, subclavian arteries and veins). for this, use of a dedicated head and neck coil is fundamental to avoid frequent artefacts arising from air and the passage between different surfaces. only in case of thoracic outlet evaluation, a dynamic angio-mri study should be performed and this means the use of a surface coil. mri protocol of the lower neck should include t -and t weighted sequences. both fat-saturated proton density and t with stir sequences can be used to overcome the inhomogeneity of the magnetic field, especially with large fov. sand bags can be placed on either side of the neck and suprascapular region of the patient to improve image quality. also, flow saturation bands can be utilised to limit blood flow artefacts. also, volumetric sequences are in common use to obtain a quick examination. breath or cardiac gating can be helpful. abnormal findings of brachial plexus consist of nerve signal abnormalities with mild or marked hyperintensity on t -weighted, being aware of magic angle effects and swelling. in case of thoracic outlet syndrome, mri protocol should define the compression of brachial plexus components arteries and or veins, both in indifferent and dynamic mri acquisition. learning objectives: . to learn how to overcome difficulties in performing a lower neck study. . to understand how to avoid the most common pitfalls. . to become familiar with differential diagnosis. c. ct and mri of temporal bone: user's guide f. veillon; strasbourg/fr ct and mr imaging of the temporal bone must be performed with a precise technique. in ct it is important to locate the box of the study above and not in the orbit to avoid the lenses. irradiation is divided by compared with a study through the orbit. the axial sections must be parallel to the lateral semicircular canal the coronal, sagittal sections are completed by oblique coronal views through the long process of the incus and the head of the malleus to get the ossicular v. double oblique sections through the componants of the v permit a view of the stapes and also the malleus and incus in d (mip : mm). mri must be performed parallel to the roof of the orbit permiting very good axial sections in the plane of the lateral semicircular canal (t and t ). the internal auditory meatus and the inner ear must be analysed with mm axial sections (se) after intravenous gadolinium injection completed by a high resolution t (gradient echo or se) . - . mm, depending on the machine ( t, , t). the middle ear in chronic otitis media must be studied with t , diffusion and high resolution t . there is no need of contrast medium injection apart from the complication: fistula of the lateral semicircular canal, thrombosis of the sigmoid sinus. the different pathologies are then discussed: external auditory meatus and middle ear pathologies: ct first. mri is useful for postoperative cholesteatomas. inner ear malformations, otosclerosis, trauma: ct. labyrinthitis, inner ear hemorragia, schwannomas, internal auditory canal content: mri. revascularisation time windows for patients with acute ischemic stroke are generally restricted up to . hours in the anterior and up to hours is the posterior perfusion area. later treatment attempts require more accurate prediction of risk and benefit, as safety and efficacy at these time strata are less well. thus, rapid and effective imaging is important for decision-making concerning intrarterial catheter based recanalisation and/or thrombolytic therapy. advanced imaging techniques identify irreversible infarction as well as tissue at risk. diffusion-weighted mri detects ischemia within minutes of onset, whereas perfusion-weighted mri and ct perfusion studies disclose the ischemic penumbra. combined, they provide information on mismatched tissue, i.e. potentially salvageable brain. in addition, non-catheter angiographic techniques like ct or mr angiography are a useful adjunct to localise arterial occlusion. as an attempt to a reliable emergency examination, the following protocol has been proven to be robust: for the anterior perfusion area, a non contrast ct may exclude cerebral bleeding and is followed by ct angiography (including supraaortic and intracranial vasculature). if technical available, ct perfusion should be performed in addition. in ischaemic strokes of the vertrebrobasilar region, cta is essential to exclude basilary stenoses or thrombotic occlusion. if the stroke onset remains unclear or might extend the above mentioned time window, mr stroke imaging (i.e. diffusion, flair and perfusion sequences) is suggested as mr offers a higher sensitivity. anyway, the best method for each emergency stroke imaging center is depending on clinical availability h/ days, technical equipment and -finally -individual experience of the emergency team. some recent publications have questioned interventional treatment of stroke as an alternative to iv thrombolysis only. these papers -albeit published in highranking sources -usually do not describe the modern concepts of interventional stroke treatment. interventional radiologists, therefore, are convinced by their practical experience that the modern concept of combining iv thrombolysis with mechanical thrombectomy by stent retrievers offers a benefit to a subgroup of patients with severe stroke. this includes anatomical level of occlusion -basilar artery or single vertebral artery, proximal carotid occlusion with distal tandem occlusion, carotid t obstruction and m occlusion. m occlusions are debatable. besides location, the clinical status of the patient before stroke and time of onset, absence of early ct signs of stroke or bleeding and clinical contraindications to iv thrombolysis such as recent surgery influence the decision-making. more difficult than the description of technical success is prediction of clinical success. there are a couple of scores such as thrive available that may be used for outcome forecasting. the amount of collateral flow is frequently used as a decision tool, but is not always easy to quantify. mismatch scores and penumbra have been questioned recently. in conclusion, anatomical factors are pretty easy to identify to indicate treatment, but the clinical and functional setting still lacks quick and reliable parameters that allow a clear decision-making, particulary in borderline cases. the refresher course addresses the current state-of the-art use of different mechanical revascularisation strategies, devices and potential complications. in addition, multimodal imaging applications with a focus on patient selection for endovascular recanalisation therapies, as well as new techniques to guide endovascular therapy within the angio suite are presented. finally, some organisational aspects important for providing an interdisciplinary interventional stroke service are discussed. the ultimate goal of an acute endovascular stroke intervention is neurological recovery or improvement. recanalisation of an arterial occlusion is key in achieving this goal. clinical data suggest that endovascular stroke treatment results in higher recanalisation rates and may provide superior clinical outcomes when compared with intravenous thrombolytic therapy only. however, these higher recanalisation rates are far away in being paralleled by equally higher rates of favourable outcomes in recanalised patients. thus, patient selection remains crucial. besides the careful neurological assessment, brain imaging is here of major importance. the case presentations illustrate that imaging may help in patient selection for subsequent thrombolytic/endovascular therapies by differentiation of patients who may profit from intravenous or interventional therapy in an even extended time window from those who do not. there are a number of key areas supported by evidence-based medicine necessary for a high-level interventional stroke service. as a precondition, a neurointerventional stroke service has to be organised within a multidisciplinary acute stroke team. inside the hospital, it is all about streamlined pathways. any possible delays should be minimised at every step. sacroiliac joint pain may arise from a number of conditions including inflammatory arthritis, degeneration, fractures and tumours. studies suggest a prevalence of % to % pain arising from the joint in patients with positive clinical signs. temporary effect is provided by a mixture of local anaesthetics with steroids with a response varying between % and % in reported series. dual blocks using agents of differing duration are considered more precise, but are less often used in practice. imaging including mr and scintigraphy are of limited predictive value. injections may be into the synovial joint, around the joint or adjacent to the nerve innervation of the joint. there is evidence that para-articular sources of pain are common and injection outside the joint may be more effective. sl-joint injections are performed through a dorsal approach guided by ultrasound, fluoroscopy or low-dose ct. shortacting agents may have lasting benefit, but radiofrequency ablation has been employed in an attempt to obtain long-term response. the evidence for lasting therapeutic response to intra-articular or periarticular injection of steroids and conventional radiofrequency neurotomy is weak. there is fair evidence of longterm response to cooled radiofrequency neurotomy. facet joints account for - % of all low back pain. they are affected by osteoarthritis, joint space narrowing, intra-articular vacuum phenomenon/fluid, osteophytes, synovial cyst and ligament hypertrophy. conservative therapy is initially proposed. percutaneous facet joint steroid infiltrations are minimally invasive procedures involving injection of corticosteroid with or without local anaesthetic inside the joint. they also can provide diagnostic verification of a certain facet joint acting as the pain source. the injectate usually contains a long-acting corticosteroid mixed with a local anaesthetic. sodium hyaluronate solutions or ozone were tested; however more and extensive studies are necessary. other options are either percutaneous ablation or surgical arthrodesis. fluoroscopy, computed tomography or magnetic resonance can be used for guidance. fluoroscopy has the advantage of real-time imaging. cone-beam ct can also be used. computed tomography provides better anatomy information, but has increased radiation dose for the patient. magnetic resonance has higher cost and longer duration. a recent study concluded that it is twice the cost of ct-guided infiltrations. mri can be used in combination with focal ultrasound for ablation, a technique which is still under investigation. success depends upon patient selection ( - % immediate and - % long-term relief). the level of evidence is moderate for lumbar spine concerning short-and long-term improvement. however, the most recent guidelines released (american society of pain physicians) state that it is the oldest and most commonly used technique. the success rates with its safety profile and least invasiveness seem to make it an attractive therapy. although promising for early assessment of response to treatment, these newer functional biomarkers need extensive validation and standardisation for their wide clinical use. validation includes the assessment of reproducibility and accuracy, whereas standardisation concerns image acquisition and postprocessing. the added value of the more complex functional biomarkers relative to the viability parameters should also be shown. viability and functional imaging biomarkers are evolving and emerging parameters for the early assessment of response to treatment. mri biomarkers must be able to show how tumours respond to specific treatment. they need to allow assessment of the effectiveness of new treatment more rapidly than classical clinical end points. these biomarkers must be easy to obtain to facilitate a large spread of the technique. they have to be reproducible. the longest diameter of the tumour remains the easiest biomarker that can be obtained from any kind of morphologic acquisition with no need of post-processing. additional information about the tissular organisation and cellularity can be now easily obtained using modern scanners through diffusion-weighted sequences. the ease with which those sequences are obtained for a while masked the necessity to perform a more complex postprocessing than the one initially done to get reliable biomarkers. there are numerous mri biomarkers of microcirculation, reflecting o consumption, blood volume, blood flow, vessel permeability and extravascular volume. to get them, we need more sophisticated acquisitions and image processing that take into account the t of the tissue, arterial input function, respiratory motion, etc. most of these new mri biomarkers are now used in research and in phase i studies, but have not been validated in more advanced clinical trials or in clinical practice. to use them widely and reliably, we need to perfectly understand the consequences of the choices we make during the acquisition and post-processing of these biomarkers. new targeted treatments in cancer can be effective without significantly reducing tumour size. there are already a large number of targeted treatments that are licensed to treat a range of cancers. for some of these cancers, there is currently no reliable method to tell whether the drug is effective and new response, predictive and prognostic biomarkers are required. functional imaging techniques such as diffusion-weighted mri, dynamic contrastenhanced mri and fdg-pet imaging are being developed or applied as response biomarkers. however, for these to be useful in a wider multi-centre setting, the measurements need to be precise, repeatable and reproducible. we discuss these properties in the context of emerging imaging response biomarkers. learning objectives: . to understand imaging biomarker precision (repeatability and reproducibility) and accuracy and how it is evaluated. . to learn how to interpret biomarker precision and accuracy in the context of the biomarker's intended use. coronary artery disease (cad) and its related cardiac disorders are still the number one cause of death in the usa and the western world. up to date, single photon computed tomography (spect) using traditional radiotracers like thallium- or tc- m sestamibi is the most utilised imaging technique for the assessment of myocardial perfusion. however, over the past decade, there has been a growing interest in cardiac imaging with positron emission tomography (pet) and, indeed, a paradigm shift has been witnessed in the use of myocardial perfusion imaging (mpi) with pet taking advantage of the superior imaging properties of pet over spect. therefore, pet mpi is now being increasingly used for routine clinical evaluation of patients with known or suspected cad. furthermore, it is being used not only at large academic institutions, but also at community hospitals and even in private practice. several factors contribute to this shift in the use of pet mpi, including the growing availability of combined pet and computed tomography (ct) systems, mainly driven by oncological applications, radiotracer, like rubidium- or fflurpiridaz, which can be used in clinical routine, changes in reimbursement, and the increasing clinical evidence supporting the value of pet/ct mpi. the lecture "pet for evaluation of perfusion, absolute myocardial blood flow and coronary flow reserve" will cover several aspects of the growing field of pet mpi. besides the visualisation of coronary morphology, computed tomography (ct) has shown feasibility to also assess myocardial perfusion. currently, there are two different approaches to ct-based myocardial perfusion imaging: singleshot and dynamic, sequential acquisitions over a predefined scan time. the presentation will cover basic concepts of both approaches and highlight protocol details and findings in these stress acquisitions. also, emerging scientific results with respect to diagnostic accuracy, the detection of hemodynamically relevant coronary stenosis and prognostic implications will be discussed. over the past few years, cardiovascular magnetic resonance imaging (cmr) has been increasingly established as an important method in the diagnosis of cardiovascular disease. many studies have shown the equality or even superiority of cmr compared to other imaging modalities (e.g. nuclear medicine and echocardiography). cmr offers important advantages like the absence of ionising radiation, high spatial resolution, and the combination of perfusion imaging with tissue characterisation. the main clinical applications in the assessment of coronary artery disease (cad) include ventricular function, myocardial viability and perfusion. in clinical routine, myocardial perfusion is determined by contrast-enhanced first-pass perfusion techniques during pharmacological stress using coronary vasodilators (e.g. adenosine) or ßadrenergic agents (e.g. dobutamine). non-invasive characterisation of myocardial microcirculation is thought to reflect myocardial tissue supply much better than mere luminographic detection and quantification of epicardial coronary stenosis, and has been shown to be useful for planning of revascularisation procedures and cardiac risk stratification. in several studies on the prognostic value of cmr in cad assessment, normal stress perfusion cmr was highly predictive for a good prognosis, thus able to identify patients in whom invasive angiography can be deferred safely. the purpose of this lecture is to demonstrate how it is possible to sensitise the mr signal to water molecules diffusion in tissue and how to use calculated indices to reflect structural integrity. the concept of diffusion-weighted imaging will be introduced with particular emphasis on the pulsed gradient spin echo (pgse) sequence. methods to calculate the apparent diffusion coefficient (adc) will be described and the concept of the diffusion tensor (dt) will be explained. image processing of diffusion data includes steps like eddy current distortion correction, model fitting and potentially registration of maps to a reference space. indices that are reproducible and rotationally invariant will be described, such as fractional anisotropy (fa), mean diffusivity (md), axial diffusivity (ad) and radial diffusivity (rd). examples of when to use the adc maps or the dt indices will be given in relation to pathologies such as stroke, multiple sclerosis and neurodegenerative diseases. strategies for result presentation such as region of interest approach, histogram analysis and tractbased methods will be shown. limitations and advantages of diffusion imaging methods such as dt do not preclude the use of this technique in research and clinical radiology for investigating structural changes in disease. diffusion imaging methods have a lot of potential to be used in clinical practice. however, although diffusion-weighted imaging has been increasingly applied, clinical use of diffusion tensor imaging is limited to date. this is in part due to the lack of standardisation and the need for more complex analysis tools to evaluate the data. during this lecture, an overview will be provided of some analysis methods for diffusion-weighted and tensor imaging. i will discuss the different parameters that can be obtained as well as some advantages and limitations of the different analysis methods. it is highly recommended to include diffusion-weighted imaging (dwi) in the routine protocols for mri of the brain. dwi as well as automatically calculated apparent diffusion coefficient (adc) map is used for evaluation. the adc values of gray and white matter are identical in the adult brain. restricted diffusion (high signal on dwi and low signal on adc) is seen not only in acute stroke, but can also be present in some brain tumours, the necrotic centre of abscesses, some acute mr plaques, some contusions, encephalitis, creutzfeldt-jakob disease, metabolic diseases, etc. this finding is thus not specific, but is very helpful combined with clinical information and the signal pattern on other sequences. acute stroke has restricted diffusion during the first - days and the diffusion gradually increases to become very high in a chronic infarct. the diffusion changes in ischemic brain and spinal cord tissue are usually irreversible, but may be reversible. brain tumours with high cellularity, such as lymphoma, glioblastoma multiforme, medulloblastoma and metastases from small cell lung carcinoma, usually have restricted diffusion. the surrounding vasogenic oedema has increased diffusion. in the central necrosis of a pyogenic abscess the diffusion is restricted, while it is increased in the necrotic centre of a malignant brain tumour. reversible diffusion restriction in the cortex, the hippocampi and thalami can be seen in patients with status epilepticus. diffusion tensor imaging has so far had limited clinical use, but may be useful, e.g. for the preoperative evaluation of brain tumours. learning objectives: . to understand the differential diagnostic possibilities of high signal intensity lesions on diffusion weighted images (dwi) of the brain and spinal cord. . to become familiar with the appearance of acute, subacute and chronic stroke on dwi. . to learn about the appearance of cerebral tumours, infection/inflammation, neurodegenerative diseases and traumatic lesions on dwi. . to understand the present use of diffusion tensor imaging (dti) and diffusion tensor tractography (dtt) in clinical neuroradiology. the signal intensity in diffusion-weighted imaging (dwi) reflects the cell density in the tissue. dwi, including apparent diffusion coefficient (adc) maps, can therefore be used to differentiate highly cellular from acellular regions of tumours, distinguish cystic from solid lesions, and monitor change in tumour cellularity over time, reflecting response to therapy. in general, tumours have high signal intensities in dwi, but low corresponding adc values compared to normal/benign/reactive tissues. dwi has a wide range of clinical applications, which includes cancer imaging, imaging of infections and inflammations, evaluation of trauma and visualisation of peripheral nerves. of these, the most promising application appears to be in oncological imaging. there is, e.g. now evidence to recommend inclusion of dwi in mri protocols for lesion detection and characterisation in the liver. the advent of whole body (wb) mri including wb-dwi (from root of the neck to groin) has introduced tumour imaging with a systemic approach compared to established multi-modal diagnostic algorithms. it has been found valuable for staging, therapy evaluation and surveillance of tumours, especially in children. however, dwi is generally recommended to be incorporated into oncologic mri protocols of both wb-mri and of selected organs, because it provides additional valuable information to the conventional mr sequences. dwi of the body is frequently prone to imaging artefacts, which can obscure or mimic lesions. to minimise misinterpretations, analysis of the raw b-value images directly in conjunction with adc maps and conventional coregistered sequences is recommended. spinal surgery is most frequently performed to decompress (disc herniation, stenosis, malignant infiltration), fuse and stabilise (particularly following trauma or infiltrative destructive processes) and correct deformity. often, there may be a combination of these procedures at one operation. surgical instrumentation or bone graft is sometimes employed. patients may present themselves with symptoms early or late following the procedure. this interactive session seeks to address the variety of surgical procedures undertaken and subsequently imaged post-operatively because of symptoms. the session aims to help one to understand and become familiar with the expected post-operative imaging appearances related to the surgical procedure, learn about abnormal pathological features as a cause of symptoms in the acute and more chronic situation and explore the diagnosis and differential diagnosis. this may include post-operative fibrosis versus recurrent disc herniation versus post-operative infection. failure of fusion due to failure of instrumentation or inadequate take of bone graft can give rise to pseudoarthrosis. recurrent stenotic symptoms may relate to an inadequate decompression, recurrent disc herniation, postoperative haematoma, extension of a malignant process or ischaemic damage. joint replacement surgery for the treatment of arthritis most often offers the patient excellent results. however, there are potential complications that a radiologist should know about. it is essential to understand the importance of pre-and postoperative imaging for evaluating patients. most commonly, standard radiographs are used to assess the patients after joint replacement. however, ct, nuclear medicine methods as well as mr imaging play an increasing role in such patients. the radiologist should be aware of the most common type of prosthesis and the most common complications after joint replacement. these complications include postoperative prosthesis loosening, prosthesis fractures, periprosthetic fractures, postoperative infection, rotation failure of the prosthesis, and soft tissue abnormalities such as surrounding tendon tears. this interactive session seeks to address the variety of joint replacements which are undertaken and subsequently imaged postoperatively as a result of symptoms. the session aims to help one to understand and become familiar with the expected postoperative imaging appearances related to joint replacement, learn about abnormal pathological features as a cause of symptoms and explore the diagnosis and differential diagnosis. learning objectives: . to learn about changes related to surgery. . to understand changes related to non-surgical treatments. serbia is a beautiful country where east and west merged and often collided for centuries, and where nowadays eastern cultural heritage meets and mixes with the western heritage in a lovely and unprecedented way, with a lot of charm and with a variety of extraordinarily natural beauty and plenty of both traditional and gastronomical wonders to explore. it extends from the edges of the pannonian flatland in the north, over the danube and sava rivers to the gradually growing wonderful mountains in the south. already in , the first x-ray unit was installed, and only twenty years later x-ray units are present in most state-owned and private hospitals in serbia. nowadays, slightly more than half of the thousand radiologists in serbia perform a broad variety of diagnostic imaging and interventional techniques in different radiological units, including numerous ct, mri, and few pet/ct units distributed in five university centers, a number of public clinical centers and hospitals, and also in the private sector. several centers are fully equipped with pacs and ris systems, and are capable of performing teleradiology services. there are still significant challenges in serbian radiology in the field of education and research, planning and implementation of national radiology networks, improvement of standard clinical practice and financing the new equipment. yet since radiologists' enthusiasm overwhelms most of the difficulties, radiology in serbia provides nowadays a broad variety of modern and competent diagnostic and interventional procedures, improving the management and treatment of our patients. radiology in serbia, since its beginning, has been inextricably linked to european radiology. there are written documents testifying to the fact that the first x-ray appliances in serbia had emerged and had been used for medical purposes only two years after wilhelm conrad röntgen discovered x-rays in . the real beginnings of diagnostic radiology in serbia can be linked to the establishment of the general state hospital in , where the first x-ray cabinet was installed. later discoveries in the field of radiological techniques, materials and contrast agents were also immediately accepted by the serbian radiology community. the first cerebral angiography was performed in , which may be considered as the beginning of neuroradiology in serbia. the second half of the twentieth century is characterised by the introduction and wide application of ultrasound, ct and mr diagnostics and outbreak of vascular and nonvascular interventional radiology procedures in the areas of neuroradiology, uroradiology, and cardiovascular and gastrointestinal radiology. for years, serbian interventional radiology has successfully kept pace with achievements of the most relevant centres worldwide. nowadays, serbian radiologists monitor and enforce the most complex modern procedures in different areas of radiology. the rapid development of science and information technology has enabled the daily monitoring of all modern developments, methods and approaches and their increasingly faster introduction into practice. non-ischaemic cardiomyopathies (nicm) refer to myocardial diseases caused by mechanical and/or electrical disorder in the absence of significant coronary artery disease, valvular heart disease, hypertension, or congenital heart disease. nicm often present with genetic mutations, but no clinically apparent disease. in some cases, the presence of fibrotic tissue could cause adverse events and, therefore, the use of late enhancement (le) post-gadolinium technique is necessary in evaluating these patients. le suggestive of fibrotic tissue could be found in up to % of patients with nicm. in the majority of cases (up to %), midwall/subepicardial enhancement could be found; patchy enhancement, often at septal junctions, has been registered in % of patients, while the least common pattern of le was subendocardial ( %). in ischaemic cardiomyopathy (icm), subendocardial or transmural is a typical pattern of hyperenhancement and is related to coronary artery distribution. furthermore, le has the potential to provide important information for risk stratification in clinical practice. in nicm, the extent of fibrosis has been shown to be independently associated with increased rates of future adverse events including all-cause mortality, while in icm myocardium with le in more than % of wall thickness is unlikely to recover contractile function following coronary revascularisation. as many nicm disorders are associated with the presence of scar tissue, le in nicm is nonspecific and should be correlated with clinical presentation and history, which is critical in the evaluation of these patients. interlude: hop-on, hop-off sightseeing tour of serbia s. stojanovic; novi sad/ rs (tupsons@gmail.com) in the interlude between scientific lectures, you are most welcome to hop on a sightseeing tour around serbia during which we shall stop at a few stations where the natural and cultural heritage of our country will be shown. nota bene: some of the sights will be visible to everyone and some only to radiologists. ten thousand years of human effort and five billion years of european soil refinement will blink in front of your eyes through the window we have made with red churches' walls, azure skies and a silver sparkle of our spirit. all the time, a bit of grayscale shadow will supplement the picture as we in radiology are so used to. fragments of past and present will make a mosaic, the glance of which will hopefully light up your day. when you hop off our tour, we believe, some pictures will become part of your emotional memory and maybe will make you wish to see them in vivo. the role of prenatal mri in foetal central nervous system abnormalities: a case-based pictorial review k. koprivsek; sremska kamenica/rs (katarina.koprivsek@gmail.com) mri provides a unique opportunity for studying in vivo central nervous system development. its higher contrast resolution compared with prenatal sonography allows better visualisation of sonographically occult normal cns structures as well as structural abnormalities. in clinical praxis, prenatal mri has become a mandatory tool in evaluating: a) foetuses that have abnormalities suspected on the basis of foetal sonography; b) foetuses with increased risk for brain abnormalities even in the setting of a normal prenatal sonogram (family history of cns anomalies or a genetic/metabolic disorder); c) foetuses potentially at risk due to maternal illness; d) foetuses with congenital malformation, which are candidates for prenatal or neonatal surgical treatment; e) foetuses that could not be evaluated by sonography due to oligohydroamnion, maternal obesity, difficult position of the foetal head, or us reverberation on foetal calvaria in advanced gestational age. we will present a selection of foetal cns abnormalities detected in our institution during the last years, including ventriculomegaly, abnormalities of the posterior fossa, agenesis of the corpus callosum, cerebral cortex developmental abnormalities, spine developmental abnormalities and a variety of encephaloclastic lesions. in all previously listed cases, prenatal mri could provide either crucial or additional information, which can lead to the accurate diagnosis of different cns developmental abnormalities (cortical, commissural and posterior fossa malformation), specific disorder or syndrome, further enabling adequate pregnancy management and parents' counselling. this lecture will cover the standard mammographic views required, the reporting systems for mammograms together with birads and other european systems, breast density, feature analysis, information the clinician requires in a cancer case and how to approach a b lesion. acr practice guidelines ( ) recommend obtaining previous mammograms as you can dismiss an abnormality that is unchanged for years or that has been previously worked up and are able to detect subtle new lesions more easily, although this has not been confirmed in the screening situation. in a structured report the following information is recommended: indication, breast density, description of lesion, size, location, comparison to previous findings, overall assessment, management recommendations and a score to indicate the level of suspicion. examples of different common conditions seen on mammography will be shown including soft tissue masses, microcalcification, architectural distortion and asymmetry. breast ultrasound is one of the main imaging modalities in breast radiology, it allows us to characterise lesions and also guide interventional procedures. the bi-rads categorisation of ultrasonographic findings facilitates the diagnostic approach and also helps the radiologist to use a common language, understood not only by the rest of the radiological community, but also by other breast cancer professionals. ultrasound can be a diagnostic procedure on its own, but is mainly a modality that characterises the findings of other modalities (mammography and mri) and, as such, correlation between all these techniques is the mainstay of everyday clinical practice. this act of correlating and integrating the information of all modalities is what makes a breast radiologist a key actor in the diagnosis, staging and follow-up of breast cancer and other benign or high-risk entities. the final product of this integration will be the radiological report, the means by which we convey all the information we have gathered through all the procedures to our clinical colleagues. this report shall also follow some composition rules to be clear and concise. as with any other modalities, breast magnetic resonance imaging (mri) examinations should be reported in a structured way following the guidelines of the respective national, continental or international societies. adequate nonclinical information (i.e. patient name, date and type of examination, etc). is indispensable. any breast imaging report has to follow a stringent structure including indication, clinical history, clinical findings, brief description of technology used, assessment of parenchymal density, detailed description of significant findings, comparison with previous imaging studies and final assessment according to bi-rads. indications and contraindications of breast mri will be discussed. significant findings at breast mri include foci (small contrast-enhancing spot, nos, < mm), mass lesions, "non-mass-like enhancement" (no mass lesion, partly diffuse regional contrast enhancement of various size) and associated findings. furthermore, as breast mri is a functional study, the different appearance patterns of kinetic contrast enhancement will be presented. the current status and the appropriate use of the bi-rads mri lexicon will be discussed. any breast mri report should not only follow the guidelines, but also follow a red thread, be consistent, express confidence and be comprehensible to clinicians. the overall final bi-rads assessment is based on the most worrisome finding, taking into account both breasts and all imaging methods (mammography, ultrasound, mri) evaluated. furthermore, adequate communication of the result, as well as do's and don'ts of the report wording will be discussed. the prostate is a small glandular organ, whose main function is to secrete seminal fluid. in young men it comprises of mainly the peripheral zone ( %) and a smaller central gland. however, the central gland enlarges with age to form the larger part. the main diseases of the prostate are inflammation, hyperplasia, and cancer (the most important). approximately % of cancers arise in the peripheral zone. the main applications of mri are for cancer detection, staging, and recurrence. mri is increasingly used for radiotherapy planning owing to its good soft-tissue contrast when compared with ct scanning. endo-rectal rf receiver coils, usually inflated with air or perfluorocarbon but sometimes of a rigid design, improve signal detection of the prostate. phased-array surface coils may also be used or (preferably) in combination. t -weighted imaging helps to distinguish haemorrhage caused by biopsy. on t -weighted images the peripheral zone appears brighter, owing to a larger proportion of prostatic ducts, while tumours generally appear darker. more sophisticated mr methods are increasingly used to help diagnosis. in diffusion-weighted images (dwi) tumours appear relatively bright, but dark in the corresponding calculated map of apparent diffusion coefficient (adc), owing to the more cellularly-dense nature of tumours, and hence, reduced diffusion. in dynamic contrast-enhanced mri (dce-mri) tumours appear bright owing to increased vasculature. magnetic resonance spectroscopic imaging (mrsi) of normal prostate is dominated by high levels of citrate from the prostatic ducts; in cancer this is reduced while choline is increased. prostatectomy samples allow one to verify image contrast against histology. recent studies on prostate cancer have provided a number of relevant targets for imaging and treatment purposes. today, imaging plays an important role in different aspects of the disease, but its role should grow in answering clinical questions at various phases of the disease. relevant targets for imaging include metabolites (including glucose, acetate, choline, and amino acids), antigens (including prostate-specific membrane antigen), receptors (grp receptor, cxcr , androgen receptor), proliferation, angiogenesis, and hypoxia. in this presentation, a range of radiotracers for potential use in the imaging of prostate cancer will be discussed, as well as options to tailor nuclear imaging tracers to the various phases of the heterogeneous disease. the fusion of morphologic (ct and mri) and functional (pet, spect) imaging modalities (pet, spect) has become widely available and part of the standard diagnostic workup in cancer patients. for many years, neurosurgeons have already relied on multimodal imaging data during brain tumour surgery to identify hyper-or hypometabolic tissue. the availability of pet and spect data during percutaneous ablation procedures may also be helpful to facilitate treatment planning, probe placement, probe re-positioning, and early detection of residual disease following percutaneous image-guided ablation of cancer. however, up to now conventional us-and ct-guided thermal ablation procedures rely on morphologic information only. intraoperative implementation of multimodal data requires the application of frame-based or frameless stereotactic techniques, both relying on the establishment of an accurate relationship between the patient's preoperative image space and the intraoperative physical space. in image-guided neurosurgery, ct/mrt/spect/pet data are registered to the patient using rigid body transformation. due to respiratory motion and different patient positioning during image acquisition and the actual intervention, soft tissue deformations in the liver occur. thus, the images and the surgical presentation do not match between preoperative imaging and intervention, leading to an extensive degradation of spatial guidance. this presentation illustrates solutions for these fundamental problems that occur during d-navigated liver interventions, including patient immobilisation and repositioning, respiratory triggering and intraoperative imaging. r. bale: equipment support recipient; isys has supported the section of microinvasive therapy with testing equipment. patent holder; rb is a (co-) inventor of the atlas aiming device and the bodyfix immobilisation device and a (co-)shareholder in its financial returns. the goal of ultrasound-triggered, image-guided drug delivery is to increase the therapeutic index and decrease adverse effects of drugs. the bio-effects of focused ultrasound can lead to local tissue heating, cavitation, and radiation force, which can be used for ) local drug release from nanocarriers circulating in the blood, ) increased extravasation and cellular uptake of drugs and/or carriers, and ) enhanced diffusivity of drugs. thermo-sensitive liposomes have been suggested for local drug release in combination with local hyperthermia more than years ago. microbubbles may be designed to enhance cavitation effects. real-time imaging methods, such as magnetic resonance, as well as optical and ultrasound imaging have led to novel insights and methods for ultrasound-triggered drug delivery. image guidance of ultrasound can be used for: ) target identification and characterisation; ) spatio-temporal guidance of actions to release or activate the drugs and/or permeabilise membranes; ) evaluation of biodistribution, pkpd; ) physiological read-outs to evaluate the therapeutic efficacy. liposomes may carry both hydrophilic and hydrophobic drugs in their aqueous interior and lipid bilayer membrane, respectively. the circulation half-life may be increased by incorporating polyethylene glycol (peg)-lipids in the bilayer. recent publications have shown that ultrasound-triggered delivery is feasible. realtime imaging methods, such as magnetic resonance, optical and ultrasound imaging may lead to novel insights and methods for ultrasound-triggered drug delivery. up to now, the success of surgical tumour resection has always been limited by the surgeon´s vision. the human eye is not an accurate detector of small cancer cell clusters and it cannot accurately differentiate cancerous from healthy tissues due to lack of "visible" contrast. by combining a fluorescent probe targeting the folate receptor and a multi-spectral real-time fluorescence camera to observe the operating field, we found that, using fluorescence molecular imaging, -fold more lesions can be identified compared to conventional surgery. these first in-human results point to molecular-based clinical decision-making in surgical and endoscopic procedures as a paradigm shift over decision-making based on human vision. the talk describes current progress with instruments, methods and applications in the field of intraoperative imaging. pre-clinical and clinical results are presented and the advantages and limitations of the method as well as future directions will be discussed. the emerging field of multispectral optoacoustic tomography (msot) is also outlined. mysteries of the human brain unveiled: imaging of white matter microstructure and neuroplasticity p.m. parizel; antwerp/be (paul.parizel@uantwerpen.be) the human brain remains one of nature's great mysteries, and is considered science's final frontier. this greyish lump of tissue with a weight of . kg contains some billion neurons, each of which are connected to thousands of other nerve cells in an intricate network of white matter fibers. in the previous century, the brain was perceived as a fixed three-dimensional landscape, with brain functions confined to certain locations (e.g. motor and sensory cortex, visual cortex, auditory cortex). this concept of neurolocalisationism was in line with the philosophy that there should be "a place for everything, and everything should be in its place". advanced quantitative mri techniques for acquisition and data analyis (fmri, dwi, dti, vbm), help to unravel white matter connectivity of the human brain, and are able to show that the brain can modify its structure and function in response to changing circumstances (such as learning, memory, hormones). this process, which is known as neuroplasticity, occurs at different levels and different time scales. for example, in response to injury, changes may occur at cellular level as well as on a larger scale with cortical remapping. some processes may take months or years (e.g. physical therapy and training) whereas some forms of neuroplasticity happen within hours or days (e.g. changes in brain volume and connectivity during the female menstrual cycle, which have been linked to behavioral changes). in summary, quantitative mri techniques help to unveil the mysteries of the human brain and have opened exciting new fields of active research such as white matter connectivity and neuroplasticity. there are a host of inflammatory and infective insults that can manifest focally or diffusely within the musculoskeletal system. the appearances of the underlying pathological processes in both the soft tissues and skeleton cover a very wide imaging spectrum. the appearances vary, depending on the timing and degree of inflammatory insult and the host response in the involved tissues. the approach of this lecture will cover the imaging manifestations using all modalities covering radiography, ultrasound, ct, scintigraphy and magnetic resonance imaging. the basic knowledge that is required will be displayed in major musculoskeletal categories covering disorders involving the soft tissues, joints, bones and entheses. the imaging manifestations will also be linked with the evolution of the pathological processes covering acute, sub-acute and chronic stages of the inflammatory/infective disorders. by the end of the session the audience should have a clear understanding in making best use of the imaging modalities in the correct diagnosis of a wide variety of inflammatory and infective conditions that can affect the musculoskeletal system. arterial pta and stenting is firmly established as primary treatment in the management of athero-occlusive disease, particularly of peripheral limb arterial disease (pad). patients are selected on the basis of symptoms such as short distance claudication or critical limb ischaemia for lower limb disease or appropriate ischaemic symptoms in other territories in the renal and mesenteric territories and head and neck vessels. commonly used grading systems such as the fontaine or rutherford scores can be useful in patient selection. where treatment is required, noninvasive imaging is utilised to look for the site, severity and extent of arterial disease. most centers use duplex imaging as the primary imaging modality; mra or cta are often used with a higher sensitivity and specificity; and invasive angiography is reserved for problem solving or immediately prior to intervention. the tascii classification has been devised to select patients for either endovascular or surgical intervention. however, most centres will adopt an endovascular approach first. all patients should be on good medical therapy, i.e. aspirin and statins, with good blood pressure and diabetic control where appropriate. when carrying out interventions, an access sheath is used, peri-procedural heparin administered and lesions crossed using selective catheters and commonly hydrophilic guidewires. subintimal crossing of occlusions can be much simpler than trying to cross lesions luminally. balloon angioplasty and or stenting may be applied differently depending on the site and extent of the lesions. the evidence for drug-eluting technologies has also been growing with improved patency rates compared to standard balloon angioplasty. during the efrs meets russia session, radiographers have the opportunity to get information about the role and education of radiographers in the different european countries. the radiographer is a health-care team member who interacts with other professionals in the primary and secondary health-care environment to provide an optimum diagnostic or therapeutic outcome. radiographer education therefore requires that the curriculum covers a wide range of scientific, medical, pathological, sociological, ethical and technical subjects together with the development of appropriate clinical skills. the curriculum should also include the development of research and audit skills to ensure the constant improvement of service quality for the benefit of service users. the session will include a panel discussion about the role of the radiographer in image acquisition and processing. the tasks of the assistant to the radiologist are: filling of the protocol of research, survey of the patient, instructing the patient according to safety measures, positioning the patient, placement of coils of strengthening, beginning of magnetic and resonant research -the research is approved by the doctor, introduction of contrast substance (in the presence of the certificate of the procedural sister) and supervision over the patient during mr research. furthermore, the other tasks are briefing on patient safety, excluding introduction of the patient to metal objects on mr tomography, explaining the procedure of the study, informing about the duration of the study, wearing noise-cancelling headphones, warning about possible vibration and loud sounds, and providing a globular button to call the nurse. today coronary ct-angiography has become a well-established and proven diagnostic modality. quality of coronary and cardiac cta datasets has tremendous significance for correct diagnosis. a radiographer has a pivotal role in performance of coronary cta. coronary cta is one of the most challenging examinations for radiographers because even a small mistake at any stage of examination may ruin the whole study. before the scanning procedure, the radiographer performs a check for possible contraindications to contrast media injection (history of adverse reactions to contrast media and impairment of renal function are the most important ones). the radiographer checks the patient's heart rhythm and takes part in administration of betablockers for control of the heart rate. a detailed knowledge of different scanning modalities of ct-machine is a must. radiation exposure to the patient from coronary cta examinations has been one of the major public concerns. this is why the radiographer should be aware of different approaches to the performance of low-dose cta (prospective gating, tube current modulation, high-pitch scanning) according to patient body composition. the radiographer should have knowledge of when and how to use radiation dose control in an appropriate way. another big issue is injection protocols. selection of optimal bolus timing and iodine load results in highquality cta images. the radiographer has to know the basics of ct image reconstruction and interpretation in order to perform different types of reconstructions from the raw data according to the radiologist's requests and be able to recognise image artifacts. clinical examples of the radiographer's role for performance of coronary cta will be given. every country is famous for its architecture, history, literature, music, museums, etc. however, there are some distinctive features for russia. "russia is a riddle wrapped in a mystery inside an enigma." these words by the famous british statesman winston churchill aptly throws light on the pulsating art and culture of russia. the different aspects of russian art and culture find its best expression in the rich heritage. just feeling the nature and boundless expanses of the country can understand the mysterious russian soul, works of art and real masterpieces. cardiac mdct in children with congenital heart diseases v. bereznitskiy, k. serkova; moscow/ ru (vsber@mail.ru) in ct studies of children with congenital heart diseases, it is mandatory to keep the x-ray dose, amount of contrast agent and study time as low and as short as possible and simultaneously get the best diagnostic image quality. how can we reduce the x-ray dose? by minimising the volume coverage, reducing the voltage, minimising the effect of "overranging", use of x-ray protective equipment, use of tube current modulation technique, use of iterative reconstruction technique. how can we reduce the amount of contrast agent by volume? by covering of only necessary anatomic volume, minimising scanning time, use of adequate speed injection in ml/sec, which depends on catheter position and size, blood flow and anatomic structures. how can we reduce the amount of iodine concentration in the contrast agent? by lowering the voltage we may reduce the iodine concentration and get higher absorption ct values (hu). how can we reduce the time of cardiac ct studies? by preparing the study protocol ahead, preparing all necessary equipment in the ct room, warming up of the contrast agent before the study. what is the radiographer's role in cardiac ct studies? to take care along with the responsible radiologist the above-mentioned needs, to take care of adequate room and instrument temperature, to take care that only absolutely necessary people with adequate x-ray protection are in the study room, for performing the necessary image post-processing, archiving and distribution of studies. the purpose is to evaluate the quality of imaging in forced position of patients with anesthetic support. the role of laboratory technician in ct post processing. we analysed images of unconscious patients on artificial lung ventilation on -and -slice computer homographs ge and siemens and monitored them through the infusion. during investigation the patients were in forced positions, as a result they got artifacts from upper extremities on the abdominal cavity. we analysed patients -hands under the butt, patients -hands on the chest (abdomen), patients -arms along the body. according to the images the smallest number of artifacts was identified when the patient was on the table with hands under the butt. different variations of the patient's hands position and the problem of choice of this position will be offered for researching. the reconstruction the laboratory assistant can execute and also the results of tests will be presented. by order of the doctor the laboratory technician builds d and d reconstructions of fractured ribs, pelvis, facial skeleton, sagittal and coronary reconstructions of spine in case of its fracture. gastrointestinal stromal tumours (gist) are a rare disease that metastasises in up to % of patients with subsequent median progression-free survival (pfs) of around months. tumours are characterised by activating mutations in the kit or the pdgfra gene and treatment is mainly based on tyrosine kinase inhibitors designed to block mutated receptors. however, drug resistance is often based on mutations changing the conformity of the receptor, leaving little effective therapeutic options. to date, second line chemotherapy offers a median pfs of - months and external beam radiotherapy is limited by organs at risk close to the tumour. alternative approaches like endoradiotherapy or minimally-invasive ablation techniques are effective for local control but are inconsistently used and are not tailored to the individual patient's type of disease. to address these issues, the mitigate project proposes a closed-loop personalised treatment concept combining endoscopic-assisted tissue sampling, inline biotechnology and targeted molecular pet imaging probe development combined with minimally-invasive treatment monitored by new mr imaging techniques. a consistent value chain across european research institutes and smes will be established for mass spectrometry of tumours, linkage of radiochemical molecular imaging probes, design of new animal models and targeted therapeutic radiopharmaceuticals. this closed-loop platform will minimise fragmentation of treatment approaches by a coherent molecular-based multimodality concept, thus providing new treatment options. the mitigate platform can be expanded to further patient cohorts with oligometastatic diseases such as other sarcomas or renal cell carcinoma. gastrointestinal stromal tumours (gist) are characterised by highly specific genetic mutations. several specific targets are overexpressed in a majority of the tumours. on the other hand, secondary resistancies limit the usability of highly specific chemotherapeutics such as imatinib. instead of applying cascades of alternative tki inhibitors in order to find an efficient one, quantitative molecular imaging and targeted endoradiotherapy could be considered. for the detection of gist by imaging, ffluorodeoxyglucose (fdg)-pet is widely accepted to visualise the tumour burden. however, as fdg gives no molecular information of potential targets for treatment, new radiopharmaceuticals have to be developed to visualise and quantify other target-structures expressed by gist that would be able to be addressed. this molecular information can be used both for designing a conventional treatment or an advanced strategy: i.e. targeted endoradiopharmaceuticals. compared to conventional chemotherapy this method has the great advantage that not only tumour cells expressing the targeting vector are affected but also tumour cells within the range of the radiation of the decaying radiopharmaceutical. this method is used with great success in the case of neuroendocrine tumours using labeled octreotate derivatives (a small cyclic peptide binding to the somatostatin-receptor) and non-hodgkin's lymphoma applying y- labeled zevalin (a monoclonal antibody binding to the cd antigen). the success of these methods relies on the crossfire-effect, meaning that a certain margin of tissue surrounding the cell targeted by the specifically accumulating endoradiopharmaceuticals is destroyed as well, depending on the penetration range of the emitted radiation. thus, the development of new radiopharmaceuticals for the specific diagnosis and treatment of gist would strongly improve the outcome of the tumour patient. stereotactic radiofrequency ablation of liver tumours: does improved targeting increase tumour response? r. bale, g. widmann, p. schullian, m. haidu, w.r. jaschke; innsbruck/at (werner.jaschke@i-med.ac.at) the purpose is to describe stereotactic radiofrequency ablation (srfa) and to review its inital results in the treatment of patients with primary and secondary liver tumours. one retrospective review includes consecutive patients with srfa sessions for the treatment of hepatocellular carcinomas (hcc) and metastases ( ). in two other studies the outcome after srfa of intrahepatic cholangiocellular carcinomas (icc) ( ) and colorectal liver metastases (crlm) ( ) was evaluated. the overall technique effectiveness was . % with a local recurrence at year of . %. technique effectiveness was not significantly different for lesions< cm ( . %) and - cm ( %). after treatment of inoperable consecutive patients with iccs a median overall survival of months was achieved. a median os of months and os rates of %, % and % at , and years in patients with resectable crlm were achieved. tumour size did not affect os and dfs. rfa probes can be precisely planned, positioned and distributed by means of stereotaxy. especially in large liver tumours the local recurrence rate can be greatly reduced by precise stereotactic placement of multiple radiofrequency probes. these improved local control rates result in better long-term survival rates. author disclosure: r. bale: shareholder; coshareholder atlas aiming device. other; coinventor atlas aiming device. functional and molecular imaging in tumour therapy response assessment s. aime; turin/ it (silvio.aime@unito.it) in the mitigate project further development of currently used mri and ct techniques will be tackled in order to obtain functional and metabolic information which are mandatory to detect early response to the targeted radiopharmaceutical approach. new gd-based agents are under scrutiny in order to improve dce-mri procedures and attain more precise information on the tumour microvascularity level as well on the vessel permeability and the assessment of extracellular ph and mmp activity. the x-nuclei mri ( na sodium) is a non-invasive imaging technique, which enables the measurement of the tissue sodium concentration (tsc) in humans. the direct link of the tsc with the tissue integrity and viability provides a promising approach for monitoring tumour tissue, and could also help to assess cytoxicity and cell death by means of breakdown of the sodium-potassium-pump. however, na mri is challenging because of the low in vivo abundance, the fast transversal relaxation rate and the low gyromagnetic ratio of the na ions in human tissue. new mr measuring sequences for x-nuclei mri will be developed to establish a standardised tsc measurement method within the eu for better comparability. furthermore, the x-nuclei mr data will be reconstructed, scaled and fused with further imaging modalities. lung cancer is the leading cause of death related to cancer. most patients are inoperable as they present with advanced stage disease or even a localised tumour associated with poor general condition, limited cardiopulmonary function or a too high surgical risk. according to the stage of the disease, chemotherapy, radiotherapy and percutaneous ablation therapies are the current therapeutic options for inoperable patients. it is important that radiologists are familiar with the various response and complication imaging patterns related to each of those treatments. the timeline modifications after radiation therapy and percutaneous ablation and the diagnostic management of drug-induced lung disease will be reviewed. this presentation will summarise the current evidence and how to detect early recurrences after those treatments. learning objectives: . to learn about changes after radiotherapy. . to learn about sequela after percutaneous ablation of lung tumours. . to understand changes after chemotherapy of lung cancer. cardiovascular medicine owes much of its spectacular development to the parallel evolution of imaging techniques in the last thirty years. the complex contemporary techniques in interventional cardiology, electrophysiology, and cardiac surgery require advanced imaging modalities. in current times, a wide spectrum of imaging techniques -such as fluoroscopy, mri, non-contact mapping, echo techniques -is performed in organised cardiovascular labs while computed tomography and nuclear techniques are provided by the collaborative departments of radiology and nuclear medicine. it is indeed the collaborative spirit among specialists that bring about the results patients desire. cardiac magnetic resonance (cmr) is a very versatile imaging technique for the assessment of patients with left ventricular dysfunction and has become a central method for characterising the etiology of the dysfunction. indeed, wall thinning less than mm and aneurysmal motion are morphological signs of transmural necrosis. furthermore, a low dosage of dobutamine ( - microg/min) is used to detect functional reserve in the case of viable tissue. a further option offered by cmr is late contrast enhancement (le) imaging, which allows identifying the presence of fibrotic tissue as well as necrotic infarcted myocardium. the sensitivity and specificity of late hyperintensity is, respectively, . and . . similar results can be obtained with mtctetrofosmina g_spect. there is a relation between transmural extension of hyperenhancement and the recovery of contractile function after coronary revascularisation. the chance of recovery decreases progressively with the transmural extension of late hyperintensity, since the average value of the latter is ± % in the segments that recover and ± % in the segments that do not recover contractile function. cmr was also shown to be able to predict response to cardiac resynchronisation therapy differentiating between nonischemic and ischaemic cardiomyopathy le-cmr may allow to precisely delineate the presence and the location of fibrosis, avoiding the placement left ventricular leads in necrotic areas and in particular when the scar is located in the posterolateral area. at the beginning of the presentation, a short overview will be given on the relevance and prevalence of valvular heart diseases with special focus on europe and the data collected in the euroheart survey. also, the aetiologies of the various valve diseases will be briefly mentioned. in the second part, special attention will be given to aortic stenosis (as) and mitral regurgitation (mr), as these two entities are responsible for up to % of all valvular heart diseases. echocardiography is well accepted as the backbone examination of any valvular heart disease evaluation. echocardiographic criteria for severe as and mr are reviewed as well as their importance for the indication of valve repair or valve replacement. in the third part, we will focus on newer "cross-sectional" imaging technologies such as cardiac mr and ct. in particular, the strengths of cardiac mr in the assessment of regurgitant lesions will be demonstrated. in addition, the value of cardiac mr for the pre-interventional evaluation of congenital heart diseases will be discussed. similarly, the crucial role of cardiac ct in the workup for transaortic valve implantation (tavi) will be illustrated. finally, the yield of these novel techniques in the context of combined valvular and ischaemic heart disease will shortly be reviewed. learning objectives: . to better understand the role of cardiac mri in valvular heart disease. . to appreciate the added value of mri vs other imaging modailities. cardiac resynchronisation therapy (crt) and transcatheter valve heart (thv) interventions have been important therapeutic breakthroughs for heart failure patients and patients with valvular heart disease and contraindications for surgery. patient selection is crucial to optimise procedural outcomes and therapeutic efficacy. multimodality imaging plays a central role in patient selection and procedural strategy planning. assessment of left ventricular dyssynchrony, cardiac venous anatomy and extent and location of myocardial scar are key to identify heart failure patients who will respond to crt. stepwise use of non-invasive imaging modalities, including echocardiography, nuclear imaging, magnetic resonance imaging and multidetector row computed tomography (mdct), has been common practice to select patients for crt. recent technological advances have allowed integration or fusion of imaging modalities to create -dimensional models that provide relevant information. multimodality imaging is also crucial to optimise the results of thv interventions. detailed anatomical and geometrical evaluation of the mitral valve with current -dimensional imaging techniques has permitted better selection of patient candidates for transcatheter edge-to-edge mitral valve repair and accurate procedural guidance. for transcatheter aortic valve implantation, accurate measurement of the aortic annulus with -dimensional echocardiography or mdct allows us accurate selection of the prosthesis size to minimise the risk of complications, and evaluation of the procedural access (transarterial or transapical) with mdct permits accurate procedural strategy planning. the learning objectives of this session include: providing an overview of current imaging modalities to select patients for crt and thv interventions and how to use them in clinical practice. the inner layer of the anal canal consists of squamous and columnar epithelium with the transitional zone at the dentate line. the muscular component of the anal sphincter consists of an inner layer of circular smooth muscle (internal sphincter), extending downwards from the rectum, and an outer striated muscular layer extending downwards from the levator ani muscle, comprising the puborectalis muscle and the external sphincter. between these layers is the fat-containing intersphincteric space, including the continuation of smooth-muscle fibers of the longitudinal muscle of the rectum. outside the anal sphincter is the fat-containing ischioanal space. magnetic resonance imaging (mri) and endoscopic ultrasonography have become the mainstay for preoperative imaging of perianal fistulas. for complex tracts, mri seems preferable. mri can be performed using an endoluminal coil or a phased-array surface coil. a state-of-the-art imaging protocol should include t tse sequences in three orthogonal planes, with the axial and coronal sequences angulated at the anal canal. addition of a fat-saturated t tse sequence is recommended for optimal conspicuity of inflammatory changes and post-contrast t -weighted imaging can also be helpful. intersphincteric infection is the principal feature of perianal fistulas; this is generally not found in other conditions. veins can be mistaken for fistulas, but in contrast to fistulas, veins usually are thin-walled, tortuous, symmetric structures. a pilonidal sinus may resemble a fistula, but absence of extension to the intersphincteric space helps one to discriminate between them. haemorrhoids and anal tags may resemble small submucosal fluid collections, but are easily diagnosed at clinical examination. this lecture will describe the pathogenesis of fistula-in-ano, with a focus on cryptoglandular disease, so that the radiologist can understand how the various classifications of fistulas arise. the park's classification for fistula-inano will be described with reference to cryptoglandular disease and other aetiologies. the surgical questions that need to be answered by imaging will be presented, followed by a description of what the radiologists need to include in their report for it to be clinically useful. the role of anal ultrasound and mri for preoperative fistula imaging will be described, with explanation as to why the latter is fundamental to modern management of the disease. perianal fistulising disease develops in approximately half of the adult and paediatric patients with crohn's disease (cd), with a relevant impact on their quality of life. in patients with cd, particularly those with severe fistulising ileal or colo-rectal disease, complex ramified anal fistulas associated with abscesses (parks' classification type - or s.james hospital classification type - ) are more frequently observed than in other patients. perianal disease thus represents a severe complication of cd, which may change disease management, by requiring specific pharmacological and/or surgical treatments. a non-responsive disease eventually may lead to total proctectomy with ileostomy. mri represents the gold standard diagnostic modality, because it provides a comprehensive staging of both enteric and perianal disease, with high accuracy and without invasiveness. moreover, mri is the ideal tool for monitoring disease response to therapy, being able to detect the inflammatory activity of perianal fistulas with high accuracy. so far, several clinical indexes have been proposed to measure fistula's activity, including the perianal disease activity index (pdai). similarly, several mri classifications of fistula's activity, based either on t -weighted or t -weighted contrast-enhanced imaging, have been proposed, although a widely accepted imaging severity score is not available yet. several cases of complex perianal fistulising cd of increasing severity will be shown, with anatomical and clinical correlations, staging and activity description, particularly in patient follow-up and treatment monitoring. finally, differential diagnoses with other benign conditions which may affect the anal canal, including inflammatory infective diseases, hydradenitis and pilonidal disease will be discussed. ground glass opacity (ggo) is characterised on hrct by the presence of a hazy increase in lung opacity that does not cause obscuration of underlying bronchial and vascular margins. although a very common finding, it also constitutes a very nonspecific term since it can be seen in a variety of different intraalveolar and interstitial processes with different histology including inflammatory, infectious and neoplastic diseases that have a common physiologic mechanism: partial displacement of air. ground glass opacity may even be seen in normal processes such as poor ventilation in dependant lung areas and in expiration. moreover, ggo can represent either an ongoing, active and potentially treatable disease or an irreversible process. to interpret correctly this highly nonspecific but very significant finding, it is crucial to attempt to further classify the different large main entities in which this radiological finding appears. are there specific radiological and hrct findings that can help us differentiate ggo in autoimmune inflammatory conditions from infectious and neoplastic processes? are there associated findings other than ggo, such as nodules, reticulation or focal disease, and distribution of findings that can narrow the differential diagnosis? systematic evaluation of ggo and associated findings as well as integration with clinical information (acute, subacute or chronic symptoms) is essential in defining ggo subtypes to improve the radiological diagnosis. radiologists who regularly review high resolution ct (hrct) should be aware of the range of patterns and, more importantly, their potential pathological meaning. a pattern of ground-glass opacification is one of the more common hrct findings but, to the unwary, its interpretation can be problematic. an important underlying principle is that a ground-glass pattern may be caused by any process -physiological or pathological -which partially displaces air. physiological (i.e. non-disease-related) ground-glass opacification is perhaps most commonly seen in subjects who, for whatever reason (e.g. breathlessness, obesity), are unable to maintain or achieve a satisfactory inspiratory effort during scanning. a generally increased lung density (in contrast to adults) is also a feature in infants and young children simply because there are fewer alveoli in the developing lung. finally, it is worth noting that intravenous contrast administration (presumably because of a relative but temporary increase in capillary blood volume causing partial displacement of air) can unpredictably increase lung density. disease processes which lead to partial filling of the air spaces, thickening of the interstitium, partial collapsing of alveoli, and/or increased capillary blood volume will also manifest as a pattern of ground-glass opacification. in clinical practice, the recognised causes of ground-glass opacities on hrct include pulmonary oedema (cardiogenic or otherwise), infections (e.g. pneumocystis jiroveci pneumonia) and some of the idiopathic interstitial pneumonias (e.g. non-specific interstitial pneumonia and respiratory bronchiolitis associated interstitial lung disease). the presentation will review and revise the causes of physiological and disease-related ground-glass opacification on hrct. ground-glass opacity (ggo) is defined as increased attenuation of the lung parenchyma without obscuration of the pulmonary vascular markings on ct images. ggo may be the result of a variety of interstitial and alveolar infectious and noninfectious inflammatory diseases. as an imaging finding alone, ggo does not usually allow a specific diagnosis. ggo in inflammatory disorders is often present in the company of other interstitial or alveolar findings. however, the number of diseases that cause diffuse isolated ggo or ggo as the predominant finding is relatively small and can be prioritised with clinical information. the most common cause of diffuse isolated ggo in immunocompromised hosts are a variety of diffuse, opportunistic pneumonias, e.g. pneumocystis jiroveci pneumonia (pcp), cytomegalovirus pneumonia (cmv) or herpes simplex pneumonia (hsv), which constitute the first differential. chronic onset disorders in immunocompetent patients include cellular nonspecific interstitial pneumonia (nsip), subacute hypersensitivity pneumonitis (hp), organising pneumonia, air-space sarcoid, and drug-induced lung disease. in these disorders, ancillary findings such as an associated reticular pattern with traction bronchiectasis/bronchiolectasis (nsip), mediastinal lymphadenopathy (sarcoidosis), superimposed nodularity or cysts or may help to refine the diagnosis. in patients with collagen vascular disorders, e.g. scleroderma, ggo secondary to pulmonary involvement needs to be differentiated from drug-induced lung disease. this refresher course will put ggo in the context of outpatients versus inpatients, the acuity of clinical symptoms, e.g. fever, cough and dyspnoea, signs of massive systemic inflammation, and the clinical situation such as inhalational history, pneumotoxic drug administration, immunocompromise, or bone marrow suppression. in this course, we will review the dysplastic and neoplastic conditions that are associated with persistent ggo in the lung parenchyma. we will separate these conditions into those that are responsible for localised diseases such as single nodular ggo and those responsible for more extended diseases. nodular ggo can be separated into pure or mixed or part-solid nodules. pathology-radiology correlations show that nodular ggo are related to atypical adenomatous hyperplasia (aah), adenocarcinoma (adc) in situ (ais), minimally invasive adc (mia), and invasive adc according to the new iaslc/ats/ers lung adenocarcinoma classification. differential diagnosis includes exceptional metastases of angiosarcoma and melanoma as well as infection, inflammation and localised fibrosis. diffuse ggo related to neoplastic conditions is rare and may be due to lepidic adc (former advanced adc with bac component), diffuse large b-cell non-hodgkin's lymphoma, intravascular lymphomatosis (ivl) or mucosa-associated lymphoid tissue (malt) lymphoma. these neoplastic diseases should be differentiated from infectious and inflammatory causes of diffuse ggo. we will review the value of different morphological ct criteria to differentiate benign from malignant localised ggo, such as the size, the morphology (round, oval, flat), presence of mixed vs. pure ggo, and the multiplicity of nodular shadows. discussion will also include the changes that may occur within the nodule as well as the mean doubling time. the role of pet ct and transthoracic biopsy will be discussed. finally, we will present the current recommendations regarding the management of nodular ggo. it is the purpose of this lecture to briefly discuss ankle distortion-related lesions with emphasis on failed radiographic diagnosis, discuss their significance and management implications and define the diagnostic pathways in the acute and subacute stage. significant lesions are those with no return to sports activities after months; these have our major interest. in the acute setting of ankle distortion, the ottawa clinical decision rules are accepted to decide whether or not radiographic evaluation is needed; about % of radiographic examinations can be avoided. additional evaluation is restricted to patients with residual pain during reevaluation one week after trauma. assessment of fractures with the lauge hansen classification has a major advantage, as it defines the stability at the talocrural and distal tibiofibular joint. only in restricted cases, additional examinations may be needed to rule out instability. although radiographs easily detect displaced fractures, occult fractures may occur; also, grade ii-iii ligament lesions and peroneal tendon dislocation may go undetected. additional imaging evaluation should focus on the detection of significant lesions. significant lesions are talar fractures and complete calcaneofibular ligament tears. the latter is explained by the instability at the level of the subtalar joint with associated sinus tarsus syndrome. in case of residual local tenderness posterior and inferior to the lateral malleolus, the fibulocalcanear ligament and retinaculum peroneorum lesions are best evaluated with (dynamic) ultrasound. mri or ct is used to detect occult fractures in case of residual talocrural joint effusion with anterior talar tenderness during endorotation and plantar flexion. the ankle and foot can be affected by inflammation from a number of diseases. the main focus of this lecture will be inflammation secondary to infection and systemic inflammatory disorders. due to its function in locomotion and weightbearing, the foot is specifically susceptible to infections secondary to penetrative trauma including foreign bodies or to abnormal repetitive pressure. in addition, both seropositive and seronegative arthropathies can affect the foot. other unusual causes of inflammation include chronic recurrent multifocal osteomyelitis, osteoarthritis, mechanical disorders and sensory loss. this lecture will deal with the various patterns of inflammation in the context of pathogenesis and discuss the imaging features that aid in diagnosis. the importance of the clinical context in diagnosis will also be discussed. characterising tumours before deciding on the most appropriate treatment is a general rule in oncology. cystic tumours are now adequately graded based on bosniak's classification. however, this pre-therapeutic characterisation is not currently systematic in case of solid renal tumours, as it remains difficult in clinical practice due to the high prevalence of renal cell carcinomas (rcc) and the lack of reliable imaging criteria for recognition of benign versus malignant tumours. as a result, approximately % to % of surgically excised renal masses are actually benign. to avoid these unnecessary ablations, pretherapeutic image-guided biopsy has been proposed, but its use is still debated as it is invasive and time consuming. new validated imaging criteria, able to accurately differentiate the most common tumour types but also indolent vs more aggressive malignant lesions, would be useful to reduce the number of unnecessary biopsies or to consider the most appropriate treatment for a tumour or active surveillance. among these, mr imaging plays a major role based on chemical shift gradient echo (gre) sequences, signal intensity on t -weighted images, dynamic contrast-enhanced sequences, diffusionweighted sequences and late contrast-enhanced images. multiparametric mr imaging is now performed in clinical practice in most primary care centres. therefore, using different combinations of two or several parameters, it is now possible to distinguish certain renal tumours. a larger validation of all these combinations is still necessary to define those having a clinical significance for routine practice. targeted therapies such as vegf mab bevacizumab, vegf tyrosine kinase inhibitors (sunitinib, pazopanib, axitinib and sorafenib) and mtor inhibitors (temsirolimus and everolimus) have been approved and included in european guidelines. pre-therapeutic imaging prerequisites are mainly based on the natural history of mrcc. this justifies imaging through a thoracoabdominal ct scan. outside clinical symptoms, there is no need for bone imaging or brain ct scan; the latter nevertheless could be done because of influencing the therapeutic strategy. pet scan should not be done due to low sensitivity. the evolution of metastatic sites by comparison from previous imaging is useful to evaluate the natural history. outside clinical trials or research imput the strategy is to use the drug in an optimal way to increase pfs. so far, monitoring has to inform about change in recist criteria for cr, pr, sd or pd, and if pd is a real pd such as recist pd or a slowing pd. in conclusion, standard ct scan and recist are adapted to real life. nevertheless, more information on the mode of action of targeted drugs should be interesting for knowledge and research purpose, without any impact on the management of patients. additional imaging could be done with additional criteria than recist on ct scan, by vascular functional imaging and pet scan. breast mri is recognised as a useful tool for a number of clinical indications, but remains relatively challenging. recognising the importance of an evidencebased approach to the development of protocols will influence the further integration of this technique into everyday clinical practice in the management of breast cancer patients. there remain concerns regarding the potential of over-diagnosis from breast mri. the aim of this integrated rc is to inform the clinical practice with regard to the establishment of breast mri in specific clinical and imaging scenarios, namely, using mri for surveillance in high-risk patients, monitoring response to neo-adjuvant chemotherapy and developing protocols for the indeterminate imaging scenario of non-mass-like enhancement. the establishment of protocols to maximise the specificity and sensitivity of the technique of breast mri in such indeterminate clinical and imaging scenarios will be discussed. non-mass like enhancement is a frequent finding in breast mri. it relates to the fact that enhancement occurs in the normal-appearing fibroglandular tissue that surpasses that of the other parts of the parenchyma. there is no associated space-occupying lesion. in pre-contrast non-fat-suppressed or fatsuppressed t -and t -weighted images, there is usually no correlate observable. the differential diagnosis of non-mass-like enhancement is between benign nonspecific fibrocystic disease/adenosis, hormonal stimulation, and subclinical mastitis on one hand, vs dcis or (less likely) diffusely infiltrating (usually lobular) cancer on the other. key components of differential diagnosis is configuration of the enhancement (does it follow the orientation of the milk duct or not?) and symmetry (symmetric or asymmetric). less important criteria are internal enhancement (internal architecture) and enhancement kinetics. it is important to realise that enhancement kinetics can only be used to corroborate the suspicion of dcis -but they cannot be used to alleviate the indication to biopsy a finding which, based on configuration and asymmetry, is suspicious. management depends on the different constellation of clinical, mammographic, and mri findings. it usually includes short-term follow-up ( months) and, if stable/persistent, mr guided vacuum biopsy. assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics. tumour shrinkage and time to the development of disease progression are important end points in cancer clinical trials. however, these end points are useful only if based on widely accepted and readily applied standard criteria. criteria, known as recist, were published and are updated on a regular base. the revised recist includes a new imaging appendix and underlines the importance of moving from anatomic unidimensional assessment to either volumetric anatomical assessment or functional assessment with pet or mri. the goal of the lecture is to discuss the value of the different mr imaging techniques (e.g. mr spectroscopy, diffusion-weighted imaging, angiogenesis mapping, pet-mri), which evaluate response to treatment in breast cancer. participants will learn about particular imaging challenges of assessing response to neo-adjuvant chemotherapy. in addition, they will learn to understand clinical aspects of neo-adjuvant chemotherapy based on recist. currently, the esr has been using social media in many successful ways to improve the contacts among members and to boost our fast development as one of the most advanced scientific communities in the world. our session "the role of social media in radiology" presents the view of experts, acknowledged leaders of international it projects. it seems to be important to discuss the major implications of social media for radiology, the leading clinical discipline in information technology. davide caramella will clarify the relationship of social media to professional societies and especially to the esr, including their basic features. the "social media generation" has developed from schoolkids to students and, recently, to teachers as well. alexander sachs represents the young professional expert of elearning in radiology and will reflect the current user behaviour. osman ratib will share his view on how social networks enhance the communication between radiologists, nonradiologists and patients. critical aspects of the pros and cons of large communication scenarios are followed by some ideas of future developments. jürgen brandstätter will indicate the patient´s view. most patients see social network communications with their radiologist as useful for, e.g. appointment management or other non-sensitive communication. besides communicating personal health data, a wide area of potential useful other possibilities are at hand, like anonymised health data for reviewing purposes, second opinion or education of patients. the fast development of social media may induce hopes and fears; the four speakers of this session will present them in a panel discussion. the widespread use of social networks in all professional activities has attracted a great interest in the recent years. in medical applications, the main concerns include the possible consequences in terms of patients' confidentiality protection, perceived role of the physician, patient-physician relationship, and caregivers' distraction during professional activities. there are no doubts, however, that social networks are beneficial in enhancing the information flow between scientific societies and their professional members, without any interference at the point of care. social networks have proved to be extremely effective in updating members about relevant news concerning their areas of interests and in allowing them to be informed about the educational activities promoted by their scientific societies. this presentation focuses on the social network activities promoted by the esr via facebook, youtube, twitter and other blogs. impact of social media on the training of radiologists a. sachs; vienna/ at (alexander.sachs@meduniwien.ac.at) in modern times, social media have gained more and more important value in exchanging first experiences in radiology from resident to resident. social networks such as facebook, twitter, google plus and others are used to start discussion groups about cases and share the growing knowledge with different educational concepts in each hospital. growing e-learning modalities as moocs, applications for smartphones or tabs and web-based case series or learning platforms support the training of radiologist in social media. modern elearning platforms use social media as their first choice of sharing knowledge around the whole world about certain illnesses, cases or different decisions of therapy. though sharing information seems to be easier and shows several advantages than in former times, social media can also highlight new problems. this lecture focuses on user behaviour to improve learning, the pedagogic evidence for large group learning with networks and the importance of using networks to manage time. social media networks in communication between radiologists, nonradiologists and patients o. ratib; geneva/ch while social networks have gained unprecedented popularity in our daily environment, they have only limited utilisation in medical applications. the paradigm of communication within a given community for exchange and sharing of imaging data would certainly have its place in a medical environment where there is an increasing need for multidisciplinary collaborative work. the required security and confidentiality in management of sensitive patient data have often precluded the usage of existing public social networks. professional proprietary systems have emerged in a more restricted way with much less flexibility leading to limited use. the exchange of medical images adds a level of complexity due both to the size of the data and the need for appropriate browsing and visualisation tools. traditional pacs and teleradiology system offer such features, but in a very limited way, far from the desired convenience of social networking between groups of users. a prototype of such a system aimed essentially at the community of users that need to exchange anonymised medical images and data for academic and research purposes will be presented and discussed. the project nicknamed dicom sandbox is being tested and evaluated by some users in europe under the coordination of the esr subcommittee of ehealth and informatics. developed with open source software components, it allows using existing cloud-based storage services with additional layers of secure dicom file management and visualisation. it allows the community of users to share dicom data with all social networking and notification features beyond simple peer-to-peer exchange. interactions between patients and radiologists through social media j. brandstätter; wiener neudorf/ at (j.brandstaetter@codewerk.at) social networks have become integral parts of most citizen's use of the internet. especially, the younger generation uses social networks extensively; however the way those tools are used should be chosen carefully. it is one thing to use a social network for private interests, but a different one to use it as transport media for sensible data like personal health-care data. the sensitiveness of citizens regarding privacy has been increased recently by different events of misuse or fraud, especially accelerated by the recent privacy affairs caused by governmental agencies. though most patients see social network communications with their radiologist useful for, e.g. appointment management or other non-sensitive communication, personal medical reports or images shall not be shared across this media. besides communicating personal health data, a wide area of potential useful other possibilities are at hand (e.g. anonymised health data for reviewing purposes, second opinion, education of patients, …). future developments shall make use of social media where useful, but always with deep respect to the patient's privacy rights. apart from the historical, but ever present clinical expectation from the neuroradiologist is the answer to the most important question if the patient has a brain tumour or not. nowadays, due to the outstanding technological advances in imaging techniques during the last decades, the stakes are growing much higher and it is the neuroradiologist on whom lies the initial responsibility of answering a large number of questions that are of utmost importance for further brain tumour patient care and treatment. having the opportunity to provide the usual and generally basic information regarding tumour morphology and exact location and to narrow the differential diagnostic possibilities, neuroradiologic expertise now opens a wide spectrum of techniques, especially those derived from mri, such as mr spectroscopy, mr perfusion, dwi, dti, swi, etc. these provide us the unique possibility of not only obtaining and comparing images, but also of exploring multiparametric brain maps, allowing us to gain insight into the internal architecture of the tumour and the functional and molecular features of the tumorous tissue. this consequently defines the actual stand of neuroradiology, indicating the uprising clinical urge not only to provide the answers regarding the tumour type, grade and possibilities of the most appropriate and patient-individualised therapy modality, whether surgical or nonsurgical, but also to accurately assess the post-treatment tumour behaviour and status, by differentiating the true tumour progression from pseudoprogression, represented by inflammatory responses to the radio-and/or chemotherapeutical treatment, and to monitor other neurooncological response assessment criteria. a. differential diagnosis and pseudo-tumoural lesions h.r. jäger; london/uk (r.jager@ucl.ac.uk) conventional contrast-enhanced mr imaging gives an indication about the likely tumour type and histological grade, but advanced mr imaging methods, including perfusion-weighted (pwi) and diffusion-weighted (dwi) imaging, mr spectroscopy (mrs) and pet imaging provide additional information which helps to refine the diagnosis of intrinsic brain tumours. contrast enhancement can be a feature of low-grade (pilocytic astrocytoma and ganglioneuromas) as well as high-grade gliomas (who grade iii anaplastic gliomas and who grade iv glioblastomas). infiltrative low-grade (who grade ii) astrocytomas do not usually enhance, whereas who grade ii oligodendrogliomas can enhance. higher-grade glial tumours (who grade iii and iv) tend to have an elevated relative cerebral blood volume (rcbv) on pwi, a decreased adc on dwi and increased choline turnover on mrs and pet imaging. a raised rcbv can, however, also be seen in low-grade oligodendrogliomas, particularly in those with a p/ q chromosomal translocation, which is associated with a better response to chemotherapy. pwi and dwi are useful in the differentiation of glial neoplasms from cerebral lymphoma, which has an increasing incidence in the immuno-competent population. dwi and pwi are also very useful in the differentiation of enhancing pseudo-tumoural lesion such as cerebral abscesses, tumefactive demyelination, pseudoprogression and radiation necrosis. perfusion imaging plays an important role in the characterisation and management of brain tumours. low-grade brain tumours may transform into high-grade gliomas at some point, which is a transformation that is highly variable and difficult to predict in an individual patient. conventional contrastenhanced computed tomography (ct) and magnetic resonance (mr) imaging are found to be insufficient to depict this transformation and angiogenesis and therefore to detect malignancy. however, perfusion imaging provides additional information over conventional imaging in terms of tumour physiology and haemodynamics, providing important biomarkers for malignancy and prognosis. perfusion ct and mr perfusion techniques such as arteriel spin labelling and dynamic susceptibility-weighted perfusion imaging are more practical and widely used compared to nuclear medicine methods. these perfusion techniques should be considered and used in routine clinical workup of brain tumours to asses grading and prognosis. maximal safe resection, radiation therapy and temozolomide chemotherapy are the current standard of care for newly diagnosed high-grade gliomas. still, hgg have a poor survival rate. a contributing factor to the poor survival is the inability of currently available imaging techniques to accurately delineate the tumour, with the result that targeted focal treatment my not be effective. conventional imaging is not able to give an early assessment of the effectiveness of radiation and/or chemotherapy. in addition, conventional imaging has difficulties in differentiating pseudo-progression, which is a common phenomenon in conventional chemo-radiation therapy, from true progression. early identification of patients who suffer from tumour recurrence can be of great advantage: it provides the opportunity to adjust individuals more rapidly, sparing patients unnecessary morbidity and delay in the initiation of other, maybe more effective, treatment. in recent years, different functional imaging approaches such as perfusion mri, diffusion-weighted imaging and spectroscopy, have been complementarily used for imaging evaluation of treatment response. in this lecture, different advanced mr and ct imaging methods used to support differentiation between pseudo-progression and true tumour progression to assess treatment response will be discussed. in addition, a novel recently published promising technique, the parametric response mapping (prm), a novel voxel-wise analytical method of monitoring physiological and environmental changes in a tumour volume during treatment will be presented and compared to the traditional methods used. finally, the aim of the lecture is to consolidate the present knowledge and novel ideas in brain tumour imaging for assessment of pseudo-progression versus true tumour progression. learning objectives: . to understand the challenges and limitations of routine mri in monitoring brain tumour treatment. . to become familiar with the role of advanced imaging biomarkers for early assessment of treatment response. . to learn how to integrate routine and advance mri into clinical practice after tumour therapy. the purpose of this lecture is to describe the role of functional radiological imaging modality-ct and mr perfusion in the evaluation of head and neck tumors. conventional contrast-enhanced ct and/or mr imaging are the current standard techniques for the diagnosis and treatment evaluation of the head and neck tumors. however, this method is limited in its ability to depict the angiogenesis which is a hall-mark of tumor growth. perfusion imaging provides a rapid evaluation of tissue perfusion and can be easily implemented in every head and neck ct or mr protocol. the determination of tissue perfusion is based on examining the relationships between the arterial, tissue and potentially the venous enhancement after the introduction of a bolus of contrast material. the quantification of the perfusion values helps to outline the malignant tissue as well as to differentiate recurrent disease from nonspecific post-therapeutic changes and can be used as a therapeutic monitoring tool during and after tumor therapy. in recent years diffusion-weighted mri (dwi) gained increasing importance and also acceptance in head and neck radiology. although this functional technique is challenging due to air tissue interfaces, its ability to improve the diagnostic accuracy is widely accepted. dwi can be applied to detect lesions not only in adults, but also in children. it is helpful in lesion characterisation and has a great potential to differentiate recurrence from posttherapeutic changes. initial promising results to improve lymph node staging however are difficult to reproduce. image interpretation is performed qualitatively based on visual assessment of the high b-value images (b= - sec/mm ) and the corresponding apparent diffusion coefficient (adc) map. quantitative image analysis is based on the measurement of the underlying adc value. solid tumors including recurrences are bright on the high b-value images and dark on the corresponding adc map, whereas posttherapeutic changes are bight on both the high b-value images as well as the adc map. cystic and necrotic lesions are typically dark on the high b-value image and bright on the adc map. furthermore, malignant lesions tend to have a lower adc compared to benign and cystic lesions provided that no necrosis is present. therefore, image interpretation always has to be performed together with morphological images to avoid misinterpretation of functional images. pet/ct has established itself as a robust, rapid and reliable technique in head and neck oncology. it is mainly used to stage nodal disease, to detect distant metastases and synchronous tumours, to identify unknown primary tumours in patients with metastatic neck nodes, to assess treatment response and prognosis after chemoradiotherapy and for radiotherapy planning. mri with diffusion-weighted imaging (dwi) is routinely used for the assessment of submucosal tumour spread, to stage nodal disease, to monitor treatment response and to detect recurrent disease. the information provided by pet/ct and mri is often complementary and the recent implementation of hybrid mr/pet systems in clinical settings holds promise because it can combine morphologic, functional and molecular information. this lecture focuses on clinical applications of pet/ct and mr/pet in the head and neck. current evidence about the combined use of pet/ct and mri with dwi is discussed. the principles of mr/pet data fusion are summarised as well as current knowledge regarding the diagnostic performance of mr/pet in the head and neck. typical radiologic findings of tumour manifestations are reviewed with particular emphasis on the early detection of lesions, their appearance on different imaging modalities and the added value of hybrid imaging techniques. the variable appearance of functional phenomena mimicking disease as well as the potential pitfalls of image interpretation and how to avoid them are equally addressed. major emphasis will be put on how to report the findings in a comprehensive way. multi-energy and functional imaging ct has reached a robustness allowing the use of this new technology in clinical routine for a variety of different clinical questions. this presentation will discuss the basic principles and the strengths and limitations of the techniques. implementations of multi-energy methods for material characterisation and of ct methods for functional imaging will be discussed. contrary to normal single-energy ct systems, multi-energy ct scanners allow simultaneous scanning at two peak x-ray energies. when the attenuation is measured at two energies, their values are not exactly proportional to each other, which open new diagnostic possibilities. measurements at two spectra can be achieved using multiple kvp and/or filtration or with detectors with energy discrimination. these methods have different pros and cons such as sensitivity to subject motion and dose efficiency. to be able to acquire functional data such as perfusion, images are acquired dynamically following the injection of a contrast agent and physiological models are used to convert the measured contrast agent concentration to perfusion estimates. methods that acquire multiple images have the potential to increase the radiation dose to the patient, so ct protocols need to be optimised. in computed tomography, d images are reconstructed from a number of x-ray radiographs that were acquired at different angles. tomographic reconstruction relates to the generation of a d image based on these acquired radiographs. most tomographic reconstruction methods are based on a technique called filtered back projection (fbp) in which a sharpened version of the radiographs are back projected to generate the d image. while it has been the standard reconstruction method, mostly due to its speed and good quality if many radiographs are available, iterative reconstruction methods are emerging. the reason for that is that fbp suffers from important disadvantages. in this talk, the basic concepts of iterative reconstruction are explained and its virtues are detailed. the flexibility of iterative reconstruction methods is demonstrated for the field of x-ray computed tomography. finally an outlook is given with respect to future research on tomographic reconstruction. interventional radiology (ir) has been increasingly applied in the management of obstetric and gynaecological haemorrhage. national reviews of maternal deaths from post-partum haemorrhage have recognised that maternal deaths may be prevented by ir and that all obstetric units should have protocols and arrangements in place to ensure appropriate and timely referral to ir. the important role that irs play in the management of fibroids has also highlighted how these techniques can be applied to other gynaecological conditions which may result in haemorrhage. this session will start by describing which gynaecological disorders may result in haemorrhage and the technical aspects of treatment followed by the published evidence for embolisation. the session will then focus on obstetric haemorrhage, with an emphasis on prophylaxis and how women deemed at high risk for haemorrhage might be managed safely. the techniques used for prophylaxis of haemorrhage will be described in detail and the published data presented. the final presentation will concentrate on the technical aspects of embolisation when haemorrhage has occurred to ensure the best results by knowing the relevant anatomy and appropriate technique of embolisation. the published evidence of the results of embolisation in pph will be presented. these presentations will be followed by a panel discussion on how irs can reduce the radiation dose whilst simultaneously ensuring successful outcomes for their therapies, an important issue in a young and fertile group of women. gynaecologic massive bleeding related to benign and malignant causes is under the scope of all radiologists because of being diagnostic and also because of its implication in interventional radiology procedures. the causes are uterine fibroids (uf) and post-partum hemorrhage (pph). however, oncologic disease, arterio-venous abnormalities, or iatrogenic injuries are less commonly known to be eligible for embolisation procedures. usually, surgical homeostasis attempts or radical hysterectomy is preferred to embolisation procedures. despite the good clinical outcome for hysterectomy and the hazardous success rate of conservative treatment, both are unsatisfactory to patients. pelvic artery embolisation (pae) could dramatically change the patients' clinical issue. the purposes of this lecture are to: revise the pelvic arterial anatomy (possible arterial anastomosis or variation); outline the aetiology of non-obstetric massive menometrorrhagia; expose the typical clinical presenting features; describe the imaging appearances of the etiologies; and discuss patient section, procedure technique, pitfalls and complications. obstetric haemorrhage occurring mainly in the postpartum period is a significant cause of maternal morbidity and death. blood loss of over and ml after vaginal delivery or caesarean section, respectively, complicates % of deliveries. major blood loss of more than ml occurs following less than % of all deliveries. the causes include uterine atony, retained placenta products, placental abnormalities, uterine rupture, lower genital tract laceration, cervical ectopic pregnancy and coagulopathies. generally, treatment is based on administration of uterotonic drugs, vaginal packing, surgical ligation of uterine arteries and even hysterectomy is sometimes needed. transcatheter embolisation of uterine, pudendal, vaginal arteries and ovaries is considered to be superior and should be the first-line treatment for intractable obstetric haemorrhage where interventional radiology is available. angiography reveals extravasation of contrast agent in more than % of these patients. the most frequent extravasation is from vaginal artery, and then from pudendal and uterine arteries. depending on the extravasation location and haemodynamic stability of a patient, f catheters or coaxial microcatheter technique is utilised for catheterisation. gelatin foam, microparticles acrylic glue and microcoils are the most frequent embolic agents. the embolisation procedure usually does not require general anaesthesia and can be repeated if bleeding continues. primary success rate in bleeding control is reported from to %. the most commonly reported long-term side effects after embolisation were transient buttock numbness and urinary frequency. the transcatheter pelvic artery embolisation for obstetric intractable bleeding is a fertility-preserving alternative to hysterectomy. medical imaging has nowadays integrated the diagnostic armamentarium of anosmic patients regarding not only qualitative assessment of the olfactory tract, but also quantitative evaluation of olfactory bulb volumes which are known to closely correlate to the olfactory function. many clinical studies on various pathological conditions have evidenced the value of such measurements in the workup of olfactory dysfunction for both aetiologic and prognostic purposes. imaging workup also plays a role in the medico-legal evaluation of post-traumatic anosmia together with electrophysiological and clinical olfactory tests. technical improvements in fibre tracking (ft) using diffusion-tensor imaging (dti) and appropriate designs of olfactory stimulation at bold-based functional mri (fmri) are expected to allow insights into the neurophysiological processes and circuitry of olfaction in the very near future. imaging workup of the anosmic patients will be the cornerstone of this lecture. the relevance of the different imaging techniques will be detailed. beyond the workup of anosmia, a comprehensive overview of the most common lesions of the olfactory tract seen in clinical practice will be given. additional review of lesions observed at the anterior cranial fossa in the near vicinity of the olfactory tract will be done, which comprehensively includes all commonly observed developmental, traumatic, inflammatory and neoplastic conditions not arising from the olfactory tract. their potential impact on the olfactory function or on other sensory/neurological functions will be underlined. clues to clinical/radiological differential diagnoses of the most common conditions and radiological features of the anterior cranial fossa will be highlighted. the central skull base, the floor of the middle cranial fossa, has a complex anatomy and is pierced by a variety of foramina and canals providing crossroads for spread of disease between the extra-cranial head and neck and the intracranial compartment. disease spread into the intracranial compartment indicates a dismal prognosis, as often it becomes inoperable due to involvement of vital structures including cranial nerves, carotid artery and/or brain parenchyma. imaging plays a pivotal role in the assessment of these structures which are not amenable to clinical inspection and can dramatically change the patient's management. in this complex anatomical area, ct and mr have a complementary role in providing a comprehensive roadmap for treatment planning. of major importance is the pterygopalatine fossa, the cavernous sinuses and orbital apex. the former, lying between the pterygoid plates and the maxillary sinus, is a major crossroad between the intra-and extracranial compartments and should be carefully inspected. pathologies affecting the central skull base are varied and may originate from the skull base proper, from the middle cranial fossa or from the extracranial head and neck. by looking at the centre of the lesion, its tissue characteristics and pattern of growth, it is often possible to provide a useful differential diagnosis and, most importantly, to map the lesion's extent. here, we present a radiologist-friendly approach to central skull base pathology highlighting the most important features in the differential diagnosis and treatment planning. . the jugular foramen: the jugular foramen is an opening in the skull base. the radiologic evaluation requires high-quality imaging with ct and mr. angiography is reserved for preoperative embolisation. it is important to recognise the "pseudo lesions". the most common tumour of the jugular foramen is the paraganglioma. the second is the schwannoma of the lower cranial nerve, and the jugular foramen meningioma is the third most common. the differential diagnosis shall be discussed. . the cerebellopontine angle (cpa) and the internal auditory canal (iac): the iac is a bony conduit for several nerves and a vessel, the neurovascular bundle. the cpa is a cistern of the peripheral cerebral spinal fluid, and several anatomical structures pass through this. it is also the place of some frequent disease processes. most of the lesions in the cpa are benign tumours with order of frequency: vestibular schwannoma and meningioma. the third most common lesion is a benign cystic lesion: the epidermoid cyst. in the iac, you can encounter the same benign tumoural lesion as in the cpa, but also inflammatory lesions, viral lesions and malignant lesions. why is it important in your imaging protocol of the iac and cpa region to use gadolinium? the differential diagnosis of different lesions shall be discussed. learning objectives: . to learn about the imaging techniques and anatomy in the posterior cranial fossa. . to become familiar with the imaging findings of common posterior cranial fossa pathologies. . to learn how to differentiate between the lesions in the posterior cranial fossa. health care is characterised by several specific features making it different from traditional markets. two of the key features are: the impossibility of patients to make choices, due to asymmetry of knowledge between them and their health-care providers; the fact that patients create an agency relationship with health-care providers, delegating to them the decision about the care delivered. due to these characteristics and to the fact that patients are fragile when they need care, there is a natural tendency for patients to rely on healthcare professionals. it is in this complex socio-technical environment that radiographers must be aware of their roles and responsibilities and ensure professional autonomy and accountability; demonstrate an ethical and knowledgeable understanding of the profession; apply professional practice in securing, maintaining or improving health and well-being; develop knowledge, skills and competences that underpin their education and training, contributing to the wellbeing of the patient; understand that professional advancement arises out of evidence-based practice and is acquired through focused research. this demands for a focus on patient care and safety, based on high professional standards. ebp is the best way to achieve this desideratum, as it combines the best research evidence with clinical knowledge and expertise, addressing the patient in a holistic way. since the radiographer is the ultimate interface between patient and technology, it is crucial to create a real teamwork concept, using guidelines for the roles and responsibilities of each team member as the pathway to minimise practice error, maximising patient and staff safety. the use of ionising radiation in medical exposures is well documented across countries. recent studies indicate that a substantial fraction ( to %) of these procedures is unnecessary when taking into consideration patient clinical indication. defensive medicine, economic interest, poor patient clinical information, patient pressure and the lack of knowledge about other alternative procedures, taking into account the benefits and risks, are the principal causes of unnecessary radiological examinations. patients must be referred to a medical imaging department for an examination that should be justified according to clinically appropriate image criteria and informed of the potential benefits and risks. following justification, the optimisation of practice is essential to ensure the minimal exposure of radiation dose to the patient whilst diagnostic efficacy is maintained. the principal aim of optimisation is getting a narrower dose distribution, with lower mean and th percentile values of the diagnostic reference level. optimisation processes need to consider several factors including the type of examinations, body region, clinical information, available equipment technology and image processing tools. to implement this process, a multidisciplinary teamwork is essential where radiographers, being the pivot between patient and technology, have an essential role. to understand and apply optimisation procedures, radiographers should be aware of the international guidelines, standards and directives. all medical imaging procedures must be audited to analyse if the workflow processes (referral, justification, optimisation and radiation protection principles) are according to the recommendations to create a radiation protection safety culture. although we are approaching the year , a lot of clinical radiography is not based on best evidence. lot of clinical decision-making is based on, for example, traditional practices that we cannot argue as being the best possible ones. in this presentation, barriers to using research and other sources of evidence and facilitators of evidence-based (eb) radiography are described. the role radiographers have in developing eb guidelines and procedures may vary according to educational level and work description. developing eb guidelines is not the work of every radiographer, but obeying them is. the speaker gives some suggestions on what to do in a situation if there are no eb guidelines and procedures in ones' country or institution and no group that develops them. with the framework of "the new work order" and increasing implementation of new work processes, professionals are faced with new modes of collaboration requiring communicative skills as well as multiprofessional competencies between all the stakeholders across the hospital. some evidence about the consequences of ineffective communication in the field of radiography is presented. in addition to benefits associated with the procedure of clinical audit, uniform good quality protocols for examinations and uniform national/international criteria help to perform comparisons between radiology units. clinical audit also works as an educational tool and as a feedback tool for the staff on their performance. it also points out the need for corrective actions. initiatives from professional organisations are probably the most powerful engines for the construction of europe, and in many cases open the road for legal and political advances. many medical specialties felt that there was a need for the harmonisation and standardisation of medical training over europe. the esr has shared this opinion and has elaborated a unanimously appreciated training curriculum, which is constantly updated. establishing the ebr (european board of radiology), with the mission to organise a european diploma was the logical next step. today, examinations have already been organised and more that candidates from european countries and abroad have applied. the trainee who passes the examination proves his professional skills and has reached the objectives assigned in the curriculum. in this session, we will explain how esr organises the diploma. we will review, capitalising on our current experience, the main lessons learnt from the past editions, the keys for success and reasons for failure, as seen by the examiners. we will also learn about the "diploma adventure", from the point of view of a successful candidate. national radiology training programmes in europe differ to a large extent, regarding length of training, content, and the presence or absence of a national board examination for certification. thus, for cross-border radiologic activities, the level of training and expertise applying to radiologists is difficult to assess under these circumstances. there is an increasing number of medical subspecialties, which organise european diplomas. more than subspecialties (e.g. anaesthesiology, ophthalmology, urology, etc). organise european examinations, which are well received among the respective communities. growing numbers of residents in training successfully stand this test of knowledge and practical skills. recognition of european diplomas by national authorities is an issue, which will increase the level of acceptance. the present status of the recognition process in european countries will be summarised. case material for the diploma will test knowledge in general radiology at a standard to be expected at the end of training as outlined in the esr curriculum. all ten esr-recognised subspecialty areas of the curriculum will be tested. the written exam comprises two computer-based sections, a multiple response section, and a short case section. there will be multiple response questions. these questions comprise both multiple options format, a single stem with answer options, and short imaging studies where candidates are asked to either annotate the image from a drop-down menu, or select the radiological features displayed or differential diagnosis from the options given. a special scoring system has been developed to prevent guessing. the short case section comprises or case-based questions. you may practice using the self-assessment tests on the esr website which follow the same format as the written examination. for the oral cases, you must have a systematic method and perform under pressure, which takes practice. you may rehearse with experienced radiologists who feedback on your performance. you can break a radiology report into areas, observations, interpretation and conclusion. conclusions should take into account the clinical information. candidates often forget this under pressure, so ask for it to be repeated. your differential diagnosis should be logical and comprehensive. the commonest causes of an abnormality is a good topic to revise. suggest if further imaging tests are indicated and give an indication of urgency. each case is marked separately. as a well-known statement in the academic world of education, "assessment drives learning". with the help of carefully prepared and performed examinations, it is possible to emphasise and instill the training curriculum. due to different reasons, training of radiology in european countries is highly varied. like in our experience in turkey, a central examination system, accompanied by a neatly prepared training charter and curriculum, is a good starting point to solve the problem. we believe that a common european assessment system like edir will contribute a great deal to the harmonisation of radiological training and establishment of quality standard in every country. the need for harmonising the training is not unique to radiology. this is why in more than medical disciplines, european diploma examinations are now being organised. furthermore, in some disciplines like urology, annual and online "in-service assessment" of residents and practising urologists allows the participants to evaluate their current knowledge base against the current european standards, and also provides the trainers and directors knowledge about the teaching and learning process in education centres. although there are huge diversities among different european centres, the urgent need of harmonising radiology training and setting a standard of quality are felt by all radiologists in europe. establishing and institutionalising a common assessment system in european radiology appears to be the shortest way to reach this goal. this is why we should support "european diploma in radiology" by any means and work hard to promote its recognition throughout the continent. the majority of emergency ct studies reported by junior radiologists or general radiologists out-of-hours comprise brain scans. brain ct studies are often performed to detect acute life-threatening abnormalities, such as stroke, intraparenchymal or subarachnoid haemorrhage, cerebral edema, etc. misrecognition of these often subtle, but life-threatening abnormalities can lead to inappropriate patient management and worsen patient outcome. errors in interpretation can generally be categorised as either perceptual or cognitive in nature. perceptual errors are those in which the radiologist does not see the abnormality, resulting in a false-negative interpretation (e.g. basilar artery thrombosis, deep cerebral venous thrombosis, pres,…). cognitive errors, on the other hand, are those in which an abnormality is identified but the meaning or significance of the abnormality is not recognised. cognitive errors can result in false-positive interpretation if, for example, a normal anatomic variant is mistaken for a pathologic condition. while the more common normal variants and artefacts often do not present a problem to experienced clinicians and neuroradiologists, less experienced individuals should beware of these diagnostic hazards. to reduce false-negative and false-positive reporting, a checklist of the review areas (blind spots) to be verified on any brain ct scan will be offered and the most frequent normal variants will be discussed. pitfalls in brain imaging comprise perceptual or cognitive errors of interpretation of imaging findings. errors of perception refer to a missing of a pathology that is present on an image, while cognitive errors consist of a wrong interpretation of a seen structure or pathology. interpretation may be false negative or false positive. in addition, a wrong conclusion may be drawn resulting from missing, incomplete or false clinical information, or as a consequence of a lack of knowledge of differential diagnoses. perception errors are frequently the consequence of incomplete examination protocols where lesions are missed (for instance, acute ischaemic changes without the use of diffusion-weighted imaging) or signals, for instance, flow-related phenomena are misinterpreted. asymmetric positioning of the patient`s head may also lead to misinterpretation of side differences, especially in the temporal lobe. another source of perception errors might be reduced attention (especially at night shifts) and have been proved to occur in regions that are "potential blind spots", as the sulci, cavernous sinus, meckel cave, dural sinuses, brainstem, and skull base foramina. perceptual errors may be avoided by following a checklist when reading images. all sequences should be used for comparison of signal intensities to distinguish artefacts from pathology. another very important fact to avoid misinterpretation lies in a profound knowledge of morphologic and metabolic age-related changes of the brain and of anatomical normal variants (such as, for instance, accentuated virchow robin spaces in certain locations). cystic liver lesions can be classified based on their nature as benign and malignant. in the benign category are, among others, developmental and infectious/inflammatory cysts, while neoplastic cyst can be subdivided into primary and secondary. developmental cysts originate from abnormal ductal plate malformation and consist of hepatic (bile duct) cyst, bile duct hamartomas, caroli's disease and polycystic liver disease. infectious/inflammatory cysts include, among others, abscesses (pyogenic and amoebic) and hydatid cysts. primitive neoplastic cystic lesions are cystoadenoma and cystoadenocarcinoma. secondary lesions can originate mostly from mucinous tumours such as colon and ovary. the role of crosssectional imaging in the detection and characterisation of these entities will be discussed, with an emphasis on the differential diagnosis with ct and mr imaging. benign hepatocellular neoplasms are being recognised with increased frequency using cross-sectional imaging. one of the main goals is to be able to make a clear-cut differential diagnosis between focal nodular hyperplasia (fnh) and hepatocellular adenoma (hca) since patient management is substantially different. despite the sound knowledge acquired in the last few years about the morphological features of fnh using various cross-sectional imaging techniques, new players in the field have arisen such as diffusionweighted mr imaging (dwi) and use of hepatobiliary contrast agents. these new biomarkers offer a different view over fnh and allow a more accurate characterisation even in more atypical cases. concerning hca, current knowledge implies that the sub-types of this neoplasm should be known since, again, patient management differs and these patients are no longer seen as compulsory surgical candidates. these sub-types will be further discussed and the role of imaging for risk stratification (haemorrhage and malignant transformation) will be addressed. further, illustrative cases of combined fnh/hca cases will be demonstrated along with the main imaging clues for a successful differential diagnosis. imaging in the early postoperative period is complex. it is essential for radiologists to know the new anatomic arrangement after surgery and to understand the range of normal postoperative appearances. this latter aspect can be particularly difficult, because the radiological findings are affected by the type of operation performed (open vs. laparoscopic) and the complexity of the surgery (such as the presence of adhesions or haemorrhage) as well as the underlying comorbidity of the patient. patients may be considered in broad categories: haemodynamically unstable patients who may be bleeding; patients with distension or unopened bowels who may have obstruction or ileus; patients with sepsis in whom to search for an intraabdominal collection or leak; and patients who do not follow an expected recovery for which the cause is unclear. ct is the primary imaging technique, with ultrasound reserved predominantly for liver and renal transplants or assessment of perihepatic collections, and fluoroscopy for routine postoperative assessment of upper and lower gi anastomoses. ct protocols should be optimised to detect particular complications with positive luminal contrast for assessment of anastomotic leaks ( %), triple phase imaging for bleeding (without positive oral contrast) and delayed phase imaging to detect ureteric injury. since each operation has a specific range of expected complications, these should be considered when deciding on the protocol and in light of the patient's clinical status. excellent communication with the surgical team is required to make an accurate diagnosis and in particular where haemostatic compound or mesh for hernia repair was used. learning objectives: . to understand the best imaging options for investigating suspected postoperative complications. . to appreciate the normal appearances of the abdomen and pelvis after surgery, in particular with regard to free fluid, haematoma and free gas, and when to suspect complications. radiologists should be aware of the newer surgical techniques and expected post-operative alterations, to yield a correct interpretation of a post-surgery imaging examination, thus being able to differentiate a normal post-operative finding from a potential complication. in this setting, it is crucial to perform a technically adequate imaging examination, so that post-operative anatomical and functional findings may be evaluated. therefore, the aim of this lecture is to give an overview of the contribution of various imaging modalities in the diagnosis of late post-operative complications following gi tract surgery. it will include a mention of the technical issues that need to be considered to achieve better diagnostic accuracy, as well as a description and illustration of the main imaging findings of late post-operative complications. those include diseaserelated (recurrence for malignancy or inflammatory disease) and procedurerelated (anastomotic strictures, internal herniation, adhesions and intussusception, among others) complications. focus will be placed on crosssectional imaging techniques, which at present constitute the workhorse for detecting and characterising late post-operative complications after gi tract surgery. in this way, imaging has an obvious and pivotal role in planning therapy, since some late complications are usually treated in a conservative way while others require a surgical approach. lung biopsy of a suspected lung cancer remains a well-established technique for histopathologic examination in patients with suspected lung cancer. complications can nevertheless occur and therefore indication should be given after carefully balancing the benefits and drawbacks for a particular patient. the method should be clearly considered complementary to alternate methods of tissue sampling, fiberoptic endoscopic, mediastinoscopy or us-guided endoscopy, surgical biopsies and resection during a multidisciplinary discussion. several steps are needed in the preparation of the biopsy procedure, including informed consent, management of anticoagulation and anti-platelet medications, imaging assessment of the lesion and its environmental lung, and planing of the needle trajectory procedure. the choice of the guiding method and the most appropriate biopsy needle is still largely dependent on local skills and habits. ct-guided percutaneous biopsies using coaxial automated core biopsy needles offer many advantages. needle manipulation can help to reach difficult targets. participation of the patient is needed in terms of respiratory manoeuvres and breathhold. complications may occur such as pneumothoraces haemorrhage and air embolism. knowledge of the respective risk factors and the potential method of prevention or treatment by operators are essential. the therapeutic response of lung cancer can be objectively evaluated on the basis of changes in the tumoural size or depiction of metastases, such proposed in the recist criteria (response evaluation criteria in solid tumours). recent advances in cancer biology have triggered development of novel targeted therapies designed to disrupt specific biologic pathways. among them, antiangiogenic drugs represent a promising strategy for non-small cell lung carcinomas (nsclc). these agents are more cytostatic rather than cytotoxic, explaining the limitations of tumour response assessment based on morphological criteria. dynamic contrast-enhanced imaging techniques have the potential to quantify tumoural angiogenesis. in particular, dynamic contrastenhanced multidetector-row ct (dce-ct) represents a promising tool to provide non-invasive and repeatable assessment of the angiogenic process within non-small cell lung cancers (nsclc), offering the possibility to generate morphological and functional information from the same examination. dce-ct allows the calculation of regional tumour blood flow, blood volume, flowextraction product, and permeability-surface area product, over the entire tumoural volume, using mathematical models and dedicated softwares. dce-ct can depict early changes in lung cancer vascularity, before tumour shrinkage, that could help predict response to antiangiogenic drugs. becoming familiar with this technique enables the radiologist to integrate it into clinical practice and to assist the thoracic oncologist in the pre-therapeutic and follow-up evaluation of nsclc patients treated by antiangiogenic drugs. this new approach should improve patient's selection for targeted therapies. a- : it is now accepted that pet-ct is of value in the staging of lung cancer and reduces the number of unnecessary thoracotomies. its role has been further clarified by recent publications on its value in assessing mediastinal nodal involvement, tumour aggressiveness using either standardised uptake value or total glycolytic volume, and response to neoadjuvant chemotherapy. more recently, mri has been investigated as a tool to detect distant disease using diffusion-weighted imaging, and there are a number of trials that have compared both pet-ct and dwi mri retrospectively and prospectively. this presentation will summarise the current available data and the likely benefits of either imaging modality neurological deficits in children are an urgent condition that depends significantly on imaging for a prompt and accurate diagnosis because of the significant overlap present in clinical history, presentation and neurological examination. different imaging modalities, such as ultrasound, computed tomography (ct) or magnetic resonance imaging (mri), are utilised dependent on the age of the patient and neurological symptoms. the purpose of the present lecture is to discuss the causes and imaging appearance of acute neurological conditions in childhood, broadly classified into stroke, infection, inflammatory demyelination, metabolic disorder, cerebral neoplasm or neurotoxicity. imaging also plays an outstanding role in the management of paediatric oncology patients presenting with acute neurological symptoms related to disorders of blood cell counts, immunosuppression, neurotoxicity of therapy, or progression of the primary malignancy. a review of the main indications to perform a neuroimaging procedure in these children will be undertaken as well as a differential diagnosis based on representative cases selected from the daily routine in a paediatric tertiary hospital. practical algorithms with the preferential use of either ct or mri will be developed for each section. ct continues to be the first imaging modality in these patients in many centres, despite the accompanying radiation, because of the easy availability and no requirement of sedation. however, mr imaging is nowadays better for imaging these children owing to no radiation, the more completely provided information and the useful advanced techniques that can be used, such as diffusion imaging (di), spectroscopy, arterial spin labelling (asl), and susceptibility weighted imaging (swi). learning objectives: . to learn about the currently limited role of ct in the non-traumatic acute setting. . to become familiar with radioprotection strategies and protocols adapted to children. . to consolidate knowledge on the role of mri as the modality of choice for acute non-traumatic neurologically ill children, with an emphasis on newer techniques. . to become familiar with imaging findings and the main differential diagnosis of acute neurological conditions in children. b. imaging of acute chest pain and distress in children c.e. de lange; oslo/no (clange@ous-hf.no) acute chest pain in children is a common complaint in the emergency department, but patients rarely present with significant distress or lifethreatening symptoms requiring immediate care or resuscitation. the most frequently reported cause is benign musculoskeletal pain followed by respiratory and gastrointestinal causes, while cardiac causes are less frequent. a thorough clinical history and careful physical examination will determine, in most cases, the patients in need of further investigation to establish a diagnosis. in this regard, radiology plays an important role, especially in the emergency setting in patients with more serious associated symptoms like acute breathing difficulties, swallowing problems, fever or sepsis. when choosing the appropriate technique for investigation, the consequences of radiation exposure in children must be considered. plain radiography and fluoroscopy still remain the most important and frequently used tools to gain information on various acute chest/pulmonary problems. ultrasonography is the first choice for diagnosis/treatment of pleural effusions. multidetector computed tomography and magnetic resonance imaging are mainly used for investigating pulmonary/mediastinal masses and congenital abnormalities of the great vessels and the lungs. this lecture will discuss the choice of imaging technique and the urgency of radiological management depending on the symptoms and age of the patient. the imaging characteristics of the different causes of acute chest pain and/or distress in children will be reviewed, represented by the more common conditions involving the chest wall, respiratory tract, oesophagus and the heart, as well as less frequent causes such as tumours, manifestations of congenital malformations and nonaccidental trauma. outcome data from trauma series have demonstrated improved patient survival by the prompt diagnosis of a range of injuries and the recognition of life-threatening sequels, principally that of active arterial haemorrhage. widely used trauma scoring systems are applicable in the paediatric population, although the mechanisms and combination of injuries may differ from those encountered in adults. a ct diagnosis of active haemorrhage demands early operative or non-operative intervention with embolisation or use of alternative endovascular techniques including deployment of vascular stents. this principle is applicable to blunt or penetrating liver, splenic, renal or pelvic trauma. it is also applicable in some cases to severe mediastinal and limb vascular injury. important caveats are firstly the use of ct in an overall trauma service and avoidance of any inappropriate irradiation. secondly, in paediatric interventional practice, due regard needs to be given to the delivery of implantable devices that may have adverse sequels in later life. nevertheless, the demand for immediacy in intervention may outweigh any such consideration. this presentation will summarise the importance of imaging and intervention in both the early and delayed complications of trauma with an emphasis on abdominal and thoracic trauma. brachial plexus originates from the ventral branches of the cervical nerve roots from c to t . it is composed of roots, trunks, divisions, cords, and branches, topographically divided into supraclavicular (roots and trunks), retroclavicular (divisions), and infraclavicular sections (cords and branches). mri has the advantages of multiplanar imaging, high tissue contrast, and relative paucity of artefacts. the t -weighted sequences display topographic anatomy including muscles, blood vessels, and nerves stressed by tissue fat planes. the nerves appear as elongated fibres that are isointense to the scalene muscle, posteriorly and superiorly to the curvilinear flow void of the subclavian artery. the fat-suppressed pd and t -weighted and stir sequences detect signal alterations of the bp. general abnormal findings include: loss of fat planes around part or all bp components, nerve signal abnormalities with mild or marked hyperintensity on t -weighted images that can be associated with swelling, focal or extensive enhancement of the nerves after gad injection on t fat sat images. differences in signal intensity should be judged by visual inspection, which is susceptible to a subjective point of view; the comparison of both sides of bp has a relevant role in judging the presence of signal alterations, especially when they are smooth and/or focal. the pathology of brachial plexus can be divided into nontraumatic and traumatic brachial plexopathies. among nontraumatic brachial plexopathies, we find radiation fibrosis, metastatic breast cancer and primary or metastatic lung cancer. other pathologies are tumours and inflammatory disease or thoracic outlet disease. the peripheral nerves of the upper limb are affected by a number of entrapment and compression neuropathies. these syndromes involve the brachial plexus as well the musculocutaneous, axillary, subscapular, ulnar, radial and median nerves. clinical examination and electrophysiological studies are traditionally the mainstay of diagnostic workup. however, ultrasonography and magnetic resonance imaging (mri) may provide key information about the exact anatomic location of the lesion or may help to narrow the differential diagnosis. in certain patients with the diagnosis of a peripheral neuropathy, imaging using either ultrasonography or mri may help establish the cause of the condition and provide information crucial for conservative management or surgical planning. in addition, imaging is particularly valuable in complex cases with discrepant nerve function test results. a variety of peripheral neuropathies can be encountered in the lower limb. most are entrapment syndromes affecting many nerves, such as the sciatic, gluteal, femoral, lateral femoral cutaneous, obturator and pudendal around the hip, the peroneal and its branches and the saphenous at the knee, the superficial peroneal at the lateral leg, the tibial with its plantar and calcaneal branches at the ankle, the deep peroneal and the interdigital nerves in the foot. although clinical examination and nerve conduction studies are the mainstay of the diagnostic workup of peripheral neuropathies, ultrasound (us) and magnetic resonance (mr) imaging may provide key information about the exact anatomic location of a lesion and the nature of the constricting finding or may help narrow the differential diagnosis. in patients with peripheral neuropathies of the lower extremity, us and mr imaging may provide critical information for planning an adequate treatment strategy. although us and mr imaging have followed parallel paths for nerve imaging with little comparison of the two modalities, us seems to have some advantages over mr imaging, including higher spatial resolution, time effectiveness, the ability to explore long nerve segments in a single study and to examine tissues in both static and dynamic states. advances in diagnosis of acute stroke have been achieved by brain imaging. ct or mri distinguish ischaemia from haemorrhage and may identify acute clot (dense artery sign) or vessel wall pathology by "black blood mri". dwi provides evidence of early infarction. ct and mra enable identification of large vessel pathology as potential source of embolic or haemodynamic ischaemia. supplementary techniques are ct or mr perfusion. on mri perfusion, a mismatch between the area of restricted diffusion and perfusion (pwi) is a signature of the penumbra. the tissue of pwi restriction outside of the dwi abnormality represents "tissue at risk". similarly on ct perfusion, the region of reduced cerebral blood volume presumably represents irreversible infarction and the area of reduced cbf and extended mtt visible beyond the cerebral blood volume abnormality represents potentially reversible ischaemia. morphologic imaging and advanced standardised perfusion/penumbral stroke protocols aim at identifying lesions that are amenable to acute stroke therapy and exclude pathologies that mimic stroke but do not represent vascular disease. since iv tpa has become an approved therapy from , the number of acute stroke patients entitled for treatment has remained limited (~ ) despite extension of the time frame from to . h. dwi-flair mismatch and an individualised assessment of the ischaemic penumbra may serve in the identification of patients within the appropriate time frame. by selection of patients with advanced brain imaging and initiation of appropriate therapy, a further increase in good outcomes and reduction of the incidence of symptomatic haemorrhage may be achieved. in recent years, the role of imaging in the patient admitted with an acute neurologic deficit has changed significantly, due to the arrival of new treatments for acute stroke, aimed at re-establishing blood flow, reducing infarct size and protecting the brain at risk. the first goal is to differentiate haemorrhagic from ischaemic stroke and to rule out other stroke mimics. this can be achieved by performing nonenhanced ct scan of the brain. the next strategic imaging objectives include: demonstration of major blood vessel occlusion (e.g. by ct angiography) and identification of potentially salvageable brain tissue, the so-called "penumbra" (e.g. by ct perfusion). ct angiography is performed during rapid intravenous bolus injection of a high-concentration iodinated contrast agent. the fov should cover not only the intracranial arterial circulation, but also the arteries of the neck, to exclude dissection. ct perfusion is also achieved by bolus injection of contrast, followed by a series of fast images or volume acquisition. ct densities change over time and reflect the iodine concentration. perfusion images are processed to generate parametric maps, which reflect: regional cerebral blood flow (rcbf), blood volume (rcbv), mean transit time (mtt), and time to peak (ttp).the combination of ct angiography and ct perfusion provides a unique insight into the pathophysiology of the cerebral circulation. these techniques are now essential tools in the management of acute stroke and in selecting those patients who are potential candidates for advanced therapies such as thrombolysis or thrombectomy. learning objectives: . to become familiar with a comprehensive imaging protocol in patients with suspected stroke. . to understand the advantages and limitations of cta and perfusion in the initial work-up of stroke patients. . to recognise the different imaging patterns in stroke and their prognostic value. a- : b. stroke mimickers and pitfalls p. vilela; lisbon/pt (ferrovilela@sapo.pt) "stroke mimic" is classically used to describe nonvascular diseases that present with acute focal neurologic deficit corresponding to a consistent vascular distribution, which may resemble or may even be indistinguishable from stoke. it is estimated that up to % of stroke-like presentations are due to mimickers. there are several neurological and psychiatric disorders that can have such a clinical presentation, such as seizures and/or postictal status, the most frequent one. the other classical clinical stroke mimickers include: multiple sclerosis, migraine (specially hemiplegic migraine), metabolic disturbances (more commonly hypoglycaemia/hyperglycaemia), intracranial tumours or infections and the conversion reactions. brain imaging plays a key role in the diagnosis and management of acute stroke by differentiating ischaemic from haemorrhagic lesions, identifying the vessel occluded and estimating the viable brain tissue that is at risk for stroke. imaging is also important to exclude some of the aforementioned stroke mimics. the more comprehensive stroke imaging protocols, with ct perfusion/angiography and/or with mri, have reduced significantly the misdiagnosis of stroke. mri-dwi is the most sensitive and specific imaging modality for depicting ischaemic stroke. however, it is also essential to be aware that there are some pathological processes that can mimic stroke in imaging studies. these include some disorders that may present themselves with lesions associated with restricted diffusion, like transitory postictal brain abnormalities, migraine and encephalitis. the author reviews the most common clinical and imaging stroke mimics and highlights the importance of brain imaging in depicting these mimickers and avoiding the potential adverse effects of stroke therapy in these patients. learning objectives: . to learn the differential diagnosis of stroke. . to understand the role of ct and mri in the work-up of stroke and related disorders. . to recognise imaging patterns that may mimic stroke clinically and radiologically. imaging plays a central role in the management of stroke, which is an important health issue according to the number of patients involved and the severity of the disease. it helps to select patients who will benefit from a revascularisation therapy (iv thrombolysis or endovascular treatment) at the acute phase of stroke. if the value of perfusion/diffusion mri mismatch in the evaluation of penumbra is still a matter of debate, other imaging factors are associated with the clinical outcome including length of clot, flair positivity, and collateral circulation. if iv thrombolysis using rtpa is still the reference treatment, endovascular treatment is emerging since several years as a feasible and efficacious alternative singularly since the appearance of stent retrievers. recent neutral randomised trials comparing iv thrombolysis and endovascular treatment have shown the critical role of appropriate imaging in the selection of patients who can benefit from acute revascularisation as well as the importance of using the most efficacious endovascular devices. prevention of stroke is partially based on the treatment of cervical and intracranial stenosis. several randomised trials comparing carotid angioplasty and carotid endarterectomy were initially negative, but a recent meta-analysis showed that below the age of years both techniques were equivalent. the place and value of endovascular treatment of intracranial arterial stenosis is still controversial after the publication of the sammpris results. the management of thyroid nodules has been continuously evolving. i hope that during this session you will understand the important differences in the upto-date national and international guidelines on thyroid nodule management and understand the role of the radiologist in the multidisciplinary thyroid meetings. the features that are suggestive of benign, indeterminate and malignant nodules will be demonstrated. advances in both radiological and cytological techniques such as us elastography and braf mutation analysis that may help triage patients with thyroid nodules will be covered. the differing biopsy techniques (fine needle aspiration, non-aspiration (fna and fnnac) and trucut biopsy) and their roles will be highlighted. there will be time for an open question and answer discussion with all the speakers before the end of the session. the management of thyroid nodules and the guidelines of the various interested parties, surgeons, endocrinologists, nuclear medicine physicians, radiologists and ultrasound specialists, vary across the world, indeed between different countries within the eu, and are constantly evolving. i will discuss how the thyroid multidisciplinary meeting (mdt) works at our institution and the role of the radiologist in it. the current differing international guidelines on the management of thyroid nodules will be mentioned, highlighting their salient points and differences. the role of the differing imaging modalities used in the management of thyroid nodules will be discussed based on differing clinical scenarios. finally, the management of the common clinical scenario of the incidental thyroid nodule will also be discussed. learning objectives: . to understand the role of the radiologist as part of a multidisciplinary team. . to learn about current guidelines on the management of the thyroid nodule. . to understand the role of various imaging modalities in the patient with thyroid nodule. thyroid disease is ubiquitous and usually benign; therefore accurate imaging of the thyroid is a major challenge for radiology. significant advances in conventional ultrasonography allow superb visualisation and anatomic characterisation of thyroid pathology and the impact of broader bandwidths, higher frequencies, spatial compound imaging and novel signal processing techniques will be discussed in this session. the key b mode features of thyroid nodules are discussed with reference to relevant clinicoradiological guidelines, specific pitfalls and limitations. a significant number of nodules remain indeterminate after conventional assessment, and imaging advances that enable more accurate, non-invasive thyroid characterisation are highly attractive, potentially reducing unnecessary biopsy and surgery for a large number of patients. ultrasound elastography offers a potentially useful adjunct to conventional sonography in thyroid disease with a growing evidence base indicating that thyroid malignancies are typically stiffer than benign lesions and that a 'soft' cutoff value with a high negative predictive value is feasible. however, elastography studies have included a variety of different techniques, patient/nodule selection and assessment methods; therefore the current role of elastography will be discussed. fine needle biopsy of the thyroid nodule f. campoy-balbontín, m.c. jurado-gomez; sevilla/es (fcampoy @gmail.com) thyroid nodules are very common. the clinical importance of thyroid nodules rests with the need to exclude thyroid cancer, which occurs in - %. ultrasound (us) has been widely attempted to differentiate benign from malignant nodules and to guide fine needle biopsy (fnb). however, considerable overlap between benign and malignant characteristics has been found. nowadays, there are a number of different guidelines for the management of thyroid nodules. at our hospital, we have adopted the guideline proposed by the society of radiologist in ultrasound ( ). the different elements necessary to perform the fnb procedure are demonstrated; the transducer probe, the needles, the slides, the syringe. the way of managing these elements is shown by figures and videos, with different skills and performances to optimise the procedure and get the best sample. uscontrol fnb can be in parallel or perpendicular, both methods are demonstrated. thyroid fnb is usually non-aspirated, but sometimes it has to be undertaken with aspiration; when and how to change from one method to another is explained. with good technique, the insufficient cytological rate can be significantly reduced, with which the need for core biopsy diminishes. although the complication rate for core biopsy is low, fnb is safer and if performed correctly has a high diagnostic yield. core biopsy should be limited to those nodules with a second insufficient fnb cytological result, with us findings suspicious for malignancy. multimodality breast imaging is emerging as radiologists have access to new technologies coinciding with the refinement of operative techniques. one of the challenges for radiologist remains the correct preoperative staging, especially the metastatic involvement of axillary lymph nodes. multimodality imaging has new accurate solutions. the imaging follow-up of patients with sophisticated oncoplastic techniques is another challenge where multimodality breast imaging is the solution. coincident with this increasing contribution to the diagnostic process is the emerging role of the breast imager as a therapeutic clinician, making use of innovative image-guided procedures. in this integrated rc, experts will present a clinical update on these newer techniques and there will be an opportunity to discuss how the evolution of such techniques is changing the nature of the modern multidisciplinary team meeting. a. conventional, functional and interventional lymph node assessment r.m. pijnappel; utrecht/nl (r.m.pijnappel@umcutrecht.nl) metastatic involvement of axillary lymph nodes has been known to be one of the most important prognostic factors for women with breast cancer. the traditional approach to staging the axilla is either lymph node sampling procedures or sentinel node biopsy. the main diagnostic features of potentially malignant involvement of the axilla are abnormal lymph node morphology (shape and cortical thickness). there has been a concerted effort in recent years to find imaging techniques that might facilitate accurate axillary staging. so far, no imaging technique alone (ct, mri, scintigraphy and ultrasound) has been capable of differentiating between positive and negative lymph nodes of the axilla in breast cancer. recent techniques like gadofosveset-enhanced magnetic resonance imaging and high spatial resolution -t mri imaging appear promising; however ultrasound-guided sampling of suspicious lymph nodes by core or fna remains the standard of care in assessing the axilla prior to treatment planning. ultrasound-guided axillary lymph node sampling is an effective method of assessing the axilla. a recent meta-analysis shows that ultrasound can be expected to achieve sensitivity approaching % for detecting abnormal nodes in those that eventually prove to be nodal metastatic disease. the false-negative rate where biopsy is performed is around %. it is impossible to detect the sentinel node by ultrasound alone. therefore a new promising technique was introduced, injecting an ultrasound-contrast agent around the nipple. using this method, it is possible to detect the sentinel node in % and therefore lower the false-negative rate of us-guided biopsy with another %. oncoplastic breast procedures were introduced to fill the gap between comprehensive oncologic surgical treatment of breast cancer and the achievement of cosmetic results that fulfill patient expectations in both, body imaging and psychological well-being. due to its complexity and relevance for the patient, the decision of performing these procedures must be made as part of the multidisciplinary approach of breast cancer treatment. as a consequence, the role of breast radiologists has expanded beyond the anatomic region of the breast and the usual imaging techniques. basic knowledge of the different oncoplastic techniques is mandatory to understand the spectrum of findings from a multi-modality approach. implants and/or autologous reconstruction techniques (pedicle, free or perforator flaps, as well as lipofilling techniques) are widely applied. the role of the radiologist in the multidisciplinary team is twofold: assessment during the planning stage, and imaging evaluation at follow-up. the assessment during the planning stage includes the determination of the local extent of the disease that makes the choice of the appropriate surgical technique possible, and the imaging study of the donor site in those cases where autologous reconstruction is elected. imaging evaluation at follow-up comprises the recognition of changes and potential pitfalls after reconstruction, the identification of short/mid/long-term reconstruction complications, and the detection of recurrent/second carcinomas. controversial aspects will be reviewed, such as the probability of recurrence after oncoplastic surgery, the need to establish multimodality follow-up protocols and the interrelations between the autologous tissues and the mastectomy bed or remaining breast. the use of image guidance for surgical planning has only recently been accepted. the use of intraoperative ultrasound in women undergoing lumpectomy is associated with a higher rate of negative margins. the combination of image guidance and radiological intervention techniques also harbours the possibility of tumour treatment without surgery. most techniques make use of the placement of needles within the tumour. treatment is performed by heating, freezing or extracting the tumour tissue. currently, radiofrequency ablation under ultrasound guidance is being furthest evaluated. however, in rfa even after optical complete tumour ablation, residual vital tumour tissue is still found in many cases. this is mainly dependent on tumour size with poorer results ( - % success rates) in tumour over cm, and better results (~ % success rate) in smaller tumours. adequate tumour size estimation is thus of vital importance. currently, since remaining vital cells cannot be excluded, the technique is limited to use in patients who cannot undergo surgery due to poor health state. larger series in which rfa is combined with radiotherapy have not been reported. it is therefore not clear whether it is important to actually excise residual vital tumour. similar restrictions currently hold for cryotherapy, laser ablation and hifu. large vacuum-assisted needles and the breast lesion excision system can be used to remove the tumour through a minimal incision in the skin. however, margin evaluation is difficult. nevertheless, these techniques are already optional for the removal of high-risk lesions and can potentially be combined with (focused) radiotherapy. the müllerian ducts are paired embryologic structures that undergo fusion and resorption between the th - th weeks of gestation to give rise to the uterus, fallopian tubes, cervix, and upper two-thirds of the vagina. non-development, defective vertical or lateral fusion, or resorption failure of the müllerian ducts can result in formation of müllerian duct anomalies (mdas), whose reported prevalence ranges between . % and %- %. the classification revised by the american society for reproductive medicine in is the most widely accepted. obstructive mda can occur in infants as palpable pelvic mass, at menarche with cyclic pelvic pain, or pelvic mass, and primary amenorrhea. complications include hematocolpos, hematometra, hematosalpinx, endometriosis, pelvic adhesions, and obstruction of urinary tract. mdas are commonly associated with renal and other anomalies; thus, identification of both kidneys is important. accurate diagnosis of an mda is essential because of the high associated risk of infertility, endometriosis and miscarriage, and since the management approach varies depending on the type of malformation. hysterosalpingography (hsg) is routinely used in evaluation of infertility. because a key component of mdas characterisation is the external uterine fundal contour, hsg is limited for this purpose. ultrasonography (us) is initially performed to evaluate uterine anatomy and to assess for associated renal abnormalities. mri is reserved for complex or indeterminate cases to characterise the uterine anomaly and evaluate the possibility of a vaginal abnormality, or after a seemingly normal us when clinical opinion ensures its use, or to make decisions on management strategies and preoperative planning. this refresher course will focus on the radiologist's approach to using pet-ct within the context of the gynaecologic oncology multidisciplinary meeting. the current indications for using fdg-pet/ct will be discussed for cervix, endometrial and ovarian cancer as well as the potential use of fdg-pet/ct in rare gynaecologic cancers. the value of adding fdg-pet/ct to the patient management pathway will be presented alongside the potential pitfalls in interpretation as well as controversies. future developments, including potential new tracers, will be mentioned. cystic lesions account for the vast majority of ovarian masses and are detected incidentally in - %. their spectrum ranges from non-neoplastic cysts to benign tumours, e.g. cystadenomas and dermoids to the rare ovarian cancer. diagnostic criteria in us, ct and mri are based on the clinical background (age, menopausal status, medical history, and tumour markers) and the morphology of the ovarian mass. typical of a benign cystic lesion is its pure cystic structure or thin septations, fatty or haemorrhagic contents, and mild enhancement of solid components in a complex solid and cystic ovarian mass. thus, patients can be categorised into different risk groups. sonography has been established as the first-line imaging modality to assess the ovaries. recently, management guidelines have been adopted for cystic ovarian lesions. in these guidelines, also cystic adnexal incidentalomas are included. mri is most useful as a complementary technique in sonographically indeterminate masses. an algorithmic approach will render a specific diagnosis in the vast majority of cases. in complex cystic lesions, integration of dwi and dynamic contrast-mri allows differentiation of rare benign complex tumours, e.g. cystadenofibroma from ovarian cancer. pitfalls of cystic ovarian tumours include cystic fibroids, peritoneal cysts, and extraperitoneal cystic tumours. compared to us, both ct and mri are superior in assessing large cystic pelvic masses. criteria to differentiate between intra-and extraperioneal origin include displacement patterns and identification of the vascular pedicle. careful analysis of imaging and clinical findings usually allows differentiation of inflammatory tumours from ovarian cancer. learning objectives: . to learn about specific imaging algorithms of ovarian cystic tumours. . to understand certain imaging features that can differentiate ovarian from non-ovarian cystic tumours in the pelvis. . to become familiar with the pitfalls in imaging of ovarian cystic tumours and the lessons to be learned from them. the diagnostic methods available in patients with conductive hearing loss are: personal and family history, otoscopy, audiology, imaging, surgical inspection and counseling. the most important reasons for imaging are: atypical history, suspicion of congenital hearing loss, suspected otoscopic image, asymmetric bone conduction thresholds, profound mixed hearing loss and suspected tympanometry. ct can be used to detect otosclerosis, tympanosclerosis, posttraumatic ossicular lesions, superior semicircular canal dehiscence and cholesteatoma. mri can be used to exclude schwannoma, congenital cholesteatoma and residual and recurrent cholesteatoma after prior surgery. this lecture will illustrate the value of ct and mri in the evaluation of cholesteatoma patients as well as prior to first stage surgery and prior to second look surgery. different subtypes of surgery will be highlighted and illustrated. the growing importance of mr imaging and diffusion weighted (dw) imaging in particular will be illustrated in the evaluation of cholesteatoma patients. the role of echo-planar and non-echo-planar dw imaging will be discussed as well as the eventual use of delayed gadolinium-enhanced t weighted imaging. mr is the modality of choice in patients with congenital or acquired sensorineural hearing loss (snhl) and the complete auditory pathway from the cochlea to the auditory cortex must be studied in these patients. the labyrinth, internal auditory canal (iac) and cerebellopontine angle (cpa) are best studied using submillimetric heavily t w images, showing the intralabyrinthine fluid and nerves. but submillimetric gd-enhanced t w images or d-flair images remain more sensitive. the auditory pathway in the brainstem is best studied with a multi-echo sequence (m-ffe/medic/merge) or t w tse sequence and the auditory cortex is best studied on t w tse images. the clinical information provided by the otologist will direct the radiologist to a certain part of the auditory pathway or will let him use certain imaging techniques. for instance, congenital malformations in the labyrinth and iac must be excluded in case of congenital snhl, and in case of mixed hearing one will start with ct to exclude otosclerosis. the most frequent pathology in the labyrinth (labyrinthitis, intralabyrinthine schwannoma, congenital malformation, post-traumatic lesions), the iac and cpa (cochleovestibular schwannomas, meningiomas, epidermoid tumours and facial nerve neuritis) and central auditory pathway (ms, infarction, tumor and trauma) will be illustrated using clinical examples and the important "otologist-radiologist" team work will be stressed. for tumours that nearly always arise from the investing mucosa, like in the larynx and hypopharynx, it is endoscopy that directly maps the superficial extent and grades the functional impairment (arytenoid and vocal cord movement, pyriform sinus distensibility). in addition to white light, the recent use of narrow band imaging endoscopic technology, enhancing fine capillaries in the mucosal surface, enables the detection of neoangiogenesis caused by early squamous cell carcinoma. conversely, submucosal spread is the domain of cross-sectional imaging techniques. therefore, it is the integration of the two classes of data, along with the information about patient conditions, which permits the choice of the most proper treatment strategy. in early and advanced glottic cancer, treatment planning is modulated by information about deep neoplastic invasion into the paraglottic space, the cartilage or the suprasubglottis subsites. this information can be derived by discriminating the tumour tissue from intra-laryngeal muscles, fat spaces and the cortical rim of ossified cartilages. though mr shows a greater contrast resolution than ct, it is hampered by a significantly longer acquisition time. this means more artefacts caused by breathing and movement. nevertheless, mr has the potential to unravel the signals from submucosal tissues, separating tumour from oedema, muscles, fat and ossified cartilages. advanced laryngeal and hypopharyngeal cancers need to preliminary assess local (nodes) and distant (metastases) spread. ct-pet is the more accurate tool. the multidisciplinary approach to the processing of the whole frame of data is essential to offer the patient the best care. traditionally, x-ray ct scanners were equipped with a single or a few detector rows only, image reconstruction was assuming parallel slices, which was a good approximation for these fan-beam systems. about a decade ago the number of slices increased to or more and the parallel slice approximation was no longer valid. the cone-beam nature of these multi-slice ct (msct) scanners had to be taken into account by specific cone-beam reconstruction algorithms. while these msct systems -today they are simultaneously acquiring up to slices -are cone-beam ct systems in a general sense, the notion of cone-beam ct (cbct) is also associated with a specific kind of conebeam ct, namely those equipped with flat detectors, i.e. the non-diagnostic or non-clinical ct systems. msct, in contrast, is a cone-beam ct system for diagnostic use, i.e. a clinical ct system. this distinction between msct and cbct is useful, as there are decisive differences in application, performance, and in image reconstruction. these differences will be reviewed in the presentation, with a particular focus on why image quality in msct is so much better than in cbct. cone-beam (cb) imaging with flat detectors is performed on a variety of different imaging systems. the most important area is cb imaging using interventional c-arm systems. the minimally invasive procedures carried out on these systems benefit from the availability of high-resolution d images for intervention planning, guidance and outcome control. interventional cb imaging was first applied in neuroradiology using rotational angiography acquisitions. today, it is used for a variety of procedures in interventional radiology, cardiology and oncology based on angiographic and soft tissue protocols. one of the inherent advantages of this approach is the direct registration of the volume images into the interventional procedure. other application areas of cb imaging using different scanning systems are onboard imaging in radiation therapy or the integration of flat detector tomography and spect. this part of the course teaches the generation of d volume information from flat detector systems and its utilisation in different clinical applications. image acquisition protocols, scan modes, and system design parameters are explained. application-specific calibration and processing steps are introduced to show how cb imaging is tailored for specific clinical applications. examples are presented for angiographic and soft tissue volumetric imaging. medical applications utilising the tomographic images for diagnosis, intervention planning, guidance, or outcome control are discussed. in the last decade, three-dimensional dentomaxillofacial imaging through conebeam ct (cbct) technology has become widely available. dental cbct (digital volumetric tomography; dvt) equipment is compact and often affordable to dentists. the driver for dental cbct was implant dentistry, but its use has spread to other areas, including paediatric applications. radiation doses are variable. some systems offer a fixed, large, field of view and others fixed exposure factors, obstructing attempts at optimisation. typically, doses are at least an order of magnitude greater than for "conventional" imaging. image quality is also variable, which means that certain equipment may be unsuitable for some clinical applications. there is often scope for lower exposure factors to be used than those recommended by manufacturers. a key aspect of using cbct relates to justification. imaging in three dimensions may be perceived by dentists as inevitably superior, a view which is often implicitly encouraged by those selling equipment. the research on diagnostic efficacy is, however, limited. in , the european commission published "radiation protection : evidence-based guidelines on cone beam ct for dental and maxillofacial radiology". this provides a comprehensive set of recommendations, including referral criteria, a quality assurance programme and optimisation strategies. priorities for future research relate to exposures to the necessary image quality requirements for specific clinical applications, along with research on the impact on clinical outcomes of cbct-based treatments. it is clear that much work remains before the place of cbct in dentistry can be established. the role of nonvascular interventional radiology of thorax for both diagnosis and treatment has significantly increased in the last years. although these procedures are technically easy with highly successful results, thoracic nonvascular interventional procedures are not unfortunately routinely performed in all of the interventional units. the most commonly performed procedures generally under ct guidance are transthoracic biopsies of the lung, mediastinal lesions and pleura. the others include percutaneous drainage of thoracic collections such as pleural effusions, empyema and mediastinal collections. image-guided tumour ablation performed by either radiofrequency ablation (rfa) or microwave (mw) as a nonvascular thoracic intervention has become a serious treatment alternative in patients with lung tumours (either non-small cell lung cancer or lung metastasis) since the year . interventional radiologists are expected to understand the clinical indications of these procedures at the first step. in addition, the techniques of the procedures and possible risk of complications in their management methods should be learnt by interventional radiologists as well. this refresher course will help us to discuss the main indications, techniques and complication management of these procedures. a. lung biopsy t. sabharwal; london/uk (tarun. sabharwal@gstt.sthames.nhs.uk) lung biopsy is most commonly now performed under ct guidance. it has a high technical success rate. common complications include pneumothorax, bleeding, sepsis, pain and failure. air embolism is a rare complication. pet scan is a useful tool to guide for appropriate target. ultrasound is useful for biopsying pleural-based lesions. drainage of thoracic fluid collections is a relative emergency. we will review the different thoracic fluid collections that can be drained by radiologists: pleural (parapneumonic, empyema, and malignant effusions), mediastinal, chest wall, pulmonary (lung abscesses and infected tumours) and pericardial effusions. we will answer the following questions about the main thoracic fluid collections: how to diagnose, when and how to drain, which guidance (ultrasound or ct-fluoroscopy), and procedures to perform before and after the drainage. the choice of imaging to detect thoracic fluid collections and guide drainage depends on the availability of the modalities, the imaging characteristics, location of the collection, and the comfort and expertise of the operator with the specific modalities. we will also review the main complications of percutaneous drainage of thoracic fluid collections (pneumothorax, pain, drain dislodgement and drain blockage) and compare these complications with those related to large-bore chest catheters inserted by thoracic surgeons. the incidence of lung cancers continues to increase and primary lung cancer remains the leading cause of cancer-related deaths in both women and men. therapy of lung tumours includes resection, radiation therapy, chemotherapy, thermal ablation or a combination of these treatment modalities. image-guided percutaneous thermal ablation therapies are minimally invasive techniques established in the local treatment of hepatic, renal, or osseous tumours. among these techniques, radiofrequency ablation (rfa) has now attained consideration for therapy of small pulmonal tumours. other ablation techniques that have been used for treatment of lung tumours include cryoablation, laser (litt) and more recently microwave ablation (mwa) and irreversible electroporation (ire). ablative techniques may produce a complete and irreversible tumour tissue destruction through application of either hot or cold thermal energy, or through permeabilisation of the cell membrane while using ire. ct is currently the imaging modality that is most widely used for planning, monitoring the ablation's course and for assessment of treatment response. only patients with stage i and stage ii lung cancer and those with small metastases are potential candidates for ablation. the medical history and physical examination of the patient as well as recent imaging with ct should be evaluated to determine the indication for thermal ablation. percutaneous lung rfa is considered as a safe procedure with an overall morbidity rate from . % to . % and mortality rate from % to . %; it requires less costs and offers faster recovery, and reduced morbidity and mortality. sorafenib, a tyrosine kinase inhibitor, has shown clinical efficacy in patients with hepatocellular carcinoma (hcc) and is the standard of care for patients with advanced-stage hcc. nowadays, many targeted therapies are evaluated in hcc either as sole treatment or in combination with other treatments such as tumour ablation, chemo-embolisation, and surgical resection. therefore, there is a need to assess the efficacy of targeted therapy in hcc. recist is the reference method to evaluate treatment efficacy in solid tumours, but does not seem appropriate in evaluating targeted therapy as objective responses are seen in very few cases in patients treated with sorafenib or sunitinib. new criteria have been proposed to evaluate the treatment efficacy of nonsurgical treatments in patients with hcc. the most common ones are the choi criteria, the easl criteria, and the modified recist criteria. all these criteria mainly focus on internal tumour changes such as appearance of necrosis or disappearance ot tumour hypervascularity. many examples will be shown during the lecture. another approach is based on functional imaging and especially perfusion-related imaging. contrast-enhanced ultrasound, ct perfusion and dynamic contrast-enhanced mr imaging have the capability to assess perfusion changes in patients under treatment. the advantages and disadvantages of these modalities will be discussed. lastly, other functional tools that are not routinely used will be presented. the evaluation of treatment efficacy is a key issue with prognostic and patient survival implications. it is crucial to have objective and reproducible criteria for specific groups of patients. the goal of ablative therapies of hcc is to induce tumoural tissue destruction. complete response (cr) after initial chemical and thermal percutaneous ablation, defined as the absence of contrast enhancement of the treated tumour at ceus, dynamic ct or dynamic mr, has been reported to correlate to long-term survival. nevertheless, the clinical effectiveness of imaging techniques to assess initial treatment success differs according to tumour size. the success rate of rf has been demonstrated to be superior to pei in hccs > cm, and depends on the ability to ablate all viable tumour tissue including an adequate tumour-free margin all around the lesion of . to cm. thus, the effectiveness of rf directly depends on the tumour location and size. rf is considered an effective treatment in lesions cm and its effectiveness is progressively reduced along with tumour size and it is not effective in lesions > cm. ceus beyond month may confirm or detect residual tumour, deserving a final ablation procedure. ct and mr are more effective in the follow-up to confirm cr and detect local recurrence, or additional hcc lesions in the liver parenchyma. the presence of transient hyperaemic inflammatory changes in the periphery of the treated area is a common finding that should be considered to avoid overestimation of the recurrence rate. one of the major characteristics of medical imaging in the twenty-first century is the dramatic influx of novel technology. this impact of new technology and techniques is experienced in all imaging modalities. the continuous development and implementation of highly sophisticated medical products and devices is key to the evolution of medical imaging leading to the improvement of patient care in terms of quality and positive outcomes. this session will analyse state-of-the-art displays (monitors, smartphones, tablets) and their applications in modern imaging. the session will provide a brief overview of displays in the current imaging chain. it will then evaluate the various specifications and parameters associated with displays. the session will evaluate current qa standards of modern displays as well as the challenges surrounding such novel technologies. image quality can be described in terms of resolution and contrast. an image displayed on a monitor consists of differences in brightness. the display monitor is at the end of the image chain in radiology, which starts at the x-ray tube. there are several factors in this chain that have influence on the contrast displayed on the monitor. diagnostic image quality can be described as observed contrast, which is not only dependent on the displayed image, but is also influenced by ambient conditions. for the primary class displays, typical characteristics of display monitors; such as resolution, homogeneity, luminance, contrast, monochrome or color, must be appropriate for the radiologist to execute a reliable diagnosis. calibration of display monitors is also important. which parameters are significant and what is the effect of variation of these parameters. there are standards like dicom gsdf and technical standard from acr-aapm-siim. both within and outside the clinical environment, the use of smartphones and tablet computers is increasing. reported applications range from teaching and education to navigation in surgical procedures. interest in the use of smartphones and tablets for viewing radiological images has been growing. however, these portable displays can differ significantly from conventional radiological displays. in order to determine where and how smartphones and tablets can be used appropriately, it is important to understand these displays and the challenges associated with them. this presentation will outline the current and potential uses of smartphones and tablet computers in radiology and compare their performance with other radiological displays and standards. the possible limitations/benefits of smartphones and tablets as display devices for radiological images will be discussed. recent research in the field will be reviewed, with emphasis on studies of diagnostic efficacy. in modern clinical environment, diagnostic monitors have replaced glowboxes and films and have become an important part of the imaging chain. the required specifications and the quality of monitors largely depend on their purpose, beginning from quite simple monitors used for the preview of radiographic images placed on modality or in control room to monitors used by high-end diagnostic workstations. decision about the kind of monitor for certain workplace is also very important from the economic standpoint as there are large differences in their prices. besides monitor specifications, also ambient conditions and ergonometry in the reading rooms are also very important issues which need to be considered to ensure optimal environment for clinical image reading. some of good and bad examples will be given in the presentation. as with other radiological equipment, also diagnostic monitors need to be controlled to ensure their optimum performance. quality control begins with monitor acceptance testing and setting up measurement parameters which are to be followed. practically all monitor vendors include some qc software within their workstations which can, together with some independent measurements, form an efficient quality control programme. in the last steps, how to deliver all information regarding image quality and possible presets on the diagnostic monitor and how not to confuse the user are important. sitting an examination is always a source of anxiety. the edir exam is no exception. this workshop is dedicated to those who want to take the edir exam, or become examiners, and would like to learn more about its format and discover some tips and tricks. the edir organisers and examiners have decided to build an interactive, friendly and enjoyable session in order to teach the essentials. some will play the role of the examiners, some the role of the candidate. in order to simulate the candidate's experience, this session will have no safety net. some senior members will expose themselves to real difficult questions in general radiology. fortunately, we hope that the attendees will be able to help the "candidates" to succeed. hopefully, you will enjoy this session and get some very useful information for your edir exam. abdominal malignancies are an important health problem in mexico. like in many other middle-income countries, there has been an epidemiological transition with an overall increase in oncologic diseases. colorectal, gastric and liver carcinomas are some of the frequent abdominal malignancies. colorectal cancer is a disease that is curable if detected early and even preventable if precursor polypoid lesions are removed. imaging plays a critical role in staging at diagnosis. additionally, virtual colonoscopy is an accepted modality in cancer screening. high-resolution magnetic resonance imaging (mri) has become a pivotal modality in the pretreatment assessment of rectal carcinoma. computed tomography (ct) is an excellent modality in the preoperative staging of gastric cancer and follow-up after treatment. positron emission tomography (pet) combined with ct (pet/ct) is particularly helpful for gastric and colonic carcinoma staging. hepatocellular carcinoma (hcc) is also common. cirrhosis related to alcohol and hepatitis c infection are by far the commonest aetiologies. ultrasound (us) in conjunction with alpha-protein is the most widely used modality for screening purposes. ct and mr are confirmatory modalities. the advent of hepatospecific gadolinium contrast agents has been very helpful in the characterisation of focal lesions in cirrhotic patients. the use of multidetector ct (mdct) in pancreatic carcinoma for the detection of vascular and adjacent organ invasion is crucial in treatment planning. over the last few decades, there has been an important improvement in imaging techniques resulting in better quality images. imaging is critical not only for the diagnosis, but also for treatment planning and follow-up. learning objectives: . to learn about the imaging of common oncologic gastrointestinal diseases. . to understand the importance of imaging in liver and colon cancer. . to learn how imaging supports oncologic institutions. activity, ultrasound is readily available and gives detailed local information but is limited by the restricted field of view, communication of results to clinicians and comparison of examinations on time. computed tomography (ct) is fast, readily available and gives a detailed, reproducible overview, but radiation exposure and contrast resolution are limitations. magnetic resonance imaging combines a good, reproducible overview with high contrast resolution, dynamic information and no radiation exposure and is therefore preferable in many situations, but the longer examination times than for ct, availability and costs are limiting factors. for the diagnosis of stenoses, fistulas and abscesses, either technique can be used, although the unrestricted view of ct and mri favour these techniques in many situations. in acute situations, us and ct are more accessible than mri. in that setting us can be considered, but when the examination is inconclusive or the patient has clear inflammatory signs, ct is preferable. endoscopy is currently considered the reference standard for the evaluation of colonic pathologies, including colitis. it allows direct visualisation of the mucosa and in obtaining tissue sample. however, it has major limitations including the invasiveness of the technique, incomplete endoscopy and risk of perforation. endoscopy cannot, therefore, help to estimate the depth of involvement of transmural inflammation and extraluminal complications. by contrast, an evolving role for cross-sectional imaging in the evaluation of patients with colitis has been increasingly recognised, especially in the setting of crohn's disease (cd), since cross-sectional imaging has been demonstrated to have a high diagnostic accuracy not only for assessing the presence and extension of luminal disease, but also for evaluating cd-related acute or chronic complications. establishing the ultimate cause of colitis may sometimes be challenging and histology cannot be conclusive. however, cross-sectional imaging may provide additional information that is useful in the workup of colitis. the use of cross-sectional imaging has been increasing in the evaluation of inflammatory bowel disease. following their presentations on imaging protocols and features of small bowel disease and colitis, each speaker will present a case to illustrate the learning points covered in their lectures. the session will be moderated by the chairman and the audience will have full opportunity to ask questions of all the panel. multimodality imaging is essential in a wide variety of oncology situations. anatomic imaging, whether using us, ct or mri, is mandatory for tumour localisation. moreover, the evaluation of treatment response mostly relies on size assessment, whether uni-or bi-dimensional. with the advent of new targeted bio-therapies, functional imaging has progressively been integrated in the imaging strategies whether for better tumour characterisation or for optimal evaluation of treatment response. hence, assessment of molecular targets by pet is supplemented by the recent developments of diffusion mri, reflecting tissue architecture and cellularity, tissue perfusion, reflecting angiogenesis, and magnetisation properties of tissues. hcc is a primary liver tumour where the use of multimodal anatomic, functional and metabolic imaging appears of particular interest. according to easl and aasld recommendations, noninvasive diagnosis of hcc can be performed using dynamic contrast enhanced cross sectional imaging. liver mri provides optimal sensitivity and specificity for the detection of as small as cm large hcc. recent reports have suggested that the prognosis of hcc lesions could be anticipated based on the combined analysis of metabolic f -fdg pet ct, as well as with diffusion weighted imaging. the objective of this lecture will be to highlight the potential of combining both metabolic and multimodal cross sectional imaging in order to improve the management of patients with hcc. the (extra)ordinary night shift at the er k. petrovic; novi sad/rs (smakap@sbb.rs) besides the accuracy, working at the er requires maximal shortening of the diagnostics time, which has a significant influence on the patient's outcome. thus, it is the radiologist's duty to be familiar with the pathophysiological mechanism of the disorders, specific protocols, possibilities and limits of certain examinations, and also to be aware of all possible pearls and pitfalls, to make the correct diagnosis. pathology encountered at the er has an extremely wide range and requires expertise in all imaging modalities from head to toe. the more the radiologist is aware of all possible situations, the more is the diagnosis accurate, and information given to the clinician is more valuable. the aim of this presentation is to point out the possibility of encountering different pathological conditions in different body regions. moreover, it is important to be reminded that in radiology there are different modalities, each of which has its own indications and limits. this lecture reviews the selected series of cases from the er department of clinical center of vojvodina, pointing out the most common possible differential diagnosis and possible diagnostic mistakes, which often occur due to the lack of experience. learning objectives: . to point out the in-depth knowledge and experience in all imaging modalities and all body regions required for a radiologist to perform a routine work at the er. . to present a series of cases that are most and less often encountered at the er, discuss the possible differential diagnosis and mistakes which could potentially be made. diagnosis and management of pancreatic cystic lesions r.j. méndez; madrid/ es (ramiro.mendez@salud.madrid.org) pancreatic cystic lesions are frequently diagnosed in patients with clinically suspected pancreatic disease, but they are also increasingly detected on imaging studies performed due to other abdominal processes. the prevalence of pancreatic cysts increases with patient's age. most symptomatic cysts will be surgically resected, whereas asymptomatic lesions should be managed depending on the likelihood of causing harm to the patient. cystic lesions can be inflammatory or neoplastic. the incidence of pseudocysts is low without a history of pancreatitis. some pancreatic cystic neoplasms are malignant, but even benign lesions can become symptomatic depending on its size and location in the pancreas. the radiologist detects most of the pancreatic cystic lesions and should also play an important role in the clinical decision-making process. cyst size, morphology, calcifications, contrast enhancement, location in the pancreas, relation with pancreatic ducts, patient's age and gender are important data to classify the lesion. a specific radiological diagnosis is not possible in every patient, but in many cases this information is enough to decide on a conservative approach with imaging follow-up. if a more aggressive lesion is a concern, then endoscopic ultrasound and fluid analysis can help to better characterise some pancreatic cystic lesions. cyst puncture is only recommended if fluid analysis results will modify the patient's management. patient's age, status and preferences should also be taken into account. when follow-up is recommended, the preferred imaging technique and interval should be indicated. the chair will set the scene for the need for effective radiation protection in clinical radiology and highlight the role of clinical audit as a tool in achieving this. clinical audit is defined as a professionally led method of improving patient care through the systematic examination of systems, processes and outcomes against chosen and agreed standards. it can readily be carried out by individuals, groups or whole departments. if properly conducted, clinical audit can be an effective way of examining what we do to provide reassurance on performance, and to improve patient care. the clinical radiology audit committee (crac) of the royal college of radiologists (rcr) co-ordinates national radiology audit activity. it promotes and facilitates audit through nominated audit leads in each hospital, who act as a link between the rcr and their department. at least one national audit is carried out annually, with data collected via electronic submission and the anonymised results presented at an annual audit forum. individual departmental results are analysed using statistical process control (spc) methodology. this enables identification of departments underperforming against the national mean, and recommending corrective action, by redesigning the process being audited, or by identifying and eliminating specific root causes locally. the committee has developed a web-based tool for facilitating local audit, "auditlive", a fully searchable collection of templates which can be downloaded and adapted. fellows are also able to submit their own templates for publication hence sharing best practice. trainees are encouraged to participate in audit through audit poster competitions at national radiology scientific meetings. our experience leads us to believe that audit succeeds when relevant, locally owned and properly structured, and multi-professional, and the rcr model encourages this. models of external audit in the netherlands s. geers-van gemeren; utrecht/nl in the netherlands clinical audit is legally obligatory for healthcare professions in order to be able to practise since . clinical audit is a tool designed to improve the quality of patient care, experience and outcome through formal review of systems, pathways and outcome of care against defined standards, and the implementation of change based on the results. the quality of the provision of care by professionals is assessed by peers. in the fields of radiology, nuclear medicine and radiotherapy, different models of clinical audit are used. for radiotherapy a multidisciplinary audit has been used since . for nuclear medicine a multidisciplinary audit has been implemented since . for radiology the clinical audit for radiologists and for radiographers are separate. implementation of the multidisciplinary audits needs requirements and adjustments of the audit system. this process is complex and needs approval of the members of all involved societies. to support the clinical audit a web based tool adas (general digital audit system) is used. the development of professional standards is a prerequisite to start clinical audit. the use of adas in multidisciplinary audits is a requirement to be able to audit different professions and focus on the content and the quality of their contribution to patient care. clinical audit is a good tool to improve the quality of patient care. important are the professional standards, the culture of learning and willing to improve by the professionals. "every defect is a treasure." learning objectives: . to learn about the different dutch models of external clinical audit. . to comprehend the importance of professional standards, the culture of learning and willingness to improve. . to become familiar with the use of a digital audit system to support multidisciplinary clinical audit. external regulatory audit in finland r. seuri; helsinki/fi (raija.seuri@hus.fi) directive / /euratom states that the clinical audit of medical imaging should be carried out in accordance with national procedures. the finnish solution has been regulatory external audits every five years by radiological professionals with special training for audits. all radiological units have so far been audited at least twice, and the third time is performed on site in the unit. although the purpose is to audit the process of radiological practises compared to "good practise", special focuses are recommended by the finnish advisory committee for clinical audit, set by the national institute for health and welfare. at the beginning focus was on the organisation and documentation of the structure and processes of imaging practise like justification, optimisation and quality control, but also encouragement and guidance to self-assessment. later special focus has been on paediatric imaging and ct, and the third cycle will target deeper to ct practises. the auditing group includes at least a radiologist and a radiographer to audit a small unit, and a medical physicist if the unit has high-dose modalities like ct. during the audit the auditors work for an independent organisation. multi-professionality gives both insight and the possibility to contact all professionals in imaging practise. the focus of clinical audit is on quality improvement; it is a way to both give and get feed-back and education. it is not control or inspection, but encouragement and guidance to self evaluation and implementation of good practises. we often think of the scientific researcher as detached, objective, and dispassionate, nobly labouring without any expectation of reward. nothing could be further from the truth. scientists are as subject to ambition, competitiveness, envy and even guile as any person. lifting the veil on scientific discovery reveals to us the human dramas that underlie not only the coveting of recognition, but also great conflicts over priority and credit. nowhere are the stakes higher than for that pinnacle of scientific honour: the nobel prize. mri has had a notably tempestuous genesis -a cogent episode that has much to teach us. it involved an explosive clash of personalities; deceit and rampant self-interest; challenges to the basic concept of scientific behavior; legal suits and validation by the united states supreme court; and declamations of denunciation in the international press. it persisted as a year battle -a prize fight, a blood feud -between two protagonists: one whose seminal contribution established the biologic basis of mri, and the other whose flash of insight served as a cornerstone of diagnostic imaging. . metabolic disorders of the skeleton involve the mineralised components of the skeleton. they affect all bone components histologically, but involvement patterns may vary depending on the age of the patient (growing versus adult skeleton) as well as the type of bone (cortical versus trabecular bone). they can be depicted on radiographs and ct images, but remain occult on mr images because the bone marrow is spared in the vast majority of these disorders. mr imaging can help in the assessment of local complication such as fractures. . metabolic disorders of the bone marrow can affect either red (anemia…) or yellow marrow as well as the balance between these marrow types in the body. medical imaging plays a limited role in the assessment of these disorders, but marrow changes associated with these metabolic conditions must be recognised to avoid confusion with neoplastic conditions. in primary and secondary malignant tumours of solid organs, in most of the cases surgical resection is considered the curative treatment. however, this is possible only in about % of the cases with tumour-dependent recurrence rates of % and even more. the main components for adjuvant, neo-adjuvant and finally palliative therapy are the permanently growing number of chemoand antibody therapies. nevertheless, in many cases these therapies provide no definitive or long-lasting success, necessitating multimodality treatment concepts. in the meantime, local ablative techniques represent the main components of these concepts. three main minimally invasive tumour-ablative techniques can be differentiated: chemo-ablation (percutaneous alcohol injection, transarterial chemo-embolisation, chemotherapy, chemo-perfusion), thermo-ablation (radiofrequency-, microwave-, laser-ablation, high-intensified focused ultrasound, cryo-ablation) and radio-ablation (radio-embolisation, interstitial brachytherapy, percutaneous stereotactic radiation). these ablation techniques differ significantly among each other with respect to their mode of action and indications; nevertheless, their benefit is high tolerance and at the same time high therapeutic efficacy, which can easily be combined with other treatment modalities. the different minimally invasive techniques will be discussed together with specific short-and long-term results and complications. missed lung lesions are one of the most frequent causes of malpractice issues. chest radiography plays an important role in the detection and management of patients with lung cancer, chronic airways disease, pneumonia and interstitial lung disease. among all diagnostic tests, chest radiography is essential for confirming or excluding the diagnosis of most chest diseases. however, numerous lesions of a wide variety of disease processes affecting the thorax may be missed on a chest radiograph. the chest radiograph will also help narrow a differential diagnosis, help to direct additional diagnostic measures, and serve during follow-up. the diagnostic usefulness of the radiograph will be maximised by the integration of the radiological findings with the clinical features of the individual patient. ct has a tremendous spatial resolution that helps detect lesions in the chest and has proven to be more sensitive and specific than chest radiographs. however, missing lesions or misinterpreting lesions in ct of the chest is not uncommon. in this session, we will provide interactive cases of chest examinations (radiographs and ct) in which lesions have been missed and or misinterpreted, with a special focus on how correlation with mdct of missed lung lesions can help improve interpretation of plain chest radiographs. this session will explore the value of imaging for facilitating precision medicine, in which molecular data (including genomics, proteomics and metabolomics) is used to classify patients into subpopulations and tailor treatments to the specific molecular characteristics of their diseases. imaging already plays a limited role in precision medicine, primarily through the use of molecular imaging techniques (e.g. pet/ct, mri/pet and hyperpolarised mri) and theranostics (the combination of an imaging agent with a therapeutic entity). in the near future, the role of imaging in precision medicine will increase at a gradually accelerating pace through the development of new molecular imaging probes and theranostic agents and through progress in radiogenomics (the correlation of radiologic findings with genomic features). this session will discuss recent findings and methodologies in radiogenomics as well as the use of nanotechnology for designing novel molecular imaging probes and theranostics. in addition, as theranostics is often considered the essence of precision medicine, the session will provide an in-depth look at current and emerging theranostic strategies and their special benefits for treatment selection, assessment of dose distribution of targeted therapies, and treatment follow-up. radiogenomics and personalised (precision) medicine g.p. krestin; rotterdam/nl (g.p.krestin@erasmusmc.nl) "precision medicine" as well as related notions, such as personalised medicine, or stratification medicine, all revolve around the idea that the consideration of individual characteristics -molecular and otherwise -can improve medical research and practice. precision medicine is a multi-faceted approach to medicine that integrates molecular and clinical research with patient data and outcomes. individual assessment of the location and extent of an alteration is and always has been the basis of medical imaging, whether the 'alteration' is a disease, a malformation, or an injury. as such, medical imaging intrinsically enables "precision medicine". the addition of genomic data in the last twenty years allows new correlations to be made between cellular genomics and tissue-scale imaging. structural and functional imaging and the automated analysis of large amounts of image data have only recently reached a stage where they can be used on a large scale and in a population setting. identifying common genetic variants that contribute to explain variance in imaging phenotypes by a systematic analysis of the genome is based on genome-wide association studies (gwas). the power of gwa analyses has been recently demonstrated with the identification of susceptibility genes involved in a range of imaging phenotypes like coronary artery calcifications, intracranial volume, or size of the hippocampus. these developments highlight new etiological pathways and are expected to improve the understanding of the molecular basis of some diseases. correlation between genotype and imaging phenotypes may be relevant for further characterising the development of disease states. use of nanotechnology, imaging and therapy t. lammers; aachen/ de (tlammers@ukaachen.de) advances in nanotechnology and chemical engineering have led to the development of a significant number of novel materials for diagnosis and therapy. many different diagnostic and therapeutic nano-and micro-materials have been designed and evaluated over the years, including, e.g. gadoliniumcontaining dendrimers, uspio nanoparticles and microbubbles for functional and molecular imaging, and drug-loaded liposomes, polymers and micelles for temporally and spatially controlled drug delivery to tumors and to sites of inflammation. in the literature, such advanced nano-and micromaterials are generally claimed to be highly useful and broadly applicable. a critical reflection on their specific capabilities, however, as well as on their pharmacokinetic properties, biodegradability and toxicity is often lacking. in the present lecture, i will briefly introduce the rationale for using diagnostic and therapeutic nanomaterials. i will highlight several clinically relevant examples in which nano-and micromaterials hold potential for improving disease diagnosis and detail how combining diagnostic and therapeutic properties within a single 'nanomedicine' formulation can be used to individualise and improve (chemo-) therapeutic treatments. learning objectives: . to learn about the design and construction of nanoparticles for use in imaging and therapy. . to appreciate both the advantages and limitations of using nanoparticles as agents for both imaging and therapy. . to learn how nanotechnology enables multimodality imaging and therapeutic agents. theranostics w. weber; new york, ny/us precision medicine requires diagnostic tests that predict the effectiveness of specific therapeutic interventions for individual patients. this close interaction between therapeutics and diagnostics is expressed in the term "theranostics". a frequently used example for a theranostic is the staining of tumours for her expression prior to therapy with her antibodies, such as trastuzumab or pertuzumab. theranostic has also been practised since many years in nuclear medicine by using radioiodine scans to select patients for treatment with iodine- . a more recent example is the selection of patient for peptide receptor-targeted radiotherapy (prrt) by somatostatin receptor imaging. imaging is highly attractive for theranostics, because it allows investigators to study the spatial and temporal heterogeneity of target expression, whereas in vitro assays generally analyse a small part of the tumour at one point in time. several molecular imaging probes, such zr-trastuzumab or folate receptor targeting ligands, are in clinical development as in vivo companion diagnostics. imaging companion diagnostics can also be used to assess tissue pharmacokinetics and thereby help to determine the optimal dose and dose schedule of therapeutic agents. they can also identify unexpected interactions between two therapeutic agents. for example, studies with c-docetaxel have shown that bevacizumab can markedly decrease the intratumoral delivery of docetaxel. finally, imaging-based companion diagnostics can assess target inhibition, as demonstrated by the inhibition of uptake of the androgen receptor ligand f-fdht in metastatic prostate cancer treated with anti-androgens. imaging-based companion diagnostics are therefore expected to play an important role in establishing precision medicine. erus technique as well as the state-of-the-art mr imaging protocols tailored according to the presenting rectal tumor site, allowing trained radiologists to obtain all necessary information for appropriate treatment decision-making, will be described. normal cross-sectional appearances as well as morphological and signal changes encountered in pelvic structures/tissues that may be involved in primary rectal cancer will be illustrated. the influence of imaging findings on initial therapeutic approach and potential limitations of different imaging techniques will be discussed. the staging and categorisation of malignant lymph nodes in patients with rectal cancer is a topical issue and has resulted in some degree of confusion. much enthusiasm has been expended in determining whether mesorectal nodes are, or are not, involved in the primary disease process, as there is a perception that nodal disease is an important determinant of local recurrence. this incorrectly perceived association of nodal status and a high risk of pelvic recurrence have propagated the concept that this should be the primary indication for neoadjuvant therapy regardless of whether tme surgery is to be performed. furthermore, misinterpretation of involved local nodes results in over-treatment of patients, if firstly involved nodes alone are considered as a poor prognostic factor, and secondly the optimal treatment of involved nodes is pelvic radiotherapy plus a non-systemically acting but radiosensitising dose of chemotherapy within chemoradiotherapy (crt) schedules. in this lecture, the evidence for risk factors associated with nodal disease and validated risk factors for local recurrence will be reviewed. the evidence for both the optimal techniques and objective criteria for assessing lymph nodes with magnetic resonance imaging (mri) will be presented. the standard treatment for advanced rectal cancer is preoperative chemoradiotherapy (crt) followed by standard resection of the rectum and mesorectum. neoadjuvant crt allows downsizing and downstaging of the tumour, leading to improved resectability and local control. while the role of mri in rectal cancer treatment is recognised and mri is recommended as part of the standard staging workup, its role for restaging after preoperative treatment is more controversial. this lecture will provide an understanding of whether and how mri can assess treatment response in rectal cancer and how it may impact treatment decision. the attendees will learn about the difficulties in image interpretation and learn about potential new imaging techniques to improve its performance. primary tb typically presents with consolidation in the middle and lower lobes, and necrotic lymphadenopathy. fibrosis, tuberculomas and calcified nodes may result as sequelae. cavitation and tree-in-bud appearance involving the apical and posterior segments of the upper lobes and the superior segments of the lower lobes are the hallmarks of reactivation tb is typically seen in immunocompetent patients. in immunocompromised patients, primary tb findings are more commonly observed, as miliary or disseminated disease or atypical manifestations in case of severe immunosuppression. pleural effusion and tracheobronchial involvement may be observed. the "classical" appearance of non-tb mycobacteria (n tm ), less common and more indolent than tb, typically affects males more than years old with pre-existing pulmonary disease or underlying immunologic disorder. despite a great overlap in the radiologic appearances of both infections, the presence of cavities on sites other than the upper lobes should suggest an n tm infection. the "nonclassical" form related to mac infection that predominantly affects elderly women with no pre-existing pulmonary disease mainly consists in mild bronchiectasis and centrilobular nodules predominantly located in the lingula and middle lobe. a high rate of lymphadenopathy and disseminated disease are seen in immunocompromised patients. the radiologist has to ensure the diagnosis of active tb and mention scarring before starting specific treatments; to suggest n tm infections, immune reconstitution inflammatory syndrome with paradoxical worsening in haart treated hiv-infected patients as multi-drug resistant tb; to appreciate the extent of disease and follow-up; to diagnose the complications; to propose mri or pet scans in some situations. learning objectives: . to appreciate the imaging features of primary and post-primary infections in tb. . to learn about the similarities and differences between tb and non-tb mycobacterial infections. . to understand the radiologist's role in diagnosis. the appropriate investigational technique, frequently targeted differential diagnosis, and the special needs of immunocompromised patients need to be understood by the referring physician as well as by the radiologist. thus, an intensive interdisciplinary co-operation on a patient basis, as well as on a department basis is essential. early detection of a focus is the major goal in febrile neutropaenic patients. as pneumonia is the most common focus, chest imaging is a special radiological task. the sensitivity of chest x-ray, especially in the supine position, is known to be low. therefore, the very sensitive thinsection multislice-ct became the gold standard in neutropenic hosts and might be cost-effective in comparison to antibiotic treatment. the infiltrate needs to be localised, so that this information can be used as guidance for invasive procedures for further microbiological workup. furthermore, the radiological characterisation of infiltrates gives a first and rapid hint to differentiate between different sorts of infectious (e.g. typical bacterial, atypical bacterial, fungal) and non-infectious aetiologies. follow-up investigations need careful interpretation according to disease, recovery, and concomitant treatment. due to a high incidence of fungal infiltrates, interpretation of the follow-up of an infiltrate must use further parameters besides the lesion size. besides the lungs, also other organs systems such as brain, liver and paranasal sinuses need attention and are to be imaged with the appropriate technique. despite advances in diagnosis and treatment, new pulmonary infections have been diagnosed. streptococcus pneumoniae remains the main aetiological agent in outpatients with community-acquired pneumonia (cap). elderly patients or those with toxic habits and various comorbidities favour the development of severe cap. in addition, the development of nucleic acid amplification techniques has emphasised the role of concomitant bacterial and viral pneumonia in the outcome of cap in elderly patients. healthcareassociated pneumonia has been recently defined as a different infectious condition by the american thoracic society/infectious diseases society of america (ats/idsa). the main concern of this new disease is the risk of having an infection due to multidrug-resistant pathogens. with the advent of haart and increased long-term survival of hiv-positive patients, the range of pulmonary manifestations has also evolved. in patients with haematological malignancies or after hsc transplant, aspergillus is a common infection. actually, aspergillus spp. isolation from lrt samples in copd may indicate an increased diagnosis possibility of ipa. new emerging viruses such as human metapneumovirus (hmpv), sars-associated coronavirus, and avian influenza caused by the h n virus have been diagnosed. in , an outbreak of a novel swine-origin influenza a (h n ) virus was reported. the clinical diagnosis of new pulmonary infections as well as the presence of concomitant bacterial and viral infections has been significantly enhanced by improved laboratory methods. a systematic approach to the radiological evaluation of lung infections is essential and includes not only chest imaging pattern recognition, but also integration of available demographic, clinical and laboratory information. the paediatric central nervous system is a complex structure undergoing rapid development. as such, there is a rapid, continuous modification of what is "normal" in relation to age and the stage of development. knowledge of the normal patterns of brain development in the clinically relevant ages from to years is necessary to interpret neuroimaging findings correctly. knowledge of embryology and normal variants is also greatly helpful. mr imaging equipment and parameters need to be adjusted and optimised for paediatric studies. pitfalls often occur from the misunderstanding of normal conditions that are perceived as abnormal based on a comparison with the appearance of the normal brain in adults. this includes, for instance, the evaluation of the brain in the first - years of life during the course of the process of myelination. a summary of the most frequent conditions that may lead to misinterpretation of findings will be provided. a wide spectrum of anomalies of thoracic and abdominal organs may be encountered on radiologic evaluation. these anatomic variants and developmental anomalies can all pose a diagnostic challenge to the radiologist. familiarity with these anomalies, the imaging techniques available for their study, and their variable imaging manifestations is necessary for differentiating them from pathology. a basic understanding of the embryologic development and normal anatomy of thoracic and abdominal organs and vessels is also essential for identifying these anomalies. this review explores the wide variability in appearance of the normal thoracic and abdominal organs during imaging, stressing a thorough understanding of normal anatomy to recognise normal variants. the skeleton of a child is a developing system with a variety of changing normal appearances. imaging studies, especially plain films, are requested for many clinical reasons, and the radiologist is in the position to determine if an image is a normal finding or we are dealing with a lesion. the way the physis and epiphysis grow, ossify, and fuse constitutes a great source of physiologically bizarre appearances, which the radiologist must be familiar with. this talk will concentrate on the plain film diagnosis of some of the most common musculoskeletal variants. other imaging modalities will also be shown when appropriate for the case. irregularities, asymmetries, partial fusions, hypo-or hyper-dense bone areas, accessory bones, prominent normal structures, external artifacts, and potential fracture lines are the most often encountered pseudolesions. a defective radiological technique may also be potentially misleading. patient age, location of the supposed "abnormality" and lack of significant local symptoms are key factors. usually plain films, correlated with regional clinical findings, are the only imaging method that is required. however, in certain doubtful situations, ultrasound, ct, mri, bone scan, or even biopsy may be needed to reach the right diagnosis. unnecessary overuse of these imaging modalities, and the subsequent family anxiety that ensues from this overuse, should be avoided with careful analysis of the x-ray and clinical findings. the purpose of this lecture is to cover the clinical presentation, underlying pathological processes and essential mri features of relatively common conditions affecting the hip. as the hip is afflicted by different conditions according to age, this is how the various pathological entities will be presented. a simple imaging algorithm is presented showing the role of mri. the role of mr arthrography in the assessment of the dysplastic hip and femoroacetabular impingement is covered. a structured approach to mri reporting is outlined. (claudia.schueller-weidekamm@meduniwien.ac.at) mri of the hand requires high spatial resolution, perfect immobility, and homogeneous fat suppression. the hand can either be placed in the superman position, which often is uncomfortable for the patients, or both hands can be placed above the abdomen next to each other while the patient is in the supine position. standard sequences are axial pd, followed by coronal t tse, and t tse fs in the coronal and sagittal planes. additional d gradient echo sequences with fat saturation are recommended to assess ligaments and cartilage, as well as the triangular fibrocartilage complex (tfcc). in certain cases, mr arthrography with thin-slice t fs is helpful for further evaluation of the wrist ligaments. in inflammatory diseases, such as rheumatoid arthritis, static or dynamic t fs sequences are useful to assess tenosynovitis and synovitis. the most common injuries and inflammation of the hand and wrist are discussed with special emphasis on key findings for an accurate diagnosis. the awareness of advantages and drawbacks of other imaging modalities, such as conventional radiographs and ct, should be strengthened. the clinical impact of the radiological report is discussed to strengthen the importance of proper terminology for the description of pathological findings. the structure of the report should be clear and concise, and should allow an interaction and broad communication with clinicians. gastro-enteropancreatic neuroendocrine tumours (gep-net) are a heterogeneous group of cancers that differ in their biology and clinical presentation. diagnosis of these tumours has been improved by advances in pathology and classification and by the combined use of structural imaging and functional imaging modalities. multimodal imaging is increasingly recognised both in detecting and staging disease and also in characterising biological patterns of lesions that may be relevant to the selection and delivery of therapy. in this course, the complex nature of gep-net and the intrinsic uses and limitations of each diagnostic imaging modality will be underlined. insights to hybrid structural and molecular imaging techniques will be provided and discussed. a. tumour biology, pathogenesis and classification b. wiedenmann; berlin/ de (bertram.wiedenmann@charite.de) neuroendocrine tumour cells are characterised by the coexpression of neuronal and epithelial proteins and cellular organelles such as synaptic vesicles containing synaptophysin of neurons and intermediate filaments/cytokeratins of the epithelial cells. based on the presence of secretory vesicles and the continous, uncontrolled vesicular release of biogenic amines, neuropeptides and hormones, patients suffer in half of the cases of so called functional symptoms and syndromes. examples are the carcinoid syndrome (excessive release of serotonine) or the zollinger-ellison syndrome (excessive release of gastrin). activation or inhibition of certain g-protein coupled receptors (e.g. somatostatin receptors) or channel proteins (r-type calcium channels) can lead to the control of the hypersecretion or so called functionality of the affected patients. medical interference with signal transduction pathways involving tyrosine kinase receptors as such mtor and channel proteins can lead to an inhibition of cellular and tumour growth. these observations have led to the establishment of new therapies, especially for pancreatic nets using especially mtor and tyrosine kinase inhibitors. whereas the tumorigenesis is unknown in the case of sporadic nets, hereditary nets appear to develop via a menin mutation through the intermediate stage of hyplasia before they develop the full metastatic potential. based on the above given tumour biological and histopathological findings, a rather robust classification for nets has been developed by the european neuroendocrine tumor society (enets) using a tnm-classification together with a gradingsystem. furthermore, the formerly used terms such as apudoma, neurocrestoma, carcinoid, etc. have been largely replaced by the meanwhile generally accepted term neuroendocrine tumour. this presentation will focus on the pivotal role of nuclear medicine in the diagnosis and treatment of neuroendocrine tumours (nets). the metabolic and molecular imaging capabilities of both positron emission tomography (pet) and single photon emission tomography (spect) have made a great impact on the clinical management of patients with these tumours. a poster child of molecular imaging in oncology is scintigraphy of the somatostatin receptor (ssr). in-dtpa-octreotide has a substantial value in detection, diagnosis and staging of net and more particularly in gastroenteropancreatic nets. newer ssr-binding radiopharmaceuticals have been developed for pet, mainly with gallium- as radiolabel, with higher affinity and more advantageous pharmacokinetics. when used with high-resolution and rapidthroughput multimodal whole body imaging of modern pet/ct cameras, these tracers provide the current state-of-the art ssr imaging. we will also discuss the clinical value of metabolic tracers, such as [ ] -hydroxytryptophan) for amino acid metabolism imaging. the clinical merits and indications of these tracers will be explained. the continuously evolving quest to develop tracer for other receptor systems expressed on nets will be illustrated, e.g. bombesin, vip, cck and glucagon-like peptide receptor ligands. finally, the role of imaging as selection for metabolic and peptide receptor radionuclide therapy will be discussed. gastroenteropancreatic neuroendocrine tumours (gep-nets) are a heterogeneous group of neoplasms that arise from cells of the diffuse neuroendocrine system and may present with a wide spectrum of clinical presentations. their prognosis is mainly related to their biology, proliferation and differentiation. the main goals of imaging are the diagnosis and the staging of these tumours. the diagnostic challenge is very different in functional tumours where clinical presentation and laboratory parameters are of utmost importance and in nonfunctional tumours where imaging may show characteristic features such as hypervascularisation and calcifications. staging is also essential as locoregional involvement and distant metastases (such as liver metastases) may change the therapeutic approach and are major prognostic factors. multimodal workup included morphological imaging modalities with ct and mr imaging, and endoscopic ultrasound was the most useful and functional imaging. the latter includes somatostatin receptor scintigraphy, fdg pet and more recent functional tools such as pet using ga and f-dopa. imaging may also play a role in assessing prognosis in combination with tumour differentiation and tumour proliferation, obtained from pathologic examination. last, imaging is useful in evaluating tumour response after treatment. although surgery remains the only potentially curative therapy for patients with primary gep-nets, other available treatments include chemotherapy, interferon, somatostatin analogues, and targeted therapies. imaging criteria rely not only on changes in tumour size, but also on internal tumour changes. the purpose of this session is to bring the audience up to date with a novel mri method capable of measuring brain perfusion. this method is called arterial spin labelling (asl) and provides a complete non-invasive means to quantitatively assess cerebral blood flow (cbf). as with any mri technique, asl relies on proper setting of many technical parameters to provide an adequate image quality, with minimal influence from potential artefacts. a recent position paper, co-signed by members of the perfusion study group from the international society for magnetic resonance in medicine and the european cost-funded action on 'asl in dementia', has established a series of simple guidelines to help promote this technology in clinical practice. these guidelines will be provided within this session. the created cbf maps will then be analysed, and a simple description of the main features and clinical characteristics of these physiological images will be given to the audience. in particular, a proper difference in the meaning of cbf in several diseases will be highlighted, as it can be either causative, such as e.g. in stroke and cerebrovascular diseases, where a reduced cbf leads to a breakdown in tissue homeostasis, or consequential, as in e.g. dementia, in which a reduction of cbf is the mere reflection of impaired metabolism, combined or not with an underlying brain atrophy. following this session, the radiologist or clinician should be able to better appreciate asl-based sbf maps in several neurological conditions. perfusion is an important parameter to assess the status and liability of organs and tissue. typically, exogenous contrast agents are administered to measure this quantity. arterial spin labelling (asl) is capable of estimating perfusion without the use of exogenous contrast media by labelling inflowing blood magnetically. this labelling process can happen either in a short time over an extended region or over a longer time period, but in a localised area. these techniques are called pulsed asl (pasl) or continuous asl (casl), respectively. for quantification, a critical parameter is the time the labelled blood takes to flow from the region of labelling to the imaging region. this time is typically called bolus arrival time (bat) or arterial transit time (att). it is important to either reduce the influence of this transit time on measured signal intensity or directly estimate it. applying proper bio-physical models, the perfusion-weighted data can then be converted in absolute measures of perfusion. more sophisticated methods allow measuring of the main feeding artery of each imaging voxel (vascular territory mapping) or assessing other parameters beyond perfusion, allowing more detailed assessment of tissue status and function." the use of asl in cerebrovascular disease j. hendrikse; utrecht/nl (j.hendrikse@umcutrecht.nl) obvious applications of arterial spin labelling in clinical mr protocols are cerebral blood flow measurements in patients with acute or chronic cerebrovascular disease. in patients with acute stroke, the cerebral blood flow measurements may indicate the infarct core, with severely decreased perfusion and the infarct penumbra, with decreased perfusion but still viable brain tissue. in chronic cerebrovascular disease, arterial spin labelling cbf measurements show the regionally impaired haemodynamics distal to a carotid obstruction. with adequate collateral blood flow, these areas may be relatively small and with a failure of compensatory mechanism the cerebral blood flow may fall below a critical level. in acute stroke patients, asl mri may show compensatory hyperperfusion in stroke regions after the recanalisation of an occluded artery. other applications of arterial spin labelling are clinical mr protocols in children. in addition to cbf-weighted images, asl mri has also the ability to measure timing parameters: typically, the time it takes for the magnetically labelled arterial blood to flow from the arteries in the neck to the brain tissue, which may be delayed in patients with cerebrovascular disease. furthermore, asl mri has the ability to visualise the (collateral) perfusion territories of the brain feeding arteries in many clinical applications. in patients with cerebrovascular disease, a pitfall may be the absence of label in brain regions due to delayed (collateral) flow, which also may result in high asl signals in (collateral) arteries. learning objectives: . to appreciate the different roles of asl in cerebrovascular diseases. . to become familiar with the different types of calculated images obtained from multi-time points and selective pulses asl. . to become familiar with the limitations and pitfalls of asl. the use of asl in non-vascular brain disease m. smits; rotterdam/nl (marion.smits@erasmusmc.nl) arterial spin labelling (asl) is a non-invasive mri technique with which cerebral blood flow (cbf) can be measured quantitatively. although the first publications of asl mri date over years back, it is only now that asl is commercially available on mri systems from all major vendors and is making its way into clinical practice. the main areas of interest for current and future nonvascular clinical application of asl mri of the brain are dementia and neuro-oncology. asl is proposed as a diagnostic alternative to fluorodeoxy-dglucose (fdg)-pet in the workup of dementia patients. asl has several advantages over fdg-pet. crucially, it can easily be added to the routinely performed structural mri examination. feasibility studies show that asl provides reliable cbf maps in dementia. in patients with established alzheimer's disease and frontotemporal dementia, hypoperfusion patterns are seen that are similar to hypometabolism patterns with fdg-pet. current and future studies in this field will need to demonstrate the validity of asl in the diagnostic workup of the individual patient, early in the disease process. studies on asl in brain tumour imaging indicate a high correlation between areas of increased cbf as measured with asl, and increased cerebral blood volume as measured with dynamic susceptibility contrast-enhanced perfusion imaging. the major advantages of asl for brain tumour imaging are the fact that cbf measurements are not influenced by breakdown of the blood brain barrier, as well as its quantitative nature, facilitating multicentre and longitudinal studies. the analysis of a sinonasal tumour requires mri for differentiation between tumour and secretions or polyps, to assess the local extension and spread into adjacent compartments (skull base, intracranial, orbit, deep facial compartments) and to depict perineural spread. t , t and high-resolution postcontrast series preferably in three, but at least in two different planes, are needed. ct provides additional information of bony structures and serves as a road map for surgical navigation. a fascinating benign sinonasal tumour is inverted papilloma, which has a high recurrence rate if not removed in toto and may harbour carcinoma in < % of patients. ct may show the attachment of the tumour as an area of increased sclerosis, which directs the surgeon to plan the operation. in patients with recurrent inverted papilloma, providing information to the radiologist about its presumed localisation is important, the more so in patients suffering from polyposis. malignant tumours are uncommon and of a large histologic variety. about % arise in the maxillary sinus; % are squamous cell carcinomas. they are often large at diagnosis, because clinical symptoms of nasal obstruction or headache are non-specific. diagnosis is by biopsy. in view of the rapid development of advanced endoscopic techniques, preoperative imaging is extremely important to assess accurately tumour extension. the skull base and dura as well as the lamina papyracea should be scrutinised for tumour locations to foresee an additional cranioendoscopic approach to a standard endonasal endoscopic approach. finally, imaging may play a role in differentiating non-nasal disease, e.g. primary bone tumours, from mucosal disease. to discuss risk/benefit considerations in medical imaging from the perspective of patients and highlight some of the pre-requisites to ensure trust and confidence. this presentation will draw on the work of the european patients' forum on patient safety, quality of care, health literacy, and patient empowerment, to explore what are the key factors to consider in radiation risk analysis, from a patient's perspective, recognising that 'one size does not fit all'. it will examine what constitutes quality information in this environment, effective dialogue between the patient and the radiologist, and the interdisciplinary team, informed consent and transparency of data. it will also highlight some of the particular challenges regarding vulnerable patients, and those requiring on-going treatment due to chronic disease (s). the justification for medical procedures is based on the assumption that the benefit outweighs the risk. this presentation looks at the radiation risk factors from recent high-profile papers (pearce et al., ) and publications from international bodies such as beir and icrp. at lower radiation doses (< msv), quantifying, understanding and communicating radiation risk to staff, patients and referring clinicians presents a range of challenges. advances in health information systems will facilitate more precise dose risk relationships. there are a number of approaches to stochastic radiation risk assessment such as organ-/age-based assessment and effective dose equivalent assessment. at-risk groups, such as children and pregnant women, need special focus. eu directives demand special attention for high-dose interventional procedures and ct scans. these techniques, particularly if repeated, require further risk assessment regarding potential deterministic effects such as erythema, hair loss, and radiation-induced cataractogenesis. this paper looks at strategies in consenting, monitoring, and follow-up of such high-dose effects. the practical implications of the new occupational icrp eye dose limits for interventional practice are also examined. with the advent of higher field scanners in clinical practice and the construction of 'mri compatible' implanted devices, the list of the do's and don'ts while performing an mri examination changes constantly. in this presentation basic safety guidelines and rules will be explained regarding static magnetic field effects, time varying magnetic field effects, radiofrequency field effects and acoustic noise effects both with regard to the patient as well as the personnel using the equipment. due to the advances in medical technology the list of possible 'safe' and 'unsafe' items changes almost daily. therefore it is very important to have all the information about the patient's condition and implants prior to the mri procedure in order to asses possible contraindications in advance. while until a couple of years ago cardiac pacemakers and neurostimulators were contraindicated in the mri environment, the advent of 'mri compatible' pacemakers and other implanted devices introduces challenges in patient safety. in fact these devices are only safe in certain configurations and also in a lot of cases specific mri scan sequences and rf antennas are only allowed. following the european emf directive, where the mri part is derogated, the protection of staff working with em fields also became a topic of debate. what are the possible risks for staff working with mri magnets and how can one implement practical rules for the safe use of the mri equipment. the field of image-guided ablation has expended recently with new ablation techniques like micro-wave, irreversible electroporation, cryoablation. nevertheless, after each treatment, whatever the technique used, we will leave in place in the treated organ, a scar instead of the tumour. follow-up of these treated areas are done by radiologists using ct of mr or contrast enhanced ultrasound. standardisation of terms has been done in by an international committee presided by dr. goldberg. this allows reporting criteria identical from one center and from one country to another. furthermore, it allows a more homogeneous literature and evaluation of success. nevertheless, techniques are not all the same and the cellular and tissue damage in the tumour and around it in the healthy parenchyma are not identical and does not have the same evolution over time. thermal ablation is frequently used to treat liver, lung and bone tumoural lesions because of its safety, efficacy and tolerability. one issue is the lack of reliable imaging modality to assess treatment efficacy and to detect early relapse. several papers have demonstrated that fdg pet/ct is a useful tool to follow-up ablated liver tumour, detecting residual disease easily and earlier than conventional imaging. few reports evaluating the usefulness of fdg-pet/ct in the follow-up of ablated lung lesions are available, but prospective studies show promising results, with a high negative predictive value of this technique. very few data are available on bone lesions and further studies are needed to assess the role of fdg-pet/ct in the follow-up of these lesions. in general, the in vivo typical aspect of completely ablated lesion on fdg-pet/ct is a ring shape, diffuse, peripheral, homogeneous fdg uptake at the treated lesion; on the other hand, the presence of heterogeneous and focal uptake is more frequently related to disease relapse. suvmax (standardised uptake value) is not a reliable indicator. it is higher in case of disease relapse than in completely ablated lesions, but also in case of important inflammatory reaction. finally, the best time point to evaluate ablation efficacy still remains to be defined, but fdg-pet/ct should be performed at least months after treatment to avoid dubious or inconclusive findings due to inflammatory reaction. the aim of thermal ablation treatment is to generate an area of thermocoagulation whose diameter is larger or at least equivalent to that of the tumour. this necrotic scar usually shrinks with time, but most often very slowly. therefore, the criteria of response based on size measurement cannot be applied. the pattern of thermal ablation is similar whatever the thermo-ablation technique used. on ct imaging, thermal ablation areas are well circumscribed and oval shaped. the criterion commonly used to assess the efficacy is the absence of enhancement in the thermal ablation necrosis, which corresponds to tissue devoid of viable tumour. on mr imaging, the thermo-ablation areas are typically hyperintense on unenhanced t due to the presence of proteinaceous material, and hypointense on t , explained by the dehydrating effect of thermal damage. the residual tumour is typically round in shape and located at the periphery of the necrotic area or in contact with large vessels. mr imaging allows earlier detection of residual liver tumour than ct imaging. neurodegenerative diseases, cancer and heart disease perhaps summarise the major challenges to medicine in this century, a challenge in accurate diagnosis and also in treatment. recent technological advances in medical imaging technology mean that these challenges can be dealt with more efficiently. anatomy can be studied faster, safer and with higher spatial resolution and precision. in addition to anatomy, the study of function has become feasible; more sophisticated hardware and software are being used to get the required data to map out the functionality and understand how this relates to anatomy to offer a more comprehensive view of normal development and explain pathological conditions. at the same time, researchers and clinicians are urged to create a platform for reciprocal communication to facilitate translation of the research findings to a graspable clinical benefit for the patients. this translational platform will allow flagging the major clinical questions, inform current and future research experiments and at the same time help utilise recent research findings in the clinical setting. this session will review state-of-the-art mri techniques and document different approaches to translational imaging. it will also allow understanding the obstacles and remedies in implementing translational medicine. many neurological diseases are associated with progressively reduced cognitive function. recent evidence suggests that proficient cognitive function depends on an appropriate interaction between large-scale cognitive control networks in the brain. it is hypothesised that damage to white matter microstructure, as found in many neurological diseases, disrupts the integrated operation of these networks and results in impaired cognitive function. diffusion tensor imaging (dti) has been used to investigate alteration to white matter micro-structure and resting state fmri (rsfmri) has proven to be a useful technique to assess brain function in multiple cortical systems. however, the combined use of these techniques in the clinical setting has not yet taken hold. in this presentation, i will demonstrate the flexibility of these mri techniques in assessing brain structure and function and address their feasibility of use in a clinical setting. imaging in oncology is a growing field within radiology. different tomographic techniques are used either isolated or as multimodality-multivariable imaging, as there is an increasing need to combine morphological and functional information. different cutting-edge modalities, such as pet-ct, dw-mr, ce-mr and mr-spectroscopy, are standard in most clinical scenarios. new images have advantages providing excellent soft-tissue contrast and multidimensional functional, structural and morphological information. the development of new diagnostic imaging research areas, mainly in the field of oncology, cardiology and neuropsychiatry, will impact the way medicine is performed today. both clinical and experimental multimodality studies, in humans and animals, will have to demonstrate an efficient use of the imaging information provided by the modalities to affect the future of medical imaging. we will comment on the impact of continued technological developments in medical imaging on patients with cancer (diagnosis, staging and follow-up) and the challenges of imaging technologies from research into clinical reality. the recent advances and developments in measurements and biomarkers which have led to a greater understanding of cancer will be commented, together with the morphologic, metabolic and functional oncological imaging research and clinical practice. finally, the role of the radiographer in advanced oncological imaging techniques will be evaluated. when imaging the head and neck region with ct or mri, teeth are always present. we frequently encounter radiolucent or radiopaque lesions of the jaw on scans performed for other indications. familiarity with typical dental conditions is necessary to subject the patients to the right therapy. to correctly evaluate and describe those lesions, this special focus session on dental imaging gives the radiologist a tool to report dental lesions. the anatomy of panoramic and ct images will be reviewed in the first talk. technical details as well as pitfalls will be presented. in the second talk, the focus is on pre-and post-surgical imaging with ct where typical lesions of the jaw will be presented. an insight into imaging the teeth with mri will be given by the third speaker. the discussion on the impact of radiologists on dental images will complement this special focus session's theme. panoramic radiography produces a single image of the maxilla, mandible, teeth, temporomandibular joints and maxillary sinuses. during the exposure, the x-ray source and the detector rotate synchronously around the patient producing a curved surface tomography. this horseshoe-shaped zone of sharp image is called the focal trough/image layer. advantages of this technique are a good overview of lower facial hard tissues, the convenience of an extraoral examination, a low patient radiation dose, and low costs. disadvantages are limited width of the sharply imaged layer, variable magnification, and oblique projection, especially in the upper premolar region. patient positioning is most important for obtaining a detailed panoramic radiograph. in addition to patient position errors, patient movement during exposure and metal objects can cause artefacts. also, ghost images caused by structures located between the x-ray source and the rotation centre can hamper diagnostics. cbct is a radiographic imaging method that allows accurate d imaging of hard tissues. during a cbct scan, the scanner rotates around the patient's head ( °- °) obtaining multiple sequential planar projection images by a d detector. the scanning software collects the data which is processed to create a volumetric data set with isotopic voxels with varying fov. disadvantages of cbct imaging are poor soft tissue contrast and artefacts. in addition to normal panoramic and cbct anatomy, after this presentation the audience will be familiar with the panoramic and cbct techniques as well as common errors and pitfalls of these techniques. pre-surgical and post-surgical imaging with mdct and cone-beam ct a. gahleitner; vienna/at (andre.gahleitner@meduniwien.ac.at) multislice-ct and more recently cone-beam-ct have become an established method for anatomic imaging of the jaws prior to dental implant placement. commonly referred to as "dental-ct", these high-resolution imaging techniques have gained importance in diagnosing dental-associated diseases of the mandible and maxilla. especially in patients with inflammations, cysts, oro-antral fistulas, odontogenous sinusitis, impacted teeth and dental fractures, new indications have emerged. unfortunately, most radiologists have had little experience in this area and many of the dental-ct findings remain undescribed. hence, we will determine the ct appearance of frequent dentalrelated diseases of the jaws and demonstrate typical pre-and postoperative findings. this presentation reflects our experiences from years of performing dental-ct with . investigations, closely working together with dentists and oral surgeons. learning objectives: . to learn about the typical findings from pathological conditions of the jaw, which confront dentists and oral surgeons. . to understand these findings in cross-sectional imaging like multislice and cone-beam ct. . to learn about the usual treatments for these conditions in order to know how they are used in dental radiology. dental mri s. rohde; dortmund/ de (stefan.rohde@klinikumdo.de) this lecture will discuss the potential of dental mri in the field of inflammatory and neoplastic disease of the periodontal space. experimental and preliminary clinical data from high-field dental mri will be presented with a special focus on the visibility of critical anatomical structures on high-resolution sequences. the results will be compared to high-resolution cone-beam ct. based on representative cases, we will review the main causes of thoracic non-traumatic vascular emergencies (acute aortic syndrome, pulmonary thromboembolism and haemoptysis); mdct angiography has become the firstline imaging test for the diagnosis of these entities. as acute aortic disease is the most common fatal condition in patients with chest pain and prompt recognition and treatment are of paramount importance, we will review the spectrum of acute aortic pathology focusing on the distinctive findings of each entity (classic dissection, intramural haematoma and penetrating aortic ulcer) and upgrading the clues for their diagnosis. acute pulmonary embolism (pe) remains a common clinical challenge. mdct pulmonary angiography has become the first-line imaging study in the diagnosis of pe because of its speed, accuracy, low interobserver variability and ability to provide alternative diagnoses. we will review the role of mdct in the evaluation of acute thrombotic pe: findings of acute pe (including how to evaluate the severity of an episode of pe at ct pulmonary angiography) and some potential pitfalls. massive haemoptysis is a life-threatening condition that is associated with a high mortality rate. haemoptysis usually involves bleeding from the bronchial arteries or, less frequently, from nonbronchial systemic arteries. haemoptysis of pulmonary arterial origin is rare, estimated at less than % of haemoptysis cases. mdct angiography permits noninvasive, rapid, and accurate assessment of the cause and consequences of haemorrhage into the airways and helps guide subsequent management. acute respiratory failure can have multiple underlying causes including infection, fluid overload, immunological diseases or exacerbation of preexisting lung disease. since the clinical symptoms are nonspecific, imaging plays an important role. the first imaging method is mostly the chest radiograph, easy to access and to obtain, but non-diagnostic in many cases. (hr)ct offers more possibilities to define the differential diagnosis. the option of this interactive workshop will be to get familiar with the spectrum of diseases that can cause acute respiratory failure and learn about key findings in radiography as well as ct to reduce the differential diagnosis. the interaction between preexisting lung disease, clinical information (e.g. chemotherapy, rheumatoid arthritis, copd) and imaging findings will be discussed using clinical case studies. options and also limitations of imaging findings will be illustrated. the following scenarios will be taken into account: acute cardiac failure and various appearances of oedema; acute immunological-toxic disorders including druginduced lung disease and inhalational injuries; exacerbations of preexisting lung disease including fibrotic and obstructive lung disorders; severe infections causing respiratory failure and their complications. contrast-enhanced ultrasoud (ceus) and elastography are evolving us techniques that have already found their ways into clinical practice (ceus) or will do so in the next few years (elastography). ceus is performed with nd generation us contrast media, but these contrast media are not available worldwide. in many european countries, sonovue® (bracco, it) is the only available contrast, consisting of micro-bubbles less than the size of red blood cells. in contrast to ct and mr contrast media, these bubbles are strictly intravascular. for us imaging, low mechanical index us techniques are used to see the resonance of sound by these bubbles. ceus is excellent for the differential diagnosis of focal liver lesions based on vascularisation and specific contrast uptake (imaging the wash-in and wash-out of us contrast over time with excellent temporal resolution) and increases us sensitivity to liver metastases in colorectal cancer patients. however, ceus is only useful when there are excellent us conditions. in pancreatic us, ceus allows to differentiate adenocarcinoma from neuroendocrine tumours based on vascularisation (us contrast uptake). whereas elastography (strain elastography or shear wave elastography) is established for the diagnosis of liver fibrosis, there are no general recommendations for using these various techniques to measure the "hardness of a focal lesion" in focal liver and pancreas lesions. diffusion-weighted mr imaging (dw-mri) provides information on tissue cellularity, extracellular space tortuosity and integrity of cell membranes by measuring the motion of water molecules in tissues modified by flows (blood vessels, glandular ducts,.). and interaction with cellular components. integrated in conventional-mr acquisition protocol, dw-mri increases sensitivity for lesion detection. the apparent diffusion coefficient (adc) can be calculated using a mono-exponential relationship between signal attenuation and b-value. this fitting is influenced by microcapillary perfusion. a more sophisticated approach (intravoxel incoherent motion, ivim) would enable estimation of parameters that separately reflect tissue diffusivity and microcapillary perfusion. using ivim-analysis, the derived quantitative parameters describe tissue diffusivity, perfusion and perfusion fraction. by providing qualitative and quantitative information, dw-mri is applied in oncology to characterise malignancy, including lesion aggressiveness, and to monitor treatment response. perfusion imaging is a useful tool to achieve information concerning tissue vasculature, microvascular permeability and interstitial space characteristics. dynamic contrast-enhanced techniques (dce-ct, dce-mr) are based on the analysis of the contrast agent (tracer) biodistribution in tissues. quantitative parameters are obtained using pharmacokinetic models, as transfer constant ktrans, extracellular-extravascular space fraction ve, vascular tissue fraction vp and the rate constant kep. quantitative dw-mr and dce-mr parameters are increasingly used as imaging biomarkers to predict tumour response and/or to monitor the effects of therapy, especially when anticancer agents with novel models of action are used (anti-angiogenic, tyrosine kinase inhibitors and several others). therefore, these new imaging biomarkers may have a pivotal role in correctly evaluating tumour response and stratify and managing cancer patients. elderly and the young can all present special problems that require a greater depth of understanding to obtain a diagnostic study. this session will help you in your quest for reliable high-quality investigations for all. a. coronary cta in patients with severe arrhythmias and high heart rate c. loewe; vienna/ at (christian.loewe@meduniwien.ac.at) besides all advances in scanner technology, heart rate remains a critical issue for coronary cta, and motion artefacts due to cardiac function represents still the most frequent reason for limited diagnostic image quality in cardiac cta. thus, the target heart rate is defined depending on the scanner system used and ranged between below bpm and below bpm. however, in a number of patients heart rate control is not possible or not successful (i.e. children, emergencies, heart transplant recipients), whereas a relevant proportion of ctas are performed in patients with heart rates higher than the target frequency. during this presentation, the possibilities for heart rate control by beta blocker injection and beyond will be discussed and possible workflows will be presented. furthermore, examination strategies for patients with high heart rates will be presented including reverse dose modulation, high-pitch scanning, systolic scanning and more. finally, tools for reconstruction and assessment of patients scanned at higher heart rate will be introduced. different to high heart rates and even more critical with regard to image quality is arrhythmia. due to the complexity of cardiac synchronisation, a ct suite is not the place for cardiac resynchronisation, whereas the indication to cta has to be reevaluated depending on referring diagnosis and severity of arrhythmia. since there are patients undergoing cta because of arrhythmia including patients prior to ablation treatment, strategies for examination and image reconstruction in case of arrhythmic patients have to be established and will be presented. cardiac computed tomography (ct) has become a widely available diagnostic tool used in a range of heart conditions. the commonest application of this technique is in the evaluation for coronary artery patency (coronary ct angiography) in patients with chest pain. when coronary arteries are heavily calcified, or post-coronary angioplasty with stent implantation, diagnostic problems can occur. in these circumstances, the evaluation of the coronary arteries on ct is hampered by the occurrence of high-density artefacts caused by calcifications and stent struts. these artefacts may preclude the appropriate assessment of the coronary lumen. the presence of motion artefacts in the dataset or image noise in very large patients may exacerbate the problem. in this scenario, accurate patient selection and preparation remain key to ensure that the diagnostic yield of the cardiac ct study is good. optimisation of scan parameters (kv), contrast injection protocol and use of appropriate postprocessing techniques (e.g. dedicated convolution filters) play an important role in daily clinical practice. recent technical developments include dualenergy scan techniques and gemstone spectral detector systems that acquire simultaneously high and low kilovoltage datasets. this is done to achieve tissue differentiation. in principle, by using monochromatic image reconstruction, the effect of high-density artefacts may be decreased. using a similar principle, high-density structures can be subtracted from the image. the introduction of iterative reconstruction algorithms may play a role in that these algorithms are theoretically more accurate in the modeling of physical noise and tissue geometries. lack of movement artefacts is one of the major prerequisites for good image quality in cardiac mr. it is crucial to have the minimum possible image acquisition time. it is important to make both te and tr as short as possible. data acquisition should be synchronised with patient's ecg or pulse. special attention should be paid to good quality of ecg recordings (good contact of electrodes with the skin, electrodes positioning, using of dielectric pad). in patients with arrhythmia, prospective ecg synchronisation should be used instead or a retrospective one, or special protocols may be applied for arrhythmia correction. breathing artefacts are usually not a problem for cardiac mri, because most sequences are acquired during a single breath-hold. using ssfp and parallel imaging allows obtaining a complete set of cine mr images through the whole heart in - short breath-hold periods. the technique of realtime cardiac mr is a good way to perform successful examinations even in difficult patients, especially the ones with heart failure. other systemic mrartefacts (aliasing, chemical shift, magnetic susceptibility, off-resonance) should be recognised and diminished or eliminated by the operator. these artefacts are more prominent in case of t systems. late-enhancement studies with gd are very dependent on the correct selection of the ti time. phase-contrast mri requires venc calibration in cases of valve stenoses. to meet the challenges and the benefits of cardiac mri, one must balance the constraints of signal-and contrast-to-noise ratios, spatial and temporal resolution, scan time and image quality. scoliosis, a common spinal deformity in teenagers, especially girls, progresses during their growth until the end of puberty. therapeutic choices, which are either medical -with corset -or surgical, depend on this progression. follow-up is mainly clinical. however, radiographs are often indicated to give precise information: ap and lateral views of the spine in standing position remain the basis of this follow-up. obtaining a good image quality at all levels of the spine has been a technical challenge for a long time, and the question of radiation dose is also a main concern, as these radiographs require a high radiation dose. fortunately, radiographic techniques have greatly improved over the past few years: from the conventional or cm film to digital screens and now flat screens, we now obtain better quality images with less radiation. today, eos system using xenon chamber is the best to give good ap and lateral views. it allows d reconstructions with minimal radiation dose. on these radiographs, measures can be performed, essentially cobb's angle. it helps in evaluating progression of the curves and making surgical decisions. other imaging techniques are requested only in particular situations as in the presence of neurological symptoms or general disease such as neurofibromatosis, or in young children with malformative scoliosis and sometimes preoperatively. ct is best to study the vertebrae; it objectivates vertebral malformations (agenesis, hypoplasia, blocks). mr will be requested to study the cord, nervous roots, craniospinal junction and the soft tissues. collaboration between the radiologist and spinal surgeon is essential. the key elements in the diagnostic process, as for most bone lesions, are: the age of the patient, the type of bone and bone segment involved, the location within the bone, the presence of signs of aggressiveness (type of osteolysis, limits, presence and type of periosteal reaction). conventional x-rays should never be absent from the initial workup of a focal bone lesion in a child, as they provide essential features for differential diagnosis and, in most cases, eliminate the need for other more costly techniques. the need and priority for other imaging techniques, such as ct, mri and bone scintigraphy, are decided on a case-by-case basis and sometimes a combination of these techniques, which complement each other, is needed. it is the radiologist's responsibility to recommend histological analysis of a lesion via biopsy whenever the imaging aspect is not characteristic or indicates signs of possible malignancy. learning objectives: . to recognise the most common benign bone tumours and pseudo-tumours. . to understand the differences between benign bone tumours, pseudotumours and malignancies in children. . to understand imaging modalities that could help in the differential diagnosis of benign bone tumours and pseudo-tumours in children. a- : a.c. offiah; sheffield/uk (amaka.offiah@nhs.net) the nosology and classification of genetic skeletal disorders subdivides conditions into groups defined by molecular, biochemical and/or radiographic criteria. conditions are associated with mutations in at least one of different genes. some of these conditions are rare or even extremely rare (occurring in fewer than in , of the population). clearly, the general paediatric radiologist cannot be expected to correctly recognise and diagnose all of these conditions. the approach is to perform a set of radiographic images dependent on the patient's age/size and to develop a standard system for reviewing these images. the standard set of images for a patient over to years of age consists of ap and lateral skull, ap chest, ap pelvis, lateral thoracolumbar spine, ap one upper limb, ap one lower limb and dp left hand. variations on this routine dysplasia skeletal survey will be discussed and a standard system for interpreting the images will be presented using radiographs of the commoner skeletal dysplasias as examples. in the last few years, interest in body composition (bc) analysis, which is the quantification and characterisation of relative amounts of muscle, fat, bone, and other vital parts composing the human body, has grown rapidly for clinical, research and epidemiological purposes. studying body composition has gained great importance for the comprehension and decoding of a multitude of patho-physiological processes (e.g. obesity, diabetes and endocrine diseases and also gastrointestinal, renal, nervous, infectious diseases, etc). and physiological and para-physiological conditions as in athletes or growth and ageing processes. although the main imaging techniques, which include dualenergy x-ray absorptiometry (dexa), computed tomography (ct), and magnetic resonance imaging (mri), offer a differentiated and attractive analysis of bc, they still need to find a definite position in clinical practice. through 'programming' low birth weight is associated with increased rates of coronary heart disease, stroke, hypertension & non-insulin dependent diabetes. prediction of morbidity and mortality from body composition, particularly fat, stimulates the importance and application of accurate and precise methods for quantitative assessment of body composition; the gold standard for which is cadaver analysis, but other methods have to be implemented in vivo. body composition alters in many chronic diseases, starvation cases, metabolic syndromes, and senescence stages, and is a key component of health. several techniques are available which vary in simplicity and complexity of use. each make assumptions and may not measure body composition directly, but make predictions from other measurements made. skinfold thickness measurements assess regional fat and are quick and simple to perform at all ages. reproducibility is good, but less so in obesity. there is some limitation of reference data to express results as standard deviation scores (sds). body mass index (bmi; weight/height ) is widely used as an index of relative weight expressed as sds for gender, age and ethnicity. waist circumference (wc) is a measure of central fat, and can also be expressed as a ratio to hip circumference. bioelectric impedance analysis (bia) measures body impedance to a small electric current, which estimates total body water (tbw) from which can be derived fat free mass (ffm). tbw can also be measured by neutron activation. air displacement plethysmography (bod pod) is a new method for body composition assessment. learning objectives: . to understand normal body composition in children and adults. . to learn how body composition can be altered by disease. . to appreciate the clinical relevance of assessing body composition. . to understand the non-imaging methods available for measuring body composition, with their advantages and limitations. computed tomography: what does it measure and how? j. damilakis; iraklion/ gr (damilaki@med.uoc.gr) ct allows measurement of total body fat and enables differentiation of subcutaneous from visceral adipose tissue. body fat can be estimated using the conventional technique of manual planimetry. using planimetry, the user delineates manually the boundaries of subcutaneous and visceral fat in each ct image. however, this method is labour intensive, time-consuming, and, therefore, not easily applicable in routine clinical practice. another ct method used for the estimation of abdominal fat is the semiautomatic measurement of adipose tissue area. abdominal fat is assessed in a ct slice by using a fixed range of hounsfield units to define the area of adipose tissue. a limitation of this method is that the attenuation range of fat may vary among individuals. the stereological volume estimation method is based on the cavalieri's principle. according to this principle, the volume of an object can be measured by cutting it into equally spaced slices and measuring the area of the object on each slice. to measure body fat using stereology, a square grid of test points is randomly superimposed on each ct section. all points lying inside the fat tissue region are selected by the user and the software automatically calculates the total number of points hitting the fat. stereology provides the possibility for efficient fat volume assessment. however, research studies are needed to optimise the stereological estimation of fat and compare stereological measurements with those from other adipose tissue measurement ct techniques. learning objectives: . to appreciate the role of ct imaging in body composition analysis. . to learn how to measure visceral and subcutaneous adipose tissue using ct. . to understand the advantages and limitations of ct techniques (planimetry, thresholding, stereology) in evaluating adipose tissue. mri: current and future applications d.c. karampinos; munich/ de (dimitrios.karampinos@tum.de) mri has been emerging as an ionising radiation-free imaging modality to measure fat distribution in the human body and fat content in different organs. the present talk will first introduce mri methods to measure fat distribution, including the well-established t -weighted imaging and the emerging dixon imaging approaches. the challenges related to the data acquisition and image post-processing of the two imaging approaches in the study of fat distribution will be reviewed. examples will be shown from the current use of mri in investigating adipose tissue distribution alterations or differences in patients with metabolic disorders, including obesity and diabetes. quantitative mri methods enabling the measurement of fat content with high spatial resolution will be then presented, with a focus on water-fat separation methods. the technical challenges associated with the establishment of mri-based fat content, as an accurate and reproducible imaging biomarker will be discussed. the selection of pulse sequence parameters and image reconstruction algorithm in a state-of-the-art water-fat separation experiment will be explained. applications will be shown from the growing literature of mri-based fat quantification in abdominal organs (e.g. liver) and in skeletal muscles, aiming to show the great premise of quantitative water-fat mri in quantifying fat content with high spatial resolution in different body parts. at the end of the talk, the potential of quantitative water-fat mri will be discussed in the emerging application of measuring bone marrow fat content and its association with bone health and metabolic disorders. the key role of dual-energy x-ray absorptiometry (dxa) in the management of metabolic bone diseases is well known. the role of dxa in the study of body composition and in the clinical evaluation of disorders which directly or indirectly involve the whole metabolism as they may induce changes in body mass and fat percentage is less known or less understood. dxa has a range of clinical applications in this field, from assessing associations between adipose or lean mass and the risk of disease to understanding and measuring the effects of pathophysiological processes or therapeutic interventions, in both adult and paediatric human populations as well as in pre-clinical settings. dxa analyses body composition at the molecular level that is basically translated into a clinical model made up of fat mass, non-bone lean mass, and bone mineral content. dxa allows total and regional assessment of the three abovementioned compartments, usually by a whole body scan. since body composition is a hot topic today, manufacturers have steered the development of dxa technology and methodology towards this. new dxa machines have been designed to accommodate heavier and larger patients and to scan wider areas. new strategies, such as half-body assessment, permit accurate body scan and analysis of individuals exceeding scan field limits. although dxa is a projective imaging technique, new solutions have recently allowed the differential estimate of subcutaneous and intra-abdominal visceral fat. the transition to narrow fan-beam densitometers has led to faster scan times and better resolution; however, inter-or intra-device variation exists depending on several factors. in cancer patients, disease-free survival is a good indicator for tumour response, but for many common cancers, treatment of disseminated disease is often noncurative. the increased duration of survival is related to changes in tumour size after treatment. however, the anatomical determination of tumour response has some limitations, especially when non-cytotoxic targeted therapies are used. with these new treatments options, the lack of progression may be associated with a good improvement in outcome, even in the absence of major shrinkage of tumours. new imaging biomarkers are therefore needed to assess therapeutic response. molecular imaging is now playing a prominent role in the monitoring of cytostatic targeted therapies. pet-ct, dynamic contrast enhancement studies or diffusion-weighted imaging are the most promising ones. the aim of this session is to present the state of the art in tumour response assessment with regard to new therapeutic regimens. in early oncologic times, treatments of different malignancies were reported in different ways. c. gordon zubrod and others first articulated the model of multicentre clinical trials and argued for standards to be agreed for included and excluded subjects, the method of assigning treatment and in measuring response. nowadays, we have better knowledge of tumour biology; however, we continue using the classical response criteria (who and recist) and overall survival as a primary goal for effective treatment in most of the malignancies. in the last few years, different criteria for responses have been reported to evaluate the disease and a lot of discussions between authors have been reported. now, we can use the recist criteria v . , implement the percist criteria and also forget the immunotherapy criteria. furthermore in the last few years, different treatments such as vaccines, antiangiogenics and targeted therapies have increased our arsenal in the treatment of different malignancies such as kidney cancer, prostate cancer, breast cancer and so on. another problem for our patients is that those diseases have a long evolution after the first-line treatment. we have to be able to define in each disease the treatment line and type of treatment to determine which evaluation criteria are necessary and which is the objective of treatment, pfs or os. we have to be aware that if we are not able to define such topics, we may be losing active treatments. recist . are the criteria most often used in studies to evaluate response to treatment in solid tumors. on each follow-up examination, response is defined by a combination of unidimensional measurement of 'target lesions', qualitative evaluation of 'non-target' lesions, and presence/absence of 'new lesions'. ct and mri are the preferred modalities for recist evaluation, and evaluations must be performed using the same modality, in the same plane. we will review anatomic locations which should be avoided, and how to deal with intercurrent events resulting in the impossibility of measurement. cases when recist seems inadequate will be discussed, including evaluation of bone metastases, and focal therapy. finally, though these criteria were developed for drug trials, they may provide a frame for reading examinations and writing reports in routine practice. reproducible, objective and quantitative criteria help to define or in the obese patient. ct is especially helpful in those with suspected retroperitoneal pathology, in the investigation of immunocompromised patients and those with complex post-operative problems. ct guidance may be required to facilitate percutaneous abscess drainage, particularly for deep pelvic collections. in addition, ct plays a vital role as a 'problem-solver' when ultrasound has failed to fully answer the clinical question posed. this short presentation will utilise clinical studies to illustrate the benefits of ct in the investigation of the acute abdomen, both as the initial imaging modality and as a second line tool following ultrasound. learning objectives: . to understand the advantages of ct as a primary imaging modality for children with acute abdomen. . to learn about clinical scenarios in which ct is relevant. . to appreciate the use of ct as an adjunct to ultrasound. abdominal trauma: us is better v. miele; rome/it (vmiele@sirm.org) ultrasonography (us) is a reliable technique whose advantages are rapidity, portability and accuracy in depicting intraperitoneal fluid without interrupting resuscitation and without radiation exposure. in the haemodynamically unstable paediatric patients, it represents the first line together with the x-ray evaluation. us for trauma has become more standardised and is worldwide known with the acronym of fast (focused abdominal sonography for trauma) or e-fast (extended-fast) used in depicting also pleural and pericardial effusions and pneumothorax. nevertheless, many parenchymal injuries are not correctly visualised at baseline us and some traumatic solid organ lesions can occur without hemoperitoneum. in case of haemodynamically stable patients, who have suffered a low-energy trauma, the greater time available allows the use of specific us contrast agents, enabling a better identification of traumatic organ injuries. contrast-enhanced ultrasonography (ceus) has a greater sensibility and specificity in the identification of parenchymal traumatic lesions, both in the first evaluation and follow-up, and could avoid unnecessary radiation and iodinated contrast medium exposure. in case of haemodynamically stable paediatric patients, who have suffered a high-energy trauma, us is not recommended as first-line investigation, because ce-mdct should be performed first. only in the follow-up, ceus can be considered an alternative to ct. in conclusion, e-fast and ceus should be considered as a useful tool in the assessment and monitoring of paediatric trauma. this examination can be performed at the patient's bedside, representing a useful alternative to ct in the paediatric traumatised patients and in the follow-up of a known abdominal injury. learning objectives: . to understand the differences in the diagnostic paths of paediatric patients. . to learn about the diagnostic efficacy and limitations of ultrasonography. . to become familiar with the use of the contrast-enhanced ultrasonography (ceus). abdominal trauma: ct is better m. raissaki; iraklion/gr (mraissaki@yahoo.gr) ct has been considered a sensitive, specific, and accurate test in the identification and grading of injuries, especially in the severely injured child. it should be overemphasised that traumatised children differ from adults: haemodynamically stable children may actually be actively bleeding and rapidly deteriorate. conversely, children have smaller calibre vessels, stronger vasoconstriction, and stronger solid organ capsules; bleeding may stop spontaneously, organ rupture is more difficult and delayed rupture is rare. this is why few children will undergo laparotomy or trans-arterial embolisation. the goal of imaging is to clear the abdomen in multi-traumatised children, identify those that may rapidly deteriorate because of clinically silent active bleeding, increase the surgeon's confidence level and define short-and long-term medical management. due to children's increased radiosensitivity, all ct scans should be indicated based on appropriate early clinical evaluation, assessment of risk factors for abdominal injuries and evaluation of the closely monitored child. alara includes the availability of outside scans upon admission, avoiding non-contrast scans and multiple phases and applying age-and weight-dependent exposure parameters. ct should not be performed as follow-up unless there is clinical deterioration. ct has the advantage of rapidly identifying and delineating with high resolution solid organ, vascular, mesenteric, bowel injuries and pending oligaemic collapse (hypoperfusion complex or shock bowel). important fractures and thoracic injuries may be simultaneously revealed with ct. the objective documentation of intraabdominal injuries is extremely important in suspected child abuse. evaluation of mr imaging in a patient with an intramedullary lesion should focus on key features: a) the location of the lesion on the cross-sectional area of the cord, best evaluated on axial images, b) the length of the lesion evaluated on sagittal images, c) the presence of cavitation and cysts, d) signal intensity on t -wi, e) the presence of enhancement and enhancement type, and f) associated leptomeningeal enhancement. the knowledge of the presence or absence of the brain lesions is important information for narrowing the differential diagnosis. the clinical picture and the onset of symptoms will help the differentiation between the neoplastic and inflammatory and vascular lesions. in this lecture, the imaging characteristics and typical patterns of intramedullary lesions will be presented. a diagnostic algorithm, which includes imaging, clinics and csf analysis, will be discussed. a common clinico-radiological situation is the differentiation between spinal infection, degenerative changes and osteopaenia, and spinal tumour. in most cases, conventional ct and/or mri will allow a certain differentiation, and additional biopsies are mainly used to obtain tissue for bacteriological or histopathological classification. advanced mr techniques such as dwi may sometimes help in increasing diagnostic certainty, but are seldomly used in day-to-day practice. spinal infections typically present around the intervertebral disc, but may also present as isoloated spondylitis without disc involvement, and sometimes the infection quickly spreads to the epidural space. degenerative changes my sometimes mimic infection due to strong gadolinium enhancement. the main differential diagnosis of spinal tumorous processes is osteopaenic changes (oedema), and ct may be helpful in such cases, for example to demonstrate degenerative gas in the vertebral body. rare causes of spinal abnormalities such as atypical pathogens and rare tumours may cause diagnostic problems; often the fastest road to a diagnosis is biopsy in those cases. the correct clinical diagnostic approach to spine disease is mandatory in the selection of patients to be treated. the anatomy and the relationship between different structures must be known in detail to understand the source of the pain and so to treat it percutaneously. mr, ct, dynamic x-ray and nm bone scan in selected cases can be used to understand the reason for the pain. mr with t stir sequence or t fat supp technique is mandatory to show bone marrow oedema and to decide on which metamer to perform the treatment. ct is often necessary after mr in primary and secondary spine tumours. disk disease can be seen either on ct or mr. two major treatments must be considered: discogenic pain and vertebrogenic pain, and for this reason disk treatment and vertebral treatment. disk treatment includes many mini-invasive systems to use; however, no treatment has been shown to be superior to the others, with good clinical results in - % of the cases, even at long-term follow-up. vp and assisted techniques are available for the treatment of not within a few minutes following ablation, ct of the ablation zone will demonstrate an extensive area of ground glass opacity (ggo). a ggo of at least . mm peripheral to the tumour is predictive of complete ablation. as early as hours post-treatment, the entire ablated region usually appeared as a well-demarcated homogeneous dense opacity on ct that corresponded to necrotic tissue and its surrounding rim of granulation tissue. this zone of ablation is the "baseline post-ablation imaging" for follow-up. then, a relatively slow involution of the ablation zone will occur with various patterns, including nodular, fibrosis, disappearance, cavitation and atelectasis. morphologic features of local tumor progression are an increase in the overall size or a change in the shape of the ablation zone (even without enhancement). it is generally considered that an ablation volume that does not increase in size on subsequent imaging after the baseline post-ablation imaging is a complete ablation. the relatively slow decrease in size of the ablation zone renders ct morphologic evaluation responsible for late discovery of local tumour progression. pet/ct is able to discover incomplete ablation earlier than ct at a stage the disease remains small. patients who have very early evaluation with pet/ct are at risk of either false-positive result due to early inflammation process, or false-negative result due to early inflammation masking active tumor foci. or months after ablation can be a reasonable time for pet/ct. learning objectives: . to consolidate knowledge on the imaging aspects of successful ablation. . to become familiar with the main pitfalls of post-ablation imaging. . to learn about the imaging aspects of most common complications. a- : c. follow-up imaging of thermal ablative therapies for kidney tumours d.j. breen; southampton/uk (david.breen@uhs.nhs.uk) image-guided ablation of kidney tumours has been increasingly set to become the standard of care treatment for smaller (< cm) renal tumours, yet ablation remains a non-extirpative technique and is therefore paramount, in this curative setting, that imaging follow-up should reliably confirm complete tumour eradication. early on in radiofrequency ablation (rfa), control remained problematic and inadequate treatment was evidenced by residual marginal crescents of viable, enhancing disease. in the current era of more definitive ablation with multipolar techniques, cryo-and microwave ablation (mwa), this pattern of treatment failure should rarely, if ever, be encountered. typically following adequate ablation imaging should confirm a completely nonenhancing tumour and a related cortical ablation zone. whilst nonenhancement is an accepted surrogate of tumour non-viability, most practitioners look for additional collateral features such as the 'halo' sign, appearing as a soft tissue ring in the adjacent peri-renal fat, usually a sound marker of complete tumour eradication. follow-up data have shown that cryoablation (cra) can yield robust outcomes, but often incurs notable haemorrhagic change and a 'rind-like' feature around the ablation zone. cra also appears to induce faster involution of the treated tumour, whereas rfa and mwa can induce a persistent granulomatous mass which only very slowly involutes over a number of years. late local recurrence is increasingly rare at around - %, but can occur as nodules of enhancing disease as late as - years after the initial treatment. subtraction mr can be useful, but to date pet and perfusion techniques still lack resolution and specificity. multiple percutaneous image-guided therapies are currently available for thermal ablation of bone tumours. thermal sources for these treatment modalities include high-intensity ultrasound, laser, microwave, radiofrequency, and cryotherapy. the predictability of thermal ablation is adequate to limit collateral damage and complications, however, is limited by biologic and anatomic variability of tissue. clinical evaluation is essential in symptomatic tumours. close imaging follow-up with ct, mri, bone scan, and pet plays a vital role in the management of the post-thermal ablation patient and detection of complications. recurrences or regrowth can be considered for repeated thermal ablation if the lesion is discovered early, before the tumour geometry, location, or distribution become unfavourable. the imaging features could vary with the different ablation method. the radiologist reporting the follow-up imaging should be familiar with different ablation methods. mri with dynamic contrast enhanced imaging and subtraction allows to detect recurrences in hypervascular tumour. contrast enhancement on t -weighted mri imaging seems to be predictive of clinically unsuccessful ablation. on ct scan, bone reconstruction can be visualised but is a slow process, particularly in adults. pet scan is an excellent morphologic and metabolic image to follow-up the tumours. however, the inflammation produce after ablation can be misleading, particularly during the first three months. imaging follow-up plays an essential role in the management of the post-thermal ablation patient and detection of complications. interventional radiology (ir) is an evolution of radiology that treats many diseases, originally treated by traditional surgery. the clinical importance of ir has been demonstrated over the years by performing procedures that offer the benefit of therapeutic treatments, competitive from the point of view of a shorter hospitalisation time. indeed, thanks to ir, patients are treated in a less invasive manner, hospitalisation is limited and thus promotes the containment of social costs. to maintain standards clinical oversight needs to focus upon correct organisational, functional and technological appropriateness of practice. to achieve correct ir performance, it is necessary to guarantee that all the instrumental guides (fluoroscopy, ultrasound, computed tomography equipment) function optimally, the procedural equipment including guides/catheters/stents, etc. are chosen according to their technical features and their characteristics are appropriate for use, incorporating cost considerations. as the complexity and variety of interventional procedures grow, there is an increasing need to ensure the appropriate training of specialised ir staff. consideration of dedicated education and continued professional development options for radiographers working in ir is of priority. the italian association of interventional radiographers (aitri) is very important in sharing guidelines in a multidisciplinary environment to standardise and harmonise the knowledge and skills of the team in hybrid theatre and interventional suites. interventional radiology technology is rapidly expanding and, to maintain safe and efficient practice, careful consideration of current and potential future organisational needs and the training of staff within an ir suite require detailed consideration. the lecture will discuss where new and current knowledge about radiation risk and effects are coming from. a brief overview of the different sources of knowledge, including hiroshima and nagasaki life span study, will be given. the most important stakeholders involved in research and formulating guidelines for radiation protection, with special emphasis on the new main publication from the international committee on radiological protection (icrp), and the impact on radiographic practice will be discussed. new tissue weighting factors for breast glandule gives a significant higher risk for females today, especially in the pubertal age. on the other hand, they have the risk for hereditary effects significantly decreased. estimation of risk, both in general and in the individual, will be discussed. regarding staff protection, there is a new recommendation for annual dose limit for the eye lens. the previous annual dose limit was msv, and this is now recommended to be decreased to msv averaged over five years with no single year exceeding msv. the new recommendation can be a limiting factor in interventional radiology and cardiology, if sufficient protection is not used. learning objectives: . to understand the importance of radiation protection in interventional radiology for patients and staff. . to appreciate the latest recommendations for staff radiation protection in interventional radiology. . to appreciate the important role of the interventional radiographer in radiation protection. a- : the improvement of patient care and aims for the highest possible levels of service are to the forefront of the modern "interventional suite". role development experiences will be explored, considering need, effect and management of development. service demands, the need to extend those provided, the limited number of radiologists, financial constraints and the requirement for continuous professional development at state level provide much stimulus for professional radiographic role development. increased job satisfaction, reduced waiting lists and improved patient experience all provide largely positive results it appears. resistance from radiologists, multidisciplinary team members and radiographers themselves however, can provide unnecessary barriers to change. once abridged the blurring of professional lines and insecurity within multidisciplinary team members may also occur. various experiences would suggest that only by allowing ownership of change by all the clinical stakeholders involved, thus empowering them, leads to successful development. on examination clear guidelines and distinct protocols must be established, taking account of current workload, to create the ideal scenario for good multidisciplinary team ethos, where members have overlapping yet clearly defined roles. professional accountability, responsibility and an understanding of those role's are all key, but without correct training, including support and resources, no regime for role development can be achieved successfully. clinical audit not only ensures the delivery of high quality and effective care in line with best practice, whilst ensuring cost effectiveness, but also provides the confidence for all involved, especially the interventional patient. learning objectives: . to understand the factors influencing change in professional roles within interventional radiology. . to learn about the potential impact of enhanced professional roles and a multidisciplinary team approach on service delivery and patient outcomes. . to understand the need for clear protocols and guidelines along with appropriate training and audit of practice when implementing such changes. there have been many attempts to develop gene reporters for mri, however these give relatively modest image contrast that can be difficult to detect. i will describe in this talk a reporter that gives intense and positive contrast in mr images (up to ~ x increase in signal), which can also be used with radionuclide imaging, thus combining the sensitivity of radionuclide imaging with the spatial resolution of mri. the contrast obtained is directly related to the degree of gene expression and is readily reversible, thus allowing longitudinal studies of changes in expression. the transplantation of pancreatic islet into the liver is an excellent example of successful cell therapy. transplanted islet visualisation in vivo using a noninvasive imaging method, for example mri, is necessary to prove technical success. monitoring of transplanted islets in vivo and long-term tracking their fate using mri requires their labelling by a suitable contrast agent in vitro prior to transplantation. under encite project we successfully performed animal experiments, which proved therapy potential of labelled pancreatic islets. labelled islets implanted into the rat liver were viable and induced long-term normoglycemia in diabetic rats. mri proved their viability and even distribution in the host tissue. these results allowed performing a clinical study on a group of patients, which were transplanted by iron labelled pancreatic islets from cadaver donors. the successful pilot experiment enabled introducing of transplantation of native islets into routine clinical practice. search for better alternative sites, improved immunosuppression and alternative insulinproducing cells require multimodal and multifunctional molecular probes. currently we test polymer meshes as artificial transplant sites, effect of mesenchymal stem cells as a supportive net for beta cells, and novel cellular probes combing h, f labels and fluorescent ones. optical imaging in the clinic j. dijkstra; leiden/nl (j.dijkstra@lumc.nl) recently a lot of developments have been done in the field of optical imaging. new sensitive devices made it possible to use both visible and near infrared light as diagnostic tool and guidance tool. the advantage of near infrared is that the penetration depth in tissue is much better than for visible light, allowing to see deeper. by using techniques like augmented reality, the data from infrared, both anatomical and functional, can be presented to the operator in real-time. optical imaging is used e.g. as an evaluation tools for mammography where the optical spectral properties of the tumor cells is used to monitor the effectiveness of chemo treatment. the spectral properties of the breast are measured using a laser at different wavelengths and a camera to create tomographically a d volume. dedicated near infrared probes which bind to certain tissue types make it possible to look for e.g. remaining tumor tissue in resection margins during surgery. this techniques also allow to visualise structures which should be avoided during procedures like nerves. by adding multispectral imaging, the endogenous contrast can be used. different tissues have their own absorption spectrum which can be shown as additional information, for instance the ration hb/hbo . optical imaging also allows for acquiring images at near microscopic resolution real time in-vivo by using optical coherence tomography. this modality is being tested to provide information about the presence of certain cell types very fast where otherwise histology is needed. mesenchymal stem cells constructs for image-guided cell therapy in myocardial ischemia and digestive fistulas o. clément, e. blondiaux, g. rahmi, l. pidial, a. silva, f. gazeau, c. wilhelm, g. autret; paris/fr (olivier.clement@inserm.fr) regenerative medicine has recently emerged as a potential therapeutic tool. a number of preclinical and clinical trials have been conducted in many diseases ranging from diabetes to myocardial infarction and neuro-regenerative diseases that assess the feasibility and benefits of injecting stem cells. however, outcomes relating to graft survival remain generally unsatisfactory, whether the process of injection is direct, intravenous or catheter-guided. to overcome such issues, tissue engineering has potential to improve cell engraftment and therapeutic response including functional parameters. this work aimed to evaluate mesenchymal stem cell constructs for image-guided cell therapy in myocardial ischemia and digestive fistulas. we tried to options: . fibrin patches based on fibrinogen monomers polymerised with thrombin and seeded with cells. . constructs based on d multilayers of confluent cells sheets. tissue constructs were labelled with iron oxide particles and evaluated in a model a myocardial infarction for the fibrin patches or digestive fistula for the d constructs. mri at . was performed at various time points after treatments using a high resolution coil. fibrin patches could induce a therapeutic effect by increasing the left ventricular ejection fraction compared to sham. d constructs induced an increased number of fistula healing and enhanced micro-vasculature density compared to controls. mri of labelled stem cell constructs allowed a good evaluation of the models and showed increased therapeutic efficacy. the proposed paracrine mechanisms will be discussed. is cell imaging relevant for the clinic? lessons to be learned from preclinical research u. himmelreich; leuven/be (uwe.himmelreich@med.kuleuven.be) non-invasive imaging of therapeutic cells has become a popular field of research over the last decade. this interest was mainly based on the hope that the location, migration but also function of immune, stem and other cells can be visualised over time in individuals. the development of novel contrast agents and mechanisms for mri but also other imaging methods has resulted in exciting basic research findings. in particular, the application of relatively biotolerant iron oxide based nanoparticles has fostered the hope for direct translation into clinical research and general practice. however, pre-clinical research has also highlighted several limitations of nanoparticle based cell imaging by using mri including the generation of unspecific contrast, difficulties to quantitatively image engrafted cells, unambiguous contrast, adverse effects on cell biology, limitations for longitudinal follow-up or the lack of functional information. such shortcomings are traditionally overcome in preclinical research by combining mri with other imaging modalities like bioluminescence imaging or positron emission tomography. our research focuses on the optimisation of cell labeling strategies for robust, sensitive and potentially quantitative visualisation of stem and progenitor cells in therapy models in vivo to assess cell behavior after engraftment. the sensitivity, stability, toxicity and adverse effects on the cell biology by the labeling procedure were studied for iron oxide based particles. the potential of gdchelates and f labeled compounds for cell labeling has been assessed in vitro and in vivo. based on our preclinical research finding the potential of future applications in patients will be explored. cardiac ct is becoming the imaging modality of choice for an increasing number of clinical indications, not only to rule out coronary artery disease but also to evaluate cardiac morphology and function, and to determine patient outcome after coronary artery revascularisation. however, as with any other imaging tools, appropriate interpretation of cardiac ct examinations is required to assess the clinical value of this newly established diagnostic imaging modality. this process requires performance of thorough cardiac ct acquisition protocols, detailed knowledge of standard cardiac anatomic and physiologic terminology, as well as appropriate postprocessing, reading and reporting. in particular, radiologists need to recognise and be aware of the imaging findings that may confound and lead to interpretation errors. this lecture will summarise the practical aspects of postprocessing, reading and reporting of non-invasive cardiac ct examinations. the value and limitations of every available ct postprocessing technique including two-dimensional multiplanar reformations, curved multiplanar reformats, maximum intensity projection (mip) and volume rendered images will be explained. moreover, hints for improving reading results by recognising technical causes for various artefacts in cardiac ct will be elucidated and reading approaches to diminish false positives, false negatives and inaccuracies when assessing coronary artery stenosis will be suggested. cardiac magnetic resonance (cmr) is a complex imaging technique due to the intrinsic anatomical and technical peculiarities of the exam. these include the non-orthogonal cardiac orientation within the chest cavity requiring dedicated acquisition planes and the complex respiratory and cardiac motion to which the heart is subject and requiring a combination of ecg-gated and breath-hold sequences. potential additional anatomical pitfalls also include normal structures and variants like the moderator band, papillary muscles, and the presence of prominent crista terminalis or myocardial trabeculations, whose recognition is mandatory and may mimic in some cases a pathological condition. technical issues of cmr concern the continuous intracavitary inflow of protons and the associated "slow-flow" artifacts (limiting visualisation of endomyocardial border in some cases) pitfalls related to ecg gating, like inadequate synchronisation or the t-wave swell phenomenon; and finally a series of specific artifacts intrinsically related to the use of different pulse sequences that may interfere with image quality. an additional, more complex issue to consider is also the widespread diffusion of high-field magnets which have further enhanced those aspects. knowledge of the spectrum of those cmr peculiarities is mandatory to approaching and providing a correct diagnosis according to the main clinical request. the present lecture will review the most important anatomical and technical pitfalls of cmr examination and offer, when possible, practical solutions to overcome those limitations. shoulder imaging and intervention are becoming increasingly important in clinical practice. this session considers the indications, techniques, imaging findings and relative merits of diagnostic ultrasound and mri of the shoulder. the indications, techniques and results of us-guided interventional procedures are also considered. a panel discussion will deal with controversies in shoulder imaging such as the accuracy of us and mri in assessing rotator cuff tears, tendinosis, impingement and muscle atrophy, and the efficacy of us-guided interventions. audience participation in the discussion will be welcome. the shoulder is an anatomic area that is very commonly evaluated with musculoskeletal ultrasound. ultrasonography is widely recognised as a reliable means of assessing rotator cuff disease with accuracies reaching % for fullthickness tears and - % for partial-thickness tears. diagnostic accuracy depends mostly on the skills and experience of the examiner. a comprehensive ultrasound (us) examination requires, first of all, sound knowledge of the anatomy. a specific scanning protocol must be adopted in every us examination in patients with shoulder disease, because focal symptoms do not correlate with the location of the disease. the greatest importance of ultrasonography in rotator cuff assessment lies in its dynamic character. several dynamic manoeuvres can reveal pathologies such as subacromial impingement. last, but not least there are several scanning pitfalls such as anisotropy. anatomy key structures as well as the us technique and scanning protocol will be presented in this lecture. dynamic manoeuvres will be described and demonstrated with videos. scanning pitfalls will be emphasised. advantages and disadvantages of the us examination compared to other imaging modalities will be discussed. guidelines concerning the mr examination technique of the rotator cuff will be presented in this session. on intermediate-weighted mr images, tendinopathy and partial and complete tears of the rotator can be differentiated with high diagnostic accuracy. indications for mr arthrography, especially for the detection of small articular sided partial tears in athletes, will be presented as well. established classification systems for the description of rotator cuff tears will be discussed. besides characterisation of rotator cuff lesions, especially in view of therapeutic decision-making, recognition of the underlying pathomechanism is necessary. therefore, the role of imaging is to detect different structural findings that are suggestive of a possibly underlying impingement syndrome. in primary impingement syndromes imaging abnormalities of the rotator cuff, the overlying bursa and the coracohumeral arch represent the centre of imaging findings. primary extrinsic impingement is caused by structural abnormalities of the coracoacromial arch, whereas secondary extrinsic impingement is related to glenohumeral instability. types of internal impingement (posterosuperior and anterosuperior impingement) are secondary to rotator cuff and/or capsular dysfunction. posterosuperior impingement can be diagnosed on mr arthrograms by identification of the socalled "kissing lesion" pattern, with corresponding lesions of the undersurface of the rotator cuff, posterosuperior labrum, greater tuberosity and superior glenoid. imaging abnormalities of this condition will be discussed. the shoulder is one of the joints in the human body that is most subject to a number of pathologic conditions, both in young and in elderly subjects, such as subacromial-subdeltoid bursitis, calcific tendinopathy, and degenerative conditions. being inexpensive, readily available, and radiation-free, ultrasound is the imaging modality of choice to guide interventional procedures around the shoulder. thanks to its high resolution and multiplanar capabilities, ultrasound can be used to guide needles precisely in the tendons of the rotator cuff or within the joint space, both gleno-humeral and acromio-clavicular. this approach can be used to perform a number of different procedures. when dealing with bursitis, a needle can be guided within the subacromial bursa to aspirate fluid and to inject anti-inflammatory drugs. in case of calcific tendinopathy, one or two needles can be used to dissolve calcium deposit and drain it, providing patients prompt relief. in selected patients with overuse tendinopathy, ultrasound can be used to guide intratendinous injection of platelet-rich plasma that has been reported to be helpful in stimulating tendon healing. although minimally invasive, these procedures should be performed in an ultrasound ward with a high degree of sterility, as risk of infection can be concrete. multi-detector computed tomography (ct) offers new opportunities in the imaging of the gastrointestinal tract. its ability to cover a large volume in a very short scan time, and in a single breath-hold with thin collimation and isotropic voxels, allows the imaging of the entire oesophagus, stomach, and the whole chest and abdomen with high-quality multiplanar reformation and threedimensional reconstruction. preparation of the patients by fasting from solid food approximately hours prior the examination is important. proper distention of the oesophagus and stomach by oral administration of effervescent granules and water, and optimally timed administration of intravenous contrast material are required to detect and characterise the disease. preoperative staging of oesophageal and gastric carcinoma appears to be the main indication for mdct and may replace endoluminal ultrasound (eus) in the staging of advanced cancers. the use of various reconstruction techniques, including virtual gastroscopy (vg) using a volume-rendering (vr) technique, is promising for the detection of early gastric cancer. the application of the texture analysis technique to distinguish between the different types of gastric and esophageal tumors is still evolving. finally, the introduction of fdg pet, in combination with mdct, has resulted in further optimisation of the diagnostic workup of oesophageal cancer, as well as specific types of cases of gastric cancer. by providing morphologic and functional information in the same setting, this technique has come to be the modality of choice, when available. the diagnosis of oesophageal and gastric cancer is usually based on endoscopic findings accompanied by biopsy. however, staging is a matter for diagnostic imaging and is the major determinant of disease management. this should be discussed within a multidisciplinary forum (multidisciplinary team [mdt] meeting) in which the radiologist plays a crucial part. accurate stagingusually based on the tnm staging criteria -is essential and the radiologist's report should reflect this pivotal role. the tnm staging of oesophageal cancer and gastric cancer will be discussed in detail. the phases in staging is essentially a filtering process which seeks to initially exclude distant metastasis and/or advanced local disease, initially by optimally protocolled ct scanning, if ct shows advanced disease, treatment is palliative, but even under these circumstances imaging will help determine the method of palliation. conversely, if ct demonstrates localised disease, f fdg-pet scanning for oesophageal cancer and for selected cases of gastric cancer is indicated. if this, too, shows no nodal or distant metastasis, accurate t staging with eus will help determine whether the patient proceeds directly to surgery or undergoes neo-adjuvant chemo/radiotherapy prior to surgery, or in the case of oesophageal cancer may be suitable for emr. the role of staging laparoscopy in gastric cancer will also be discussed. in summary, the radiologist and nuclear medicine physician are crucial in determining treatment. their reports are lynch pins in the mdt discussion of patient management. it is therefore essential that the imaging report should optimally inform this discussion. learning objectives: . to learn about the latest tmn staging in oesophageal and gastric cancer. . to appreciate the imaging criteria for local, nodal and metastatic disease, and understand the accuracy of imaging staging. . to become familiar with the structure of a perfect imaging report. a- : c. assessment after treatment a.m. riddell; london/uk (angela. riddell@rmh.nhs.uk) it is now established that for the majority of patients with oesophageal and advanced gastric cancer, there is survival benefit from the use of neoadjuvant therapy. therefore, there is a requirement for imaging to accurately restage the tumour and to assess the response to neoadjuvant therapy, to provide prognostic information and to direct future management. restaging following therapy is challenging, as differentiating treatment-related fibrosis/oedema from viable tumour is problematic with both ct and endoscopic ultrasound. the t and n staging accuracy for both modalities falls following neoadjuvant therapy. inconsistencies in measurements due to alterations in the degree of gastric/oesophageal distension can also limit the accuracy of recist criteria to determine the response. functional imaging techniques such as pet-ct offer an improved method for assessing response. alterations in the standardised uptake value (suv) occur much earlier than changes in size; therefore a metabolic response can be detected sooner, allowing for more rapid alterations in treatment strategies. acute complications following oesophagogastrectomy generally occur within the thorax and are either related to a leak at the anastomosis/mediastinitis or respiratory complications such as pneumonia or a pleural effusion. intra-abdominal collections may develop following oesophagogastrectomy and gastrectomy. late complications following both procedures are often due to tumour recurrence: locoregional such as lymph node recurrence or at the anastomosis; metastatic spread such as haematogenous spread or via the peritoneum or pleura. currently, there is no consensus on the most appropriate timing or frequency of postoperative imaging. a. an overview of pulmonary artery hypertension n.j. screaton; cambridge/uk (nicholas.screaton@papworth.nhs.uk) pulmonary hypertension is defined by increased mean pulmonary arterial pressure > mmhg at rest or > mmhg during exercise. ph causes significant mortality and morbidity, but commonly presents with non-specific clinical signs and symptoms resulting in significant delay in accurate diagnosis and specific treatment. untreated ph is progressive with increased pulmonary vascular resistance leading to right ventricular failure and ultimately death. the current dana point classification of pulmonary hypertension is clinically based. it groups diseases with similar pathophysiological mechanisms and therapeutic approaches. groupings include conditions characterised by diffuse small vessel narrowing (group and group '), ph secondary to left sided cardiac disease (group ), chronic hypoxic pleuro-parenchymal disease (group ), chronic thrombo-embolic pulmonary hypertension cteph (group ), and a miscellaneous group of diseases with either unclear or multi-factorial aetiologies (group ). in the dana point classification, small vessel diseases are subdivided into group which primarily affect the pulmonary arterioles and group ' affecting the capillary/venous pulmonary circulation (pulmonary capillary haemangiomatosis and pulmonary veno-occlusive disease). the differentiation of group from group ' diseases is important since in group ' arteriolar dilatation treatments can cause life-threatening pulmonary oedema. group is synonymous with cteph with other causes of large vessel obstruction (vasculitis and pulmonary artery tumour) being considered as group disorders. recent advances include an increased understanding of molecular mechanisms underpinning pah, facilitating targeted therapy development, a rapidly expanding role of surgical pulmonary endarterectomy in proximal cteph, and recognition of imaging as a potential therapeutic end point. ct allows depicting pulmonary hypertension (ph) and helps identifying its cause, therefore playing a crucial role in the diagnostic workup. ct features of pulmonary arterial hypertension include dilatation of the pulmonary artery trunk, with a diameter greater than or equal to mm, a ratio to the aortic diameter greater than : and a segmental artery-to-bronchus ratio greater than : in at least three pulmonary lobes. on ecg-gated ct, right pulmonary artery distensibility shows the best diagnostic value with % sensitivity and % specificity for a cutoff value of . %. among the various causes of secondary ph, ct is especially useful for detecting signs of chronic thromboembolic pulmonary hypertension, including wall-adherent thrombi, bands, webs or chronic arterial occlusion, mosaic lung attenuation and systemic collateral supply. ct shows signs of pulmonary edema, such as thickening of the interlobular septa, centrilobular ground glass opacities, mediastinal lymph node enlargement and pleural effusion in ph caused by pulmonary veno-occlusive disease, left heart diseases or mediastinal fibrosis. signs of lung parenchyma diseases may be indentified on ct; ph is a late complication in patients with pulmonary fibrosis, sarcoidosis or chronic obstructive lung disease, but may affect systemic sclerosis patients with limited lung parenchyma involvement. congenital cardiac abnormalities with untreated right-to-left shunting resulting in eisenmenger syndrome, such as ventricular or atrial septal defect and patent ductus arteriosus are easily recognised on ct. conversely, signs of peripheral pulmonary arteriovenous shunting in portopulmonary hypertension and ph caused by hepatopulmonary syndrome are more difficult to assess. learning objectives: . to learn about the ct diagnosis of pulmonary artery hypertension. . to become familiar with the causes of pulmonary artery hypertension on ct. a- : c. mri in pulmonary artery hypertension j. biederer; heidelberg/ de (juergen.biederer@med.uni-heidelberg.de) for the assessment of pulmonary arterial hypertension (pah), the dedicated min mri protocol would comprise a free breathing and noncontrastenhanced examination, short t -w sequences, dynamic contrast-enhanced perfusion imaging, a high-resolution angiogram, a d breath-hold acquisition, dynamic steady-state free precession or gradient echo sequences of the heart and a study of myocardial late enhancement. the morphologic sequences show typical features of pah: right atrial/ventricular dilatation, enlargement of the pulmonary trunk/main pulmonary arteries and peripherally attenuated pulmonary vessels. incidental infiltrates, nodules or masses of the lung, mediastinum and chest wall would be covered. the first pass contrastenhanced perfusion imaging demonstrates an increased mean transit time/decreased pulmonary blood flow, but a relatively homogeneous lung perfusion (important to differentiate from cteph, where multiple segmental perfusion defects would be expected). the cardiac part shows right ventricular mass, wall thickness and functional changes correlating with elevation of pulmonary arterial pressure: distortion of the interventricular septum, area change of the pulmonary trunk, right ventricular volume/stroke volume as well as pathologic right/left ventricular end-diastolic volume indexes. late enhancement of the right ventricular wall would correlate with myocardial fibrosis. furthermore, optional experimental velocity-encoded sequences (ideally for multidirectional flow visualisation, " d flow") show a decreased pulmonary artery blood flow velocity, increased retrograde flow and inhomogeneous velocity profiles. in conclusion for the near future, given the availability of scanner time and appropriate experience of the team, thoracic mri is probably the most comprehensive and effective single examination for the diagnosis and follow-up of pah. in the era of organ-based radiology, the group of diseases known as multisystemic malignancies represents an obvious challenge to both radiologists and oncologists. the necessity to match the growing possibilities of different imaging modalities with widespread multisystemic pathology and clinical sufficiency resulted in upgrading well-known diagnostic algorithms. the precise knowledge of clinical staging systems and classification, and the pathologic and physiologic mechanisms of the disease pathways are important for planning imaging modalities and specific protocols. perfect imaging of multisystemic malignancies now includes not only traditional anatomic-based modalities, but also much more often different types of whole body scanning such as ct, mri, pet and their combination in spect/ct, pet/ct and now even pet/mri. new imaging modalities and growing possibilities of traditional imaging techniques obviously influence the current clinical guidelines for this disclosure: c. heussel: consultant boehringer ingelheim, grifols, novartis. a common language between radiologists and clinicians, so that the latter can make an informed treatment decision based on sound conclusions to become familiar with the conditions necessary to implement them to understand the limits of their application to learn useful lessons from these criteria for routine clinical practice chairman's introduction a. palko this requires a thorough knowledge of the relevant brain anatomy, choice of appropriate structural and molecular imaging modalities and interpretation of mri and pet/spect in the most prevalent disorders in a structured fashion the presentation has the objective of giving the audience a synthesised panorama of our country situated in north america, with more than million inhabitants and a large prehispanic history based on the aztec, toltec and maya cultures, and also of interesting facts related to the three centuries of colonial existence under the spain influence and dominium until the war of independence. after , mexico has never had an international war; the last was against the northern border country, the united states. also, we will give important data on how in the mexicans rebelled against a -year dictator, general porfirio diaz. the mexican revolution was a long and cruel war, but later opened the doors to democracy and a complex developmental era began that is still in process. some demographic and contributions to health, science and culture issues will be mentioned and also the works of mexican scientists, writers and philosophers who have been presented awards including the nobel prize. in relation to well-known mexican artists such as diego rivera and frida khalo, some facts of their works will be presented. interventional radiology in oncologic patients g. elizondo-riojas; monterrey/ mx (elizondoguillermo@hotmail.com) interventional radiology (ir) is becoming an increasingly prominent subspecialty in the care of oncologic patients. its role extends from initial diagnosis to minimally invasive treatment of the malignancy and its complications. image-guided biopsies are increasingly performed using minimally invasive techniques. also, an integral part of care of these patients is vascular access as a means of medication, chemotherapy or parenteral nutrition, and interventional radiologists can place required the devices with well-established safety and efficacy. ir also plays a substantial role in the therapy of oncologic patients, through local tumor treatments such as transarterial chemo-embolisation and locoregional control with radiofrequency/cryo ablation, as well as management of complications of malignancy such as pain, obstruction (biliary, ureteral, etc) ., venous thrombosis and drainage of thoracic and abdominal collections. in mexico, ir is a growing subspecialty, and more medical students nowadays want to be radiologists and eventually become interventional radiologists. this is a paradigm shift. more and more radiologist wants to be involved with patient management and to be more than just "observers" in the process of patient care. we have to be prepared to offer this opportunity to our residents; otherwise other specialties will "have to fill the empty space" that we have left. interventional oncology has all the advantages to fulfil this opportunity. it is our chance to contribute to the advancement of medical care. learning objectives: . to appreciate the role of interventional radiology in the management of oncologic patients. . to learn how interventional radiology changes the quality of life for patients with cancer. . to understand the impact of interventional radiology procedures in the outcome of some neoplastic diseases. interlude: origins and development of radiology in mexico m.e. stoopen-rometti; mexico/mx (mstoopen@clinicalomas.com.mx) mexican radiology started in , just a few months after the discovery of xrays. during the last few decades, as well as in other countries, there has been a great development both in public and private sectors, which will be described in this interlude. learning objectives: . to learn about the history of radiology in mexico. . to learn about the development of radiology in mexico. . to learn about the present and future of radiology in mexico. modern issues in oncologic ultrasound j. mexico/mx (jtanus @hotmail.com) advances in ultrasound (us) technology allow confident characterisation of masses. these include harmonic imaging, compound imaging, power doppler, faster frame rates, higher resolution transducers, three-dimensional ( d) us, us contrast agents and, more recently, elastography and fusion imaging. highfrequency transducers provide superb spatial and soft-tissue resolution, permitting substantially improved differentiation of subtle lesion, margin resolution, and lesion conspicuity in the background of normal tissue. elastography features such as size ratios, shape, homogeneity, and maximum lesion stiffness complement conventional us in the analysis of lesions. ultrasound contrast agents have overcome some of the limitations of doppler ultrasound techniques with demonstration of irregular branching central or penetrating vascularity within a solid mass raising suspicion of malignant neovascularity (neoangiogenesis). ultrasound contrast agents can provide important information in the assessment of lesions to be treated by locoregional therapies, which include ablation (feeding vessels), trans-arterial chemo/radio-embolisation, detecting viable tumour persistence following this treatment; facilitation of needle positioning in cases of poor lesion delineation, and assessment of local tumour progression. it facilitates needle positioning in cases of incomplete or poor lesion delineation on unenhanced ultrasound. us contrast agents are an important key during the evaluation of the immediate treatment effect of ablation and guidance for immediate re-treatment of residual tumour. learning objectives: . to understand the role of ultrasound in the management of oncology patients. . to learn how ultrasound is used in large oncology centers. . to learn about the modern concepts of ultrasound in oncology patients. the aim of this lecture is to give an overview of the techniques for imaging inflammatory bowel disease (ibd) of the small bowel and the colon with either ultrasound (us), multidetector row computed tomography (mdct) or with magnetic resonance imaging (mri) and compare the different modalities for its strength and weakness. optimal imaging of the bowel begins with the preparation phase. the small bowel has to be distended for a concise examination. this is mainly done orally, which is named enterography. a solution of . % mannitol seems to be the one preparation technique mostly used for small bowel distension. another technique is the enteroclysis, application of contrast after intubation of the small bowel. the comparative advatages and disatvantages of the two preparation methods will be discussed. this intraluminal contrast gives a neutral contrast in ct and a biphasic signal in mr. the colon can be prepared in a fashion similar to colonoscopy meaning total cleansing. another possibility is the so called fecal tagging whereas the stool will be contrasted with an additive to standardised food. therefore no cleansing is needed for preparation. imaging parameters will be discussed for mr and ct. the aim of imaging for the bowel should be to establish the following: ) presence, severity, and extent of disease; ) activity of the disease and ) extra-intestinal complications. us, mr and mdct have proven to be a good tool to evaluate the extent, the activity of the disease and the presence of extraluminal complications. pros and cons will be discussed when to use which technique. learning objectives: . to understand state-of-the-art mri, ct and us protocols for imaging ibd. . to appreciate the comparative advantages and disadvantages of enterography and enteroclysis protocols. . to learn about protocol modifications when evaluating the colon.a- : b. small bowel disease j. stoker; amsterdam/nl (j.stoker@amc.uva.nl) classification of small bowel crohn's disease is helpful for assessing disease activity and treatment monitoring. similar to clinically based classification, also imaging-based classification systems have been developed, of which some have been externally validated. important imaging features for determining disease activity include bowel wall thickness and vascularity/enhancement; at mri, also wall oedema plays a role. stenoses, fistulas and abscesses are important sequels. for assessment and monitoring of small bowel disease the breast imaging reporting and data system (bi-rads®) for mammography of the american college of radiology (acr®) consists of several components, a standardised lexicon of terms to be used during reporting, a -step coding system for the mammographic density as a surrogate parameter for the mammographic sensitivity, and a group of assessment categories ranging from to for structured communication regarding the recommended further management. the goal of bi-rads® is to improve the quality of breast imaging reporting and communication. in addition, by providing structured reports it facilitates regular quality assurance measures. the bi-rads® atlas for mammography is currently in its fourth edition and was released in . the upcoming th edition is expected soon and will be incorporated into the course as it becomes available. the breast imaging reporting and data system (bi-rads) was first developed by the american college of radiology for standardising the reporting of mammography. since its first publication in , new editions have also addressed breast ultrasound (us) and mr imaging examination. the new (fifth) edition will be published soon. on the form, this new version was designed to include a web-based format. substance includes updates in lexicon descriptors, e.g. masses, calcifications, associated features (now comprising surrounding tissue with stiffness assessment), and special cases. us descriptors will be reviewed in the lecture. of note, guidance on how to link bi-rads descriptors with management recommendations has been added in the report section. a new approach to outcome assessment (audit section) is being proposed for screening us. the appropriate use of descriptors is expected to increase the accuracy of imaging interpretation. for relevant patient management, us analysis is to be integrated with other available imaging, as well as with clinical data. learning objectives: . to learn about the bi-rads lexicon. . to understand the usefulness of bi-rads system. a- : c. mri k. pinker-domenig, p.a.t. baltzer; vienna/at (katja.pinker@meduniwien.ac.at) dynamic contrast-enhanced magnetic resonance imaging (dce-mri) of the breast is a well-established non-invasive imaging technique. it has clinical application in the screening of high-risk patients, diagnosis and staging of breast cancer, monitoring neoadjuvant chemotherapy and post-treatment follow-up. to standardise the reporting of dce-mri of the breast and minimise false-positive results without compromising sensitivity, the american college of radiology (acr) introduced the breast imaging-reporting and data system (bi-rads®) mri lexicon in . bi-rads relies on the combined analysis of morphological appearance and lesion enhancement kinetics. it is widely used for reporting dce-mri of the breast and is applicable at any given field strength. it aims to provide an up-date report on the bi-rads® lexicon and instill confidence in using bi-rads® descriptors. the bi-rads® system may be placed in a broader clinical context to highlight its value for standardised reporting of dce-mri of the breast. mr-guided focused ultrasound is a new therapeutic modality which can allow selective destruction and or heating of tissues in deep body areas under close image guidance control. these talks will introduce the field and allow you to understand the areas of current work and areas of future development in this rapidly expanding field. session objectives: . to become familiar with mr-guided focused ultrasound. . to understand the advantages of focused ultrasound. . to learn in which areas focused ultrasound is evolving successfully. description of technique c. moonen; utrecht/nl (c.moonen@umcutrecht.nl)high-intensity focused ultrasound (hifu) is the only clinically viable technology that can be used to achieve a local temperature increase deep inside the human body in a non-invasive way. mri guidance of the procedure allows in situ target definition and identification of nearby healthy tissue to be spared. in addition, mri can be used to provide continuous temperature mapping during hifu for spatial and temporal control of the heating procedure and prediction of the final lesion based on the received thermal dose. the primary purpose of the development of mr-guided hifu was to achieve safe non-invasive tissue ablation. the technique has been tested extensively and is now accepted in the clinic for ablation of uterine fibroids. mr-guided hifu for ablation shows conceptual similarities with radiation therapy. however, thermal damage generally shows threshold-like behaviour with necrosis above the critical thermal dose and full recovery below. mr-guided hifu is being clinically evaluated in the cancer field. this presentation will cover the basic technologies for treatment of stationary tissues, and some advances towards treatment of mobile abdominal organs. for state-of-the-art mr liver and pancreatic imaging, a field strength of at least . t is required. all non-blood pool gadolinium chelate-based contrast agents are suitable for dynamic liver and pancreatic mri. all gadolinium chelates should be routinely administered at a rate of - ml/s followed by a ml saline flush at - ml/s using a power injector. to obtain hepatobiliary phase imaging in addition to dynamic phase imaging, the use of liver-specific contrast agents is required. gd-eob provides the highest hepatocyte enhancement, but an overlap between delayed phase and hepatocyte phase has to be considered during dynamic evaluation. the hepatocyte phase can be considered adequate when contrast is detected in the intrahepatic bile ducts. hepatobiliary phase imaging benefits from a gradient echo high flip angle, depending on magnet field strength. in the absence of liver function impairment and biliary obstruction, contrast-enhanced mr cholangiography can be obtained with gd-eob at - minutes, and with gd-bopta at - minutes. when the differential diagnosis is primarily between solid benign lesion vs. metastasis, the use of a liver-specific ca is recommended, due to the ability to diagnose fnh confidently. the combined interpretation of dynamic and hepatobiliary phase improves diagnostic accuracy of mr imaging for the detection of hcc.hemangiomas and intrahepatic ccc result in relative hypointensity in the late vascular phase after gd-eob administration. when combined with t weighted mrcp, contrast-enhanced mrc allows morphologic and functional assessment of the biliary system. gastrointestinal stromal tumours (gist) are rare malignant tumours arising within the wall of the gut from the interstitial cells of cajal, which act as pacemaker cells controlling peristalsis. the crude annual incidence of clinically detected gists is approximately cases per million in europe. the median age at diagnosis is approximately years, and % of patients are older than years. however, a small number of cases do occur in younger people and children, and these are usually syndromic gists. gists can occur at any site of the gut from the oesophagus to rectum, although they can also arise in the extra-gastrointestinal abdominal and pelvic locations, so-called e-gists. the commonest location is the stomach ( %), followed by the small intestine ( %) and rectum ( %). diagnosis is by biopsy, with spindle cell or epithelioid morphology, and immunohistochemical staining for cd (the protein product of the kit gene) and/or dog- receptors. approximately, % of gists have mutations in the kit gene, % have mutations of the pdgfra gene, and the remaining % have no mutation (wild-type) or rare gene mutations. early stage disease is managed by surgery, followed by years of adjuvant imatinib (a tyrosine kinase inhibitor with activity against kit and pdgfra receptors) for cases at high risk of relapse. advanced metastatic disease is treated with imatinib, with a median duration of response of approximately years. at disease progression, second-line treatment is with sunitinib, with a median duration of response of approximately months. imaging plays a major role in the detection, characterisation and staging of gastrointestinal tumours (gists). imaging of gists depends on the mode of presentation and the local availability. endoscopic ultrasound and computed tomography (ct) are the most widely used imaging methods. gists have a spectrum of radiological appearances depending on tumour size and site of origin, but often show certain key radiological features. multiphase multidetector row ct is necessary to detect and stage gists and multiplanar imaging is important so as to define the likely organ of origin of the mass, which may be a challenging task. the clinical diagnosis of a gist is based mainly on imaging, as biopsy runs the risk of tumour rupture or seeding of the biopsy tract. in patients with an unresectable primary tumour or metastatic disease at presentation, biopsy confirmation is important before starting medical treatment. ct or/and mri are used to assess primary tumour extension, local invasion and the presence of metastases, with main sites of metastasis being the liver and the omentum. gastrointestinal stromal tumours (gists) are treated with targeted therapy regimes. these treatment strategies are based on the suppression of tumour vasculature using the tyrosine kinase inhibition pathway. drugs like imatinib and sunitinib exhibit specific changes in tumours and metastases that can be detected on cross-sectional imaging. these changes differ significantly from standard treatment effects of cytotoxic chemotherapy. while the latter leads to destruction of tumour cells and thereby to a reduction of tumour size, the former will cause a decrease in vascularity and thereby in attenuation and enhancement of lesions while the size may remain unchanged. radiologists have to be aware of these specific patterns of response to treatment. this presentation will include a review of the choi criteria which have been developed for the assessment of gist lesions under treatment. also, current imaging strategies focusing on time-resolved ct imaging (ct perfusion imaging) will be presented. the aim of this lecture is to provide a practical approach to response imaging in gist patients integrating both existing and novel strategies. radiological response evaluation using anatomical imaging was developed in the s in early phase ii clinical trials. potential new anti-cancer agents were assessed by measuring tumour size before and during therapy and a predetermined reduction in size constituted response. radiological response represents an objective surrogate for patient benefit and was the primary end point in early phase ii studies. if a pre-defined percentage of patients achieved the required response, then the agent proceeded to large phase ii and iii studies where clinical time to progression or progression-free survival comprised the primary end point. between and , there were extraordinary advances in cross-sectional imaging techniques which became widely available. different imaging techniques were introduced piecemeal with different co-operative groups adding different requirements, so meaningful comparisons from one trial to another could not be made. in , the recist criteria were introduced requiring specific imaging stipulations and a minimum baseline tumour size to unify the different criteria and enable meaningful comparisons from one study to another. further advances continue to be made regarding anatomical and functional imaging. not all anti-cancer agents are cytocidal and many studies now use time to progression or progression-free survival defined by radiological imaging as the primary end point. certain tumour types respond in a unique manner requiring the employment of specific response criteria in these tumour types to adequately demonstrate response. some of these tumour types and their specific response criteria will be discussed. learning objectives: . to learn about the role of radiological response evaluation in clinical trials. . to understand how radiological response evaluation has evolved and continues to evolve. . to understand which response criteria are utilised in specific tumour types. emerging biomarkers for response assessment: pros and cons m.c. roethke; heidelberg/ de (m.roethke@dkfz.de) non-invasive response assessment of new specific anti-cancer therapies is an emerging field of oncologic imaging. in the past few years, large efforts were undertaken to develop new functional biomarkers to enable an earlier diagnosis, improved risk stratification and treatment monitoring of oncological diseases. imaging biomarkers reflect changes in tumour biology, which can be differentiated into certain categories (e.g. cell density, tumour heterogeneity, iron concentration, elastic properties, or cellular receptors). in a first step, alternative qualitative and quantitative imaging biomarkers for the different modalities (mri, ct, pet) are elucidated. for magnetic resonance imaging, new techniques with potential for treatment response monitoring such as diffusion-weighted imaging, susceptibility weighted imaging, and elastography will be assessed. then, quantification of iodine uptake of contrast-enhanced ct as an imaging biomarker will be addressed. novel pet imaging strategies for therapy monitoring will be mentioned with focus on receptor targeting tracers (e.g. psma, dotatoc). furthermore, the role of pet-ct/mri is mentioned to facilitate functional techniques in oncological imaging with imaging biomarkers. the potential clinical use of prior introduced biomarkers is demonstrated for several cancer entities (e.g. hcc, prostate cancer, malign melanoma, multiple myeloma, glioblastoma). advantages and disadvantages of the illustrated imaging biomarkers are discussed during this part of the lecture. the goal is to image the right patient, at the right time, using the right test and with the right interpretation so that patients will be advised on the right therapy. ultimately, the aim is to maximise patient outcomes at an affordable cost. this session will cover the state of the art in ebr, cer, and hta and demonstrate how the results are used in imaging decisions. the application of evidence-based medicine to medical imaging was relatively delayed in comparison to other specialties. radiologists should be aware of the necessity to justify radiological examinations and imaging-based interventional procedures on the basis of the best available evidence. diagnostic tests can be evaluated with studies exploring their value in terms of: . technical performance; . diagnostic performance; . diagnostic impact; . therapeutic impact; . patient outcome; . societal impact. notably, this is a one-way logic chain. while improvement at the upper levels implies improvement at some of the lower levels, the vice versa is not always true (e.g., a better diagnostic performance does not always imply a therapeutic impact or a better patient outcome). moreover, different degrees of recommendations are based on different levels of evidence, with experts' opinion as the lowest level of evidence and meta-analyses of high-quality homogeneous studies and multicentre studies being the best level of evidence. the quality of studies needs to be evaluated in terms of internal and external validity, the former regarding study implementation (protocol violations, reference standard, measurements, and readers' independence), the latter regarding study planning (study design, subjects selection, methods, and statistical analysis). biases influencing the internal validity limit the intrinsic value of study results, while those influencing external validity limit the generalisability of study results to clinical practice. finally, high-quality research must be planned to build the evidence in favour of radiological procedures, especially for new technologies which tend to enter the market without any preliminary demonstration of efficacy. state-of-the-art methods in ebr, cer, and hta relevant to imaging u. siebert; hall i. tirol/at more and more, clinical guideline developers and reimbursement decision makers need to base their work and decisions on solid evidence. this presentation will introduce the key concepts and principles of evidence-based medicine (ebm), comparative effectiveness research (cer), and health technology assessment (hta) and their application to the field of radiology. in particular, it will be discussed which role observational studies, clinical trials, and decision-analytic modeling play in ebr, cer, and hta and when each of these study types is needed to assess imaging technologies. specific topics include the assessment of bias, optimising cutoffs and multiple test strategies, making causal inferences, explicitly weighing benefits, risks and costs, and considering ethical, legal and social implications (elsi). the excitement generated by the discovery of x-rays led to the early adoption of this technology in many hospitals around europe. over the last three decades, the explosion of new medical imaging technologies together with the recognition by clinicians of the value of these for their patients has meant that imaging budgets have increased exponentially. evidence based radiology (ebr) is a relatively new approach designed to inform clinicians of the most appropriate technique to use in a given clinical scenario. the comparative effectiveness research (cer) is used by healthcare systems to develop a strategic approach to rationalise the availability of imaging investigations. the health technology assessment (hta) funding approach is a mechanism to assess new and emerging imaging technologies in a systematic timely manner. the uk has a nationally funded healthcare system which is designed to deliver equitable care for the population free at the point of delivery. the challenge for the uk has been to ensure the highest quality service by delivering the most appropriate technology and care for patients in a timely manner. the national institute for clinical excellence (nice) is an independent body which gives guidance on new drugs and medical devices. this body requires robust scientific evidence on which to base their decisions. to create the evidence base, the imaging studies need to be of a certain standard to be included (consort, stard, etc). an example from oncologic imaging will be used to show how ebr influences daily practice. acute abdomen and abdominal trauma are both emergencies with potential fatal sequela when under/ misdiagnosed. imaging plays a crucial role in the diagnosis and management. us is the imaging technique of choice in most cases, as it is rapid, portable, lacks radiation and there is no need for sedation in young infants. us accuracy can be enhanced by iv contrast agents administration. however, limitations may occur in obese children, in deep structures, or because of gas filled bowel loops. on the other hand, ct provides excellent visualisation without limitations by obesity, gas, or deep lesions. however, there is always the radiation exposure risk of the radiosensitive paediatric patient, while sedation is required in non co-operative young children. the aim of this session is to understand "which" is the modality of choice and "why", for the most common paediatric abdominal emergencies. the acute abdomen: ct is the answer a. paterson; belfast/uk (anniezunz@gmail.com)abdominal pain is a common symptom in children, and whilst the majority will have a self-limiting condition, in some the pain may indicate an acute medical or surgical condition that requires prompt investigation and treatment. in the paediatric setting, the primary imaging modality for those with an acute abdomen is ultrasound. however, there are certain patient groups -often older children or adolescents -in whom ct plays an important role. it is well acknowledged that ct is non-operator dependent: an important factor for children presenting to emergency departments outside children's hospitals. the speed of a ct exam is valuable in the acute setting, as is the capability to obtain images without having to touch the tender abdomen of a distressed child. ct offers a global perspective of the abdomen, and image quality is not hindered by the presence of excessive bowel gas, an abnormal body habitus only porotic fragility fractures, but also of primary and secondary spine tumours such as traumatic fractures. a wide variety of lesions in and around the orbita can impair eye movement. ct and mr imaging is frequently used to confirm or exclude lesions in and around the orbit in patients with impaired eye movement. first of all, it is very important to know the exact clinical history of the patients. ct is excellent for confirming a mass; however mri is more sensitive and arrives often at a single most likely diagnosis. characteristic imaging features may help distinguish among lesions that have overlapping clinical presentations. this review focuses on some of the common orbital masses. in this lecture common benign and malignant lesions will be discussed. vascular lesions include capillary (infantile) haemangioma, cavernous haemangioma, and lymphangioma. benign tumours include optic nerve sheath meningioma, schwannoma, and neurofibroma. malignancies that are reviewed include: lymphoma, metastasis, rhabdomyosarcoma, and optic glioma. in addition, benign and malignant lesions affecting the eye movement from outside of the orbit (e.g. from the paranasal sinuses, nasopharynx and skull base) will be discussed. trigeminal neuralgia is a unique form of facial pain, defined by the international association for the study of pain as a sudden, unilateral, brief, stabbing, recurrent pain in the distribution of one or more trigeminal nerve branches, triggered by a specific event. additional diagnostic criteria of the international headache society include paroxysmal, stereotypic pain attacks and absence of associated neurological deficits. it is due to trigeminal nerve compression at the root entry zone, a transitional zone between central and peripheral myelination, where the myelin sheath is thinner and more prone to compression and electrical stimulation. the most common cause is vascular compression, by aberrant loops of the sca, aica, pica or vertebro-basilar dolichoectasia, leading to a neurovascular conflict. small size of the prepontine and cpa cisterns has been identified as a predisposing factor. occasionally, expansile lesions of the skull base or cns compress the root entry zone and lead to atypical trigeminal neuralgia. mr imaging is the modality of choice to evaluate these patients and requires specific tailored protocols to depict its causes, including d heavily t w images reconstructed in the three planes and an angiographic sequence for the depiction of neurovascular conflicts. as neurovascular contacts are quite common in the general population, strict imaging criteria for the diagnosis of nvc have emerged. the offending vessel needs to cross the nerve perpendicularly and deviate or indent its course at the rez. a pictorial review of the most common causes of trigeminal neuralgia and trigeminal neuropathy will be presented. learning objectives: . to understand the causes of trigeminal neuralgia and its clinical symptoms. . to learn about the relevant anatomy and appropriate imaging methods. . to become familiar with the relevant radiological images, differential diagnosis and limitations of the method. c. facing problems of the face: facial pain, tics and palsy b. verbist; leiden/nl (b.m.verbist@lumc.nl) facial impairments may be due to neuropathies of the trigeminal and facial nerve. this lecture will focus on the seventh cranial nerve. this nerve is a complex, mixed nerve with motor fibres, parasympathetic fibres, sensory fibres to the external auditory canal and special sensory (taste) fibres to the tongue. the most common presentation of facial nerve dysfunction is facial palsy. the paresis or paralysis of facial muscles may be caused by several conditions such as developmental abnormalities, infectious or inflammatory disease or tumoural lesions. other presentations of facial nerve dysfunction are facial tics or hemifacial spasm and pain. the indications for imaging, choice of imaging modality and possible imaging findings in case of facial palsy, facial tics and facial nerve-related pain will be discussed. in this presentation, the procedures used to create the standard will be reviewed and some of the most recent changes discussed. as a collaboration of professional societies and companies, integrating the healthcare enterprise (ihe, www.ihe.net) seeks to establish methods wherein health computer systems can communicate to achieve specific functional objectives. these involve development of methodologies to implement standards such as dicom, hl , etc. in this presentation, the procedures used to create the ihe profiles will be reviewed. patient dose tracking is rapidly growing in the usa as a large number of commercial products are available in response to user demand. these products leverage the work that has gone into the development of the dicom dose structured report and the proliferation of digital imaging systems. medical physicists are crucial team members as they are most capable of performing patient dose measurements and calculations. noteworthy is that the 'toolbox' of the medical physicist is expanding. informatics with patient dose tracking tools invariably includes familiarity at some detail with dicom structure and tags, dose structured reports (sr), sr readers, ris content and orders, modality work list broker content, modality (imaging) specific content as well as pacs, archive rules for storage/retrieval and emr. patient-specific information and the highly detailed specifics of the individual dose prescription are necessary for advanced estimates of information. a dose tracking system (a qa tool outside of the normal imaging device that uses content provided by dose sr and other information systems) usually strives to elevate the quality of the dose estimate, using informatics tools such as patient and organ models, dosimetry engines, and predictive statistics. general use cases for dose tracking will be presented including advanced dose estimations for individual patient exams and qa review for both ct and fluoroscopy. examples of tracking of prescriptions by patient, protocol/procedure and operator for determination of patient dose history, 'outliers', continuous improvement (using dmaic tools) or for meeting regulatory or accrediting bodies will be included. with the introduction of digital radiology, it is possible to have automatic systems to collect and archive patient dose data individually, in addition to demographic, geometric, and other procedural parameters, as part of the dicom header or through other dicom services. these automatic systems mean significant benefits for patient dosimetry and quality control. different approaches were used, depending on the availability and level of implementation of the dicom standard, including extracting the technical information from the headers, using the radiation dose structured reports (which contain accumulated dose over several irradiation events), analysing the mpps messages sent by the modalities to the radiology information system, and implementing optical character recognition techniques on saved screen images. before issuing a formal patient dose report, the medical physicists should verify and correct all patient dose data. all these approaches allow managing more information and provide better capacity to audit the full imaging procedure and to help with the optimisation. the current level of technology allows doing so at a reasonable cost and with a great benefit for the clinical practice. automatic detection of abnormal patient doses or mistakes in the technical parameters used and their prompt correction is possible. diagnostic reference levels will be effortlessly reviewed with such systems. some examples of pitfalls and possible optimisation actions will be presented. pathology. finally, the perfect assessment of clinical course of the disease and possible outcomes, the understanding of tumor response criteria and therapyinduced changes are significant for image interpretation in patients with multisystemic malignancies. multiple myeloma is a haematologic disorder characterised by the infiltration and proliferation of monoclonal plasma cells mainly in the bone marrow. the main symptoms are hypercalcaemia, renal impairment, cytopaenia/anaemia and bone disease -summarised as crab-criteria. symptomatic multiple myeloma is consistently preceded by asymptomatic premalignant stages called monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. these stages also present with detectable monoclonal protein and/or monoclonal plasma cells in bone marrow, but do not show any end organ impairment. staging of multiple myeloma is based on the measurement of the monoclonal protein in serum and urine as well as the assessment of impairment of haematopoiesis, renal function and mineralised bone. in the last decade, the development of novel therapeutic agents has led to an increase in response rates and survival time of patients with multiple myeloma, which further stresses the value of response assessment by imaging. cross-sectional imaging like mri, ct and pet-ct is currently replacing conventional radiological surveys in the initial workup and follow-up of patients with monoclonal plasma cell diseases. recent studies demonstrate the added value of mri in improving initial staging by unravelling a diffuse infiltration of bone marrow by plasma cells, a focal pattern or a combination of both. also, pet-ct can detect response to therapy earlier than conventional response criteria. furthermore, recent studies revealed that a complete remission of myeloma confirmed by mri or pet-ct goes along with a better prognosis compared to a complete response based only on serological parameters. learning objectives: . to learn about the role of clinical staging systems and imaging in work-up and classification of plasma cell disorders with a focus on multiple myeloma and to learn about parameters of disease activity. . to understand the pathophysiologic mechanisms of multiple myeloma and to learn about the effects of abnormal plasma cells on bone remodeling cells. . to become familiar with response criteria and therapy-induced changes and to compare the significance of imaging and serological markers for response evaluation in multiple myeloma. . to learn about recent studies on imaging based response assessment and prognostic significance.a- : over the last years, there have been numerous efforts to classify lymphoid malignancies, culminating in the who classification introduced in . so it is clear that malignant lymphomas require a sophisticated diagnostic approach based on clinical features, morphology, immunophenotyping and genetic analysis. it is essential that such an approach underpins the clinical management of these diseases, many of which are amenable to cure. the same situation is present in radiology staging procedures -it has a multidisciplinary approach. a wide range of staging procedures can include all radiology methods from cxr and chest and abdominopelvic computed tomograph to whole body mri, scintigraphy and pet-ct scans. lesions of the regional lymph node system. distant spread of mm is thought to transpire intra-and extravascularly (along the external vessel lattices) supported by specific mechanisms of extravasation and protection of mm cells against the local immune system. to date, many imaging methods, such as ultrasound, computed tomography (ct), magnetic resonance imaging, and positron emission tomography/ct, are used in the diagnosis of mm and its metastases, whereas lymphoscintigraphy has become an important tool for workup of the lymph node drainage patterns. radiological challenges include improved staging and re-staging of multi-systemic mm. accordingly, current imaging guidelines and the role and applications of the different imaging modalities in advanced mm (stage iii / iv) are reviewed with regard to their usefulness in patient management. however, standardised imaging protocols and integration of functional information to morphological imaging are needed in the future to allow for improved detection and guidance of treatment in patients with mm. the original atlanta classification of acute pancreatitis established in is outdated. in , an international working group has modified the atlanta classification for acute pancreatitis to update the terminology and provide new morphologic classifications.the revised classification of acute pancreatitis identified two phases of the disease: early (first week) and late (after the first week). acute pancreatitis is subdivided into two types: interstitial oedematous pancreatitis and necrotising pancreatitis. if the diagnosis of acute pancreatitis is established by abdominal pain and by increases in the serum pancreatic enzyme activities, a contrast-enhanced ct is not usually required for diagnosis in the early phase. this revised classification introduces new terminology for pancreatic fluid collections. depending on the presence or absence of necrosis, acute collections in the first weeks are called acute necrotic collections or acute peripancreatic fluid collections. once an enhancing capsule develops, persistent acute peripancreatic fluid collections are referred to as pseudocysts and acute necrotic collections, as walled-off necroses. all can be sterile or infected. this classification of acute pancreatitis allows a consistent, worldwide classification and should avoid confusion in the terminology of pancreatic fluid collections. the role of diagnostic imaging in chronic and inflammatory pancreatitis and ipmns is to detect structural changes of the ducts and of pancreatic parenchyma, assess the functional integrity of the gland, detect associated complications, and assist in management. these goals are generally fully achieved using mdct and mr imaging. in this lecture, the advantages and limitations of each technique will be discussed and illustrated. key features allowing differential diagnosis of both entities will be underlined. autoimmune pancreatitis (aip) was first described in and represents a rare form of immune mediated chronic pancreatitis which is characterised by a marked infiltration of lymphocytes and plasma cells into pancreatic tissue. whilst the majority of cases present with diffuse gland involvement, approximately % of patients demonstrate either segmental or focal involvement of the pancreas. clinical presentation is very variable with patients describing a range of symptoms; severe pain however is uncommon. imaging plays a central role in the diagnosis and management of aip and knowledge of the radiological appearances, which can vary significantly due to the various degrees of fibrosis and inflammatory infiltrate, is critical. cardinal features include focal or diffuse pancreatic enlargement with the loss of normal lobular architecture. in addition, pancreatic duct involvement as demonstrated by single or multiple focal strictures with limited more proximal dilatation is common. whilst these appearances may suggest a diagnosis of aip correlation with clinical history, serology and histopathology is mandatory to accurately diagnose atypical cases. in contrast, paraduodenal pancreatitis is a specific and rare form of segmental chronic inflammation characterised by fibrous tissue formation in the "groove" area between the duodenum, head of pancreas and lower common bile duct. the pathology was first described in and has since been subdivided into pure, segmental and non-segmental forms. whilst the radiological diagnosis of both aip and paraduodenal pancreatitis remains challenging, the presentation will emphasise relevant imaging strategies as well as provide tips and tricks for accurate diagnosis. bone scintigraphy is often used in combination with ct and clinical information for staging and therapy response evaluation of bone metastases. magnetic resonance (mr) imaging is a technique that is known to be valuable both for detection of bone metastases and for evaluation of their response to treatment. integrated positron emission tomography with computed tomography (pet/ct) combines the functional data from pet with anatomic information of ct in a single examination. f-fluoride is a non-specific pet tracer that has recently shown very high sensitivity for bone metastases. for accurate response evaluation, it is important to recognise not only changes in bone metastases, but also the effects of treatment on unaffected, normal parts of the bone marrow. these latter therapy-related benign changes could otherwise be misinterpreted as disseminated disease or vice versa. despite the fact that the methods mentioned above, alone or in combination, have improved the assessment of bone metastases, they often remain non-specific. a specific diagnosis can in many cases only be achieved with a bone biopsy. this refresher course will give you an overview of the present imaging methods for detection and characterisation of bone lesions. indications for, and how to perform, ablation and cementoplasty of bone metastases will be presented. optimal algorithms for treatment follow-up of bone metastases and advantages and disadvantages with different imaging methods will be reviewed. also, future development of diagnostic and therapeutic methods will be included in the presentations, e.g. potential role of emerging pet imaging probes for assessing bone malignancies. author disclosure: h. ahlström: research/grant support; astrazeneca. a. diagnostic approach: the role of hybrid imaging k. herrmann; würzburg/ this presentation will include a short review of the epidemiology of primary and metastatic bone disease, its classification and staging definitions. then we discuss the role of radionuclide imaging in initial and subsequent treatment strategy considerations. another aim is to provide guidelines for the appropriate use and applications of diagnostic radionuclide approaches for the assessment of bone diseases. the focus of this presentation will be on the role of radionuclide imaging in metastatic prostate, breast and lung cancer in the context of other available diagnostic imaging approaches. the ability of hybrid imaging technologies to achieve improved diagnostic accuracy will be emphasised and when appropriate the potential role of emerging pet imaging probes for assessing bone malignancies discussed. if feasible, the availability and effectiveness of radionuclide-based therapeutic approaches for malignant bone diseases will be reviewed. skeletal metastases are associated with significant morbidity and have high impact on health costs. effective palliative treatments are available, but less than % of patients respond in terms of tumour markers, pain or quality of life and all treatments are associated with some toxicity. it is generally accepted that the current imaging techniques are inadequate for measuring treatment response in a clinically relevant time frame such that skeletal metastases are usually considered as non-measurable disease in clinical routine and trials. there is therefore a need for non-invasive, objective methods to evaluate treatment response of skeletal metastases at earlier time points to guide clinical care. in addition to imaging structural changes in bone (e.g. x-ray, ct), it is now possible to image a number of biological characteristics of bone metastases including tumour metabolism, tumour cellularity, and osteoblast and osteoclast activity. methods currently available, or being actively investigated, include m tc-mdp spect/ct, f-fluoride pet/ct, f-fdg pet/ct, c/ f-choline pet/ct, rgd-spect/pet and dw-mri. some of the tracer methodologies will potentially be applicable for and complementary to pet/mri. the timing of follow-up imaging after commencing treatment is still under investigation. it is likely that tumour-specific methodologies may reflect response/non-response earlier than bone-specific methods due to a prolonged flare in reactive bone in responding metastatic sites. learning objectives: . to understand the techniques and quantitative parameters used for treatment response evaluation. . to learn the optimal timing for follow-up imaging after treatment. . to become familiar with common pitfalls in the interpretation of posttreatment mri and pet. panel discussion: how to differentiate between bone metastases and chronic inflammatory or treatment-induced changes : structured reporting is an opportunity and a challenge at the same time. expert speakers of this session will present and discuss their views on the subject, contributing to the clear vision of the members of audience on this complicated subject, convincing us to take this technique as an opportunity to improve and standardise the quality of our reporting activities. even though structured reporting (sr) has been appreciated as one of the effective methods of electronic reporting, there are not that many real applications to facilitate utilisation of this technique in practice. why it is so?the radiologists want a flexible tool to create clear, concise reports in a reasonably short time. like all template-based reporting systems, the application must be tailored to preferences of multiple users in a radiology department. the report templates should also be flexible in terms of length to avoid inappropriately detailed reports. the final appearance of the report is critical for acceptance by clinicians. accordingly, the technical challenges of development of sr systems may be grouped as: "user interface", "database structure", and "output file/document" problems. flexibility to comply with different user preferences will lead to both user interface design and database structure challenges. one of the major technical challenges is the transformation of structured data to a final text to be acceptable and applicable for the referring physician. also, exporting of reports to dicom format using dicom-sr concepts is still a challenge. multi-media formats are becoming more and more popular specially in sr reports. effective communication of radiology results is critical to high-quality health care. to that end, the radiological society of north america (rsna) has developed a library with more than best-practice radiology reporting templates. the templates are freely available online (www.radreport.org) and have been accessed more than , times. the new ihe "management of radiology reporting templates" (mrrt) profile builds upon the web's hypertext markup language version (html ) to provide an international standard for describing and exchanging reporting templates. this presentation will describe the rsna report template library, introduce the international mrrt standard for report templates, and describe opportunities for esr members and affiliated societies to participate. the broad goals of this initiative are to improve the quality of radiology reports, increase the productivity of radiologists, promote the use of practice guidelines, and advance data-driven health care.learning objectives: . to explore a library of 'best practices' radiology reporting templates. . to become familiar with international standards for radiology reporting templates. . to understand how structured reporting will promote the use of practice guidelines and will advance data-driven health-care. structured reporting in europe: the esr initiative o. ratib; geneva/chthe rsna has initiated a new initiative called radreport with the aim of helping promote standard reporting and improve reporting practices by creating a library of clear and consistent report templates (http://reportingwiki.rsna.org/). this project also supported in part by the national institute of biomedical imaging and bioengineering (nibib) has already gained the participation of numerous countries around the world, contributing with reports in different languages. these report templates are "structured" in the sense that they incorporate reusable knowledge, or meaning, to the clinical reporting process. structured interpretation and reporting for detecting significant prostate cancer is crucial, as it allows comparing inter-observer interpretation variability, reduces this variability by stimulating discussion of the individual scores, enhances communication with the clinicians in a uniform way, facilitates quality assurance plus research, and in this way improves patient outcome. in this presentation, the pi-rads scoring system will be shown and discussed, and fast effective structured reporting using computer software will be presented. in a rapidly ageing society, dementia prevalences are sharply increasing. furthermore, knowledge about disease mechanisms is constantly evolving. a more nosologic approach in the workup of dementia is required to improve prognostication, patient management as well as select appropriate treatment. a. anatomy of the limbic system t.a. yousry; london/uk (t.yousry@ucl.ac.uk)the term "limbic" has been used in many different connotations. to understand the anatomy, we have to define the term first. the clearest definition stems from broca: "le grand lobe limbic". defined as such, the limbic lobe is composed of main structures: the limbic and the intralimbic gyri. . the limbic gyrus is composed of the subcallosoal gyrus anteriorly, followed in an arc by the cingulate gyrus, isthmus and parahippocampal gyrus. the latter is composed of parts: i) a posterior narrow segment, the superior surface of which is called subiculum, and ii) a more voluminous anterior segment, also known as the piriform lobe. the latter consists of the anterior part of the uncus and the entorhinal area. . the intralimbic gyrus arches within the limbic gyrus. it is divided into parts: i) anterior (prehippocampal rudiment); ii) superior (indusium griseum); and iii) inferior (hippocampus). the latter consists of lamina rolled inside each other: the cornu ammonis and the dentate gyrus, with the cornu ammonis consisting of neuronal fields (ca - ). to understand the function, we have to understand the connections that define this function. the interplay with the insula is of particular importance. in summary, we will review the mri characteristics of the components of the limbic lobe, their connections, and their function, using . t, t and . t high field imaging. at the end of this lecture, you will know definition (s) of the limbic lobe, its major subdivisions, connections and functions. structural neuroimaging is increasingly used in the diagnosis of neurodegenerative diseases. in a memory clinic setting, computed tomography (ct) and magnetic resonance imaging (mri) have become the most important paraclinical diagnostic tools. recent guidelines on the diagnosis and management of disorders associated with dementia state that neuroimaging should be performed at least once during the diagnostic workup. in the past, neuroimaging had been performed to exclude potentially treatable causes of dementia. however, this exclusionary approach of neuroimaging in the diagnosis of dementia has been replaced by an inclusionary approach driven by conclusive evidence that ct and mri can substantially support the clinical diagnosis by the demonstration of a distinct atrophy pattern and the assessment of vascular (co)morbidity. for these purposes, the use of visual rating scales allows a fast and reproducible assessment of global/regional cortical atrophy and vascular white matter pathology. more recently, new imaging markers such as cerebral microbleeds and superficial siderosis haven been identified and linked to alzheimer pathology. in addition, next to structural mri, advanced and quantitative mri methods have been introduced in the clinical setting. mri perfusion techniques such as arterial spin labelling (asl) demonstrated a diagnostic value in memory clinic patients, particularly in those showing no or inconclusive pathology on structural mri. de (horst.urbach@uniklinik-freiburg.de) cognitive decline is a clinical symptom in many neurodegenerative disorders. mri is typically performed in the initial diagnostic workup of these patients. as a structural imaging modality, mri is often unrevealing while several molecular imaging modalities show disease-associated alterations: f-fdg-pet shows reduced glucose metabolism in neocortical association cortices, mainly in the posterior cingulate, precuneus and temporoparietal regions. since glucose metabolism is normally higher in the posterior cingulate and precuneus, reduced glucose metabolism must be specifically sought for or highlighted by voxel-based analysis. dynamic imaging of swallowing from the mouth to the duodenum is the only clinical test providing a fast and accurate diagnostic overview of the upper gi function. swallowing disorders are divided into those with dysphagia that means problems during eating or drinking, with suspicion of aspiration as an important subgroup and those with sensations like the globus syndrome or noncardiac retrosternal pain. oropharyngeal dysphagia in patients with neuromuscular diseases or postoperative conditions can be evaluated precisely and within the same session as oesophageal motility disorders, stenoses or postoperative problems are detected and in a complementary fashion to endoscopy, ph monitoring and manometry. the exclusive ability of dynamic imaging of swallowing is to diagnose combined disorders of the pharynx and the oesophagus, to detect and localise subtle and multiple benign stenoses of the upper gi tract and to combine visualisation of pathophysiology and bolus transport as well. radiologic evaluation concentrates on functional units, which represent the visible "moving areas" of deglutition, where evident pathologic conditions can be found: ) oral cavity and tongue, ) soft palate, ) epiglottis, ) hyoid and larynx, ) pharyngeal constrictors, ) pharyngoesophageal segment, ) oesophagus and stomach. this lecture intends to explain the common causes of dysphagia, the approach to a tailored examination and the use of an advanced imaging technique. further, the basics of taking the swallowing history and the structure of reporting swallowing disorders along the seven functional units will be provided. hoarseness is defined as a rough or noisy quality of voice. the possible causes of hoarseness are manifold, ranging from benign diseases such as the common cold to malignant tumours. therefore, hoarseness as a symptom should always be taken seriously. evaluation of a patient with hoarseness by a head and neck specialist will always starts with a history and a physical examination including laryngoscopy. after these examinations, a diagnosis can be established in most patients without additional imaging. the aetiologies of hoarseness are: ) inflammation/infection, ) trauma, ) neoplasms, ) others (including medical conditions, e.g. hypothyroidism) and ) vocal cord paralysis. this presentation will focus on imaging of vocal cord paralysis. vocal cord paralysis should not be considered a diagnosis, but as a symptom of (possible) underlying disease. when vocal cord palsy is discovered, this is frequently a reason to perform cross-sectional imaging. the radiological workup needs to include the full course of the vagus nerve. moreover, reporting radiologists need to be able to recognise the radiological signs of vocal cord palsy in the absence of hoarseness, since many patients with cord palsy are asymptomatic (up to %). the anatomy of the vagus nerve and its laryngeal branches that innervate the intrinsic muscles of the larynx will be discussed. then the (expected) course of the vagus nerve and recurrent laryngeal nerve will be shown. finally, radiological signs of vocal cord palsy will be discussed using examples from daily practice. in contemporary medicine, endovascular techniques often replace conventional methods of treatment, including surgery, in the management of an increasing range of diseases. this requires development of specific methods assessing the effectiveness of treatment and able to detect complications that may be much different from those occurring in conventional therapy. this is first of all seen in the endovascular treatment of patients suffering from vascular lesions and neoplastic diseases. commonly, there is a high initial technical success of endovascular treatment, but the durability is not always satisfactory and needs to be further examined. endovascular treatment is bound to the risk of specific complications, often without clinical symptoms. therefore, there is a need to use imaging follow-up of these patients.interventional radiologists are aware of the importance of those issues and should play an important role in developing and deciding about the follow-up scheme and choice of the best imaging methods for these patients. besides indepth knowledge of the treatment, radiologists are also familiar with the possible complications and can offer an optimal, minimally invasive and cost effective diagnosis and treatment. the potential imaging methods for follow-up after angioplasty (pta) and/or stenting include doppler ultrasound, cta and mra. although excellent images can be obtained by cta and mra, the drawbacks of these studies for routine follow-up are obvious. (access to ct and mr equipment, cost, contrast medium, ionising radiation, etc). in the uk, the most common imaging method is duplex ultrasound. there is no established role for the use of ultrasound contrast agents. ultrasound is freely available in the majority of centres, is inexpensive and complication free. follow-up by ultrasound may be undertaken by radiologists, although more usually by technologists in vascular laboratories. in practice, few patients are followed up by any imaging study at all unless they develop symptoms. the main category of patients who undergo some form of imaging follow-up after pta/stenting are patients with surgical bypass grafts, who are usually routinely followed up whether they have undergone angioplasty/stenting or not. in view of the fact that this is a lecture on follow-up after intervention, procedural complications are excluded from the discussion. the complications of angioplasty and stenting are similar. the main early complications are restenosis or reocclusion. other early complications are related to the arterial puncture site and include haematoma, dissection, occlusion and pseudoaneurysms. the main late complications are restenosis and reocclusion. treatment of restenosis and reocclusion usually involves additional angioplasty or stents using conventional or drug-eluting balloons or stents. cutting balloons, atherectomy and cryotherapy have a controversial role based on limited evidence. imaging follow-up of oncologic patients after embolisation procedures j.i. bilbao; pamplona/es (jibilbao@unav.es)the term "embolisation" groups different procedures in which imaging guidance is fundamental for both performing the procedure and for the early detection of complications. it has been demonstrated by several studies that "tumoural response" is tightly associated with survival, thus it is of major interest to measure accurately how the tumour is modified by the treatment. the "world health organisation" -who -first published the objective criteria for the evaluation of response. these criteria were slightly modified in and named as "response evaluation criteria for solid tumors"-recist. accordingly, "complete response" (cr) corresponds to the disappearance of the tumour, "partial response" (pr) is defined when there is a decrease in the tumour size equal to or higher than % and "progressive disease" (pd) is applied when there is an increase equal to or higher than %. "stabilisation of the disease" (sd) corresponds to measurements in between > % (pr) and < % (pd). tumours (until five nodules in the same viscera), no matter if necrotic or viable, were evaluated with one measure (its largest diameter). a new version (" . recist) has introduced modifications, among which is the number of nodules ( instead of ) that needs to be evaluated. in some circumstances, when morphologic criteria (recist and who) fail to predict the outcome, then new functional criteria have been recently established. "mrecist" (which only measures the tumour that uptakes contrast) is an accurate classification for hcc. new methods "beyond recist" have been established for some specific treatments such as targeted therapies. in this session, the audience will have a comprehensive overview of the elastography, its principles and current state-of-the-art clinical applications. the session will deliver an overview of currently available methods of both ultrasound elastography (use) and magnetic resonance elastography (mre), their physical principles, technical and equipment requirements as well as the influence of various factors for obtained results. following this session, the audience will have insight into clinical applications of elastography in liver, prostate and brain diagnostics. the strengths and weaknesses of elastographic modalities will be compared and discussed under consideration of more established imaging modalities. the session will present potential developments of use and mre and possible future clinical applications. panel discussion will aim at defining the place of elastography in current and future diagnostic algorithms. the well-known sensitivity of the palpating hand for detecting lesions is related to the incredibly wide range of values of the shear modulus in the body, spanning over eight orders of magnitude. elastography was invented to exploit this high variability of constants by introducing the shear modulus into the image contrast of medical ultrasound or magnetic resonance imaging. today, both ultrasound elastography (use) and magnetic resonance elastography (mre) are in clinical use, predominantly for staging liver fibrosis or discriminating tumours in the breast, liver, and prostate. the talk reviews the physical principles, technical requirements and current methods of both use and mre. furthermore, the strengths and weaknesses of elastographic modalities are compared and discussed under consideration of more established imaging modalities. an outlook of elastography is given, highlighting the real-time feasibility of use and the sensitivity of mre to tissue pressure. suspicion of prostate cancer (pca) exists in the case of elevated psa serum values and/or suspicious findings on digital rectal examination (dre). systematic biopsy (sb) will be done to confirm or rule out pca. unfortunately, an elevation of psa serum values often is caused by benign changes, e.g. prostatitis or adenomyomatosis and not every cancer is palpable on dre. furthermore, sb may miss clinically significant disease in up to %. therefore, a more targeted approach would be desirable and imaging of pca is currently under strong effort. one possibility for visualisation of pca is the representation of tissue elasticity. usually, cancers have higher cell and vessel density than the normal surrounding tissue and therefore are associated with increased stiffness. in contrast to dre, where only the posterior parts of the prostate can be reached, rte does not have this problem, since all anatomical regions can be evaluated. furthermore, this noninvasive technique is time-and cost-effective and targeted biopsy or focal therapy of the prostate can be done under real-time conditions. another important issue is that rte can be performed by both urologists and radiologists. nevertheless, rte is of limited value in the detection of small cancer lesions and there may be problems in visualising pca with predominantly gleason pattern . the lack of data about inter-and intraobserver variability and of multicentre studies (now in process) are probably the reasons why rte has not been included in the guidelines of urological societies so far. cerebral tissue structure is altered in many neurodegenerative diseases, but also during physiological processes like maturation or ageing. structural changes directly affect the mechanical tissue properties. magnetic resonance elastography (mre) is an imaging technique capable of assessing biomechanical brain parenchymal properties non-invasively. viscoelasticity can be quantified by analysing the propagation of mechanically elicited shear waves in the investigated tissue. thus, mre could be a helpful tool to detect physiological or pathological processes influencing the cerebral tissue integrity. learning objectives: . to appreciate the advantages and limitations of a virtual palpation of the brain. . to become familiar with mechanical wave induction and detection in cerebral measurements. . to learn about current and potential clinical applications. . to learn about the relationship between microscopic and macroscopic, as well as focal and globally diffuse biomechanical brain parenchymal alterations. are based on the generation of shear waves inside the liver tissue with specific mr liver drivers and ultrasound probes. subsequently, phase images revealing the displacement of the waves will be investigated for healthy and pathological (alcoholic fibrosis) livers. moreover, the development of phantoms mimicking the stiffness of biological soft tissues (liver, muscle, …) will be also presented. the viscoelastic (elasticity and viscosity) properties of healthy and fibrotic livers were measured, and the relevance of these parameters, used as a liver diagnostic marker, was analysed. in parallel, an increase of the wavelength as a function of the stiffness was obtained for the developed set of phantoms. the characterisation of the elastic properties is an excellent marker to differentiate minor and major fibrosis. a summary of the advantages and disadvantages of us and mr elastography techniques will be presented. a- : the breast lesion excision system (bles) has evolved as a breast radiological technology over the last decade and is now in widespread use in europe and across the world. it was designed as a large biopsy device, but more recently due to its unique capability to obtain a single large breast tissue specimen in only a few seconds by utilising a radiofrequency cutting and cauterising wave, it has increasingly been explored in the therapeutic setting. it is easy to use under ultrasound or mammographic guidance with procedures taking a similar length of time to that of a vacuum biopsy, and with patient preparation and anaesthetic essentially identical. the technical aspects of performing these procedures will be detailed as well as its use specifically to perform excisional biopsies. this is limited by patient and lesional factors, all of which will be discussed in more detail. following a bles, the post-procedure appearances need to be considered so that follow-up imaging can be interpreted accurately. the risks and complications of this procedure are outlined as well as a discussion made of the latest papers in this field that may suggest future applications and developments. learning objectives: . to understand the mechanism of the bles technique. . to become familiar with the post-bles aspects of various types of imaging. during the past few years, it has been shown that there is not a single disease entity called "breast cancer". there are different subtypes that entail diverse recurrence risks. this is the first issue to take into account, and patients will be stratified accordingly before any follow-up is planned. imaging findings in a patient treated for breast cancer will depend on the type of treatment: breast conserving therapy (bct), mastectomy (and all the reconstructive techniques), radiotherapy and minimally invasive techniques. to differentiate between fat necrosis and other common post-treatment changes from relapse, it is important to know the timeline when all these changes take place and also schedule the follow-up imaging procedures accordingly. other important issues to take into account are the limitations and indications of the different modalities (mammography, ultrasound and mri). although ultrasound and mammography have traditionally been used in the follow-up of these patients, mri is being used more and more often due to its superior multiplanar capabilities and the functional information not supplied by the other techniques. blood clot formation in the veins is referred to as venous thrombosis (vt). vt is most common in the deep veins of the legs and pelvis. if the thrombus dislocates to the pulmonary arteries this is referred to as pulmonary embolism (pe). the combination of deep vein thrombosis (dvt) and pe is referred to as venous thromboembolism (vte). the diagnosis of dvt and vte is essential, as vte is potentially fatal. furthermore, undiagnosed, non-fatal dvt may result in negative long-term pathologies (e.g. post-thrombotic syndrome). major risk factors for the development of vte are thrombophilia, history of dvt, age > , surgery, obesity, long travel, cancer, immobility and pregnancy. in addition, underlying congenital abnormalities or compression syndromes (may-thurner syndrome) are also important to diagnose. diagnosis of vte is not always easy. primary diagnosis includes clinical (wells score) and lab testing (d-dimer). first line imaging testing is done by leg ultrasound (us). if pe is suspected ct is indicated immediately. ct of the pulmonary arteries (ctpa) may be combined with indirect ct venography (ctv). the question of when to combine ctpa and ctv still remains. a favourable approach is to add ctv in a negative ctpa. recently mr venography (mrv) is emerging as comprehensive imaging tool especially in patients with chronic dvt to assess the extent and underlying causes. in this respect imaging without radiation dose with high spatial delineation of vascular abnormalities facilitates intervention for thrombolysis or interventional therapy including recanalisation and stenting. alternatively, intravenous unfractionated heparin is used in situations when a quick reversal is necessary. b) non-medication: early mobilisation has been widely adopted to activate the muscle pump. if early mobilisation is not possible, compression stockings and/or pneumatic compression boots are applied to better empty the veins. . treatment: a) anticoagulation: the main goal of anticoagulation is to prevent progression and recurrence of dvt. typically, anticoagulation is started with lmh, followed by vitamin k antagonists (coumadin). the first dvt is generally treated for - months; recurrent dvt for months. b) compression therapy: compression stockings ameliorate pain and leg swelling of acute dvt. in addition, the development of a post-thrombotic syndrome (pts) should be reduced. c) thrombolysis: the main goal of thrombus removal is prevention of pts. in addition, thrombolysis is used for severe ilio-femoral dvt, especially with phlegmasia coerulea dolens. there are different ways of thrombolysis: systemic thrombolysis was abandoned because of high bleeding complications. catheter-based thrombolysis has shown to reduce the bleeding risk, but it is quite time and resource consuming. the latest development is pharmaco-mechanical catheter thrombus removal which combines thrombolytic drugs with a mechanical maceration. recent studies (cavent,torpedo) have shown a reduction of pts compared to anticoagulation. the use of inferior vena cava filters (ivcfs) is a controversial method for the prevention of pulmonary emboli. there are large variations in their usage; often with ten to one hundredfold differences in placement between different countries. ideally, ivcf usage is based on sensible protocols derived from clinical experience and trials. in practice, this is less frequently the case. indications, contraindications and questionable indications (mainly during venous thrombolysis) will be discussed. familiarity with ultrasound guidance will be stressed. the key technical steps in the insertion and removal of ivcfs will be discussed. the question that this refresher course is aimed to answer is whether novel it tools may actually help in improving quality and workflow efficiency in daily radiological practice. in fact, since the early installations of pacs, it tools have often been considered as mere productivity tools rather than enabling technologies for fostering quality in medical care. the three distinguished lecturers in this course will address the following topics: improving quality and efficiency of computerised order entry through decision support, improving quality and efficiency of reporting through structure and templates, and improving quality and efficiency of dose management through exchange between modalities and registries. they will cover all aspects of the radiological workflow: from the selection of the most appropriate diagnostic procedure, to the efficient reporting of diagnostic and non-diagnostic data (such as radiation dose information and contrast media information). they will demonstrate how newly adapted it tools may provide assistance throughout the radiological workflow, with potentially enormous gains in terms of patients' safety and total quality management. session objectives: . to appreciate the need for it tools to ensure quality control. . to understand how to collect data concerning radiation dose. a. improving the quality and efficiency of computerised order entry through decision support p. mildenberger; mainz/ de (peter.mildenberger@unimedizin-mainz.de) electronic communication of requests for radiological procedures is a logical and relevant extension to integrated information systems in health care. this communication of orders and the entry (oe) into ris improve the workflows. but, quality improvements require additional efforts to link order-entry-solutions with health knowledge for ordering the appropriate imaging procedure. these clinical decision support (cds) tools should be based on generally accepted and implemented criteria, e.g. evidence-based medicine. it is known that the acceptance of such systems, if successful and efficient implementations are given, is very good. it concepts for cds are well known and standards for classifications are available, but semantic interoperability is still a developing area. actually, clinical information systems provide different levels of integration of oe and cds. further developments could be an implementation of interoperability profiles and the representation of cds knowledge in webbased services of non-commercial organisations. b. improving quality and efficiency of reporting through structure and templates e. neri; pisa/it (emanueleneri @gmail.com)the report represents the final stage of the diagnostic imaging process, for which the radiologist is responsible. this process is driven by an accurate selection of the diagnostic tests, based on the clinical question. therefore, the report should be an expression of this path, depending on the question asked by the clinician. the structure of a radiology report for the same clinical problem and the same method of investigation varies from country to country and between different radiologists. this diversity can be a problem in the global world where a patient can have imaging tests from different places with different reporting languages, or when patient data is transmitted and shared between different centres. there is, therefore, the need to standardise the report as much as possible; finalising its structure and contents to a specific clinical problem, and possibly using a standard terminology. an attempt to solve this problem is in progress with the joint initiative on structured report esr-rsna (http://www.rsna.org/reporting_initiative.aspx), aimed at improving reporting practises by creating a library of clear and consistent report templates. the main expected benefits of structured reporting templates are report uniformity and improvement of communication between referring physicians. literature evidences that structured reporting can also quicken report turnaround, and reduce costs and lexical errors; thereby improving the quality and safety of radiological practise. the european directive on medical exposures requires the assessment and evaluation of patient doses, especially in procedures involving high doses to the patient. in the current draft of the new directive on basic safety standards, some requirements on patient dosimetry in diagnostic and interventional radiology have been reinforced: x-ray systems should provide dosimetric information with the capability of being transferred to the examination report (for all ct and interventional systems). diagnostic reference levels (drls) shall be reviewed regularly. these requirements will push the industry and the users to develop better strategies to evaluate patient doses, transfer these values to patient reports (contributing to the patient exposure tracking system) and also use available software to process these dosimetric data and perform some automatic analysis. this analysis should: a) include periodic calibration factors for patient dose quantities, b) include automatic detection of high dose values (especially relevant for interventional procedures), c) include statistical analysis to update drls and compare with the existing ones and d) suggest corrective actions to fulfil the quality assurance programmes and the clinical audit requirements. dicom radiation dose structured reports represent a significant advantage, but more efforts will be necessary for the automatic process of the relevant data contained in the report to verify that the radiological risk is acceptable and to suggest, if appropriate, corrective actions to improve clinical practice. without these last steps, patient dosimetry efforts and european regulations for radiation safety could only have a moderate impact. gastrointestinal tumors include a variety of lesions, with the most frequent being adenocarcinoma of the small and large intestine, small bowel lymphoma, neuroendocrine tumours (nets) and gastrointestinal stromal tumours (gists). according to histology, location and initial imaging staging, those lesions may require completely different therapies: surgery alone, adjuvant chemotherapy (cht), neoadjuvant cht followed by surgery or a combination of neoadjuvant chemoradiotherapy (crt) followed by surgery. after treatment, imaging follow-up is mandatory. the most common post-operative findings after small bowel or colonic resections will be presented, together with clues for early detection of recurrence. in those cases which underwent adjuvant cht, imaging findings and diagnostic criteria related to the use of either cytotoxic or cytostatic drugs will be shown, to facilitate the interpretation of radiologists in assessing response to therapy. finally, tissue changes following neoadjuvant crt will be discussed, particularly in rectal cancer. the possibilities of different imaging modalities in assessing either complete or partial response to therapy will be presented, with a critical analysis of different imaging findings. unlike infectious enteritis, in patients with crohn's disease (cd) the changes in clinical activity have poor correlation with changes in inflammatory lesions after medical treatment. mucosal healing (mh) and improvement in patient's symptomatology are usually considered the main objectives of medical treatment. however, improvement in clinical symptoms is not always associated with mucosal healing and the persistence of severe inflammatory lesions augurs a more aggressive disease course in terms of flare-ups, hospitalisation requirements and the need for surgery. endoscopy is the gold standard for the assessment of luminal lesions in cd, but given the good correlation shown between endoscopy and cross-sectional imaging in assessing the activity and severity, imaging is increasingly introduced as a tool to monitor medical treatment. there is some evidence indicating that crosssectional imaging can be considered a responsive and reliable tool as it detects meaningful changes in patients' status over time after therapeutic interventions. besides this, cross-sectional imaging is capable of monitoring the colon and the small bowel and penetrating lesions that cannot always be assessed by endoscopy. becoming familiar with the radiological changes during and after treatment will be key in the decision-making process. degeneration is routinely defined as a morbid change of cells, tissues and even organs. in the msk system degeneration occurs in bones, joints (synarthrosis and diarthrosis), muscles and tendons. primary degeneration implies ageing as well as overuse, based on mircrotrauma. the latter may be related to constitutional, professional or sports-related factors. a distinction between ageing and overuse is not possible with the use of histology and imaging. only the intensity of the changes, which may be inadequate in relation to the age of the patient, may give a hint. on the contrary, the term "secondary degeneration" should be used for clearly defined events or diseases, which finally will result in the degeneration of tissues. the causes are inflammation (ra, infection), metabolic disease (e.g. cppd) or trauma. other ways to classify degeneration of the msk system are related to the anatomy. accordingly, degeneration of the particular parts of the peripheral or axial skeleton, muscles and tendons has to be discussed. one has to have in mind that bones, cartilage, muscles and tendons form a complex unit. the single elements of these complex units jointly undergo degenerative deterioration, e.g. bone, cartilage, fibrocartilage and capsule are jointly involved in case of oa of the knee joint. the same holds true for the synchondroses of the spine. at the rotator cuff not only the tendons, but also the underlying bone and the muscle tissue are changed. (o.m.vandelden@amc.uva.nl) there are many different types of embolisation, but all share many basic principles. the specific approach, technique, materials and equipment used may differ depending upon many variables such as the type of vascular territory involved (venous, arterial, small vessels, large vessels), clinical setting (elective or emergent procedure), and type of underlying disease to be treated (e.g. tumor embolisation, acute haemorrhage, vascular malformation, arteriovenous fistula, etc). pre-procedural imaging and planning are essential for most embolisation procedures and intra-procedural navigation can be done with fluoroscopy, dsa, and new d-techniques. with proper imaging workup prior to embolisation procedure time, radiation dose and contrast load can be significantly reduced. embolisation materials can be roughly divided into liquid agents (alcohol, glue, polymers), particulate agents (pva, calibrate microspheres, drug-eluting beads) and coils (detachable, non-detachable) and plugs (amplatzer®-plugs). plugs and coils are deployed at the exact site of destination and usually easy and safe to use. particles and liquid agents reach their site of destination by flow guidance and can be more difficult and unpredictable in their use. complications include puncture-site complications (thrombosis, dissection, haematoma), systemic complications (contrastinduced nephropathy, allergic reactions) and specific embolisation-related complications (non-target organ embolisation, end-organ ischaemia, postembolisation syndrome). when used with expertise and proper experience, most types of embolisation have good results with acceptable complication rates. although there has been advancement in imaging techniques, several pitfalls in the assessment of diseases of the pancreas, small bowel and rectum remain. the differentiation and the correct characterisation of tumours and inflammatory disease in some cases may be difficult. also, atypical presentation of common tumours or uncommon tumours persists and is a challenge. problematic situations are constantly represented as intestinal bleeding and unexpected findings. in this session, we point out the procedure of the best imaging modality and protocols of challenging cases. a. pancreas c. triantopoulou; athens/gr (ctriantopoulou@gmail.com)pancreatic imaging and interpretation of focal lesions remains a challenging issue. despite the advances in imaging techniques and the dedicated protocols that are now in use, a possibility for pitfalls remains. these pitfalls are related either to the inability of the early recognition of a lesion, or to the wrong characterisation of a "mass". both pitfalls are of great importance, taking into account the lethal pancreatic cancer and the possible complications that may follow an unnecessary pancreatic surgery. there are many variants of the pancreatic parenchyma, the ducts or even vessels, and deep knowledge of the pancreatic anatomy and embryology is needed, to be able to recognise these variations in imaging. a pancreatic variant may not only be misinterpreted as a severe pancreatic disease (e.g. ectopic spleen vs neuroendocrine tumour), but may also be the underlying cause of pancreatic inflammatory lesions (e.g. ectopic pancreas on the duodenal wall causing groove pancreatitis). other pitfalls are related to the atypical presentation of a common lesion (e.g. isoattenuating pancreatic adenocarcinoma), the presence of uncommon tumours, diffuse or multifocal diseases, the co-existence of two different entities and the heterogeneous or overlapping appearance of cystic lesions. in any challenging case, a focused methodology should be applied and the diagnostic procedure based on predefined imaging parameters, taking also into consideration the clinical and laboratory findings. excluding pancreatic cancer should be the first goal and every attempt should be made to differentiate between surgical and non-surgical cases. endoscopy is the gold standard in small bowel diseases, but it is a challenging technique: the pillcam is a commonly used tool and multidetector ct is a diffuse investigation technique. ct enteroclysis/enterography is a worldwide tool in intestinal exploration. throughout the investigation of the small bowel, morphologic anomalies or embryonal development defects may be present (meckel's diverticulum, duplications of intestinal tracts). artefacts may be determined and there may be misunderstanding. mdct is the first tool in emergency diagnosis; imaging pitfalls are possible. unsuspected diseases may be revealed: we will see a case of gist in a patient affected by intestinal bleeding of an obscure origin. ct enteroclysis may find unknown or unsuspected diseases: correct technical parameters have to be respected, as artefacts may be derived from an improper acquisition technique, such as a limited distension or poor intravenous enhancement. in follow-up, mr is preferred to investigate the intestine, mainly in the young population. unexpected findings may be due to rare pathology: we met a case of endometriosis, with ambiguous presentations; patients affected by autoimmune pathologies (pyoderma gangrenosum or lupus erythematosus), with unknown inflammatory intestinal chronic diseases. in oncology, pet-ct imaging is the main diagnostic tool, but there are abdominal pitfalls that limit its effectiveness (intestinal hot spots, artefacts from peristalsis): the small bowel may frequently obstruct an easy diagnosis. in case of emergency, if the radiological diagnosis is not clear, the surgeon determines the management of the patient. in case of a defective study technique, a correct examination may be repeated. endoscopy or pillcam may help to detect mucosal lesions invisible at ct. mri plays a key role in the assessment of disease of the rectum and in particular for the staging (and restaging) of rectal cancer. in this session, the relevant mr anatomy of the rectum will be discussed. furthermore, the strengths and weaknesses of mri in the assessment of rectal cancer during primary staging and restaging after chemoradiotherapy will be highlighted using various rectal cancer cases. finally, we will discuss some rare tumours of the rectum (including gist and carcinoid). optimisation of ct and mr techniques has provided new challenges for imaging in the assessment of airway and lung diseases. phenotypic abnormalities which can be recognised on visual and quantitative evaluation of ct images in copd patients may improve the diagnostic accuracy, help optimise treatment and provide a framework for clinical trials. although expiratory ct helps assess air trapping due to small airway obstruction and excessive dynamic collapse of large airways, potential tricks in technique and interpretation of ct images must be known. owing to multiple and successive improvements over years, functional and morphologic evaluation of the lung using mri has become reality for clinical practice. already regarded as a favoured cross-sectional imaging in paediatric chest radiology, mri of the lung is gaining new indications also in lung diseases occurring in adults. the potential for high-resolution computed tomography (hrct) to uncover several morphological subtypes that come under the umbrella term chronic obstructive pulmonary disease (copd) is now more familiar to both radiologists and specialist respiratory physicians. a complete approach to the classification of copd would ideally assimilate several parameters through a combined visual-quantitative hrct analysis. the insight that some subjects given the label of copd have "pure" airways diseases or emphysema can be readily provided by a simple visual evaluation. the subtypes -centrilobular, panlobular, and paraseptal emphysema -can be reliably distinguished on hrct images. the visual assessment of bronchial abnormalities and accompanying smoking-related interstitial lung disease may also complete the phenotypic classification of copd. furthermore, it is now possible to objectively quantify the global extent of emphysema, gas-trapping, and bronchial metrics by two types of softwares which are now increasingly available on latest ct workstations. learning objectives: . to learn about the classification of copd. . to appreciate the role of hrct in the classification of copd. a- : this presentation will examine the role of expiratory ct in the diagnosis of small and large airways diseases. small airways disease or air trapping may be a feature of asthma, copd and hypersensitivity pneumonitis, and is typically characterised by a mosaic attenuation pattern on ct. tracheobronchomalacia and excessive dynamic airway collapse (edac) are large airways conditions that may be recognised by tracheal narrowing on inspiratory and/or expiratory ct. the typical clinical and ct manifestations of these diseases will be reviewed. additionally, a number of important caveats with regard to ct in small and large airways disease will be discussed: ) the comparative strengths and limitations of ct, bronchoscopy and lung function testing in making the diagnosis; ) the overlap in appearances that exists between diseased and healthy individuals; ) the variability in definitions of conditions such as tracheobronchomalacia. the optimal ct technique for imaging of airways disease, including the role of dynamic expiratory ct, will also be reviewed. for routine clinical applications, a standardised mri protocol has been widely implemented. it addresses the major challenges of mri of the lung, i.e. low proton density, susceptibility artefacts as well as respiratory and cardiac motion. beyond visualisation of lung morphology, which is done in an inspiratory breath-hold, functional imaging has become an integral part of the routine protocols: perfusion, blood flow, ventilation, respiratory motion, diffusion. for perfusion imaging, inspiratory or expiratory scans can be used, blood flow measurement should be performed during shallow breathing, and ventilation and diffusion are mainly assessed in inspiration. respiratory motion is best assessed by dynamic image acquisitions. continuous breathing can also be combined with triggering or navigators to improve image quality or derive functional maps. mri is recommended as the first-line cross-sectional imaging modality in paediatric chest radiology, including cystic fibrosis, complicated pneumonia, any pulmonary or cardiovascular anomaly, as well as the assessment of mediastinal masses in children and adults. mri is also challenging pet/ct in the staging of lung cancer (tnm) as well as ct and echocardiography in the assessment of pulmonary arterial hypertension. mrieven without contrast -is an alternative in the diagnosis of acute pulmonary embolism if iodinated contrast medium is contraindicated or in pregnant women. mri should also be used in complicated pneumonia, e.g. in immunocompromised patients as well as for the functional assessment of chronic obstructive pulmonary disease (copd) or severe asthma. the role of mri in interstitial lung disease stills needs to be determined. unlike the simple forms of cranisynostosis whose modalities and timing of surgical correction are well established, the management of faciocraniosynostoses requires a multispecialistic and repeated evaluation of the single patients. their evolution, in fact, depends on the specific genetic anomalies but also on the phenotype, which can vary in time, of their clinical expression which may lead to different degrees in severity of the associated functional disturbances (csf dynamics impairment, visual deficits, respiratory anomalies, etc). consequently these conditions may require several surgical steps the timing of which are dictated by the exact clinical diagnosis and the evaluation of the functional status at different ages. current management of faciocraniostenoses is thus based not only on the radiological studies but also on the functional assessment of the brain function (e.g. mri imaging studies, metabolic and cerebral blood circulation investigations, respiratory pathways volume evaluation, sleep recording). today's surgical multidisciplinary management may benefit a large variety of techniques which extend from free bone cranioplasty with intraoperative active fixed expansion to more dynamic and less invasive methods which exploit the physiological brain expansion in infants or the gradual cranial vault expansion mechanically stimulated by springs or distractors. in the present report, we will review the decision making process and the rationale on which, at the necker-enfants malades, we base the use of the currently available techniques for skull expansion and correction of cranial malformations according to the accurate dynamic radiological and functional evaluation at different stages of the disease. learning objectives: . to learn about the imaging patterns of faciocraniosynostoses. . to learn how and when to image. . to become familiar with associated brain anomalies. b. all about the paediatric pituitary gland m.i. argyropoulou; ioannina/ gr (margyrop@cc.uoi.gr) mr is the imaging modality of choice for the assessment of the pituitary gland (pg) and the hypothalamus. the normal adenohypophysis is bright during the first two months of life and appears isosignal to the brain parenchyma afterwards. the neurohypophysis is bright, provided that the child is well hydrated. the pg height decreases during the first year of life and then increases until puberty. adenohypophyseal deficiency has been associated with a small pituitary size, an ectopic neurohypophysis, a hypoplastic or absent pituitary stalk, hypothalamic gliomas, craniopharyngiomas and iron overload states. precocious puberty may be idiopathic, but it has also has been associated with hypothalamic hamartomas, craniopharyngiomas and hydrocephalus. diabetes insipidus may be secondary to histiocytosis x, germinomas and trauma causing pituitary stalk interruption. the hypothalamopituitary axis is evaluated by using sagittal and coronal t -weighted images without and with contrast administration. dynamic contrast enhancement may be useful in the evaluation of disorders responsible of diabetes insipidus. magnetisation transfer imaging may be useful in the evaluation of pituitary deficiencies or precocious puberty. familiarity with orbital and ocular anatomy is crucial to the understanding of disease processes of the orbit. lesions of the orbit may be divided into those which are intraocular and those which are extraocular. the underlying aetiology and geneses of many different lesions that can occur in the orbits vary depending on the location of the lesions and sometimes on additional nonorbital conditions. ct and mri play crucial roles in the evaluation of orbital pathology where often mri still is a complement to ct examination in the evaluation of orbital lesions familiarity with the radiologic appearance of common orbital lesions is important, as many of these lesions will not be seen on physical examination. after a very brief anatomic overview, most of this lecture will focus on the more common benign and malignant lesions as well as differential diagnosis involving the orbit and lachrymal gland in both the paediatric and adult population. the lecture will also present suggested imaging protocol and standard of care with respect to imaging. learning objectives: . to understand the embryology and imaging findings of the most common malformations. . to learn about space-occupying lesions and the differential diagnosis of tumours and inflammatory conditions. . to be aware of the role of conventional and advanced mr sequences in the diagnostic approach to lesions in the orbit. room e the hand and wrist injury to the wrist and hand is an important clinical problem. first, such injury is relatively common. second, the spectrum of abnormalities is complicated. the purpose of this presentation will be to learn more about the imaging appearances of soft tissue and osteoarticular injury of the wrist and hand using multiple imaging techniques. emphasis will be placed upon pathomechanics and characterisation of greater and lesser arc injury patterns of the wrist. the various posttraumatic instability patterns of the wrist will be also discussed. rheumatoid arthritis (ra), psoriatic arthritis (psa) and other inflammatory disease can be diagnosed and sometimes differentiated in the early stages of the disease on the basis of mri and/or pdus features of the hand and wrist. rheumatoid arthritis (ra) activity is closely correlated with inflammation. the synovial membrane is the principal site of inflammation in which the inflammatory process enhances capillary perfusion and permeability. doppler ultrasonography (dus), using the amount of colour pixels in the region of interest, and dynamic magnetic resonance imaging (de-mri) are both able to detect this inflammation in the wrist and hand. although these techniques are both capable of monitoring synovium inflammation modifications after ra treatment, pdus has become an essential tool for ra joint monitoring in routine practice in view of its sensitivity in the detection of synovitis, feasibility in outpatient clinics, and low cost. (ellopis@hospital-ribera.com) radiological study of the wrist and hand is challenging due to its complex anatomy with many small structures and the number of normal bone and soft tissue variants that might mimic injuries. moreover, many findings can be asymptomatic. their knowledge is important to avoid misdiagnosis. during this lecture we will also review the role of the different imaging modalities, such as plain films for wrist alignment and bone structures as well as the important role of us and mr in differentiating tumour from tumour-like conditions. we will become familiar with some specific radiological findings that allow us to make accurate diagnoses of soft tissue and bone lesions. learning objectives: . to learn more about the spectrum of intra and para-articular soft tissue tumours, and soft tissue tumour-like lesions. . to become familiar with us and mri findings of specific soft tissue lesions. room e oncologic imaging chairman's introduction c. pfannenberg; tübingen/ de (christina.pfannenberg@med.uni-tuebingen.de) with recent advances in cross-sectional imaging, the frequency of detecting "incidental findings" has markedly increased. incidental findings (=incidentaloma) are defined as unexpected, asymptomatic abnormalities detected by imaging performed for an unrelated reason. these incidentalomas have created a management dilemma for both radiologists and clinicians, particularly in the cancer patient in whom any mass warrants further evaluation. discovery of incidental findings often leads to a cascade of additional tests that is costly, provokes anxiety and exposes patients to the risk of unnecessary radiation and intervention. the workup of incidentalomas varies widely by physicians, and strategies for optimising patient management are only beginning to emerge. in this course, guidelines concerning a rational approach to some of the more common incidental abnormalities in cancer patients are presented. basic principles and tools for interpretation of incidental findings, common pitfalls and protocol issues regarding the differentiation of benign and malignant lesions as well as treatment-induced abnormalities will be addressed with a focus on the liver, lung and skeletal system. at the end of the session, the speakers will discuss the role of functional imaging techniques for characterisation of incidental lesions. session objectives: . to become familiar with basic principles and common pitfalls in interpretation of incidental findings in the lung, abdomen and skeletal system. . to learn how functional imaging (dwi, pet/ct, bs) can help in lesion characterisation. . to provide attendees with clear and practical messages for the management of the most common incidental findings in cancer patients. a. abdomen: common pitfalls and protocol issues a. ba-ssalamah; vienna/ at (ahmed.ba-ssalamah@meduniwien.ac.at) an incidentaloma is quite a frequent diagnosis in medicine, in general, and in radiology, in particular. by definition, an incidentaloma is an abnormality or a tumour found by coincidence without clinical symptoms or suspicion. these incidental findings have long posed challenges to physicians, and particularly to radiologists as well as health-care providers due to the resulting high costs. the scope and scale of these challenges have increased with the introduction of new technologies, in particular cross-sectional imaging, such as mdct and mri using sub-millimetre thin slices. incidentalomas still cause a management dilemma for clinicians, radiologists and even for the patients themselves. this dilemma is particularly pertinent to oncology patients. therefore, a precise knowledge of the broad spectrum of incidental findings is crucial. based on this knowledge, we can choose the appropriate radiologic examination that will provide a confident diagnosis. this way, needless uncertainty, for both the patient and the physician in charge, is avoided. furthermore, invasive procedures, such as biopsies, with the potential for complications, as well as cost-intensive follow-up examinations, can be reduced. furthermore, mri is usually used to detect the side effects of chemotherapy of the liver. simple steatosis is usually reversible, unless the liver receives a 'second hit' of damage from other causes leading to other manifestations, including chemotherapy-associated steatosis, sinusoidal obstructive syndrome, nodular regenerative hyperplasia, veno-occlusive disease, peliosis, pseudo-cirrhosis, and sclerosing cholangitis largely due to microvascular injury. finally, the effects of chemotherapy on peritoneal and mesenteric structures after performing intraperitoneal chemotherapy will be discussed. this presentation will discuss the complex topic of incidental findings in thoracic imaging of oncological patients. incidental findings will be presented with respect to their respective organs and anatomical regions. the presentation will emphasise the clinical relevancy of the findings as well as the specific of risk estimation in oncological patients. finally, the presentation will discuss the usefulness (or lack thereof) of current management guidelines for incidental findings, as designed for the general population. illustrative clinical scenarios will be discussed. radiographs and ct often detect incidental observations in bones, corresponding either to normal variants or benign conditions, which require additional imaging to rule out malignant conditions. mri most often provides nonambiguous explanation for these observations. beside this, mri, targeting either the whole body or only the axial skeleton, often including diffusionweighted (dwi) sequences, is increasingly used for bone tumour detection in many "osteophilic" cancers and haematologic malignancies, without need for contrast material injection and without irradiation, with unparallelled sensitivity to bone lesions. an important advantage and also a challenge for musculoskeletal radiologists are the all organ screening capabilities of dwi, demanding careful study of the huge information provided and knowledge extending far beyond bones in terms of organs and metastatic spread of different cancers. a second major advantage is its ability to detect lesion changes under therapy. however, benign lesions and non-neoplastic conditions, as well as artefacts may also lead to confusing observations on mri, and particularly on dwi. anatomical mr sequences as well as other imaging modalities are of utmost help to recognise these pitfalls. whole body mri including dwi sequences has to position itself among other diagnostic tools, bone scan, spect, and especially pet with its variety of tracers, in the currently evolving strategy of bone screening techniques, which will most likely vary according to the primary cancer. learning objectives: . to present most frequent x-ray and ct pseudo lesions and benign conditions and show how mri often enables straightforward interpretation of these abormalities. . to highlight the strengths of mri with diffusion weighted imaging (dwi) for malignant lesion detection and characterisation within bones, but also beyond bones. . to highlight the typical appearance of malignant lesions on projectional and cross-sectional imaging. . to learn to differentiate these lesions from normal marrow variations, stress lesions, bony pseudo-lesions and other benign conditions, and to become familiar with treatment induced changes within lesions and their environment. . to situate mri amongst other functional imaging techniques (pet, spect, ). colorectal cancer is the rd most commonly diagnosed cancer in the world with % of cases diagnosed in the developed world. with an estimated . million new cases clinically diagnosed and over , people killed worldwide by this disease on an annual basis, colorectal cancer is a true public health concern. survival of colorectal cancer is directly related to the extent of disease and specifically presence of liver metastases. imaging plays a key role in the initial staging of colorectal cancer and is the gold standard in evaluating extra colonic disease, primarily liver metastases. imaging is also widely used for therapy monitoring and staging. ct, mri, pet/ct and pet/mri are the key imaging modalities. in addition, tumour response therapy assessed with morphological and functional biomarkers is increasingly used by advanced gastrointestinal oncologic programs. furthermore, image-guided therapy is widely used for patients with unresectable lesions. liver colorectal metastases were the first liver metastases to be treated with image-guided ablation techniques. a gamut of ablative techniques exists ranging from transarterial embolisation, radiofrequency ablation, highly intensified focused ultrasound, brachitherapy etc. in short, diagnosing, characterising and finally assessing tumour response after neoadjuvant and image-guided therapy are all functions where imaging plays a pivotal role. this course is divided into three logical segments dealing with current treatment options, morphological and finally functional biomarkers and it is followed by a panel discussion which includes audience participation. a. current treatment options t.k. helmberger; munich/de (thomas.helmberger@klinikum-muenchen.de) hepatic metastases in colorectal cancer may occur in % to % of the cases. considering the general oncological (isolated hepatic tumour load; prognostic benefit), and technical (size, number, location of hepatic metastases; expected hepatic functional reserve) framework, surgical resection is still considered to be the method of choice -even if this statement never had been verified by rtcs. nevertheless, in clinical reality only - % of patients with liver metastases may qualify for resection. in consequence, the majority of patients need other or at least modified therapeutical pathways including adjuvant or neoadjuvant chemotherapy and more and more image-guided local ablative therapies. the latter encompass chemo-(transarterial chemoperfusion/-embolisation), thermo-(radiofrequency-, laser-, microwave ablation, high intensified focused ultrasound), and radio-ablative (radio embolisation, interstitial brachytherapy, etc). techniques. particularly, thermalablative techniques gained wide acceptance over the last years, since ample evidence could be presented showing that this method can be applied as primary and also complementary therapies in resectable and non-resectable metastatic disease. furthermore, recent data confirm that in multimodality therapy concepts, progression free survival and overall survival in patients with primarily unresectable and with unfavourable prognosis is comparable to surgery with -year survival rates more than %. minimally invasive, imageguided therapies will not replace surgical resection; however, these therapy modalities are eligible in a large number of cases and should be implemented consequently in multimodality treatment regimens according to the interdisciplinary consensus of oncologists, interventional radiologists, and surgeons. colorectal liver metastases are typically identified as low attenuation lesions on portal venous phase ct. planning of optimal therapy depends on accurate localisation and characterisation of all focal liver lesions and this is best achieved with mri, which should include diffusion-weighted imaging and use of hepatocyte-specific contrast medium. the typical mri signature of colorectal metastases includes low signal on t w, moderately increased signal on t w, irregular peripheral arterial phase enhancement with low signal on portal venous phase, restricted diffusion and absent hepatocytes. morphological tumour response can be assessed with either modality. size-based systems for assessing tumour response are widely applied, with recist . the most widely used at present. recist . includes several modifications that make it more user friendly than recist . . more advanced morphological criteria have been described for new targeted and molecular therapies, including overall attenuation, the tumour-liver interface and the appearance of the peripheral rim of enhancement. as hepatic surgeons become more aggressive in their approach to resection in patients with liver metastases, it is important to understand that disappearance or calcification of liver metastases after treatment does not necessarily equate to a complete pathological response. the timing of imaging is therefore critical in assisting the surgeon to remove all previously affected hepatic segments after chemotherapy. learning objectives: . to learn about the algorithm for detecting and characterising liver metastases. . to understand conventional imaging criteria for assessing tumour response. . to learn about the rationale for monitoring patients after radical and palliative treatments. conventional size measurement criteria remain the most widely used method to determine the response of colorectal liver metastases to treatment. however, tumour size reduction is assessed relatively late (e.g. weeks after treatment) and new targeted treatment may be effective without reducing tumour size. new functional imaging techniques can be applied to quantify different aspects of tumour biology and to develop response, and predictive and prognostic biomarkers. we discuss the use of diffusion-weighted mr imaging, dynamic contrast-enhanced mr imaging and fdg-pet imaging in the evaluation of treatment response in patients with colorectal liver metastases. digital breast tomosynthesis (dbt) is a promising technique for breast imaging based on a full-field digital mammography (ffdm) platform. the x-ray tube moves through a proscribed arc, and several low-dose projection images are acquired. images are reconstructed into a stack of mm slices. the radiation dose is about the same or slightly higher than for ffdm. the most important advantage of dbt is the elimination of superimposed tissue, which improves detection of lesions otherwise hidden by dense breast parenchyma and reduces the interpretation problems caused by overlapping tissue. dbt is suggested to improve sensitivity as well as specificity in women with dense breast. dbt is superior to ffdm in tumour size assessment and for mass visibility and cancer conspicuity. dbt is comparable to ffdm for evaluation of microcalcifications. dbt is superior for the detection of spiculated masses and architectural distortion. the potential to improve sensitivity and specificity is of interest for screening. an open question is whether dbt should be applied in one or two views. two-view dbt would mean a doubling of radiation dose, but a solution is the implementation of synthetic d images reconstructed from the d dataset of dbt. the synthesised images are created by summing and filtering the stack of reconstructed dbt slices. using synthetic d allows "combo mode" to be implemented in screening with the same radiation dose as for conventional d. results using dbt in breast cancer screening are very promising. different study design of published studies may explain the variations of results. magnetic resonance imaging of the breast provides a multitude of techniques for detection of breast cancer and differentiation of benign from malignant lesions. in the last few years, significant improvements of scanner hardware and equipment in terms of coils as well as sequence software have been achieved. to date, multiparametric quantitative measurement of perfusion, diffusion and tissue chemistry is possible at field strengths up to tesla. although higher field strengths and improved sequence protocols provide higher signal and allow faster imaging, specific technical issues have to be considered to avoid artefacts and pitfalls. this talk aims to demonstrate the possibilities and limitations of multiparametric and (ultra-)/high-field mri. furthermore, these new techniques are put into the broader clinical context to determine the potential value for breast lesion detection and differentiation. positron emission mammography is a recently developed imaging device using positron emission technology. after injection of a positron-emitting radiotracer, the radiation is detected by a dedicated high-resolution camera, providing high spatial resolution. commercially available systems include cameras where the breast is compressed and which display a d image similar in its layout to a mammogram and hanging breast devices where a d image similar in its layout to mri is produced. these devices have been compared to pet/ct and have shown higher spatial resolution, accuracy and sensitivity in detecting malignant breast lesions. the most widely studied tracer in pet/ct and in pem is fluorodeoxyglucose (fdg). fdg is a glucose analogue and has had a major impact on oncology imaging with pet/ct. breast carcinomas demonstrate increased glucose consumption and the intensity of the uptake has been correlated with prognosis, hormonal receptor and her status, ki and nodal involvement. current potential indications for pem are detection and characterisation of breast lesions, local staging in patients with known breast cancer and baseline assessment prior to neoadjuvant chemotherapy. future developments of pem will involve new tracers and fusion with other breast imaging modalities. fluorothymidine is a proliferation tracer that seems promising in early assessment of response to chemotherapy. fluoroestradiol has the potential to image oestrogen receptor status in vivo. the possibility of pem-guided biopsy is a very exciting development and has the potential to select lesions with the highest intensity of uptake. fusion with mri, us and mammography will increase the diagnostic accuracy. the presentation will focus on two frequent findings on mri with increasing incidence during ageing, notably "unspecific" hyperintense lesions on t /flair and cerebral mircobleeds (cmbs) on t * or swi images. clinicoradiologic studies suggest that these t /flair lesions are associated with increased risk of cognitive decline, stroke and death. the clinical relevance of these lesions probably depends on periventricular versus deep white matter location. radiologic-histopathologic studies correspondingly indicate that the degree of histopathologically confirmed demyelination also depends on the location of these t /flair lesions. cerebral mircobleeds (cmbs) are punctate hypointense lesions on t * or swi images. while multiple cmbs are associated with diseases such as cerebral amyloid angiopathy (caa), clinicoradiologic studies demonstrate increased incidence of sporadic cmbs in mild cognitive impairment (mci) and alzheimer dementia, indicating a degrading effect of cmbs on cognition. on the other hand, radiologic-histopathologic studies show that not all black spots on t * or swi correspond to cmbs. cmb mimics include micro-calcifications. the presentation will demonstrate typical manifestations of these "unspecific" t /flair lesions and cmbs during ageing and provide tips for the interpretation of these lesions during daily clinical routine. with the increasing use of mri, it has become more common to discover incidental brain findings. these findings may be non-specific or have some morphological characteristics and geographical distribution highly suggestive of a demyelinating disease. the term "radiologically isolated syndrome" (ris) was introduced by okuda in to describe those asymptomatic patients with radiographic abnormalities highly suggestive of multiple sclerosis (ms). sometimes, these lesions may even meet the mri criteria for dissemination in space, which are currently used to predict future development or conversion to ms in patients presenting a clinically isolated syndrome (cis). however, we must not forget that these radiological criteria should be applied only when the patient had experienced any clinical manifestations suggestive of a demyelinating disease. therefore, what happens in those patients in whom we found highly suggestive lesions but have never had symptoms? due to lack of knowledge about the natural history or evolution of this new syndrome, clinical and therapeutic management of these patients is not well established, nor is the risk of conversion to ms. recent data, however, indicate that the presence of gadolinium-enhancing cervical cord and cortical lesions significantly increases the risk of conversion to cis or ms. all these data have improved the characterisation of ris subjects and in our understanding of risk factors for initial symptom development. incidental findings on brain imaging are defined as previously undetected abnormalities of potential clinical relevance that are unexpectedly discovered and unrelated to the purpose of the imaging. incidental findings are increasingly detected in clinical practice, with screening, and in the research setting. data on the prevalence of these abnormalities are scarce, the clinical course of the findings is often unknown, and the management of such lesions is not clear. the prevalence of incidental findings can be expected to vary depending on the purpose of the imaging exams. with improvements in imaging technology (higher field scanners, new pulse sequences), the number of detected incidental findings will increase dramatically. another important point is the advent of imaging biomarkers. advanced techniques for postprocessing and analysis, such as automated segmentation of brain structures or voxel based morphometry, will lead to the discovery of imaging biomarkers. once the predictive value of these markers has been established, most mri studies of the brain, both in the clinical and research setting, will reveal information that might be relevant for the well-being of patients or participants. although still incidental, these findings can unfortunately no longer be considered unexpected. we will soon face large medical, ethical, and practical problems as a result of technical improvements. in this lecture, the most important incidental findings and their prevalence will be reported. the management of incidental findings in the clinical and research setting will be discussed. finally, recommendations for follow-up will be provided. the primary assessment of laryngeal cancer is provided by endoscopy, which is accurate in delineating both the superficial extent and functional impairment. imaging techniques are recommended to grade submucosal invasion, local and distant spread. in the last few decades, open and endolaryngeal surgical procedures as well highly sophisticated rt techniques have been developed to treat the tumour while preserving critical laryngeal functions. for example, early glottic tumours (tis-t ) can be treated by endoscopic laser excision or rt. the integration of information acquired by endoscopy and imaging is essential for proper treatment planning. the radiologist has to know that the site of origin (supraglottis vs glottis or subglottis) and local extent (superficial and submucosal) are the key tumour-related factors in planning the type of treatment. submucosal invasion has a variable impact depending on the location of the primary tumour. the key issues in glottic cancers include the invasion of: the posterior paraglottic space, crico-arytenoid joint, and anterior commissure and contralateral true vocal cord, and vertical spread towards supra and/or subglottis, thyroid or cricoid cartilage. the key issues in supraglottic cancers encompass the invasion of: base of the tongue, preepiglottic space, piriform sinus, vertical spread into glottis and subsequent cartilage invasion (observed exclusively in transglottic cancers). functionsparing surgical techniques -as supracricoid laryngectomies -can be applied in advanced cancers when sparing of the posterior commissure, the ipsilateral crico-arytenoid joint, the mucosa investing the upper cricoid and the outer perichondrium of the thyroid cartilage is demonstrated by endoscopic and imaging mapping. the detection of recurrent laryngeal carcinoma is often challenging. to better appraise the expected findings after initial surgery of laryngeal cancer, the classical partial laryngectomy and laser laryngeal surgery are briefly presented.(chemo)radiotherapy has become an important treatment modality for laryngeal carcinoma. the recurrence rate in t -t laryngeal carcinoma is reported to be between % and %. the difficulty in differentiation between radiation reaction (such as oedema, fibrosis and soft tissue and cartilage necrosis) and recurrent disease is discussed. a histologic study on wholeorgan sections of recurrent glottic carcinomas is also presented: recurrent disease presents with different tumour spread than does a primary carcinoma, resulting in difficulties in estimating the extent of tumour recurrence. currently, selected recurrences of early glottic carcinoma are, whenever possible, treated by larynx-preserving salvage surgery. in those cases, a precise evaluation of the recurrent tumour extent is mandatory for planning larynx-preserving salvage surgery. this is especially true in critical regions such as the preepiglottic space, infiltration into cartilage, contralateral tumour spread and subglottic tumour extension. the accuracy of crt-classification is relatively low: many patients with signs and symptoms suggesting tumour recurrence present with post-radiotherapy changes; small tumor foci, often localised in the subglottic region, are undetectable by imaging studies. tissue changes in the neck treated by surgery and/or radiotherapy (rt) make the detection of residual or recurrent tumour more difficult. clinical evaluation of the neck is also hampered by these changes. rt-induced fibrosis and postsurgical scar tissue make palpation of the neck very difficult. endoscopy is hampered by endolaryngeal oedema which can persist for many months post-rt. therefore, any (non-invasive) method helping in the detection of recurrence is welcome. patients at risk for local failure after rt can be successfully identified by a post-rt ct (or mr) study between to months after rt. the optimal time point to perform such a 'baseline study' seems to be about to months post-rt. patients with indeterminate findings are candidates for 'imaging surveillance'; i.e. follow-up imaging every to months up to a period of years after rt. however, ongoing studies suggest that metabolic imaging (fdg-pet) may detect local recurrences with a higher accuracy than 'conventional' anatomically based imaging techniques, such as ct and mr. ct and/or mr-findings in the treated neck are frequently inconclusive. at present, new techniques are available to detect recurrent cancer. pet-ct is widely applied in the post-treatment setting. also, advanced mr-techniques such as diffusion weighted imaging (dwi) and dynamic contrast-enhanced mr (dce-mr) can be applied. focusing on the larynx, the advantages of these techniques as well as the limitations will be shown using imaging examples from daily practice. during the last years, several hundred new radiotracers for pet imaging of cancer have been developed and tested preclinically. these tracers are based on proteins (e.g. antibodies and antibody fragments), peptides (e.g. g proteincoupled receptor ligands) or small molecules (e.g. radiolabelled protein kinase inhibitors or metabolic substrates). using these radiotracers, the expression and function of a variety of proteins can be studied in patients, including for example glutamine/glutamate metabolism, neutral amino acid transport, psma, grpr, sstr, cxcr , folate and alpha-v beta- integrin expression. some of these radiopharmaceuticals are potential companion diagnostics and may allow selection of patients for treatment with radiopharmaceuticals or targeted drug conjugates. preclinical and initial clinical data are promising for several new radiotracers, but the key challenge is the clinical validation and dissemination of these compounds. validation and dissemination have been hampered so far by regulatory hurdles as well as by the lack of standardised trial designs for the validation of imaging agents and the lack of accepted and appropriate end points to prove clinical utility. addressing these issues will be critical for the future clinical use of pet and other molecular imaging technologies. imaging targets in cancer range from simple size measurements to more specific biomarkers on functional, cellular, metabolic and molecular levels. as our understanding of basic tumour biology has advanced, techniques have been developed to exploit this information to produce increasingly specific molecular imaging tools. the biodistribution of these molecular imaging probes should be more specific in diagnosing and assessing cancer than the morphological information acquired using anatomical imaging alone. this lecture will discuss current and emerging functional and molecular imaging techniques using mri and their applications in oncology. functional measures of tumour blood flow and vascular permeability can be made using dynamic contrast-enhanced mri. diffusion-weighted imaging is a surrogate for the cellular content of the tumour and emerging methods can be used to probe features of the extracellular space such as tumour ph and stromal content. on the molecular level, cell surface expression of specific proteins and enzyme activity within the cell can be imaged; labelled probes have been developed which bind to these proteins and a new mr technique is being developed for assessing tumour glucose in a similar way to pet. hyperpolarisation methods are emerging to overcome the major limitation of mr: low sensitivity. one such approach is dynamic nuclear polarisation, which can probe carbon metabolism non-invasively in patients with cancer. functional and molecular imaging techniques with mri will increasingly be used in radiology in conjunction with anatomical imaging methods to improve diagnosis and prognosis, target biopsies, as well as predict and detect response to treatment. with mr-spectroscopy, diffusion-weighted imaging, pet-and spect-ct, as well as pet-mri, molecular imaging has already become part of clinical routine diagnosis. also, some contrast agents such as spio for mps-labelling and scavenger-receptor binding gadolinium chelates are clinically applied for liver and lymph node imaging. however, there are still a number of highly promising novel tools that are expected to emerge clinically in the near future. in this context, the first part of the talk will give an overview on how optical imaging basically works and which future clinical applications can be expected. in this context, raman spectroscopy, fluorescence optical reflectance imaging, fluorescence mediated tomography, photoacoustic imaging and cerenkov luminescence imaging will be addressed. the second part of the talk introduces molecular ultrasound imaging as a safe and preclinically wellevaluated method. besides the diagnostic use of molecular ultrasound contrast agents, which have been already evaluated in clinical trials, the potential of this method also for theranostic purposes will be highlighted. the assessment of the amount of arterial calcification with computed tomography is a standard method in the risk stratification of coronary heart disease. coronary calcium detection by ct has been shown to identify atherosclerotic plaque and to quantitatively assess coronary calcium. many studies have demonstrated the association between the degree of coronary calcium, the burden of atherosclerosis, and the risk for cardiovascular events associated with coronary calcium. the cac scoring can provide individual risk assessment and reclassify the low and particularly intermediate framingham risk cohort into lower-and higher-risk strata. the absence of cac is associated with a very low risk of future cardiovascular events, with modest incremental value of other diagnostic tests in this very low-risk group. the role of cac in the workup of symptomatic patients is under discussion and there is evidence that the absence of cac has a high negative predictive value for ruling out acute coronary syndrome. although cac measurement is highly standardised, some technical aspects have to be considered and all possibilities of dose reductions utilised. this presentation will show the technical and epidemiological fundamentals of cac scoring and discuss the clinical applications of the method. coronary cta has gained an important role in the evaluation of patients with chest pain, suspected of coronary artery disease (cad). in comparison to invasive coronary angiography, coronary cta with -multidetector ct has an excellent sensitivity for coronary stenosis. specificity for stenosis is less excellent, but has improved with newer ct generations. the strongest impact of coronary cta has been on the exclusion of stenosis in symptomatic patients at low-intermediate pre-test probability. in contrast to invasive angiography, coronary cta yields more information than just the severity of stenosis. coronary cta also allows determination of plaque types (calcified, non-calcified, partly calcified) and quantification of the atherosclerotic plaque burden. also, new developments point to the possibility to assess the haemodynamic significance of stenosis based on ct density measurements in the coronary arteries, or evaluation of myocardial perfusion. thus, coronary cta yields quantitative imaging biomarkers that could be used for risk stratification in the future. recent studies have shown that whether or not a patient has stenosis and plaque, as well as the type and burden of plaque, affects the risk of myocardial infarction and mortality. therefore, the impact of coronary cta imaging biomarkers reaches beyond the mere assessment of stenosis for symptomatic treatment and could potentially alter medical management of patients for improvement of long-term prognosis. a- : c. added value of carotid and peripheral artery imaging for risk assessment l. natale; rome/ it (lnatale@rm.unicatt.it) technical protocols optimisation of mra and cta of carotid and peripheral arteries is crucial for image quality and to complete the analysis of both lumen and vessel wall. furthermore, mra protocol needs to be integrated with dedicated pulse sequences in order to obtain vessel wall imaging that is already included in cta datasets. new ct and mr scanners allow this optimisation in terms of radiation exposure, contrast media dose reduction and spatial resolution. all these parameters will be discussed for both techniques. according to international guidelines, non-invasive imaging indications will be discussed, with particular attention to high risk population (e.g.: diabetic patients). some possible imaging biomarkers of plaque composition will be discussed. learning objectives: . to become familiar with optimal technical considerations for performing cta and mra of the carotid and peripheral arteries. . to understand clinical indications for carotid and peripheral cta and mra. . to discuss the role of cta and mra parameters including plaque imaging as biomarkers of cardiovascular disease. key: cord- -i on authors: nan title: abstracts dgrh-kongress date: - - journal: z rheumatol doi: . /s - - - sha: doc_id: cord_uid: i on nan im namen der dgrh, der dgorh und der gkjr begrüßen wir sie ganz herzlich zu unserem diesjährigen kongress visualisierung therapeutischer effekte von vasodilatantien beim sekundären raynaud-syndrom mittels fluoreszenzoptischer bildgebung di. stellenwert der gelenksonographie bezüglich diagnose, behandlung und therapiekontrolle der bursitis intermetatarsalis -einer häufig übersehenen differenzialdiagnose. fünf fallbeispiele wegen der deutlich eingeschränkten nierenfunktion konnten therapeutisch keine nsar angewandt werden. wir haben mit × , mg colchicin täglich behandelt. die anfänglich schwerkranke bettlägerige patientin konnte innerhalb von h mobilisiert werden. um eine abschließende sicherung der diagnose einer uratinduzierten sakroiliitis erreichen zu können ist die patientin mit einem dual-energy-ct (dect) untersucht worden. ergebnisse. mit dieser methode konnten gichttophi in beiden sakroiliakalgelenken dargestellt werden, ebenso an beiden mtp -gelenken. schlussfolgerung. aktuell liegen bisher noch keine weiteren berichte vor, dass diese methode auch für die diagnostik einer gicht im bereich der sakroiliakalregion zuverlässige ergebnisse liefern kann. zudem zeigt dieser krankheitsverlauf, dass sich die gicht durchaus primär im bereich des achsenskeletts manifestieren kann und nicht in erster linie an den peripheren gelenken zu entsprechenden beschwerden führen muss. a. glimm , s. werner , s. ohrndorf , c. schwenke , g. schmittat , g. burmester einleitung. typische pathologische veränderung bei der rheumatoiden arthritis (ra) ist die synovialitis. auch bei der osteoarthrose (oa) lassen sich entzündliche veränderungen der gelenke finden. diese können mittels fluoreszenzoptischer bildgebung (foi) und dem gelenkultraschall (us) sichtbar gemacht werden. ziel der studie: vergleich der foi mit dem us bei patienten mit ra und oa. methoden. es wurde bei patienten ( ra, oa) die foi beider hände sowie die us des handgelenks (hg) und der fingergelenke (mcp, pip, dip) der klinisch beschwerdeführenden hand von dorsal und palmar sowohl im b-bild (b-us) als auch mit power-doppler (pd-us) durchgeführt. synovialitis und tenosynovitis im us sowie die intensität des fluoreszenzsignals im bereich der gelenke in der foi wurden qualitativ als auch semiquantitativ nach standardisierten verfahren für den primavistamode (pvm) und drei verschiedene phasen (p - ; [ ] ) bewertet. in der statistischen analyse wurden anschließend sensitivitäten und spezifitäten für die foi bei der ra und oa getrennt für synovialitis und tenosynovitis, dorsal und palmar jeweils für b-us und pd-us als referenzmethode berechnet. ergebnisse. in abhängigkeit von der betrachteten phase zeigen sich für die ra und oa moderate sensitivitäten und spezifitäten. für die ra wurden in der phase des foi die höchsten sensitivitäten mit % für b-us und % für pd-us berechnet. auch bei der oa ergaben sich die höchsten sensitivitäten in der phase des foi mit % für b-us und % für pd-us als referenzmethode. die höchsten spezifitäten für beide diagnosen wurden in der foi in phase erreicht. hierbei lag die spezifität bei der ra für b-us bei % und für pd-us bei %. der höchste spezifitätswert bei der oa sowohl für b-us als pd-us war % (. tab. background. pet is a nuclear imaging technique that depicts functional processes within the body with high sensitivity by detecting annihilation radiation from radioactive decay of a positron-emitting radionuclide that was labeled to a biologically active molecule (tracer) and introduced into the body. f-fluoride ( f) can be used for pet as a bone-seeking agent reflecting bone perfusion and remodeling. we inaugurated a pilot study with simultaneous pet/mr to examine whether addition of pet provides different and additional information in comparison to mri in axspa patients. methods. eleven axspa patients, median age y, disease duration range . - y, mean basdai . , were examined by pet/ -tesla mri minutes after injection of a mean dose of mbq of f using a integrated whole-body pet/mr scanner (siemens biograph mmr®). t-mris were scored blinded to patient's clinical characteristics by two readers ( rheumatologist and radiologist/nuclear medicine specialist) using the berlin mri score and also by recording inflammatory lesions on a vertebral edge (ve) level. in a second step pet/mris were read blindly by the same readers also based on the ve involvement of individual vertebral bodies. results. the procedure was successful in all patients. the resulting mean effective radiation dose per patient was . msv. co-registration of pet/mri fusion images was highly accurate, allowing a precise comparison of mri and pet. in the direct comparison of the mri and pet signal the two readers saw consistent signals in almost % of the sites studied. however, there were areas where signals differed, e.g. within existing syndesmophytes where pet signal was increased but conventional mris showed no signal, or the sternum area and lateral or posterior spinal elements such as facets and spinous processes. conclusion. the new technique of integrated pet/mri provides similar imaging signals as conventional mri. however, we observed differences between the two modalities in areas with less inflammatory activity but where bone metabolism seemed to be active or in areas with blurred resolution on conventional mri. the possibility that pet detects osteoblastic activity in areas where no inflammatory signal is detected with mri seems to be of interest. einleitung. sensitiven bildgebenden verfahren wie der hochauflösenden arthrosonographie kommen bei der detektion initial entzündlicher veränderungen im rahmen der frühdiagnostik der psoriasisarthritis (psa) eine große bedeutung zu. die vorliegende prospektive studie untersucht die diagnostische und prognostische wertigkeit der sonographischen befunde im vergleich zur klinischen untersuchung auf ebene einzelner gelenke bei früher psoriasis-arthritis (psa). methoden. rekrutierung von patienten mit therapienaiver früher psa. sonographie von gelenken mit semiquantitativer graduierung (grad - ) von b-bild (gsus) und power-doppler-aktivität (pdus; baseline, monate). klinische parameter: anzahl druckschmerzhafter und geschwollener gelenke (tjc , sjc ), visuelle analogskala, das -crp, health assessment questionnaire haq. für jede followup-visite erfolgte eine kategorisierung des klinischen ansprechens nach eular-response-kriterien und der für die psa validierten minimal-disease-activity(mda)-kriterien (coates et al.). ergebnisse. baseline patienten, nach monate patienten, erkrankungsdauer ( ± , monate). patienten ohne therapie ( ), mit nsar ( ), steroid i.a. ( ) , dmards ( ), biologicals ( ). bei diagnosestellung zeigte sich eine signifikante korrelation zwischen dem us synovitis score und folgenden klinischen parametern: tjc (r= , ), scj (r= , ), das -crp (r= , ). nach monaten zeigte sich eine gute korrelation zwischen der relativen veränderung des us synovitis scores und der relativen veränderung folgender klinischer parameter: tjc (r= , ), haq (r= , ), pasi (r= , ), das -crp (r= , ). zu baseline waren von gelenken sonographisch auffällig, davon zeigten kein klinisches korrelat (subklinisch). nach monaten zeigten % der initial subklinischen gelenke einen unveränderten befund, % waren sonographisch nicht mehr auffällig und % wurden klinisch manifest. bei den klinischen respondern war der rückgang deutlicher ausgeprägt. schlussfolgerung. der ultraschall-synovitis-score korreliert mit klinischen aktivitätsparametern sowohl zum zeitpunkt der diagnosestellung als auch im krankheitsverlauf unter immunsuppressiver therapie. die subklinischen veränderungen bilden sich unter immunsuppressiver therapie zu einem großen teil zurück, deutlicher bei klinischen respondern. ein geringer anteil der initial subklinischen gelenke wird im verlauf klinisch manifest, in höherem maße bei klinischen non-respondern. t. diekhoff , k. hermann charité -universitätsmedizin berlin, radiologie, berlin einleitung. die gicht ist mit einer prävalenz von , - , % insbesondere in den industrieländern eine häufige erkrankungen, die mit gelenkschmerzen einhergeht. bei typischer symptomatik und laborkonstellation ist die diagnose der arthritis urica oft einfach zu stellen, ein atypisches beschwerdebild kann jedoch gelegentlich die abgrenzung zu anderen erkrankungen erschweren. besonders die kalziumpyrophosphat-kristallarthropathie (cppd oder pseudogicht), die selbst mit sehr variabler symptomatik auftreten kann, ist eine relevante differenzialdiagnose, besonders bei älteren patienten. methoden. mit der dual-energy-computertomographie (de-ct) steht ein modernes, innovatives verfahren zur verfügung, das eine detektion von harnsäurehaltigen weichteilverkalkungen ermöglicht und darüber hinaus eine sichere abgrenzung zu kalziumhaltigen verkalkungen gewährleisten kann. das prinzip der de-ct ist relativ simpel und seit längerem bekannt: die messung des untersuchungsvolumens mit zwei unterschiedlichen röhrenspannungen macht es möglich, einen schwächungskoeffizienten zu errechnen, der spezifisch für das untersuchte material ist. allerdings ermöglichten erst moderne cts mit zwei röntgenröhren die klinische anwendung. in jüngster zeit werden jedoch anstrengungen unternommen, die de-ct auch für ein-röhren-systeme verfügbar zu machen. ergebnisse. mit der de-ct können gichttophi sicher vom knochen aber auch von anderen verkalkungen getrennt und zum beispiel farblich kodiert dargestellt werden. im gegensatz zum konventionellen röntgenbild verspricht die de-ct jedoch nicht nur eine höhere sensitivität für tophöse veränderungen, sondern als schnittbildverfahren auch eine bessere abgrenzung und einordnung von anderen morphologischen veränderungen wie zum beispiel von erosionen. schlussfolgerung. dieser vortrag fasst die vor-und nachteile der de-ct in der detektion und abgrenzung von weichteilverkalkungen bei kristallarthropathien zusammen und gibt darüber hinaus einen ausblick auf zukünftige entwicklungen in diesem gebiet. background. anionic glycosaminoglycans interact with a variety of soluble and membrane bound molecules. chondroitin sulfate was shown to have anti-inflammatory properties but its role in arthritis is controversial. methods. we have analyzed the effect of chondroitin sulfate on collagen induced arthritis starting treatment before and after induction of arthritis and in mice with established arthritis. results. in all of these settings chondroitin sulfate significantly reduced the severity of arthritis. it prevented joint destruction, diminished the inflammatory infiltrate and reduced proinflammatory cytokines in joints and plasma. splenocytes restimulated with collagen produced less il- and more il- and il- . the beneficial effects of chondroitin sulfate were transient and closely correlated to the suppression of the collagen-specific humoral immune response. chondroitin sulfate, but not other glycosaminoglycans induced a direct btk and syk-dependent proliferation of b cells and markedly expanded the number of plasma cells in the spleen. in immunized mice chondroitin sulfate reduced the number of antigen specific plasma cells in the bone marrow and was able to suppress established humoral immune responses. conclusion. displacement of disease inducing plasma cells from the bone marrow might contribute to the beneficial effects of chondroitin sulfate and could be an attractive strategy to suppress antibody mediated autoimmunity. background. in rheumatoid arthritis a functional deterioration of the hpa-axis in form of inadequately low secretion of glucocorticoids in relation to severity of inflammation can be detected. the reasons for this phenomenon are not known. the purpose of this study was to find possible reasons responsible for adrenal insufficiency during arthritis. methods. da rats were immunized with type ii collagen in incomplete freund adjuvant to induce arthritis. plasma corticosterone was evaluated by ria and plasma acth by elisa. adrenal cholesterol was quan-titatively studied by sudan-iii staining and scavenger receptor class bi (sr-bi, the hdl receptor) by immunohistochemistry. fluorescent nbd-cholesterol uptake kinetics were analysed by flow cytometry. ultrastructural morphology of adrenocortical mitochondria and lipid droplets was studied by electron microscopy. results. initially increased corticosterone and acth levels were reduced to baseline levels in the later phase of the disease. serum levels of corticosterone relative to il- β were markedly lower in arthritic than control animals (inadequacy). cholesterol storage in adrenocortical cells and expression of sr-bi did not differ between immunized and control rats. however, number of impaired mitochondria largely increased during the course of arthritis (maximum on day ), and this was paralleled by reduced numbers of activated cholesterol droplets (inhomogenous droplets relevant for generation of glucocorticoids). in addition, number of normal mitochondria positively correlated with serum corticosterone levels. conclusion. this first study on adrenal reasons for inadequate glucocorticoid secretion in arthritis demonstrated impaired mitochondria and altered cholesterol breakdown paralleled by low corticosterone levels in relation to ongoing inflammation. justus-liebig universität gießen, kerckhoff-klinik gmbh, rheumatologie u. klinische immunologie, osteologie, physikalische therapie, bad nauheim, agaplesion markus krankenhaus, akademisches lehrkrankenhaus der johann wolfgang goethe-universität, klinik für orthopädie und unfallchirurgie, frankfurt/main, universitätsklinikum gießen und marburg, orthopädische klinik, labor für experimentelle orthopädie, gießen, universitätsklinikum gießen und marburg, orthopädie und orthopädische chirurgie, gießen, universitätsklinikum erlangen, medizinische klinik , rheumatologie und immunologie, erlangen background. obesity is a risk factor in osteoarthritis (oa), but there is limited information about the interaction between bone formation and adipose tissue-derived factors, the so-called adipokines. adipokines such as adiponectin, resistin or visfatin are associated with the pathogenesis of rheumatoid arthritis (ra) and oa. adipokines are produced also by other cell types than adipocytes in ra and oa joints, for example osteoblasts, osteoclasts or chondrocytes. however, in contrast to their joint-destructive role in ra, their role in oa joint remodeling is unclear. therefore, adipokine expression in osteophyte development and bone forming cells as well as their effect on these cells was analyzed. methods. osteophytes and bone were obtained from oa patients during joint replacement surgery. serial sections of bone tissue were stained (masson trichrome, trap) and scored from grade one (no ossification, mainly connective tissue and cartilage) to five (ossified, mineralized osteophyte, < % connective tissue, ossified remodeling zones). immunohistochemistry against alkaline phosphatase, collagen-type ii, adiponectin, resistin, and visfatin was performed. oa osteoblasts were stimulated with adiponectin and measurements of il- , il- and mcp- were performed in cell culture supernatants. results. adiponectin, resistin and visfatin were detectable in osteoblasts and all osteophyte grades. in non-ossified osteophytes (grade ), especially adiponectin and to a lower extend resistin and visfatin were localized in connective tissue fibroblasts. in ossified osteophytes (grade - ), resistin, visfatin and to a lower extend adiponectin protein expression was co-localized with osteoblasts. resistin and visfatin were expressed by osteoclasts. visfatin was found in chondrocytes of all osteophyte grades ( % of chondrocytes) and adiponectin was detectable in blood vessels. osteoblast stimulation with adiponectin increased the release of the inflammatory mediators il- ( . -fold), il- ( . -fold), and mcp- ( . -fold). zeitschrift für rheumatologie suppl · | conclusion. the expression of adiponectin and visfatin expression in osteophyte connective tissue and cartilage suggests their involvement in early osteophyte formation. resistin and visfatin expression by osteoblasts and osteoclasts in ossified osteophytes indicates a role in bone remodeling of osteophytes at later stages. osteoblasts respond to adiponectin stimulation with the release of inflammatory mediators. therefore, adipokines are most likely involved in osteophyte formation at different stages affecting different cell types of bone remodeling. free fatty acids contribute to promotion of arthritis k. frommer , a. schäffler , s. rehart , a. sachs , u. müller-ladner , e. neumann justus-liebig universität gießen, kerckhoff-klinik gmbh, rheumatologie u. klinische immunologie, osteologie, physikalische therapie, bad nauheim, universitätsklinikum regensburg, klinik und poliklinik für innere medizin i, regensburg, agaplesion markus krankenhaus, akademisches lehrkrankenhaus der johann wolfgang goethe-universität, klinik für orthopädie und unfallchirurgie, frankfurt/main background. obesity is a known risk factor for several arthritic diseases and mechanical stress has been shown not to be the only factor. due to increased levels of free fatty acids (ffa) in obese compared to nonobese individuals and due to the involvement of ffa in inflammatory cardiovascular and metabolic diseases, we hypothesized that ffa play a role in the promotion of arthritic diseases. therefore, we therefore investigated the effect of ffa on various effector cells of arthritis. methods. rheumatoid (ra) synovial fibroblasts (sf), osteoarthritis (oa) sf, psoriatic arthritis (psa) sf, human primary chondrocytes (hch), human osteoblasts (ob), human macrovascular (huvec) and microvascular (hbdmec) endothelial cells were stimulated in vitro with different ffa within their physiological range of concentrations. immunoassays were used to quantify ffa-induced protein secretion. sulfosuccinimidyl oleate sodium (sso) was used to inhibit fatty acid translocase (fat). results. ffa dose-dependently increased the secretion of the proinflammatory factors (il- , il and mcp- ) as well as matrix-degrading enzymes (mmp- and mmp- ) in rasf (e.g. for lauric acid [ µm] with rasf/il- : . -fold increase; il : . fold increase; mcp- : . fold increase; pro-mmp : . -fold increase; mmp- : . fold increase). saturated and unsaturated ffa had similar effects on rasf. however, saturated ffa induced strong secretion of il- in chondrocytes, while unsaturated ffa only had a weaker effect on this cell type. at µm, both saturated and unsaturated ffa significantly increased il- secretion by osteoblasts to a similar degree as for sf. a high concentration of ffa ( µm) significantly induced il- secretion in huvec and hbdmec, whereas a low concentration of ffa ( µm) did not have a significant effect (p> . ) on human endothelial cells. blocking ffa transport into rasf by using sso almost completely abolished the effect of palmitic acid on il- secretion. conclusion. ffa are not only metabolic substrates but can also directly contribute to articular inflammation and degradation mediated by various effector cells of arthritis. our data also show that ffa transport into the cell is required for ffa-induced effects in sf. background. chronically inflamed tissues in ra are characterized by local hypoxia and enhanced angiogenesis. the hypoxia inducible factor (hif)- and (hif)- serve as key regulators of adaptation to hypoxia thereby promoting both angiogenesis and metabolic adaptation of endothelial cells. to investigate the impact of hif- /hif- on the angiogenic and metabolic transcriptome under hypoxia ( % o ) versus normoxia ( % o ) we performed a knockdown of either hif- α or hif- α in human microvascular endothelial cells (hmec). methods. specific knockdown of either hif- α or hif- α was achieved using shrna-technology. angiogenic and metabolic transcriptome of hmecs was studied by performing an agilent human whole genome microarray under normoxia vs hypoxia. significantly regulated genes were allocated to angiogenic and metabolic processes using panther database. results. in comparison to normoxia the incubation of untransduced hmecs under hypoxia resulted in regulated angiogenesis related genes and regulated cellular metabolism related genes. in both hif- α and hif- α knockdown cells, hypoxia was still capable of inducing a differential gene expression pattern, but with a much less pronounced effect compared to control cells. analysis of angiogenesis related processes (vegf-pathway, hif-activation, egfr-pathway) showed that % of the differentially expressed genes are controlled by both hif- and hif- . another % of the regulated genes are controlled by hif- . the remaining % of regulated genes are under control of hif- . the differentially regulated genes involved in the cellular metabolism (atpsynthesis, glycolysis, tca-cycle) were found to be to % controlled by both hif- and hif- . the remaining % are dependent on the presence of hif- . conclusion. hif- and hif- are both key regulators of the adaptation of endothelial cells towards hypoxia with overlapping functions. however, they do differ in their capacity to regulate cellular energy metabolism and angiogenesis. this leads us to conclude that hif- affects angiogenesis via indirect effects on cellular energy metabolism as indicated by the regulation of metabolic transcriptome to one fifth. hif- does more influence angiogenesis directly via regulating the synthesis of proangiogenic factors (as has been previously shown).these findings provide new insights into the divergent regulation of angiogenesis in inflamed (hypoxic) tissues by hif- and hif- and are, therefore, considered to be of clinical relevance in ra. background. membrane bound glucocorticoid receptors (mgr) play a pivotal role in pathogenesis of chronic inflammatory diseases as indicated by clinical observations. patients with sle show high frequencies of mgr positive monocytes, sometimes even higher than found in patients with active ra. with increasing glucocorticoid dosages expression of mgr on monocytes of sle-patients is downregulated, suggesting a negative feedback loop to control glucocorticoid action. these receptors represent an effective target for diagnosis and monitoring of different inflammatory diseases, but a feasible detection method is still necessary. objectives. we compare two methods of high-sensitive immunofluorescence staining -the well established liposome procedure with the commercialized faser-technique. methods. hek t cells were cultured for h with/without µg/ml brefeldin a in a humidified incubator at °c. human cd positive t cells and cd positive monocytes were isolated via magnetic-activated cell sorting and subsequently cultured in rpmi . monocytes were incubated for h with/without µg/ml lps. for liposome based highsensitivity immunofluorescence staining cells were incubated with the monoclonal (digoxigenin conjugated) anti-gr antibody, followed by incubation with anti-digoxigenin/anti-biotin matrix. subsequently biotinylated cy liposomes were added. faser technique was performed as described by the manufacturer (miltenyi biotec). dead cells were excluded by adding pi before cell acquisition, using a bd facs calibur flow cytometer. the acquired data were analyzed using flowjo . . software. results. the human mgr, which cannot be reliably detected with conventional staining methods, is detectable with the liposome procedure as well as with the commercialized faser-apc technique. furthermore, the faser-apc-procedure is more sensitive ( . % vs . %) and more specific ( . % vs. . %) compared to the liposome technique. additionally, minor changes of mgr expression can also be demonstrated with the faser technique. the faser procedure shows technical advantages: the commercially available faser-apc-kit is performed according to a standarized protocol and is less time consuming compared to the liposome procedure. conclusion. the human mgr is easily detectable with the commercialized faser kits, which represent an alternative due to a consistent quality and a standardized production. this method facilitates the analysis of the role that mgr play in the pathogenesis of chronic inflammatory diseases and perhaps provoke new insights in glucocorticoid therapy. background. in previous studies we detected th-positive, catecholamine-producing cells in inflamed hypoxic synovial tissue. therefore, the aim of our study was to investigate the influence of hypoxia induced catecholamines on inflammatory responses in arthritis. methods. synovial cells of rheumatoid arthritis (ra) and osteoarthritis (oa) patients were isolated and cultivated under normoxia or hypoxia with/without stimulating enzyme cofactors of th and inhibitors of th. expression of th and release of cytokines and catecholamines was analyzed. the effect of th+ cells was tested by adoptive transfer into dba/ mice with collagen type ii-induced arthritis (cia). th+ cells were generated from mesenchymal stem cells by defined dopaminergic factors. results. hypoxia increased th protein expression and catecholamine synthesis and decreased release of tnf in oa/ra synovial cells compared to normoxic conditions. this inhibitory effect on tnf was reversed by th inhibition with alpha-methyl-para-tyrosine (αmpt). incubation with specific th cofactors (tetrahydrobiopterin and fe +) increased hypoxia-induced inhibition of tnf, which was also reversed by αmpt. adoptive transfer of th+ cells reduced cia in mice, and hydroxydopamine, which depletes th+ cells, reversed this effect. conclusion. in summary, this study presents that th-dependent catecholamine synthesis exhibits anti-inflammatory effects in human ra synovial cells in vitro, which can be augmented under hypoxic condi-tions. in addition, the anti-inflammatory effect of th+ cells has been presented the first time in experimental arthritis in mice. background. previously, we demonstrated that long-lived plasma cells contribute to the pathogenesis of antibody-mediated diseases and should therefore be considered as a promising therapeutic target in systemic lupus erythematous (sle). in bone marrow stromal cells expressing the chemokine cxcl organize these niches that provide for the plasma cell survival. cxcl is the ligand of cxcr expressed on plasma cells. in this study we investigated the contribution of cxcl -cxcr interaction to the longevity of plasma cells in the murine model of lupus. methods. plasma cells purified from spleens of nzb/w mice were incubated with the cxcr blocker amd and then adoptively transferred to immunodeficient rag −/− mice. after days we analyzed the number of plasma cells in bone marrow. furthermore, ova immunized nzb/w mice were treated intraperitoneally with amd after boost; anti-ova secreting plasma cells in bone marrow were checked on day and after boost. the effect of plasma cell depletion was investigated in nzb/w mice using amd alone or combined with bortebomib for two weeks. results. two weeks after adoptive transfer the number of plasma cells treated with amd was lowered by % in bone. after secondary immunization with ova the amd treatment resulted in a significant reduction of anti-ova secreting plasma cells in bone marrow by % on day and by % on day . after days the number of mhc class ii negative anti-ova secreting plasma cells significantly decreased by % in bone marrow of treated mice. amd efficiently depleted plasma cells including long-lived. after two weeks treatment, total plasma cell number was decreased by % in spleen and % in bone marrow; long-lived plasma cells were reduced by % in spleen and % in bone marrow. the combination of bortezomib with amd in nzb/w significantly enhanced the depletion of long-lived plasma cells compared to monotherapy. conclusion. cxcr blockade with amd can reduce the homing of plasma cells to the bone marrow and the survival of long-lived plasma cells. the combination of bortezomib with amd shows synergistic effects on plasma cell depletion. the findings highlight the importance of the cxcr -cxcl axis for the plasma cell niche. zeitschrift für rheumatologie suppl · | er. tnfr expression defines synovial tissue infiltrating cd + t cells in patients with rheumatoid arthritis k background. one hallmark of rheumatoid arthritis (ra) is the infiltration of the synovial membrane by cd + t cells. it has previously been shown that infiltrating cd + t cells differ from non-infiltrating ones in their increased expression of tnfr . furthermore, tnfr is expressed on a fraction of circulating cd + t cells from ra patients, but not from healthy controls. aim of the study was the characterization of tnfr + cd + t cells in patients with rheumatoid arthritis. methods. peripheral tnfr + cd + t cells from ra patients were analyzed by flow cytometry. the expression of naive and memory t cell markers (cd ra and cd ro), markers for t cell activation (cd , cd and cd ) and of icam- as well as the frequencies of the positive cells were determined. to identify the t helper cell signature of tnfr + cd + t cells, intracellular staining of the th , th and th master transcription factors t-bet, gata- and ror-γt, respectively, was performed. results. peripheral tnfr + cd + t cells have neither a preferential naive nor a memory phenotype, but showed higher expression of the activation markers cd , cd and cd than tnfr -cd + t cells. tnfr + cd + t cells express higher frequencies of the t-bet and rorγt than tnfr -cd + t cells. there is no difference in gata- expression between tnfr positive and negative cd + t cells. functionally, it has been shown that the cytokine tnf acts as chemokine to attract cd + t cells to the rheumatoid joints. beside this direct effect of tnf, there are known indirect effects of tnf including the upregulation of cell adhesion molecules like icam- . therefore, icam- expression of migrating tnfr + t cells was investigated. the results show, that migrating tnfr + t cells recovered from synovial tissue are more frequently icam- positive than non-migrating ones. conclusion. tnfr + expression characterizes cd + t cells functionally capable of infiltrating the rheumatoid synovium in an icam- dependent manner. the results show, that tnfr expression defines a pathogenic subset of activated cd + t cells with th and/or th signature in patients with rheumatoid arthritis. hypoxia increased the production of interleukin- β in lps-primed human monocytes n background. monocytes are major players in the innate immune system and are recruited to sites of inflammation, where the environmental conditions vary extremely compared to the interstitium under physiological conditions. for example, in rheumatoid arthritis the inflamed joints are severely hypoxic. this decreased oxygen level could be a triggering factor for the activation and survival of monocytes. aim of the study was to analyze the influence of hypoxia on lipopolysaccharide (lps)-induced cytokine production in primary human monocytes methods. immunomagnetically separated monocytes from the blood of healthy donors were cultured for h under hypoxic conditions ( % oxygen). results. cytokine measurement in the supernatant with elisa showed increased concentrations of interleukin- β ( . ng/ml vs. . ng/ ml, p= . ) and interleukin- ( . ng/ml vs. . ng/ml, p= . ), but not of tnf, after hypoxia and lps-stimulation. cleavage of the il- β proform to its active form is dependent on the assembly of the inflammasome and the recruitment of caspase- followed by their activation. when inflammasome assembly was blocked with high extracellular k+-buffer or by inhibiting intracellular ca-signalling with the ca-chelator bapta-am, hypoxia induced il- β release was abrogated. similarly, il- β release after culture under hypoxia was also abolished in monocytic thp -cells, which are genetically made deficient for the inflammasome components nlrp and asc. one activating signal for the inflammasome was shown to be the release of reactive oxygen species (ros), since mitochondrial ros staining with mitosox revealed an increased mitochondrial ros release under hypoxic conditions. accordingly, the induction of mitochondrial ros through decoupling of the electron transport chain with rotenone also triggered an increase of il- β release under normoxic conditions. analysis of blood monocyts from ra patients showed no difference in lps and hypoxia induced il- β release compared to healthy controls ( . ng/ml vs. . ng/ml). conclusion. this study shows, that hypoxia leads to the activation of the inflammasome, the recruitment of caspase- and the subsequent cleavage and release of interleukin- β in human primary monocytes. intracellular calcium mobilization and mitochondrial ros production were shown to be essential mechanisms triggering inflammasome assembly. background. cell-derived membrane-coated microparticles have been identified as important mediators in intercellular communication. during the process of apoptosis, dying cells start to dynamically release microparticles. polymorphonuclear neutrophils are the most abundant type of leukocytes, representing - % of all white blood cells. due to their very short lifespan, they are the source of massive amounts of apoptotic cell-derived microparticles (admps). while the interaction between neutrophils and t lymphocytes has been focus of extensive research, the influence of neutrophil-derived microparticles on t cells has not been analysed yet. in this study, we investigated the effect of membrane-coated microparticles released by apoptotic neutrophils on different t helper cell subsets. methods. different cd + t cell subtypes were sorted according to the expression of cd , cd , cd ra and cd ro and co-cultured with admps or apoptotic cell remnants purified from uv-irradiated neutrophils isolated from the peripheral blood of healthy donors. t cells were stimulated by okt and anti-cd antibodies and cell proliferation was measured by h-thymidine incorporation or pkh -staining. secretion of cytokines was quantified by elisa. results. admps released by neutrophils selectively suppressed the proliferation of cd +cd -cd + tc in a dose-dependant manner and prevented the upregulation of cd on the t cell surface, while maintaining the expression of cd . the secretion of tumor necrosis factoralpha (tnfα) by t cells stimulated in the presence of admps was significantly reduced. interestingly, in contrast to admps, the apoptotic cell remnants of neutrophils exerted no effect on t cells. the suppressive effect of admps could be completely abrogated by the addition of interleukin(il)- or il- or by the presence of cd +cd +cd + t cells. conclusion. neutrophil admps suppress the proliferation of cd +cd -cd + t cells under conditions of limiting il- and il- concentrations. this could represent an important mechanism to prevent inappropriate activation and expansion of resting t helper cells in the absence of sufficient stimulation and cytokine production. t. alexander background. recent reports have shown dysregulated micrornas in murine lupus models, among them increased expression of mirna- , which has been demonstrated to target the transcription factor foxo in activated cd + t cells. the loss of foxo activity in t cells is associated with spontaneous t cell activation, clonal expansion and autoantibody production, all of which are present in systemic lupus erythematosus (sle). methods. expression levels of microrna- and foxo were analyzed with rt-pcr in magnetic purified peripheral blood cd + t cells from patients with sle and healthy controls (hc). multicolor flow cytometry was performed to analyze cd + t cell expression for ccr , cd ra, ki- , foxp , the interleukin- receptor-α and phosphorylated stat- a (pstat ). analysis of serum il- levels was performed with elisa in sle patients and hc (r&d systems). results. mirna- was significantly upregulated in cd + t cells from sle patients compared to hc (median expression . × e- vs. . × e- , p= . ) while foxo mrna levels were decreased, yet without reaching statistical significance. analysis of ki- expression revealed an increased percentage of proliferating cd + t cells in sle ( . % vs . %, p= . ). overall, cd + t cellular proliferation in sle was associated with increased frequencies of cd ra-ccr -effector memory t cells and enhanced basal pstat levels (median mfi . vs . , p= . ), suggesting a recent stimulation with common gamma chain(γc)-signaling cytokines. in this regard, tcons from sle samples displayed decreased expression levels for the foxo target gene cd (mfi vs. , p= . ) and serum il- levels were significantly higher in sle compared to hc ( . pg/ml vs. . pg/ml, p= . ). conclusion. mir- expression has been shown to be dependent on stat activation and to promote clonal expansion of activated cd + t cells. our data suggest that enhanced il r/stat signaling mediates induction of mir expression, which in turn promotes the proliferation of tcons in sle. the relative contribution of il r/mir- /foxo axis on the enhanced proliferative capacity of sle tcons remains elusive and merit further investigation. collectively, our data provide new insights in the pathophysiology of t cell hyperactivity in sle and identifies mir- as a candidate target for future therapeutic approaches. background. cell activation and apoptotic cell death leads to the formation of membrane-coated vesicles (mcvs). mcvs have previously been identified as mediators of cell-to-cell communication and carriers of microrna. an impaired clearance of apoptotic debris caused by an increased rate of apoptosis or a defect in phagocytic-cell clearance has been observed in sle patients. in this study, we analyzed the microrna content of activated and apoptotic lymphocytes and their corresponding mcvs from both normal healthy donors (nhds) and sle patients. further we investigated the immunomodulatory effect of mcv uptake by monocytes. methods. microrna content of activated and apoptotic lymphocytes and corresponding mcvs of nhds and sle patients were compared in an agilent microrna array and validated by qpcr. apoptosis was induced by uvb-irradiation. mir- expression in monocytes after uv-mcvs engulfment was determined by qpcr. expression of mir- target protein tab- was analyzed by western blot. results. mir- * levels were decreased after apoptosis induction in lymphocytes and apoptotic mcvs compared to their viable correlates. mir- , mir- a and mir- b were decreased in apoptotic lymphocytes compared to viable ones but increased or not significantly changed in apoptotic mcvs compared to viable mcvs, indicating a directional transport of microrna into mcvs. mir- a was expressed at higher levels in viable sle lymphocytes and mcvs compared to nhds. mir- b expression was decreased in uv-lymphocytes and uv-mcvs of sle patients. functional assays confirmed higher mir- levels and consecutively decreased target protein levels in monocytes after engulfment of uv-mcvs. conclusion. within this study we could show an unequal distribution of distinct microrna into mcvs released by activated or apoptotic lymphocytes. further the microrna content was regulated in whole apoptotic cells after uvb-irradiation. this suggests a directional transport rather than a random distribution. thus, cells regulate their microrna as well as the microrna content within released mcvs. we could show a microrna and protein expression change in phagocytes after mcv engulfment. hence, our results suggest mcvs could serve as a transport vehicle for microrna to mediate cell-to-cell communication and influence intracellular processes in phagocytes. disturbances of this system might contribute to the pathogenesis of sle. results. we found in the spleens of nzb mice -times higher numbers of long-lived plasma cells and megakaryocytes compared to wildtype, in nzw mice equal numbers and in nzb/w mice numbers between those for nzb and nzw or wildtype. moreover, in the spleen a fraction of plasma cells clustered around megakaryocytes. we also detected a missense mutation in the c-mpl gene of nzb mice leading to an amino acid replacement within the essential tpo-binding site. upon tpo stimulation of splenocyte and bone marrow cultures nzb cultures responded significantly stronger resulting in the double amount of megakaryocytes compared to nzw cultures. conclusion. in summary, our data indicate that augmented megakaryopoiesis enables the accumulation of a greater number of autoreactive plasma cells in lupus prone nzb/w mice. thus, we assume that enhanced megakaryopoiesis and higher megakaryocyte numbers are contributing to the development and/or pathogenesis of sle. background. baff is a cytokine important for the stimulation and survival of autoreactive b cells and therefore might play a role in several autoimmune diseases, e.g. autoimmune arthritis. in psoriasis arthritis, baff correlates with disease activity and testosterone, but only in male patients, suggesting a role for sex hormones in the regulation of baff. therefore, we wanted to determine if baff production in rheumatoid arthritis and osteoarthritis fibroblasts was regulated by neuroendocrine mediators. methods. fibroblasts were isolated from synovial tissue of ra (n= ) and oa (n= ) patients and cultured in vitro under different conditions. baff was determined by elisa. results. isolated fibroblasts were cultured in the presence or absence of interferon-gamma (ifn-γ), il- , lipopolysaccharide (lps), tumor necrosis factor (tnf), cpg, poly i:c, and cortisol in different combinations for and hours to determine the optimal stimulation strategy for induction of baff production (measured by elisa in supernatants) in fibroblasts. ifn-γ best induced baff in ra and oa fibroblasts. ifn-γ-induced baff production in fibroblasts was decreased by dihydrotestosterone in a concentration dependent manner. the effect was specifically inhibited by nilutamid, a testosterone receptor antagonist. furthermore, stimulation of beta-adrenoceptor increased, whereas stimulation of alpha-adrenoceptors did not change inf-γ-induced baff in synovial fibroblasts. in general the effects were more pronounced in ra as compared to oa fibroblasts. conclusion. taken together, inf-γ-induced baff production in synovial fibroblasts is decreased by testosterone and increased by betaadrenergic stimuli. therefore, neuroendocrine regulation of inflammation in the inflamed joint might be in part mediated by regulating baff production in synovial fibroblasts. a. grützkau , c. kyogoku , b. smiljanovic , j. grün , r. biesen , t. alexander , f. hiepe , a. radbruch , t. häupl deutsches rheuma-forschungszentrum (drfz), berlin, charité -universitätsmedizin berlin, medizinische klinik mit schwerpunkt rheumatologie und klinische immunologie, berlin background. gene expression profiling experiments using peripheral blood mononuclear cells (pbmcs) revealed a crucial role of type i interferon (ifn) in the pathogenesis of systemic lupus erythematosus (sle). however, it is almost unknown how particular leukocyte subsets contribute to the overall type i ifn signature described for pbmcs. furthermore, a detailed analysis of how ifn signatures differ in autoimmune disease from that observed after viral infection is missing so far. therefore, we compared expression levels of ifn signature genes in peripheral cd + t helper cells and monocyte (mo) subsets isolated from patients with sle, healthy donors (nd) and nd vaccinated against yellow fever by global gene expression profiling. methods. peripheral blood from patients with sle and nd were recruited. same nd were examined before and after immunization by yellow fever vaccine. after sorting cells, isolated rna were applied to affymetrix human genome u plus . array. data analysis was done using bioretis database, genesis software and ingenuity pathway analysis (ipa). results. comparing gene expression profiles of yellow fever immunized individuals and active sle patients it was possible to identify a "common" and an "autoimmune-specific" ifn signature. although major ifn signature genes were commonly expressed in cd + t cells and mo of patients with sle and immunized nd, expression magnitudes of them were higher in patients with sle compared to immunized nd. in sle, in addition to the typical "viral-induced" ifn signature, genes that are involved in apoptosis signaling, antiviral pkr signaling, fcγ receptor-mediated phagocytosis and il- -/il- -/il- -mediated jak/ stat signaling pathways were identified by ipa. conclusion. this study demonstrated that ifn signature in autoimmunity and that in viral infection are quite different in the number of ifn-related genes activated and their expression magnitudes. autoimmunity is characterized by a much stronger expression of ifn signature genes and is obviously modulated by a separate set of co-regulated genes defining the "autoimmune-specific" ifn signature. in summary, "common" and "autoimmune-specific" ifn signature genes are of potential interest as clinical biomarkers in sle diagnostics to differentiate between a disease flare and a viral infection. of peripheral blood lymphocytes (pbl). there is currently no data available about nk cells in gpa. the aim of this study was to evaluate the presence of nk cells in gpa granulomas and their proportions in pbl as a basis for a potential role in gpa. methods. paraffin sections of granulomas of gpa, sarcoidosis and tuberculosis patients were stained with a cd monoclonal antibody. nk cell (cd -cd +) proportions of pbl in gpa patients and healthy controls (hc) were analysed by facs analysis. clinical data was extracted from medical records. results. contrary to granulomas from tuberculosis and sarcoidosis which showed a considerable infiltration by cd positive cells, there was not a single cd positive cell in granulomas from gpa patients. therefore, the tissue destructive character of gpa granulomas is associated with a lack of nk cells. gpa patients with inactive disease [birmingham vasculitis activity score (bvas) = , n= ] possessed a significantly higher nk cell proportion in pbl (mean ± standard deviation: . ± . %) than both gpa patients with active disease (bvas> , n= , mean= . ± . %) (p= . ) and hc (n= , mean= . - . %, p= . ). thus, clinical remission is accompanied by an increase in the nk cell proportion in pbl. interestingly, patients with inactive disease that had "normal" nk cell proportions of less than % of pbl (n= ) showed a more severe disease course than those with more than % of pbl. conclusion. nk cells might, therefore, be helpful to limit granulomatous inflammation. whether nk cell proportion in pbl might be a useful biomarker in gpa, e.g. as predictor for relapses, will be further evaluated in our future studies. v. gerl background. plasmacytoid dendritic cells (pdcs) are considered a crucial element in sle pathogenesis due to their potency to produce high levels of ifn-α. this innate immunological function of pdcs is lost by terminal differentiation into a professional antigen-presenting cell (pdc-derived dc), thereby upregulating costimulatory molecules and downregulating innate characteristics, e.g. bdca- and ifn-α expression. pdc-derived dcs have not been described in vivo yet, probably due to the fact that they lose their specific markers during differentiation. furthermore, pdcs can differentiate into myeloid dcs by various stimuli. in sle, where low expression of bdca- is commonly seen, this differentiation could be relevant and point to such a lineage switch as well as to an activated state of pdcs. aim. to characterize pdc subsets of differentiation/activation in human peripheral blood and to study their impact on autoimmune inflammation in sle. methods. -color-flowcytometric analyses were performed on whole blood of healthy donors and sle patients. pdcs were identified by cd -/cd -/cd -/cd high//bdca- +/hla-dr+ expression and characterized for cd c, bdca- and the macrophage-associated siglec- , expressed on monocytes of active sle patients in an ifn-α dependent manner. cd and cd expression were measured in parallel. results. we found a small subpopulation of siglec- expressing pdcs in human peripheral blood. compared to siglec- negative pdcs, siglec- positive pdcs express significantly lower bdca- and cd , higher hla- dr background. agonistic autoantibodies against the angiotensin ii receptor type (at r) and the endothelin receptor type a (etar) have been identified in patients suffering from systemic sclerosis (ssc). here we examined the expression of at r and etar in human immune cells and pathological effects mediated through these receptors by corresponding autoantibodies (aabs). methods. at r and etar protein expression on peripheral blood mononuclear cells (pbmcs) from healthy individuals and ssc patients was analyzed using flow cytometry, mrna expression was examined by real-time pcr in pbmcs from healthy donors. in addition, pbmcs from healthy donors were stimulated in vitro with affinity-purified immunoglobulin g (igg) fractions from ssc patients positive for at rand etar-aabs, and with igg from healthy donors serving as control. alterations in cell surface marker expression, cytokine secretion and chemotactic motility were analyzed using flow cytometry, elisa, and chemotaxis assays, respectively. results were correlated with characteristics/clinical findings of the igg donors. results. both at r and etar were expressed on human peripheral lymphocytes and monocytes. protein expression of both receptors was decreased in ssc patients when compared to healthy donors and correlated negatively with disease duration. in addition, igg fractions of ssc patients induced t cell migration in an anti-at r and anti-etar aab level-dependent manner. moreover, igg of ssc patients was capable of stimulating pbmcs to produce more il- and ccl than igg of healthy donors. all effects could be significantly abrogated by the application of selective at r and etar antagonists. statistical analysis revealed a negative correlation between ssc igg-induced il- concentrations and disease duration, between ssc igg-induced ccl concentrations and time since onset of lung fibrosis as well as an association of ccl concentrations with vascular complications of the corresponding ssc igg donors. conclusion. we demonstrated the expression of both, at r and etar, on human peripheral t cells, b cells and monocytes and found signs for a chronic receptor activation in ssc patients. the inflammatory and profibrotic effects upon aab stimulation in vitro, and their associations with clinical findings suggest a role for autoantibody-mediated activation of immune cells mediated through the at r and etar in the pathogenesis or even the onset of the disease. the bioenergetic role of hif- and hif- during angiogenesis of human microvascular endothelial cells background. hypoxia and angiogenesis are features of inflamed and injured tissues. the transcription factors hypoxia inducible factor (hif)- and (hif)- regulate the cellular and metabolic responses to reduced oxygen tensions thereby promoting angiogenesis with implications on the pathogenesis of ra. we investigated the effects of a knockdown of either hif- α or hif- α in human microvascular endothelial cells (hmec) on angiogenesis and bioenergetics under hypoxia ( % o ) versus normoxia ( % o ). methods. specific knockdown of either hif- α or hif- α was conducted by shrna-technology. to assess angiogenesis of hmecs both tubuli and node formation under hypoxia versus normoxia were investigated. expression of hypoxia driven genes involved in the metabolic response to hypoxia (gapdh/pgk/glut /ldha) was quantified by realtime rt-pcr. the bioenergetic status of the cells was quantified via atp/adp measurements. results. knockdown of hif- α/hif- α resulted in a loss of hypoxia induced angiogenesis. focusing on bioenergetic aspects, we found hypoxia to significantly induce pgk, ldha and gapdh in control cells. knockdown of hif- α and hif- α, respectively, did not affect the hypoxic induction of pgk and ldha. in hif- α and hif- α knockdown-cells, hypoxia was still capable of inducing gapdh, with a less pronounced effect in hif- α knockdown-cells. hypoxia did not significantly up-regulate glut , neither in control nor in hif- α or hif- α knockdown-cells. the knockdown of hif- α resulted in significantly decreased expression of glut under hypoxia. we also found the atp/ adp ratio to be similar in control, hif- α and hif- α knockdown-cells under normoxia. under hypoxic conditions hif- α knockdown-cells showed significantly reduced atp/adp ratios -indicating that less atp is available -compared to hif- α knockdown-cells. conclusion. hif- α and hif- α are both key regulators of angiogenesis. however, they do differ in their potency to regulate cellular energy metabolism. this leads us to conclude that hif- α does directly influence angiogenesis via regulating the synthesis of proangiogenic factors (as previously shown), whereas hif- α affects angiogenesis via effects on cellular energy metabolism as indicated by the reduced expression of gapdh and the diminished atp/adp ratio. these findings provide new insights into regulation of angiogenesis in inflamed (hypoxic) tissues and are, therefore, considered to be of clinical relevance in ra. low baseline complement levels, autoantibody persistence and delayed thymic reactivation are risk factors for development of relapses after hematopoietic stem cell transplantation for refractory sle background. our previous research has provided the evidence that an autoreactive immune system can be "reset" into a healthy, tolerant state by immunoablative treatment to eradicate pathogenic effector cells, followed by transplantation of hematopoietic progenitor cells (hsct). nevertheless, disease flares may occur in a subset of these patients posttransplantation. here, we longitudinally analyzed the immune reconstitution of these patients to identify markers for favorable long-term responses. methods. since , patients with refractory sle received a cd +selected autologous stem cell transplantation after immunoablation with antithymocyte-globulin (atg) and cyclophosphamide as part of a monocentric phase i/ii clinical trial. autoantibody titers were evaluated with elisa, peripheral t-and b lymphocyte subsets immunophenotyped using multicolor flow cytometry. results. clinical remission (sledai ≤ ) could be achieved in all patients, despite immunosuppressive drug withdrawal, associated with disappearance of anti-dsdna antibodies and marked reduction of protective antibodies in serum. unfortunately, two patients died due to transplant-related infections. from the remaining eight patients, five patients are in long-term clinical remission for up to years after hsct, while three patients suffered a relapse of sle at , and months post-transplantation, respectively. patients with early relapses (≤ months) had decreased baseline complement levels, showed persistence of antinuclear antibodies (ana), less significant reduction in protective antibody levels and had slower repopulation of cd + cd ra+ thymic-derived cd + t cells after hsct (< /µl at months) when compared to long-term responders. in addition, flow cytometric analyses revealed an expansion of circulating plasmablasts and increased coexpression of siglec- on monocytes (as surrogate marker for type-i interferon signature), preceding the clinical flares by ~ months. conclusion. low baseline complement levels, persistence of ana and delayed thymic reactivity post-transplantation could be identified as risk factors for development of lupus flares after hsct. since atg-mediated cell lysis is complement-dependent, we conclude that low serum complement is directly associated with incomplete depletion of immunologic memory cells in these patients, which provides a rationale for complement substitution before immunoablation. moreover, lupus flares may be predicted individually by flow cytometry with plasmablast expansion and recurrence of type-i interferon signature. background. systemic lupus erythematosus (sle) is a chronic autoimmune disease characterized by the generation of pathogenic antibodies directed against a variety of autoantigens. we have previously shown that long-lived autoreactive plasma cells can contribute to chronicity and refractoriness of sle. our study is aimed to develop new methods for depletion of long-lived plasma cells in nzb/w mice, a model of sle. methods. we studied different treatment protocols on plasma cell survival: irradiation-based and more selective depletive treatments. - week-old nzb/w f mice were exposed to three different irradiation doses ( , , and gy in two splitted doses with a -h interval). the following protocols were also investigated: ) two bortezomib (bz) injections ( , mg/kg, i.v.) combined with anti-mouse cd ( mg/kg, i.v.), ) three bortezomib injections combined with anti-mouse cd , ) three bortezomib injections combined with anti-lfa- and anti-vla- antibodies (affecting directly the plasma cell niche; µg, i.p.) in a -d interval, plus anti-mouse cd and anti-b ( µg, i.v.). the plasma cells were analyzed in spleen and bone marrow by facs and elispot. results. the frequency of remaining plasma cells in bone marrow after , and gy irradiation were , and , % respectively, and in spleen were almost , and , %. short-term treatments with agents that affect plasma cells (bortezomib, anti-lfa plus anti-vla ) effectively deplete plasma cells including long-lived plasma cells in spleen and bone marrow of nzb/w mice. because of the b cell hyperactivity in nzb/w mice, we observe a rapid regeneration of autoreactive plasma cells in spleen and bone marrow. therefore, plasma cell depletion protocols were combined with b cell depletion. especially, the combination of plasma cell targeting with bortezomib, anti-lfa and anti-vla with b cell targeting (anti-cd plus anti-b ) interrupted the repopulation of autoreactive plasma cells in spleen and bone marrow. conclusion. very high doses of irradiation result in effective depletion of long-lived plasma cells but lower doses not. depletion of long-lived plasma cells can be achieved by the proteasome inhibitor bortezomib and by targeting both adhesion molecules lfa and vla . the combination with b cell depletion is needed to prevent regeneration of autoreactive plasma cells. varicella-zoster-virus(vzv)-specific lymphocytes and igg antibody avidity in patients with juvenile idiopathic arthritis or rheumatoid arthritis background. varicella zoster virus (vzv) is a herpes virus that establishes a life-long latent infection with risk of reactivation (shingles) particularly in immunosuppressed patients with autoimmune disorders. patients with rheumatoid (ra) or juvenile idiopathic arthritis (jia) have a high risk for disseminating varicella zoster virus (vzv) infection or herpes zoster. this study was aimed to investigate the humoral and cellular immune response to vzv including assessment of igg-anti-vzv avidity and vzv-specific reactivity of lymphocytes in ra (n= ) or jia patients (n= ) on different treatments, including biologic agents, such as anti-tumor-necrosis-factor(tnf)-alpha or anti-interleukin- (il- ) receptor inhibition (tocilizumab), compared to healthy adults (ha) and children (hc). methods. igg-anti-vzv concentrations and avidities were quantified by an adapted elisa. vzv-specific interferon-gamma-producing lymphocytes (spot forming units, sfu/ , , cells) were analyzed by elispot. results. no significant differences in the vzv-igg concentrations or avidities were found between the groups. however, lower igg-anti-vzv concentrations were found in tocilizumab-treated ra compared to ha and ra without biologic agents. ra showed lower median sfu ( / , , cells) than ha ( / , , cells), with lowest sfu in adalimumab-treated ra ( / , , cells). sfu were not altered in tocilizumab-treated ra and after incubation with anti-il- in vitro. no differences regarding igg-anti-vzv concentrations, rai and cellular reactivity were found between jia and hc. conclusion. our study demonstrated that ra and jia patients are still able to maintain humoral and cellular immune responses to vzv despite immunosuppressive therapy or biologic agents. in ra, the role of lower cellular reactivity for risk of herpes zoster has to be considered for recommendations on vaccination. cmv-specific cd + t cells from ra patients contribute to autoimmune disease zeitschrift für rheumatologie suppl · | . increased frequency of lir- (also called cd j or ilt ) on cd + t cells has been associated with autoimmune disease. furthermore, it has been shown that latent cytomegalovirus (cmv) infection contributes to the expansion of cd − t cells. hence we were interested in the influence of cmv infection on the lir expression on t cells in ra patients. methods. we were interested in the role of lir + t cells in ra patients, which potentially contribute to the autoreactive t cell pool, especially in cmv+ patients. therefore, we investigated the expression and function of lir- on cd + t cells in peripheral blood mononuclear cells (pbmc) from patients with rheumatoid arthritis by flow cytometry and cytotoxicity assay. results. flow cytometry analysis revealed higher frequencies of lir- + cd + t cells in cmv seropositive ra (n= , mean%: . ) compared to cmv+ hd (n= , mean%: . , p= . ). using hla-a* /cmvpp dextramers we analyzed cmv-specific cd + t cells. patients with ra had higher frequencies of cvm specific cd + t cells (n= ; mean%: . ) compared to healthy individuals (n= ; mean%: . , p= . ). phenotypically, cmv-specific cd + t cells are mainly cd negative and express lir- . analysis of the cytolytic potential by cd a expression revealed higher numbers of cd a+cd + t cells in ra patients (n= , mean%: , ) compared to healthy donors (n= , mean%: , ). importantly, we found a significant correlation (p= . ) of high numbers of cd +lir- + t cells with high disease activity score (das ) in ra patients without immunosuppressive treatment (n= , r= , ) . tab. . conclusion. this is the first demonstration of significantly increased frequencies of lir- +cd + t cells and of cmv-specific cd + t cells in patients with rheumatoid arthritis. these cells are characterized by a terminally differentiated phenotype. the higher cytolytic potential of cmv-specific t cells likely can be attributed to their function in containing latent cmv infection and to prevent cmv disease, but might potentially contribute to disease severity in ra patients. background. systemic lupus erythematosus (sle) is an autoimmune disease characterized by an acquired il- deficiency, which leads to a homeostatic imbalance between regulatory t cells (treg) and effector t cells (tcon; humrich et al. ). we recently demonstrated that treg homeostasis in lymphoid organs of diseased (nzbxnzw) f mice can be restored by treatment with recombinant il- (il- ) resulting in an amelioration of kidney disease. the aim of this study was to investigate the impact of il- therapy on intrarenal foxp + treg and kidney infiltrating conventional cd + t cells (tcon) in the (nzbxnzw) f mouse model of lupus nephritis. methods. (nzbxnzw) f mice with active nephritis were treated with recombinant il- either for a short period of days or for a longer period of days in total. absolute numbers, phenotype and proliferation of kidney infiltrating cd + t cell subsets were determined by flow cytometry at different time points. results. short-term il- treatment resulted in an enhanced proliferation and increased numbers and frequencies of intrarenal cd +foxp + treg compared to untreated control mice. on the other hand, long term il- treatment did not result in a persistent expansion of the intrarenal foxp + treg population. however, total numbers of kidney infiltrating cd + tcon with a memory/effector phenotpye were diminished and cd + tcon showed markedly reduced signs of cellular activation. conclusion. our data indicate that short term il- treatment is able to expand the size of the intrarenal treg pool. in contrast, long term il- treatment decreases the numbers of kidney infiltrating memory/ effector t cells and reduces cellular hyperactivity suggesting that treg suppress the activation and expansion of infiltrating tcon. these results may in part explain the amelioration of disease induced by treatment with il- and underline the important role of intrarenal treg for the suppression of kidney disease in lupus mice. these results also provide additional important rationales for an il- based immunotherapy of human disease. from transcriptome to protein biomarkers in ra: joint compartment and monocytes outperform serum and whole blood background. a main challenge in disease-management of ra is to establish objective criteria relevant for diagnosis and therapeutic stratification of patients. this study focused on global approaches in dissecting inflammation in ra including transcriptome analyses of synovial tissue and blood monocytes and proteome analyses of synovial fluid and serum. methods. gene-expression profiles from synovial tissues and blood monocytes of ra and osteoarthritis (oa) patients were generated by affymtetrix arrays. elisa and multiplex immunoassays were used for validation of candidate markers at the protein level in synovial fluid (sf) from ra and oa patients and in serum from the same group of patients and healthy donors. results. transcriptome analyses of synovial tissues from ra and oa revealed more than differentially expressed genes. to avoid difficulties in sampling synovial tissue and to avoid fluctuation in cellular composition of various cell types in blood, the transcriptome analyses from peripheral blood was focused on a specific cell population. monocytes were selected as the favourable cell type involved in the production of cytokines, which are often considered as therapeutic targets in ra. comparisons between ra and oa monocytes disclosed differential expression of more than genes. in total, genes that were up-regulated in synovial tissues and/or monocytes were used for validation at the protein level as potential biomarkers for ra. among these biomarkers, chemokines (cxcl , ccl , ip ), adhesion molecules (vcam , icam , e-and p-selectins), proteolytic enzymes (mmp , a at), and the shedding form of cell surface molecules (cd , cd ) background. idiopathic membranous nephropathy (imn) is a common cause of nephrotic syndrome in adults and has recently been identified as an autoimmune-mediated disease [ ] . autoantibodies directed towards the m-type phospholipase a receptor (pla r) are fairly specific for idiopathic mn and only found to a small percentage in sera from patients with secondary mn [ ] . the outcome of patients with imn is quite diverse: about one third of patients have spontaneous remission, another third progress to require dialysis and the last third continue to have proteinuria without progression to renal failure. we performed serological profiles of imn patients in order to compare antibody profiles to antibody frequencies found in the normal healthy population and to hopefully identify factors that help to predict disease course in imn. methods. serum samples of patients with imn were assayed for a variety of autoantibodies by elisa, addressable laser bead immunoassay (albia) and to dsdna by crithidia luciliae assay. results. the prevalence of autoantibodies found in our imn cohort is summarized in tab. . anti-pla r antibodies were found in about % of imn patients whereas the frequency of other antibodies was mostly below %. the one exception is anti-dfs that was found in . % of imn patients. conclusion. the prevalence of anti-pla r positive patients in our imn cohort matches what has been previously described [ ] . the frequency of the other antibodies that we determined is comparable to what has been reported in the normal healthy population. it is important to note that anti-dfs antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases (sard; [ ] ) whereas anti-ro reactivity is often regarded as a marker for sard. the absence of anti-ro and the high prevalence of anti-dfs confirms that imn is a rather organ specific autoimmune disease. background. activity and the quality of movement belong to the most fundamental diagnostic parameters for neurobehavioural analysis but in the past it has been difficult to include this information into pre-clinical murine disease models. here we tested the applicability of a radiofrequency identification (rfid) based automated tracking system in the experimental murine model of ovalbumin induced arthritis. methods. c bl/ mice were immunized twice with cationized ovalbumin in freund's complete adjuvant and onset of arthritis was induced two weeks after the last immunization by direct injection of cationized ovalbumin into the knee joint of the right hind leg. severity of arthritis was assessed through measurement of joint swelling and evaluation of histological changes. additionally mice were implanted with a rfid transponder and throughout the experiment their activity level was monitored by an id-grid sensor plate placed underneath the homecage. results. the joint inflammation in the ovalbumin induced arthritis model showed a quantifiable impact on the activity levels of the mice. our experiments could also show that movement activity correlates with disease severity as evaluated by clinical and immunological parameters. in the past employing behavioral methods was often limiting by group size, observation time and reproducibility and the stress of handling and new surroundings made results difficult to interpret. in our experiments a rfid-based automated tracking system allowed us to monitor individual activity long-term without removal of the mice from their homecage environment. this allowed for the correlation of clinical parameters to behavioral factors and adds another level of analysis to an established murine model. progranulin antibodies in a wide spectrum of autoimmune diseases results. autoantibodies against progranulin, a secreted and direct inhibitor of tnf-α receptors & were frequently identified in primary vasculitides. in detail, progranulin-antibodies were found during the course of disease in giant cell arteritis/polymyalgia rheumatica ( / ), takayasu's arteritis ( / ), classical panarteritis nodosa ( / ), behcet's disease ( / ), in granulomatosis with polyangiitis ( / ), churg-strauss syndrome ( / ) and in microscopic polyangiitis ( / ). in extended screenings progranulin-antibodies were also frequently detected in autoimmune connective tissue disorders, in rheumatoid and psoriatic arthritis and in inflammatory bowel disorders. in contrast progranulin-antibodies were only detected rarely in healthy controls ( / ), patients with obesity ( / ), residents of nursing homes ( / ), not in patients with cutaneously limited psoriasis ( / ), not in patients undergone sepsis ( / ), and not in patients with melanoma ( / ). a significant association of progranulin-antibodies with active disease states in granulomatosis with polyangiitis suggested a pro-inflammatory activity of progranulin-antibodies. this was supported by an observed neutralizing effect of progranulin-antibodies on the levels of circulating progranulin in elisa and western-blot. moreover, functional assays revealed, that progranulin-antibody containing sera render wehi-s cells far more sensitive to effects of administrated tnf-α, providing evidence for the suspected pro-inflammatory effect of progranulin-antibodies. conclusion. progranulin-antibodies occur in a widespread spectrum of autoimmune diseases and have a pro-inflammatory effect by neutralizing the physiologic tnf-blocker progranulin. background. flow cytometry (fcm) is widely used in research for molecular characterization at single cell level. conventional analysis is a semiautomated process of user defined gating and investigation in -d projections. for multiple parameter analysis with hundreds of marker combinations, this manual process is most limiting and impedes high throughput analysis. therefore, we developed a new algorithm for automated and standardized analysis of multiplex fcm data. methods. automation included asinh-transformation of data, cell grouping, population detection and population feature extraction. for grouping of cells, an unbiased unsupervised model based t-mixture approach with expectation maximization (em)-iteration was applied. populations were identified by meta-clustering of several experiments according to position and extension of cell-clusters in multi-dimensional space and by including a general procrustes analysis (gpa) step. for validation, peripheral leukocytes from healthy donors and patients with rheumatoid arthritis (ra) were prepared by hypoosmotic erythrocyte lysis and stained with different sets of lineage-specific antibodies. in parallel, different leukocyte samples were depleted of one of these populations by magnetic beads. qualitative and quantitative characteristics of major populations were compared with conventional manual analysis. results. whole blood leukocytes stained simultaneously with up to markers were correctly distinguished in all major populations including granulocytes, t cells and their subpopulations, monocytes, b cells, and nk-cells. the result was comparable to the "gold standard" of manual evaluation by an expert. the new technology is able to detect subclusters and to characterize so far neglected smaller populations based on the new parameters generated. automated clustering did not require fluorescence compensation of data. cell-grouping is applicable even for large fcm datasets of at least parameters and more than million events. comparing the cell-clusters between ra and healthy controls, differences were detectable in several cell (sub-)populations, stable enough to perform correct classification into controls and disease. conclusion. this new approach reveals promising results for automated and time-saving analysis of large datasets from multiplex fcm. the algorithm avoids operator-induced bias, is able to detect unexpected sub-clusters and to characterize so far neglected populations. this may reveal not only new markers for disease activity but also for therapeutic stratification. background. lasp- localizes at focal adhesions, along stress fibres and leading edges of migrating cells regulating metastatic dissemination of different tumors. since rasf have been implicated in the spreading of disease by leaving cartilage destruction sites, migrating via the bloodstream and re-initiating the destructive process at distant articular cartilage surfaces, the underlying mechanisms are of special interest. therefore, we investigated the role of lasp- in sf migration and its effects on ra. methods. to identify lasp- expression and its sub-cellular distribution in human sf as well as in hind paws of wt and htnftg mice, we performed western blots and immunofluorescence. the migration of sfs derived from wt, lasp- -/-, htnftg and lasp -/-/htnftg mice was studied in a modified scratch assay as well as in live cell imaging studies. furthermore, a transmigration assay using sf from all four genotypes and murine endothelioma cells (bend. ) as an endothelial barrier was carried out. sf transmigration under inflammatory conditions was also evaluated by tnf-alpha stimulation of the endothelial cells in vitro. results. lasp- expression was up regulated in rasf and in sf from htnftg mice compared to healthy controls and was found at structures of cell adhesion and invasion. the scratch assay as well as the live cell imaging studies showed a significantly reduced migration of lasp- ( ng/ml) was applied. in parallel, il- stimulation significantly amplified the expression of anti-apoptotic bcl- in sle treg but not tcon. conclusion. in analogy to our previous findings in lupus-prone mice, treg from sle patients show the classical hallmarks of il- deficiency with loss of cd expression and a homeostatic imbalance between treg and tcon. these findings could be associated with a reduced il- expression by cd + t cells in sle patients. on the other hand, low-dose il- stimulation in vitro could restore these defects, underlying the potential of il- as a novel therapeutic option in sle. the glucocorticoid-dependent modulation of immune-mediated inflammatory arthritis by osteoblasts in mice is t cell independent background. at present, the role of adiponectin in rheumatoid arthritis is still controversial. there is some evidence indicating anti-inflammatory effects, for example adiponectin reduces the tnf release by macrophages. in contrast to its anti-inflammatory role, adiponectin also exerts pro-inflammatory effects locally in joints, inducing for example pro-inflammatory factors and matrix-degrading enzymes in ra synovial fibroblasts. moreover, our immunohistochemical analysis of ra bone tissue showed a co-localization of adiponectin with key cells of bone remodelling (osteoblasts, osteoclasts). however, the role of adiponectin in bone remodelling of ra still needs to be defined. in this study, we therefore focussed on adiponectin and its immunomodulatory properties on ra osteoblasts and osteoclasts. methods. human osteoblasts and osteoclasts were isolated from bone tissue and blood samples of ra patients. immunocytochemistry and rt-pcr were used to analyze the expression of adiponectin and its receptors in osteoblasts and osteoclasts. osteoblasts and osteoclasts were treated with adiponectin ( µg/ml). adiponectin-mediated effects on the cytokine expression in osteoblasts and osteoclasts were analyzed using elisa. results. the expression of adiponectin and its receptors (adipor , adipor , and paqr ) by cultured ra osteoblasts and osteoclasts could be confirmed on translational and transcriptional level. stimulation of primary ra osteoblasts and osteoclasts with adiponectin resulted in an alteration of cytokine release. osteoblasts showed a time-and dose-dependent increase in il- production. furthermore, adiponectin induced the secretion of il- and gro-alpha and significantly increased the il- and mcp- production (il- : -fold, p= . ; mcp- : -fold, p= . ). stimulation with adiponectin resulted in an increase in il- production in pre-osteoclasts ( -fold) but not in osteoclasts. the secretion of il- was increased in pre-osteoclasts ( -fold) and osteoclasts ( -fold). the results of the present study confirm the pro-inflammatory potential of adiponectin in ra. the cytokines released after adiponectin treatment by osteoblasts and osteoclasts promote osteoclastogenesis or the migratory potential of osteoclasts and monocytes. together with the finding that adiponectin is present in the bone compartment of ra suggest an involvement of adiponectin in articular destruction. acknowledgement: funded by the german research society (spp , immu-nobone, ne / - ). novel mechanisms of glucocorticoid therapy in arthritis anti-inflammatory acting glucocorticoids (gcs) are an important component of rheumatoid arthritis (ra) therapy. but their beneficial usefulness, especially in ra therapy, is hampered by severe side effects like glucocorticoid-induced osteoporosis (gio). until now the molecular mechanisms underlying the beneficial and side effects of gc therapy are poorly understood. gcs exert their actions via the glucocorticoid receptor (gr) that alters gene expression by either binding as a dimer to gc response elements in the promoter region of target genes or by interacting with and thus interfering with other transcription factors. for a long time gr dimerization was considered as the molecular base of side effects. interference of pro-inflammatory transcription factors, such as ap- and nf-κb by the gr monomer was believed to contribute to the therapeutic effects of gcs. in a model of gio we previously showed that unexpectedly interaction of the gr monomer with ap- , but not nf-kb in osteoblasts is decisive for bone loss (cell metabolism : ). in contrast, in antigen-induced arthritis (aia), we could demonstrate that gcs act in the acute inflammation of ra via the dimerized gr. particularly, gc therapy suppressed th and th cell derived pro-inflammatory cytokines in a dimerization dependent manner. furthermore th , rather than th cells seem to be the most crucial targets for an efficient gc therapy since il- -/-mice were resistant to gc therapy whereas ifnγ-/-mice responded as efficient as wild type mice to steroid treatment (pnas : ). in a more chronic arthritis model, the k/bxn serum transfer induced arthritis, we demonstrate now that, unexpectedly, dimerization of the gr in non-hematopoietic cells also contributes to the anti-inflammatory effect of gcs. thus, for immunosuppression of arthritis the gr is required in distinct cell types. taken together, for anti-inflammatory actions the gr dimerization dependent gene regulation is decisive in ra, whereas gio depends on the suppression of ap- dependent gene expression. intriguingly for anti-inflammatory activities of gcs immune and non-immune cells are involved. our approaches give new insights into gc action on arthritis and bone that can be translated into new concepts for anti-inflammatory therapies preventing gio. background. new bone formation and ankylosis are a hallmark of ankylosing spondylitis (as). the impact of cytokines and different mechanisms of new bone formation (endochondral vs. membranous) to syndesmophyte formation and joint ankylosis in as are still poorly understood. in order to analyze cartilage hypertrophy -as a potentially important element of endochondral bone formation -and to assess the possible influence of cytokines, we performed an immunohistochemi-cal study of the hyaline articular cartilage of facet joints of as patients in comparison to autopsy controls and patients with osteoarthritis (oa). methods. the cytokines interleukin(il)- , il- and il- , as well as the marker of cartilage hypertrophy runt-related transcription factor (runx ), matrix metalloproteinase (mmp ) and collagen type (col ) were determined in facet joints from patients with as (undergone correction surgery of rigid hyperkyphosis), oa patients (undergone surgery of the lumbar spine, because of neurological deficits) and controls (autopsies without spinal diseases). immunohistochemistry was performed and the entire cartilage area was analyzed for the frequency of positively stained chondrocytes. background. immunization with glucose- -phosphate isomerase (g pi) induces arthritis in susceptible strains of mice. depletion of regulatory t cells (tregs) prior to immunization switches the usually acute, self-limiting course to a non-remitting, destructive arthritis. this provides a possibility to study molecular switches for the transition from acute, self-limiting to chronic, destructive arthritis within one mouse model. to examine the role of fibroblast-like synoviocytes (fls), which are known to modulate immune responses via the production of pro-and anti-inflammatory mediators, the phenotype and function of fls from mice with either acute, self-limiting or non-remitting, destructive arthritis was studied. methods. fls from dba/ mice that developed either the acute or the chronic form of arthritis were isolated from joints over a time course of days. to investigate the phenotype of fls elisa studies as well as zymography have been performed. for the functional clarification of those cells the matrix-associated transepithelial resistance invasion (matrin) assay and a cartilage attachment assay have been used. furthermore, fls have been transferred in vivo into the knee joints of immunodeficient mice and the joints have been scored histologically. results. fls from treg-depleted mice produced significantly more cytokines (e.g. interleukin (il- )) upon stimulation with other cytokines, growth factors and tlr ligands. this increased susceptibility to cytokine stimulation in chronic animals compared to acute ones is observable throughout the disease course ( days). furthermore, the secretion and activity of matrix metalloproteases (mmps) was enhanced in the fls from chronic mice compared to samples from acute ones. additional functional differences include the collagen-destructive potential and the potential to attach and eventually invade wild type cartilage. here, fls from treg-depleted chronic arthritic mice showed a higher invasive and destructive potential. ultimately, fls from treg-depleted mice were able to destroy cartilage in immunodeficient mice. conclusion. our results are compatible with the hypothesis that uninhibited inflammation in the early phase of treg-depleted mice causes the acquisition of an autonomously aggressive phenotype of synoviocytes which contribute to the switch from acute to chronic arthritis even in the absence of late support from t and b lymphocytes. collagen-induced arthritis modulates reactivity to sympathetic neurotransmitter stimuli during osteoclastogenesis of bone marrow-derived macrophages from da rats background. osteoclast(oc)-mediated bone destruction contributes to increased disease burden in rheumatoid arthritis. simultaneously, changes in synovial tissue innervation occur, leading to a reduction in catecholaminergic nerve fibres. studies on sweat gland innervation revealed that catecholaminergic fibres are capable of phenotypic transition to cholinergic nerves. the sympathetic neurotransmitters norepinephrine (ne) and acetylcholine (ach) affect osteoclastogenesis oppositely prompting us to study osteoclastogenesis at different phases of collagen-induced arthritis (cia) in an altered neurotransmitter microenvironment. methods. for induction of experimental arthritis, da rats were immunized with bovine collagen type ii while controls received isotonic nacl solution. to generate oc, bone marrow-derived macrophages (bmm) were isolated and differentiated with recombinant m-csf and rank ligand. the influence of ne and ach stimulation on osteoclast differentiation and activity was compared between arthritic and control animals at the acute ( days post immunization, pi) and the chronic ( days pi) disease state. as the nicotinic α ach receptor subunit is involved in the cholinergic anti-inflammatory reflex, we also applied a specific agonist, arr- . additionally, the gene expression profile for ne and ach neurotransmitter receptors was analyzed. results. ach stimulation generated significantly more osteoclasts in controls ( days pi). arr- mediated effects were similar to ach. ne decreased osteoclastogenesis via β-adrenoceptors and enhanced via α-adrenoceptor stimulation. cells from arthritic animals were less affected by ne and ach stimulation.oc from arthritic animals showed tendentially decreased activity in an enzymatic cathepsin k activity assay. ach and arr- stimulation decreased cathepsin k activity days pi, but the effect disappeared days pi, representing the chronic arthritis state. ne stimulation significantly inhibited enzyme activity days pi, but has little effect under chronic conditions. the receptor gene expression profile changed in the time course of arthritis. days past immunization muscarinic ach receptors m and m were significantly upregulated whereas after days adrenoceptors α d and α b were significantly downregulated. conclusion. we conclude that cia differentially modulates neurotransmitter influence during oc differentiation and activation but the underlying processes remain still unknown. the observed time pointdependent changes in neurotransmitter receptor gene expression may constitute a regulatory mechanism to counteract alterations in the local neurotransmitter composition. background. the generation of memory t lymphocytes allows effective and fast immune responses during antigen re-challenge and represents a hallmark of adaptive immunity. previous work from our group has demonstrated that murine memory cd + t cells reside in specific bone marrow niches and are characterized by the high expression of cd and ly- c. these cells were designated as resting in the context of gene expression and proliferation. here, we aimed to phenotypically and functionally characterize human memory t lymphocytes in peripheral blood and bone marrow of healthy individuals. methods. mononuclear cells were isolated from paired blood and bm samples from individuals undergoing hip replacement surgery. phenotypic analysis and cytokine profile of distinct memory t cell subsets were assessed by flow cytometry. proliferation and cell cycle status were analyzed using ki- and propidium iodide (pi) staining, respectively. results. distinct populations of cd -expressing cd +cd ra-and cd +cd ra-t cells were detected in bone marrow but not in the periphery. ccr and cd l expression was reduced on bone marrow cd +cd +cd ra-and cd +cd +cd ra-t cells compared to their cd -counterparts in bone marrow and peripheral blood. cell cycle analysis and ki- expression levels demonstrated the nonproliferative state of bone marrow memory t cells. furthermore, bone marrow resident memory t cells showed reactivity against various pathogenic agents, such as tetanus, measles and cmv. conclusion. we have identified a population of cd -expressing cd +cd ra-and cd +cd ra-t cells in the bone marrow. despite cd expression, which is generally regarded as early activation marker, the cells were resting in terms of proliferation. bone marrow cd + memory t cells have downregulated ccr and cd l indicating reduced homing capacity to secondary lymphoid organs. our data underline the role of the bone marrow as a major reservoir for resting memory t lymphocytes. therapeutic methods exerted an influence on satisfaction and future expectations in patients with rheumatoid arthritis (ra). methods. when visiting their rheumatologist, patients with ra were asked to complete a questionnaire at home after the consultation and then return it to an independent opinion research centre, where the data was collected and analysed. the form comprised various areas, namely demography, aspects of the diagnosis, medical care, therapeutic measures, and the illness in a personal context. results. patients ( females/ males) from the whole of austria with a particular emphasis on lower austria, upper austria and tyrol completed the questionnaire (of distributed), resulting in a response rate of %. % of the patients lived in settlements of under , inhabitants; a further % in settlements of under , inhabitants.. the rheumatologist attended could be reached within one hour for % of the patients and within minutes for %. in slightly fewer than % of the respondents the diagnosis was made within three months, in % within six months. in %, the diagnosis was made by a rheumatologist. after experiencing the first symptoms, % contacted their general practitioner. a high degree of satisfaction appears to originate from the information supplied by the rheumatologist attended. most patients felt they were involved in decisions regarding their therapy. % of the respondents were employed prior to their illness; as a consequence of the disease % had to leave their jobs. conclusion. the majority of the respondents came from rural areas. the correct diagnosis was made within six months for almost half of the patients questioned. most patients felt well informed by their rheumatologists and involved in therapeutic decision-making. , combinational therapy of synthetic dmards ( . ; . - . ), and biological-monotherapy ( . ; - ). all of these differed significantly on later observation periods. comparing the prescriptions separately by sequential treatments there were no differences in retention rates for the individual dmard classes. regarding retention, in the first treatment synthetic dmards showed the longest retention, but from the second on this was the case for tnfi-combinational treatment and non-tnfi-biologicals (. abb. ) conclusion. traditional dmards are the starting point of therapy and mtx is the anchor drug for the first and all subsequent courses. already at the second sequential course, the combination therapies of mtx+tnfi become numerically more relevant, and their retention is better than mtx. therapie der rheumatoiden arthritis im letzten jahrzehnt -was hat sich verändert? abb. | ev. anzahl eingeschlossener patienten nach einschlussjahren und therapie sowie zeitlichen entwicklungen im das und der eular-response cal features of ra (erosive arthritis with classical radiological features) plus specific laboratory markers (ccp-antibodies). the third patient, a -year-old female presented initially with features of ra and sle simultaneously (alopecia, subcutaneous nodules, leucopenia, positive ccp-antibodies, high titres of ana and dna-antibodies). the fourth patient, a -year-old patient presented with severe polyarthritis in the upper and lower limbs, subcutaneous nodules, fever and cervical lymphadenopathy, she had high titres of ccp-antibodies ( u/ml by a normal range of less than iu/ml), ana of (normal less than ), and dna of iu/ml (normal less than iu/ml). conclusion. the take home massage of this presentation is to be aware of rhupus if the sle patient develops erosive arthritis or subcutaneous nodules, or if the ra patient develops features of sle like leucopenia, active urine sediment, or clinically significant serositis. rhupus seems to be a distinctive entity and should be kept in mind while dealing with patients having ra or sle as it can affect the treatment and outcome. vorgeschichte. bei der abklärung eines akuten thoraxschmerzes sind auch seltene ursachen, so zum beispiel der einbezug thorakaler organe in eine entzündliche systemerkrankung, zu bedenken. anhand eines besonderen falles möchten wir den weg zur diagnose bei einem schwer kranken notfallpatienten zeigen. leitsymptome bei krankheitsmanifestation. ein -jähriger mann wird bereits zum dritten mal mit akuten thoraxschmerzen in die notaufnahme aufgenommen, jeweils war eine kardiale ischämie ausgeschlossen und ambulante diagnostik empfohlen worden. nach der schmerzcharakteristik, der vorgeschichte von rezidivierenden thoraxschmerzen und entsprechenden risikofaktoren wird bei massiver symptomatik jetzt von einem akuten koronarsyndrom ausgegangen und die invasive diagnostik durchgeführt. eine akute koronare ischämie kann jedoch ausgeschlossen werden. fieber, hohe entzündungszeichen, hinfälligkeit und gewichtsverlust von mehr als kg in den letzten wochen lassen dann eine infektbedingte oder tumorbedingte ursache vermuten, abdomensonographie und röntgen-thorax sowie ausführliches labor samt immunologie führen nicht weiter. wegweisende weitere organbefunde finden sich nicht. die behandlung mit antibiotika hat keinerlei effekt auf klinik oder entzündungsparameter. nach tagen wird der krankheitsverlauf kritisch evaluiert, eine nichtinfektiöse ursache der beschwerden wird in betracht gezogen, eine transösophageale echokardiographie wird zum ausschluss einer endokarditis und zur beurteilung der aorta (leitsymptome thoraxschmerzen und fieber!) durchgeführt. dabei zeigen sich die klappen sämtlich unverdächtig, die aorta ascendens weist eine massive echoarme wandverdickung auf. zum sicheren ausschluss eines intramuralen hämatoms wird sofort eine ct der thorakalen aorta durchgeführt, die eine ausgeprägte zirkuläre wandverbreiterung ohne hinweise auf dissektion zeigt. diagnose. riesenzellarteriitis mit aortitis. therapie. steroide, einleitung einer remissionsinduzierenden therapie mit cyclophosphamid boli. weiterer verlauf. innerhalb von tagen ist der patient beschwerdefrei, die entzündungsparameter sind halbiert, der bettlägerige patient lässt sich mobilisieren und verlässt nach tagen die klinik. bei der diffe-renzialdiagnose des akuten thoraxschmerzes sollten eine unklare entzündungsserologie und eine b-symptomatik frühzeitig an eine aortitis denken lassen. in diesem fall fand sich bereits in tee und ct ein ausgeprägter befund, der sich am ehesten durch den langen verlauf vor diagnosestellung erklären lässt. einleitung. die progressive familiär intrahepatische cholestase (pfic) gehört zu einer heterogenen gruppe seltener, autosomal rezessiv vererbter erkrankungen der gallensäurenexkretion mit intrahepatischer cholestase, hohem risiko der leberzirrhose bereits im kindesalter und hepatozellulärem karzinom. das auftreten eines sle bei pfic ist bisher in der literatur nicht beschrieben. methoden. wir berichten über eine jetzt -jährige patientin mit genetisch gesicherter pfic- (defekt der atp abhängigen gallensalz-exportpumpe bsep), biliostomaanlage im kindesalter, therapie mit udca und kontinuierlicher hepatologischer betreuung. / manifestierte sich ein sle mit az-minderung, florider polyarthritis, polyserositis, splenomegalie, anämie und leukozytopenie. die ana waren mit > : homogen erhöht, die dns-ak im elisa mit u/ml, ena und antiphospholipid antikörper waren negativ. eine steroidtherapie wurde mit prednisolon mg/tag begonnen. bei guter verträglichkeit und stabilen cholestaseparametern wurde die therapie um chloroquin mit mg an tagen der woche ergänzt. die betreuung wurde interdisziplinär fortgesetzt. ergebnisse. unter der steroidtherapie waren gelenkbeschwerden und serositis gebessert, das crp, die leukozytopenie und anämie normalisiert. die dns-antikörper fielen auf u/ml, c und c stiegen um %. es persistierten lediglich physiotherapeutisch behandelte muskuläre schmerzen und schonatmung nach pleuritis. bei steroidreduktion unter mg traten die gelenkbeschwerden wieder auf, die dns-antikörper stiegen auf u/ml und c /c fielen um %, das crp blieb normal. die steroiddosis wurde auf mg/tag und die chloroquindosis auf × mg/woche erhöht. neue organkomplikationen im rahmen des sle sind nicht aufgetreten. die gallensäuren waren mit µmol/l (norm < ) im jahr (letzte messung vor manifestation des sle) deutlich erhöht, bei manifestation des sle mit µmol/l bereits deutlich gebessert und unter hoch dosierter steroidtherapie mit , µmol/l nach woche sowie , µmol/l nach monat normalisiert. unter prednisolon mg/tag stiegen sie bei inaktiviertem sle auf µmol/l nach monaten an, bei steroidreduktion unter mg auf µmol/l. nach erneuter steroiddosiserhöhung auf mg prednisolon/tag fielen sie auf µmol/l ab. schlussfolgerung. die pfic- schützt nicht vor der manifestation eines sle. eine behandlung mit steroiden und chloroquin ist auch bei pfic sicher und wirksam. der floride sle und die höher dosierte steroidtherapie senken trotz bestehenden genetischen defekts unabhängig voneinander und synergistisch die gallensäurenspiegel im serum bei genetischer störung der atp-abhängigen sekretionspumpe bsep. augenentzündungen. eine ausgeprägte b-symptomatik mit fieber, nachtschweiß und abgeschlagenheit seit ca. zwei jahren hatte sich jeweils unter der therapie der hörstürze verflüchtigt. die mr-angiographie der aortenwand zeigte den typischen befund eines ausgeprägten wandenhancements der thorakalen aortenwand sowie der supraaortalen gefäße, duplexsonographisch fand sich eine zirkuläre wandverdickung der proximalen und mittleren acc beidseits ohne relevante stenosen. bei fehlendem nachweis zerebraler vaskulitischer oder embolischer veränderungen im kraniellen mrt und bei normalem eeg wurde der cerebrale krampfanfall als gelegenheitsanfall dd im rahmen der hochaktiven grunderkrankung interpretiert. diagnose. takayasu-arteriitis mit assoziiertem cogan-syndrom und rezidivierender polychondritis. therapie. steroidstoß, darunter rasche reduktion der entzündungszeichen und promptes ansprechen der b-symptomatik, beginn einer steroidsparenden therapie mit mtx. bei anhaltender krankheitsaktivität und hohem steroidbedarf wird der patient aktuell mit tocilizumab behandelt. schlussfolgerung. der präsentierte fall zeigt, dass mittels neuer bildgebender verfahren gelegentlich eine großgefäßvaskulitis detektiert werden kann, obwohl das klinische bild (hier: kopfklinik) eine kleingefäßvaskulitis vermuten lässt. das cogan-syndrom ist häufig mit einer großgefäßvaskulitis assoziiert, in diesem fall auch mit einer polychondritis. umgekehrt erweitert sich unser wissen um das befallsmuster der großgefäßvaskulitiden, die zwar überwiegend große, aber auch mittelgroße und kleine gefäße einbeziehen können. in unserem zentrum ist dies der zweite fall einer takayasu-arteriitis mit assoziiertem cogan-syndrom in einem kollektiv von fällen. diagnostik. im rahmen einer vorstellung in unserer rheumatologischen ambulanz zur abklärung eines möglichen sjögren-syndroms, konnte in der lungenfunktionsdiagnostik eine leichte restriktion und Überblähung festgestellt werden. in einem auswärtig durchgeführten mrt der halsweichteile zeigten sich die glandula parotis und submandibularis beidseits inhomogen und kräftig kontrastiert, ebenfalls mehrere grenzwertig große lymphknoten. aufgrund der erneut pathologischen lungenfunktion und dem verdacht auf eine lungenbeteiligung bei sjögren-syndrom erfolgte ein ct-thorax. hier zeigte sich eine zysti-sche rarefizierung vor allem der zentralen lungenanteile, differentialdiagnostisch mit einer langerhans-zell-histiozytose vereinbar. auch erschien der diabetes insipidus passend zur histiozytose. die immunologischen untersuchungen waren unauffällig, insbesondere konnten keine ssa-/ssb-antikörper oder eine hypergammaglobulinämie nachgewiesen werden. somit erschien ein sjögren-syndrom unwahrscheinlich. zur weiteren abklärung erfolgte eine bronchoskopie, in den biopsaten konnte immunhistochemisch eine langerhans-zell-histiozytose nachgewiesen werden. in einer pathologischen nachuntersuchung auswärtiger parotis-biopsate bestätigte sich diese, zudem konnte eine mutation des braf-proto-onkogens nachgewiesen werden. im abschließend durchgeführten pet-ct konnte eine vermehrte kontrastmittelaufnahme des hypophysenstiels, eine vermehrte stoffwechselaktivität der parotis beidseits sowie kutan axillär links diagnostiziert werden. abschließend lag somit eine langerhans-zell-histiozytose mit befall von hypophyse, lunge, parotis, haut, lymphknoten sowie einem fraglichen befall des darms vor. therapie. in absprache mit der adulten langerhans-zell-histiozytose studiengruppe erfolgt nun eine therapie mit cytarabin. weiterer verlauf. der weitere verlauf nach geplantem therapiebeginn bleibt abzuwarten. einleitung. die anti-gbm-erkrankung (goodpasture-syndrom) ist eine prototypische autoimmunerkrankung mit ernster prognose, wenn sie als "pulmorenales syndrom" mit der trias rapid-progressive glomerulonephritis, alveoläre hämorrhagie und nachweis von autoantikörpern gegen glomeruläre basalmembranen (anti-gbm-ak) auftritt. Über weniger aggressive verläufe ist wenig bekannt. in der literatur wird die bedeutung der frühen diagnosestellung für die prognose der patienten betont. wir berichten über eine -jährige patientin, die sich mit abgeschlagenheit, müdigkeit und blutbeimengungen im sputum vorstellt. sie betreibt einen nikotinabusus. methoden. wir sehen eine blasse patientin (hb , mmol/l, normochrom, normozytär), die keine weiteren auffälligen befunde in der körperlichen untersuchung zeigt. die apparative diagnostik mittels endoskopie und sonographie ergibt keine befunde, die die anämie erklären können; in der bronchoskpie zeigt sich das bild einer alveolären hämorrhagie ohne aktive blutungszeichen. neben der ausgeprägten anämie bestehen eine milde proteinurie mit mg/d sowie eine geringe erythrozyturie. die immunologische diagnostik ergibt gering erhöhte anti-gbm-ak, negative ana und anca. die nierenbiopsie zeigt eine rapid-progressive glomerulonephritis mit halbmondbildung in einem glomerulum, zusätzlich können lineare igg-ablagerungen in der immunfluorenz dargestellt werden. es ist ein glomerulum in der biopsie betroffen, die anderen glomeruli sind unauffällig. es bestehen einzelnen erythrozytenzylinder, diffuse entzündungszeichen lassen sich nicht nachweisen. die nachträglich durchgeführte immunfluoreszenz in der lungenbiopsie bestätigt den befund linearer igg-ablagerungen. ergebnisse. in unserem fall sehen wir eine junge patientin in einem relativ guten allgemeinzustand mit gering erhöhten anti-gbm-antikörpern und einer gering ausgeprägten nierenschädigung mit einem befallenen glomerulum in der biopsie. es wird angesichts des jungen alters der patientin und der geringen ausprägung der erkrankung eine therapie mit cyclophosphamid nach dem "euro-lupus-protokoll" von f. hossiau eingeleitet. im verlauf steigt der hb auf , mmol/l, die alveoläre hämorrhagie sistiert und die proteinurie ist rückläufig. schlussfolgerung. das goodpasture-syndrom mit einer inzidenz von , - , / mio. einwohner und jahr ist eine sehr seltene autoimmunerkrankung mit ernster prognose. möglicherweise spielen umweltfaktoren (hier: nikotinabusus) eine rolle für die manifestation der erkrankung. interessant ist, dass die erstbeschreibung im rahmen einer influenza-epidemie -wie auch in diesem jahr bei unserer patientinerfolgte. Über die therapie gibt es wenige informationen. die meisten empfehlungen gibt es zum pulmorenalen-syndrom, über weniger aggressiv verlaufende manifestationen gibt es nur wenige informationen. einleitung. wir berichten über einen -jährigen raucher mit akut aufgetretener polyarthritis und neu aufgetretenem raynaud-phänomen. auffallend war die diskrepanz zwischen nur geringer systemischer entzündungskonstellation und einer hochaktiven polyarthritis mit schwerem raynaud-phänomen. im verlauf kam es zu einer spontanen thrombophlebitis der v. cephalica. methoden. pathologische werte: crp maximal , mg/dl (norm < , ), zellzahl im gelenkpunktat . leukozyten/µl. im normbereich lagen: bsg mm/ h, ana, ena, ds-dns-ak, rheumafaktoren, anca, kälteagglutinine, kryoglobuline, tumorsuche initial ohne befund (ct-thorax, bronchoskopie, ct abdomen und becken, coloskopie, gastroskopie, skelettszintigraphie), fdg pet-ct: zwei suspekte lymphknoten rechts cervical sowie suspekte rechte tonsille. ergebnisse. selbst unter mg prednisolon weiterhin hochaktive polyarthritis. nach unauffälliger initialer tumorsuche veranlassten wir ein fdg-pet ct mit nachweis zweier suspekter lymphknoten rechts cervical sowie einer suspekten rechten tonsille. die biopsie der klinisch sich nur in der palpation diskret induriert darstellenden region ergab ein gering differenziertes, gering verhornendes plattenepithel mit %iger sequenzhomologie mit hpv typ . nach resektion des tumors und radiatio sistierten sowohl die polyarthritis als auch das raynaud-phänomen ohne weiteres rezidiv auch nach absetzen der glukokortikoide. schlussfolgerung. eine akut auftretende hochaktive polyarthritis mit hohem glukokortikoidbedarf in kombination mit einem raynaud-syndrom, auffallend niedriger systemischer entzündungsaktivität und fehlendem autoantikörpernachweis sollte insbesondere bei einem langjährigen raucher anlass zu einer intensiven tumorsuche geben. ein fdg-pet-ct kann bei okkulten tumoren zielführend sein. bemerkenswert ist hier der nachweis von hpv- im tumor als weiterer risikofaktor neben dem zigarettenrauch. methoden. bei der klinischen untersuchung fielen ein beidseits positives menell-zeichen und deutlicher klopfschmerz über dem lumbosakralen Übergang auf. labordiagnostisch konnte ein erhöhtes c-reaktives protein und ein positiver hla-b nachgewiesen werden. der bath ankylosing disease activity (basdai) index betrug , . die beckenübersichtsaufnahme zeigte eine definitive bilaterale sakroiliitis grad gemäß den modifizierten new-york-kriterien. der befund der kontrastmittelunterstützten mrt der iliosakralgelenke bewies das vorliegen einer bilateralen floriden sakroiliitis. bei gesicherter hla-b positiver ankylosierender spondylitis wurde die indikation zur einleitung einer biologikatherapie mit einem tnfα-inhibitor gestellt. während der abklärung von kontraindikationen wurde in der konventionellen röntgen-thorax-aufnahme eine rundliche, glatt begrenzte zystische läsion mit flüssigkeitsspiegeln im rechten mittellappen entdeckt. die weitere abklärung mittels nativer thorax-ct, bronchoskopie und biopsieentnahme bestätigte den verdacht auf eine bronchogene zyste. die erregerdiagnostik in der bronchoalveolären lavage zeigte lediglich eine kontamination mit der residenten standortflora. ergebnisse. in anbetracht der geplanten immunsuppressiven therapie, die mit einem erhöhten infektionsrisiko einhergeht, wurde die bronchogene zyste im september operativ entfernt. zur linderung der beschwerden erhielt die patientin eine schmerztherapie mit nsar. als sich die patientin sechs monate später erneut zur einleitung der biologikatherapie vorstellte, berichtete sie, dass die schmerzen etwa einen monat nach der operativen resektion praktisch verschwunden seien. die klinische untersuchung war unauffällig, der basdai-index lag bei , . auch das zur verlaufskontrolle angefertigte mrt der isg zeigte im vergleich zur voruntersuchung einen deutlichen rückgang der floridität. schlussfolgerung. es handelt sich um den ersten fall einer kompletten klinischen und radiologischen remission einer hla-b -positiven ankylosierenden spondylitis nach operativer entfernung einer bronchogenen zyste als potenziellen entzündlichen fokus. bei der systemischen verlaufsform der erkrankung treten neben kutanen erscheinungen zusätzlich muskuloskeletale, hämatopoetische ( - %), renale (ca. %), kardiale, cerebrale und pulmonale ( - %) manifestationen auf. eine polyserositis ( - %) ist häufig. mit - % werden im sle-schub abdominelle schmerzen beschrieben. nur in seltenen fällen (amerika , %, asien , - , % aller sle-patienten) kommt es zum bild einer lupusassoziierten mesenterialen vaskulitis (lmv). die Ätiologie der lmv ist weitestgehend unklar, eine genetische präsidsposition sowie auslösende faktoren (bakterielle darminfektionen, medikamente wie nsar, phosphodiesterasehemmer) werden diskutiert. pathogenetisch wird eine mesenteriale ischämie durch eine mikroangiopathie (arteriolen, venolen) bei inflammatorischer immunkomplexpräzipitation sowie thrombembolischen ereignissen angenommen. radiologisch/sonographisch zeigt sich ein segmentales darmwandödem mit darmdilatation. endoskopisch dominieren oberflächliche ulzerationen, perifokale hämorrhagien bis hin zur gangrän. eine erhöhte perforationsneigung wird beschrieben. mikroskopische befunde zeigen eine fibrinoide nekrose subseröser gefäße mit leukozytoklasie der gefäßwand bzw. ein submuköses Ödem mit nur diskreter invasion mononukleärer zellen. die prognose der lmv scheint abhängig von genetischer prädisposition, raschem beginn einer immunsuppression sowie restriktivem einsatz operativer interventionen und wird je nach literaturquelle mit einer letalität bis zu % angegeben. background. we report a patient with tma in the context of sle treated successfully with the c inhibitor eculizumab. the patient had sle with lupus nephritis (ln). before she developed tma with renal failure and neurologic manifestations, she was treated with various immunosuppressive regimens for mucocutaneous and musculoskeletal manifestations and later for ln. the diagnosis of atypical hemolytic uremic syndrome (ahus) was made based on the presence of coombs-negative hemolytic anemia, thrombocytopenia, renal failure, seizures due to cerebral ischemia and signs of tma in the renal biopsy. plasma exchange and hemodialysis were started immediately and could stabilize her condition. six weeks after the beginning of plasmapheresis but still severely compromised renal function and thrombocytopenia, complement inhibition with eculizumab became a therapeutic option. after the first infusions, renal function, anemia and thrombocyte counts markedly improved. dialysis could be stopped. extensive genetic testing of mutations associated with the overactivation of the alternative complement pathway was negative. after months, when the patient was still in remission, eculizumab infusion intervals were widened and it was finally stopped after months of treatment. since then, renal function remained stable with nearly normal glomerular filtration rates. background. il- signaling plays an important role in inflammation but is restricted by different regulatory mechanisms. these mechanisms include the decreased availability of gp , the signal transducing chain of the il receptor, on the cell surface. the aim of this study was to determine whether the inflammatory environment in the arthritic joint has an impact on monocytic gp surface expression and the extent to which regulatory processes in the synovial fluid (sf) can be transferred to an in vitro model. flow cytometry and live cell imaging were used to measure the cell surface expression and internalization of gp . stat phosphorylation was monitored by flow cytometry and western blotting. results. the level of cell surface gp expression on sf monocytes was reduced compared to peripheral blood (pb) monocytes from patients with juvenile idiopathic arthritis (jia). this reduction could be reproduced by stimulating pb monocytes from healthy donors with sf and was dependent on p mapk. the induction of p by il- β in pb monocytes interfered with il- signaling due to the reduced cell surface expression of gp . the results suggest that p -mediated pro-inflammatory stimuli induce the downregulation of gp on monocytes and thus restrict gp mediated signal transduction. this regulatory mechanism could be relevant in the inflamed joints of patients with jia. kr. sjia patient characteristics of those who successfully discontinued corticosteroids during canakinumab treatment: secondary analysis from a pivotal phase trial background. interleukin- β (il- β) is a key driver in the pathogenesis of systemic juvenile idiopathic arthritis (sjia). canakinumab (can), a selective fully human anti-il- β monoclonal antibody, has been shown to be efficacious in the treatment of sjia [ ] . corticosteroids (cs) are a mainstay of therapy for sjia, however due to the well-known long-term side effects, reduction of cs dosage is desirable. objectives. to assess patient features associated with cs discontinuation during can therapy. methods. patients ( - years of age) with active sjia received s.c. can ( mg/kg to mg max) every four weeks during the maximum week cs-tapering phase [ ] . cs tapering was to be initiated when at least an adapted acr was achieved and no fever. a -year-old boy presented with nocturnal tingling paresthesia affecting his feet and his calves. no excessive leg movements were noted at night. within a few months, his symptoms worsened. the paresthesia occurred both during the day and at night. moreover, the paresthesia came to be triggered by merely standing up. affecting a sharply demarcated area not corresponding to dermatomes, symptoms resolved promptly with movement. the paresthesia was associated with local skin erubescence in spots that slowly began spreading all over the affected area. symptoms did not occur while the patient was seated. mild painless swelling around both of the ankles was noticed in the evenings. approximately one and a half years after the initial manifestation, painful triphasic color changes of all fingers and toes triggered by cold or stress occurred. the family history was positive only for psoriasis. extensive laboratory studies excluded inflammatory and hematological conditions as well as occlusive arterial diseases known to be associated with secondary raynaud's phenomenon. polyneuropathy and other neurological disorders were excluded as well. inflammatory joint disease suspected from the initial imaging with magnetic resonance of the feet and ankles was not confirmed by repeated investigations and scintigraphy. the only consistent abnormality was a reduced pulse amplitude corresponding to vasospasm, which was revealed by photoplethysmography of toe vessels. additionally, paradoxical amplitude reduction after application of nitroglycerine was seen in finger vessels. placing his hands or feet in cold water did not trigger raynaud's phenomenon. initial treatment with non-steroid anti-inflammatory drugs, topical isosorbiddinitrate and local steroid instillation (suspicion of inflammation of tibialis posterior tendon) was ineffective. systemic therapy with the calcium channel blocker amlodipine was initiated. the initial dosing of mg ( . mg/kg/day) was slowly increased to mg ( . mg/kg/day) which lead to complete resolution of the patient's ailments. after three years of pharmacotherapy and . years in remission, a weaning off the treatment is planned. based on the patient's positive response to calcium channel blocker, we conclude that the lower-leg paresthesia was of vascular origin and can be considered an atypical presentation of raynaud's phenomenon. background. the initial treatments of choice for jdm are high-dose corticosteroids and methotrexate. however, no consensus exists about second line therapeutic options in refractory or recurrent cases. results. we present a -year-old boy who was diagnosed with jdm due to severe proximal muscle weakness, dysphagia, a heliotrope rash, gottron's sign, nail teleangiectasia and a characteristic muscle biopsy. creatine kinase levels were within normal range and no antinuclear antibodies were present. over a period of seven years, the patient was treated with high-dose corticosteroids, methotrexate, intravenous immunoglobulins, oral steroids, mycophenolate mofetil, rituximab and infliximab. despite all treatment efforts, skin and muscle inflammation persisted and the boy developed severe subcutaneous calcifications, rendering him wheelchair-bound. as il- production correlates with disease activity in adult and juvenile dm, treatment with tocilizumab ( mg/kg every weeks) was initiated, leading to a complete resolution of skin inflammation within months. within months of treatment, the disease activity score (das) decreased from to (out of ), the childhood myositis assessment scale (cmas) increased from to (out of ) and the kendall manual muscle test (mmt) increased from to (out of ). in daily life the wheelchair was no longer necessary. treatment was well tolerated but accompanied by a moderate increase in liver transaminase activities. interestingly, therapy with rituximab was associated with a decline in igm levels only, whereas igg and iga stayed markedly elevated. in contrast, following initiation of tocilizumab treatment, igg levels rapidly declined to normal range, emphasizing the role of the humoral immune system in the pathogenesis of dm. conclusion. taken together, treatment of a severely affected jdm patient with tocilizumab was safe, well tolerated and led to a significant improvement in disease activity. further investigations of il- -blocking agents as a treatment option in otherwise therapy-resistant jdm patients are warranted. functional capacity of jia patients with an initial adjustment to an anti-tnf-alpha therapy background. thirty three percent of patients with polyarticular jia are treated with biologics [ ] . despite substantial improvement achieved by anti-tnf-α treatment according to disease activity [ ] patients have joint-specific impairments. this factor should be considered when analyzing the functional effects on joint limitations while performing daily activities. methods. in a prospective study on polyarticular jia patients treated with anti-tnf-α therapies plus functional therapies we study the longitudinal effects on joint function. the measurements include -d gait analysis (eight vicon f cameras, omg, london, balance control (s -check, tst, großhoeflein), pedobarography (emed plate ( sensors/ cm², novel, munich), daily activity assessment (step watch, orthocare innovations, ok usa), acr pedi and joint mobility testing. we here present the cross-sectional data of the first patients ( . ± . yrs, . ± . cm, . ± . kg, pain-level: . ± . / vas, active joints: . ± . , chaq: . ± . ). results. preliminary results demonstrate that the ability to walk is slightly limited. patients have a reduced push off power generation within the ankle joint (patients: . ± . w/kg; healthy controls: . ± . w/ kg). further on they show limited sensory motor control and stability in comparison to patients with an inactive disease status while performing balance tests (patients: sensory index: . ± . , stability-index: . ± . , patients with inactive status: sensory-index: . ± . , stability index: . ± . (p< . ). note: lower indices values are better results. conclusion. it is one of the first studies which show functional joint-specific deficits during every day activities in patients who receive an initial anti-tnfα-therapy. the limited stability and motor control might be due to limited joint integrity in the ankle joint. this is supported by the impaired push off function while walking. the next study step will show possible effects of the anti-tnfα-therapy. background. the role of sport as a therapeutic tool in treating patients with jia is becoming more important recently [ ] . effects of exercise therapy are reviewed beneath others by takken et al. [ ] . they state that short-term effects look promising but the effects of long-term studies remain unknown. methods. the preventive mobility workout (pmw) is a whole body home-exercise-therapy ( min each day) for patients with an inactive diseases status. it counteracts the deficits which were observed during functional studies in the past [ ] . it consists of exercises for muscular strengthening (squads: hamstring to quadriceps ratio), hamstring flexibility (lift and raise), core stability (prone bridge -time-to-failure), shoulder griddle mobility (horizontal extension) and ankle joint integrity (mechanical power while walking . for statistical analysis an anova was calculated and the level of statistical significance was set to p< . . results. preliminary results show a group effect of the pmw for the hamstring to quadriceps ratio (h-q-r) for the right side (p< . ) and a tendency for the left side (p= . ). the h-q-r for the right side has changed in the tg and cg from . ± . to . ± . and from . ± . to . ± . , respectively. it has changed for the left side in the tg and the cg from . ± . to . ± . and from . ± . to . ± . , respectively. all other parameters regarding flexibility or joint integrity show low or no effects. we have re-tested n= out of so far and the pmw training show little training-effects. the preliminary results might be a reasonable proof for long-term effects. a possible reason for the little effects might be that patients are supposed to train every day but the training diaries show that they exercise approximately three times a week. the authors would like to thank the "deutsche kinder-rheumastiftung" for supporting the study. conclusion. we will validate these proposed definitions prospectively in a jia associated uveitis cohort. based on the results, we will weight these measures to develop an overall scoring system. background. minute walk is a primary outcome measure in studies in pulmonary hypertension. currently we have a two of sets of data [ , ] regarding test results in the minute walk test ( mwt) in healthy children with a large span in the norm values in the different age groups. aim of the study was to establish norm values for healthy german children for the minute walk test. methods. the team of an occupational therapist and a study nurse were visiting schools. permission from the parents was give before the test. always just probands from one class were invited to participate. the test were performed according the international guidelines [ ] . the demographic data of the probands were collected and the parents filled out a short survey regarding the physical activity and the health condition. children with chronic diseases, which decrease the stamina were excluded. up till now probands participated from the age to years. of them were female. the mean minute walk continuously increased with age (. tab background. juvenile idiopathic arthritis (jia) is the most common chronic disease in pediatric rheumatology which often results in foot impairments [ ] . patients with jia are reported to have smaller pressure loads underneath the foot while walking [ ] . the aim of the study was to analyze the peak plantar pressure distribution of a well described cohort of jia patients with an active symmetrical ankle joint arthritis and no history of foot involvement. [ ] ) wurden in bezug auf therapie und outcome anhand der wallace-kriterien beurteilt: "active disease" (ad), "inactive disease" (id), "clinical remission under medication" (crm), "clinical remission off medication" (crom; [ ] background. familial mediterranean fever (fmf) is one of the most common autoinflammatory diseases (aid). pathogenomic relevant mutations in the mefv gene show autosomal recessive inheritance, but co-dominant mutations have been described. we aimed to evaluate correlations between ethnic origin, phenotype and genotype for fmf patients in the german aid-net-registry. methods. we used two common scoring systems modified for children (mor et al., pras et al.) to assess disease severity in fmf patients of the aid-net-registry. for the five most frequent mutations, we tested for a correlation of the genotype with the phenotype, mean crp and ethnic origin, respectively. furthermore, we evaluated the applicability of the two severity scores for children. results. among the patients, we detected a total of pyrin mutations and different sequence variants, including one new mutation (p.gly asp). the five most frequent alterations were p.met val ( %, n= ), p.met lle ( %, n= ), p.val ala ( %, n= ), p.glu gln ( %, n= ) and p.met ile ( . %, n= ). ethnic origin could be determined in cases; the prevailing ancestry was turkish ( %, n= ), % (n= ) were lebanese. p.met val in homozygous form ( %, n= ) was correlated with a more severe disease activity, based on the score by mor, as well as with a higher mean crp ( mg/l, n= , mg/l, n= ) compared to patients without this mutation (p= . and p< . , respectively). the score suggested by pras did not yield a significant genotype-phenotype correlation; indeed, the two scoring systems were inconsistent with each other (κ< . ). although a typical distribution of mutations in different ethnic populations was obvious, this trend was not statistically significant, probably due to the divergent number of cases. conclusion. the homozygous p.met val substitution was associated with a more severe disease activity. there was no origin-genotype correlation in this fmf population. the well-known severity scores for children (mor, pras) are inconsistent. the aid-net is working on a new scoring system. . all patients with rp should be investigated by capillaroscopy. capillaroscopy will be classified into "normal", "aspecific changes" or "scleroderma pattern". . all patients who have additional symptoms pointing to a definite connective tissue disease should be evaluated according to disease specific guidelines. . ana-negative and capillaroscopy-negative patients should be followed-up at least every months. . ana positive patients without disease-specific antibodies and with negative capillaroscopy findings should be followed-up at least every months. . ana and disease-specific antibody positive patients should have organ specific evaluation according to symptoms, examination and relevant to that particular disease e.g. patients who are ana and scl- positive may need organ specific evaluation for jssc as per the juvenile systemic sclerosis inception cohort protocol (www.juvenilescleroderma.com). . ana-positive patients, who have no disease specific antibody but have positive capillaroscopy results, should be followed-up at least every months. . ana-negative patients with positive capillaroscopy result should be followed-up at least every months. . the group could not reach an agreement regarding treatment, due to a lack of data for the paediatric age group. the group agreed that implementation of adult recommendations conclusion. the group made a suggestion for a standard of good clinical practice for rp in children. our aim is that this will facilitate a large multicentre prospective follow-up study of children with rp. background. chronic non-bacterial osteomyelitis (cno) is an inflammatory disorder of the skeletal system of unknown etiology. long-term follow-up and response to treatment data have rarely been reported. the aim of the study was to characterize the clinical, radiological, histological and laboratory data at juvenile cno onset, and to analyze the long term treatment response. methods. the course of disease of juvenile patients with non-bacterial inflammatory bone lesions was evaluated retrospectively. clinical, radiological, histological and laboratory data were assessed at disease onset and for a median time of disease of months. results. the mean age at disease onset was . years, the mean time between the first symptoms and the diagnosis of cno was months. % of the patients had multifocal bone lesions. biopsy was performed in patients. only when bone biopsy was taken within months of symptom onset, cellular infiltrates could be observed. at later time points, fibrosis, hyperostosis and bone edema predominated. the initial treatment consisted of non-steroidal anti-inflammatory drugs (nsaids). % of the patients required second line therapy consisting of sulfasalazine and short term oral corticosteroids, % of the patients required bisphosphonates or tnf-blocking agents. the number of clinical lesions decreased to % within . months and reached . % after months of treatment. the number of radiological lesions, however, declined to only . % after months of treatment. in detail analysis of the tre-atment response revealed that initiation of sulfasalazine treatment in nsaid non-responders led to a significant and sustained decline of the clinical, as well as the radiological number of lesions. conclusion. the rapid clinical improvement in cno, following initiation of therapy with nsaids, is not accompanied by a likewise decrease of the number of radiological lesions. treatment with sulfasalazine is effective in childhood cno. background. exercise has a wide variety of beneficial health effects. it stimulates bone formation and maintains bone strength as well as decreases the risk of falls. moreover, exercise at regular intervals is also assumed to positively affect immune functions. conversely, in more than % of the astronauts during/after space flight and under simulated weightlessness immune functions are suppressed. to assess the effects of simulated weightlessness during the nd berlin bedrest study (bbr- ) on immunological parameters. furthermore, to compare the effects of two different exercise performances (resistive vibration exercise and resistance exercise without vibration). methods. physically and mentally healthy male volunteers ( - y) experienced days of six degree head down tilt bed rest. they were randomized to groups: resistive vibration exercise (n= ), resistance exercise without vibration (n= ), inactive controls (n= ). blood samples were taken days before bed rest, on day and after beginning of bed rest. composition of immune cells was analyzed by flow cytometry. cytokines and neuroendocrinologic parameters were analyzed by a multiplex suspension array/ elisa in plasma. general changes over time were identified by paired t-test, exercise-dependent effects by -group repeated measurements anova. results. for all cases pooled, the number of granulocytes (p< . ), nkt cells (p< . ) and hematopoietic stem cells (p< . ) increased during the study; the concentrations of dhea (p< . ) and eotaxin (p< . ) decreased. different impacts of the specific types of exercise on the change over time were shown for lymphocytes, nk cells, nkt cells, tcell subpopulations and the concentrations of ip- and rantes. conclusion. we found immobilization/simulated weightlessness to significantly impact immune cell populations, and cytokine and neuroendocrine factor concentrations. exercise was able to specifically influence immunologic parameters. interestingly, these changes resemble those found during the aging process. background. novel therapies have made remission and low disease activity (lda) achievable goals in ra. we assessed the impact of treatment with subcutaneous abatacept or adalimumab on these goals and on functional and radiographic outcomes in ample (abatacept versus adalimumab comparison in biologic-naïve ra subjects with background methotrexate), the first head-to-head trial of biologics in ra patients with inadequate response to mtx (mtx-ir). methods. ample is a -year, phase iiib, randomized, investigator-blinded study. biologic-naïve ra patients with mtx-ir were randomized to receive mg abatacept weekly or mg adalimumab biweekly, combined with a stable dose of mtx [ ] and radiographic non-progression (defined as change in modified total sharp score ≤ . ) were analysed in patients achieving or not achieving remission or lda at days or . results. baseline clinical characteristics of abatacept and adalimumab treatment groups were balanced, as was clinical, functional and radiographic efficacy and safety at day [ ] . the proportions of patients meeting each of the remission criteria or lda at day were similar for both groups, but significantly more patients achieved das (crp) remission compared to cdai, sdai or rapid remission, and the smallest proportion achieved boolean remission. compared to remission, a higher proportion of patients achieved lda. across all definitions of remission or lda, > % of the patients achieving remission at days and were haq responders at day . more than % of patients achieving remission or lda at days and were radiographic nonprogressors at day . improvement in physical function and radiographic outcomes were consistent between the two treatment groups in both remission and lda populations (. tab. ). conclusion. through year, patients treated with subcutaneous abatacept or adalimumab in ample achieved comparable rates of remission and lda. similar improvements in physical function and radiographic outcomes were observed. these data help to illustrate the relationship between remission, lda and functional and radiographic outcomes independent of treatment with subcutaneous abatacept or adalimumab. background. previous small studies suggest that responses to some immunizations may be attenuated by intravenous abatacept but remain clinically meaningful [ , ] . we investigated the magnitude of response to pneumococcal and influenza vaccination in a larger number of patients receiving subcutaneous (sc) abatacept therapy. the objective of the study was to evaluate the antibody response to the standard -valent pneumococcal polysaccharide vaccine and the - seasonal influenza trivalent vaccine in adult patients with ra on sc abatacept and background dmards. these multicentre, open-label sub-studies of the -valent pneumococcal polysaccharide vaccine and seasonal influenza vaccine enrolled patients in the acquire (pneumococcal and influenza) or attune (pneumococcal) studies. patients were enrolled at any point during their sc abatacept treatment cycle after completion of ≥ months' abatacept treatment. all patients received fixed-dose sc abatacept mg/week with background dmards. a pre-vaccination blood sample was collected and vaccines administered, while continuing background sc abatacept and dmards. after ± days, a post-vacci- background. in real life, dosage increases are common with biologic agents [ ] . intravenous abatacept is administered by patient body weight ( mg/kg) and weeks after the first infusion and every weeks the-reafter [ ] totalling infusions over the first months. no adjustments to this schedule are recommended. abatacept retention rates, efficacy and safety over months in action (abatacept in routine clinical practice) have been reported previously [ , ] this study was designed to assess adherence to recommended dosing of abatacept over the first months in action. methods. action is an ongoing, -year, international, non-interventional, prospective cohort of ra patients treated with intravenous abatacept. all patients on abatacept treatment for ≥ months, and with infusion data available at initiation and at months, were considered in this analysis. good adherence was defined as correct dose by patient body weight and number of actual-to-recommended infusions within the range - % (i.e. - infusions). results. in total, / ( . %) patients received abatacept ≥ months and had the infusion data available. most had established ra and failed ≥ anti-tnf agent ( . %). of patients with body weight data available at initiation, . % received the recommended initial dose, . % a lower dose and . % a higher dose than recommended. good adherence to the abatacept treatment schedule was found in / ( . %) patients. over months, . % of patients received infusions, . % received infusions and . % had infusions. change in dosage over time was assessed in / patients with data available at both time points. the majority of patients ( . %) maintained the recommended dosage. / ( . %) patients received abatacept at the recommended dose for body weight and at the recommended treatment schedule over months. conclusion. in the real-world action study, adherence to the recommended abatacept treatment regimen over months was good. few patients received changes in dose and/or frequency of administration over this time period. background. in rheumatoid arthritis (ra), synovial fibroblasts (sf) secrete large amounts of il- , il- and matrix metalloproteinases (mmps) which are crucial for cartilage destruction. rasfs are sensitive to the action of cannabinoids and they express cannabinoid receptors type i and ii (cb and cb ), the vanilloid receptor (trpv ) as well as endocannabinoid degrading enzymes. cannabinoids are regarded as antiinflammatory and since anandamide (aea) is found in ra synovial fluid we investigated how this endocannabinoid affects adhesion, proliferation, and production of inflammatory mediators of rasf. methods. adhesion was assessed by the xcelligence system. proliferation was quantified by the amount of incorporated fluorescent dye into cellular dna. mmp- and cytokines were detected by elisa. in oasf, aea dose-dependently decreased the il- β induced production of mmp- (by %) in a trpv -mediated manner. il- and il- levels were only weakly modulated. in rasf however, aea decreased il- β induced production of il- ( %), il- ( %) and mmp- ( %). the effects of aea were not inhibited by cb , cb or gpr antagonists but were blocked by the trpv antagonist capsazepine. the inhibitory capacity of aea was enhanced by cyclooxygenase- inhibition in rasfs and oasfs, but was unaltered or even slightly reduced by faah inhibition. aea was even more potent in reducing above mentioned mediators when rasfs but not oasfs were incubated under hypoxic conditions and treated with tnf. furthermore aea increased adhesion of oasfs and rasfs to fibronectin. adhesion was modulated by cb , gpr , and trpv antagonists. combined faah and cyclooxygenase- blocked the stimulatory effect of aea on adhesion. proliferation was decreased by aea in rasfs and oasfs via a cyclooxygenase- but not via cb , cb or trpv dependent mechanism. conclusion. in conclusion, aea promotes an antiinflammatory phenotype of rasfs and oasfs by activating trpv . cb , trpv , and gpr act in concert to modulate adhesion of sfs and this is highly dependent on the intracellular concentration of aea. additionally, cyclooxygenase- metabolites of aea exert their anti-proliferative effects independent of cb and cb . fc. it has been reported that lower levels of czp, compared to ada or ifx, are transferred from treated mothers to the neonate [ ] . this discrepancy may be due to active transport of antibodies across the placenta thought to be mediated by the neonatal fc receptor (fcrn). however, anti-tnf binding to fcrn, and fcrn-mediated transcytosis have not been studied. the objective of this study is to quantify binding of czp, ifx, ada and eta to fcrn and to measure fcrn-mediated transcytosis. a biacore™ assay was used to determine binding of czp, ada and ifx to human fcrn. anti-tnfs were passed over an fcrn-coated chip .mdck-ii cells transfected with human fcrn were used to measure fcrn mediated transcytosis. the anti-tnfs and the control antibody (p ), which possessed a fc modified to prevent binding to fcrn, were biotinylated to allow visualization. the amount of each anti-tnf transcytosed across the cell layer over hours was measured by msd assay. results. ifx ( nm) and ada ( nm) had high binding affinity to fcrn while the binding affinity of eta to fcrn was - -fold lower ( nm). in contrast, czp did not bind to the fcrn with any measurable affinity. the levels of transcytosis seen with ifx and ada were . ng/ml and . ng/ml, respectively (mean of experiments). transcytosis of eta ( . ng/ml) was lower than that of ada and ifx. in contrast, the level of czp transcytosis was significantly lower, at . ng/ml, than that observed with the other anti-tnfs and comparable to the control p ( . ng/ml). conclusion. czp didn't bind to fcrn and thus no fcrn-mediated czp transcytosis was detected. in contrast, ada and ifx had a relatively high binding affinity to fcrn and were actively transcytosed. eta showed lower binding affinity and transcytosis, but fcrn-mediated transport could still be measured. these results explain the previously observed active transport of anti-tnfs across the placenta seen in patients treated with ifx and ada, whereas only low levels were observed with czp [ ]. background. anti-cyclic citrullinated peptide (ccp) status was reported previously as predictive of abatacept response [ ] . predictors of retention with abatacept have not been published previously. this study was designed to identify predictors of abatacept retention after failing ≥ biologic agent. in routine clinical practice) is an ongoing, -year, international, non-interventional, prospective cohort including patients with ra treated with intravenous abatacept [ , ] . patients from canada, germany, greece and italy, where patient numbers were sufficient to explore between-country effects, were included. at data cut-off (february ), all patients had -year follow-up (interim analysis). abatacept discontinuations were reported by the investigator at any time point during follow-up. socio-demographics, disease characteristics and medical history at abatacept initiation, and previous and concomitant treatments were deemed potential predictive variables. clinically relevant variables and those with p≤ . (univariate analysis) were entered into a multivariate cox proportional-hazards regression model, adjusted for clustered data from one investigator. using backwards selection, variables with p≤ . were retained in the final model. . there were no interactions or effects of c-reactive protein level, rheumatoid factor status, type of previous anti-tnf failure, infection at initiation and abatacept monotherapy. sensitivity analysis, including all variables significant in univariate analysis, was consistent. conclusion. in this first report of real-world predictors of abatacept patient retention, anti-ccp positivity and failing < prior anti-tnf agents were associated with higher retention. differences in retention between some countries may reflect specificities in healthcare systems and populations. abatacept, a biologic agent with no contraindications or special warnings for cardiac comorbidity, seems to be a good option for these patients. weekly subcutaneous abatacept confers comparable onset of treatment response and magnitude of efficacy improvement over months when administered with or without an intravenous abatacept loading dose zeitschrift für rheumatologie suppl · | methods. patients from the intent-to-treat populations of the acqui-re [ ] and ample [ ] studies randomized to subcutaneous abatacept plus mtx were included. all patients received fixed-dose subcutaneous abatacept mg/week; in acquire but not ample, patients also received an intravenous loading dose (~ mg/kg based on weight range) on day . for this post-hoc analysis, assessments included acr and haq-di response (improvement ≥ . ) over months, with patients who discontinued considered non-responders. mean changes from baseline over months in das (crp) were assessed in patients with das > . at baseline (last observation carried forward) to account for differences in baseline disease activity between the two studies. results. all patients were biologic naïve at baseline, with mean disease duration of . and . years, das (crp) . and . , and haq-di . and . in acquire and ample, respectively. efficacy was compared throughout the study. for patients treated with subcutaneous abatacept with and without an intravenous loading dose, acr response rates were similar (. tab. ). haq-di response rates were also similar with and without the intravenous loading dose (. tab. ). for the overall populations, mean (standard deviation [sd]) changes from baseline to day in das were − . ( . ) and − . ( . ) in acquire and ample, respectively. for patients with baseline das > . , mean (sd) changes in das from baseline to day were − . ( . ) and − . ( . ) in acquire and ample, respectively. conclusion. time to onset and magnitude of acr and haq-di responses and das improvements were generally similar with subcutaneous abatacept with or without intravenous loading in patients with ra and an inadequate response to mtx. the findings from this posthoc analysis suggest that subcutaneous abatacept can be given effectively without an intravenous abatacept loading dose. background. ra is associated with pain and impairment of physical function, significantly impacting a patient's health-related quality of life (hrqol) and ability to perform daily activities. patient-reported outcomes (pros) related to hrqol and daily activity have become an essential part of assessment in ra. we continue to report here comparative findings from pros assessed with subcutaneous abatacept or adalimumab on background mtx in the first head-to-head study, ample. we compared changes in pros at year in patients with ra treated with abatacept or adalimumab, both on background mtx. methods. ample is a phase iiib, randomized, investigator-blinded study of months' duration. biologic-naïve patients with active ra and inadequate response to mtx were randomized to either mg abatacept weekly or mg adalimumab biweekly in combination with mtx. pros evaluated through day included: hrqol, assessed using short form- (sf- ; including physical and mental component summary subscores [pcs and mcs]); activity limitation over the previous days, using the activity limitation questionnaire (alq; [ ] ); productivity, using the work productivity and activity impairment questionnaire for ra [ ] ; physical and psychosocial independence, captured using items from haq, sf- score; and alq [ ] . other pros previously reported from ample include: patient pain, patient global assessment, fatigue, and physical function [ ] . all efficacy analyses were done using the intent-to-treat population, which included all patients who were randomized and received at least one dose of study drug. baseline characteristics were analysed descriptively and changes in pros from baseline were assessed using ancova. results. baseline demographic and clinical characteristics of the abatacept and adalimumab treatment arms were similar. improvements in all domains of the sf- , including pcs and mcs observed at day parameter baseline woche woche itt-gesamt das , mw ± sd , ± , (n= ) , ± , (n= ) , ± , (n= ) vas da pat., mw ± sd , ± , (n= ) , ± , (n= ) , ± , (n= ) sjc , mw ± sd , ± , (n= ) , ± , (n= ) , ± , (n= ) vas schmerz, mw ± sd zielsetzung der ole-studie beinhaltete die beurteilung der verträglichkeit und der wirksamkeit von czp. die retentionsraten sowie die wirksamkeit wurden bis woche und die verträglichkeitsdaten bis woche beobachtet. in die verträglichkeitsanalyse wurden alle pat einbezogen, die in die ole-studie eintraten und czp erhielten (n= ; n= kombitherapie; n= monotherapie), einschließlich der plazebo/czp-patienten, die die ausgangsstudien erfolgreich abgeschlossen/abgebrochen haben. bezüglich der wirksamkeit wurden folgende analysen vorgenommen: ) czp pat, die die ausgangsstudien erfolgreich beendet haben und zu irgendeinem zeitpunkt während der ausgangsstudien oder ole-studie andere dmards eingenommen haben (n= ; kombitherapie completer); ) czp pat, die die fast ward studie erfolgreich beendet haben und zu keinem zeitpunkt andere dmards eingenommen haben (n= ; monotherapie completer). ergebnisse. verteilung und häufigkeit der unerwünschten ereignisse (ue), einschließlich der reaktionen an der injektionsstelle (ereignisse/ patientenjahre: monotherapie , , kombitherapie , ) und der schwerwiegenden unerwünschten ereignisse (sue) waren mit dem vergleichbar, was bisher für czp berichtet wurde (. tab. ) . das auftreten von schwerwiegenden infektionen (si) und malignitätsraten war niedrig. es wurden todesfälle berichtet: kardiovaskuläre ereignis-se, infektionen, unfall und tumorerkrankung. die retentionsraten der pat, die die ausgangsstudien erfolgreich beendet haben, waren zur w in der czp monotherapie-( / , %) und der czp kombitherapie-gruppe ( / ; %) vergleichbar. der durchschnittliche das - (crp)-wert und dessen abweichung vom baseline-wert der ausgangsstudien zum zeitpunkt des eintrittes in die ole-studie und nach w der monotherapie-completer und der kombitherapie-completer, sowie die zugehörigen haq-werte sind in . tab. dargestellt. schlussfolgerung. vorliegende ole-studie konnte das günstige risiko-nutzen-profil der czp-monotherapie bestätigen. die langzeitwirksamkeitsdaten zeigten keine unterschiede zwischen pat, die czp als monotherapie erhielten und pat, die czp in kombination mit anderen dmards erhielten. background. rheumatoid arthritis (ra) is the most common disease of joints that non-or deficiently treated leads to functional loss and premature cardiovascular death within years. but nearly % of the ra patients fail to treatment with tnfα-inhibitor (tnfi) indicating a switch to rituximab (rtx). the urgency of personalized promising treatment in time presupposes predictive parameter. rheumatoid factor (rf) and anti-citrullinated protein antibodies (acpas; especially accp) are shown to be better diagnostic than less theranostic biomarkers. in that context we investigated the role of antibody subtypes against mutated citrullinated vimentin (amcv) that determine response outcome in rtx-treatment. methods. a cohort of only amcv igg positive ra patients was tested for amcv subtype igm and iga (additionally for rf igg, igm, iga and accp igg) by elisa at baseline (after failure to first approach with tnfi) and at week (after first rtx cycle). responders were characterized by a difference in their das of ≥ . (eular good-response) between baseline and week . the cohort comprises responders (rr) and non-responders to rtx (nrr). results. amcv igg, igm and iga showed higher treatment related decreases compared to rf and accp ig subtypes and additionally even diverged in both groups depending on response outcome: especially amcv iga exhibited a higher mean titer decline of rr by % at lo- wer baseline titers ( . to . u/ml) and a mean titer increase of nrr by nearly % at higher baseline titers ( . to . u/ml). at baseline rr displayed relatively more negative iga titers ( %; n= / ) than nrr, who in return showed more iga positive titers ( %; n= / ). amcv iga positive patients were more likely to show positively for rf iga ( %) and igm ( %), what could be inversely detected for iga negative patients with seronegativity of rf iga ( %) and igm ( %). conclusion. amcv immunoglobulin subtypes showed treatment dependent changes contrary to already known antibodies (accp). especially amcv iga reflects response outcome: amcv iga negativity at baseline and decreasing titers during treatment are predictive for good eular-response to rtx. einleitung. im rahmen der abklärung eines unter tocilizumab-therapie aufgetretenen arzneimittelexanthems erfolgte die bestimmung von c c und c -beide parameter waren erniedrigt. bei recht geringer und nur kurz andauernder ausprägung des exanthems wurde die therapie komplikationslos fortgeführt. die komplementfaktoren wurden im verlauf bestimmt und blieben erniedrigt. im weiteren verlauf erfolgte die konsekutive messung bei weiteren patienten. methoden. nephelometrische bestimmung von c c und c im serum vor und während der therapie mit tocilizumab (jeweils vor der nach wochen anstehenden infusion) bei patienten mit gesicherter rheumatoider arthritis (rf+, ccp+). ergebnisse. c c-und c -komplement wurden bei konsekutiven patienten mit rheumatoider arthritis vor und unter tocilizumab-therapie bestimmt. bei allen patienten fielen sowohl c c, als auch c unter der therapie mit tocilizumab ( mg/kg kg) ab. / patienten hatten eine c c-erniedrigung (bestimmter wert unterhalb des laborinternen normbereichs). / patienten hatten eine c -erniedrigung (bestimmter wert unterhalb des laborinternen normbereichs). drei patientinnen entwickelten unter der therapie ein exanthem, davon hatten eine komplementerniedrigung. keine "offensichtlich" erhöhte infektneigung in abhängigkeit von komplementspiegeln. bei verlängerten infusionsintervallen aufgrund von infekten zeigte sich, dass der effekt von tocilizumab auf die komplementspiegel reversibel ist. durch blockade des il- -rezeptors tocilizumab kann ein erworbener komplementmangel induziert werden. Ähnliche daten wurden im rahmen einer pilotstudie an sle-patienten erhoben, die mit tocilizumab behandelt wurden. der effekt ist bei der rheumatoiden arthritis nicht vorbeschrieben. der genaue umfang des komplementmangels ist bisher nicht untersucht (andere bestandteile der kaskade?) wurde in der sle-studie ausführlicher untersucht. da die verschiedenen komplementbestandteile erniedrigt waren wurde auf eine synthesestörung und nicht auf einen gesteigerten verbrauch geschlossen, was auch in dieser kohorte der fall zu sein scheint. der erworbene komplementmangel könnte einen teil der infektiösen komplikationen unter der therapie erklären. eine korrelation ist aber aufgrund der geringen fallzahl nicht möglich. schlussfolgerung. anhand dieser studie konnte eine exzellente korrelation zwischen den parametern der dxr und des bx verifiziert werden. mittels der neu entwickelten voll digitalisierten bx-technik ist somit eine quantifizierung der periartikulären demineralisation möglich und als surrogatparameter der radiologischen progression bei einer ra eingesetzt werden. jahre, die ra bestand im median seit , jahren. , % der patienten waren mit tnf-alpha-blockern vortherapiert, , % ausschließlich mit dmards. der mittlere das lag zur baseline bei , . zur woche zeigten , % der patienten eine das remission (< , ) und , % bzw. , % der patienten ein gutes bzw. moderates ansprechen gemäß eular-kriterien. Über den beobachtungszeitraum stieg der anteil der tcz-monotherapiepatienten von , % auf , %. die mtx-komedikation sank im gleichen zeitraum um , %. , % der patienten, die tcz zunächst zusammen mit einem dmard erhalten haben, konnten dieses absetzen. tcz zeigte in der mono-und kombinationstherapie eine vergleichbare wirksamkeit: , % bzw. , % der patienten erreichten eine cdai remission (≤ , ). der anteil von patienten ohne glucocorticoid(gc)-begleittherapie stieg über den beobachtungszeitraum um , % auf , % an, der anteil mit einer tagesdosis ≤ mg auf , %. bei , % war eine reduktion der gc-dosis möglich, nur bei , % war eine erhöhung notwendig. bei , % der patienten, die zur bl mit gc behandelt wurden, konnten diese komplett abgesetzt werden. die mittlere gc-tagesdosis verringerte sich kontinuierlich von , (bl) auf , mg/d (w ). schlussfolgerung. diese interimsanalyse der nichtinterventionellen studie ichiban zeigt bei den ersten patienten mit mittelschwerer bis schwerer ra über die bisherige beobachtungsdauer von wochen deutliche verbesserungen der aktivitätsparameter, sowie eine reduktionen der begleitenden dmard-therapien und des bedarfs von glucocorticoiden unter behandlung mit tcz. vergleichbar mit den kontrollierten studien ist die tcz-monotherapie auch unter praxisbedingungen der kombination mit dmards ebenbürtig. diese anhaltende wirksamkeit wird erstmals in rheumatologischen praxisdaten für den langzeitverlauf von , jahren gezeigt. zeitschrift für rheumatologie suppl · | einleitung. die arteriosklerose (as) steht als häufigste todesursache im besonderen fokus der medizinischen forschung. neuere erkenntnisse weisen auf einen starken zusammenhang zwischen parametern der systemischen entzündung und der pathogenese der as hin. patienten mit rheumatoider arthritis (ra) haben daher ein stark erhöhtes kardiovaskuläres risiko. ziel: untersuchung des zusammenhangs zwischen verschiedenen ra-krankheitsspezifischen risikofaktoren und dem auftreten einer arteriosklerose bei ra-patienten. methoden. ra-patienten, davon % weiblich, ± , jahre alt, wurden hinsichtlich der krankheitsaktivität (krankheitsdauer , ± , ; das , ± , ; serum-crp , ± , mg/dl,; anti-ccp-antikörper , ± , u/ml, radiologisches stadium , ± , ; davon , % mit erosionen), sowie klassischer kardiovaskulärer risikofaktoren der as erfasst, welche durch den score-wert (systematic coronary risk evaluation) zusammengefasst wurden. zur as darstellung wurde eine carotis-duplexsonographie mittels eines mhz-schallkopfes (ge vivid pro) durchgeführt. die mittlere intima-media-dicke (imd) der a. carotis communis wurde durch ein softwaregestütztes messverfahren ermittelt. ergebnisse. plaques waren bei patienten ( %) nachweisbar. diese korrelierten mit einer erosiven form der ra (p= , ), einer längeren krankheitsdauer (p= , ) und höheren anti-ccp-antikörpern (p= , ). die mittlere imd betrug , ± , mm. je ausgeprägter die radiologischen veränderungen sind, umso höher war die wahrscheinlichkeit der plagues (p= , ). mittels altersadjustierter partieller korrelationsanalyse wurde der das als altersunabhängiger einflussfaktor auf die imd ermittelt (p= , ). mittel-und hochgradige stenosen zeigten sich bei fünf ra-patienten ( , %), welche ausnahmslos eine erosive verlaufsform aufwiesen. normalbefunde stehen in zusammenhang mit einem crp-wert unter mg/dl (p= , ). auch die traditionellen kardiovaskulären risikofaktoren haben signifikanten einfluss auf as. der score-wert erwies sich als äußerst verlässlicher prädiktor für plaques (p< , ), imd-verdickung (p= , ) und stenosen (p< , ). durch elimination der traditionellen risikofaktoren mittels partieller score-adjustierter korrelationsanalyse bestätigte sich erneut die assoziation von pathologischen ultraschallbefunden mit dem das (p= , ). schlussfolgerung. die erhebung klassischer risikofaktoren bei ra-patienten ist unerlässlich. die nutzung des score-werts als screening-parameter ist besonders effektiv. zusätzlich sollten parameter der krankheitsaktivität von ra zum management von arteriosklerose herangezogen werden. besonders aussagekräftig hierfür sind der das , ein erosiver krankheitsverlauf, die crp-werte und die erkrankungsdauer background. apremilast, an oral small molecule specific inhibitor of phosphodiesterase- , works intracellularly to modulate inflammatory mediators. the palace - trials compared the efficacy and safety of apremilast vs placebo in patients with active psa despite prior dmards and/or biologics. the overall safety and tolerability of apremilast was assessed in a pooled analysis of the palace , and placebo-controlled phases. methods. safety data was pooled from phase , randomized, placebo-controlled studies; patients with active psa despite prior dmards and/or biologics were randomized : : to placebo, apremilast mg bid (apr ), or apremilast mg bid (apr ) stratified by baseline dmard use. at week , patients with < % reduction in swollen and tender joint counts were required to be re-randomized (early escape) to apr or apr (placebo group) or remained on initial apremilast dose through week . stable concurrent dmard therapy was allowed (mtx, sulfasalazine, leflunomide, or combination). the analysis comprises data from the placebo-controlled periods (weeks - ). results. patients were randomized to placebo (n= ), apr (n= ), or apr (n= ) and included in the safety population. baseline demographic and disease characteristics and prior/concurrent therapy were comparable across treatment groups; . % had prior biologic exposure. adverse events (aes) occurred in . % (placebo), . % (apr ), and . % (apr ) of patients. aes occurring in ≥ % of any treatment group were diarrhea, nausea, headache, and urti (. tab. ); most occurred within the first weeks of treatment and nearly half resolved within weeks. of patients with these aes, most ( - %) were mild or moderate. rates of discontinuation due to aes were low: . % (placebo), . % (apr ), and . % (apr ). serious aes occurred in . % (placebo), . % (apr ), and . % (apr ) of patients. one death occurred (apr ) due to multiorgan failure not suspected to be treatment-related. no cases of serious systemic opportunistic infections, lymphoma, vasculitis, or reactivation/de novo tb were reported. there were no clinically meaningful differences between apremilast and placebo in terms of major cardiovascular aes, changes in blood pressure, malignancies, or effects on laboratory measurements. conclusion. apremilast was generally well-tolerated with no new safety concerns identified compared with the known profile. the aim of the current study was to investigate the relationship between worsening of functional status, clinical disease parameters and radiographic spinal progression over two years in patients with early axial spondyloarthritis (axspa). methods. in total, patients with early axspa ( with as and symptom duration ≤ years, and with non-radiographic axspa (nr-ax-spa) and symptom duration ≤ years) from the german spondyloarthritis inception cohort (gespic) were included in the current analysis based on the availability of radiographic data and data on the functional status at baseline and after years of follow-up. spinal radiographs were scored according to the modified stoke ankylosing spondylitis spinal score (msasss). functional status was assessed by the bath ankylosing spondylitis functional index (basfi), and clinical disease activity by the bath ankylosing spondylitis disease activity index (basdai). results. basfi worsening in ≥ point after years (n= , . %) was significantly associated only with higher basdai worsening over years in comparison to those without functional worsening: . ± . vs - . ± . , p< . . basfi worsening by ≥ points (n= , %) was, however, associated not only with basdai change ( . ± . vs - . ± . , p< . ), but also with a higher rate of radiographic spinal progression measured by the proportion of patients with msasss worsening by ≥ units ( . % vs. . % in patients without basfi worsening, p= . ), or with new syndesmophyte formation ( . % vs. . %, p= . ). importantly, in the multivariate analysis both basdai increase and progression of structural damage in the spine remained statistically significantly associated with basfi worsening. no other disease-related parameters (e.g. sex, hla-b positivity, symptom duration etc) were found to be significantly associated with basfi worsening over two years. conclusion. in this prospective study we could demonstrate that only factors were significantly associated with worse functional outcome over two years in patients with early axspa: ) increase of disease activity and ) progression of structural damage. elevated serum vascular endothelial growth factor is highly predictive for radiographic spinal progression in patients with axial spondyloarthritis who are at high risk for progression background. vascular endothelial growth factor (vegf) is an essential mediator of the endochondral ossification and, therefore, might play a pathogenetic role in the process of syndesmophyte formation in axial spondyloarthritis (axspa). the aim of the study was to investigate the role of serum vegf as a predictor of radiographic spinal progression in patients with axspa. methods. altogether patients with definite axspa [ with ankylosing spondylitis (as) and with non-radiographic axspa] from the german spondyloarthritis inception cohort (gespic) were included in the current study. radiographic spinal progression was defined as ) worsening of the modified stoke ankylosing spondylitis spine score (msasss) by ≥ units after years, and ) development of a new syndesmophyte or progression of existing syndesmophytes after years. serum vegf levels were detected at baseline. results. mean baseline vegf values were significantly higher in patients with msasss worsening by ≥ units after years (n= ) as compared to those without progression ( ± vs. ± pg/ml, respectively, p= . ) and in patients with syndesmophyte formation/ progression (n= ) as compared again to those without progression ( ± vs. ± pg/ml, respectively, p= . ). area under the curve (auc) was . , p= . for the msasss worsening ≥ units and . , p= . for syndesmophyte formation/progression. importantly, the performance of vegf as a predictor of radiographic spinal progression was clearly in patients who were already at high risk for such a progression due to the presence of syndesmophytes at baseline (n= ): auc was . , p= . , and . , p= . , respectively. vegf serum level of > pg/ml in high-risk patients had a sensitivity of %, a specificity of %, and an odds ratio (or)= . ( %ci . - . ) as a predictor of msasss worsening by ≥ units over years. the same serum level of results. immediately after the second session of plasmapheresis, therapy with infliximab mg/kg resumed. after weeks of hospitalization with repeated administration of infliximab had good dynamics (bas-dai . , asdas (crp) = . , basfi . ), significantly reduced pain in the joints and spine, stiffness, increased mobility in the joints and spine. the treatment continued: holding plasmapheresis followed by infliximab. after infusions patient experienced a good effect -basdai . , asdas (crp)= . , basfi . . conclusion. plasmapheresis in some patients could be effective by reducing activity and dealing with secondary tnf inhibitors failure, since this procedure deletes the macromolecular blood proteins, including tnf-, igg antibodies, and circulating immune complexes results. there were still signs of osteitis in sacroiliac joints in patients at week , in patient the mri-determined sacroiliitis has resolved completely. the patient has improved clinically and fulfilled asas improvement criteria. there was a minor decrease in sparcc sacroiliitis score (from to ) in patients at week , indicating reduction of inflammation in sacroiliac joints. sparcc sacroiliitis score stayed the same in the remained patient. conclusion. rituximab may be of some benefit in decreasing mri-evident sacroiliitis in patients with highly active as, even in patients in whom tnf-α inhibitors have failed. background. despite the differences in the pathogenesis of ra and as, neck pain is a frequent clinical symptom in both diseases. we evaluated the correlation between subjective reports of neck pain and objective signs of inflammation as assessed by f bone marrow edema (bme) on mri in ra and as patients. methods. stir-mri of the cervical spine of patients ( ra, as) were included. mris were scored by two blinded readers using a recently published mri scoring system, with quantification of the extension of bme in the atlantoaxial region, corpus, facet joints and processus spinosus of all cervical vertebrae, ranging from - points. the presence or absence of degenerative changes was also recorded. conclusion. the majority of patients with ra and as had objective signs of bme but also degenerative changes on mri at different cervical locations. assessment of bme in the atlantoaxial region is important in clinical practice, in addition to degenerative changes, since its presence seems to influence the intensity of neck pain reported by these patients. x. baraliakos , having mri data at w . of these , ten were treated with secukinumab and with placebo in the core study. mris were rescored for this study. asspimri-a scores and the occurrence of vertebral edges (ve) inflammatory and fatty lesions were evaluated by an independent blinded reader. results. all pts completed this exploratory mri substudy. in pts receiving × mg/kg secukinumab followed by × mg/kg (n= ) secukinumab, spinal inflammation was reduced compared to bl at w -similar to the results of the core study -and this reduction was sustained up to w (abb. ). also in pts who had initially received placebo switching to secukinumab at w , mri inflammation at w was reduced. of the ves evaluated, the proportion of ves with inflammatory lesions was reduced from . % (n= ) at bl to . % (n= ) at w and . % (n= ) at w . in contrast, the proportion of fatty lesions at bl ( . %, n= ) remained largely unchanged at w ( . %, n= ) and w ( . %, n= ). secukinumab reduced mri inflammation at w and w . conclusion. mri analysis suggests that the il- a inhibitor secukinumab can reduce spinal inflammation and this effect may be sustained for up to years. unlike reports with tnf blockers, secukinumab appeared to leave the proportion of fatty lesions unchanged. the potential impact of these preliminary findings on radiographic progression under secukinumab therapy will be studied in larger trials. schlussfolgerung. es zeigen sich keine signifikanten unterschiede in der krankheitsaktivität der beiden gruppen (vor einleitung der ada-therapie nach dmard-und nach anti-tnf-versagen). auch bei der patientengruppe mit mehreren vortherapien mit tnf-inhibitoren können keine signifikanten unterschiede in der ausprägung der erkrankung nachgewiesen werden. im trend wurde ein früheres einsetzen der haut-und gelenkmanifestation sowie eine stärkere systemische entzündungsreaktion in den patienten mit vorheriger tnf-therapie festgestellt werden, während die dauer der erkrankung und der bmi mit den charakteristika der patienten mit ausschließlicher dmard-vortherapie vergleichbar sind. long-term ( -week) results of a phase , randomized, controlled trial of apremilast, an oral phosphodiesterase inhibitor, in patients with psoriatic arthritis (palace ) background. apremilast, an oral phosphodiesterase inhibitor, works intracellulary to modulate a network of pro-and anti-inflammatory mediators. the palace study assessed the efficacy and safety of apremilast in patients with active psoriatic arthritis (psa) despite prior dmards and/or biologics. methods. patients were randomized : : to placebo, apremilast mg bid (apr ), or apremilast mg bid (apr ). at week , patients with < % reduction from baseline in swollen/tender joint counts were required to be re-randomized (early escape) to apr or apr (placebo group), or remained on their initial apremilast dose. at week , all remaining placebo patients were re-randomized to apr or apr through week . results. patients were randomized. at week , significantly more apr ( . %; p= . ) and apr patients ( . %; p< . ) achieved an acr vs placebo ( . %). at week , all patients had a minimum weeks of apremilast exposure. response to apremilast was generally maintained over the treatment period. at week , acr was achieved by . % (apr ) and . % (apr ) of patients (table) . exposure-adjusted incidence rates for adverse events (aes), severe aes, and serious aes were comparable between - and - weeks. the proportion of patients remaining on apremilast to week who first reported the most common gi disturbances (e.g., diarrhea, nausea, and vomiting) after week was low (ranging from . - % for apr and - . % for apr ). there were no clinically meaningful laboratory findings with exposure up to weeks. no deaths beyond the previously reported in the - week period were observed in the - week period. no safety signals with respect to major cardiac events, malignancies, and opportunistic infections were observed, consistent with the - week period. no cases of lymphoma, tuberculosis, or tuberculosis reactivations were reported for the -week period (. tab. ). conclusion. apremilast administered to patients with psa beyond weeks continued to demonstrate meaningful clinical response. for patients who completed weeks of the study, acr response rates up to % were observed. apremilast continued to be well tolerated with an acceptable longer-term safety profile. methods. to identify how conventional cd + and cd + t cells and regulatory t cells are recruited into the inflamed kidneys in ln, serum and urine samples of sle patients were analyzed for chemokines using multiplex assays. based on the assay's results a group of corresponding chemokine receptors (ccr - , cxcr and cxcr ) was chosen, whose frequencies on urinary t cells were subsequently determined in patients with acute ln by flowcytometry. results. chemokines (ccl , ccl , ccl , ccl , ccl , ccl , ccl , ccl , cxcl , cxcl , cxcl and cx cl ) were significantly elevated in the urine of patients with active ln when compared to the control group. the other chemokines (ccl , ccl , ccl , cxcl , cxcl ) and cxcl showed no significant differences between the groups. ccr and cxcr were the most prominent receptors on both urinary cd + and cd + t cells, although cd + t cells also expressed high amounts of ccr and ccr . however, when compared to t cells in the blood, urinary cd + t cells showed significantly higher expression of all examined chemokine receptors but ccr while urinary cd + t cells only had higher expression of ccr and ccr . the chemokine receptor expression on cd +foxp +cd -regulatory t cells (treg) differed from conventional cd + t cells as well. treg expressed significantly more ccr and significantly less cxcr . conclusion. ccr and cxcr are the primary receptors in the mechanism of recruiting t cells into the inflamed kidney. key chemokines are ccl , ccl , ccl and ccl as well as cxcl and cxcl . however, at least for cd + t cells, there are secondary pathways of recruitment involving ccr /ccl and ccr /ccl . also, treg recruitment seems to rely more on ccr than that of conventional cd + t cells. methods. observe is a multicenter, retrospective medical chart review study. rheumatologists from german academic and non academic centers who treat > sle patients annually and have > years of practice experience were randomly recruited. physicians identified consecutively all their adult sle patients who had received belimumab as part of usual-care. index date was the first belimumab infusion date. the primary outcome was the change in overall sle disease manifestations months after index date based on physician judgment. the overall response rates as well as reasons for early treatment discontinuation within months were assessed. changes in formal disease area indices, e.g. selena-sledai if available and changes in oral steroid dose are also reported. results. previous analyses from us patients treated with belimumab have described significant clinical improvement across relevant organ systems based on clinical judgment and formal disease activity indices and marked reductions in corticosteroid use in patients that received at least infusions of belimumab. the current study is the first description of patient characteristics and outcomes after months of therapy with belimumab outside of the us. it is also the first time overall responder rates and reasons for discontinuation with belimumab have been described in a real world setting. the study provides insights into the effectiveness and safety of belimumab in an ex-us clinical setting. larger, prospective observational studies are needed to confirm the results. commercial support grant disclosure: research funded glaxosmithkline. background. toll-like receptor (tlr- ) signaling is considered to play an important role in b cell hyperreactivity in sle. b cells from slepatients express significantly more tlr- than those from healthy donors (hd), especially if patients have positive dsdna-antibodies and high disease activity. tlr- stimulation of b cells is tightly linked to their differentiation into plasma blasts and memory cells. the objective of this study was to analyze in a comprehensive manner the effect of tlr- signaling on cytokine production by b cells from sle-patients, in comparison to b cells from hd, and in relation with disease activity. methods. b cells from sle-patients and hd were stimulated in vitro using cpg for hours, and culture supernatants were then tested for cytokines and chemokines (bio-plex). the cytokine responses were compared between both groups. in addition, within sle patients, the patterns of cytokines produced by b cells were compared with indices of disease activity. results. cpg-stimulation significantly increased cytokine production ( out of parameters; p< . ) compared to baseline. striking increases were found for il- ra ( ± pg/ml), il- ( ± pg/ml), il ( ± pg/ml) and ip- ( ± pg/ml; p< . ). there was no significant difference between both groups. remarkably, production of il- , il- , il- , il- p , il , il- , il- a, eotaxin, basic fgf, g-csf, gm-csf, ifn-γ, ip- , mip- α, and vegf correlated inversely with the sledai (p< . ) and even more (additionally il- β, il- ra, mip- β and tnf-α) with anti-dsdna antibody titers. the frequency of cd + memory b cells showed a positive correlation between the production of ip- and tnf-α in sle, whereas the levels of il- β, il- , mip- α, and mip- β showed a positive correlation with cd + b cells in hd. conclusion. the current data indicate hitherto unknown perturbations of cytokine/chemokine production by b cells in active sle. the inverse correlation of cytokines/chemokines produced by b cells from sle patients with sledai and anti-dsdna titer suggests that the known enhanced b cell proliferation and differentiation upon tlr -stimulation possibly diminishes cytokine production. background. several cytokines, including ifn-γ, il- , il- , and il- have been implicated in the pathophysiology of autoimmune disease. il- , a potent inducer of ifn-γ, enhances th responses that are thought to be synergistic and dependent on il- . we tested the hypothesis that intra-renal il- mediates kidney and systemic disease in mrl-faslpr mice. methods. by constructing il- p /il- -/-mrl-faslpr mice and using an ex-vivo gene transfer to deliver il- intra-renally, we determined that il- , independent of il- and/or il- , incites kidney disease in mrl-faslpr mice. moreover, we provide the novel finding that local intra-renal il- mediates systemic disease (lung pathology, systemic auto-abs). results. thus, our data indicate that il- is a potential therapeutic target for immune mediated kidney and systemic disease in mrl-faslpr mice. using a caspase- inhibitor, that inhibits the release of active il- and il- β, we successfully treated kidney (improved renal function, pathology) and systemic disease (skin lesions, lymphadenopathy, and splenomegaly) in mrl-fas lpr mice, while administration of an il- receptor antagonist did not influence disease progression. probing further we found that inhibition of il- activation results in an amelioration of lupusnephritis by a reduction of intra-renal infiltrating leukocytes (macrophages and t cells) and reduced activation of these leukocyte populations. moreover, caspase- inhibition resulted in decreased inf-y and il- production, indicating an altered balance of th and th cell responses in this model. conclusion. taken together, our findings indicate that il- , independent of il- β, il- and/or il- , is the major mediator of kidney and systemic disease mrl-faslpr mice. therefore, caspase- inhibition is a potential therapeutic target for autoimmune disease in the mrl-faslpr mice. background. in the treatment of giant cell arteritis (gca) glucocorticoid-related adverse effects occur frequently, particularly in patients with relapsing disease. a -year-old woman presented with a month history of fever, chills, arthralgias and cephalgias and markedly elevated serum inflammatory markers. whereas further evaluation including ultrasound of the temporal arteries was unremarkable, a positron emission tomography-computed tomography (pet-ct) demonstrated an intense fluorodeoxyglucose uptake of the aorta, the subclavian, carotid and femoral arteries. gca was diagnosed and treatment with high dose prednisone was begun. results. because of disease flares at prednisone dosages below mg/ day and the occurrence of vertebral fractures, cyclophosphamide and methotrexate (mtx) were added as glucocorticoid-sparing agents. as these treatments had to be stopped because of intolerance and mtxpneumonitis, respectively, we started tcz infusions ( mg/kg body weight). the clinical status rapidly improved. after infusions of tcz follow-up pet scan showed resolution of the previously seen uptake and we were able to taper the daily dose of prednisone to mg. treatment was well tolerated. however, the patient developed mild hyperthyroidism with a rapid rise of the initially normal levels of anti-thyroid peroxidase and anti-thyroid antibodies, anti-tsh receptor antibodies remained normal. thyroid function normalized and the antibody-levels fell without further treatment in the following months. in conclusion, this case demonstrates the successful treatment of a patient with relapsing giant cell arteritis with tcz. for the first time, we report the occurrence of a transient autoimmune thyreoiditis possibly induced by tcz. klinik für pädiatrie mit schwerpunkt pneumologie und immunologie, sektion rheumatologie, berlin, vestische kinder-und jugendklinik der universität witten/herdecke deutsches zentrum für kinder-und jugendrheumatologie organización médica de investigación arthr care res ar&t in press sp division of rheumatology diagnosesicherung: a + b) mr-morphologisch myositistypische veränderungen (os) histologie + c) generalisierte myalgien und laborchemisch dtl. elevierter ck, sowie positivem nachweis von ana und jo- -ak, pulmonales ct mit diffusen milchglasinfiltraten, in bronchoalveolärer lavage neutrophile alveolitis. ergebnisse. vormedikationen: a) glukocorticoidmonotherapie, mtx-monotherapie, mtx in kombination mit etanercept, cyclophosphamidboli, und zuletzt intravenöse immunglobuline (ivig) in kombination mit mycophenolatmofetil . b) mtx-monotherapie, mtx in kombination mit glukokortikoiden, cyclophosphamidboli, intermittierend intravenöse immunglobuline, cyclophosphamid per os (fau-ci). c) cyclophosphamidboli jeweils gutes ansprechen des ck-wertes auf jeweilige rituximabgaben mit ebenfalls ansprechen des klinischen bildes mit guter regredienz des aus myalgien resultierenden schmerzniveaus. im fall a keine beatmung mehr notwendig. im fall von c) auch gute regredienz subjektiver dyspnoesymptomatik und besserung wichtiger lungenfunktionsparameter, regredienz ctmorphologischer milchglasinfiltrate, im verlauf fehlender nachweis neutrophilie in bal. weitere rituximabgaben bei a, b und c im verlauf zum remissionserhalt nach jeweiligem klinischem befund production of cytokines by b cells in response to tlr stimulation inversely correlates with disease activity in sle-patients berlin zeitschrift für rheumatologie suppl · | das muskuloskeletale system, eines der am häufigsten betroffenen organsysteme bei sle (bei - % der sle-patienten). das ziel dieser analyse war es um diejenigen parameter zu identifizieren, die zu diesem effekt beigetragen hatten, wurde jeder der einzel-parameter zur untersuchung und symptom-erfassung innerhalb des muskuloskeletalen bilag-organsystems analysiert. die post-hoc-analyse umfasste nur patienten, bei denen ein parameter zu studienbeginn als vorhanden gewertet wurde, und jeder parameter erforderte ≥ patienten-beobachtungen pro kohorte um einen vergleich zu erstellen dadurch wurde die zahl der patienten mit einer initialen beteiligung des muskuloskeletalen systems aufgedeckt, die eine in woche auflösung der manifestation aufwiesen auch im selena-sledai-score war die rate der verbesserung bei dem arthritis-parameter in der belimumab-gruppe mit mg/ kg ( , %; n= ) und mg/kg ( , %; n= ) signifikant höher als die daten weisen darauf hin, dass mg/kg belimumab effektiv auf muskuloskeletale organmanifestationen sind akzeptiert als posterbeitrag auf dem eular klinische forschergruppe für rheumatologie (kfr), freiburg i. br., universitätsklinikum ulm, klinik für dermatologie und allergologie die physikalische therapie (pt) ist ein wesentlicher bestandteil der medizinischen versorgung von ssc-patienten patientenregister des dnss erfasst prospektiv, jährlich klinische verlaufsdaten zur organbeteiligung und therapie von patienten mit systemischer sklerodermie. die mittels freitext erfassten angaben zur verordneten pt wurden ausgewertet hivamat n= ( , %) und hylase n= ( , %) anwendung. die anzahl der verfahren, die die patienten zeitgleich erhielten, variierte zwischen mind. und max. . Über % der patienten erhielten anwendungen gleichzeitig. insgesamt wurden therapiearten genannt. , % der patienten mit gelenkkontrakturen zeigten nach einem jahr physikalischer therapie eine signifikante verbesserung der symptomatik (p= , ) gegenüber den patienten die keine physikalische therapie erhielten. nach drei jahren waren es , % der patienten (p= , ). bei den patienten mit muskelschwäche zeigten % der patienten eine signifikante symptomverbesserung (p= , ) dieser studie kann erstmals gezeigt werden, dass pt-symptome wie gelenkkontrakturen und muskelschwäche bei ssc-patienten signifikant verbessern kann. dennoch erhält weniger als die hälfte der ssc-patienten eine physikalische therapie punkten zur kontrolle einer mmf-therapie in der klinischen praxis zu untersuchen bei patienten ( -mal sle, je -mal systemische sklerose, sharp-syndrom und primäres sjögren-syndrom) die mmf erhielten, wurde , und min nach einnahme von mmf die mpa-konzentrationen im serum per hplc bestimmt. die mpa-auc wurde durch die mathematische methode der bayes %) und in der standarddosis von g/tag bei von patienten ( %) eine mpa-auc von > µg.h/ml. bei zwei patienten wurde nach der messung die dosis adjustiert: eine patientin mit einem sle mit diffus-proliferativer lupusnephritis hatte trotz einer mmf-dosis von g/tag nur eine mpa-auc von , µg.h/ ml. die dosis wurde daraufhin auf g/tag erhöht. der mpa-auc stieg danach auf max. , µg.h/ml und die krankheitsaktivität nahm ab (sledai von auf , proteinurie von auf mg/ h und prednisondosis von auf mg/tag) pharmakokinetic study of mycophenolate mofetil in patients with systemic lupus erythematosus and design of bayesian estimator using limited sympling strategies mycophenolic acid area under the curve correlates with disease activity in pupus patients treated with mycophenolate mofetil colony stimulating factor- (csf- ) -neuer aktivitätsmarker der lupusnephritis? brigham and wome's hospital, boston, renal division the authors would like to thank pfizer for supporting the study. furthermore the authors would like to thank the "deutsche kinder-rheumastiftung". einleitung. bei patienten mit früher axialer spondyloarthritis (spa) mit einer krankheitsdauer von< jahren und nachweis von akut-entzündlichen veränderungen in der ganzkörper-magnetresonanztomographie (mrt) in der wirbelsäule und/oder den sakroiliakalgelenken (sig) zu baseline [ ] untersuchten wir die langzeit-effektivität über vier jahre. methoden. in der esther-studie wurden patienten mit etanercept (eta, n= ) vs. sulfasalazin (n= ) behandelt [ ] . ab dem zweiten studienjahr wurden alle patienten mit eta behandelt (einige patienten unterbrachen zwischenzeitlich die therapie (n= ) zur untersuchung der biologika-freien remission und wurden dann (erneut) mit eta behandelt) [ ] . klinische, laborchemische und mrt-daten der patienten, die zu den jeweiligen studienzeitpunkten vorhanden waren, wurden im vierten studienjahr analysiert (as-observed-analyse). ergebnisse. von patienten, die zu baseline eingeschlossen wurden, erreichten , % das ende von jahr (n= ). in der gesamtgruppe zeigte sich ein gutes bis sehr gutes ansprechen, wobei etwa % eine asas partielle remission und etwa - % eine asdas inaktive erkrankung erreichten (. tab. ). der anteil der patienten mit normalem crp ("crp-remission") stieg von , % zu screening auf , % zu woche , während der anteil der patienten mit negativem mrt ("mrt-remission" definiert als fehlen akut-entzündlicher veränderungen in den sig und der wirbelsäule gemäß beider scorer) auf von % auf , % anstieg. , % der patienten zu woche waren sowohl in asas-remission, im status einer asdas inaktiven erkrankung als auch in mrt-remission. das ansprechen nach vier jahren war sehr ähnlich in den gruppen unabhängig davon, ob im ersten jahr sulfasalazin gegen wurde oder die therapie im jahr unterbrochen worden war (ergebnisse werden nicht gezeigt).schlussfolgerung. es zeigte sich ein konstantes und anhaltendes ansprechen bei patienten mit früher axialer spa, die mit etanercept behandelt wurden. das ansprechen scheint besser zu als bei patienten mit etablierter ankylosierender spondylitsi mit einer langen krankheitsdauer (> jahren; [ ] ). einleitung. in einer -wöchigen placebokontrollierten studie mit -wöchiger offener verlängerung bei patienten mit aktiver nichtröntgenologischer axialer spondyloarthritis (nr-axspa) wies adalimumab eine gute effektivität auf [ ] . bei patienten, bei denen es zum wiederauftreten der krankheitsaktivität nach absetzen des medikaments in woche kam, wurde die therapie wiederbegonnen ziel der studie war es, die langzeiteffektivität nach wiederaufnahme der therapie von adalimumab nach stopp über jahre zu evaluieren. methoden. bei ursprünglich in die studie eingeschlossenen patienten wurde die therapie nach wochen beendet und patienten ( % männlich, mittleres alter jahre, range - , mittlere krankheitsdauer vor therapiebeginn jahre, range - , % positiv für hla-b ) hatten, definiert durch erreichen eines % ansprechens gemäß der assessments in spondyloarthritis society-kriterien (asas ), gut auf die therapie angesprochen. bei wiederauftreten von krankheitsaktivität (definiert durch nicht mehr erreichen von asas ) wurde adalimumab mg alle wochen über jahre (woche r ) weitergeführt. die asas kriterien und der bath ankylosing spondylitis disease activity index (basdai) wurden in form einer completer-analyse berechnet. ergebnisse. der patienten mussten wiederbehandelt werden: / ( %) erreichten jahr , / ( %) erreichten jahr und / ( %) der patienten erreichten jahr der wiederbehandlung. nach jahren wiederbehandlung mit adalimumab erreichten / ( %) wieder asas und / ( %) erreichten partielle remission gemäß der asas-kriterien. nach jahren erreichten / ( %) und nach jahren / ( %) asas . asas partielle remission wurde nach jahren von / ( %) und nach jahren von / ( %) patienten erreicht. in der completer analyse fiel der mittlere basdai von , ± , zum zeitpunkt der wiederbehandlung auf , ± , im jahr (p< , ), , ± , (p= , ) im jahr und auf , ± , (p= , ) im jahr der wiederbehandlung ab. schlussfolgerung. in dieser gruppe von patienten mit aktiver nr-axspa, die ein gutes therapieansprechen über wochen mit adalimumab erreicht hatten und die bei wiederauftreten von krankheitsaktivität nach stopp der therapie in woche weiterbehandelt werden mussten, sprach die mehrheit der patienten, die in der studie verblieben, gut und anhaltend auf das fortsetzen der therapie an. tab. | sp- langzeit-effektivität über jahre etanercept-therapie bei patienten mit früher axialer spondyloarthritis. daten zu baseline (bl), jahr (w ), jahr (w ), jahr (w ) und jahr (w ). daten background. secukinumab (ain ) is a new fully human monoclonal antibody (mab) targeting il- a for the treatment of inflammatory diseases. administration of mabs can be associated with immunogenicity via the induction of anti-drug antibodies (adas). adas can lead to unwanted clinical consequences, such as loss of exposure, loss of efficacy due to altered pharmacokinetics and/or functional neutralization and, in the worst case, anaphylactic reaction and immune complex diseases. the assessment of ada formation is therefore a critical component in the assessment of biotherapeutic safety. methods. the immunogenicity assessment strategy for secukinumab follows a three-tiered approach. first, samples are analyzed for presence of ada in a screening assay which takes a % false-positive rate into account. in a second step, screening assay positive samples are tested in a confirmatory assay that identifies true positive responses. finally, true immunogenicity-positive samples are quasi-quantified via titration. a biacore-based assay was used during the early stages of the secukinumab program, and an msd-based bridging assay was applied during the later stages of the program. in addition, pharmacokinetics and clinical efficacy as well as safety data are also evaluated. samples to assess immunogenicity were obtained from individual subjects encompassing clinical studies in different indications during treatment and during follow-up. dosing regimens included single doses such as mg subcutaneously in psoriasis patients as well as multiple × mg/kg doses intravenously in ms patients over a six-month period.results. none of the subjects tested for immunogenicity developed sustained adas. in total, subjects met the definition of treatment-related, transient positive immunogenicity showing low ada titers. none of these subjects had evidence of loss of efficacy, deviating pk behavior or reported anaphylactic reaction or immune complex disease.conclusion. based on the available data, secukinumab appears to carry a low risk of immunogenicity. in the very few transient immunogenicitypositive patients identified so far, there has been no indication of altered pharmacokinetics or loss of efficacy, and no adverse event that could be linked to immunogenicity has been detected. more data from the ongoing phase studies are required to strengthen this encouraging finding in a larger patient population. risikofaktoren für eine aa-amyloidose bei entzündlich-rheumatischen erkrankungen und bei der idiopathischen aa-amyloidose methods. we report a case of an -year-old woman suffering from ulceration and signs of infection of the ulnar aspect of the right forearm due to subcutaneous calcification in association with crest syndrome.results. this case presents an unusual case of extensive subcutaneous calcification in crest syndrome requiring surgical excision due to secondary ulceration, inflammation and infection. while a surgical approach has already been described for calcification in different connective tissue diseases, only scant data of massive subcutaneous calcification related to a forearm in crest syndrome followed by surgical excision exist. conclusion. in crest syndrome, extensive subcutaneous calcification related to the forearm can occur. surgical excision followed by primary wound closure can lead to an excellent postoperative result. background. the whole blood interferon signature (wbifns) is measured in several clinical trials studying inhibitors of interferon alpha (ifn-α) in sle, but failed repeatedly -in contrast to the less sensitive ifnα -to reflect longitudinal changes in lupus activity and to guide dosage finding of rontalizumab. therefore, better ifn biomarkers reflecting disease activity over time and individual response to the inhibition of ifnα are needed to optimize the risk-benefit ratio of ifn-inhibitors. here, we show that the highly sensitive monocyte restricted ifnα response protein siglec- , also known as sialoadhesin or cd , is a useful biomarker to monitor longitudinal changes in disease activity of sle patients. methods. ifn-α and siglec- were measured by delfia and flow cytometry, respectively, in accurately characterized lupus patients over a period of up to months (overall visits). changes of biomarker and changes of disease activity (bilag ) were correlated using spearman rank test (srt). disease courses of selected sle patients were plotted to demonstrate in detail the relations of ifn-biomarkers with disease activity, sle medication and clinical manifestations. background. a -year-old woman was admitted because of sudden attack of convulsion and somnolence situation with positive canca and myeloperoxidase antibodies. cerebral magnetic resonance imaging (mri) showed thickening and marked progression of the dura-meningeal enhancement and edematous changes at pre and post central gyrus left side. based on these findings, it was diagnosed as hypertrophic cranial pachymeningitis related to anca-associated vascultis as unusual presentation. there was only temporarily und partial responce to a -month therapy with cyclophosphamide mg i.v and oral glucocorticosteroids . taking into consideration the severe, life-threatening course of the disease in the case of our patient, the decision was made to use rituximab, a chimeric, monoclonal igg antibody directed against cd , leads to destruction of b cells via complement mediated lysis and antibody dependent cellular cytotoxicity. the first administration of the medication was performed according to the pattern for rheumatoid arthritis patients treated with rituximab, i.e. infusions for mg in -day intervals in combined therapy with glucocorticosteroids. a follow-up mri at months after start with rituximab showed significant regression of the meningeal pathology at temporo-occipatel aspects (pachymeningitis) and completely resolution of edematous changes at pre and post central gyres. the complete clinical remission was achieved by introducing rituximab. conclusion. rituximab seems to be successful therapie for the induction and maintenance of remission in patients with anca-associated vasculitis (aav) with cns involvement (hypertrophic cranial pachymeningitis ) , who had previously failed to respond to standard treatment with cyclophosphamide and steroids and a range of alternative treatments [ , ] . antikörperdiagnostik. mit prednisolon-therapie ( mg/kgkg, mg/ tag) und zusätzlich methotrexat mg wöchentlich war keine anhaltende normalisierung der entzündungsserologie zu erzielen. infliximab ( mg/kg) -wöchentlich i.v. erbrachte nur kurzzeitig eine normalisierung der entzündungswerte, dann trotz weiterer infusionen einen erneuten anstieg der bsg bis auf mm, crp mg/l. nach umstieg auf tocilizumab ( mg / mg/kgkg) alle wochen konnte nach wochen eine bislang anhaltende normalisierung der entzündungsserologie erzielt werden (crp , mg/l, bsg mm . std.). der allgemeinzustand der patientin besserte sich deutlich, der hb-wert normalisierte sich auf , mmol/l. in der kontrastverstärkten sonographie fand sich ein abfall in der kontrastmittelaufnahme der a. carotis communis. die maximale intima-media-dicke reduzierte sich bislang auf , mm. schlussfolgerung. die bisherige standardtherapie der takayasu-arteriitis mit prednisolon und mtx führte auch im vorliegenden fall nicht zur remission. für infliximab fanden wir ein frühzeitiges therapieversagen des sonst erfolgreich beschriebenen ansatzes einer tnf-α-blockade bei riesenzellarteriitis. dennoch gelang mit tocilizumab eine bislang über monate andauernde klinische, sonomorphologische und serologische remissionsinduktion bei monatlicher fortführung der il- -blockierenden therapie. background. cd is the prototypic nk receptor that is also expressed on a unique population of effector cd + cells. these cd -expressing t cells are expanded in rheumatoid arthritis patients and had features of senescent cells. nkg d is another nk receptor over expressed on effector cd + cells in aav patients. cd + as well as nkg d + t cells seem to be involved in tissue injury as they are capable of mediating tcr-independent immune activation. it is hypothesized that il- is able to up regulate the expression of nk cell receptors. interleukin- (il- ) is a proinflammatory cytokine that is over expressed in aav and is linked to the expansion of cd + effector memory t cells (tem). in aav in remission a persistent expansion of these cd + effector memory t cells has been observed. in the present study we assessed the expression cd on cd + t cells of aav and if expression of these molecules was influenced by il- . methods. the distribution of cd + tem and the proportion of cd +cd + t cells and nkg d+ cd + t cells were analysed in aav-patients and hcs by facs. in vitro effects of il- on the expansion of cd + tem and up regulation of cytotoxic markers were assessed in the same way. in addition il- serum levels were measured in patients and hc by elisa. results. we observed an increased proportion of circulating cd +cd + t cells in aav as well as nkg d+ cd + t cells in patients in remission compared to hc ( . vs . p< . and vs . p< . ). % to % of these cells were cd + effector memory t cells. the percentages of the cd +cd + t cells and nkg d+ cd + t cells were constant over time. we also observed elevated il- serum levels in patients in remission compared to hc (p= . ). in vitro stimulation of pbmcs with il- increased not only the proportion of cd + memory cells (cd ro+) but also the expression of cd and nkg d on these cells. conclusion. the driving force behind the persistent expansion of a cytotoxic subset of cd + effector memory t cells expressing cd and nkg d+ and being tcr -independent is likely the increased il- expression in aav patients . ergebnisse. unabhängig von regime der remissionsinduktion und der primären erhaltungstherapie lag am ende der nachbeobachtungsperiode bei % der patienten eine renale remission vor ( %; % pr). % hatten eine persistierende proteinurie von > , g/tag bei stabiler nierenfunktion, % eine persistierende niereninsuffizienz mit erhöhtem kreatinin bei inaktivem sle, bei % wurden eine persistierende aktive ln und/oder renale rezidive beobachtet. vier patienten verstarben. patienten mit langzeit-cr waren gekennzeichnet durch einen niedrigeren tubulointerstitiellen chronizitätsindex in der initialen nierenbiopsie ( , ± , vs. , ± , ; p= , ), eine hochsignifikant geringere proteinurie nach cyc-pulsen ( , ± , vs. , ± , g/tag; p= , ) und niedrigere dsdna-ak ( ± vs. ± u/ml; p< , ) zum zeitpunkt des beginns der erhaltungstherapie. eine proteinurie von < , g/tag nach pulsen cyc zeigte eine sensitivität von % und eine spezifität von % für eine langzeit-cr. schlussfolgerung. eine proteinurie von < . g/tag nach remissionsinduktion mit pulsen cyc sowie ein geringer tubulointerstitieller chronizitätsindex in der nierenbiopsie sind prädiktoren einer anhaltenden kompletten renalen remission bei ln. background. to evaluate and compare clinical efficacy of three biomarkers for interferon activity (measured directly and indirectly) and six traditional biomarkers to indicate current disease activity in sle. methods. ifn-α (delfia), ip- (elisa) and siglec- (flow cytometry) was measured in accurately characterized lupus patients and compared to serum titres of anti-dsdna (elisa and ria), anti-dsdna-ncx elisa, anti-nuc elisa, c and c . disease activity was evaluated using bilag- and a modified sledai- (msle-dai- k). additionally, clinically quiescent patients were monitored for flares over the course of days. results. increased levels of ifn-α, ip- and siglec- were found in %, % and % of active sle patients. ifnα (r= . ; p< . ) and siglec- (r= . ; p< . ) correlated better with bilag- than ip- (r= . ; p= . ), farr assay (r= . ; p= . ), anti-dsdna-ncx elisa (r= . ; p= . ), anti-dsdna elisa (r= . ; p= . ), anti-nuc elisa (r= . ; p= . ), c (r=- . ; p< . ) and c (r=− . ; p= . ). predictors of sle flares were disease duration ≤ months, mild clinical activity (in contrast to no activity), complement c ≤ mg/dl and ifn-α ≥ pg/ml, while only lymphocyte count and age were independent predictors in multivariate analysis. conclusion. ifn-α, ip- and siglec- emerged as beneficial biomarkers for disease activity in lupus patients. therefore, implementation of ifn biomarkers in standard lupus diagnostics should be reappraised, especially in view of emerging anti-ifn-directed therapies. . ) and carried significantly more often other antibodies ( . %; p< . ), which were separated into u rnp-( . %), ro-( . %), pmscl-( . %) antibodies, followed by . % with rheumatoid factors, . % with la-, . % with dsdna-and . % with jo- -and . % with ku-antibodies. the kaplan-meier analysis of the onset of organ involvement revealed a clear inclined position of overlap patients between patients suffering from lcssc and dcssc, especially regarding lung fibrosis and heart involvement. patients suffering from pah, oesophagus involvement and kidney involvement, overlap and lcssc patients showed nearly similar curve progression (log rank < . ). furthermore musculoskeletal involvement was significantly more frequent and more progressive in patients with overlap disease, followed by patients with dcssc and lcssc (log rank < . ). conclusion. these data support the current concept, that ssc-overlap syndromes should be regarded as a separate ssc subset, distinct from lcssc and dcssc, due to a different course of the disease, different proportional distribution of specific autoantibodies and skin/organ involvement. methoden. patienten mit gpa ( mit aktiver und mit in remission befindlicher gpa) wurden durchflusszytometrisch analysiert und mit gesunden verglichen. eine färbung für cd , cd , cd , igd, iga, cd , mhcii, wurde mittels flowjo-software analysiert. die statistische auswertung erfolgte mit "graph pad prism" und p-werte< , wurden als signifikant angesehen. die studie wurde von der ethik-kommission der charité genehmigt. ergebnisse. deutliche unterschiede (p= , ) wurden sowohl für die absolute zahl als auch die frequenz der plasmazellen im peripheren blut der patienten mit gpa mit krankheitsaktivität ( , ± , /µl) im vergleich zu denen mit einem bvas von ( , ± , /µl) oder gesunden ( , ± , /µl) gefunden, ähnlich wie bei sle. bei patienten mit gpa ist außerdem eine signifikante erhöhte anzahl der plasmazellen igapositiv (p= , ). die anzahl der plasmazellen sowie die frequenz der plasmazellen an den b-zellen im blut korrelieren mit dem bvas (r= , ; p< , ). interessanterweise zeigte sich keine expansion der doppelt negativen memory-zellen, die zum beispiel beim sle beschrieben ist. für die naiven b-zellen fand sich ebenfalls ein signifikanter unterschied zwischen patienten mit aktiver erkrankung im vergleich zu gesunden. bei den t-zellen fanden sich nur diskrete veränderungen. schlussfolgerung. die anzahl der plasmazellen ist bei patienten mit aktiver gpa deutlich erhöht, was eine rolle von plasmazell-vermittelten mechanismen in der pathogenese nahelegt. ein großteil dieser plasmazellen ist iga-positiv, diese könnten eine rolle bei der hno-beteiligung spielen. key: cord- -g q gpp authors: nan title: neurocritical care society th annual meeting date: - - journal: neurocrit care doi: . /s - - - sha: doc_id: cord_uid: g q gpp nan eighty-five patients were enrolled, underwent therapeutic hypothermia, and had a poor outcome. baseline characteristics did not differ between groups, except for the use of sedatives: % of hypothermia versus % of normothermia patients (p= . ). corneal reflex, motor response and neuron specific enolase (nse), performed sub optimally in both the hypothermia and normothermia groups. however, all predictors accurately predicted poor outcome (fpr %) in patients without sedation regardless of whether they received hypothermia *numbers indicate percentages ( % ci). ‡ data not available for all patients. sedation is a confounder in the prognostication of comatose survivors after cpr. patients treated with hypothermia are more likely to receive sedation in proximity of their -hour neurological examination. hypothermia did not affect the accuracy of predictors of poor neurological outcome in this limited data set. methods: continuous eegs performed in a pediatric icu were transformed into -channel cdsa and aeeg displays. neurophysiologists and eeg technologists were trained to identify seizures using cdsa and aeeg. participants were then presented with only the cdsa or aeeg displays and asked to mark events that they suspected to be seizures. their performance was compared to seizures previously identified using the conventional - channel eeg recording. the eeg recordings contained discrete seizures over hours. the sensitivity for seizure identification and false-positive rates across all recordings are shown below. values are median (range). false-positive rate (# / hour) sensitivity (%) false-positive rate (# / hour) . ( . - . ) . ( . - . ) . ( . - . ) . ( . - . ) for individual recordings, however, the median sensitivity for seizure identification varied from % to %, and the median false-positive rate varied from /hour to . /hour. factors reducing the sensitivity included focal and low amplitude seizures. factors increasing the false-positive rate included movement and electrode artifacts, and non-ictal eeg waveforms such as periodic epileptiform discharges and a burst-suppression pattern. cdsa and aeeg are equally sensitive and specific tools for seizure identification among critically ill children. their performance is likely even better in a clinical context, when reviewers have access to the underlying raw eeg. these findings support the use of cdsa and aeeg as screening tools, with the caveat that low amplitude and focal seizures are liable to be missed using these techniques. intermountain medical center, salt lake city, utah, united states, johns hopkins hospital, baltimore, md, united states recent studies suggest that glucose variability is an important predictor for mortality in a mixed critically ill population, however, the relationship of glucose variability with sich remains ill defined. we sought to evaluate the relationship between glucose variability on in-hospital mortality during the acute phase of sich. we performed a retrospective chart review of consecutively admitted patients with sich with a minimum of glucose readings during the first -icu days. data extracted included: patient characteristics, clinical features, glucose values/insulin use, and outcomes. blood glucose indices assessed over the days included: average glucose levels (glucavg), standard deviation of glucose (glucsd), coefficient of variance (gluccv), and peak glucose (glucmax). statistical assessment of the glucose indices was assessed in relationship to in-hospital mortality. there were a total of glucose readings in patients with an overall mortality of %. univariate analysis showed the only significant baseline patient characteristics were lower admission gcs and higher apache ii in the nonsurvival group. admission glucose ( ± vs. ± ; p= . ), glucavg ( ± vs. ± ; p= . ), glucsd ( ± vs. ± ; p< . ), gluccv ( ± vs. ± ; p= . ), and glucmax ( ± vs. ± ; p= . ) were significantly higher in the nonsurvival compared to the survival group (mg/dl, respectively). logistic regression analysis showed that significant predictors for in-hospital survival include admission gcs (or . ; % ci . - . ; p< . ), glucsd (or . ; % ci . - . ; p< . ), and gluccv (or . ; % ci . - . ; p= . ). findings from this study suggest that a large variability of glucose during the acute phase of sich is associated with higher in-hospital mortality. the variability appears to be a more important predictor for outcomes than admission glucose or average glucose levels. the proportion of deaths was higher among patients in the intensive arm but this was not statistically significant ( % vs. %, p= . ). when good versus poor outcome at months was dichotomized to mrs score - versus - , respectively, there was no difference in outcome between the two groups ( . % vs. % had a poor three month outcome, p = . ). there was also no difference in icu or hospital los or days on mechanical ventilation. hypoglycemia (< mg/dl) and severe hypoglycemia (< mg/dl) was more common in the intensive arm ( % vs. %, p= . ) and ( % vs %), respectively. there was no benefit to intensive insulin therapy in this small critically ill neurologic population. previous studies of glycemic control in non-neurologic icu patients have shown conflicting results. this is the first glycemic control study specifically examining critically ill neurologic patients and functional outcome. given these results and the increased resources required to implement intensive insulin therapy, it cannot be recommended over conventional control. to improve organ donation conversion rates, neurointensivists at a level ii trauma, community hospital and the local organ procurement organization (opo) decided to diminish decoupling. decoupling is when the explanation of brain death by the physician is separated from the request for organ donation by the family support coordinator (fsc). the fsc is not present for the final explanation of declaration of brain death and the physician familiar to the family, typically, is not present for the request. we were concerned that in the transition of physician to fsc, conversion was being lost. data was retrospectively reviewed from - when decoupling was still occurring and compared to data thus far from where the physician and fsc were present together for both the final explanation of brain death (by physician) and request for organ donation (by fsc). we also compared data from two similar local hospitals that have not changed decoupling. all first person consent donors were removed from the data. in - , our hospital's conversion rate of eligible to actual donors was % and % respectively. in the first six months of , where decoupling was diminished, the conversion rate was %. the conversion rates for two other local hospitals of similar potential and patient mix were % ( ), % ( ) , and % ( ) (community based hospital); and % ( ), % ( ) , and % ( ) (university based hospital). the presence of the physician familiar to the family during the organ donation request may enhance organ donation conversion in non-first consent potential donors. physicians should consider working with the opo and fsc to try this process especially if conversion rates for organ donation are low. previous studies suggest that dynamic autoregulation in the posterior cerebral artery (pca) is less efficient compared to the middle cerebral artery (mca). we examined the role of cerebral vasodilation due to metabolic activation (i.e. visual stimulus) on autoregulatory characteristics in the two vascular territories. blood flow velocity (bfv) in the pca and mca and mean arterial pressure (map) were measured continuously in healthy volunteers ( ± years) while seated with eyes open. additional subjects ( ± years) were examined with eyes closed and open. cerebrovascular resistance index (cvr i ) was calculated as the ratio of map to mean bfv in the pca and mca arterial territories. autoregulation was assessed using transfer function gains in both the pca and mca territories in the low ( . - . hz), high ( . - . hz) and cardiac (~ hz) frequency ranges. the effects of vascular territory (pca vs. mca) or visual activation (eyes-closed vs. eyes-open) on bfv, map, endtidal co , cvr i , and transfer function coherence, gains, and phases were assessed by using a repeated-measures two-way anova, respectively. with eyes open, gains were significantly higher in the pca compared to the mca in the low (pca: . ± . vs. mca: . ± . , p= . ) and high (pca: . ± . vs. mca: . ± . , p= . ) frequencies. opening eyes increased bfv and reduced cerebrovascular resistance index in the pca but not mca. this vasodilation in the pca was associated with increased gain in the low (autoregulatory) frequency while mca gain did not change (pca: . ± . vs. . ± . , mca: . ± . vs. . ± . , p= . ). dilation of the pca territory during visual cortex activation resulted in increased pca transfer function gain without changing mca gain. thus, impaired autoregulation in the pca reported in previous literature is likely the result of metabolic vasodilation and not an inherent difference in the autoregulatory characteristics of the posterior circulation. various scales have been devised for the prediction of vasospasm following aneurysmal rupture. all such tools require the measurement of sah burden by computed tomography to predict the likelihood of symptomatic vasospasm. especially prominent in these scales is their reliance upon a subjective assessment of clot thickness which allows for variability in grading across raters. the current study seeks to compare the inter-rater reliability of the fisher and newer frontera scales when a rigid definition of thick clot is used. cases of subarachnoid hemorrhage were randomly selected from our radiographic archives. initial head cts were independently reviewed by two raters and a score for both the fisher and frontera scale was assigned to each study. the following criteria were established to characterize thick clot: . hemorrhage in any major cistern appearing on two contiguous slices; . hemorrhage occupying > % of any major cistern on a single cut; . contiguous hemorrhage with a density approximating that of bone. hemorrhage was scored as "thick" if any two of the three criteria were met. the degree of agreement in scores between raters was then assessed by way of the spearman's rho and cohen's kappa for inter-rater reliability. for both the fisher and frontera scales, a high degree of inter-rater reliability was demonstrated with rho values of . (p=. ) and . (p. ) respectively. when cohen's kappa was employed, respective values of . and . were obtained. these kappa values, which reflect the use of a stringent definition for thick subarachnoid hemorrhage, were stronger than those previously reported by ah. kramer et.al. with the use of a stringent definition for thick subarachnoid hemorrhage, an assessment of subarachnoid clot burden can be made that shows a high degree of reliability across observers. although ventilator-associated pneumonia (vap) carries significant mortality there is scarce data on vap in the neurosurgical intensive care unit (nsicu). we sought to determine the clinical factors associated with vap in the nsicu. we analyzed all admissions to the nsicu requiring mechanical ventilation for at least hours to determine factors associated with vap. we collected demographics, medical history, admission diagnosis, admission glasgow and four coma scale, tracheostomy need, ventilator days, length of stay, and mortality. for statistical analysis we performed fishers exact test (categorical variables) and students t-test (continuous variables). we used the centers for disease control vap definition. we analyzed admissions to the nsicu over one year. the sample was comprised of males and females with a median age of ( - ). the median gcs was ( - ) and the median four scale was ( - ). the median length of stay was days . diagnosis included subarachnoid hemorrhage ( %), head trauma, ( %) intracranial hemorrhage ( %), subdural hematoma ( %), spinal cord injury ( %), neoplasms ( %), and others ( %). the incidence of vap was . %. mortality was significantly higher (p < . ) among patients with vap ( %) than in non-vap patients ( %). there was no difference in clinical risk factors, admission diagnosis, and need for tracheostomy. the mean age of vap patients was and that of non-vap patients was . age < was associated with vap (p< . ). the only clinical variables associated with vap were mechanical ventilation for > days and four score < (p = . and . respectively). in the nsicu vap is frequent and carries significant mortality. duration of mechanical ventilation and four coma score predict vap. poster blood pressure decreases due to general anesthesia for intra-arterial therapy for acute ischemic stroke are associated with decreased functional relative hypotension after large vessel stroke is associated with poor outcome. general anesthesia (ga) causes peripheral vasodilation and cardiac depression, leading to a decrease in systemic blood pressure. in initial analysis of the merci registry-a prospective, uncontrolled cohort of patients treated with the merci retriever-functional outcome after stroke was worse in those patients intubated for the procedure as compared with those in whom conscious sedation or deep sedation was performed. we hypothesized that the poor functional outcomes in intubated patients resulted from decreased systemic blood pressure. the study population consisted of all patients enrolled at our institution in the merci registry from october to july . during the study period, all ia stroke interventions were performed under ga. data regarding demographics, stroke severity (nihss on presentation), recanalization (tici grade), and functional outcome at days (modified rankin scale; mrs) were prospectively collected. we retrospectively reviewed the blood pressures on presentation, prior to intubation and after intubation. : patients were identified; of these, had adequate records of blood pressure before and after intubation as well as day follow-up assessments. the average age was and % were male. compared with pre-intubation baseline, significant reductions in sbp ( . vs . , p<. ) and map ( . vs . , p<. ) were observed following intubation. controlling for well established predictors of outcome (nihss, age, location of vessel occlusion, and recanalization), the first sbp and dbp recorded immediately after intubation were significantly correlated with mrs (p= . , p= . ) with lower measurements associated with poor functional outcomes. blood pressure declined significantly as a result of general anesthesia, and lower sbp and dbp following intubation were associated with worse functional outcomes. these findings suggest that blood pressure should be aggressively supported in acute stroke patients treated undergoing ia mechanical thrombectomy. posttraumatic vasospasm (ptv) is an under-recognized cause of ischemic damage following traumatic brain injury (tbi), but little is known about its pathogenesis and risk factors. although ptv significantly differs from aneurysmal vasospasm [ , ] , it shares certain characteristics [ ] [ ] [ ] [ ] that may provide insight into its pathogenesis. in particular, the risk of aneurysmal vasospasm is increased in patients with fever [ ] [ ] [ ] [ ] [ ] [ ] or leukocytosis [ - ], but these relationships have not been previously explored in ptv. a review of consecutive patients with tbi yielded patients with severe tbi that survived beyond hours. eight patients developed clinically significant posttraumatic vasospasm (csptv), defined as unexplained decline in neurological function or brain tissue oxygenation with ct angiogram evidence of arterial vasospasm. temperature and serum leukocyte counts were compared in severe tbi patients with and without ptv. admission temperature was significantly higher in patients that developed csptv ( . . ºc vs. . . ºc, p= . ), and fever on admission (t> ºc) was associated with significantly increased likelihood of vasospasm (or= . ). csptv did not occur in patients with hypothermia (t< ºc) on admission, while % of those with fever (t> ºc) developed csptv. admission leukocyte count was significantly higher in patients that developed csptv ( . . k/mm vs. . . k/mm , p= . ). . % of patients with leukocytosis on admission (wbc> k/mm ) developed csptv, compared to . % of patients without leukocytosis. hyperthermia on admission correlates with increased likelihood of developing clinically significant ptv. serum leukocyte count on admission is higher in patients who subsequently develop csptv, suggesting that activation of inflammatory pathways and/or early infection may be involved in the pathogenesis of vasospasm. the observation that csptv did not occur in patients with admission temperatures below ºc suggests a possible protective role for early hypothermia. subarachnoid hemorrhage (sah) frequently causes stunned myocardium (sm). the predictors of sm and its impact on clinical course and outcome are not fully defined. we evaluated consecutive sah patients enrolled in the sah outcomes project from february -june . patients were excluded due to history of cardiac disease, were excluded due to non-aneurysmal sah. sm was defined as wall motion abnormalities +/-elevated troponins. demographic, clinical, and outcome data was compared between those with and without sm. results: % (n= ) of patients were hunt & hess (hh) grade - . modified fisher score was >= in % (n= ). sm was diagnosed in % (n= ). on univariate analyses, sm was associated with loss of consciousness (loc) at onset, hh grade, hijdra score, posterior aneurysm location, female gender, tobacco non-use, bmi, ivh, systolic bp, heart rate (hr), glucose, and wbc count. in a logistic regression accounting for race and age, female gender (p= . ), loc at onset (p< . ), posterior aneurysm location (p= . ), hr (p= . ), systolic bp (p= . ), hh grade (p< . ) & tobacco non-history (p= . ) were independent predictors of sm. sm was associated with in-hospital development of fever, hyperglycemia, pneumonia, anemia, seizures, global cerebral edema (gce), sodium dysregulation, and arrhythmia. after accounting for age & gender, arrhythmia (p< . ), fever (p= . ), and gce (p< . ) were independently associated with sm. after adjusting for gender, age and known risk factors for poor outcome, sm was an independent predictor of mrs > and death at months. chronic brain atrophy is regionally specific and is regionally associated with reductions in oxidative brain metabolism but not ischemia. the temporal lobe exhibit the greatest extent of atrophy, which may be related to the extent of initial trauma. leão's spreading depression (sd) of electrocorticographic (ecog) activity describes a propagating wave of neuronal/astroglial depolarization in cerebral grey matter. sd occurring in normally perfused cortex may be benign, but similar peri-infarct depolarizations (pid) cause ischemic lesion growth. here we present results of a pilot study to determine the association of depolarizations with clinical outcome in traumatic brain injury (tbi). at five hospitals, subdural electrode strips were placed in patients who required craniotomy for surgical management of tbi. sd and pid events were identified by criteria of fabricius et al. (brain : - , ) in ecog recordings made during intensive care for a median duration of hr. six-month egos scores were dichotomized to good ( - ; n= ) and poor ( - ; n= ) outcomes. in / ( %) patients, depolarizations occurred. of these, were sd type, were pid, and were mixed. the proportion of poor outcomes was % ( / ) in patients with no depolarizations, compared to % ( / ) in patients with sd and % ( / ) for patients with pid. the occurrence of pid and either type of depolarization were both significantly associated with worse outcomes (fisher exact test, p= . and , p= . , resp.), while sd alone was not ( , p= . ). there was no association of pupil reactivity ( , p= . ), gcs motor score ( , p= . ), pre-hospital hypotension ( , p= . ), or subarachnoid hemorrhage ( , p= . ) with outcome. ages of patients with good ( ± s.d.) vs. poor ( ± ) outcome did not significantly differ (p= . ). these data suggest that depolarization activity is significantly associated with poor outcome, with predictive power at least as great as established outcome predictors. prevention of depolarizations by pharmacologic or physiologic therapy may represent a novel strategy to improve tbi outcomes. an increased sample size is required for improved statistical power and to determine the independence of depolarizations from co-variates. introduction: vasospasm (vs) represents a substantial source of morbidity and mortality in patients with subarachnoid hemorrhage (sah). transcranial ultrasound (tcus) velocities indicating vs in the anterior cerebral artery (aca) are not well established. the purpose of this study is to identify aca velocities that correlate to ipsilateral aca infarction. the aca mean velocities of consecutive sah patients undergoing routine twice daily tcus were prospectively collected. the maximum (max), minimum (min), and first (fir) mean velocity value for each vessel was determined, as were the ratios for max/min and max/fir. this process was performed for the entire group, and then for only patients having at least days of readings. determination of aca territory infarction was made by evaluation of serial head ct scans performed up to day following the ictus. velocity comparisons were made between patients having and those not having aca territory infarctions on ct. for the entire group, data was available for vessels, of which had associated infarction. max velocity was somewhat greater in patients with aca infarctions ( cms/s vs cms/s, p=. ), and min velocities were substantially greater ( cms/s vs cms/s, p=. ). the group having at least days of tcus constituted vessels, of which had associated infarction. max velocity was again somewhat greater ( cms/s vs cms/s, p=. ) and min velocity was again significantly greater ( cms/s vs cms/s, p=. ). no correlation was observed for fir, max/min, or max/fir. patients ultimately developing aca infarctions have greater min velocities and tend to have greater max velocities. since only the use of max velocities is practical, our findings suggest that velocities between - cms/s may identify those vessels at risk for infarction, which is consistent with the available literature. cerebral infarction following subarachnoid hemorrhage (sah) contributes to morbidity and mortality. vasospasm (vs) has traditionally been considered the main cause, yet recent literature suggests other potential etiologies. anterior cerebral artery (aca) infarctions may result in permanent deficits of intellect and behavior. the purpose of this study is to document the prevalence of aca infarctions and to characterize the etiology of these infarctions in patients with aneurysmal sah. consecutive sah patients underwent review of cerebral ct scans as close to weeks after the ictus as possible so as to identify sah related aca infarctions. earlier scans were reviewed in patients found to have aca infarctions to determine the timing of the infarction. vs related infarctions were defined as those beginning at least days after the ictus. infarcts occurring less than days after the ictus were considered to be non-vs related. imaging was available for patients ( aca territories). overall, . % of patients developed aca infarctions in . % of aca territories. of these, only . % of patients and . % of territorial infarcts were deemed likely due to vasospasm. most aca infarct patients ( %) had aca/acomm aneurysm ruptures. of patients with aca infarction and aca/acomm aneurysms, % had infarcts within the first days (p=. ). all bilateral aca infarctions with aca/acomm aneurysms had infarctions within days of the ictus. aca infarctions are not rare in patients with sah. patients with aca/acomm aneurysms were more likely to have aca infarcts in the acute phase, prior to the usual onset of vs. the etiology of these infarctions remains to be determined, but may be related to vessel thrombosis at the time of hemorrhage, procedural/operative complications, or early vs. telemedicine holds promise as a technology-intensive method of providing rapid acute neurology expertise to local hospitals with available ct scanning, and has been proposed as a way to increase access to limited specialty expertise in a cost-effective manner. we here report the experience of a multi-state telemedicine company, working in joint effort with academic hospitals, providing acute neurological consultations to community-based hospitals. specialists on call (soc) is a california-based telemedicine company providing / specialist physicians consultations to urban, suburban and critical access hospitals via videoconferencing technology. neurological consultations are conducted by board-certified neurologists. consults requests are responded within minutes. initially, the specialists discusses the case by telephone and in a second step, the video-conference is started. teleneurological exam is conducted following established and validated guidelines, especially for nihss. recommendations and further steps are discussed with patients, family members and consulting physician. between january and may , a total of teleneurology consults were performed, among community hospitals in states. only hospitals had over beds ( and ), the rest ranged between and beds. stroke was the diagnosis in cases ( . %), of which ( %) were acute ischemic events (aie) (stroke or tia) and ( %), intracranial hemorrhages. ( . % of aie) received thrombolytic therapy with intravenous tpa. seizure was the diagnosis in patients ( . % of the total) and other diagnosis (including headache, dizziness, vertigo and chronic pain) in ( . %) patients. telestroke consultation can be useful in increasing the use of intravenous tpa at community hospitals without access to adequate on-site stroke expertise. besides thrombolytic decisions, teleconsultation can improve the care of other neurocritical conditions, including seizures, or intracerebral hemorrhage and triage to centers with neurocritical-care capability. increased intracranial pressure (icp) is associated with poor outcome in acute brain injury. in this study we examined how episodes of increased icp (> mmhg; > minutes) affected brain metabolism. twenty-one patients (mean age . + . years) with severe brain injury (gcs< ) were studied prospectively. lactate, pyruvate, and glucose were measured each hour using cerebral microdialysis (cma). brain oxygen (pbto ), mean arterial pressure (map), icp and cerebral perfusion pressure (cpp) were recorded continuously. linear mixed effects models were used to examine the relationship between episodes of increased icp and the lactate:pyruvate ratio (lpr). there were episodes of increased icp, episodes of compromised pbto (< mmhg) and episodes of brain hypoxia (pbto < mmhg). median icp ( % - % iqr) was greater during brain hypoxia ( . [ . ] vs. . [ . ]; p < . ). gee models indicated that icp > mmhg was associated with more than double the odds of brain hypoxia (or= . ; % ci: . , . , p= . ) or compromised pbto (or= . ; % ci: . , . , p= . ). however the frequency of increased icp (> mmhg) was similar among patients with compromised pbto (p= . ) or brain hypoxia (p= . ) compared to normal pbto . only half the patients with brain hypoxia had increased icp. elevated lpr (> ) was rare (n= [ . %] of icp episodes). median lpr ( % - % iqr) was greater during episodes of brain hypoxia than normal pbto ( . ( . ) vs. . ( . ), p< . ) and only slightly greater in episodes with compromised pbto compared to corresponding episodes with normal pbto ( . ( . ) vs. . ( . ), p= . ). lpr did not increase when icp was > mmhg. evidence for brain energy dysfunction is very rare when icp is > mmhg and any icp effect on lpr may be indirect and depend on pbto . rafael badenes, pablo gonzalez, laura alcover, armando maruenda, javier belda hospital clinico universitario, valencia, spain this was a pilot study to compare the cerebral neurochemical changes in patients with traumatic brain injury (tbi) who underwent conventional blood glucose level (bgl) control and intensive bgl control with continuous titrated insulin. this prospective, randomized study was conducted in traumatic brain injury patients in a surgical and trauma intensive care unit. patients admitted over an -month period with tbi were prospectively divided into two groups according to the method used for bgl control: the 'intensive' group consisted of patients who underwent continuous titrated insulin infusion to maintain a lower normoglycemic level of - mmol/l, and the 'conventional' group consisted of patients whose bgl was maintained at between . and . mmol/l using conventional 'sliding scale' bolus subcutaneous insulin administration. data on cerebral haemodynamics, interstitial brain oxygenation (ptio( )) and neurochemical monitoring were collected via microcatheters inserted in the penumbral region. we analyzed cerebral microdialysis samples. in patients treated with intensive insulin therapy, there was a reduction in microdialysis glucose by % of baseline concentration compared with a % reduction in patients treated with a conventional blood glucose level control. intensive insulin therapy was associated with increased incidence of microdialysis markers of cellular distress, elevated glutamate ( +/- % vs. +/- %, p<. ), elevated lactate/pyruvate ratio ( +/- % vs. +/- %, p<. ) and low glucose ( +/- % vs. +/- %, p<. ), and increased global oxygen extraction fraction. cerebral microdialysis glucose was lower in nonsurvivors than in survivors ( . +/- . vs. . +/- . mmol/l, p < . ). intensive glycaemic control using insulin induced a decrease of cerebral glucose and an increase in microdialysis markers of cellular distress. in patients with severe brain injury, tight systemic glucose control is associated with increased mortality. brain tissue oxygen (bto ) monitoring is used in severe traumatic brain injury (tbi) patients. how cerebral hypoxia should be treated and its response to treatment is not clearly defined. we examined which medical therapies restore normal bto in tbi patients. severe tbi (gcs less than ) patients were enrolled in a prospective observational cohort study. intracranial pressure (icp), cerebral perfusion pressure (cpp) and bto were monitored. episodes of cerebral hypoxia (bto less than mmhg) and medical interventions and therapies that improved bto were identified. three hundred seventy nine episodes of cerebral hypoxia were recorded and treated in forty nine patients (mean age +/- years). medical management successfully reversed % of the cerebral hypoxia episodes. ventilator manipulation, cpp augmentation, and sedation were the most frequent interventions. increasing fio restored bto % of the time. cpp augmentation and sedation were effective in % and % cerebral hypoxia episodes, respectively. icp reduction using mannitol was effective in % of treated episodes. phenylephrine was the most frequent vasopressor administered and improved bto % of the time. other interventions including head repositioning, airway suctioning, and blood transfusions, were effective in %, %, and % treated episodes, respectively. successful medical treatment of cerebral hypoxia was associated with improved outcome. survivors had a % rate of response to treatment (n= ) and nonsurvivors had a % rate of response (n= ; p= . ). cerebral hypoxia occurs in tbi patients despite traditional practices to maintain cpp. medical interventions other than those to treat icp and cpp can improve bto , increasing the number of therapies for severe tbi in the icu. poster intravenous dantrolene for the treatment of cerebral vasospasm after subarachnoid hemorrhage -final results of a prospective phase i cerebral vasospasm (cvsp) after subarachnoid hemorrhage (sah) is the major cause of disability and death. treatment options are limited. dantrolene blocks ryanodine receptor-mediated intracellular calcium release from the sarco-endoplasmic reticulum. it attenuates cerebral vasoconstriction, potentates the action of nimodipine on cerebral vessels and is neuroprotective in animal models. we performed a prospective phase i study examining the safety and effects of a single-dose of dantrolene on cvsp after sah. in an irb approved, prospective, open-label single-blinded phase i study, sah patients with elevated transcranial doppler (tcd) velocities and lindegaard indices suggesting cvsp were enrolled. after baseline tcds by a single, trained operator, patients receive a one-time infusion of dantrolene over minutes with dose escalation (first five patients . mg/kg, the following five patients . mg/kg). infusions, ventilator and ventriculostomy settings were kept unaltered, so that physiological data could be followed. hr, bp, icp, cpp, cvp and body temperature were recorded at infusion start (time ), every min during the infusion and with every tcd thereafter. serum abg, chem and osmolarity were measured at time and min, and lfts at time and hrs. tcds were repeated at , and min after time . statistical analysis was performed with repeated measures anova for the physiological values and change ( ) in systolic, mean and diastolic tcd in the vessel in cvsp from time , followed by post-test bonferroni's multiple comparison test with bonferroni p-value adjustment for significant findings. laboratory values were analyzed by wilcoxon matched pairs test. ten patients (n= each group with . mg/kg and . mg/kg dantrolene) were enrolled. over the entire study period, hr, map, dbp, icp, cpp and body temperature remained stable, except for sbp which decreased (p= . ). posttest bonferroni's multiple comparison test with p-value adjustment (p= . ) showed a trend towards a difference between time points and min (mean - . mmhg), and and min (mean - . mmhg), although this was not significant. significantly different laboratory changes were na (mean - . meq/l, p= . ), cl (mean - . meq/l, p= . ) and alkaline phosphatase (mean - . mg/dl, p= . ); the degree of change, however, was considered clinically insignificant. none of the other laboratory values changed. systolic and mean tcd velocities decreased significantly over time compared to time (systolic p= . ; diastolic p= . ; mean p= . ). post-anova linear trend testing indicates the magnitude of change: systolic (slope - . , p= . ); diastolic (slope - . , p= . ) and mean tcd (slope - . , p= . ). a one-time infusion of dantrolene appears safe, although the mild changes in na, cl and alkaline phosphatase warrant monitoring. most importantly, transaminases did not change. dantrolene decreases tcd velocities over time, presumably due to inhibition of cerebral vasoconstriction. we have insufficient data to comment on the duration of this effect. our results warrant further study with repeated or continuous dantrolene dosing for treatment or prevention of cvsp after sah or other vasoconstriction syndromes. status epilepticus carries a mortality rate up to %. newer, intravenously (iv) applicable antiepileptic agents might be powerful adjunctive therapies. we report our experiences with iv levetiracetam in a prospective patient cohort with status epilepticus. we treated patients with convulsive status epilepticus with an institutional protocol consisting of iv lorazepam followed by iv phenytoin, iv levetiracetam as third line agent or second line agent if there were contraindications for iv phenytoin, and iv propofol and/or midazolam as fourth line agents. primary outcome was treatment success of iv levetiracetam. secondary outcome measures were time to treatment success, modified rankin scale (mrs) at and months, and complications. of the patients had cerebral structural abnormalities, an infection, and hyponatremia as underlying etiology for status epilepticus. median age was (range - ) years, patients were male. baseline gcs was ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . levetiracetam successfully treated status epilepticus in patients. median time to treatment success was ( - ) minutes in all patients. at months patients had died, support had been actively withdrawn in patients. the mrs was in patients, in patients, in patient, in patients, in patients and in patients. at months, patient with a mrs of had progressed to . the most common complications included hyperglycemia ( %), hypotension ( %), acute renal failure ( %), anemia ( %), thrombocytopenia ( %), urinary tract infection ( %), and seizure recurrence ( %). levetiracetam offers a feasible alternative strategy to break status epilepticus as adjunctive third line therapy in a paucity of patients before administration of sedatives with a broad spectrum of adverse effects and needs to be studied in a standardized trial. stroke is the third leading cause of death in industrialized nations.the treatment pathway for ischemia is often determined by assessing the extent of permanent damage aided by imaging modalities such as mri.diffusion weighted imaging (dwi) is an accepted mri technique that is sensitive to water diffusion.the restriction of water in damaged cells is used as a surrogate measure of cell death.although cells may have taken on water,this surrogate measure may be inaccurate,frequently leading to overestimation of the severity of ischemia.measures of sodium are reported to be more accurate indicators of cell death and can also be used to determine stroke onset time because of a linear relationship between ischemia and sodium concentration.we have developed a multinuclear coil and radiofrequency current source that permit simultaneous high-speed proton and sodium imaging so that treatable ischemia can be better ascertained. an -channel,broadband,radiofrequency,phased array and current source were built enabling targeted,accelerated,and simultaneous spectroscopic imaging of water,helium,and sodium on a . t ge mr scanner.it was tested on phantoms of known sodium and water concentrations and in rats with known inhaled helium concentrations. high quality imaging of protons and sodium in phantom models of known sodium concentration were obtained.additionally, high quality helium imaging in rats demonstrated the ability of the system to image other nuclei and proved the quantitative and qualitative imaging capabilities of the array in vivo. mars imaging provides a new, simultaneous multinuclear approach to determine the extent of ischemia quickly and quantitatively.high quality images with this system can be obtained in humans with the same hardware and can be used with standard . t mr scanners. septic shock is often associated with relative vasopressin (avp) deficiency that may be related to impaired avp synthesis and release by the neurohypophyseal system, which includes the neurohypophysis and magnollecular neurons of the paraventricular and supraoptic nuclei. neurohypophyseal system has never been assessed in human septic shock and only partially in experimental sepsis. we investigated avp synthesis and release by the neurohypophyseal system in septic rats and in human septic shock. design: ex vivo human and animal study. setting: university research laboratory in the human study, post-mortem examination of the neurohypophyseal system was performed in patients who died from septic shock (n= ) or other causes (n= ). in the experimental study, sepsis was induced by fecal peritonitis in conscious, fluid-resuscitated male adult wistar rats. rats either early died spontaneously from septic shock in average at hours (septic early death, n= ) or were sacrificed in average hours after induction of sepsis (septic, n= ). post-mortem examination was performed in both groups. comparisons were made against sham operation controls (n= ). avp protein and mrna were assessed by immunohistochemistry and in-situ hybridization. in both septic shock patients and septic rats with early death, the avp content in the neurohypophyseal and supraoptic magnocellular neurones was decreased while it was increased in the paraventricular magnocellular neurones. no significant change was observed in avp mrna expression in either paraventricular or supraoptic magnocellular cells. in septic shock, avp post-transcriptional synthesis and transport are altered in the supraoptic and paraventricular magnocellular neurones, respectively. this suggests that supraoptic and paraventricular nuclei are liable to distinct pathogenic mechanisms, which may account for relative avp deficiency. introduction: dual brain death (dbd) examination has been historically followed to determine irreversible brain damage. a policy was introduced in our hospital to utilize single brain death examination (sbd) including an apnoea test and a confirmatory test for cerebral blood flow in patients with catastrophic neurological injuries to determine brain death. we investigated if organ procurement would be affected by sbd. the database of gift of life (the designated organ recovery organization for michigan), was screened for our institution patients meeting brain death criteria between jan and july . for each patient, age, sex, primary cause of mortality, number of brain death examinations performed, type of confirmatory tests used to declare brain death, medical exclusions for organ donation and number of organs procured was obtained. continuous variables were analyzed using the student t-test and categorical variables using fischer's exact test with p values set at . . seventy patients met brain death criteria between january and july and were excluded due to incomplete records. there was no difference between the age and sex composition between the two groups. twenty seven patients were diagnosed with brain death using sbd while were diagnosed using dbd. twenty four patients with sbd and with dbd were eligible for organ donation (p= . ). each of eligible sbd and dbd patients donated organs (p= . ); organs were procured from each group (p= . ). single brain death examination did not preclude the rate of organ donation in our patient cohort. dual brain death examination can be substituted by a single brain death examination along with a confirmatory test for cerebral blood flow in patients with catastrophic neurological injuries without affecting the rate of organ donation. this may result in a less time delay before declaring death and minimize physician workload. etiologies for spontaneous intracerebral hemorrhage (ich) or intraventricular hemorrhage (ivh) vary. mri can often identify underlying vascular lesions, but conventional catheter angiography remains the gold standard. guidelines for the use of catheter angiography are non-specific. we aimed to determine the diagnostic yield of catheter angiography in addition to mri in patients with ich or ivh who met pre-defined criteria. consecutive patients with spontaneous ich or ivh were enrolled. in addition to non-contrast brain ct and laboratory testing, all patients underwent gadolinium enhanced mri/mra. catheter angiography was pursued if the following criteria were met: . lobar ich or isolated ivh and age years or . deep ich and no history of hypertension and age years or . any other indication based on the opinion of the treating neurointensivist. of prospectively enrolled patients, ( %) met criteria for catheter angiography. seven were excluded from angiography because a definitive ich cause was established by mri and because of a coagulopathy explaining the ich. forty-four ( %) patients underwent catheter angiography, which identified the ich etiology in ( %). in of these, the diagnosis was already suspected based on mri, but in cases catheter angiography increased the diagnostic confidence. in one patient a small avm was diagnosed by angiography alone. thirteen patients ( %) had both contrast angiography and pathology. of these, had a vascular abnormality as the cause of the ich. five of these were diagnosed by angiography. in one patient the pathology showed an avm while the angiogram and the mri were negative. two patients with cavernous malformations were diagnosed by mri alone. the diagnostic yield of catheter angiography in spontaneous ich or ivh is limited if patients also undergo gadolinium enhanced mri/mra. patients with anticoagulation-related intracerebral hemorrhage (ich) commonly are treated with fresh frozen plasma (ffp) for anticoagulation reversal. one risk of ffp is thought to be related to volume overload and pulmonary edema (ped). however, this has neither been validated, nor quantified compared with the natural risk following ich. we hypothesized that patients with anticoagulation-related ich are at higher risk of ped in-hospital, and that this increased risk would be related to dose of ffp used. retrospective review of a prospectively collected cohort of consecutive patients with primary ich presenting to a single center between august -may . of included patients, % were male, and mean age was +/- years. % were on warfarin at presentation, with a median inr of . (iqr . - . ). of these patients, % received ffp, at a median dose of (iqr - ) units. overall, patients ( . %) developed ped, at a median time of (iqr - ) days after presentation, and these patients showed a longer hospital length of stay [median (iqr - ) days vs. (iqr - ) days, p= . ]. anticoagulated patients were at higher risk of developing ped during hospitalization ( % vs. %, p= . ). patients receiving ffp were also at higher risk than those who did not ( % vs. %, p< . ). in multivariable analysis with a cox proportional hazards model, use of ffp was an independent predictor of developing ped (hr . per unit given, % ci . - . ), and the effect of warfarin fell out of the analysis when ffp was included. patients with anticoagulation-related ich are at increased risk of ped during hospitalization, accounted for by ffp use. each additional unit of ffp confers an approximately % increased risk of this complication. ventilator associated pneumonia (vap) is an infrequently studied morbidity in neurointensive care, despite high historical rates ranging from . to . infections per device days. in comparison, mean rates in medical icu's have been substantially lower: . - . . in our neurocritical care unit (nccu), vap incidence was initially near the national nosocomial infection surveillance (nnis) th percentile for neurosurgical icus ( . infections per ventilator days) necessitating an evidence-based performance improvement initiative to reduce vap rates. prospective surveillance study of vap incidence in a -bed nccu over a month period. vap rates were defined by national healthcare safety network (nhsn) criteria. interventions included an aggressive hand hygiene campaign, use of the ventilator bundle, oral care every hours, and introduction of the hi/lo endotracheal tube. ventilator bundle compliance was assessed. : patient days with a total of ventilator days were monitored. in september , concomitant to an acinetobacter outbreak, vap rates were infections per ventilator days. by january , hand hygiene compliance had increased from to % and rates were . following institution of frequent oral care in combination with the emphasized vap bundle, by may , rates had decreased to . at this point, all new intubations performed in the unit employed the hi/lo ett. by june , vap incidence decreased to . infections per ventilator days (< th nnis percentile). compliance with components of the ventilator bundle ranged from % to %. despite caring for patients at high risk of vap, concerted efforts with multiple evidence-based performance measures and interventions can significantly reduce the incidence of infection. feedback with compliance may be essential to maintain low vap rates. the use of hmg-coa reductase inhibitors (statins) has increased among subarachnoid hemorrhage (sah) patients for cerebral vasospasm prophylaxis. statins increase risk of myopathy, but additional factors may also be causative. myopathy rates in this group of critically ill patients are not well characterized. sah patients were prospectively entered into an institutional database; those with myopathy were retrospectively identified. serum creatine kinase (ck), aldolase (at time of suspected myopathy diagnosis), and catecholamines (at admission), muscle biopsy results, and medication administration records were evaluated. four ( . %) of aneurysmal sah patients treated between jan , through july , were newly diagnosed with myopathy. two were hunt/hess , and each: grade and . one was fisher , others were fisher . all had symptomatic hydrocephalus, were treated endovascularly with paralysis paraprocedurally, given simvastatin mg daily within hours of sah (none had prior statin use). all were insulin resistant, requiring high dose sliding scale insulin. two received steroids. all had elevated catecholamines. maximum ck levels (u/l) were , , , and , respectively. aldolase was checked and elevated in patients. the forth underwent muscle biopsy revealing necrotic fibers; this patient had the lowest maximum ck. the myopathy rate in this cohort is times higher than that reported in healthy patients treated with statins. since all sah patients did not receive statins, this rate is underestimated and much higher than reported in other trials evaluating statins in sah, assuming risk is solely attributable to statins. the contribution of other etiologic variables (critical illness, paralytic, steroid) is not clear, and potentially are additive. aldolase may be an additional means of identifying subclinical cases. these findings need to be confirmed and pathogenic factors better elucidated. neurocritical care is a relatively new discipline and its practitioners come from a variety of backgrounds. salaries are likely to differ based on primary appointment, geographic location, practice setting, and time spent on clinical effort. it is not known how many neurointensivists practice full-time critical care, and it is likely that many also have responsibilities as consultants, researchers and administrators. a survey will be emailed to all members of the neurocritical care society. information that will be collected regarding salary, icu directorship, primary appointment, practice setting, hospital type, geographic location, percent effort on clinical responsibilities, sources of income including salary incentives, patient population, board certification and subspecialty training, etc. the results will be reported at the meeting and compared to the previous survey done by the authors. the information gathered in this survey enhances the understanding of the current practice of neurocritical care throughout the united states. this data may be valuable to neurointensivists during contract negotiations, to hospital administrators trying to assess the feasibility of hiring a neurointensivist, and to neurologists-in-training as a way of generating interest in neurocritical care as a career choice. therapeutic hypothermia (th) is being implemented with an increase for multiple indications in the neuro-icu. the risk of developing renal dysfunction with th is thought to be low, but is not clearly defined in neurologic patients. retrospective chart review of prospectively identified patients. per institutional th protocol, patient's goal temperature was c. baseline serum creatinine (cr) level and creatinine clearance (crcl) were obtained and followed at least daily during th and rewarming. data was evaluated for changes in cr and crcl during and following th induction and any impact these changes had on treatment. thirty five patients received th (for post-cardiac arrest and intracranial pressure control related to subarachnoid haemorrhage, intracerebral haemorrhage or traumatic brain injury). maintenance of goal temperature varied from to hours. nine ( %) had an increase in cr and crcl within normal limits; of these, occurred following induction, occurred during th maintenance, and during rewarming. three ( %) patients had an elevation in cr above normal limits; all of these elevations arose after beginning rewarming, and none led to chronic renal failure. there was a direct relationship in the change in cr and crcl (p< . ). of the patients who had an abnormal change in cr, had an abnormal change in crcl. overall, % of the patients demonstrated some form of elevation in cr and decrease in crcl. no patient experienced clinically significant changes in renal function requiring changes in therapy. this cohort experienced changes in renal function that were not associated with clinical relevance. the majority of changes occurred during th or rewarming and were not chronic. any contribution of th induced muscle injury to cr changes would need to be assessed with future study. initial hematoma size, coagulopathy, and hypertension are recognized predictors of hematoma progression in intracerebral hemorrhage (ich). we aimed in our study to assess if the absolute number of wbc and/or increase in the wbc number within hours of progression can predict hematoma progression. data of consecutive patients with primary, supratentorial ich, admitted within h of onset were reviewed, identifying patients with progression (wp) and no progression (np). hematoma progression was defined as % increase of hematoma size, subsequent intraventricular bleeding or increase of the preexistent amount of intraventricular blood. we compared the two groups for demographic data, risk factors, admission neurological status, neurological deterioration occurence, and wbc, coagulation profile, and blood pressure (bp) at admission or within hours of hematoma progression, using univariate and multivariate analysis. we identified cases (np) and (wp). baseline variables were similar, except for the systolic bp that was higher in wp than in np group ( + mmhg versus + mmhg, p= . ). neither wbc at admission ( . + . x /mm versus . + . x /mm , p= . ) nor the variation of the wbc admission -within h of progression ( . + . x /mm versus . + . x /mm , p < . ) was significantly different between the np and wp groups. neurological deterioration and mortality were more frequent in the wp than np group ( % versus %, p< . ; % versus %, p= . respectively). logistic regression showed that the change in wbc from admission to within hours of progression and systolic bp were associated with hematoma progression (wald statistic . , p< . ; wald statistic . , p < . ). the variation of wbc within hours of progression and systolic bp seem to be independent predictors of hematoma progression. heparin-induced thrombocytopenia (hit) is a dreaded complication of heparin related products. we analyzed the risk factors and outcomes of subarachnoid hemorrhage (sah) patients in whom hit was suspected and either confirmed as present or absent by platelet factor (pf ) antibody test. all patients with presumed aneurysmal, non-traumatic sah and a pf test were identified through the massachusetts general hospital's research patient database. charts, laboratory values and images were analyzed retrospectively. we identified patients with sah who were tested for hit. of these patients, ( %) had a positive antibody test. there was no difference between mean platelet nadirs of hit+ and hit-patients, vs. th/mm , respectively. univariate analysis identified gender, magnesium prophylaxis, fisher group , clipping vs. coiling, presence of angiographic spasm, number of vasospasm treatments and day of hit testing as potential risk factors associated with hit. a multivariate analysis showed that female gender (or . , %ci . - . ), greater number of vasospasm treatments (or . , %ci . - . ), later day of hit testing (or . , % . - . ) increased the risk of hit and coiling reduced the risk compared to clipping (or . , %ci . - . ). those patients in whom hit was present had more infarcts on ct, longer icu and hospital stays and worse modified rankin scores on discharge. the presence of hit in sah has adverse consequences and is more likely in female patients, who have undergone aneurysm clipping and require more than one endovascular vasospasm treatment. coagulopathy-associated intracerebral hemorrhage (cich) leads to over % mortality and is associated with secondary thromboembolic (te) complications. rapid coagulopathy reversal improves cich outcome. activated factor viia (fviia) rapidly reverses coagulopathy and causes local hemostasis, but is associated increased te. we examine a large case series of cich patients treated with fviia to determine te rates in this population all cich patients are treated with standardized protocol with emergent intravenous vitamin k, fresh frozen plasma (ffp), and are eligible for fviia mcg/kg. we identified consecutive fviia-treated cich patients from database from - and identified patients. were excluded for no identifiable coagulopathy or fviia use for severe trauma. were analyzed. we collect data on diagnosis, coagulopathy etiology, history of ischemic heart disease (cad) and te. we examined the incidence of troponin elevation, ekg changes, symptomatic coronary ischemia, venous thrombosis, and stroke following fviia use. subjects had average age . years. over % had abnormal ekg on presentation. % fviia-treated cich patients had history of venous thrombosis (dvt) or pulmonary embolism (pe), % had cad, % had atrial fibrillation, and % stroke. troponin elevation above . ng/ml developed in % patients. only / patients developed clinically symptomatic cardiac ischemia. % developed dvt/pe, and / ( . %) developed ischemic stroke. there is a trend towards correlation of cad history with degree of troponin elevation (p= . ). coagulopathy-associated ich patients have high burden of prior ischemic heart disease and venous thromboembolism. though low level troponin elevations occur, incidence of fviia-related symptomatic cardiac ischemia, stroke, or venous thrombosis is low in fviia-treated cich patients. this low incidence justifies a prospective controlled study to evaluate risk versus benefit of fviia use for emergent coagulopathy reversal in cich. assessing neurological function is important in critical illness, but in sedated patients neurological examination is considered to be non interpretable. this prospective multicentre observational study assessed neurological responses in critically ill patients who required to be sedated with midazolam (± subfentanyl). their relationship with -day mortality and altered mental status (delirium or coma within three days after sedation discontinuation) was also assessed. daily neurological examination included the glasgow coma scale, the assessment to intensive care environment score (atice), eye position and movement, pupil size and response to light, corneal reflex, oculocephalic response, grimace to noxious stimuli and cough reflex. at awakening, mental status was assessed with using atice or confusion assessment method for the icu ( neurological examination is interpretable and may be useful for prediction of outcome of critically ill sedated patients. daniel evans , gail tudor , deborah cushing , jeffrey florman , david seder maine medical center, portland, me, united states, husson college, bangor, me, united states, we evaluated complication rates, outcomes, and the cost of care of patients with good-grade (hunt and hess grades i-iii) aneurismal subarachnoid hemorrhage (ggsah) admitted directly to an intermediate care unit (imc). retrospective chart review of all ggsah admitted to a tertiary referral center from to . we recorded demographics, vital signs, and pertinent aspects of the hospital course. a multivariate logistic regression model including hunt and hess grade was employed to evaluate for association between admission location and radiographic or clinical vasospasm or infarction. among ggsah admissions to imc or the intensive care unit (icu), mortality was . %. thirty-three grade i patients ( %), grade ii patients ( %), and grade iii patients ( %) were admitted directly to imc. none of these patients died, and ( %) suffered cerebral infarction. factors associated with imc admission were lower hh grade (p< . ), gcs of (p< . ), and no ventricular drain placement (p=. ). age, medical comorbidities, and clipping vs. coiling were not associated with admission location. eight patients ( %) admitted to imc were subsequently transferred to icu. patients admitted to icu were more likely to die ( % vs. %, p=. ), to suffer respiratory failure ( % vs %, p=. ), and fever ( % vs %, p=. ). in multivariate logistic regression, imc admission was unrelated to vasospasm or infarction. admission to icu was associated with higher median patient charges ($ , . vs. $ , . , p< . ). we found no evidence that imc admission (primarily among hunt and hess i and ii patients) was associated with increased morbidity, and the in-hospital mortality rate of imc admissions over years was zero. given the higher cost of care among patients admitted to icu, it may be appropriate to consider imc admission for selected patients. wei xiong, matthew koenig, xiaoxu kang, xiaofeng jia, adrian puttgen, nitish thakor, romeryko geocadin johns hopkins university, baltimore, md, united states neurologic injury from cardiac arrest (ca) continues to be a significant problem, in part due to the lack of real-time monitoring of brain injury and recovery. somatosensory evoked potentials (sep) are a reliable marker of poor outcome because they are relatively resistant to physiologic and therapeutic perturbations. we tested the hypothesis that early recovery of cortical sep would be associated with better outcome after resuscitation from ca. sixteen adult male wistar rats were subjected to asphyxial cardiac arrest. half underwent mins of asphyxia (group ca ) and half underwent mins (group ca ). continuous seps from median nerve stimulation were recorded from these rats for hours immediately following ca. additional serial seps were recorded at , , and hours after ca. clinical recovery was evaluated using the neurologic deficit scale ( - , normal = ), which was performed at , , and hours after ca (primary outcome measure). all rats in group ca survived to hours, while only rats in group ca survived to that time. mean nds values in the ca group at , , and hours after ca were . , . , and . ; while in group ca , they were . (pvalue . ), . (p-value . ), and . (p-value . ), respectively. the n (first negative peak at approximately ms) amplitude differed significantly between the two groups within hour after ca. rats that suffered longer ca durations showed later recovery of n . the n latency was similar between the two groups. although early recovery of n showed a trend towards better -hour nds scores, this was not significant. a smaller n peak was consistently observed to recover earlier in all rats, which may represent the thalamic component of sep. the delayed recovery of n is associated with longer ca times in rats. early recovery of n shows a trend towards better outcomes. n , which may represent thalamic activity, reappears much earlier than cortical responses (n ), suggesting thalamocortical desynchrony in early recovery. sep after ca is a dynamic and promising tool to monitor early neurologic recovery after ca. evidence suggests a role for inflammation in vasospasm after subarachnoid hemorrhage (sah). recent studies suggest that systemic inflammation may lead to vasospasm. to test the hypothesis that systemic inflammation worsens vasospasm we evaluated the effect of lps on vasospasm. c bl/ j mice received either ug/animal lps i.p., or saline. hours later, animals had either sah induction or sham surgery. in a separate group, neutrophils were depleted prior to lps administration. to test whether neutrophils in the csf from the sah are required for vasospasm, we injected blood from lps-sensitized, neutrophil-depleted mice to the csf of lps-sensitized, non-depleted mice and the converse (adoption studies). at hours post injection, animals were perfused with saline, formalin and india ink, and the brains were removed for quantitative evaluation of basal cerebral vasculature for vasospasm. the mean differences in diameter of mca segments at mm distal to bifurcation were compared. a separate set of animals were perfused with saline and formalin for immunohistochemical staining of neutrophils and microglia. in saline-injected animals with sah, the mean vessel diameter was significantly smaller compared to the salineinjected sham group. there was no difference in the means of vessel diameter between saline-or lps-injected sham groups. lps injection in the animals with sah exacerbated the vasospasm. neutrophil depletion prior to lps ameliorated vasospasm. neutrophil extravasation into the brain and microglial activation was increased in the lps group compared to controls but was reversed by neutrophil depletion. in the adoption studies, depletion of neutrophils in the csf blood ameliorates vasospasm but neutrophil depletion in the systemic circulation did not. systemic inflammation induced by lps exacerbates vasospasm. the effect is reversed by neutrophil depletion in the csf. this suggests that inflammation in the brain is a more important contributor than systemic inflammation in vasospasm. malnutrition in the intensive care setting is associated with increase mortality presumably secondary to increased infections. acute ischemic and hemorrhagic stroke patients in the icu often experience a delay of enteral nutrition due to delays in swallowing evaluation and diagnostic procedures that require a period of food abstinence. serum albumin levels are often used as markers for malnutrition. this study was retrospective analysis of patients admitted from january/december with the diagnosis of ischemic or hemorrhagic stroke. the goal of the study was to determine the association between albumin levels less than . mg/l during the first hours of icu admission and mortality. t-tests were used to identify significant difference between means. chi-square tests were used to examine the distribution of categorical variables across discharge statuses. after identifying variables that were significantly different, a logistic model was built to determine if admission day albumin levels are independently associated with mortality. there was no difference in mean serum albumin levels between non-survivors ( . mg/l) or survivors ( . mg/l (p= . )). there was no difference between non-survivors and survivors in day albumin levels or in the change from day to day . a logistic model controlling for age and dyslipidemia (factors significantly or marginally significantly elevated in non-survivors) showed that admission day albumin was not an independent predictor of outcome. in our study, there was no correlation between serum albumin levels and mortality. we did not analyze the incidence of infections in this study population. this study validates the may critical care medicine guidelines on nutrition support in the icu. they concluded that albumin was not a valid nutrition assessment tool in the icu. future studies should examine the relationship between hypoalbuminemia, prealbumin levels and the incidence of infections in the stroke patient population. tnf-is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. recent studies have suggested that tnf-may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (sah). we studied comatose sah patients who underwent multimodality neuromonitoring with intracranial pressure (icp), cerebral microdialysis, and brain tissue oxygen (pbto ) as part of their clinical care. continuous physiological variables were time-locked every hours and recorded at the same point that brain interstitial fluid tnf-was measured in brain microdialysis samples. significant associations were determined using generalized estimation equations. each patient had a mean of brain tissue tnf-measurements obtained over an average of hours of monitoring. tnf-levels rose progressively over time. predictors of elevated brain interstitial tnf-included higher brain interstitial fluid glucose levels ( = . , p< . ), intraventricular hemorrhage ( = . , p< . ), and aneurysm size > mm ( = . , p< . ). there was no relationship between tnf-levels and the burden of cisternal sah; concurrent measurements of serum glucose, or lactate-pyruvate ratio. brain interstitial tnf-levels are elevated after sah, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels. experimental studies have demonstrated that tumor necrosis factor-(tnf-) plays a crucial role in the onset of hemolysis-induced vascular injury and cerebral vasoconstriction [ ] . we hypothesized that tnf-measured from brain interstitial fluid would correlate with the severity of vasospasm following aneurysmal subarachnoid hemorrhage (asah). from a consecutive series of asah patients who underwent cerebral microdialysis (md) and evaluation of vasospasm by computed tomographic angiogram (cta) or digital subtraction angiography (dsa), tnf-levels from md were measured at hour intervals from sah days - using enzyme-linked immunosorbent assay (elisa). a blinded attending neuroradiologist independently evaluated each cta and dsa and assigned a vasospasm index (vi). five patients had vi< and patients had a vi> , where the median vi was (range - ). median log tnf-area under the curve (auc) was . (pg/ml)*day (interquartile range . - . ) for the vi< group, and . (pg/ml)*day (interquartile range . - . ) for the >= group (p< . ). in this small series of poor-grade asah patients, the area under the curve of tnf-levels from sah days - correlates with severity of radiographic vasospasm. further analysis in a larger population is warranted based on our preliminary findings. mild therapeutic hypothermia (th, - ºc) reduces mortality and improves neurologic outcomes after ventricular fibrillation cardiac arrest (ca). the relationship between time to achieve th and outcomes remains undefined. we hypothesized that a shorter interval from ca to achieve th would be associated with improved neurologic outcome. we retrospectively reviewed all subjects with in-or out-of-hospital ca treated with th between november and april at our institution. the time to target temperature was defined as the interval between witnessed ca and first measurement of hypothermia ( ºc) and further categorized as early (< hours) or delayed (> hours). outcomes were assessed at the time of death or discharge by the cerebral performance category score (cpc). good neurologic outcome was defined as cpc or . fisher's exact test was used to assess the univariate relationship between time to target temperature and neurological outcome. patients were treated with th after in-hospital ( %) and out-of-hospital ( %) ca. subjects that did not reach target temperature or with unwitnessed ca were excluded. of the remaining patients, % ( / ) survived to discharge and % ( / ) achieved a good neurologic outcome. five patients ( / ) reached early target temperature; % ( / ) of those had a good neurological outcome. % ( / ) of subjects with delayed target temperature achieved a good neurological outcome. the univariate relationship between time to target temperature and neurological outcome was statistically significant (p= . ). attaining th within hours of in-or out-of-hospital ca is associated with a greater likelihood of a good neurological outcome at discharge. time from ca to achieved th should be included as a clinically important covariate in future studies of predictors of outcome after ca. cerebral autoregulation tests have gained importance for the assessment of patients with a variety of brain disorders. in critically ill patients, testing of dynamic autoregulation is safe and practical, but the ability to respond to steady state change in blood pressure is probably more clinically relevant. the purpose of this study was to compare static autoregulation testing with two different dynamic autoregulation tests (cuff deflation and carotid compression tests) in patients with severe traumatic brain injury. twenty-two studies were performed in tbi patients. changes in middle cerebral artery flow velocity (mcafv) were observed by transcranial doppler. static autoregulatory index (sari) was determined from the steady-state response of mcafv to phenylephrine-induced rise in blood pressure. dynamic autoregulatory index (dari) was determined by the cuff deflation method as described by aaslid ( ) and the transient hyperemic response ratio (thrr) was calculated as described by smielewski ( ) . these dynamic tests were performed in triplicate at baseline prior to inducing hypertension with phenylephrine, and the values were averaged to give a single index value. since the anatomy of the brain injury varied from patient to patient, the autoregulatory indices were summarized for the worst and best sides of the brain based on the appearance of the initial ct scan. the sari averaged . + . on the side of the brain that was more injured, and . + . on the less injured side. thrr was closely correlated with the sari, both on the side that was more injured (r=. , p=. ) and on the less injured side (r=. , p=. ). the dari was significantly correlated with sari only on the side that was more injured (r=. , p=. ). these data suggest the ability of dynamic autoregulation to predict static autoregulation may vary with the type of test chosen. published guidelines from the american society for gastrointestinal endoscopy considers peg tube placement a high-risk procedure for bleeding and recommends discontinuation of clopidogrel, to days before peg placement. unfortunately the perioperative time period is associated with increased ischemic events, length of stay (los) in the hospital and resource consumption. this is a retrospective review of prospectively collected data that sought to examine the safety of peg tube placement in patients while on clopidogrel alone or in combination with aspirin. patients admitted into our neuro-icu who met the set criteria during the period january to july were included in the study. mean duration on antiplatelet therapy prior to peg placement was days. one patient had a new stroke during hospitalization, unrelated to the procedure. no post-operative complications, bleeding or neurologic changes were noted in any of the patients. relevant blood indices remained largely unchanged. although peg tube placement is considered a high-risk procedure for bleeding, in the absence of pre-existing bleeding disorder it may be safe to perform this procedure in patients taking clopidogrel. there may be no need to consider reversion to aspirin alone, in those on combination therapy. timely placement of peg tubes in this subgroup of patients may reduce their los and decrease the risk of new ischemic events. introduction: hunt and hess grade sah is accompanied by high rates of mortality and severe disability. mortality in these patients is driven by withdrawal or limitation of care. some patients do enjoy good functional outcomes. we seek to describe the frequency and predictive factors for good outcome following grade sah. we will also describe risk factors for limitation of care following grade sah. we identified consecutive patients with sah and worst hunt and hess grade of within hours of admission (mean age years; % female) in a prospectively collected registry of aneurysmal sah patients. the frequency of good outcome (modified rankin through ) at months was calculated. we performed univariate analysis of pre-admission and admission characteristics to identify associations with good outcome. independent risk factors were identified through multiple logistic regression analyses. we performed a multivariate analysis of risk factors for limitation of care. good functional outcome occurred in ( %) of patients. white ethnicity (or . %ci . - . ), employment at the time of sah (or . %ci . - . ), lack of limitation of care (or . %ci . - . ), and normal papillary reactivity on admission (or . %ci . - . ) were independently associated with good outcome. in a subgroup of patients in whom care was not limited, ( %) had good outcomes; white ethnicity(or . %ci . - . ), employment status(or %ci . - . ), and absence of fever(or . %ci . - . ) independently predicted good outcome. among patient characteristics analyzed, admission gcs(p< . ) predicted limitation in care. a substantial proportion of patients with grade sah who receive full medical support enjoy a good recovery at months. age, pre-morbid co-morbidity, and clinical and radiographic measures of hemorrhage severity do not predict good outcome in our study, but socioeconomic factors may. intracerebral hemorrhage (ich) is the most lethal type of stroke. hypertensive ich (hich) is the most frequent ich subtype. we aimed to evaluate predictors of -day mortality after hich. retrospective cohort. this study was approved by our irb. we found patients with hich amongst patients admitted to our hospital from july to june . mortality was % (n = ). thirty-two patients ( %) were male, and ( %) were black. mean age was ± years ( patients were years). initial pulse pressure ± mm hg, and mean gcs score was ± . mean ich volume was ml (range, . to ml) measured on first head ct scan with the use of the abc/ method, and patients ( %) had intraventricular hemorrhage (ivh). fifty-five patients ( %) had supra-and patients had infra-tentorial ich. the mean ich score (hemphill, et al. stroke. ; : - ) was . points (range, to points). one of patients with ich score of , and patients with scores of or died. in univariable logistic regression modeling, all independent predictors used to develop the ich score, except age years (p = . ), were associated with day mortality: initial gcs (p = . ), ich volume (p = . ), ivh (p = . ), and infra-tentorial ich (p = . ), and the ich score (p = . ) accurately predicted mortality at days. in multivariable logistic regression analysis, only gcs alone was predictive of -day mortality. the roc/auc analysis demonstrated that gcs was a powerful predictor of mortality with an auc = . . gcs was the most powerful predictor of mortality. our study suggests that gcs is a powerful predictor of -day mortality after hich. further research is warranted. pneumocephalus is found in % of postcraniotomy computed tomographies of the head (ctoh) and is considered a benign complication of surgery. occasionally, however, it may lead to lethargy, headache and, if under tension, signs of elevated intracranial pressure or brain herniation. high percentage supplemental oxygen is frequently used as a treatment, but data regarding its effectiveness are very limited. postcraniotomy patients admitted to the neuro-intensive care unit with pneumocephalus received % fio on-off every hours for at least hours (treatment subgroup). during the off period, this subgroup, as well as the controls remained on room air (or % fio if mechanically ventilated). the assignment to each subgroup was based on the neurosurgeon's preference. the intracranial air volume on the ctoh was measured before and after the intervention via an image j analysis package. twenty-two treated patients and controls (mean age and years, and % women, respectively) were identified. the most common diagnoses were subdural hematoma (in % vs % for the treatment and control subgroups, respectively) and tumor ( % in both). there was no difference in the number of ventilated patients or in those with external ventricular drainages, in the lapsed period between the initial and final ctoh and the initial and final volume of air between the two subgroups. the percentage of air volume change (after adjustment for the lapsed time) and the rate of air absorption were significantly higher in the treated group ( % vs %, p = . and . . %/hour vs . . %/hour, p = . , respectively). this pilot study suggests that intermittent oxygen administration in patients with craniotomy decreases the pneumocephalus volume and increases the rate of intracranial air absorption. in a recent publication (wijdicks et al. neurology. oct ; ( ): - ), the safety of apnea testing in the declaration of brain death was evaluated at a single tertiary care center. one major conclusion was that apnea testing was safe in hemodynamically compromised patients in most circumstances and rarely aborted. determinants of apnea test completion failure are unknown. we calculated the alveolar-arterial oxygenation gradients (a-a gradient) in the previously studied cohort. arterial blood gas values were obtained prior to the initiation of apnea testing. patients that completed the procedure during the declaration of brain death were compared to those whose studies were aborted. statistical analysis was performed using nonparametric wilcoxon rank-sum test. of the original patients studied, a-a gradients were calculated for patients. seven of these patients had aborted apnea testing because of hypoxemia and/or hypotension. seventy-nine percent of patients that completed apnea testing had gradients larger than mm hg compared to % in those whose study was aborted, % versus % with gradients greater than mm hg, and % versus % with gradients greater than mm hg. the a-a gradient median values for completed and aborted apnea tests were mm hg (range: - - ) and mm hg (range: - ), respectively (p value= . ). the apnea test can be performed safely in most hemodynamically compromised individuals with large a-a gradients undergoing brain death evaluation. a larger percentage of patients that failed completion of apnea testing had significantly greater a-a gradients. predicting apnea test failure with this respiratory parameter warrants further validation in a larger population. cerebral glucose metabolism and energy production are affected by serum glucose levels. the objective of this study was to assess whether serum glucose variability and the ratio of cerebral-to-serum glucose are associated with cerebral metabolic distress and outcome after severe brain injury retrospective cohort study conducted in a neurological intensive care unit of a university hospital. we studied consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring.continuous insulin infusion was used to maintain target serum glucose levels of - mg/dl. general linear models of logistic function utilizing generalized estimating equations were used to relate these predictor variables to cerebral metabolic distress (defined as a lactate/pyruvate ratio [lpr] ) and mortality. the ratio of brain-to-serum glucose was calculated every to hours. daily serum glucose variability was expressed as the standard deviation (sd), mean amplitude glycemic excursion (mage), and glycemic lability index (gli) of all serum glucose measurements. a total of neuromonitoring hours and days were analyzed. after adjustment for glasgow coma scale scores, cerebral perfusion pressure, and serum glucose levels, brain/serum glucose ratios below the median ( . ) were independently associated with increased risk of metabolic distress (adjusted or= . [ . - . ], p< . ). increased serum glucose variability was also independently associated with higher risk of cerebral metabolic distress (adjusted or= . [ . - . ], p< . for sd and adjusted or= . [ . - . ], p= . for mage). low brain/serum glucose ratios and all three measures of increased serum glucose variability were also independently associated with in hospital mortality after adjusting for age and apache-ii scores (all p . ) reduced brain/serum glucose ratios and increased serum glucose variability are associated with cerebral metabolic distress and increased hospital mortality after severe brain injury. in critically-ill neurological patients, cerebral perfusion may be optimized by manipulating cerebral perfusion pressure and cardiac output. the objective of this study was to investigate the relationship between cardiac output (co) response to a fluid challenge and changes in brain tissue oxygen pressure (pbto ) in patients with severe brain injury prospective observational study conducted in a neurological intensive care unit of a university hospital. normal saline ( ml) or albumin % ( ml) boluses were given according to a standardized fluid management protocol. the relationship between co and pbto was analyzed using generalized estimating equations with an exchangeable correlation structure we studied fluid challenges administered to consecutive comatose patients that underwent multimodality monitoring with co, intracranial pressure (icp), and pbto . diagnoses included subarachnoid hemorrhage (n= ), intracerebral hemorrhage (n= ), cardiac arrest (n= ), traumatic brain injury and status epilepticus (n= each). of the fluid boluses analyzed, ( %) resulted in a % increase in co. median absolute (+ . vs+ . mmhg) and percent ( % vs %) changes in pbto were greater in co responders than in non-responders. in a multivariable model, a co response was independently associated with pbto response (adjusted or . , %ci . - . , p= . ) after adjusting for mean arterial pressure, icp and end-tidal co . stroke volume variation showed a good ability to predict co response with an area under the roc curve of . and a best cutoff value of %. bolus fluid resuscitation resulting in augmentation of co can improve cerebral oxygenation after severe brain injury little current data exists regarding outcome, cost and length of stay after subdural hemorrhage (sdh). we sought to examine predictors of discharge disposition, icu and hospital length of stay (los) and direct, indirect, icu, surgical and imaging charges for sdh. a retrospective review was conducted of acute, chronic and subacute sdh patients, aged > years admitted to our hospital between - . disposition was characterized as dead or poor (discharged to a nursing home, hospice, subacute or chronic care facility). multivariable logistic regression analysis was performed to identify predictors of each outcome variable. of sdh patients, the median age was . ( - ), and the median admission glasgow coma scale (gcs) was ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . the sdh was characterized as acute in ( %), subacute in ( %), chronic in ( %) and acute, subacute and chronic in ( %). craniotomy was performed in ( %) of patients, burrhole drainage in ( %) of patients and both in ( %) of patients. death occurred in ( %) of patients and poor outcome in ( %). significant predictors of death or poor outcome included age, admission gcs and hospital los (all p< . ). surgery was protective against poor outcome (odds ratio [or] . , % confidence interval [ci] . - . , p= . ). median hospital los was ( - ) days and median icu los was ( - ) days. both were associated with gcs (all p< . ). median total direct charges for hospitalization were $ , ($ -$ , ). icu and hospital los were significant predictors of direct charges, overhead, imaging and surgical charges (all p< . ). herniation, sdh thickness, type of sdh, type of surgery and gender did not predict discharge disposition, cost or los. despite good admission neurological status, death or poor discharge outcome is common after sdh. though surgery mitigates against poor discharge disposition, los and charges remain high. sathees thayapararajah, bryan young, irene gulka, ahmed al-amri, sujit das lhsc, university of western ontario, london, on, canada introduction: acute fulminant hepatic failure (afhf) is common in tertiary care centers with transplant facilities. cerebral edema frequently threatens the lives of such patients. we reviewed cases of afhf in the neuroicu, noting the incidence of cerebral edema with ct scans and factors associated with mortality. patients were captured through hmri classification of acute liver/hepatic failure. chart review included tabulation of: demographics, inr; serum bilirubin, creatinine, albumin; in-hospital mortality. ct scans were re-read with blinding to clinical information and catalogued for changes in sulcal markings, ventricular size and gray-white differentiation (gwd). inclusion criteria: age greater than years, encephalopathy, hepatic failure within weeks of onset of liver disease, ct scans of head performed. acetaminophen toxicity was the most common etiology ( cases). twelve patients had cerebral edema on ct, including of the with acetaminophen toxicity. decreases in sulcal markings and ventricular size preceded conspicuous alterations in gwd. fourteen died, including all with cerebral edema. none of the hematological or biochemical variables correlated significantly with mortality. acetaminophen toxicity is a common cause of afhf; this combination has a strong association with cerebral edema. early development of cerebral edema occurs in almost all the afhf cases with acetaminophen overdose and can be detected in its early stages. this facilitates management for prevention of fatal brain herniation. afhf patients develop the changes on brain parenchyma within hours of onset of symptoms, during grade i-ii encephalopathy, most strikingly with aod. levetiracetam is increasingly being considered for seizure prophylaxis following tbi. although its acquisition cost is higher than phenytoin, the complete cost of therapy remains unknown as levetiracetam does not require therapeutic drug monitoring and has less pharmacokinetic variability. we developed a cost-minimization model to compare total costs associated with phenytoin and levetiracetam when used for seizure prophylaxis following tbi. five scenarios were tested based on drug, initial method of administration (iv vs. po) and whether or not po conversion occurred. factors considered in the analysis were drug costs, monitoring costs and likelihood of achieving a therapeutic concentration. treatment duration consisted of days. for arms that included po transition, po therapy began after day . decision trees were developed and a single-payoff method was used to identify the least costly scenario. hospital acquisition costs using us dollars were used to assess all costs. the scenario associated with the lowest cost was iv phenytoin followed by po levetiracetam ($ /patient). this was followed by iv levetiracetam transitioned to po levetiracetam ($ ), iv phenytoin transitioned to po phenytoin ($ ), iv phenytoin ($ ) and iv levetiracetam ($ ). the factor associated with the most variability in the model was timing of po transition. a two-way sensitivity analysis which altered timing of po transition revealed iv phenytoin followed by po levetiracetam as the least costly scenario except when iv to po transition occurred after day . in this scenario, iv levetiracetam followed by po levetiracetam was preferred. iv phenytoin followed by po levetiracetam will result in the lowest overall cost when used for a total -day course in patients with tbi. this illustrates the importance of considering all costs associated with a therapy when evaluating the total cost of medication therapy. the joint commission accreditation standards require hospitals to develop policies which address donation after cardiac death (dcd). optn/unos published the "model elements" for dcd protocols that describe suitable dcd candidates to primarily have "non-recoverable and irreversible neurological injury" resulting in ventilator dependency; a description we suspected to be highly inaccurate. we sought to more accurately clinically characterize those considered dcd eligible to facilitate constructive improvement of relevant policies and processes. local opo quarterly audits over months identified patients who were considered eligible for dcd and died within the requisite minutes of treatment withdrawal (dcdep). all cases were reviewed to determine the frequency/nature of any neurological abnormalities and whether they were "non-recoverable and irreversible." we also characterized the mechanism of respiratory failure and death. ( %) of dcdep had an identified neurological injury. only / ( %) had "non-recoverable and irreversible neurological injuries. / ( %) of dcdep were seen by a neuro-specialist, and / ( %) had brain imaging. / ( %) had a neurological injury that could compromise ventilatory drive, and at least / ( %) died of airway compromise with variable approaches to palliative care regarding sedation and oral airway usage. . % of dcdep had no neurologic injury. . only patients ( %) had neurologic injuries that could be correctly characterized as "non recoverable and irreversible" leading to "ventilatory dependency." . airway compromise is an important cause of death in dcdep and demands better uniformity of palliative care to assure equivalent treatment of dying patients independent of "donor status." . the published "model elements" for dcd protocols do not accurately represent the patient population. ventilator-associated pneumonia (vap) is the most common nosocomial infection among medical intensive care unit (icu) patients and associated with increased mortality and length of stay (los). neurologic disease is a risk factor for vap development, but the relationship between vap and outcomes in neurologic patients remains largely unknown. all mechanically-ventilated patients over a two-year period with neurovascular disease were included. data collected included patient demographics, dates of admission and discharge, los, and ventilator hours. vap was defined using standard published criteria. comparisons between neurologic patients who did and did not develop vap were made using univariate and multivariate analysis. of intubated neurovascular patients, ( . %) developed vap. compared with those who did not develop vap, those with vap were younger ( . ± . versus . ± . , p= . ), had increased los ( . ± . days versus . ± . , p< . ), and more ventilator hours ( ± versus . ± , p< . ). there was no difference in mortality between patients with and without vap ( . % versus . %, p= . ). vap was not an independent predictor of mortality in a multivariate model (or . , p= . ). subsequent case-control analysis of patients with and without vap demonstrated an increase in transports for cross-sectional head imaging ( . transports versus . , p= . ). vap in neurocritical care patients is associated with increased los and ventilator hours, but does not lead to increased mortality, contrary to prior studies in medical icu patients. the significance and frequency of vap in neurologic patients is different from patients in other icus because reasons for intubation vary. neurologic patients with vap have more imaging-related transports compared to controls, suggesting an association with ventilator disconnections. introduction: ich causes the highest mortality of all strokes. admission to a neuro-icu has been associated with reduced mortality following ich. this is leading to several hospitals routinely transferring ich patients to hospitals with neuro-icus. however, delays in optimizing management prior to and during transfer often leads to deleterious consequences. our objective was to compare functional outcomes in ich patients admitted to our neuro-icu directly from our ed with inter-hospital transfer admissions. records of consecutive spontaneous supratentorial ich patients admitted to our neuro-icu were reviewed. patients with ich related to trauma or underlying lesions (brain tumors, aneurysms, avm) were excluded. we compared outcomes at discharge in patients admitted directly from our ed and inter-hospital transfers (iht) using dichotomized modified rankin scale. other factors potentially impacting outcomes such as age, ich volume, ivh volume and admission gcs were included in the multiple logistic regression analysis. patients were included in the analysis (ed . %; iht . %). there were no significant differences between the groups in mean age (ed . +/- . ; iht . +/- . , p . ), ich volume (ed . +/- . ; iht . +/- . , p . ), ivh volume (ed . +/- . ; iht . +/- . , p . ) and gcs (ed . +/- . , iht . +/- . ; p . ). . % ed patients had good outcomes at discharge compared to . % iht. this difference was statistically significant following univariate (p= . , % ci= . - . ) and multivariate analysis (p= . , % ci= . - . ). odds (adjusted) of ed admissions having good outcomes was times higher than inter-hospital transfers. ich patients brought to the neuro-icu directly from our ed had significantly better outcomes than inter-hospital transfers. although this could possibly be caused by delays in optimizing ich management, other equally plausible hypotheses need to be prospectively tested. isis duran, storm liebling, michael moore, andrew naidech northwestern university, chicago, united states hospital acquired pneumonia (hap) is a significant cause of morbidity and mortality. hap increases costs, impacts quality metrics and will soon be designated as a medicare "never event". the us centers for disease control have published standard guidelines for the diagnosis of pneumonia, but few confirmatory data exist. we sought to determine the inter-rater reliability of diagnosing pneumonia by cdc criteria in patients admitted for brain hemorrhage. patients with intraparenchymal or subarachnoid hemorrhage admitted to our neuro/spine icu in were included in this irb-approved study. utilizing cdc criteria, pneumonia was diagnosed prospectively by a neurointensivist and institutional infection control (ic) personnel. following a thorough review of the electronic medical records, chest radiographs, and microbiology results, a neurocritical care fellow and a pulmonary critical care attending physician made an independent retrospective assessment of the diagnosis. analysis of the inter-rater reliability of the diagnosis of pneumonia was performed using kappa statistics. one hundred three patients were identified. the male:female ratio was : . pneumonia was diagnosed in patients by ic personnel, by the neurointensivist, by the fellow, and by the pulmonologist. overall inter-rater reliability was poor, with a median kappa value of . [ . - . ]. the highest inter-rater agreement was between the fellow and the pulmonologist (kappa= . ), while the lowest was between the pulmonologist and ic personnel (kappa= . ). the diagnosis of hap by cdc criteria, despite highly trained reviewers and clear diagnostic criteria, had poor interrater reliability in a sample of high risk patients. the diagnosis of hap should not be a measure of quality of care, nor should it be used as a determinant of payment unless the inter-rater reliability can be markedly improved. recent studies have reported excess hospitalization costs for aneurysm coiling compared to clipping after subarachnoid hemorrhage (sah). we aimed to compare categories of charges, length of stay (los), and discharge disposition in patients who underwent surgical versus endovascular aneurysm repair. a retrospective review was conducted of spontaneous sah patients between / - / . charges captured in the hospital database and were categorized as direct, overhead, icu, surgical and radiographic/angiographic. analysis was adjusted for age, hunt-hess grade, aneurysm size, aneurysm location and los. discharge disposition and los were compared between clipped and coiled patients using logistic regression or mann whitney u-nonparametric test. of sah patients, ( %) were clipped and ( %) were coiled. coiled patients were significantly older ( versus years; p= . ), and had larger aneurysms ( versus mm; p= . ). there were no differences in hunt-hess grade, aneurysm location, or modified fisher score. compared to coiled patients, median radiographic/angiographic charges were lower in the clipped group ($ versus $ , , adjusted or [aor] . , % ci . - . , p< . ), but median surgical charges were higher ($ , versus $ , aor , % ci - , , p< . ). total median direct charges were similar ($ , for clipped versus $ , for coiled patients, p= . ), as were icu direct charges ($ , versus $ , , p= . ) and overhead ($ , versus $ , , p= . ). median icu los ( days for each group) and hospital los ( days for each group) were similar as were discharge dispositions after adjusting for age, hunt-hess grade and aneurysm size: % of clipped patients died versus % of coiled patients (p= . ) and % versus % had a poor discharge disposition (p= . ). though surgical and radiographic/angiographic charges differed between sah patients who had surgical versus endovascular repair, icu charges, overhead and total direct charges were similar as were icu and hospital los and discharge disposition. osmotic diuretics and hypertonic saline (hs) are commonly used to treat traumatic brain injury (tbi). the untoward effects of mannitol, including hypotension, rebound intracranial hypertension, decreased potency and effect duration have lead to research of alternative treatments. hypertonic saline has been increasingly used to treat cerebral edema, however, efficacy and safety of repeated boluses has not been established. this preliminary prospective trial assesses the ability of single ml . % saline bolus to lower icp without losing potency while maintaining hemodynamic stability. thirty-five individual boluses of . % saline were given in tbi patients (aged - ) during a -month period. included tbi patients sustained icp elevation (> mmhg x minutes) despite full sedation, paralytics, temperature control and minimal stimulation. starting at bolus initiation, icp, cerebral perfusion pressure (cpp), heart rate (hr), systolic blood pressure (sbp), sodium level (na), and serum osmolality (sosm) were recorded regularly for hours. if repeated boluses were given in the same patient (icp re-elevated > mmhg x minutes), recording of parameters was restarted at a new zero time-point to assess the effect of each bolus individually. statistical analysis included power analysis, normalization testing, anova (analysis of variance) and scheffe test. within minutes of administration a statistically significant decrease in icp was sustained up to hours (power > %, p< . ). mean icp at initiation declined from mmhg to < mmhg by minutes (> % reduction, p< . ). the mean cpp before treatment increased from mmhg to mmhg by minutes ( % rise, p< . ). mean hr and sbp remained constant. sodium levels ranged from to and sosm from to . small volume . % saline boluses can be used repeatedly in patients with tbi to significantly lower icp and improve cerebral perfusion. repeated boluses resulted in a sustained magnitude and duration of icp reduction up to hours. introduction: intraventricular hemorrhage (ivh) can result from different etiologies all are intracranial in location. in this unique case we describe a case of ivh secondary to an extracranial vascular source. retrospective chart analysis for a patient that was taken care of at our institution's neurocritical care unit with cerebellar hemorrhage. patient was a year old male who presented with severe headache and imbalance. ct scan revealed a cerebellar hemorrhage and minimal intraventricular hemorrhage. patient underwent suboccipital craniectomy with evacuation of the hematoma. patient had an external ventricular drain (evd) placed in the or through the occipital horn. patient recovered over the following few days with minimal neurological deficits. suddenly patient suffered from a profuse bleeding from the scalp site of the evd. bleeding was controlled by pressure and suture. next day patient suffered from a similar episode. during the control of the bleeding the patient deteriorated neurologically and had to be intubated. patient ct scan showed massive intraventricular hemorrhage. angiography revealed an occipital artery pseudoaneurysm that was the cause of the bleeding and probably resulted from the evd insertion. the aneurysm was coiled without complication and patient was discharged later to long term care facility. pseudoaneurysms of the external carotid artery branches could result from trauma induced during evd insertion. in the presence of evd tract the hemorrhage that occurs from these pseudoaneurysms could track along under pressure to cause intracranial hemorrhage. this is an unusual and unfortunate experience that we wanted to raise awareness about. veena yashaswi, ravi patel, adham kamel, jonathan naysan, juliuse gene latorre, tara ramachandran, ziad el-zammar, yahia lodi upstate medical university, syracuse, ny, united states surgical treatment of fusiform intracranial aneurysm is extremely difficult and associated with poor outcome. endovascular stent-assisted treatment of fusiform intracranial aneurysm without sacrificing the parent artery has been introduced into clinical practice recently as an alternative option. objective: the objective of our study is report our experience of stent-assisted treatment of fusiform intracranial aneurysm. consecutive patients who underwent stent-assisted treatment for fusiform intracranial aneurysm were enrolled from to . patient's demographics including the hunt & hess grade, fished scale, location and size of aneurysm including the rate of radiographic evidence of aneurysm occlusion were collected. additionally a days outcome measurement was obtained using glasgow outcome scale (gos). five female patients, median age years (ranges to ) with five unruptured symptomatic intracranial fusiform aneurysms were treated with neuroform stent. four of which required staged coiling in addition to stenting and one required stenting only. three aneurysms were located at the internal carotid artery (two at the carotid bifurcation, one at the origin of ophthalmic artery) one at the middle cerebral artery and one at the vertebral artery. there was no intraoperative or post operative complication related to the stent-assisted treatment. immediate near complete occlusion was observed in one and subtotal occlusion in cases. in months follow-up angiography, complete occlusion of aneurysm was observed in patients (vertebral artery and carotid bifurcation ), near complete occlusion in two (carotid ophthalmic one and carotid bifurcation one) and subtotal in one (middle cerebral artery). good outcome was observed in all cases (gos ). endovascular stent-assisted repair not only provides a safe alternative option for the treatment of intracranial fusiform aneurysm, but also improve progressive occlusion of aneurysm with good outcome. wilson cueva, obi iwuchukwu, fernando goldenberg, agnieszka ardelt, jeffrey frank university of chicago medical center, chicago, il, united states hyperammonemia is a well recognized precipitant of cerebral edema (ce) and an important cause of death in acute liver failure. however, isolated hyperammonemia can occur in patients with enzymatic deficiencies important for ureagenesis. extreme hyperammonemia from newly diagnosed ureadysgenesis in adults has been reported, most often leading to disabled outcome or death from ce. we present the clinical, therapeutic and outcome details of two patients with newly symptomatic ureadysgenesis-induced hyperammonemia who developed profound ce and intracranial hypertension (ich). both are the only survivors ever reported with their degree of extreme hyperammonemia (peak and mcg/dl) with normal neurological outcome. case- : a healthy year-old male developed seizures followed by profound encephalopathy associated with ammonia level of mcg/dl without liver failure. case- : after a successful lung transplant, a year-old man developed severe encephalopathy associated with ammonia level of mcg/dl without liver failure. ornithine transcarbamylase deficiency was discovered in case and acquired glutamine synthetase deficiency was suspected in case . steroids provoked symptomatology in both cases leading to severe ce and ich. both required intracranial pressure monitoring, cerebral perfusion pressures directed therapy, promotion of ammonia clearance (cvvhd, lactulose), catabolism limiting treatments (hypothermia, insulin administration, infection control, nourishment), protein restriction, and the use of alternative pathway therapy. both patients fully recovered. -hyperammonemia should be suspected in patients presenting with unexplained ce even in the absence of liver failure. -multidimensional contemporary neurocritical care strategies can optimize survival and improve functional outcome from this historically disabling and deadly condition. -extreme hyperammonemia should not deter aggressive proactive management in these patients now that we report normal neurological outcome in these unique survivors. we is a known neurological complication of thiamine deficiency. although it usually manifests among alcoholics, na patients with either malabsorption, poor dietary intake, severe vomiting or increased metabolic demands are prone to develop we. we present three clinical cases in whom typical brain mri and pathology findings led to the diagnosis of na-we. case- : year-old na female became comatose after a two months history of severe vomiting secondary to a gastrointestinal disease. case- : year-old na female with breast cancer became comatose in the setting of weeks history of severe vomiting after chemotherapy. case- : year-old na female became comatose status-post cardiac arrest of very short duration, not enough to explain the severity of the encephalopathy. severe alteration of the level of consciousness without focal deficits was the prominent clinical finding in all patients; nystagmus was present in case . brain mri showed t /flair signal abnormalities in bilateral mamillary bodies, thalamus and periaqueductal area in cases and and an autopsy in case revealed findings consistent with we. despite intravenous thiamine supplementation, cases and did not improve clinically and eventually expired. case had complete neurological recovery within the first hours of treatment with intravenous thiamine. -we should be considered in all patients with unexplained confusion or deteriorating mental status even in the absence of a prior history of alcohol abuse. -in the presence of atypical or incomplete clinical picture of we, appropriate brain mri findings can help establishing the diagnosis. -early diagnosis of we is critical given that the success of the treatment depends on the urgent thiamine supplementation. -failure to recognize and treat we may result in devastating neurological outcome. arterial venous carbon dioxide removal (avco r) is a technique that uses a pumpless extracorpeal circuit for carbon dioxide removal. avco r has been used in adult and pediatric patients with severe hypercapnea. the system is placed at bedside using the seldinger technique to cannulate the femoral vessels. normally this system requires anticoagulation but can be performed without anticoagulation. case reports of avco r used to control ph and pco after neurotrauma. a male suffered extensive head injury after mvc progressing to brain death. organ harvest was planned. because of extensive lung injury complicated by hypercapnea and academia, donor viability was in jepody with paco rising to and ph of . . avco r was placed for ph and carbon dioxide control. the paco and ph promptly corrected to and . . after a brain death exanimation he remained on avco r until organ harvest. a male presented with a cervical injury at the c- level. imagining showed cervical fractures, disc herniation and cord contusion involving c- to t- .the patient developed respiratory distress. chest x-ray revealed ards. in aprv the ph was . and pco of . the patient had a subsequent cardiopulmonary arrest. after successful resuscitation avco r was started. within hours the ph and pco were . and without manipulation of the ventilator settings. he was on aco r for days and eventually weaned off mechanical ventilation after surgical decompression and fusion and discharged to rehabilitation. neither case required anticoagulation. . avco r is a simple extracorpeal technique that can be used to manage life threatening hypercapnea in patients with critical neurologic illness or injury . the technique can be inserted at bedside and used without anticoagulation continuous renal replacement therapy (crrt) is preferred over intermittent hemodialysis (ihd) in patients with acute brain injury (abi) due to increased intracranial pressure (icp) seen during ihd [ , ] . despite the preference for crrt in this patient population limited data is available on icp changes during therapy. there is some support for the early stability of icp for patients with fulminant hepatic failure that underwent continuous arteriovenous hemofiltration [ , ] . retrospective observational study (over a year period) of patients with abi and icp monitoring whom also underwent crrt. icp and fluid volumes were analyzed for the hours before and after initiation of crrt. four patients met criteria. table- describes the sample population. three patients had developed refractory intracranial hypertension (rih) prior to initiation of crrt ( in pharmacologic coma) and patient developed intracranial hypertension on ihd that resolved with crrt. no changes in medications were made in the hours prior to starting crrt except pentobarbital coma was initiated one patient six hours prior to crrt without lowering of icp. no attempts were made to lower icp in the hours following crrt. a decline in icp was seen at , , and hours following initiation of crrt in rih patients ( given the decrease in icp at one hour and relatively small percentage of total fluid balance removed, it seems unlikely that fluid removal or improved systemic oxygenation decreased icp. early improvement in icp may be due to removal of cytokines and myocardinal depressants seen with ultrafiltration and membrane absorption which is maximal during the first hour of filter use due to filter charge [ ] . given the mortality and morbidity associated with rih, further research is warranted. isoflurane, an inhalational anesthetic, is an alternative treatment for refractory status epilepticus (rse). it is effective, has rapid onset of action, and is easily titrated to produce burst-suppression patterns on the electroencephalogram. little is known regarding potential human toxicities caused by isoflurane. we present two cases of prolonged rse treated with prolonged high dose isoflurane who developed abnormal t hyperintensity lesions on magnetic resonance imaging (mri), which improved after taper or discontinuation of isoflurane. we report two patients with prolonged refractory status epilepticus who were treated with prolonged high-dose isoflurane (defined as an average end tidal concentration > . % for seven or more days) and developed new changes on brain mri. we collected demographic information, daily dosing of all antiepileptic medications and anesthetics received. we reviewed and analyzed the results of serial mri scans. patient one had prolonged rse for days and was treated with isoflurane for days with . % concentrationhours. patient two, currently hospitalized, has had rse for at least days and was treated with isoflurane for days with . % concentration-hours. in both patients, serial brain mris showed progressive t signal hyperintensity involving bilateral thalami, cerebellar hemispheres, and cerebellar vermis after treatment with - weeks of high dose isoflurane. these findings improved following taper and/or discontinuation of isoflurane. these cases raise the possibility that isoflurane is neurotoxic when used in high doses for prolonged time periods. though we cannot be certain of the exact cause of brain lesions, the timing of their appearance after isoflurane initiation and subsequent improvement after taper or discontinuation suggest a possible association with isoflurane. further studies are needed to clarify the safety of prolonged isoflurane use in rse cerebral edema is common in severe brain injury and can lead to harmful elevations in intracranial pressure (icp). hyponatremia, typically associated with excess levels of vasopressin (adh), frequently complicates acute brain injury and can worsen edema and icp. conivaptan, a vasopressin-receptor antagonist, has been shown to correct hyponatremia in these high-risk patients by inducing loss of free water (aquaresis). it is unknown whether raising sodium with a bolus of conivaptan can also acutely reduce icp. we prospectively assessed the change in serum sodium (na + ), icp, and cerebral perfusion pressure (cpp) after a bolus of conivaptan was given for the treatment of hyponatremia in a patient with cerebral edema associated with traumatic brain injury (tbi). a -year old suffered severe tbi with left carotid dissection, complicated by hemispheric infarcts and worsening edema. conivaptan mg iv was given as a bolus when na + rapidly dropped to meq/l. its aquaretic effect peaked between and hours after the dose, with hourly urine outputs of ml/hour. eight hours postadministration, na + had risen to meq/l. icp had been stable at - mm hg for several hours prior and remained in this range for the first hours after conivaptan, but then fell to mm hg at hours, remaining mm hg after hours. cpp, initially stable at - mm hg, rose to mm hg after hours. a single bolus of conivaptan not only resulted in rapid correction of hyponatremia but also a significant fall in icp temporally associated with peak aquaresis. confirmation of this novel osmotic effect is required, as is further delineation of the role of such agents in the management of brain edema. financial support: the authors have received speaking honoraria from astellas pharma. seizures are a known complication of aneurysmal subarachnoid hemorrhage (sah). they can increase cerebral metabolic demand and lead to cardiopulmonary compromise. this could be detrimental in the setting of delayed cerebral ischemia (dci), when brain tissue is vulnerable to further reductions in oxygen delivery or increases in demand. an association between seizures and worsening ischemia could influence the decision to use antiepileptic drug (aed) prophylaxis in patients with vasospasm. case report of a patient who developed irreversible neurological deficits and cerebral infarction immediately after a seizure in the setting of initially stable vasospasm with dci. a year-old woman developed confusion, aphasia, and right hemiparesis on day after sah. angiography confirmed severe anterior circulation vasospasm. the patient responded to hypertensive therapy with almost complete resolution of her ischemic neurological deficits. on day , however, she had a single generalized seizure and required intubation after brief oxygen desaturation. she had a concurrent drop in blood pressure, necessitating an increase in previously stable dose of vasopressors post-ictally she developed recurrent aphasia and worsening hemiparesis which did not resolve despite further hemodynamic augmentation. subsequent head cts revealed new infarcts in the left anterior and middle cerebral artery territories. she had received prophylactic phenytoin for only the first days of her icu stay per our sah protocol. aed prophylaxis is typically used early after sah when risk is high and a seizure may precipitate aneurysmal rebleeding. this case illustrates how a seizure occurring later, in the setting of vasospasm, can lead to decompensation of dci with potential for irreversible infarction. therefore, patients with vasospasm may benefit from extended duration of prophylaxis to prevent such complications. dural sinus thrombosis is a rare cause of stroke. anticoagulation is the preferred treatment; however, some patients experience rapidly progressive neurological deficits and poor outcomes despite adequate anticoagulation. mechanical thrombectomy via a trans-femoral approach is an effective alternative treatment, but technical limitations can make this approach impossible in some patients. we report two cases in which angiojet® (medrad-interventional/possis) thrombectomy was performed via a transjugular approach. in the first patient, trans-jugular access was preferred due to the presence of bilateral deep vein thromboses in the femoral and iliac veins and an inferior vena cava filter. in the second patient, the trans-femoral approach was impossible due to the length of the catheter ( cm xmi), which was insufficient to access to the anterior two thirds of the superior sagittal sinus via a trans-femoral approach. in both patients, the trans-jugular access was obtained utilizing direct ultrasound and fluoroscopic guidance. a stabilizing guidewire was placed to deliver the angiojet® catheter to the superior sagittal sinus. the first patient was a year-old woman with heparin-induced thrombocytopenia, a large intracranial hemorrhage and refractory increased intracranial pressure. the second patient was a year-old man who presented with dehydration and a rapidly declining neurological exam. in both patients, antegrade blood flow was restored within the dural sinuses after mechanical thrombectomy via the trans-jugular approach. computed tomography scans after thrombectomy did not show evidence of increased hemorrhage and there were no complications from the procedure. the first patient died despite successful thrombectomy from other complications of her underlying disease. the second patient made a full recovery. mechanical thrombectomy has been shown to be a successful treatment for dural sinus thrombosis for patients with progressive symptoms despite adequate anticoagulation. the trans-jugular approach is a valuable alternative variation of mechanical thrombectomy in patients who have contraindications to the trans-femoral approach. we retrospectively reviewed data from patients with stbi admitted to the neuroscience icu (nsicu) of an urban tertiary care level trauma center who had a cerebral oxygen monitor (licox ) in place and were administered inhaled nitric oxide (ino) per institutional protocol. data were collected from bedside flow sheets. two patients met inclusion criteria. patient # was admitted after a motor vehicle collision with stbi and pulmonary contusions. she developed adult respiratory distress syndrome (ards) on hospital day # requiring ino at ppm. prior to ino therapy, pbto was . mm hg, pao = mm hg and icp = cm h o; within hours of ino initiation, pbto climbed to mm hg (+ %), pao rose to (+ %), and icp remained cm h o (+ %). patient # sustained a stbi and pulmonary contusions after a motorcycle collision. he developed ards on hospital day # requiring ino at ppm. prior to ino therapy pbto was . mm hg, pao = mm hg and icp = cm h ; within hours of ino initiation, pbto rose to mm hg (+ %), pao rose to mm hg (+ %) and icp climbed to cm h o (+ %). patients admitted to the nsicu after stbi may develop complex physiologic derangements, including ards. the use of ino may benefit both cerebral and pulmonary dysfunction, and may warrant further investigation. amar dhand, kazuma nakagawa, wade smith, tarik tihan university of california, san francisco, san francisco, ca, united states introduction: ventricular free wall rupture is a fatal complication of myocardial infarction (mi). although described in mi patients who receive thrombolytic therapy, this complication is not well known in ischemic stroke patients who receive intravenous (iv) t-pa. here, we report a patient who had cardiac rupture and hemopericardium immediately following iv t-pa administration. case report. a -year-old woman with history of coronary artery disease presented with acute onset of left hemiparesis and right gaze preference (nihss ). ct angiography showed right middle cerebral artery (mca) occlusion at the bifurication, a filling defect in the left atrial appendage suggestive of left atrial thrombus, and right segmental pulmonary embolism. an electrocardiogram showed st elevations in the v -v distribution with initial troponin i level of . ug/l. iv t-pa was administered hour from symptom onset. one hour after completing t-pa infusion, the patient suddenly became unresponsive, bradycardiac, and rapidly demonstrated an asystolic arrest. given the established dnr/dni status, she was not resuscitated. autopsy study showed subacute myocardial infarction ( - days old), rupture of the anterolateral wall of the left ventricle, and cc of hemopericardium. pathological study of the brain showed an old hemorrhagic infarction in the left occipital lobe, evidence of remote hypoxic/ischemic injury and % occlusion of the basilar artery, but no evidence of intracranial hemorrhage. this case report illustrates a fatal cardiac complication of iv thrombolytic therapy that was used for acute ischemic stroke treatment in the setting of subacute myocardial infarction. the speculated mechanism of this phenomenon is alteration of collagen metabolism by thrombolytic therapy. although mi is not an absolute contraindication for iv t-pa administration, clinicians should be aware that cardiac rupture may occur when iv t-pa is given to patients with concomitant stroke and mi. anti-nmda-receptor encephalitis (nmdare) is a rare autoimmune encephalitis associated with antibodies that antagonize nmda receptors. although nmdare is an uncommon disorder, we present confirmed cases treated in our neuro-icu over months. we report three cases of nmdare including the first reported case during pregnancy. all patients were women between and years of age. all had a prodrome of psychiatric symptoms and had orofacial and limb dyskinesias at presentation. each developed progressive unresponsiveness, required mechanical ventilation secondary to hypoventilation and had autonomic instability. one required a transvenous pacer for symptomatic bradycardia. all were evaluated for ovarian teratoma. all underwent oopherectomy. two were found to have ovarian teratomas by pathology. patients were treated with a combination of ivig, steroids and plasma exchange. all patients improved and were discharged from the hospital to inpatient rehabilitation. one patient was weeks pregnant at admission. she delivered via cesearean section at weeks gestation. the neonate had mildly increased tone but appeared otherwise healthy and was discharged home at days. the csf of the neonate was negative for nmda antibodies. nmdare is a reportedly rare cause of encephalitis which may be more common than reported. it has characteristic features that should not go unrecognized. high suspicion for ovarian teratoma is appropriate. imaging may not accurately differentiate between benign cysts and teratoma. oopherectomy for any ovarian abnormality may be reasonable, given poor correlation of pathologically confirmed teratoma with radiographic imaging. this is the first reported case of nmdare during pregnancy. nmda receptors play an important role during fetal development and the long-term sequelae for children exposed to nmdar antibodies in utero are unknown. csf hypovolemia is typically diagnosed in patients presenting with positional headaches. however, severe intracranial hypotension and brain sagging may cause orthostatic coma. we present a case that illustrates this uncommon presentation. a yr old male who presented with acute onset of headache, nausea, vomiting and disequilibrium. extensive diagnostic work-up, including head ct, mri/mra and lp, was initially unremarkable. his headaches became progressively worse with a prominent postural component. a csf leak was suspected at the lumbar level diagnosed with ct myelogram and treated with a blood patch at the outside hospital with temporary resolution of his symptoms. a repeat mri/mra revealed bilateral subdural hematomas without mass effect and diffuse dural enhancement, consistent with decreased csf pressure. due to worsening level of consciousness, the patient underwent urgent evacuation of the left subdural without any change in his mental status subsequent imaging showed reaccumulation of the hematoma. over the next few days, the patient became increasingly stuporous and had an acute respiratory decline requiring intubation. the patient was subsequently transferred to our institution. head mri revealed dramatic sagging of the brain showing the pontomedullary junction at the opening of the foramen magnum. there was reproducible improvement in his cognitive status and cheyne stokes breathing with trendelenburg positioning. he underwent a repeat ct myelogram which showed a csf leak at t and possibly at c -c . the csf leaks were repaired with localized blood patches with significant improvement in his neurological exam. csf hypovolemia may cause coma from distortion and downward displacement of the thalamus-brainstem structures. evacuation of subdural fluid collections-typically without mass effect-may be detrimental in these patients contributing to further reduction of csf volume. instead, identification and treatment of the responsible csf leak is curative. infection with human immunodeficiency virus (hiv) has been associated with the development of intracranial aneurysms. although the pathogenesis of aneurysm formation in hiv infected patients is unclear, one purported mechanism is direct invasion of cerebral vessels by the virus itself. here, we report a unique case of an hiv infected patient whose intracranial aneurysm rapidly enlarged during a period of anti-retroviral therapy non-adherence. case report. a year-old hiv infected female (cd count cells/ml) was admitted with a subarachnoid hemorrhage. cerebral angiography revealed a dilating vasculopathy of multiple large intracranial vessels along with fusiform aneurysms of the right and left proximal anterior cerebral arteries (aca). a saccular aneurysm measuring x . mm arose from the right fusiform aca aneurysm and was successfully treated with endovascular coiling. four weeks later, the patient was re-admitted with a decreased level of consciousness. head ct revealed recurrent subarachnoid hemorrhage. the patient had not adhered to her anti-retroviral therapy and her cd count upon re-admission was cells/ml (hiv load copies/ml). cerebral angiography revealed enlargement of the previously coiled aneurysm which now measured x x . mm. infectious vasculitides were excluded with serum and cerebrospinal fluid (csf) testing, including negative blood and csf cultures, negative serum and csf antibodies for syphilis, and negative serum antibodies and csf polymerase chain reaction for varicella zoster virus. the co-occurrence of rapid aneurysmal enlargement with non-adherence to antiretroviral therapy suggests an elevated hiv burden may accelerate vasculopathy. rapid enlargement and re-rupture of intracranial aneurysms may be seen in hiv infected patients with an elevated viral burden. identifying the unique clinical and radiological features of hiv vasculopathy may lead to earlier recognition and novel therapeutic approaches. patients with de novo refractory status epilepticus are often referred to as having norse. the clinical course is often prolonged (range: - days), and morbidity and mortality is high ( %). cjd is a rare cause of refractory convulsive and non-convulsive status epilepticus. we describe here a patient with norse who had probable sporadic cjd. year old, kg, caucasian female with a past medical history of systemic hypertension, pulmonary hypertension, and prior pulmonary mai complex presented to the er with delirium and accelerated hypertension. initial examination revealed encephalopathy. patient had generalized tonic clonic seizures, with rapid progression to status epilepticus which was refractory to dilantin ( mg tid), keppra ( mg bid), phenobarbitone ( mg tid), midazolam ( mcg/kg/min), and propofol ( mcg/kg/min) infusion. she was then put in pentobarbital coma ( m/kg/hr) for hours, and was found to be refractory to withdrawal of pentobarbital. on day of her status epilepticus the patient had an episode of massive pulmonary hemorrhage and went into pea, from which she couldn't be revived. workup for norse including mri brain, ct chest, abdomen and pelvis, failed to reveal any evidence of stroke, press, neoplasm, meningo-encephalitis. paraneoplastic antibody panel was negative. toxicology, metabolic, haematological, vascular, and immunological workup was negative. csf analysis revealed a wbc of , protein and glucose and protein - - was positive. to our knowledge this is the first case report of norse complicating cjd. norse complicating cjd is associated with high mortality. our case is also unique for its acute onset, absence of myoclonus, and absence of extra pyramidal features commonly seen in cjd. in patients with refractory status epilepticus with no obvious cause, cjd should be considered in the differential diagnoses. predicting recovery after cardiac arrest continues to challenge neurointensivists. updated aan practice parameters add two new evidence-based elements to traditional clinical examination criteria ) absence of bilateral n response on sseps and ) neuron-specific enolase (nse) > µg/dl as measured within days. concurrently moderate hypothermia has emerged as an efficacious therapy, with the possibility of modifying the predictive power of criteria established independent of such intervention. case: a year old woman undergoing breast lumpectomy was resuscitated following interoperative asystole. rosc was secured by mins; but she arrived to nsicu comatose with only minimal pupillary and corneal reflexes. moderate hypothermia with target temperatures of - o c was achieved by hours and maintained for hours before slow re-warming. at hours, n s were bilaterally present, but nse was µg/dl. brain mri at day was normal. over weeks she remained comatose with absent motor response requiring aggressive therapy for bouts of refractory non-convulsive status epilepticus. she continued to have intermittent transient myoclonic movements months after cardiac arrest. eye opening without awareness of surroundings began at icu week with gradual return to consciousness. subsequently she has made slow steady improvement, conversing appropriately with memory of family names and past experiences. now months post-arrest on the inpatient rehabilitation unit she moves all extremities with - / muscle strength. her most recent fim score is . prognostication after cardiac arrest remains complex. application of hypothermia may alter the validity of predictors established previously. confounders and convergent evidence must be considered over any single data point. as in the past, time remains the final arbiter of certainty. near infrared spectroscopy is a non-invasive method of monitoring cerebral oxygenation. by employing time and spatial resolution of several light wavelengths, cortical blood flow, volume and oxygenation can be quantified (cerebral oximetry). we present a case utilizing cerebral oximetry in a patient with cerebral vasospasm after subarachnoid hemorrhage (sah) with concurrent use of brain tissue partial pressure of oxygen (pbto ) monitoring. a year old woman developed severe diffuse vasospasm following sah. we monitored intracranial pressure (icp) as well as tissue oximetry (pbto ) via licox (integra) catheter placed in the distribution of the left mca. over a -hour period during the third day of vasospasm, cerox (ornim) monitoring was applied over the left fronto-temporal area to evaluate the relationship between pbto and non-invasive cerebral oximetry. there were episodes of pbto desaturation (< mmhg for > mins) over the period of dual monitoring. over % of these pbto desaturations were preceded by > % decline in cerox values from baseline. there were episodes of cerebral oximetry desaturation (< % for > mins). less than % of cerox desaturations were temporally related to a decline in pbto to less than mmhg. hemoglobin was stable at mg/dl and icp was well controlled (< mmhg) during the entire hours. in this subject, desaturations of pbto appeared to be related to desaturations by non-invasive cerebral oximetry; the converse was not the case. perhaps cortical oxygen desaturations (cerox) occur with increased frequency compared to subcortical oxygen desaturations (pbto ) in diffuse vasospasm after sah. cerox monitoring may provide an enhanced understanding of oxygen delivery and utilization during periods of ongoing cerebral ischemia. further studies are required to substantiate these findings. status epilepticus refractory to conventional anti-epileptic drugs typically carries a poor prognosis, but patients may recover well if seizures can be stopped. case reports suggest that electroconvulsive therapy (ect) may stop seizures in patients with refractory status epilepticus, and we sought to examine its effectiveness in a series of patients. three consecutive patients with refractory status epilepticus at our institution were treated with ect after other therapies had failed. all patients were women, with age ranging from to years, and none had a significant medical history. extensive diagnostic testing was unrevealing, and all patients were empirically treated for infectious and autoimmune encephalitis. ect was begun because of ongoing seizures despite potent combinations of conventional anti-epileptic drugs, multiple trials of complete eeg suppression with anesthetic agents, and trials of more infrequently used therapies such as inhaled anesthetic agents and ketamine. ect stopped seizures in of patients. one patient recovered completely, and in outpatient follow-up had a normal neurological examination and a score of on the mini mental state examination. the second patient was left with mild cognitive impairment and epilepsy, but returned to independent living. in the third patient, seizures continued despite ect, and care was withdrawn at the family's request. autopsy revealed evidence of active meningoencephalitis despite treatment with antiviral therapy and high-dose steroids. ect stopped seizures in of patients with refractory status epilepticus. our results and those of prior case reports suggest that ect may be an effective therapy for refractory status epilepticus, and warrants further study for this indication. wendy wright, bill asbury, susan samuel, jane gilmore, owen samuels emory university hospital, atlanta, ga, united states conivaptan, an avp-receptor antagonist, has been used in neurocritical care patients to treat euvolemic hyponatremia. therefore, it would stand to reason that the aquaretic effect of conivaptan could also be used to induce a state of therapeutic hypernatremia. therapeutic hypernatremia is one of the standard modalities for the treatment of cerebral edema. conivaptan bolus +/-continuous infusion was administered to three patients with cerebral edema in the neurocritical care unit. all patients were initially treated with conventional measures to induce therapeutic hypernatremia, yet were not meeting the desired serum na goal. conivaptan was used in these patients to augment the effects of hypertonic saline. one patient received a single mg bolus of conivaptan in addition to . % nacl and his [na] increased an average of meq/l. one patient received a single mg bolus in addition to . % nacl + % nacl + nacl tablets + fludrocortisone and his [na] increased an average of meq/l. a third patient received conivaptan boluses + infusion in addition to % nacl and his [na] increased an average of meq/l. fluid balances were not adversely affected in any of these patients. conivaptan added to hypertonic saline therapy appears to be a rational strategy for achieving therapeutic hypernatremia in patients with cerebral edema without adversely affecting fluid balance. further study is needed to assess the effects of conivaptan on intracranial pressure, cerebral perfusion pressure and intravascular volume. financial support: dr. wright has served as a consultant for astellas pharma us delayed cerebral ischemia from vasospasm is an under-recognized, yet potentially treatable cause of morbidity and mortality in meningitis. while cerebral vasospasm has been documented via transcranial doppler sonography in patients with meningitis, few reports document vasospasm by cerebral angiography in this population. we report two patients who suffered neurological decline resulting from angiographically documented vasospasm during treatment for meningitis. the first patient was a -year-old woman who developed acute aphasia and hemiplegia during treatment for meningitis. formal cerebral angiography demonstrated left anterior circulation vasospasm. she was treated with verapamil into the left internal carotid artery and aggressive hypervolemia and hypertension. within hours, she was neurologically normal. the second patient was a postpartum woman with meningitis who presented with aphasia and hemiplegia. magnetic resonance imaging showed areas of diffusion restriction consistent with her examination. although she initially made clinical improvement with antibiotic therapy and was discharged, she re-presented days later with severe left anterior circulation vasospasm and massive left hemisphere stroke and later died. in our cases, as well as those described by the tcd literature, neurological decline and vasospasm occurred within days from the diagnosis of meningitis. this suggests that the "window" for vasospasm secondary to meningitis may be similar to that of vasospasm from sah. the development of focal neurologic symptoms in patients with meningitis should prompt radiographic evaluation for vasospasm. current treatment algorithms do not include the routine use of cerebrovascular imaging during treatment for meningitis, and thus this potentially treatable complication may be under diagnosed. prospective studies evaluating cerebrovascular complications in acute meningitis using neuroimaging coupled with directed hypervolemichypertensive therapies should be undertaken and may lead to a reduction in the persistently high morbidity and mortality associated with this common disease. opsoclonus-myoclonus syndrome (oms) is typically associated with a paraneoplastic syndrome or viral encephalitis. various locations, including the crerebellum, have been proposed as anatomic correlations to this syndrome. oms as a result of posterior reversible encephalopathy syndrome (pres) has not been previously described. a yo man with past medical history of poorly control hypertension, hyperlipidemia, and peripheral neuropathy presented with confusion and visual difficulties. initial exam demonstrated a fever of , bp= / (max / ), and lethargy. laboratory studies revealed acute renal insufficiency (ari) (cr= . ) and rhabdomyolysis (cpk= ). mri showed faint hyperintensities in the cerebellum and paieto-occipital subcortical areas (image ). the patient subsequently developed agitation with diffuse multifocal myoclonus and pronounced opsoclonus. repeat mri (image ) showed extensive hyperintensities in the subcortical hemispheres bilaterally and in the cerebellum, consistent with pres (image ). eeg showed diffuse slowing, and lp showed elevated protein ( mg/dl). csf cultures, vdrl, lyme antibody, listeria antibodies, west nile virus pcr, hsv pcr, and jc virus pcr were all negative. ct scan with contrast of the chest, abdomen and pelvis, revealed no neoplasms. results of serum paraneoplastic antibodies are pending. elevations in spep and upep were determined to be due to monoclonal gammopathy of unknown significance. we present a unique case of pres presenting as oms. involvement of the cerebellum may have been causative in this case. the most likely explanation for the development of pres was hypertension with ari. the acute onset, negative viral studies and body ct scan, resolution of symptoms with control of hypertension and reversal of ari, and the characteristic mri findings all supported pres as the cause of oms. we describe the clinical, imaging, and follow-up details of two patients who developed bsevad in the peripartum period to enhance the early recognition of this uncommon but important and potentially disabling complication. both patients were initially misdiagnosed with post-dural puncture headaches (pdph). both patients were in their thirties (ages and ), had epidural anesthesia, and developed their symptoms within days of delivery. patient # developed postural headache within hours of delivery, and patient # developed severe neck pain and bioccipital headache days after delivery. both received epidural blood patch for presumptive diagnosis of pdph without any significant relief. patient # developed nausea, vomiting, and ataxia days postpartum with a follow-up mri revealing acute bilateral cerebellar infarcts and a unilateral pontine infarct. patient # performed unusual physical positions during her pushing phase of labor (drawing provided). initial neuroimaging with ct, mri brain in both were reported as normal. however, -vessel cerebral angiography in both patients revealed bsevad. both patients did well with medical therapy without sequelae. the risk factors, diagnostic clues, and therapeutic considerations are discussed. . bsevad is a rare peripartum complication. . bsevad presents with clinical features that resemble pdph but have some distinguishing features to facilitate differentiation. . bsevad can lead to stroke similar to non peripartum cerebral arterial dissections. . early recognition of this rare complication can potentially lead to protecting patients from devastating posterior circulation strokes. the late-onset form of pompe's disease presents generally with limb girdle weakness. respiratory failure develops later and is the most frequently reported cause of death. we describe a case of late onset pompe's disease emphasizing the need to incorporate this rare entity into the differential diagnosis of patients with ventilatory failure a year old man presented with progressive weakness and shortness of breath. - years previously he noticed gradual lower extremity weakness. he began having difficulty breathing while lying flat. he was admitted to the neuroicu due to progressive respiratory failure. neuromuscular junction disease, neuropathy and typical myopathies were excluded. emg: normal nerve conduction studies. needle exam showed complex repetitive discharges, myotonic discharges and fibrillation potentials consistent with a myopathic process. muscle biopsy: myopathic changes associated with features of a vacuolar myopathy with abnormal glycogen accumulation and markedly increased acid phosphatase reactivity consistent with acid maltase deficiency. dried blood spot serum assay for acid -glucosidase was undetectable. pompe's disease is a rare condition that is now recognized as a treatable entity. therefore, it should be included in the differential diagnosis of adult patients with gradually progressive myopathy and respiratory muscle weakness. its treatment, enzyme replacement with recombinant human alpha-glucosidase (rhgaa), although not yet fda-approved for patients over years of age, has shown significant clinical benefit when started early in the course of the disease. owing to the success of therapeutic hypothermia (th) post cardiac arrest, additional indications are now being explored. this case report documents successful application of th for treatment of refractory intracranial hypertension due to poor grade subarachnoid hemorrhage (sah) without the need for decompressive hemicraniectomy. a -year-old male (da) became unconscious after complaining of a bad headache. in the ed, da was listed as unresponsive to all stimuli. ct revealed a hunt/hess grade sah. an aneurismal clipping was performed the following day. on day , he experienced severe vasospasm not amendable to angioplasty and refractory to osmotherapy, cerebrospinal fluid drainage, and mild hyperventilation. at one point the intracranial pressures exceeded mmhg and his left pupil became fixed and dilated. a ct showed extensive edema and a worsening midline shift. it was then decided to initiate th in anticipation for worsening vasospasm. once the target temperature of degrees c was achieved, the icp stabilized. attempts to re-warm on days and led to increases in icp therefore aborted. finally, on day (th day ), da was re-warmed successfully. ct results that originally showed a large area of edema and midline shift was resolved. da was extubated day , a vp shunt was placed on day and discharged to home after a rehabilitation stay with a good neurological recovery on day . considering the mortality of a high grade sah can exceed %, we believe th contributed significantly to a good neurological outcome. a recent study described the need for a decompressive hemicraniectomy prior to attempting mild hypothermia. our case report documents successful application without invasive surgery and may be an option for others. amaurosis is an uncommon complication of pregnancy encountered by neurologists. two common causes of blindness in during the peripartum period are: ( ) reversible posterior leukoencephalopathy syndrome (rpls), and ( ) preeclampsia. case report: a -year old woman delivered twins at -weeks because of severe preeclampsia. in the early postpartum period, she developed altered mental status, and by postpartum day # , she was responsive only to first name, unable to follow commands, and increasingly combative. blood pressures were elevated up to mmhg systolic, and mmhg diastolic. she had limited vision by absence of blink response to confrontation bilaterally. head ct and eeg were unremarkable. based on findings on cerebral magnetic resonance imaging (mri), a diagnosis of hypertensive encephalopathy was made. however, the occipital lobes are clearly spared. her condition substantially improved, and by postpartum day she was able to cooperate with visual acuity and funduscopic examinations. visual acuity was / bilaterally. bilateral fundi showed discrete patches of retinal whitening located between the arterioles and venules, few retinal hemorrhages, and normal optic discs .by discharge, her blood pressure and mental status were at baseline, her vision improved to / , and repeat mri showed resolution of the earlier findings. cause of blindness in this patient was related to purtscher's retinopathy. we believe that this is the first documented case of a patient with a hypertensive encephalopathy and purtscher's retinopathy. this observation indicates that transient visual loss in the setting of elevated systemic blood pressures does not have to be cortical in nature. continuous eeg monitoring of neurocritical care patients is becoming more common. over % of critically ill patients with altered sensorium are diagnosed with non-convulsive seizures or status epilepticus. as continuous eeg is increasingly used with critically ill patients, it is important for practitioners to recognize artifacts that may mimic clinically relevant pathologic discharges. we describe a newly discovered artifact from an invasive hemodynamic monitoring device. seven patients who had a ref/ox (edwards lifesciences) continuous cardiac output pulmonary artery catheter (cco) placed for hemodynamic monitoring and were simultaneously monitored with continuous eeg were retrospectively identified. all patients were cared for in a bed neuroscience icu in an urban level trauma center. all eegs were interpreted by a board certified epileptologist. all patients' eegs demonstrated a distinctive artifact believed to be associated with the cco catheter. this artifact has not been previously described with other pulmonary artery catheters. the eeg was characterized by an intermittent high amplitude, narrow complex, spike-like artifact followed by a high amplitude slow wave. it is hypothesized that this signal results from current flow to the thermal element of the catheter. neurocritical care patients frequently undergo multi-modality monitoring. this newly identified eeg artifact with cco monitoring has an appearance that may be confused with epileptic spike/wave discharges or burst suppression. the impact of this potential artifact generated by the use of cco devices requires further characterization. as neurocritical care patients increase in complexity and are subjected to more invasive monitoring, the identification of new eeg artifacts may become more common. the diagnosis of gullian-barre syndrome (gbs) is based on a combination of clinical and laboratory features. gbs typically presents as a monophasic, subacute, symmetrically, predominantly motor neuropathy. in rare cases, gbs can present with acute quadriparesis and cranial nerve involvement. we report two cases of patients who presented in a state mimicking brain death with complete dysfunction of efferent nerves which turned out to be fulminant gbs. two cases with rapidly progressive weakness presented to our institution with very rapid deterioration requiring mechanical ventilation. over a very short course of time, both patients became paralyzed with complete absence of brainstem reflexes. brainstem function tests were performed as part of full neurological examination which revealed that both patients had non-reactive mydriasis with complete internal and external ophthalmoplegia. rest of the neurological exam including deep tendon reflexes showed no reponse. due to lack of identifiable cause of patient s condition, further diagnostic test were carried out. both patient s underwent csf analysis which revealed evidence of albuminocytological dissociation. a diagnosis of severe guill i a n-barre syndrome with involvement of peripheral and cranial nerves was suspected. electrophysiological studies were performed that showed this was suggestive of severe, axonal, sensorimotor peripheral polyneuropathy with profuse ongoing denervation in bulbar, cervical and lumbosacral innervated muscles. extensive laboratory evaluation including gq b antibody were carried out. after prolonged course, both patients made some functional recovery. both these cases proved that in rare cases, gbs can present with signs of coma and absent brainstem reflexes. brain-death protocols require that before the declaration of brain-death, an etiology needs to identified that could explain the clinical picture and all reversible causes are excluded. these cases illustrate the importance of electrophysiologic, laboratory and imaging studies in patients with suspected brain death where a cause is not clearly determined. hyperperfusion syndrome is a serious complication after carotid revascularization procedure associated with poor outcome, developing between day to days after procedure. in addition to increased cerebral blood flow, clinical manifestation include headache, seizure and intracerebral hemorrhage. equally rare is stent thrombosis especially in patients who were adequately treated with antiplatelets prior to procedure. distinction between the two condition requires prompt diagnosis to achieve good outcome. case report and medical record review m presented with acute l hemiparesis and was treated with iv tpa. nihss was on admission and after hours. ct brain did not show any acute infarction. cerebral angiogram showed % r ica stenosis.the patient underwent r carotid stenting on day . postprocedure map was maintained between - mmhg using oral and iv antihypertensive agents. hours post procedure the patient developed l hemiparesis, dysarthria, right gaze preference and l hemianopia. blood pressure was augmented to map - mmhg while en route to ct/mri and angiography for suspected acute stent occlusion. patient's hemiparesis worsened. ct brain showed unilateral subtle r hemispheric edema but no hemorrhage. mri showed patchy dwi along r hemisphere with subtle cortical and meningeal enhancement. emergent angiography showed patent stent. blood pressure was immediately controlled to map - mmhg and patient improved. within hours, patient was ambulatory. repeat ct brain did not show any acute infarction. months after discharge, he was asymptomatic. hyperperfusion syndrome can develop even with relatively controlled blood pressure post-carotid revascularization. emergent vascular imaging is necessary to differentiate acute stent occlusion from hyperperfusion syndrome so that appropriate measures may be done. when aggressively managed, symptoms associated with hyperperfusion syndrome are fully reversible if not associated with hemorrhage. fulminant hepatic failure (fhf) or diffuse anoxic injury can lead to the development of cerebral edema and increased intracranial pressure. hypothermia has been utilized in both clinical scenarios in attempt to prevent the development cerebral edema and manage elevated intracranial pressure. in this case, we sought to determine a correlation between brain and core temperatures in specifically in intravascular therapeutic hypothermia (iht) this observation was conducted in a year-old woman with grade iii hepatic encephalopathy (he) due to fhf. iht using coolgard® icy catheter (zoll medical) was started immediately as the patient progressed to grade iii he. esophageal and foley temperature probes were utilized for recording core body temperature. monitoring of brain temperature and intracranial pressure was conducted via licox® system (integra). goal temperature range for iht was between - ° c. brain and core temperatures were recorded hourly during iht which was a period of hours. data was collected and plotted to show correlation between the three temperatures over time. measurements were obtained over the course of hours to log temperatures. the results showed: brain temperature: y=- . x + . . r = . . bladder temperature: y = - . x + . . r = . . esophageal temperature: y = - . x + . . the results show a direct linear correlation between brain, esophageal, and bladder temperatures accurate correlation between brain and core temperatures was demonstrated during ihs. further investigation using larger number of subjects is needed to confirm this. the cerebral circulation is normally pulsatile except for short periods of time in patients subjected to extracorporeal circulation, commonly used during cardiac surgery. a new generation of left ventricular assist devices (lvad) generates continuous, non-pulsatile blood flow. in patients with implantable continuous flow lvad (cflvad), peripheral arterial pulsatility will exist as long as the native heart is capable of maintaining enough contractility to generate some stroke volume during systole. we explored the intracranial circulation with transcranial doppler (tcd) in patients that had a cflvad implanted and were neurologically intact. doppler insonation was performed through the routine temporal and occipital bone windows and proximal intracranial vessels were surveyed. transthoracic echocardiogram was performed in all patients to assess the lv function. / patients ( %) that had some preservation of the native heart function exhibited an intracranial flow pattern consisting of: high end diastolic flow velocity, very low pulsatility index and sometimes a sinusoidal wave appearance coincident with the native heart's systolic contraction. / patients ( %) that had extremely poor heart contractility exhibited a distinctive pattern of continuous flow where it was impossible to distinguish between systolic and diastolic flow. with the advent of new mechanical cardiac support for patients with end-stage heart failure, new peripheral and cerebral blood flow patterns develop and clinicians need to be aware of these distinctive and novel findings. this scenario opens an enormous opportunity to understand and better characterize a new physiological situation. it could also limit the usefulness of bedside tcd as a complementary method for the diagnosis of cerebral circulatory arrest given the lack of pulsation, known generator of the isolated systolic spikes or the "to and fro" pattern considered pathognomonic findings of the absence of intracranial circulation. edgar samaniego , gregory kapinos the advanced cardiovascular life support (acls) and advanced trauma life support (atls) provider courses are excellent resuscitation tools directed towards respiratory and hemodynamic stabilization, nevertheless, survival rates with good neurological outcome are dismal. the neurological content of acls and atls training manuals was reviewed. an advanced neurological life support (anls) course is proposed based on the deficiencies of acls and atls (table) . the neurological content of acls is % and covers only ischemic stroke, with no mention of hemorrhagic stroke or other neurological emergencies. the neurological content of atls is %, with a brief description of intracranial hemorrhages, increased intracranial pressure and spinal cord injuries management. both courses overlooked frequent devastating neurological emergencies like status epilepticus, anoxic encephalopathy, acute paralysis and meningitis. many basic concepts of neurological critical care management are missing in advanced resuscitation courses. we advocate the creation of an anls provider course to improve neurological outcomes of patients who undergo resuscitation. animal studies have shown that even a temperature elevation of one degree celsius can worsen neuronal injury after brain ischemia. since the skull acts as a thermal insulator, we hypothesized that decompressive hemicraniectomy lowers brain temperature by facilitating the heat convection from the brain to its surrounding air. fifty patients with severe brain injury (tbi= , ich= ) requiring continuous brain temperature monitoring (licox, integra lifesciences, plainsboro, nj) from january to march were retrospectively studied and grouped into "hemicraniectomy" (n= ) or "no hemicraniectomy" group (n= ). the core body (t core ) and brain (t br ) temperature measurements were recorded at -min intervals over ± icu days. as a surrogate marker for the degree of external heat loss from the brain, t br-core was calculated as the difference between t br and t core with each recording. t-tests were used to initially assess the difference between groups. then, in order to account for clustering of observations in individual patients, generalized estimating equations (gee) were used to assess association of hemicraniectomy with t br-core , adjusting for core body temperature and diagnosis. ). however, after adjusting for intraindividual variability using gee, only higher core body temperature, but not hemicraniectomy, was associated with difference in t br-core (p= . for t core ; p= . for hemicraniectomy). this suggests that the t br-core temperature difference is larger at higher body temperature. substantial variability exists in the brain-to-body temperature gradient across patients and core body temperatures. however, this difference is not due to the presence of a hemicraniectomy. the assumption is often made that young people would want decompressive hemicraniectomy after a large stroke as a life-saving measure. however, this assumption favoring aggressive life-saving treatment, and the perception of quality of life after neurological disability, have not been adequately studied. we conducted a cross-sectional questionnaire-based survey that consisted of demographic information (age, sex, race, marital and family status, religion, income, education level, access to healthcare), and attitude towards neurological disability (based on the highest acceptable modified rankin scale (mrs) that they would be "willing to live with"). young adults in the los angeles county were surveyed and grouped by whether or not they would want hemicraniectomy after a large stroke despite a high likelihood of disability. findings from the two groups were compared using student's t-test and chi-square test. logistic regression analysis was used to determine the factors predicting willingness to accept decompressive hemicraniectomy. in this pilot study, young adults (mean age: ± ) were surveyed. the highest acceptable mrs ( - ) participants felt "willing to live with" were: . % ( ), . % ( ), . % ( ), . % ( ), . % ( ), . % ( ) . despite a high likelihood of severe disability, of ( %) reported they would undergo hemicraniectomy after a severe stroke. neither the demographic factors nor the highest acceptable mrs were associated with the willingness to seek aggressive treatment and hemicraniectomy. the results from our preliminary study support the commonly held assumption that young adults are generally willing to accept decompressive hemicranietomy as a life-saving measure. however, a substantial subset (~ %) were not willing to accept this aggressive measure, which emphasizes the importance of discussing the individual's previously stated wishes, even in the young population. further study in larger populations is needed to better characterize the factors impacting young adults' decisions regarding aggressive care. . ) , but a trend was noted for ne levels (p=. ), and a significant correlation was seen for dhpg (p=. ). our study supports the theory of a cns mediated adrenergic mechanism for nc, based on the presence of increased csf levels of ne and its dhpg metabolite. recent studies have suggested that recurrent stroke during aspirin treatment might have been caused by biochemical aspirin resistance (bar). we hypothesized that patients with bar would develop early recurrent ischemic lesions (erils) on diffusion-weighted imaging (dwi) more than those without bar. we included consecutive patients who: ) were admitted to our center within hours of stroke onset; ) had a final diagnosis of acute ischemic stroke, confirmed by dwi, or tia; ) underwent follow-up dwi within seven days after initial dwi; ) received aspirin therapy; and ) underwent tests for bar. aspirin was administered to patients soon after initial imaging study. bar was measured using the veryfynow rapid platelet function assay-aspirin (accumetrics inc., san diego, ca). an aru was defined as bar. erils were defined as new lesions on followup dwi with decreased apparent diffusion coefficient, which were not detected on initial dwi scans. the bar is associated with the development of erils during the first week after development of ischemic stroke. this suggests that increased thrombogenicity is one of important mechanisms of erils and that aggressive antiplatelet therapy is warranted during the acute phase. in this study we examined the effects of mannitol % on brain metabolism and brain tissue oxygenation (pbto ) in severely brain-injured patients with intracranial hypertension. twenty-two episodes of raised intracranial pressure (> mm hg) resistant to standard therapy that required infusions of mannitol were prospectively studied in comatose patients with multimodality monitoring of intracranial pressure (icp), pbto , and microdialysis. we compared mean arterial blood pressure (map), icp, cerebral perfusion pressure (cpp), pbto , and brain lactate, pyruvate, and glucose using cerebral microdialysis, for hours preceding and hours after hyperosmolar therapy. time series data were analyzed using a multivariable general linear model (glm) utilizing generalized estimating equations (gee) for model estimation to account for within-subjects and betweensubjects variations over time. g/kg of % mannitol solution led to a maximal reduction of icp at minutes (from ± to ± mm hg, p < . ). cpp increased at a peak of minutes (from ± to ± mm hg, p = . ) after mannitol infusion was started, whereas map and pbto did not change significantly. compared to lactate-pyruvate ratio (lpr) at the time of osmotherapy ( ± ,) , mannitol resulted in a an % decrease over hours (to ± , p = . ). brain glucose levels remained unaffected. mannitol effectively reduces icp and augments cpp, and appeared to benefit oxidative metabolism as measured by the lpr. twenty-eight comatose sah patients that underwent multimodality monitoring with intracranial pressure and microdialysis were studied. mc was defined as lactate/pyruvate ratio (lpr) and brain glucose < . mmol/l. time series data were analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes. multimodality monitoring included hours of observation (mean ± hours per patient). in exploratory analysis, serum glucose significantly decreased from . mmol/l ( mg/dl) hours before to . mmol/l ( mg/dl) at the onset of mc (p< . ). reductions in serum glucose of % or more were associated with new onset mc (adjusted odds ratio [or] . , % confidence interval [ci] . - . ). this association was independent of the absolute serum glucose level. in a second model we chose an elevation of the lpr by % or more as the outcome variable. again, reductions in serum glucose of % or more were independently associated with an lrp rise (adjusted or . , % ci . - . ). all analyses were adjusted for significant covariates including glasgow coma scale and cerebral perfusion pressure. acute reductions in serum glucose, even to levels within the normal range, may trigger brain energy metabolic crisis and lpr elevation in poor-grade sah patients. hyponatremia develops in up to one-third of patients after subarachnoid hemorrhage (sah), and is usually attributed to cerebral salt wasting or siadh. our goal was to identify risk factors for hyponatremia after sah, and to determine its impact on outcome. we analyzed consecutive sah patients enrolled in the columbia university sah outcomes project between july and june . hyponatremia was defined as sodium level meq/l occurring at any point during hospitalization. multivariate analysis was performed to identify risk factors for hyponatremia. functional disability was evaluated at discharge and months with the modified rankin scale (mrs, score - ) and barthel index (bi, score < ) the frequency of hyponatremia in or cohort was % ( / ). hyponatremia developed on median post bleed day with most cases occurring between days and . logistic regression adjusted for gender and initial hunt- hyponatremia occurs in % of sah patients, is predicted by older age, fever, renal failure and hydrocephalus, and is associated with reversible functional disability at discharge. failure to correct hyponatremia my potentially interfere with rehabilitation and recovery after sah. previous studies have reported that younger patients have a higher incidence of clinical deterioration from vasospasm after subarachnoid hemorrhage. we sought to determine the relationship between age, with the incidence of vasospasm defined by angiographic, tcd, or clinical criteria. we analyzed consecutive sah patients enrolled in the columbia university sah outcomes project between july and june . vasospasm was assessed using angiography and/or a mean flow velocity greater than cm/s in any vessel. symptomatic vasospasm was defined as clinical deterioration (i.e. a new focal deficit, decrease in level of consciousness, or both) and asymptotic vasospasm included a new infarct on ct that was not visible on the admission or immediate postoperative scan. a tcd velocity greater than cm/s was observed in % of patients and of the patients that had follow-up angiography performed ( %), % of those patients had vessel narrowing consistent with angiographic vasospasm. in contrast symptomatic vasospasm was observed in only % of all patients with % of patients suffering infarction attributed to vasospasm. in total % of patients had either symptomatic vasospasm or asymptomatic infarction from vasospasm. multivariable logistic regression revealed that after accounting for disease severity (hunt & hess) , modified fisher score, gender, and history of smoking, younger age was significantly related to the occurrence of angiographic (or: . , % ci: . - . ) and tcd> cm/s (or: . , % ci: . - . ) spasm, but was not significantly associated with symptomatic vasospasm (p=. ) or delayed infarction from vasospasm (p=. ). our data support the findings that younger patients are more likely to experience vasospasm defined by tcd and angiography than older patients, but in our cohort we did not observe a higher incidence of clinical vasospasm or infarction. aggressive treatment of tcd-based and angiographic vasospasm with intra-arterial vasodilators or balloon angioplasty may mitigate the effect of age. post-traumatic vasospasm (ptv) occurs in - % of patients with severe traumatic brain injury (tbi), and is an independent predictor of neurological outcome. although ptv incidence has been associated with injury severity, there are conflicting reports regarding patterns of intracranial hemorrhage that may correspond with development of posttraumatic vasospasm. some authors report that subarachnoid hemorrhage or subdural hematoma is necessary to develop ptv, while others have reported significant ptv in the absence of these lesions. we performed a review of prospectively collected ct scan data from consecutive head injured patients treated at a tertiary level i trauma center. rotterdam ct score data was reviewed from all patients in the tbi registry, and admission head ct scans from patients with severe tbi (gcs ) with (n= ) and without (n= ) clinically significant ptv (csptv) were re-evaluated by a 'blinded' investigator. csptv was defined as demonstrated neurological decline with ct angiographic evidence of arterial vasospasm. rotterdam ct score significantly correlated with the development of csptv(p= . ). the components of this score were further investigated. we found no correlation between epidural hematoma, subdural hematoma, midline shift, or cisternal compression and the development of csptv. the presence of intraparenchymal hemorrhage (p= . ) and cisternal subarachnoid hemorrhage (p= . ), however, significantly correlated with risk of csptv. all cases of csptv were diffuse in anatomic distribution, and, therefore, did not correlate with side of maximal injury. rotterdam ct score, intraparenchymal and cisternal subarachnoid hemorrhage on admission ct are significantly correlated with the incidence of csptv. this suggests that risk of cerebral vasospasm following traumatic brain injury is increased not only in subarachnoid hemorrhage, but also intraparenchymal hemorrhage, and that rotterdam ct score may be a useful metric for assessing risk of csptv in severe tbi patients. we reviewed patients from a tertiary level trauma center tbi registry and identified patients with clinically significant ptv (csptv), defined as demonstrated neurological decline with ct angiographic evidence of arterial vasospasm. patient charts were reviewed to characterize the natural history, treatment and efficacy of treatment in csptv. treatment strategies for patients with csptv included observation, "triple-h" therapy, oral statins, intra-arterial verapamil infusion and tba. the decision to pursue intra-arterial therapy was based on severity of spasm and clinical exam. observation alone was used in patients with mild, diffuse spasm on cta and rapid clinical improvement (n= ), whereas those with persistent signs of spasm all underwent medical therapy (n= ). intra-arterial verapamil infusion was used in patients with moderate to severe spasm (n= ). tba was performed in patients who had severe and diffuse spasm (n= ). in all cases, therapy was effective in reducing (n= ) or reversing (n= ) ptv. three month functional outcome data revealed no significant differences between patients with and without csptv. treatment of ptv is effective in reducing or reversing arterial vasospasm. a variety of therapies exist, which should be chosen based on clinical exam and the degree and distribution of spasm. although it is unknown if treatment improves outcome, our data suggest that patients with csptv have similar outcomes to those without csptv when they are adequately treated. a clinical pathway is presented to aid in the screening, diagnosis, and treatment of ptv. tracheostomy and gastrostomy are common procedures in patients suffering neurologic insults. we report our current data of these procedures performed simultaneously at bedside by a neurointensivist using percutaneous techniques. database of all tracheotomies, gastrostomies and combined procedures performed by the neuro-critical care team was retrospectively analyzed. also, satisfaction surveys by nursing and house staff were employed to reassess and refine the service. all procedures were completed at bedside in the neurointensive care or other intensive care units utilizing two critical care fellows, an intensive care nurse and a respiratory therapist under the direction of the neurocritical care attending. the team followed each patient daily and reported any complication until discharge. complications were categorized as major (requiring additional surgical intervention) or minor (no additional surgical intervention). to date the team has performed over combined percutaneous tracheostomy and gastrostomiesin patients with primary neurologic pathology. there were two major complications and five minor complications reported. the neurologic pathology was mixed as was the,age and weight ranges combined tracheostomy and peg tube placement can be performed safely by a neurointensivist complications rates are low and no catastrophic events reported. attendings, house staff and nursing supports the continuation of this programs the neuro-critical care service now performs the majority of these procedures in our institution based on the success of the service, non-neurologic related services are consulting the neuro-critical care team to perform these procedures. introduction: traumatic brain injury (tbi) is a complex disease state that includes disruption of the blood-brain barrier (bbb) and inflammatory changes. angiopoietins are a family of growth factors integral in maintaining endothelial integrity and controlling inflammation. angiopoietin i (ang ) induces phosphorylation of the tie ligand enhancing endothelial integrity. angiopoietin ii (ang ) inhibits this action. in animal models, ang is up regulated in tbi while ang appears unchanged. injury models in other tissues suggest that the ratio of ang to ang may be significant. little is known about their role in humans with tbi. we collected csf from patients with tbi ( patients) and compared it controls ( patients). individual levels and ratios were compared. each non-tbi csf had < cells/um, negative gram stain and cultures and normal protein and glucose levels. csf samples were collected from the tbi group within hours of drainage placement.. ang and ang were analyzed using an elisa method and reported in pg/ml. the levels of ang in the control group and tbi group were not significantly different (p value of . ). there was significant increase in ang- in the tbi group (p = . ). comparing the ratios of ang and ang , ang was times higher ( : ) in the control group than in the in the tbi group ( . : ). this data correlates with animal data that shows an increase in ang after tbi. this data further demonstrates a significant change in the ratio of ang to ang after tbi. what happens over time and how this relates to severity and prognosis is yet to be investigated. restoring an ang- to ang- ratio to normal may be a therapeutic strategy worthy of investigation. external ventricular drains (evd) and intracranial pressure monitoring equipment are used frequently in neuroscience intensive care units. because of the potential for the development of nosocomial infection prevention is important. current practice varies from using no antibiotics to continuous antibiotics while devices are in place. there is inadequate foundation to support a particular practice. to define practice patterns, a survey was sent to > , neurosurgeons, critical care, neurocritical care, and infectious diseases specialists. the same survey was also submitted to members of the neurocritical care society but filtered to exclude redundancy. ten percent of practitioners solicited responded to the survey. eighty seven percent of respondents were from north america, followed by asia, europe, and south america. twothirds practiced in academic centers and had > years experience. seventy seven percent of respondents were neurosurgeons, followed by neurocritical care, infectious diseases, and critical care. o % peri-operative abx o % use none. one third of respondents use antibiotic coated evd's there are differing practices among the specialties surveyed. a majority of the respondents use abx for the duration the devices are in place. there are differences in practice among respondents based on specialty, geography, years of practice and type of practice. eighty percent of respondents think a randomized trial comparing abx strategies is needed. retrospective chart review of prospectively identified patients. per institutional protocol, patients were cooled to a nadir of c. baseline prothrombin time (pt), partial thromboplastin time (ptt) and platelet count were obtained and followed at least daily during th and rewarming. data was evaluated for the development of new abnormalities following th induction. thirty six patients received th for various clinical indications, including cardiac arrest and intracranial pressure control (related to subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, and traumatic brain injury). duration of goal temperature maintenance varied from hours to hours. after induction of th, / ( . %) showed abnormal pt, / ( . %) had abnormal ptt, and / ( . %) patients developed thrombocytopenia (platelet count < , /µl). in those developing abnormalities, normalization was not seen for any parameter within hrs of rewarming. overall, % of the patients demonstrated some form of new abnormality following th, none of which had clinically significant bleeding episodes. overall, -day mortality was %; no mortality was attributable to th. we concur with the previously reported findings that th is associated with coagulation abnormalities. a high proportion of patients were found to demonstrate such abnormalities, which persisted following rewarming; the exact clinical significance of these findings is not clear. in addition to this standard laboratory testing, changes in radiographic imaging may serve as a more sensitive adjunctive measure to evaluate the significance of th related coagulopathy. transtentorial herniation (tth) is a clinical syndrome consisting of pupillary dilatation with loss of pupillary light reflex and decreased level of consciousness in the setting of a large intracranial mass lesion. reversal of tth is defined as return of pupillary light reflex with or without immediate improvement in level of consciousness. the role of renal function in the mechanism of hypertonic therapy remains unclear. we evaluated the efficacy and safety of . % saline in tth in patients with end-stage renal disease (esrd) on hemodialysis. patients with clinically defined tth and esrd on hemodialysis treated with . % saline ( to ml) were included in the analysis of a retrospective cohort. of subjects over years, we identified patients with esrd that had tth events. lesions were related to stroke (n= ), intracerebral hemorrhage (n= ), and subdural hemorrhage (n= ). all patients received a . % saline bolus, along with mannitol ( % of events), hypertonic saline maintenance fluids ( %), ventriculostomy (n= ), and hemicraniectomy (n= ). clinical reversal of tth occurred in / events ( %); of patients survived to discharge. in patients, icp recording of tth events showed a reduction from icp of . mmhg (mean sem) with tth to . . mmhg (p= . ) one hour after the . % saline bolus. serum sodium increased from . mmol/l to . mmol/l hours after . % saline bolus (p= . ). no patients were undergoing hemodialysis at the time of the tth event, and the post-infusion serum creatinine did not change. treatment with . % saline was associated with rapid clinical reversal of tth and reduction in icp in this small cohort of patients with esrd. this finding supports that hypertonic saline may be effective in cases of esrd. introduction: intubated patients with subarachnoid hemorrhage (sah) may spontaneously hyperventilate despite minimal ventilatory support. the impact of this is unclear, although hypocapnea may be harmful in traumatic brain injury. we set out to determine the incidence of spontaneous hyperventilation in patients with sah and its association with clinical outcomes. we identified consecutive, intubated patients with spontaneous sah from clinical databases ( ) ( ) ( ) . demographics, clinical and ventilation data (for the first days post-bleed) were collected. hypocapnea was defined as an arterial pco <= mmhg. primary outcomes were ( ) the presence of symptomatic vasospasm (defined by both angiographic vasospasm and clinical symptoms); ( ) death in the intensive care unit. associations between hypocapnea and outcomes were explored with multivariate analysis. we identified patients with sah and a median duration of ventilation of days [iqr - ]. hypocapnea was observed on at least one day in patients ( %), and patients ( %) had at least pco < mmhg. all hypocapnea was associated with alkalemia. ventilatory support was minimal (cpap or ps cm h o) in % of hypocanea measurements. sedation normalized pco in % of cases, and use of neuromuscular blockade was rare. median duration of hypocapnea (at least one pco <= mmhg each day) was days [iqr - ]. duration of hypocapnea was associated with increased odds of symptomatic vasospasm (or . for each day with hypocapnea; p= . ) after adjusting for fisher ct grade. duration of hypocapea was not associated with icu mortality after adjustment for apache ii and wfns grade (p= . ). the incidence of spontaneous hyperventilation is high in intubated patients with sah, despite minimal ventilator support. duration of hypocapnea was independently and statistically significantly associated with symptomatic vasospasm. few studies have evaluated physician-family interactions and decision-making in the neurocritical care unit (nccu). we sought to determine if the icu team's use of a structured checklist for family conferences (fc) would improve family satisfaction. we conducted a prospective pilot pre-and post-intervention study. we designed an -item checklist of key content for fc conducted with the intent of making significant patient management decisions. phase i was observational, with a nurse covertly documenting the key content covered during the fc. phase ii was interventional. we asked the icu team to use the checklist during fc to cover all key content. a family member and the icu team member completed an immediate post-fc written survey, and the fs-icu , a family satisfaction survey, was mailed to the family months after nccu discharge. families enrolled ( phase i; phase ii), with patient age ± years, apache iii score ± and nccu los ± days. patients died ( -pi; -pii). median key content covered was items in phase i and items in phase ii (p= . ). in phase ii, icu team member self-report of key content was higher than documented content ( vs. items; p= . ). post-fc survey scores increased from . (phase i) to (phase ii) (p= . ). the fs-icu decision-making subscale median score was . in phase i and in phase ii (p= . ). use of a fc checklist in the nccu marginally improved coverage of key elements in family conferences, however post fc family satisfaction was improved. further evaluation of the influence of checklists on patient outcomes and family satisfaction for family conferences in the nccu is warranted. h. adrian püttgen , jai madhok , xiaofeng jia , anil maybhate johns hopkins university medical institutions, baltimore, md, united states, johns hopkins university school of medicine, baltimore, md, united states, johns hopkins university, baltimore, md, united states sep's represent the brain's response to sensory electrical stimulus. current clinical methods require averaging a large number of sep waveforms for meaningful prognostication. automated sep monitoring could be used as a noninvasive bedside tool for conditions that severely affect somatosensory conduction due to elevating intracranial pressure (icp) such as cerebral oedema or intracerebral haemorrhage. adult wistar rats were used in this pilot study. to model intracranial hypertension, a latex micro-balloon ( µl maximum volume) was surgically inserted into the epidural space via a burr hole on the left hemisphere ( mm off the sagittal suture). using a micro-pump, the balloon was slowly inflated with water at µl/min for two min periods with a min pause. seps were recorded after electrically stimulating the hind limb at . hz. icp was recorded using a transducing catheter inserted in the subdural space over the right hemisphere. balloon inflation was accompanied by a steady increase in the icp. the increase in icp beyond a certain level was accompanied by the sudden disappearance of sep's within a few seconds ( to sweeps). in our pilot experiments, the peak to peak amplitude of the sep dropped steeply from about + µv to + µv before a complete and sudden disappearance when the balloon volume reached approx. + µl. this pilot study demonstrates the effect of an intracranial mass on the integrity of the somatosensory pathway. the finding of a threshold of lesion magnitude after which further expansion causes a dramatic disappearance of sep points to the possibility of using continuous sep for monitoring rapidly evolving mass lesions such as cerebral oedema or intracerebral haemorrhage. we studied the feasibility of intracortical electroencephalography (ice) including quantitative eeg (qeeg) analysis for the detection of vasospasm in a series of poor-grade sah patients. from a consecutive series of sah patients who underwent ice placement, the alpha/delta ratio ( - hz/ - hz; adr) was calculated at twenty second intervals from the ice and scalp eeg recordings. percent changes between averaged values over - hours of the baseline eeg and the eeg prior to angiography were calculated. the entire continuous qeeg recording for each patient was then reviewed to determine optimal automated alarm criteria. ice recordings revealed an improved signal-to-noise ratio when compared to surface eeg recordings. the adr calculated from the ice decreased between baseline eeg and follow-up eeg on average by % (mean adr decrease . ± . to . ± . ) for those with vasospasm (n= ) compared to % ( . ± . to . ± . ) for those without vasospasm (n= ). a sustained decrease in the adr by at least % from baseline for a minimum of hours occurred in patients with vasospasm - days before angiographic confirmation of vasospasm. this was not seen in patients without angiographic vasospasm. eeg recordings from ice are promising to reliably detect vasospasm in severely brain injured sah patients. absence of artifact allows for automated qeeg analysis of ice recordings. raising the head-of-bed (hob) js a very important step in taking care of critically ill patients, particularly in the neurocritical care, as it influences abdominal pressure, decreases incidence of pneumonia associated with aspiration secondary to the decrease in gastroesophageal reflux and reduces intracranial pressure, improving cerebral perfusion pressure. nevertheless, this relatively simple maneuver is still not widely applied. after explaining the goals of raising the hob individually, each health-care worker (hcw) attending in our -bed neurocritical care service was requested to position the hob between and degrees. as our beds are able to measure hob angulation, it was later conferred. after this simple procedure, hcw were again explained and a folder was distributed. it contained a questionnaire and pictures of hob at , , and degrees. later on, they were again requested to position hob at the adequate position. the first poll revealed that out of participating nurses did not or only partially knew the reasons hob should be positioned between and degrees and almost % of the attempts resulted in failures. among physicians, . % only partially knew the reasons. they could rightly position hob in % of the attempts. after the questionnaire, every and each one of the hcw could name the reasons of hob positioning and almost % of the attempts resulted in right results. hcw should be constantly reminded the importance of simple tasks in the care of neurocritical patients. hob elevation should not be regulated by random trials. automatic beds are very important devices, particularly when some features are present, such as hob angulation and, even though it could seem an expensive device, it will finally allow cheaper and less risky expenditures. posterior reversible encephalopathy syndrome (pres) can be caused by hypertensive crisis and is often associated with rapid fluctuations in blood pressure (bp). the role of these bp changes in the pathogenesis of pres has not been formally studied. we sought to analyze the relationship between blood pressure (bp) fluctuations and the occurrence of pres. consecutive hospitalized patients who developed pres were compared with randomly selected controls matched for age, gender, and history of hypertension. systolic bp (sbp) and diastolic bp (dbp) were collected every hours for hours before developing pres symptoms. sbp, dbp, mean arterial pressure (map), and pulse pressure (pp) changes over a -hour window was summarized for each individual by calculating an m value as described by service et al ( ) . m values were compared using wilcoxon signed rank test. tests were two sided and p values less than . were considered statistically significant. we analyzed the bp profiles in cases of pres and controls. median age of pres patients was years (range - ). of them ( %) had pre-existing hypertension. hypertensive encephalopathy was considered the etiology of pres in patients ( %). at symptomatic onset of pres, mean sbp was ± mmhg (range - ), dbp ± mmhg (range - ), map ± (range - ), and pp ± (range - ). while bp was higher in pres cases, hypertension severity was variable and bp fluctuations were not significantly more common than in controls (p values for sbp, dbp, map, pp were . , . , . , . , respectively). bp fluctuations do not appear to be more common in hospitalized patients who develop pres compared with matched controls. other predisposing factors must therefore contribute to the development of pres. technologies allowing emergent detection of focal cerebral hypoxia would be of great utility in the treatment of ischemic stroke by facilitating diagnosis, tracking reperfusion, and identifying re-thrombosis. non-invasive brain oxymetry using near-infrared reflectance spectroscopy (nirs) technology incorporated into the invos device (somanetics, troy, mi), provides direct measurement of regional oxyhemoglobin saturation (rso ) within the cerebral cortex. this study utilized the invos device to determine the predictive value of cortical rso monitoring in the assessment of ischemia in patients presenting with large hemispheric strokes. patients exhibiting acute ischemic strokes involving proximal mca or ica occlusions on ct angiography were enrolled prospectively. the invos device was applied according to the manufacturer's recommendations. rso data was recorded at s intervals for at least hr in each patient. concomitant vital signs, hgb, oxygen saturation, pao , and paco were collected. three out of patients underwent emergent cerebral angiography. a neuroradiologist, blinded to the invos results, evaluated all ct, ct perfusion, and cerebral angiography studies. ct perfusion imaging confirmed large hemispheric strokes in all patients. mean time from symptom onset to start of rso monitoring was hours (range = - ). data analysis consistently demonstrated mean ro saturation levels on the ischemic hemisphere to be either the same or higher than that of the non-ischemic hemisphere. rso levels were independent of bp, hgb, oxygen saturation, pao or paco levels. cerebral angiography demonstrated significant collateral flow over the affected hemisphere despite deep large vessel occlusions. these findings suggest that nirs technology has limited utility in the assessment of patients with acute ischemic stroke. patency of cortical collaterals and increased tissue oxygen extraction during ischemia, among other factors, may offset a decrease of cortical rso within the affected hemisphere. venous thromboembolism is a common problem in critically ill patients. neurosurgical patients even though at higher risk; often do not receive timely pharmacological thromboprophylaxis for fear of bleeding risks. recent literature points towards the safety and efficacy of early prophylaxis (scd's + heparin/lovenox); however this has not been tested extensively in a randomized controlled trial. a retrospective chart review of patients with a primary diagnosis of subarachnoid hemorrhage (sah), intracerebral hemorrhage (ich), and subdural hematoma (sdh) admitted from january to june was conducted for icd- codes of dvt and or pe, and for presence of associated risk factors. all patients received intermittent compression devices (scd's) on all patients from time of admission to time of discharge, surveillance doppler ultrasound evaluation of both lower extremities once every week, and doppler screening of symptomatic upper extremities. overall incidence of dvt was . % (n= ). the incidence of dvt was . % in sah, . % in ich, and . % in sdh. the incidence of pe was . %.the presence of intraventricular hemorrhage was seen in . % of patients with sah who had dvt. this study shows almost double the incidence of dvt than reported in the recent literature. picc line and central lines were associated with higher incidence of dvt.the timing of the diagnosis of dvt falls in a time window where intracranial bleeding risks from anti-coagulation are far less than in the acute stage. this study will provide us a unique cohort of patients whom we can compare in a prospective manner to patients who will receive subcutaneous heparin along with scd's in the future, since we are changing our policy to implement heparin thromboprophylaxis. the presence of intraventricular hemorrhage (ivh) is predictive of worse outcomes following aneurysmal subarachnoid hemorrhage (sah) [ ] . however, the amount of ivh can vary considerably. no previous studies have assessed the association between actual hematoma volume (in ml) and subsequent complications or outcomes. we performed a cohort study involving consecutive patients with concomitant sah and ivh. with investigators blinded to subsequent events, ct scans were graded using two systems. first, to determine the volume of ivh, we used the ivh score, recently shown to correlate exceptionally well with computerized volumetric assessment [ ] . second, to examine the relative amount of subarachnoid blood, we applied the sah component of the hijdra score [ ] . using logistic regression to adjust for sah score and other potential confounders, we assessed the association between ivh volume and poor neurological outcomes (glasgow outcome scale - ), as well as symptomatic vasospasm and delayed infarction. compared with patients who had a favourable outcome, those with poor outcomes had significantly larger baseline ivh volumes (mean . ml vs. . ml, p= . ). in the multivariable analysis, ivh volume remained an independent predictor of poor neurological outcome (or per ml: . , . - . , p= . ). patients in the highest quartile for ivh volume were far more likely to progress to poor outcomes compared with those in the lowest quartile (or . , . - . , p= . ). in contrast, ivh volume was not associated with either vasospasm or delayed infarction. interobserver agreement in the determination of ivh score was good. volume of ivh is a strong, independent predictor of death and poor neurological recovery, even when one adjusts for the amount of concomitant subarachnoid blood. future studies should assess whether measures aimed at accelerating the clearance of ivh (e.g. intraventricular thrombolysis) can modify this association. andrew naidech, kimberly levasseur, storm leibling, rajeev garg, michael shapiro, michael ault, sherif afifi, hunt batjer northwestern university, chcago, il, united states while many icus have implemented protocols for tight glucose control, there are few data on relative hypoglycemia and neurologic outcomes. we addressed the hypothesis that lower glucose leads to worse neurologic outcomes after subarachnoid hemorrhage (sah). one hundred seventy-two ( ) consecutive patients were treated with a protocol designed to achieve serum glucose - mg/dl. we prospectively ascertained patients on admission and recorded medical history and clinical events. glucose measurements from the hospital laboratory were electronically retrieved. (a separate analysis of bedside glucose results found similar results.) cerebral infarction was prospectively documented with neuroimaging. outcomes were assessed with the modified rankin scale (mrs) at days, days and months. worse neurologic injury at admission (p< . ) and a history of diabetes (p= . ) were associated with increased glucose variance. patients with radiographic cerebral infarction ( ± vs. ± mg/dl, p= . ), symptomatic vasospasm ( ± vs. ± mg/dl, p= . ) and angiographic vasospasm ( ± vs. ± mg/dl, p= . ) had lower nadir glucose, but maximum and mean glucose were not different. glucose < mg/dl was earlier and more frequent in patients with worse functional outcome (p< . ). progressive reductions in nadir glucose were associated with increasing functional disability at months (p= . ) after accounting for neurologic grade and mean glucose. severe hypoglycemia (< mg/dl) occurred in one patient. in patients with sah, nadir glucose below the < mg/dl is associated with cerebral infarction, vasospasm, and worse functional outcomes in multivariate models. protocols for target glucose - mg/dl effectively control hyperglycemia, but may place patients with sah at risk for vasospasm, cerebral infarction and poor outcome even when severe hypoglycemia does not occur. andrew naidech, rajeev garg, storm liebling, kimberly levasseur, micheal macken, stephan schuele, hunt batjer northwestern university, chicago, il, united states there are few data on the effectiveness and side effects of anti-epileptic drug (aed) therapy after intracerebral hemorrhage (ich). we tested the hypothesis that aed use is associated with more complications and worse outcome after ich. we prospectively enrolled patients with ich and recorded aed use as either prophylactic or therapeutic along with clinical characteristics. aed administration and free phenytoin (pht) serum levels were retrieved from the electronic medical record. patients with depressed mental status underwent continuous eeg monitoring. outcomes were measured with the nih stroke scale and modified rankin scale (mrs) at days or discharge, and the mrs at days and months. we constructed logistic regression models for poor outcome at months with a forwardconditional model. seven ( %) patients had a clinical seizure, five on the day of ich. pht was associated with more fever (p= . ), worse nih stroke scale at days ( [ - ] vs. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , p= . ) and worse mrs at days, days and months. in a forward-conditional logistic regression model pht prophylaxis was associated with an increased risk of poor outcome, or . ( . - . ) p= . , entering after admission nih stroke scale and age. excluding patients with a seizure did not change the results. levetiracetam was not associated with demographics, seizures, complications, or outcomes. pht was associated with more fever and worse outcomes after ich. posterior reversible leukoencephalopathy syndrome (pres) is characterized by seizures, headache, encephalopathy and visual disturbances associated with reversible vasogenic edema on brain imaging. status epilepticus (se) has been infrequently described as an initial manifestation of pres. the clinical and radiological features of patients with pres and se have not been well described. patients with se were identified from a mostly prospectively collected database of patients (n= ) with pres. we collected data on general demographics, clinical presentation, history of epilepsy, peak systolic and diastolic blood pressures, and predisposing conditions. brain mris were analyzed independently by two neuroradiologists for lesion location and distribution, severity, presence of hemorrhage and presence of restricted diffusion. of patients with pres, ( %) presented with se. only had a prior history of epilepsy. mean peak sbp was mm hg ( - ) and mean dbp was mm hg ( - ). etiologies of pres included hypertension (n= ), cytotoxic medications (n= ), sepsis (n- ) and other (n= ). renal failure was present in ( %) cases and ( %) had pre-existing chronic kidney disease. twelve patients ( %) had a history of autoimmunity. among patients with brain mri, ( %) demonstrated mild edema and ( %) had moderate-severe edema. the cortex was involved in only patients ( %). almost all had edema in the parietal-occipital region (n= , %). when compared with the rest of our pres cohort, we did not identify any significant clinical or radiological predictors of se. se is not an infrequent presentation of pres. its occurrence is not correlated with the severity of radiologic edema and the great majority of patients actually lack cortical involvement. recognition that pres may present with se is important because, besides anticonvulsants, appropriate treatment requires identifying and treating the underlying cause of pres. hypervolemia is known to lead to peripheral and pulmonary edema however the effect on intracranial pressure (icp) following traumatic brain injury (tbi) is unclear. there is no direct evidence in humans linking hypervolemia independently to elevated icp. compelling evidence suggests that fluid restriction should be avoided and limited evidence suggest significant hypervolemia may be associated with worse outcome following tbi [ ] . the use of fluids and vasopressors to elevate cerebral perfusion pressure (cpp) > mmhg has been to shown to increase the risk of pulmonary complications (but not clearly effect icp) following tbi and is not recommended by guidelines [ , , ] . despite this, some ancillary monitoring protocols recommend elevating cpp to treat episodes of cerebral hypoxia. retrospective observational cohort study of severe tbi patients admitted over a -year period to a neuro-trauma unit. data extracted: characteristics; fluid balance; development of refractory intracranial hypertension (rih); pulmonary complications; use of vasopressors; ancillary monitoring. patients with unsurvivable injuries, early withdrawal of care or the development of refractory intracranial hypertension (rih) within hours were excluded. forty-one patients with mean age . ; % male; % automobile accidents; % polytrauma; average best gcs of . (a subgroup presented with higher gcs with declined secondary to neurological injury). rih was associated with lower fluid balance but not hypervolemia (overall q = %, iq = %, q = %). an early low fluid balance and hypervolemia both are associated with more pulmonary complications. the use of vasopressors, and to a lesser extent licox monitoring is associated with a higher incidence of pulmonary complications and possibly rih. [tables - ] % ( / ) % ( / ) % ( / ) q = first quartile, iq = interquartile, q = fourth quartile; rih = failure of first tier therapy by brain trauma foundation; pulmonary complications = ards or pulmonary edema with p/f ratio < ; use of vasopressors = for > hours and > hours to maintain cpp > mmhg following severe tbi hypovolemia should be avoided as it's associated with increased icp and pulmonary complications [ ] . extreme hypervolemia should be avoided, if possible, to minimize pulmonary complications. ancillary monitoring protocols should be used with caution, as the components that may improve outcome versus those that may harm are incompletely defined. without correction for patient demographics, severity of illness, and head ct findings further conclusions cannot be made. invasive mechanical ventilation is required in one third of patients with guillain-barré syndrome (gbs). there are few early indicators of subsequent progression to respiratory failure. adrenal function has rarely been studied in patients with gbs. we assessed the relationship between plasma cortisol level and gbs related complications, notably respiratory failure. plasma cortisol levels were measured before (t ) and minutes (t ) after corticotrophin test in gbs patients at admission, ( %) of which were ventilated within hours from admission, ( %)ventilated after the th hour and ( %) never ventilated. the volume of subarachnoid hemorrhage (including intraventricular blood) following aneurysmal rupture is associated with the development of vasospasm. intraventricular catheters (ivc) facilitate cerebral spinal fluid (csf) drainage and may reduce the incidence or severity of vasospasm but little evidence exists from which clinicians may determine the best practice. the purpose of this study was to provide the foundation for designing a trial that will explore how different methods of csf drainage may impact outcomes in these patients. this observational pilot study enrolled adult sah patients. data was collected through chart abstraction. attending neurosurgeons determined whether each patient's ivc was primarily left open to drain csf resulting in intermittent icp monitoring (drain-first group), versus an ivc that was primarily set to monitor icp resulting in intermittent csf drainage at a set pressure threshold (monitor-first group). subjects were primarily female ( %), mean years old. subjects in the drain-first group (n= ) and the monitor-first group (n= ) had similar hunt/hess (p= . ) and fisher scores (p= . ). although there are no statistically significant differences between groups, this pilot study was not designed to test a hypothesized difference. the monitor-first group had lower mean csf output ( vs ml/day), lower rates of vasospasm ( % vs %), lower incidence of complication ( % vs %), shorter length of stay ( vs days), and lower modified rankin scores at discharge ( . vs . ). this observational study suggests that the method of ivc management may impact clinical outcomes. although the monitor-first group method appears to be favourable, it is difficult to attribute differences in a non-randomized trial. a larger randomized controlled clinical trial is now in progress. introduction: subarachnoid hemorrhage (sah) patients whose initial angiogram does not locate a bleeding source are often classified as having perimesencephalic hemorrhages. however, many patients do not fit into this benign picture and are non-perimesencephalic, angiogram-negative sah (npan-sah). though the conventional angiogram remains the gold standard for diagnosis, multiple non-invasive imaging tests, beyond a second angiogram, are often performed in the acute evaluation of npan-sah. with irb approval, we retrospectively reviewed non-traumatic sah patients admitted to our institution from january , to june , . hunt-hess and fisher scores, in-hospital complications, and imaging data were abstracted from medical charts. non-perimesencephalic angiogram-negative sah has a worse prognosis compared to perimesencephalic sah. additional non-invasive neuroimaging provided no diagnostic yield in either patient population. guidelines suggest an ideal time from injury to surgical decompression of less than four hours in patients with acute traumatic subdural or extradural haematoma. previous audits at our centre showed this standard was not consistently achieved. we looked for a relationship between the length of this time interval and adverse neurological outcome at six months. we retrospectively reviewed all patients with acute traumatic subdural (asdh) or extradural (aedh) haematoma transferred to our neurosurgical centre over a three year period (december -november ) for emergency surgical decompression. we identified the time elapsed from presentation at the emergency department to commencement of surgical decompression. we then assessed neurological function at six months post surgery using a glasgow outcome score. we were able to include patients in our study ( asdh, aedh). the mean time from presentation to surgery was : hours. at six months . % of patients had a good neurological outcome (gos - ), . % had a poor outcome . of those presenting with gcs < , % had a good outcome compared to % of those with an admission gcs of or above. achieving definitive surgery within four hours of presentation, let alone injury remains elusive. we were unable to associate prolonged length of transfer time with worse neurological outcome at six months. our study was retrospective and the numbers were small. our unit accepts a significant number of patients from outside its normal referral area, meaning there may already be a significant delay in many cases. in most cases there was no single identifiable reason for delay and a few cases showed that transfer could be achieved very rapidly. sah patients who had hunt-hess grades - , a ventriculostomy, and tcus performed for at least days were included in this study. csf ml was collected from each patient during the first hours and assayed by hplc for levels of epinephrine (epi), norepinephrine (ne), and dihydroxyphenylglycol (dhpg). mca vs was defined as a mean velocity (mv) > cms/s with a mca/ica ratio of > at any time. analyses were calculated on a per-case and per-vessel basis. of the initial patients included, were excluded due to incomplete data as a result of early mortality or absent bone windows. from the remaining patients, had only ipsilateral bone windows, resulting in a total of vessels amenable to insonation. mean age was yo, and % were female. ct scores (frontera et al.) were = %, = %, = %, & = %. on a per-case basis, patients with mca vs were younger ( yo vs yo, p=. ), but no correlation was observed between mca vs and adrenergic levels. on a per-vessel basis, hh grade tended to correlate with mca vs (p=. ), but again no association was observed between mca vs and adrenergic levels. no connection was seen between csf adrenergic levels and mca vs. our study is limited by small numbers, but our findings are consistent with the available literature whereby the association between the sympathetic nervous system and vs remains uncertain. marek mirski hospital of the university of pennsylvania, philadelphia, pa., united states, johns hopkins medical institutions, baltimore, md., united states dexmedetomidine is an alpha- adrenoreceptor agonist with sedative, analgesic and anxiolytic properties approved for the intubated adult patient in the icu setting. it possesses well described attributes for the neurological population; a rapid ability to sedate and awaken the patient allowing continuing neurologic assessment and no relevant respiratory depression. properties including neuroprotection, cardioprotection and renoprotection have been proposed and investigated in various settings. demonstrated clinical benefits in the icu neuroscience setting are just emerging. this synopsis reviews the literature in regards to clinical studies conducted to evaluate dexmedetomidine in the neurosciences. characteristics of the studies were categorized by study design, setting, patient population, and comparisons to other agents. human clinical studies were identified through a search of pubmed from - . key words include dexmedetomidine, nicu, neurocritical care and cea. study designs include randomized, observational, retrospective and case series. twenty-seven studies were included in the final analysis. the majority are case-studies or anecdotal and the literature consists of mostly surgical patients vs. the icu population. the leading hypothesis is that dexmedetomidine is safe and efficacious in the neurosurgical population and may provide neuroprotection. consistent findings are the attenuation of hemodynamic and endocrine response, smoother extubation and facilitation of neurological assessment. dexmedetomidine has gained popularity in applications beyond its labeled indication and dosage, in various icu's, and in special populations. the literature points to gained acceptance and favorable conditions for sedation without toxicity on cns parameters and a rapidity of onset and offset. there is brevity of literature which demonstrates positive outcomes in the neuroscience setting and the primary data does not represent level or evidence. more studies should be done to validate this drug for common use as there appears to be great advantages in the neuroscience population. the hijdra scale was developed to quantify the volume of blood following aneurysmal subarachnoid hemorrhage (asah). we investigated the relationship of hemorrhage quantity utilizing the hijdra scale and aneurysm size among patients with asah. we prospectively followed up a cohort of sah patients annually to document outcome events after obtaining informed consent. we abstracted demographic, clinical, and past medical history data by chart review on a subset of patients with documented asah after excluding those with cryptogenic, traumatic, and non-aneurysmal sah. the primary outcome of interest, hemorrhage quantity, was analyzed as both an ordinal measure (small, moderate, large) using tertiles and a dichotomous measure using the median. proportional odds logistical models for ordinal response measures and simple logistical regression for dichotomous responses were constructed to investigate the relationship between hemorrhage quantity and aneurysm size. from / to / a total of patients were enrolled in the rush university sah database. of these, we identified patients with documented asah; % were female; % white, % black, % hispanic; and the mean age was ± years. the mean ruptured aneurysm size was . mm and the median hijdra score was (range - ). we found no relationship between ordinal (p= . ) and dichotomous (p= . ) hemorrhage quantity and aneurysm size. no relationships were found between hemorrhage quantity and age, sex, race, apache ii score, and history of anti-platelet use. there was a trend for significance among patients with a past medical history of hypertension and having large hemorrhage quantity (or . , . - . ; p= . ). we found no relationship between aneurysm size and quantity of hemorrhage among patients with asah. future studies should focus on clinical variables such as hypertension and their role in hemorrhage quantity. stroke is the third leading cause of death in the united states. among the stroke subtypes intracerebral hemorrhage (ich), subarachnoid hemorrhage (sah), and ischemic stroke (is), ich and sah are associated with the highest mortality, followed by is. most deaths due to stroke occur within the first days, though it is unclear if any specific stroke subtype carries a significantly higher risk of early mortality (within the first hours from presentation) when compared to the other subtypes. with irb approval, we retrospectively reviewed stroke patients transferred to our institution between november and april who died during hospitalization. we collected data including primary diagnosis, confirmed by ct or mri, and time from presentation to our institution to death from any cause. among the in-hospital stroke deaths, ich was the diagnosis in ( %), sah in ( %), and is in ( % amongst in-hospital stroke deaths, ich was the stroke subtype associated with the highest likelihood of early mortality. this may indicate the severity of the disease process and a lack of effective early therapeutic measures available for ich. cerebral vasospasm is a common complication of sah and remains a major cause of death and disability after aneurysm rupture. the enos promoter (- t>c) cc genotype has been associated with a three-fold increased risk of angiographic cerebral vasospasm, however, its effect on adverse neurologic outcomes after sah has yet to be determined. we hypothesize that enos genotype would predict worse outcome, likely through its effect on risk of vasospasm. subjects included patients with confirmed aneurysmal sah enrolled in a longitudinal cohort study. we analyzed data from subjects for whom we had genotype information as well as -month follow-up assessment. patients who died prior to follow-up were excluded. univariate analyses used chi-square, wilcoxon ranksum or students t-test for the individual predictor variables. modified rankin scale score (mrs) was our primary outcome. logistic regression analysis for poor outcomes (mrs > ) included genotype and adjusted for age, sex, race/ethnicity, and hunt-hess grade. of the subjects, % were dependent or severely disabled (mrs > ) at months. older age, higher hunt hess grade and presence of vasospasm were associated with poor outcomes. the enos (- t>c) cc genotype was associated with mrs> with an adjusted or of . ( %ci . - . ). our results support a trend between enos (- t>c) cc genotype and -month poor functional outcome (mrs> ). although these results are not as robust as the association with angiographic cerebral vasospasm, it demonstrates the ability to integrate genetic information with clinical outcomes. limitations are primarily the small sample size and ability to adequately adjust for all clinical factors that could influence outcome. whether the effect on outcome of enos genotype is related to cerebral vasospasm risk will require further study. therapeutic hypothermia has been utilized in various brain injury models, including aneurysmal subarachnoid hemorrhage (sah). hypothermia has been used to treat refractory cerebral edema or severe vasospasm in this setting. however, there is very little data on hypothermia as a prophylactic measure before potential complications of sah have occurred. we evaluated the safety and feasibility of prophylactic hypothermia in patients with aneurysmal sah. we conducted a retrospective chart review of patients admitted with aneurysmal sah at a tertiary stroke center from july , to june , , who were also treated with induced hypothermia. only patients who had hypothermia initiated prior to symptomatic vasospasm onset were included. a total of out of patients were treated prophylactically with mild hypothermia ( - degrees celsius). three patients presented with hunt and hess grade i-iii, and seven patients with grade iv-v sah. average time at initiation of hypothermia was on sah day (range day - ). six ( %) patients underwent treatment of aneurysm by endovascular coiling or surgical clipping within hours of symptom onset. the average duration of hypothermia was days (range - days). nine ( %) patients developed evidence of vasospasm on computed tomography angiography or transcranial doppler. five ( %) patients survived to discharge. causes of death included irreversible global hypoxia from cardiac arrest ( ), severe refractory cerebral vasospasm ( ), and malignant mca infarction ( ) . all four patients with grade v sah died. when these patients were excluded, of the remaining patients, ( %) survived to discharge, and ( %) died. prophylactic hypothermia may be effective and safe in selected patients with aneurysmal sah. additional studies are needed to further define timing and parameters for therapeutic hypothermia in this setting. melatonin and pinoline are indolamines which have shown an antioxidative direct and indirect protection effect in vitro and in vivo models. fourteen -week-old male, c b mice underwent reversible middle cerebral artery occlusion ischemia ( . hours) followed by hr of reperfusion. the animals received pinoline ( mg/kg i.p.; n= ), melatonin ( mg/kg i.p.; n= ) or vehicle (n = ) at ischemia, immediately upon reperfusion, and at and . hr post-ischemia. another three animals in each group received the same doses but were sacrificed at . hours and used for protein oxidation quantification by western blot. rectal temperature, surgical time, time to ischemia and time to reperfusion were recorded continuously. initial neurological damage by modified stroke score was grossly assessed at ischemia, reperfusion, and at hr. infarction volume was quantified using , , -triphenyltetrazolium chloride (ttc) staining, digital photography, and imaging analysis software. means (± sd) were calculated and compared using student's t-test or anova. p . was set as statistically significant. total hemispheric infarction volume was reduced in the pinoline and melatonin-treated mice compared with the nontreated group ( ± % vs. ± %; p < . ) and ( ± % vs. ± %; p < . ) respectively. pinoline score was . vs. . in the control group at h. no statistical difference was observed in the melatonin group. optical net intensity ratio was statistically significance at cortical level on the kd band in the melatonin and kd on the pinoline groups. pinoline and melatonin treatment appeared to confer neuroprotection on a cerebral ischemia in vivo model. although its anti-ischemic mechanism needs to be elucidated, both molecules are potent free radical scavenging properties may offer a potential therapy. manisha gupte, jay joshi, sayona john, shyam prabhakaran, vivien lee rush university medical center, chicago, il, united states the "weekend effect" phenomenon suggests that admission day of the week is an independent predictor of mortality. we evaluated the effect of weekend admission on sah in-hospital mortality at a single academic center. with irb approval, we retrospectively reviewed consecutive sah patients admitted to our institution from august , to june , . weekend was defined as saturday or sunday. data was collected on day of the week admission, in-hospital mortality, aneurysm type and treatment. ct images were reviewed by the study neurologist and scored for fisher grade. of sah patients admitted to our institution, ( %) were female. the mean age was . years (range, to ). ct brain fisher score was as follows: fisher ( %), fisher ( %) and fisher ( %). the cerebral aneurysm distribution was acom ( %), pcom ( %), mca ( %), multiple ( %), and angiogram negative ( %). surgical clipping was performed in ( %) and endovascular treatment was performed in ( %). the overall sah in-hospital mortality rate was %. weekday admission accounted for %, and weekend admission occurred in %. age, fisher grade, and treatment modality were not significantly different between weekday versus weekend admission. the mean time from admission to treatment of aneurysm was . days and did not differ significantly by weekend versus weekday admission (p . ). mortality rate was % for sah patients admitted on a weekend versus % for sah patients admitted on a weekday (p . ). the weekend effect does not appear to be a significant factor in mortality outcomes of sah patients. the time to definitive aneurysm treatment does not appear to be impacted by weekend admission. the ich score is a simple clinical-radiographic scale in patients with intracerebral hemorrhage (ich) that helps estimate -day mortality. we hypothesize that the ich score can be applied to patients with warfarin ich (w-ich) to help estimate thirty-day mortality. anemia is a highly prevalent condition among hospitalized patients. we hypothesize that patients with acute cerebrovascular disease and anemia on admission have poor prognosis in terms of death, length of stay and disposition. a retrospective analysis of patients admitted to our institution with acute stroke (ischemic, hemorrhagic, subarachnoid hemorrhage) between october and march was performed. they were dichotomized based on hematocrit levels of < , >/= for women and < and >/= for men using the who definition of anemia. covariates used include diagnosis, demographic information and past medical history. the best admission hematocrit cutoff points for distinguishing between those with increased risk of death, disposition to snf (skilled nursing facility), increased los (length of stay) were identified. of the patients, ( . %) were female with a mean age of . years. of these patients ( . %) were anemic. ten patients died and nine were dispositioned to snf. while the relationship between disposition and anemic status was not significant (p= . ), there was evidence that those who died were more likely to be anemic (p= . ). los did not differ statistically between anemic and those without anemia. none of the variables were statistically significant on univariable analysis for mortality. anemia on admission did not predict death, disposition to snf or los, but there was a tendency that patients who died were more likely to be anemic. the admission hematocrit cutoff point for distinguishing risk of death, disposition to snf was slightly lower and increased los was higher than the who definition of anemia. abciximab, a glycoprotein iib/iiia receptor inhibitor (gpiib/iiia), is used during neuroendovascular procedures both to prevent and treat ischemic sequelae. experience with abciximab in this setting is limited and major bleeding complications, including fatal intracranial hemorrhage (ich), are of particular concern. we report our multicenter experience with ich following administration of abciximab during neuroendovascular procedures. we identified neuroendovascular procedures in which abciximab was used at three academic institutions from november through april . cases of periprocedural ich were identified and pertinent demographic, historical, procedural, laboratory, and radiographic data were collected. clinical outcome was measured by the glasgow outcome scale (gos) either at death or discharge. abciximab was used in neuroendovascular procedures; ich cases ( . %) were identified. procedures performed and indications for abciximab use varied. route of abciximab administration included iv bolus only (n= ), ia bolus and iv infusion (n= ), iv bolus and iv infusion (n= ), and iv infusion without preceding bolus (n= ). all patients but one received periprocedural antiplatelet, anticoagulant, or thrombolytic agents. all ich were detected within hours of abciximab administration, (except patient ; hours); were detected within hours. ich patterns varied and included subarachnoid hemorrhage (sah) with intraventricular hemorrhage (ivh) (n= ); intraparenchymal hemorrhage (iph) with ivh (n= ); sah, ivh, and iph (n= ); and a combination of sah, ivh, iph, and subdural hemorrhage (n= ). four patients died following ich (i.e. gos score of ); gos scores at discharge for the remaining cases were (n= ), and (n= ). ich was common ( . %) after neuroendovascular procedures using abciximab and was associated with a % mortality. future management strategies should focus on earlier recognition of gpiib/iiia-related-ich; development of direct gpiib/iiia antidotes; comparisons with shorter-half-life gpiib/iiia drugs; and identification of optimal abciximab dose and route. cerox is a novel noninvasive brain and tissue oxygen saturation monitor based on nirs and ultrasound technology. the purpose of this prospective observational study of patients with both traumatic and non-traumatic brain injuries is to determine if the cerox correlates with existing measures of cerebral oxygen metabolism which are currently used as part of regular care in the management of patients with severe brain injury. we enrolled patients with severe brain injury (tbi = , ich = ) who had at least one invasive cerebral oxygen monitor in addition to an intra-cranial pressure monitor. cerox adhesive patches were placed bilaterally over the frontal regions of the scalp and optical probes were attached to the patch clips. monitoring with cerox continued for up to days. high density physiological data, e.g., map, brain tissue oxygen, jugular venous saturation, icp, were collected at q minute intervals into our neurocritical care database. physiological data were then merged with cerox measurements. ten patients requiring invasive neuromonitoring were enrolled during this -month study period. the duration of noninvasive recording was - days (mean= days) with maximum length of uninterrupted recording being -hours. cerox measurements ranged from - . % (mean = %) on the left and - % (mean = . %) on the right. in this group of patients, the brain tissue oxygen tension ranged from . - . mm hg, the jugular venous saturation was . - % and the cerebral blood flow varied from . - ml/ gm/min. continuous monitoring with cerox is safe and feasible in neurocritical care setting. it has the potential of providing information about cerebral metabolism needed for close monitoring and management of patients with severe brain injury deep vein thrombosis (dvt) is a common complication of intracerebral hemorrhage (ich) and has been associated with immobility in the lower extremities. [ ] atherosclerotic risk factors (hypertension, diabetes mellitus (dm) and hypercholesterolemia) are associated with arterial thrombosis and have been postulated play a role in venous thrombosis. [ ] we hypothesized that a history of atherosclerotic risk factors increases the risk of dvt in ich patients. retrospective analysis of patients diagnosed with spontaneous ich at our institution between january and december was performed. demographics, history of hypertension, dm or hypercholesterolemia; systolic blood pressure at presentation; presence of immobility or hemiparesis and diagnosis of dvt were collected. logistic regression analysis was used to predict the risk of dvt. of patients with spontaneous ich were immobile and were selected for analysis. all patients had sequential compression devices applied on admission. the overall incidence of dvt diagnosed by lower extremity doppler was % and pulmonary embolism was . %. mean time to diagnosis of dvt was . (sd . ) days. after stepwise logistic regression analyses, significant predictors of dvt in immobilized ich patients were, history of hypercholesterolemia (or . p= . ) and sbp on admission > (or . p= . ). immobilized ich patients with a history of hypercholesterolemia were three times more likely to develop dvt. a sbp > on admission was five times more likely to predict dvt. thus atherosclerotic risk factors may play a role in the pathophysiology of dvt in immobilized ich patients, suggesting a possible etiopathologic link between arterial and venous thrombosis. acute ischemic stroke due to the occlusion of the internal carotid artery (ica) is associated with malignant stroke and poor outcome. without revascularization of ica perfusion to the middle cerebral artery (mca) and anterior cerebral artery (aca) is not possible. objective: objective of our study is to evaluate the technical feasibility of emergent carotid artery revascularization using stent and to evaluate the impact of stenting in distal cerebral perfusion. from an established stroke database consecutive patients with acute ischemic stroke who underwent emergent carotid stenting and thrombolysis/clot retrieval of the mca and aca from july to december were enrolled. patients' demographics including presenting national institute of health stroke scale (nihss), degree of revascularization, hemorrhagic conversion and days outcome data using glasgow outcome scale (gos) were collected. successful ica stenting was possible in / ( %) patients. the average age of patients was years (ranges - ) and average nihss was (ranges - ). carotid stenting facilitated successful revascularization of the mca and aca using tpa and merci clot retriever device in patients ( . %), ( %) of which has achieved complete recanalization in the mca and aca. in complete recanalization group a point or higher nihss improvement was observed in / ( . %) patients. symptomatic intracranial hemorrhage was observed in . % patients. seven of patients who achieved complete recanalization had a good outcome. five of patients who did not achieve complete recanalazation of the mca and aca died and had nihss . nihss was associated with incomplete recanalization of the mca and aca with poor outcome. emergent carotid revascularization is not only technically feasible in patients with acute ischemic stroke due to the carotid occlusion, but it also facilitates successful renalization of the mca and aca. further study is necessary. stent-assisted coiling of wide neck intracranial aneurysm requires therapeutic dose of antiplatelets to prevent stent thrombosis. stent-assisted coiling of the ruptured intracranial aneurysms also requires a loading of both loading dose of aspirin and plavix. objective: to report any potential complication associated with the use of both aspirin and plavix in stent-assisted coiling of ruptured wide neck intracranial aneurysm. consecutive patients who underwent stent-assisted coiling for ruptured wide neck intracranial aneurysm were enrolled from to . patient's demographics including the hunt & hess grade, fished scale, use of ventriculostomy catheter, location and size of aneurysm were collected. any complication such rupture of aneurysm, ventriculostomy associated hemorrhage or systemic bleeding was recorded. additionally a days outcome measurement was obtained using glasgow outcome scale (gos). results: patients with mean age of ± underwent stent-assisted coiling. a loading dose of plavix ( mg to mg) and aspirin mg were given prior to stent placement. patients received ventriculostomy catheter, cases before and cases after the procedure. there was no intraoperative ruptured of aneurysm or hemorrhage related to ventriculostomy or systemic hemorrhagic event. there were two episodes of stent thrombosis; one was an asymptomatic which developed during stent-assisted coiling procedure and resolved spontaneously, the other was symptomatic required intra-arterial administration of thrombolytic. there was no mortality and good outcome was observed in % of patient. stent-assisted coiling of the ruptured wide neck intracranial aneurysm using therapeutic dose of aspirin and plavix is not associated with increased bleeding complication such as rupture of aneurysm or intracranial hemorrhage related to ventriculostomy. however, the thromboembolic events remain the main challenge in stent-assisted coiling of ruptured intracranial wide neck aneurysm. therefore, antiplatelets should not be withheld prior to a stent-assisted coiling of ruptured wide neck aneurysm. we have used mild therapeutic hypothermia in patients with severe traumatic brain injury. in this study we investigated the effects of hypothermia on brain tissue oxygenation. brain tissue oxygen tension (pbto ) in addition to intracranial pressure (icp), cerebral perfusion pressure (cpp), and jugular venous saturation (sjo ) were monitored in consecutive patients with a glasgow coma scale score of to (ages to years). patients were cooled to a target temperature of . o c. patients with good recovery and moderate disability on the glasgow outcome scale were regarded as having favorable outcomes. a retrospective review of a six-month period in a university nccu was performed where patients were treated according to the above hypothesis. anticoagulation was usually started with heparin units sq q hr within the first hours and increased to units sq q hr after hours. anticoagulation was increased in many cases to enoxaparin mg sq q hr after another hours. of the patients who received care during the six-month period, patients ( . %) were diagnosed with lower extremity dvt that were asymptomatic in % of the cases. ivcf's were placed in patients ( % of those with dvt). two patients were diagnosed with pulmonary emboli (. %). there were no fatal pulmonary emboli. there were no significant bleeding complications or ivcf complications. surveillance lower extremity venous dopplers every - days, scd's, cs's, and escalating doses of anticoagulation as is tolerated and safe lower the risk of dvt in this high risk population and identify early asymptomatic dvt. fatal pe can be prevented with ivcf placement and more aggressive anticoagulation as permitted by the diminishing risk of bleeding as time passes from the acute injury. heparin induced thrombocytopenia (hit) is a common yet under-recognized condition in the neuro icu. it is caused by an autoimmune reaction to heparin-platelet factor (pf ) complexes which causes activation of platelets and leads to thrombosis. patients with aneurysmal subarachnoid hemorrhage treated by endovascular means are exposed to large doses of unfractionated heparin and therefore may be at high risk for hit. the medical records of consecutive patients with aneurysmal sah were reviewed. diagnosis of hit was made by clinical determination. clinically diagnosed hit is common in the sah population. patients with hit are at higher risk for cerebral infarction, in-hospital mortality and disability. a high suspicion for hit is appropriate in patients with aneurysmal sah treated by endovascular means. mild hypothermia ( - °c) has been investigated in a variety of neurologic diseases and disorders. since the s research has shown that hypothermia provides vital neuroprotection after sustaining brain/spine injury from a trauma, stroke, or cardiac arrest. hypothermia reduces increased icp and improves neurologic outcomes. [ ] [ ] [ ] [ ] translation of the research to clinical practice poses many challenges such as determination of the most effective method of cooling, maintaining hypothermia, and slowly re-warming back to normothermia. a neuro hypothermia protocol was instituted in march . patients underwent mild hypothermia using a hydrogel-pad cooling system. this retrospective study analyzed the data related to induction start times and associated variables (bmi and bsa) and sought to determine whether any correlation existed between the variables and degree/hour induction to goal temperature - + . °c. additionally, data was collected related to hours at °c and assessment of device control of ascent rate to °c. using the pearson correlation coefficient and the bonferroni standard correction method, patient charts were reviewed and data assessed to determine the statistical relevance of several variables: gender-males, age , bmi . , bsa . , induction start temperature . , target temperature . , hour to target temperature . , and temperature descent of . degrees/hour. it was determined that there was a significant statistical association between temperature changes (degrees/hour) and bmi/bsa values. the p-values for the bmi was determined to be . and the bsa . . target temperatures were maintained at °c with minimal variances. the ascent to °c was controlled at . °c/hour for the brain injured patients and . °c/hour for the spinal cord injured patients. the final analysis of the data revealed that an individual's bmi and bsa does directly affect both the induction of hypothermia and the controlled re-warming back to the targeted normothermic goal. mechanical ventilation is associated with worse outcome after intracerebral (ich) and subarachnoid hemorrhage (sah). we sought to examine the predictors of duration of mechanical ventilation. we prospectively identified patients with spontaneous ich and sah who required invasive mechanical ventilation. ventilator settings and measurements were recorded daily from the initiation of ventilation. complications were prospectively recorded. data are presented as mean +/-sd or n(%) when appropriate. variables for multiple linear regression were chosen with a stepwise algorithm (in order of decreasing significance). patients with aneurysmal sah of all clinical grades were prospectively studied. regional anterior alpha power was quantitatively analysed. we assessed alpha power and variability using the product of standard deviation and mean power over a -hour duration, repeated along a window sliding by minutes and graphically displayed. an independent clinician predicted the status of patients as improvement, deterioration or no change from the previous day. this was first done using only clinical data. ceeg trends prior to that day were then presented and another prediction made. results were compared with the true clinical states that were determined independently. clinical evolution in patients who were treated for vasospasm was correlated with daily mean alpha power. coiling followed by clot evacuation is associated with a faster time to aneurysm protection and similar outcome, los, and cost as clipping and evacuation. this may be a viable alternative treatment strategy. using cdsa, icu nurses were the most sensitive at identifying seizures, however they also demonstrated the highest false-positive rate. neurophysiologists and eeg technologists demonstrated slightly lower sensitivity, and much lower false-positive rates. however, on individual eeg recordings performance varied greatly, with group median sensitivities ranging from at % to %. neurophysiologists, eeg technologists and bedside nurses demonstrated comparable performance in seizure identification using cdsa. the observed differences in sensitivity and false-positive rates between different groups of reviewers are smaller than the variability in their performance on individual eeg recordings. coagulation disorders are common after traumatic brain injury (tbi), and may contribute to morbidity and mortality ( ) . these disorders are complex and dynamic over time, making clinical evaluation of coagulation status of the patients difficult ( ) . thromboelastography (teg) has been suggested as a tool for rapid assessment of such states. teg is a test of clot formation and lysis, providing a holistic assessment of clot formation time and strength. it is an easy to perform, point of care test that enables clinicians to differentiate hypo or hypercoagulability, and the factors contributing to each, and evolution over time. the aim of this work is to show the contribution of teg to the evaluation of coagulopathies in patients with isolated tbi. we have retrospectively inspected teg records and routine coagulation studies from patients with isolated tbi, and checked for signs of either bleeding tendency or signs of hypercoaguilation ten patients with isolated traumatic brain injury were evaluated using teg. reasons for tests included workup of suspected bleeding, assessment of hypercoagulable states, or planned invasive procedures. three of these patients showed increased ly , indicating thrombolysis, and two patient showed prolongation of the r value, indicating prolonged clotting time. two patients showed increased maximal amplitude (ma), indicating a hypercoagulable state. thromboelastography is a useful adjunct tool in the assessment of coagulation status in isolated tbi patients, and may help in clinical decision making in such patients. further work, relating thromboelastography results, prognosis and management are warranted. christine hartney, kathryn keim, diane sowa, richard temes rush university medical center, chicago, il, united states the objective of this study was to compare differences in resting energy expenditure (ree) results of critically ill neurology patients based on gender, body mass index (bmi) class and race. this study was a retrospective chart review of patients admitted to the neurosciences intensive care unit at an urban medical center who were started on enteral nutrition support. the research methods received approval from the institutional review board for human studies. the differences between gender, bmi class and race may not have been detected as a limitation of the sample size. research is needed to further explore the relationship among gender, bmi class and race and use of established predictive equations for the critically ill neurology patient. many critically ill neurologic and neurosurgical patients undergo a significant change in functional status or require end-of-life care. therefore, palliative care is an integral part of care provided by neurocritical care physicians and midlevel providers. at times, the needs of the patients and families can overwhelm these clinicians, whose focus is often on curative measure, so there may be a benefit to integrating a formal palliative care consultation service into the neuroicu. an anonymous survey was conducted among the four neuro icu physicians and nine nurse practitioners regarding the integration of a palliative care consult service into the neurocritical care service. the survey consisted of seven "yes" or "no" questions and a write-in section for comments. all providers thought that it was helpful to have the palliative care consult team in the icu, and that they provided added support not just for families, but to the physicians and nurse practitioners. / respondents stated that palliative care was only appropriate for families that wanted to decelerate care. only / responded that they were aware of the existence of formal criteria that were designed to trigger the consultation of the palliative care team. feelings were mixed regarding nurse-driven consults, with only respondents feeling that this was appropriate. in general, the formal palliative care consult service was felt to be a welcome addition. clearly, the existence of formal criteria to trigger a palliative care consult had not been emphasized enough to physician and midlevel providers, and the concept of nurse-driven consults was not accepted by the majority of number of providers. additional comments obtained will be used to improve the process by which palliative care services are obtained. most clinical trials in traumatic brain injury (tbi) have failed to demonstrate a therapeutic benefit. one factor implicated in these failures is an inadequate estimate of the smallest clinically meaningful beneficial effect -the minimal important difference (mid). in this study we surveyed the neurocritical care society (ncs) membership to determine an mid for tbi clinical trials. a survey approved by the ncs research committee was developed to assess the mid that would lead physicians to recommend a new therapy for tbi patients. the survey was distributed online to all ncs members with a -week response period. there were responses ( . %) from ncs members. respondents included neuro-intensivists ( . %), neurologists ( . %), and neurosurgeons ( . %); % were in academic practice on average . years. two-thirds ( . %) cared for to severe tbi patients monthly and . % had participated in tbi clinical trials. one third believed that % of patients would consent to minimal risk trials. the preferred primary outcome measures were mortality, glasgow outcome score (gos), and gos extended, while the sf- , neuropsychological measures and sliding dichotomy were the least preferred. the preferred secondary outcome measures were intracranial pressure (icp) control, therapeutic intensity level (for icp) and repeat imaging. organ dysfunction scores and biomarkers were least preferred. a reduction in unfavorable outcome of % (iqr - %) was reported as the mid needed to introduce a new therapy. mid rather than "number needed to treat" was the preferred method to describe trial efficacy. in this ncs survey, the preferred primary outcome measure for tbi trials was mortality or gos. a % reduction in unfavorable outcome is considered the mid. this information can be used to help define sample size for future tbi clinical trials. compare the quality and sensitivity of electroencephalography signals (eeg) obtained with a disposable template system to eeg obtained by certified eeg technicians. prospectively acquired eeg data were obtained in hour blocks (matched pairs) from leads placed by a certified eeg technician vs. those placed using a disposable template system (brainet®). quality measures included start and end recording of impedance, elapsed time from physician's order to first recorded eeg, and a blinded subjective evaluation of data quality. all segments of data were de-identified and will be read by a blinded reviewer highly experienced in eeg interpretation. analysis from the first subjects of a subject trial is presented here. average impedances in the brainet® group were within recommended guidelines, but were slightly higher than technician applied leads. groups had similar impedance variance, lead failure rates, and maximal difference in impedance at the beginning and at the end of the hour blocks. the difference in mean time to first eeg for the brainet® group ( mins) vs. technician applied leads ( mins) was statistically significant (p< . ). evaluation of sensitivity is pending collection of the remaining data sets. preliminary analysis indicates the use of a disposable template system that allows a non-technician healthcare provider to place eeg leads is feasible and safe. no significant differences in eeg quality during hours of recording were found, and use of brainnet® leads was associated with a significant reduction in the time from order to the first page of eeg data. this preliminary assessment does not allow for conclusions about the overall quality and sensitivity of disposable template leads; the complete set of eeg segments needs to be collected and undergo blinded review. outcome following aneurysmal subarachnoid hemorrhage (sah) is related to various demographic and clinical factors. biomarkers are an increasingly employed means for determining outcome in neurologically injured patients. the purpose of this study is to correlate cerebrospinal fluid (csf) adrenergic compound and metabolite levels to clinical and outcome measures. consecutive sah patients with ventriculostomy had csf collected ml within d of onset. csf was assayed for epinephrine (epi), norepinephrine (ne), and dihydroxyphenylglycol (dhpg) by hplc. levels were compared to various demographnic, clinical, and radiological measures, and to mortality at days. mean age was yo and % were female. hh grade was in %, in %, and in %. no correlation was found for age, but women had greater dhpg levels ( pg/dl vs pg/dl, p=. ). dichotomized hh score demonstrated greater epi levels in g / patients compared to g patients ( pg/dl vs pg/dl, p=. ). patients who died had also greater epi levels ( pg/dl vs pg/dl, p=. ) yet lower dhpg levels ( pg/dl vs pg/dl, p=. ), but regression analysis incorporating hh grade eliminated these associations. in sah, women demonstrate greater elevations in the ne metabolite dhpg, and greater elevations in epi are present in hh grade / patients. patients who die have greater csf epi levels which appears related to the severity of the disease. gail pyne-geithman, opeolu adeoye, jordan bonomo, carolyn koenig, jed hartings, lori shutter university of cincinnati, cincinnati, oh , united states as in clinical neurocritical care (ncc) practice, effective ncc basic science research requires organized interdisciplinary collaboration. the purpose of this abstract is to share our experience in building a basic science collaborative to facilitate the efforts of others and foster discussion regarding engagement of basic scientists in the neurocritical care society (ncs) and ncc research efforts. our institution is active in interdisciplinary ncc clinical practice and fellowship training, in addition to conducting various clinical trials relevant to ncc. collaborating with the clinicians is a core of basic scientists who are working to integrate their funded research into the fabric of care in the neurosciences icu. the composition of the team is truly interdisciplinary, spanning multiple clinical and basic science departments and colleges within our institution. frequent meetings among ncc physicians, surgeons, research nurses in the division of clinical trials and basic scientists have resulted in fruitful collaborations in teaching, research and funding. clinical responsibilities of fellows and residents limits time for bench research, so joining an existing project allows time and resources to be used productively. ncc fellows are teamed with a basic science mentor, and these collaborations often continue beyond the tenure of the fellowship. the basic scientists benefit, as current basic research needs to have translational potential to the clinical setting. basic scientists attend clinical rounds, reinforcing the benefits of truly translational research. gaining a reputation for quality research that enables consistent funding and earns respect from the ncc community requires engagement and input of basic scientists. individual institutions can solicit interested basic scientists to join in their research planning and execution and augment the training of residents and fellows, thus preparing the next generation of research-trained clinicians. the methodist hospital, houston, texas, united states the purpose of this study was to evaluate the association between tight glucose control and the incidence of ventriculitis in neuro intensive care unit with evds the hospital's computer system was used to identify patients admitted between january , and december , to the neuro icu with documented evd placement. patients' years of age or older and deemed to require insulin therapy by the admitting physician were included in the study. we excluded patients if they had evd placement or documented csf infections before admission to the unit, were treated with antibiotics a week prior to admission, and length of icu hospitalization less than seven days. the primary outcome measure was evd related infection. the secondary outcome measures were in hospital and icu length of stay and in hospital death the association between glucose control and positive csf cultures was described using the morning blood glucose for seven consecutive days stratified based on the number of blood glucose readings that fell between - mg/dl. the binary logistic regression model showed that patients with a higher percent of readings in tight blood glucose range were more likely to have cns infection (odds ratio . ; p <. ). the secondary outcomes could not be measured because we did not have enough readings to stratify our data into categories contrary to our hypothesis, the results from our study suggest a possible association between tight blood glucose and an increase in evd related infections. at this time we are unable to make recommendations based on these results given the inherent limitations of our study ; i.e., small sample size, retrospective design, single centered and single morning blood glucose reading to assess glucose control following aneurismal subarachnoid hemorrhage (sah) half the patients' die and only one third of survivors make a full recovery. the optimal hemoglobin (hgb) after sah, however, is uncertain. higher-goal hgb and more red blood cell transfusion (rbct) lead to worse outcome in general critical care. clinical series suggest that rbct may increase vasospasm risk and exacerbate outcome after sah. however other studies suggest that a higher hgb may be associated with better outcome and less cerebral infarction after sah. we now will examine the hypothesis that patient outcome after sah is better when an hgb level of . g/dl rather than an hgb of g/dl triggers transfusion. we propose a multi-center, prospective, phase iii randomized, clinical trial involving adults admitted to university based nicus within hours of sah.. eligible sah patients will be randomly assigned to one of two treatment groups, ) restrictive (hgb of . g/dl) or ) liberal (hgb of . g/dl) transfusion triggers stratified by center and sah severity. the primary objective is to determine if sah subjects who have a restrictive transfusion trigger during the first days of care, are more likely to have a favorable -month outcome than subjects transfused with a liberal trigger. the trial is designed to detect an overall absolute difference of % in the proportion of favorable outcomes (glasgow outcome score of good or moderate disability). secondary objectives include: ) determine if a restrictive policy is associated with less vasospasm. ) examine the relationship between hgb and month outcome and cerebral infarction. the number of randomized subjects is expected to be . the number of randomized subjects is expected to be . to date centers have agreed to participate. this group will receive administrative, statistical and data coordinating support from the university of pennsylvania center for clinical epidemiology and biostatistics. the proposal is under review at the nih. background: brain death (bd) is diagnosed clinically by documentation of coma, absence of brainstem reflexes, and apnea unresponsive to hypercarbia. in argentina (like other countries) other confirmatory tests are required as a part of the diagnostic criteria. the utility of cta with cerebral perfusion was reported by qureshi in and then evaluated by combes et al and they found % false negative rate for the test; moreover, greer et al reported one case of false positive. in spain, otero has reported a sensitivity of % in a series of patients who had cta and ct perfusion. accuracy of cta and ctp must be assessed. we propose that cta and ctp is a reliable confirmatory test for bd, with particular interest in cases where barbiturates or other cns depressant drugs difficult to diagnose clinically or by electrophysiological studies. prospective multicenter study to determine the accuracy diagnostic of brain death with cta & ctp in patients with suspicion of bd according clinical criteria (cc) defined by neurological criteria, apnea test; compared with electrophysiological methods and tcd evaluation. all adults of at least years of age who meet the cc of bd. intensive care unit, emergency department, neurocritical care unit, stroke unit in hospitals with availability of tcd, eeg and multi-row ct hours. in patients with cc of bd, we will be performing ctp and then cta. all the case will be made an eeg and tcd evaluation main outcome measure: evidence of cerebral circulatory arrest. absence of cerebral perfusion sensitivity and specificity, ppv and npv for cta & ctp compared with cc, eeg & tcd. accuracy of cta & ctp in patients with recent utilisation of cns depressor or nm blockers to confirm bd before eeg and tcd. complications rate associated with the use of contrast. renal failure post contrast use. we need at least patients to to achieve a sample size that allows the analysis of sensitivity, specificity and construction of roc. not started. funding is needed to support the project. quantitative diffusion-weighted imaging mri (dwi) in comatose post-cardiac arrest survivors holds promise as a prognostic tool. between and days more than % of brain volume with an adc value < x - mm /sec identifies poor outcome patients with % specificity and % sensitivity (ann neurol ; : - ). this threshold needs validation in an external dataset. we hypothesize that the capacity for recovery of consciousness in comatose cardiac arrest survivors can be predicted with quantitative dwi. multicenter observational study of dwi mris in comatose cardiac arrest survivors obtained between and days after the arrest. patient data will be recorded using a web-based data entry form including baseline characteristics, neurological examinations, results of neurophysiological testing, cause of death, and -day outcome. patients may be entered retrospectively and prospectively. brain dwi scans will be blindly analyzed centrally and an outcome measure (survival versus death or vegetative at days) will be assigned. patients who remain comatose after cardiac arrest and who have undergone dwi between and days after the arrest. main outcome measure: the specificity of the predefined dwi threshold (adc of x - mm /sec) for prediction of poor outcome (defined as death or failure to recover consciousness at days). the sensitivity of the predefined dwi threshold in comparison with the -hour neurological examination and, if available, sseps and peak serum levels of neuron specific enolase. assuming a % survival rate, and % specificity of dwi for poor outcome, patients are needed to achieve a % false positive rate for poor outcome with a % confidence interval of to %. centers are invited to participate. several investigators have expressed interest. background: there have been several randomised controlled clinical trials of weaning from mechanical ventilation which has shown quicker weaning and shorter ventilation time in abrupt discontinuation of mechanical support as opposed to gradual step-wise withdrawal. however, there have been no substantial trials of ventilatory weaning in acute brain injury patients or those with neuromuscular diseases. the neurocritically ill patient on mechanical ventilation will require slower step-wise weaning from mechanical ventilation. multicenter, randomized, non-blinded phase trial feasibility and safety trial. all patients in the neurocritical care unit expected to be on mechanical ventilation for more than days. routine scheduled post-operative patients and patients transferred from outside hospitals already on mechanical ventilation for more than hours will be excluded. neurocritical care unit. patients will be randomized to slow step-wise simv wean versus pressure support wean on cpap. length of time on mechanical ventialtion pneumonia, urgent re-intubation, hypoxia from previous studies in the medical intensice care units, patients, half with acute brain injury, half with neuromuscular diseases. despite the use of appropriate antimicrobial therapies, the morbidity and mortality associated with bacterial meningitis remains high. cerebrovascular complications from meningitis, including vasospasm, have been shown to contribute to this poor outcome. several series have reported tcd velocity elevation correlates with clinical decline and occurs in up to % of patients with bacterial meningitis. to date no systematic large trial has been completed to detect or treat this complication. . phase ii: clinically significant vasospasm in bacterial meningitis results in higher mortality compared with those with normal tcd velocities. . phase iii goal directed therapy: triple h, intra-arterial verapamil and angioplasty will increase survival in patients with bacterial meningitis at high risk for vasospasm. patients admitted to the icu with the diagnosis of bacterial meningitis. phaseii: bacterial meningitis enrolled within hours of diagnosis. subjects receive baseline cta of head/neck, daily tcds, angiography when mean velocities > , daily nihss, mortality rate at one month, and mrs at months. significant vasospasm will be defined as angiographic vasospasm with corresponding increased nihss of at least points. phaseiii: target population from phase ii. all subjects will undergo testing and data collection as outlined in phase ii. subjects randomized to aggressive vasospasm treatment vs. standard-care. in the treatment group, vasospasm will be treated with goal-directed therapy. one month mortality. independent predictors of the presence of vasospasm. rankin score at months. phase ii and iii: inference of portions (alpha . , beta . , delta . , n= subjects) current status: big idea. the outcome of devastating neurologic disease like massive ischemic stroke, intracranial hemorrhage, status epilepticus, and subarachnoid hemorrhage is presumed to be poor. mortality in studies may be influenced by premature withdrawal of care, and not by natural history or chronic complications. if these patients are given maximal supportive care chronically, their outcome will be better than expected based upon commonly accepted morbidity/mortality. randomized, controlled non-blinded clinical trial. patients with devastating neurologic conditions as listed above who require mechanical ventilation (mv) and feeding tube placement (tf). neurocritical care unit of major tertiary care centers as part of a multi-center trial. families are offered usual standard of care-either withdrawal of care or full supportive care. for those not certain about which course to take, enrolment is offered. the trial would necessarily require initial full supportive care such as tracheostomy and feeding tube placement. the patients are randomized to one of two treatment regimens: ) aggressive, long-term supportive care involving treatment of intercurrent medical complications and full resuscitation; ) basic supportive care including mv and tf but not involving these aggressive measures. modified rankin scale at one, two, and five years. continued need for mv/tf, barthel index, correlation with initial hospital care in a specialized neurocritical care unit. assuming a % event rate (severe disability or mortality) in the control group and expecting a % relative risk reduction (about % absolute risk reduction), the estimated sample size with an % power and an alpha of . is patients total ( in each arm). proposal status. how to structure randomization in concert with ethical principles and which supportive measures can be ethically restricted must be determined. intervention: continuous veno-venous hemofiltration via femoral access with total effluent rate of ml kg - h - , blood flow rate between - ml/min, high permeability glycerine free polyethersulfone membrane, filter change every hours, pre-filter replacement fluids: prismasate bgk / / . (osmo ) and sodium-citrate anticoagulant. fluid management per attending physician. minimum duration of hours with termination after - hours of icp control or at hours. secondary outcome measures: change in icp at hours and every hours thereafter; neurological outcome (glasgow outcome scale score dichotomized unfavorable ( , , ) / favorable ( , )); cytokine removal and complications. power analysis: a sample of size will be obtained to attain a power of . at % level of significance current status: idea phase renal replacement therapy in the patient with acute brain injury renal replacement therapy for the patient with acute traumatic brain injury and severe acute kidney injury early changes in intracranial pressure during haemofiltration treatment in patients with grade hepatic encephalopathy and acute oliguric renal failure continuous arteriovenous hemofiltration in patients with hepatic encephalopathy and renal failure cytokine removal during continuous hemofiltration in septic patients fluid thresholds and outcome from severe brain injury adult respiratory distress syndrome: a complication of induced hypertension after severe head injury prevention of secondary ischemic insults after severe head injury combination therapy with hypothermia for treatment of cerebral ischemia clinical study of mild hypothermia treatment for severe traumatic brain injury management of pitfalls for the successful clinical use of hypothermia treatment multicenter trial of early hypothermia in severe brain injury guidelines for the management of severe traumatic brain injury. rd edition none s neurocrit care early decompressive craniectomy for patients with severe traumatic brain injury and refractory intracranial hypertension--a pilot randomized trial renal replacement therapy for the patient with acute traumatic brain injury and severe acute kidney injury continuous renal replacement therapy for refractory intracranial hypertension introduction: many authors suggest using pentobarbital when elevated intracranial pressure or seizures are refractory to other agents. due to the lack of outcome data after the use of this agent, we investigated the outcomes of patients treated with pentobarbital over the past five years. patients were identified using a pharmacy database that tracks inpatient medication dispensing at our tertiary referral center. all patients, older than , cared for in adult icus, who received pentobarbital between and were included. inpatient mortality was compared between patients older and younger than as well as those who required vasopressors using fisher's exact test. twenty-two patients received pentobarbital. the mean patient age was (sd= ). just over half ( %) were men. pentobarbital was used in % of the patients to treat intracranial hypertension; the remainder were treated for refractory status epilepticus. the most frequent underlying disorders were toxic-metabolic disease processes.fourteen patients ( %) died in the hospital. care was withdrawn in %. of the patients ( %) who were alive at the time of discharge: ( %) were discharged to acute rehabilitation, ( %) to an extended care facility, ( %) to sub-acute rehabilitation, ( %) to hospice, and ( %) to home.hypotension, renal failure, and pneumonia were common ( - %) in patient receiving pentobarbital. there was no significant association between inpatient mortality and reason for pentobarbital use. age and need for vasopressors were not significantly associated with in hospital mortality. pentobarbital use was associated with significant morbidity and mortality (greater than %), but % of patients were discharged home or to acute rehabilitation facilities. further study is needed to better clarify the risks and benefits of pentobarbital to treat refractory intracranial hypertension and status epilepticus. the neurologic mechanism leading to unresponsiveness after acute traumatic brain injury is not well understood. posturing reflex examination in evaluating comatose patients is ubiquitous. the reliability of this practice has not been systematically evaluated. from the trauma service registry at a level trauma center, all admissions between from / / to / / where the patient had a head component of the abbreviated injury score > were identified. from this group of , patients, the records of the patients with a glasgow coma scale (gcs) on presentation and a brain ct scan performed in the ed were evaluated. ct scans were scored for injury by location and the motor component of the gcs (gcs m ) was noted from ed documentation. the study population was young (mean age . ) and predominantly male ( %). the gcs m was (indicating extensor posturing or no response) for patients and > (indicating flexor response or better) for patients. on univariate analysis, intra-axial injury above the thalamus did not correlate with the gcs m ( with gcs m , with gcs m > , p= . ). a second analysis of intra-axial injury above the midbrain again showed no reliable correlation with gcs m ( with gcs m , with gcs m > , p= . ). patients with extensor or worse exams were less likely to have a glasgow outcome score > ( ( %) with gcs m , ( %) with gcs m > , p= . ). gcs m responses of flexor or worse did not reliably correlate with injuries at the level of the thalamus or below. however, lower gcs m was still associated with poor gos. this study points to a need for reinvestigation into the neuroanaotmic basis for posturing and unresponsiveness to enhance the understanding and improve acute management of these patients. jeff chen, sandy cecil, patrick chen, susan rowland, sarah callaway, david adler legacy emanuel medical center, portland, oregon, united states since the cma cerebral microdialysis analyzer received fda approval for clinical use in in the united states, cerebral microdialysis has gained increasing acceptance as an adjunct in the multimodality monitoring of the brain after traumatic brain injury, subarachnoid hemorrhage, and stroke. we describe a single institutional four year experience with cma and recent iscus flex . the cma and iscus flex analyzers, cma pump, and cma microdialysis catheters were obtained from cma microdialysis (solna, sweden). perfusion fluid cns (artificial csf) was perfused at . ul/min, and samples collected hourly. lactate, pyruvate, glucose, glycerol, and glutamate levels were entered into the icu pilot program along with neurophysiologic parameters to analyze relationships/trends. all cerebral microdialysis catheters were implanted by board certified attending neurosurgeons at a single community-based hospital. catheters were implanted directly into the brain via a mm diameter corticectomy at the time of craniotomy. catheters were placed via twist drill hole/bolt when craniotomies were not performed. status epilepticus (se) affects , americans yearly. - % of cases fail initial therapy. refractory cases requiring midazolam, pentobarbital, or propofol fail in - % of patients. outcome is independent of the anaesthetic agent or extent of eeg suppression. hypothermia (ht) in rodent models of se abates epileptic discharges and neuronal death. case reports demonstrate ht as an effective adjunctive or primary treatment for refractory se (rse). ht effectively treats rse. multicenter, randomized, non-blinded phase iia trial of ht in rse evaluating target temperature and duration. inclusion criteria: rse patients failing initial benzodiazepines and phenytoin treatment, > yo, and > o c upon admission. exclusion criteria: immunosuppression, active infected, unstable cardiac rhythm, coagulopathy, se secondary to cardiac arrest/anoxia, active chf, pregnancy, in-place ivc filter, or dnr/dni status. eeg monitored patients with rse will be randomized. controls will be managed at the intensivist's discretion. remaining patients will be varied by ht duration ( hr v hr) and target temperature ( - o c v - o c). initially, seizure will be treated with midazolam while endovascular cooling catheters are placed, and a cold saline bolus is given. at goal temperature, midazolam will be weaned to off or the lowest dose necessary for absence of seizure activity. anaesthetic medication requirements and seizure burden (i.e. seizure frequency, duration, and number), from achieving goal temperature until icu discharge, as compared with control. total iv anaesthetic icu duration vasopressor/inotrope requirements modified rankin score at discharge infectious, device, and coagulopathic complications power analysis: > patients (> each arm) would be % powered to detect a % difference in ht vs control (alpha= . ), and a % difference of each arm vs control (alpha= . ), in the primary outcome measures of anaesthetic and seizure burden. a phase i study is underway at washington university and henry ford hospital. this study remains unfunded. traditional dogma has mandated that brain injured patients with a glasgow coma score of < need to remain intubated for airway protection. recent prospective studies have suggested that in brain injured patients with intact airway reflexes, prolonged intubation leads to an increase in nosocomial pneumonias and worse outcomes. a recent randomized trial suggested randomization of brain injured patients into early and delayed extubation is safe and feasible. brain injured patients with a gcs < and intact airway reflexes will not have worse outcomes if extubated early compared to a similar extubation group with delayed extubation until their gcs becomes > . multi-center non blinded randomized phase trial. a non inferiority trial of immediate versus delayed extubation accounting for a . change in modified rankin scores would require patients in each treatment arm for % power. immediate extubation in stable brain injured patients with intact airway reflexes as evaluated by an airway care score. hospital discharge modified rankin score. hospital and icu length of stay, nosocomial pneumonias, reintubations. all intubated adult patients with severe brain injury defined as a gcs< are potentially eligible. exclusion criteria includes: patients < , lack of surrogate informed consent, intubation for therapeutic interventions, anticipated medical or neurological worsening, intubation for airway edema, or prolonged intubation > weeks. a feasibility trial has been completed and published. the study is in search of centers and funding. outcome of patients with ich is dismal. the majority of patients succumb in the first hours to the effect of the hemorrhage causing tissue shifts and herniation. furthermore, many are comatose, ventilator-dependent because of alteration of consciousness brought upon by pressure on midline diencephalic structures. both early hemostatic therapy and surgical evacuation failed to improve outcome simple yet large decompression with durotomy in patients with large, unilateral hypertensive capsulo-ganglionic ich preceded by administration of rfviia for stabilization of clot and thereby prevention of hematoma growth upon decompression should result in less hematoma expansion (safe), reduce pressure on midline structure, and improve mentation and overall outcome study design: randomized, controlled but not blinded, feasibility and safety multi-center trial patients with spontaneous, hypertensive large ( ml) ich located in the putamen and internal capsule with evidence of mass effect on midline structure ( mm septum pellucidum shift), who are not moribund (decerebrate posturing, absent pupillary light and oculocephalic reflexes), and who present within hours from onset of bleed are eligible to be enrolled. patients should have no contraindication to receiving rfviia. patients are screened upon arrival to the er or nicu if transferred directly there intervention: mcg/kg rfviia is given prior to patients undergoing a large, fronto-temporo-parietal decompressive craniotomy with durotomy without clot evacuation. further care like blood pressure control and osmotic therapy will not be standardized. hematoma expansion, improvement in midline shift by % deterioration by points on nihss within first hours following decompression, good outcome at months (mrs ), icu and hospital los, days on mechanical ventilation with a beta level of . and alpha . , an assumed hematoma expansion rate of % in the non intervention group (fast trial placebo group hematoma growth rate) and % in the intervention group, patients are needed to be randomized not initiated yet cerebral vasospasm (cv) after aneurysmal subarachnoid hemorrhage (asah) remains a significant cause of morbidity. intravenous nicardipine has been previously studied clinically as a neuroprotectant, and shown to decrease the incidence of angiographic and symptomatic vasospasm in asah, and has the potential to avoid rescue intraarterial rescue therapy and the resultant complications. hypertensive hypervolemic vasodilatory hhvd for cv will result in a reduction in duration cv, fewer delayed ischemic neurologic deficits (dinds) and better functional outcome. randomized placebo controlled trial of hhvd versus hh therapy. patients with asah, ages - , without a history of coronary artery disease (cad), ischemic cardiomyopathy, neurodegenerative disorder, or chronic kidney disease not on hemodialysis. intervention: hhvd therapy using norepinephrine and continuous nicardipine infusion at mg/hr initiated at the onset of cerebral vasospasm, for a duration of days. intracranial hypertension (ih) is the most powerful predictor of poor outcome in severe tbi. indomethacyn (im) is a cox inhibitor with a potent vasoconstrictive effect in cerebral arterioles that has been used in tbi, avm's and intracranial neoplasm. there is a little of evidence that supports its utility in the treatment of ih with special emphasis in type a waves in patients with an impaired cerebral vasoreactivity, improving both cerebral perfusion and response to other second-tier therapeutic tools. however, large, prospective, randomised and controlled studies have not yet been performed to confirm its benefit in patients with tbi the im could be effective to treat refractory ih in severe tbi with impaired cerebral autoregulation and poor response to other therapeutic strategies. im can improve indices of cerebral haemodinamics and cerebral oxygenation decreasing neuronal ischemic damage. this therapeutic approach can reduce til to control intracranial pressure, also the length-of-stay in icu can be reduced too. im can improve long term functional outcome in severe tbi. multicenter, randomized controlled trial to evaluate the efficacy and safety of im in patients with severe tbi that presents intracranial hypertension which have reached a therapeutic intensity level that includes second-tier therapies (ie,deccompresive craniectomy, controlled hypothermia, etc) all patients (older than years old) that presents with glasgow coma scale or <, with icp above torr and with any evidence of hyperaemia (tcd, sjvo , avdo etc) or increased cbv (ct perfusion, etc) despite standard therapy (includes mechanical ventilation, evacuation of intracranial mass, profound sedation, osmotherapy, etc). intensive care unit or neurocritical care unit or neurotrauma unit at a hospital that has multimodal monitoring modality (icp, cpp, etco or pco , sjvo or ptio , tcd etc) and neuroimaging with evaluation of cbv (ct perfusion, etc) indomethacyn . - . mg/kg at loading dose, followed by continous infusion . - . mg/kg/hr or placebo in patients who develop high icp despite standard therapy for icp control. icp control (reduction of icp below torr or torr in dc), normalization of cerebral oxygenation (avdo , sjvo or ptio ). improvement of cerebral perfusion measured by cuantitative or cualitative methods neurological outcome (egos) at discharge, , , and days. overall mortality at month , and qol at month , and evidence of long-term ischemic damage we need a sample of at least patients to find statistically significative difference between intervention and placebo group. not started. financial supports is needed. hyperglycemia is very common in acute brain injury (abi) from ischemic stroke, hemorrhage or trauma and is associated with poor outcome. tight glucose control is effective in improving outcome in medical/surgical icu but its role in abi is uncertain. studies investigating brain metabolism using microdialysis showed increased brain metabolic crisis with tight glycemic control. currently the optimal glucose control for patients with acute brain injury is unclear. aggressive hyperglycemia management will result in improved outcome in abi compared with standard glucose management. multicenter, randomized, single-blinded phase ii feasibility and safety trial. inclusion criteria: patients admitted to icu for management of abi with high likelihood of requiring at least hours of intensive care. absence of health care proxy to sign consent. patient with do not resuscitate and do not intubate orders on admission history of allergy or known contraindication to insulin moderate to severe baseline disability (pre-abi modified rankin scale or greater) severe terminal concurrent medical illness with expected survival of less than three months. neurocritical care unit. treatment arm will receive continuous insulin infusion targeting blood sugar level - mg/dl. control group will receive subcutaneous insulin injection and/or insulin infusion targeting blood sugar level - mg/dl. modified rankin scale at months rate of medical complications, including infection, new neurologic abnormality, hypoglycaemia and in-hospital mortality.length of icu, hospital stay. based on our retrospective study with expected good clinical outcome of % and % relative difference in outcome between groups, the study will need patients in each arm with % power and % two-sided alpha level. protocol complete. for submission for funding. rebleeding on the first day following asah is as high as - %, and approximately half of these occur within hrs of onset. unanticipated delays in asah diagnosis and result in failure to secure aneurysms during the period of maximal rebleeding. a novel approach of acute antifibrinolysis (< h duration) has demonstrated safety, however, there have been no trials powered to demonstrate a difference in long-term outcome. therefore, a clinical trial evaluating the impact of -aminocaproic acid (eaca) on outcome following asah is warranted. acute treatment with intravenous eaca will improve twelve-month outcome in patients with asah. neurological emergency treatment trials (nett)-based multi-center, randomized, double-blind, placebo-controlled phase-iii trial. all adult asah patients presenting to nett facilities will be screened for enrollment. patients must receive study drug within h of asah onset. those with aneurysm-negative sah, anticipated treatment within h, or recent thromboembolic disorder will be excluded. subjects will be enrolled and treatment initiated in the emergency department and continued during transfer and the referral-center intensive care unit. patients will receive an intravenous placebo or eaca. a g loading dose, will be followed by infusion of g/hr, to a maximum h. favorable -month modified rankin score( - ) the barthel and lawton scales(disability scales), sip(quality-of-life scale), and a psychometric battery(cognitive/intellectual domains) will be assessed as secondary outcomes. known sequelae of asah and antifibrinolytic therapy including rebleeding, vasospasm, hydrocephalus, and thrombotic complications will be tracked. based on a analysis with = . and a power of %, subjects will be randomized. this calculation is based on conservative estimates from past studies that demonstrate % increase in favorable outcome for patients receiving acute eaca. based on a analysis with = . and a power of %, subjects will be randomized. this calculation is based on conservative estimates from past studies that demonstrate % increase in favorable outcome for patients receiving acute eaca. additionally, there are also associated nonlinear hospital system factors, hi, probably accounting for positive preclinical and single center studies, followed by multicenter failure. the severity regression equation can now be described asthis leads to the notion that the current widely accepted methods of evaluating single facet therapy to attenuate such multifaceted complex problems is generally a fruitless waste of public resources which has produced innovation paralysis.preclinical studies have demonstrated the potential for dramatic breakthrough level neuroprotection with a multifaceted approach but a rational systematic method for introduction of multifaceted therapeutic bundles is needed. multifaceted neuroprotective bundles can be used to demonstrate robust neuroprotection. can the plan-do-study-act (pdsa) qi method be used to incrementally add and evaluate individual facets of neuroprotective therapeutic bundles? single center pdsa therapeutic bundle development followed by multicenter randomized trial of a therapeutic bundle. patients with acute tbi or brain ischemia syndromes setting: ed, or, and icu multi mechanism multifaceted therapy incrementally and sequentially implemented during active post insult secondary pathophysiologic processes. surrogates for functional outcome with sequentially added facets in a therapeutic bundle ongoing evaluation of functional neurologic outcome. none yet background: refractory intracranial hypertension (rih) is associated with death or poor neurological outcome in - % of patients and clinical equipoise often exists among management [ ] . for patients with cerebral edema or intracranial hypertension who require renal replacement therapy, continuous (crrt) modes are preferred due to limited data showing improved intracranial stability over traditional intermittent hemodialysis (ihd). this is attributed to better cardiovascular stability, less rapid fluid shifts, bicarbonate and osmolality changes as well as more biocompatible, and highly permeable membranes [ ] . anecdotal reports have suggested improvement in intracranial pressure (icp) [ and verbal] during crrt and we have observed this in patients (table , figure - patients with persistent disorders of consciousness, defined as the absence of response to simple orders, days after the event unexplained by sedation. signed informed consent. inclusion of tbi and non tbi comatose patients (ischemia, sah, hematoma and cerebral anoxia). neuroicu. mri under mechanical ventilation. inclusions during years. follow up at months and one year by phone interview. electronic crf. multimodal mri with mrs (pons and csi) and dti under mechanical ventilation. controls per center. predictability of dichotomized gos at year using a composite index combining clinical data and quantified indicators from mrs (naa/cr in specific brain regions) and dti. design of specific algorithms according to the etiology of coma. with subjects, % of power to detect a variable with an or by standard deviation of . ( = %, bilateral test, proportion of patients with poor outcome = %, nquery advisor® . ). % of lost to follow-up within year and % of drop-out. total tbi to be included = . same reasoning for non tbi patients. founded in france €. european actively including patients following a similar protocol. patients already included (tbi patients, anoxia , intracerebral hematoma , sah , arterial ischemia ). mortality rate at one year %.financial support: none key: cord- -twsy oq authors: nan title: siu abstracts date: - - journal: world j urol doi: . /s - - - sha: doc_id: cord_uid: twsy oq nan introduction and objective: th e bladder is generally considered an organ for voiding and storage of urine, with the urothelium serving as an impermeable barrier. recent discovery of aquaporins in the bladder urothelium in rodents and later on also in human challenges this notion of impermeability. upregulation of aquaporins in response to dehydration or bladder outlet obstruction and downregulation following transitional cell carcinoma has been shown. th is emphasize the need to better understand the function and distribution of aquaporins, as well as their role in bladder diseases. th e present study aims at establishing basic knowledge about the expression of aquaporin (aqp ) in the porcine bladder, related to gender and gestational age. th ree pregnant sows at , or days of gestation were sacrifi ced. fetuses were removed and necropsied. th e bladder was rapidly removed and whole wall tissue samples from the bladder dome was snap frozen in liquid nitrogen and stored at - c. genetic gender determination was performed and fetuses with uncertain gender determination were excluded. aquaporin mrna expression was analyzed using qpcr and β-actin was used as the reference housekeeping gene. results were compared using two-way anova. results: a total of samples were analyzed. gestational age was either (n= ), (n= ) or days (n= ). aquaporin was expressed in all samples. aqp mrna expression was increased in the fetal porcine bladder with increasing gestational age (p< . ). however, there was no signifi cant diff erence in aqp mrna expression between genders (p= . ). conclusion: expression of aqp in fetal porcine bladder is demonstrated with increasing expression during gestation. to our knowledge aquaporins in the porcine bladder tissue have not previously been studied. th is exciting new discovery contributes to the ongoing discussion on reviewing the dogma that the lower urinary tract has an impermeable barrier function. improved contractility of the long term bladder outlet obstruction induced bladder underactivity using growth factor expressing mesenchymal stem cells introduction and objective: as the underactive bladder is diffi cult to manage, a new method of increasing bladder contractility in patients with underactive bladder is desired. mesenchymal stem cells (mscs) can serve as vehicles for the gene, proliferate and differentiate into bladder smooth muscle cells to repopulate damaged bladder. th e other is that the exogenous hepatocyte growth factor (hgf) gene can provide complementary functions as angiogenesis and inhibition of fi brosis. th is study was performed to examine the recovery of the decreased bladder contractility in the long term bladder outlet obstruction (boo) models of rats using transplantation of hgf expressing human mscs (hgf-hmscs) into the bladder wall. introduction and objective: suddenly dropping to low environmental temperature, cold stress exacerbates lower urinary tract symptoms (luts) such as urinary frequency and urgency. th is study determined if transient receptor potential ankyrin (trpa ) channels could mediate the cold-stress induced detrusor overactivity in rats. materials and methods: twenty-four female -weeks sprague dawley (sd) rats were used. th is th congress of the sociÉtÉ internationale d'urologie -siu abstract book study used hc (tocris bioscience) as trpa channel antagonist. th ree days prior to cystometric investigations, polyethylene catheters were inserted into the bladder and abdominal cavity. cystometric investigations of the unanesthetized rats were performed at room temperature (rt, ± °c) for min. following, the rats were intraperitoneally injected with vehicle, . -(low dose), or . -(high dose) mg/kg hc (n= , in each). aft er min, the treated rats were exposed to low temperature (lt, ± °c) for min. during the cystometric investigations, the micturition parameters were recorded. introduction and objective: hypoxia-inducible factors (hif , hif and hif ) play a critical role in cellular and systemic responses to hypoxia by inducing a range of diverse genes involved in cell survival, they have also been implicated in development of renal cell carcinoma. we aimed to assess the eff ect of zinc and cobalt on hypoxia-inducible factor expression in immortalized human kidney cells. to cells in mcl). esr at the observed patient aft er the seventh transfusion decreased from initial mm/ hour to mm/hour. aft er the fourth transfusion of mononuclear fraction of peripheral blood at the patient the increase in the content of the total testosterone that allowed to reduce a dose of % of dermal gel of testosterone from . ml per day to . ml per day was observed. aft er the seventh transfusion of mononuclear fraction of peripheral blood because of normalization of production of testosterone the restored number of own leydig's cells an androgen -replacement therapy was cancelled. introduction and objective: ketamine use as a recreational drug is on a rapid increase in young people. many reports have shown that long-term ketamine abuse is liable to lead to lower urinary tract symptoms that resemble interstitial cystitis (ic). ic is a disease characterised by severe and chronic pelvic pain with frequency, urinary urgency, and nocturia in the absence of bacterial infection or other diseases. th is study evaluated the therapeutic eff ect of human umbilical cord blood derived mesenchymal stem cells (ucb-mscs) in a ketamine induced cystitis (kc) rat model. for kc rat models -weekold, female sprague-dawley rats were used. sham treatment (n= ) rats were assigned to the control group. th e rats in the kc group (n= ) and kc+m-scs group (n= ) were intravenously injected with ketamine at a dose of mg/kg for days a week over a duration of weeks. aft er one week, x ucb-mscs were directly injected into the submucosal layer of the anterior wall and dome of the bladder in kc+mscs group. th e cystometric parameters and immunohistochemical results (toluidine-blue, masson trichrome, tunel staining) were measured at one week following the intervention. results: most rats in the kc group exhibited irregular voiding frequency and decreased inter-contraction interval in comparison with the control group ( . ± . vs. . ± . seconds, respectively; p< . ). th e kc+mscs group demonstrated improvement in most voiding parameters to normal levels within week. a single injection of ucb-mscs signifi cantly increased the inter-contraction interval ( . ± . , p< . ) ( figure ). in immunohistochemical analysis, the bladders in kc group were characterized by mast cell infi ltration in toluidine-blue staining, fibrosis in masson trichrome staining and apoptosis in tunel staining which were signifi cantly ameliorated in the bladders in the kc+mscs group ( figure ). conclusion: th e injection of ucb-mscs restored the damaged bladder and associated pathologies including mast cell infi ltration, fi brosis and apoptosis in the kc rat model. stem cell therapy could be valuable treatment option for painful bladder conditions such as ketamine induced interstitial cystitis. mp- . , figure . introduction and objective: currently no markers are available to predict intravesical bacillus calmette-guerin (bcg) response. among the various markers under study survivin has good sensitivity in detecting bladder cancer cases and there has been very limited number of studies regarding survivin as a prognostic marker and predictive marker. prospective evaluation of urinary survivin levels as a potential prognostic and predictive biomarker in non-muscle invasive bladder cancer cases on intravesical bcg therapy was planned in this study. from august to august a total intermediate and high risk group patients of nmibc age ranging from to yrs (mean ) planned for intravesical bcg instillation were enrolled. recurrence and progression score were calculated by using eortc genitourinary scoring system and risk table. patient's urinary samples were taken, pre and post [ (t ), (t ) and weeks (t )], intravesical bcg instillation. urinary survivin expression was studied by elisa technique. results: out of patients, ( . %) had complete remission at months th e mean survivin levels in remission group (group i) was . +/- . which was signifi cantly less than those in recurrence group (group ii) mean . +/- . . pre and post bcg, there was a signifi cant decrease in the urinary survivin levels in group i when compared to group ii where there was a signifi cant rise in pre and post bcg urinary survivin levels (p value< . ). conclusion: low pre bcg urinary survivin level can be used as a useful predictive marker for achieving complete remission in nmibc patients with on intravesical bcg immunotherapy. also pre and post bcg urinary survivin levels act as a useful prognostic marker and can be used as an adjunct to cystoscopy. introduction and objective: th e natural resistance-associated macrophage protein (nramp ) gene modulates macrophage activation in a myriad of infectious and autoimmune diseases. its single nucleotide polymorphisms (snps) have been identifi ed to infl uence susceptibility to tuberculosis and response to bcg therapy in murine models. in this study, we evaluate the predictive role of nramp snps in the oncological outcomes of asian patients receiving intravesical regimes of bcg for nmibc. a total of nmibc patients who underwent post-transurethral resection intravesical regimes of bcg ( mg or mg) or bcg ( mg) with interferon alfa from to and deemed intermediate to high risk by the european organisation for research and treatment of cancer risk tables, were prospectively recruited. from these patients and a group of healthy controls, peripheral blood samples were stored and genomic dna purifi ed. a total of nramp snps were evaluated using high resolution melt analysis. th e corresponding results were verifi ed by dna sequence analysis. kaplan-meier and cox regression methods were used to analyze the data. introduction and objective: microscopic hematuria can indicate presence of underlying urological conditions. aua guidelines recommend evaluation algorithms for microscopic hematuria. population-based studies have focused on risk pools such as heavy smokers and elderly men. we evaluated whether men interested in self-managing their lower urinary tract symptoms (luts) with an over-the-counter (otc) product should be screened for microscopic hematuria to detect undiagnosed signifi cant conditions (including urothelial malignancy) causing hematuria. materials and methods: urine dipstick testing was conducted in men who preferred to self-manage luts using an otc product. urologic assessment was conducted by a urologist to determine conditions causing/contributing to the urinary symptoms for: men < years; and men ≥ years who had traces of glucose, leukocyte, and/or blood in urine; or had an aua symptom index score ≥ . men experiencing complete urinary retention, dysuria, extreme thirst, gross hematuria, or urethral discharge ("do not use" symptoms in this study) were also assessed. men ≥ years of age who did not meet any of these criteria did not undergo urologic assessment. introduction and objective: th is fi rst experience, pilot study, was aimed to evaluate the outcome of en-bloc bladder tumor resection using the plasma-button electrode in cases of papillary non-muscle invasive bladder tumors (nmibt) from the perspectives of surgical safety and effi cacy, perioperative morbidity, histological assessment and short-term oncologic outcome. a total of patients previously diagnosed by abdominal ultrasound, contrast ct and fl exible cystoscopy with papillary bladder tumors over cm in diameter were included in the trial. th e exclusion criteria consisted in solid sessile tumors, lesions located in bladder neck area and tumors involving the ureteral orifi ce. en-bloc tumor resection using the plasma-button approach was applied in all enrolled cases. th e tumor base was subsequently biopsied by standard single-wire loop resection and followed by plasma-button coagulation. th e fi rst follow-up cystoscopy was completed at months. results: all procedures were successfully performed leading to visually complete tumor ablation. th e mean tumor diameter was . cm (range between and cm). no obturator nerve refl ex adverse events or cases of bladder wall perforation were encountered. no signifi cant postoperative hematuria and re-intervention requirements were encountered in this series. th e mean catheterization period was . days (range to . days) and the mean hospital stay was . days (range to days). th e pathological analysis confi rmed the presence of detrusor muscle in the resected biopsy specimens for all enrolled patients, thus enabling for a reliable tumor staging to be established (all nmibt histology diagnosed patients). a single case of other site residual lesion was found during the fi rst evaluation cystoscopy, while no orthotopic recurrences were described. to reduce the overdiagnosis and overtreatment of insignifi cant tumors there is an urgent need for a specifi c test to detect clinically signifi cant prostate cancer (pca). using gene expression profi ling specifi c pca-biomarkers were identifi ed. eight promising biomarkers were selected and the diagnostic accuracy was tested in urine of an intent-to-treat cohort. th e aim of this study was to clinically validate the four-gene biomarker panel (hoxc , dlx , tdrd and hoxc ) using an independent prospective multicenter study cohort. in two independent prospective, multicenter studies (cohort : n= en cohort : n= ) urine was collected aft er digital rectal examination (dre) from men undergoing prostate biopsies based on an elevated serum psa level (≥ . ng/ ml) and/or suspicious dre. klk , hoxc , hoxc , tdrd and dlx mrna levels were measured using rt-qpcr. th e assay was validated according to miqe criteria, hence the test is a standardized laboratory developed test (ldt). results from cohort were used to develop models with (combinations of) the four genes based on the comparative ct method. th e chosen model was validated in cohort , i.e. a fully independent validation cohort. results: pca was identifi ed in % ( / ) and % ( / ) of men from the studies respectively. th e model with the combination of hoxc /dlx resulted in the highest average auc ( . ) and specifi city ( %) at ≈ % sensitivity, based on cohort . furthermore, hoxc and dlx were signifi cant in the logistic regression, in % and % respectively. th is model was independently validated for the diagnosis of pca with gleason score ≥ in prostate biopsies. using roc curve analysis hoxc /dlx outperformed pca in both cohorts (cohort auc= . vs. . ; cohort auc= . vs. . ). adding serum psa to the hoxc /dlx model resulted in an auc of . and . , respectively. th is study showed the promising results of a new urine test for the early diagnosis of clini-cally signifi cant pca using a model which combines hoxc with dlx . th ese results demonstrate that this model could be used to assess the risk of pca with gleason score ≥ and therefore could reduce the amount of unnecessary prostate biopsies. introduction and objective: curcumin contains mul-introduction and objective: a family history of prostate cancer is a well-recognized high risk factor for this disease. various models for an inherited risk for prostate cancer have been described, but to date traditional linkage and association studies have only identifi ed a small number of rare tumor suppressor genes and snps involved in prostate cancer risk and development. we performed whole exome sequencing on multiple participants (n= ) with prostate cancer from families with a signifi cant history of prostate cancer to potentially identify new prostate cancer susceptibility variants. exome variants were fi ltered against a range of parameters with a subset of variants chosen for validation by sanger sequencing and segregation analysis within their respective families. each prostate cancer participant met the following criteria for inclusion if: (i) they had a verifi ed diagnosis of prostate cancer, (ii) there were multiple cases of prostate cancers in the family, iii) pathology, diagnostic and treatment notes were available, and (iv) they were classifi ed as brcax mutation status. results: essential splice site, missense and stop lost variants were fi ltered against a recently published candidate gene list, leaving shared truncating variants and shared missense variants to be genotyped through all prostate aff ected (n= ) and unaff ected male participants (n= ). th ree missense variants demonstrated complete segregation and one missense variant demonstrated partial segregation with the prostate cancers. th ree truncating variants demonstrated complete segregation and three truncation mutations demonstrated partial segregation with prostate cancer. no segregating variants between the three families were shared. conclusion: ten truncating or missense variants showed either complete or partial segregation in our three familial prostate cancer families. of interest, we detected a cyp a and parp variant in our multicase prostate cancer families. th ese two variants have previously been reported to occur in other familial associated prostate cancer families, thereby, potentially adding to the evidence that these two variants may have a role in the risk and development of prostate cancer. another eight novel variants were detected that segregated with disease and warrants further investigation. th congress of the sociÉtÉ internationale d'urologie -siu abstract book were recorded. patients with diabetes, hypertension or known cardiovascular disease were excluded. introduction and objective: traditional methods of prostate cancer diagnosis in males with an elevated or rising psa have relied on outpatient trus biopsy using local anaesthetic and taking between - biopsies. trus biopsy is painful, associated with rectal bleeding in %, uti in % and urosepsis in up to % of patients. it is also has a poor sensitivity (< %) low accuracy rates of < % and a poor specifi city of < %. from we changed to template guided prostatic biopsy (tgpb) carried out transperineally under a general anaesthetic. to date we have carried out tgpb in patients with a positive biopsy rate of % (accuracy of %; and specifi city of %). th e procedure is painless, utis occurred in %, no sepsis and no rectal bleeding. because of the large numbers of biopsies taken % of patients had transient retention. in patients who had a previous -ve trus biopsy % had a subsequent +ve tgbp and patients having tgbp on the fi rst occasion for an elevated psa ( . - ) % had a positive biopsy. results: with the advent of tesla mri and mri fusion technology we have now progressed to mri fusion biopsy using real time ultrasound imaging and fusing the abnormal mri image to perform the biopsy (biojet fusion, global prostate solutions) . th is allows for even greater accuracy of the biopsy without taking large numbers of samples. to date we have achieved a +ve biopsy rate of % with an accuracy of > % (in patients). to date there have been no cases of uti, sepsis or retention. to determine the suitability of circulating tumour cells (ctcs) as prognosticating indicator and biomarker for delivery of precision medicine. patients were recruited and screened (n= ) as a part of admet (androgen deprivation th erapy and adjuvant metformin) trial. five millilitres of whole blood was collected from patients for ctc enrichment, enumeration and propagation. enrichment was performed using cd negative selection kit (rosettesep™). ctcs were identifi ed using immunofl uorescence imaging with antibodies against prostate specifi c antigen, cytokeratin, cd and nucleus. cells were propagated in customized stem cell solution with hypoxic conditions. results: at screening, of patients demonstrated circulating tumour cells with the mean number of (range - , ± ) . in all of the enriched samples, cells could be propagated temporarily with the peak population being reached at . weeks. cells were cultured in both d and d conditions and temporary organoids could be developed from of patients. polymerase chain reaction and immunofl uorescence imaging at weeks aft er culturing demonstrated characteristics consistent with prostate cancer cells. conclusions: circulating tumour cell technology remains a viable option as a means of providing biomarker information and tumour activity indicator in delivering precision medicine. firstly, enumeration can be used to help determine the response to a treatment. secondly, temporary culture and progression into development of organoids may be used to allow for downstream analysis and therapeutic decision. transcriptionally-targeted retroviral replicating vectors: a novel strategy for gene therapy of prostate cancer introduction and objective: while hematospermia is mainly associated with genitourinary infl ammatory disorders, there are very few studies for prostatitis associated hematospermia (pah) via robust prostatitis evaluation methods. for this reason, we evaluated the incidence of pah with systematic evaluation methods for prostatitis. we evaluated hematospermia patients from a single hospital over fi ve years. we classifi ed the patients into pah versus he-matospermia without evidences of prostatitis (hwp) by using a nih-cpsi (chronic prostatitis symptom index) questionnaire and expressed prostatic secretion studies. th congress of the sociÉtÉ internationale d'urologie -siu abstract book cant diff erence in patient's the quality of life impact (table ) . introduction and objective: chronic prostatitis/ chronic pelvic pain syndrome is a chronic pain disease with high prevalence rates and substantial health care costs. chronic prostatitis syndrome is a common urological condition that many clinicians fi nd diffi cult to diagnose and treat eff ectively. th e signifi cance and diagnostic value of semen analysis in bacterial prostatitis has been extensively debated and remains controversial. our objective was to investigate the diagnostic accuracy of semen and urine culture in the diagnosis and treatment outcome of bacterial prostatitis. th e present study is based on a retrospective analysis of a database of over patients (age range - years) who met the consensus criteria for bacterial prostatitis, % of whom had dysuria, % perineal discomfort, % had obstructive luts, % infertility of unknown etiology, % erectile dysfunction and % recurrent infection of the partner. segmented urine cultures and semen culture, were performed in all patients. treatment were started as per the culture report and culture negative patients were treated empirically with quinolones group of antibiotics. patients were followed-up for year to rule out disease recurrence. results: of the patients, had positive semen culture and had positive urine culture; had negative culture for both semen and urine. of the positive cultures % of the bacteria was gram-negative microorganisms (escherichia coli was the commonest specimen isolated) and % had signifi cant positive cultures for gram-positive microorganisms. patients with positive semen culture had % response to antibiotics and full recovery was noted from the symptoms prospective aft er the full course of the antibiotic and recurrence of the disease were noted in % of the patient aft er year follow-up. patients with urine positive cultures, % had response to antibiotic, but % recurrence were noted in year. patients with negative cultures, % had symptomatic relieve but all of them had recurrence in year follow-up. conclusions: th e diagnosis of chronic prostatitis is diffi cult due to the absence of typical clinical symptoms and specifi c ultrasonographic signs. our data support the usefulness of semen analysis in the diagnostic work-up of prostatitis patients. semen culture positive patient responded well to medications and recurrence rate was very minimal compared to urine positive and culture negative patients. in our clinical work-up, semenculture are considered the only tests necessary to diagnose bacterial prostatitis and also guide us through the treatment. (rc) has been shown to be a predictor of poor outcomes in patients with bladder cancer. change in muscle volume during neoadjuvant chemotherapy (nac) administration has not been well studied. our objective was to assess for psoas muscle volume (pmv) change during the period of nac therapy and to assess if such a change was a predictor of pathologic response or survival. mp- . , figure . introduction and objective: alternative approach to the radical cystectomy for muscle-invasive bladder cancer is radical transurethral resection (tur), followed by chemotherapy/ radiotherapy. objectives: primary end points of the study were os (overall survival) and dss (disease-specifi c survival). secondary endpoint -oos survival aft er salvage cystectomy. materials and methods: sixty eight patients with t bladder cancer were treated by 'complete' tur fol-lowed by chemotherapy / radiotherapy. th e follow-up ended in june . all patients were subjected to "safety" resection. patients who had no tumor (t ), or had non-muscle-invasive (t ) tumor were given the option of follow-up with cystoscopy and adjuvant therapy or immediate cystectomy. mostly elder patients are candidates for bladder sparing. th ose with invasive tumor on the safety resection were subjected to cystectomy- patients (control group). we used spss : xi-square and kaplan-meier for statistical processing. results: five years overall survival (os) in the bladder spared group was % (n- ), and % of the cystectomy group (n- ) -p= . . th e disease specifi c survival (dss) was % and % for the bladder spared and cystectomy group respectively (p= . ). th irty four percent ( patients) with preserved bladder developed recurrent tumors. a repeated tur was conducted. fift een percent ( ) of them were with invasive tumor and the action taken was cystectomy. fift y percent ( ) of the salvage cystectomy group and % of the immediate cystectomy group survived years. of the preserved bladder patients, ( %) necessitated dj stenting and ( %) pns. pns in the cystectomy group were ( %). haematuria occurred in patients with preserved bladder and in of the cystectomy group. th e statistical diff erence between both groups according to complications is p = . . infl ammatory conditions were more common in the bladder sparing technique- orchiepididymitis, urosepsis, pyelonephritis, compared to urosepsis and pyelonephritis in the cystectomy group. conclusion: bladder conservation and radical cystectomy for muscle-invasive bladder cancer appear comparable regarding the dss until the th year. cystectomy continues to be standard of care. radical tur is successful bladder-sparing strategy in selected patients with no residual tumor on retur and lower life expectancy. introduction and objective: bladder cancer occurs commonly in the elderly patients. in some circumstance, uremic patients developed bladder cancer. we considered patients who are aged more than years old, end stage renal disease (esrd) or poor performance status (eastern cooperative oncology group, ecog >= ) as fragile patients for operation. we conducted this study to assess radical cystectomy (rc) outcomes and chemotherapy use including neoadjuvant and/or adjuvant chemotherapy in the fragile patients in routine practice. all patients undergoing rc for bladder urothelial cancer in china medical university hospital from to were enrolled. patients' basic characters, surgical and pathology reports and treatment records were retrospectively collected. patients were stratifi ed into fragile and non-fragile group. pearson's chi-square test and student t-test were used to assess parameters of these two groups. results: we identifi ed patients. th ere were patients aged more than years old, patient are uremic status and patients were performance ecog: . total patients were stratifi ed into fragile group. th e sex and pathological staging were no diff erence in these two groups. major perioperative complications defi ned as clavien-dino grade or more were . % in fragile group and only . % in non-fragile group (p= . ). chemotherapy use rate was . % and . % in fragile and non-fragile groups (p= . ). th e -day morbidity rate of non-fragile and fragile group was . % and . %, respectively. th e day morbidity was no signifi cant between these two groups ( . % of non-fragile and . % of fragile groups). in fragile group, -day mortality rate was . % and -day mortality rate was . %. th ere was no -day mortality in non-fragile group. half the patients died within months in fragile patients and fi ft y percent of patients lived aft er years in non-fragile patients. conclusions: fragile patients received radical cystectomy had higher perioperative major complications rate and higher -day mortality rate. we off ered complications and morbidity rate in these patients who received radical cystectomy. in elderly, esrd or ecog>= patients, we need more cautious care to decrease complication and morbidity rate. introduction and objective: primary management of muscle invasive bladder cancer (mibc) is cystectomy (cx). all traumas, including major surgery like cx, induce a stress response (sr), which plays an important role controlling the human immune system. a widely used parameter for systemic surgical sr is measurement of serum levels of c-reactive protein (crp). th is prospective study aims to compare the introduction and objective: several prognostic models predicting survival of patients with metastatic urothelial carcinoma (uc) have been developed, however, of them, the fi rst model by bajorin in is still the most representative and widely-used. th e aim of this study was to validate three major prognostic models constructed based on phase and trials, by using a cohort of real-world patients. we reviewed patients with metastatic uc who received fi rst-line chemotherapy at our fi ve affi liate institutions between and . using this multi-institutional cohort, we validated the following models: the "bajorin model", a model consisting of visceral metastasis and performance status (j clin oncol ; : ) ; the "apolo model", a nomogram including visceral metastasis, performance status, albumin and hemoglobin (j natl cancer inst ; : ) ; and the "galsky model", a nomogram including leukocyte count, number of sites of visceral metastases, site of primary tumor, performance status and lymph node metastasis (cancer ; : ) . cox proportional hazards regression model was used for multivariate analysis. harrell's c-index was calculated for each model. conclusion: all models were demonstrated to have high external validities in real-world patients, and of them, the "apolo model" achieved the highest c-index in the present population. further studies with larger populations are needed for establishment of the next standard model. the impact of female gender on bladder cancer specifi c death risk after radical cystectomy: a meta-analysis of patients liu s, yang t, na r, jiang h, ding q introduction and objective: bladder cancer was one of the most commonly diagnosed cancers in the world. up till now, there has been no study summarizing current studies on gender disparity and bladder cancer outcomes aft er radical cystectomy. to perform a fi rst meta-analysis on the association between female gender and cancer-specifi c death risk aft er radical cystectomy. a comprehensive literature search of the medline and embase databases was conducted for relevant studies published till november, th . th e primary goal of our study was to investigate the impact of gender disparity on cancer-specifi c death risk aft er radical cystectomy in urothelial bladder carcinoma population. th e meta-analysis was performed by estimating the odds ratios (or) and confi dence intervals (ci) through a random eff ect approach. results: a total of studies were included in the meta-analysis with a total population of patients. th e baseline characteristics of the studies were described in table . female gender was associated with a worse survival (pooled or: . , % confi dence interval . - . ) compared with male gender aft er radical cystectomy. signifi cant (q= . , p= . ) statistical between-study heterogeneity was present, with . % of variance secondary to between-study diff erences (i : . %). sub-group analysis found the correlation was signifi cant in north american, european studies (or: . , % ci . - . and or: . , % ci . - . , respectively) and studies from larger size of samples (or: . , % ci . - . ). we also found studies adjusted for the key elements (t stage, n stage and grade) obtained positive correlation (or: . , % ci . - . ). introduction and objective: pathologic response after neoadjuvant chemotherapy for muscle invasive bladder cancer is used widely as a surrogate endpoint for overall survival. controversy persists, however, whether the absence of residual cancer (pt ) or the presence of only non-muscle invasive residual cancer (pt , ptis, pta) is the optimal surrogate endpoint. we aimed to assess survival dependent on these pathologic responses in a large multicenter patient cohort. we retrospectively reviewed records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent cystectomy at contributing institutions from - . patients with ct - an m and eventual pn disease were selected for this analysis. estimated os was compared between pt and pt /pta/ptis patients. a multivariable cox proportional hazards regression model for overall mortality was generated to evaluate hazard ratios (hrs) for variables of interest (age, gender, number of cycles and type of chemotherapy regimen, surgical margin, and pt vs. pt /pta/ptis). conclusions: pt /pta/ptisn and pt n stage on the fi nal cystectomy specimen are strong predictors of survival in patients receiving nac and rc. we did not discern a statistically signifi cant diff erence in os when comparing these two endpoints. signifi cance of computer materials and methods: fift y patients were included in our study, of them presented with haematuria and a recent diagnosis of bladder carcinoma, and patients with a history of previous transurethral resection of superfi cial bladder cancer in their follow up period. th ey ranged in age years to years with a mean of . ; while male to female ratio was . : . th e main steps to perform virtual cyctoscopy incorporate proper bladder distention with air aft er draining the residual urine through foley's catheter and scanning the patient in both supine and prone positions. an excellent overview of the bladder masses was obtained in all cases and the results of virtual cyctoscopy and conventional one were comparable with excellent sensitivity rates of virtual cyctoscopy in detection, localization and morphology description of the bladder lesions at variable sizes. results: for detection of all lesions (n= ), virtual cyctoscopy alone showed sensitivity: . %, specifi ty: . % with two false positive and one false negative in comparison to conventional cyctoscopy which detected lesion while in axial ct alone the sensitivity: . %, specifi ty: % with false negative fi ndings. conclusion: ct virtual cystoscopy is a promising technique for use in bladder tumor detection of lesions larger than mm. optimal evaluation requires adequate bladder distention with the patient in both supine and prone positions and interpretation of both transverse and virtual images. is an evolving technique aiming to improve upon the diagnostic sensitivity of prostate biopsy for the diagnosis and local staging of prostate cancer (pca). diff erences in interpretation, expertise and application of mpmri may be responsible for the range of reported results. th is retrospective study aims to evaluate the diagnostic accuracy of mpmri in a cohort of patients from melbourne, australia, as compared to the gold standard of radical prostatectomy (rp). th is retrospective study was conducted in through the electronic patient records of a tertiary hospital and several private urology practices in melbourne, australia. patients having undergone rp had their records assessed for the presence of a pre-operative mri performed aft er st january which was then evaluated against the reference standard of a radical prostatectomy wholemount specimen. mri sequences typically included t weighted imaging, diff usion weighted imaging and dynamic contrast enhancement at t. mri reports were evaluated using the prostate imaging-reporting and data system (pi-rads) system. in our cohort the sensitivity and specifi city of mpmri for prostate cancer (pca) detection was found to be approximately - % and - % respectively. th e area under the curve for determining local stage was approximately . . conclusion: mpmri may have a useful role as an adjunct for prostate cancer diagnosis and directing management toward improving patient outcomes. staging information may be less reliable. a randomized prospective trial to assess the outcomes of mri/trus-guided prostate biopsy and traditional -core trus-guided prostate biopsy baco e , rud e , eri l , moen g , vlatkovic l , svindland a , eggesbø h , ukimura o introduction and objective: th e outcomes of magnetic resonance imaging (mri) and -dimensional transrectal ultrasound ( d-trus)-image-fusion-guided prostate targeted biopsy (mri-group) has not yet been compared with traditional -core trus-guided prostate biopsy (control-group) in a randomized control trial (rct) . th e aim of this study was to compare the prostate cancer (pca) detection rates (cdrs) and histopathological outcomes in the two groups. th is prospective rct included prostate biopsy (pb) naïve patients with suspicion for pca, where were randomized to mri-group and to control-group from / to / . in the mri-group, two tb of mri suspicious regions was followed by -core systematic random biopsy (rb). in the control-group, two tb towards palpable and/or trus-visible suspicious regions and -core systematic rb were performed. clinically signifi cant pca (cspca) on biopsy was defi ned as maximum cancer core length (mccl) ≥ mm of gleason score (gs) or any mccl of gs ≥ according to start criteria. cdr of all pca and cspca, and histopathological fi ndings were compared between the two groups. results: in the mri-and control-group cdrs were / ( %) and / ( %), (p= . ). cspca were detected in / ( %) in and / ( %) in control-group, (p= . ). tb (median cores/ patient) detected cspca in / ( %) in mri-and / ( %) in control-group (p= . ), respectively. concordance of gs on biopsy and radical prostatectomy specimen was / ( %, k = . ) in mri-and / ( %, k = . ) in the control-group (p< . ). upgrading of gs biopsy vs. gs-rp specimen was % in mri-group and % in control-group (p< . ). since the present study had a restricted cohort size, this may limit the generalizability of the results. no signifi cant diff erence in cdrs was found between the two groups. pca diagnosis can be achieved with few mri/trus-fusion guided prostate biopsy. gleason score on targeted biopsy was more accurate in the mri-group. introduction and objective: infection is a complication of trus prostate biopsy, despite the use of antibiotic prophylaxis. worryingly the rate of infectious complications following trus biopsy has been shown to be increasing. we aimed to determine the rate, severity, risk factors and microbiology resistance patterns associated with trus biopsy sepsis. as well the standard patterns of care surrounding trus prostate biopsy. a retrospective case-control study was conducted. using electronic coding all patients who presented to cabrini hospital with sepsis following a trus biopsy from to were identifi ed. validated cases were matched to controls in a ratio of : . eligible controls were required to have undergone a trus biopsy at the same surgical institution as the case and in the closest period of time. demographic, procedural and patient related data-points were recorded for all patients using hospital and urologist records. univariate logistic regression models were constructed and used to determine risk factors associated with infection. results: seventy-one cases developed sepsis following trus biopsy and were matched to controls. th e average rate of sepsis over the -year study period was . %. a sofa score ≥ was identifi ed in % of cases. we found a high prevalence of antibiotic resistant e. coli, with % of blood culture isolates classifi ed as multidrug resistant organisms. eight diff erent prophylactic antibiotic regimens were identifi ed. statistically signifi cant risk factors included previous antibiotic use and prior international travel within the six months prior to biopsy. th e addition of a penicillin antibiotic to standard fl uoroquinolone antibiotic prophylaxis was protective. conclusions: trus biopsy is an elective procedure and as such needs to be associated with minimal morbidity. th e patterns of care surrounding periprocedural variables for trus biopsies were non-uniform and diverse. a wide variety of diff erent prophylaxis regimens and bowel preparation routines were recorded. patients with risk factors for sepsis may represent a better target population for intervention with alternative preventative strategies. alternative preventative options include augmented prophylaxis, tailored prophylaxis or the tp biopsy approach either as a fi rst line biopsy modality or based on epidemiological risk factors. psa level) and pathological data was collected for all patients undergoing fi rst-time prostate biopsy with at least months follow-up, at music practices. from this overall cohort we identifi ed all patients whose pathology revealed multi-focal hgpin and/or asap (pre-malignant pathology) . for this subgroup, we examined the frequency of repeat biopsy across music practices and cancer detection outcomes. introduction and objective: nowadays overtreatment is recognisable challenge in pca management. overdiagnosis is possible reason for further overtreat-ment. we hypothesised that repeated prostate biopsies could not only help to cure but also harm patients with pca. consecutive patients who underwent biopsy for suspicious pca following at least one rebiopsy at single tertiary medical centre in - were included. age, initial and subsequent psa, drv, histology and biopsy features were recorded along with characteristics of subsequently diagnosed pca and chosen treatment approach. descriptive statistical methods were used for further analysis. results: basic characteristics were (mean±sd or frequency): age at initial biopsy ( . ± . years), time between initial/fi nal biopsy ( . ± . months), initial/ fi nal psa ( . ± . and . ± . ng/ml), drv (normal/suspicious . %/ . %), and number of initial/fi nal biopsy cores ( . ± . and . ± . ). initial/ fi nal histology was bph in ( . %)/ ( . %), infl ammation in ( . %)/ ( . %) and premalignant lesions in ( . %)/ ( . %) cases. finally, ( . %) pca were diagnosed ( by biopsy, by turp) performing biopsies aft er all. mean number of biopsies per patient was . in total and . to reach cancer positive histology; turp was performed in ( . %) patients. in ( . %) patients ≤ biopsy cores were cancer positive and in ( . %) patients gleason score was ≤ . gleason score ≥ was found in ( . %) cases. treatment with curative intention was held in cases (rrp , external radiotherapy ), no treatment (as/ww) in and hormonal therapy in patients. fourteen patients with minimal low grade cancer (≤ positive cores, gleason score ≤ ) underwent rrp ( % of all surgery cases). conclusion: repeated biopsy is important approach in pca diagnosis. however, based on our results we cannot exclude the risk of overdiagnosis and subsequent overtreatment with signifi cant impact on patients' quality of life, including radical surgery for low risk disease and early hormonal therapy in non-metastatic low-intermediate risk disease. th e study is retrospective, but potential bias became the advantage, since we could exclude prospective "self-control" within treatment decision making process. (siemens, munich, germany) and images were interpreted visually to evaluate uptake in biopsy districts of prostate gland. th e lesions suspicious for pca were submitted to additional targeted biopsies. introduction and objective: multiparametric mri (mpmri) and mri/trus-fusion-guided biopsy (tb) are advocated to detect index lesions and signifi cant prostate cancer (pc) within the prostate more exactly than systematic biopsies (sb) . th e aim of this study was to evaluate the detection accuracy of tumor foci by mp-mri and tb on radical prostatectomy (rp) specimen. we selected consecutive patients who were treated with rp for localized pc diagnosed by tb and/or transperineal saturation sb. on mpmri, all lesions were scored according to pirads. all lesions with pirads≥ underwent tb. on rp specimen, index lesion was defi ned as highest gleason score (gs) or highest tumor volume (tv). gs= + and tv≥ . ml or gs≥ + and tv≥ . ml were considered signifi cant. we performed spearmans correlation coeffi cient between mpmri and rp specimen and fisher's test between mpmri, tb and sb. introduction and objective: prostate biopsy is evolving to pre-biopsy multi-parametric mri (mp-mri), followed by systematic biopsy (sb) ± targeted biopsy (tb). mp-mri combined with trus-guided tb may increase detection rates of prostate cancer (pca), especially clinically signifi cant pca (cspca). however, few studies compare the detection rate of sb versus tb in the same cohort of men, as recommended by the standards of reporting for mri-targeted biopsy studies (start) consensus panel. th is study compares the diagnostic yield of sb and tb in a single cohort. th irty-three patients had a pre-biopsy mp-mri that identifi ed a target lesion. each patient then had a trus-guided sb and tb. th e cognitive fusion technique was used to perform the tb. results: among the patients, mean age was years; mean psa was . ng/ml. th e positivity rate for pca was % (n= ) for both sb and tb. th e positivity rate for cspca was % (n= ) for sb and % (n= ) for tb (p= . ). sb underdiagnosed cases ( %) of cspca that were detected through tb; tb underdiagnosed cases ( %) of cspca (p= . ) . th e positivity rate for sb and tb combined was % (n= ) for cspca (p= . ). conclusion: detection rates for pca using sb and tb were equal, but sb had a higher detection rate for cspca. combining tb with sb increased the rate of detection for cspca by %. tb alone was % more introduction and objective: active surveillance (as) has gained popularity with the intention of avoiding or postponing interventions in subjects with pca of low biological potential. unfortunately, several inclusion criteria have been proposed but many doubts still persist about their performance in predicting favorable disease. we aimed to assess the added value of biopsy factors, like maximum cancer length in a core (mcl), cumulative cancer length (ccl), cumulative length of positive cores (clpc), and percentage of cancer involvement in positive cores (cipc), to the prias criteria in patients who underwent radical prostatectomy (rp) but eligible for active surveillance (as). from january to december , consecutive subjects underwent rp. we identifi ed ( . %) patients who were eligible for as based on prias criteria: clinical stage t c or t , psa level of ≤ ng/ml, gleason score ≤ , psa-d of < . ng/ml and one or two positive biopsy cores. we calculated the diagnostic accuracy of biopsy factors in determining pathological confi rmed unfavorable disease. decision curve analysis (dca) were performed. explored, we examine the feasibility of monitoring low volume gleason sum (gs) + disease compared to gs + disease. introduction and objective: th e selection of prostate cancer patients for active surveillance (as) is based on the criteria for low risk according to protocols such as the national comprehensive cancer network (nccn) or european association of urology (eau) guidelines. we aim to compare pathological upgrading and upstaging rates between prostate cancer patients who met the above guidelines but underwent radical prostatectomy. we also aim to refi ne the selection criteria for our local population. a total of men were treated with rp at our tertiary center from to . seventy-three patients met the nccn criteria for active surveillance: ct -t a, prostate-specifi c antigen (psa) less than ng/ml, and biopsy gleason sum to . th irty-fi ve met the eau guidelines, which had additional criteria of: or less biopsy cores positive and % or less ca detected per core. results: of the patients who met the nccn criteria, ( . %) showed pathological upgrading (gleason > ) while ( . %) were upstaged (pt ). upgrading and upstaging fi gures for the patients meeting the eau guidelines were ( . %) and ( . %) respectively. analyzing the patients who met the nccn criteria, those who had % or more of the number of biopsy cores positive for prostate cancer had a far greater upgrading rate of . %, which was more than the . % (p = . ) seen in the other patients. psa density or percentage of individual core did not show any statistical diff erence in upgrading or upstaging. conclusion: a lower percentage of upgrading was seen in patients meeting the eau. upstaging fi gures were relatively the same. when counseling patients for active surveillance using the nccn criteria for low risk, we should exercise strong caution in patients with % or more of the number of biopsy cores positive for prostate cancer. biochemical recurrence rates in active surveillance candidates and the role of improving gleason grading introduction and objective: to evaluate prospectively the role of prostate-specifi c antigen (psa) density to predict gleason score upgrade in prostate cancer patients eligible for active surveillance (t /t , biopsy gleason score ≤ and psa ≤ ng/ml and ≤ positive biopsy cores). between january and november , among the patients who underwent more than core trans-rectal ultrasound guided biopsy, patients eligible for active surveillance under-went radical prostatectomy. using the modifi ed gleason criteria, tumor grade of the surgical specimens was examined and compared to the biopsy results. results: a tumor upgrade was noticed in ( . %) patients. extra-capsular disease and positive surgical margin was found in ( . %) and ( . %) patients, respectively. a statistical signifi cant correlation between the psa density and postoperative upgrade was found (p= . ); this is in contrast to the other studied parameters which failed to reach signifi cance, including psa, prostate volume, number of biopsy cores and number of positive cores. tumor upgrade was also highly associated with extra-capsular cancer extension (p= . ). th e estimated optimal cutoff value of psa density was . ng/ml , obtained by roc analysis (area under the curve . , p= . , % ci . - . ). conclusions: psa density represents a strong predictor for gleason score upgrade aft er radical prostatectomy in patients eligible for active surveillance. since tumor upgrade increases the potential for postoperative pathological adverse fi ndings and prognosis, psa density should be considered when treating and consulting patients eligible for active surveillance. surgical outcomes of south australian patients who have discontinued active surveillance plagakis s , o'callaghan m , , , moretti k , , foreman d , introduction and objective: active surveillance (as) is a recognized management pathway for patients with low risk prostate cancer (pca). diff ering protocols exist to identify suitable patients and manage their follow up. our study compares surgical pathology outcomes between patients who were initiated on, but discontinued, as and underwent radical prostatectomy (rp) with patients who received surgery immediately at the time of diagnosis. we also explore predictors of as discontinuation. our cohort comprised men diagnosed with pca from the south australian prostate cancer clinical outcomes collaborative database between - , aged - years, gleason score ≤ and psa ≤ . patients were stratifi ed into an immediate treatment group and an as group. to assess if as derivation rules aff ected outcomes, patients were sub-categorised according to enrolment criteria of university of toronto, prias and royal marsden protocols (with psa and gleason adjustment accordingly). all patients had a minimum of two years follow up. chi squared, logistic regression and cox proportional hazards modelling were used to compare outcomes between groups. results: forty-three ( %) patients in the as group underwent rp, compared with in the immediate treatment group. extra capsular extension and upgrading of histology at rp were more common in those managed by as compared to those receiving im-mediate surgery. th ese associations were supported by sensitivity analysis using prias and toronto criteria but not royal marsden selection criteria. as trended to being associated with unfavourable surgical pathology in multi-variable analysis, but this was only statistically signifi cant for prias ), p= . ). in all patients managed by as, sensitivity analysis suggested that the percentage of core positive at diagnosis is a signifi cant predictor of as discontinuation in those meeting the university of toronto selection criteria (hr . ( . - . ), p= . ). to determine if prias has increased rates of active surveillance (as) for patients with low-risk prostate cancer (pca). secondly, to determine whether urologists are operating on greater proportions of high-grade pca as a result of increasing as and what eff ect this has on surgical practice. prospective data was collected on patients from - (cohorts - , - ) who underwent trus biopsy by a urologist in geelong (n= ). positive trus biopsies (n= ) in both the pre and post prias cohorts were assessed to see if they met prias eligibility and whether they received as or active treatment (at). at patients were risk stratifi ed by gleason score and d' amico risk. data on post-prostatectomy staging, margin status and nerve-sparing techniques were collected. chi-squared test were used to calculate statistical signifi cance between cohorts. results: as increased between cohorts ( %, %, p= . ). before prias % ( / ) of patients eligible for as by prias criteria opted to undergo as compared with % ( / ) aft er the introduction of prias (p=< . ). th e relative proportion of high-grade pca (gleason score ≥ and d' amico high-risk) undergoing at increased from to % (p= . ) and to % (p= . introduction and objective: renal trauma is predominantly managed conservatively. trauma nephrectomy is reserved for patients who fail conservative or alternative management options. nephron sparing surgery is the cornerstone of renal preservation. our objective was to review the management of renal trauma at three tertiary facilities in queensland over a year period and compare these outcomes with current literature. a retrospective analysis was performed to fi nd the total number of renal traumas presenting to the princess alexandra hospital, royal brisbane and women's hospital and gold coast hospital, in queensland, australia. renal trauma patients were identifi ed using icd- codes (s . - ) and operative databases. patients requiring angioembolisation were obtained from radiological databases. we accessed the number of conservatively managed patients, trauma nephrectomies and angioembolisations for renal trauma. results: a total of renal traumas were identifi ed from june to june . six hundred and sixteen injuries were managed conservatively. th irty-three patients warranted acute exploration due to haemodynamic instability and resulted in nephrectomy in all cases. a trauma or general surgeon was the primary operator. fift een patients underwent angioembolisation for blunt renal trauma and patients for penetrating injuries. two patients proceeded to delayed nephrectomy for ongoing bleeding and for a ureteric stricture requiring nephrectomy aft er failed auto transplantation. th ese were performed by an urologist. th ere were further devascularised atrophic kidneys. seventeen of renal units were spared and of patients remained with functioning kidneys. all treated patients with angioembolisation were followed up with either mag renogram or ct triple phase and had functional kidneys at . years. conclusion: renal trauma is managed conservatively in most cases, consistent with the current literature. angioembolisation is an eff ective management option in selected patients with renal trauma. th is may prevent the need for trauma nephrectomy. in our cohort, patients requiring a trauma nephrectomy had predominantly grade iv and v injuries. general or trauma surgeons performed trauma nephrectomies in the acute setting of haemodynamic instability with rapid transfer to theatre. delayed nephrectomies were performed primarily by urologists in this cohort. introduction and objective: to review the contemporary management of traumatic extra-peritoneal bladder ruptures at an australian level one trauma centre. patients presenting with bladder injuries from july through to june were identifi ed using the traumanet database. th is was cross-linked with medical records and only patients with extra-peritoneal bladder rupture were included in the study. clinico-pathological data were collected from the database, medical records and health information services coding data. results: over the twelve-year study period, multi-trauma patients sustained an extra-peritoneal bladder rupture. of these patients, . % had a concurrent pelvic fracture and . % had co-existing intra-abdominal injury. a total of patients underwent operative repair for the bladder rupture and patients were managed conservatively with catheter drainage. of the patients managed operatively, % of cases were done at the time of another general surgical or orthopaedic operation and only two cases were done as a stand-alone repair. conclusion: extra-peritoneal bladder ruptures can be managed both conservatively and with operative repair. if operative repair is performed, it is usually done at the time of another operation for concomitant injury. management outcomes of major renal injuries following blunt trauma: changing concepts over years results: a total of / ( . %) of group i, and / ( . %) of group ii were treated non-operatively. diagnosis and grading in group i depended mainly on u/s, ivp and in some cases ct scan, while u/s and enhanced ct scan were mainly used for most of the group ii cases. in the total cohort, grade iii, iv and v renal injury were seen in ( . %), ( . %) and ( . %) patients respectively. open exploration was followed in ( . %) and ( . %) patients of group i and ii, with an overall exploration rate in / ( . %) of grade iv and v injury. th e incidence of nephrectomy have decreased from cases ( . %) in group i to cases ( %) only in group ii ( / kidneys were pathologic). double-j stenting and percutaneous drainage of urinoma was done in and cases, and chest-tube drainage to one patient with traumatic urinothorax in the conservatively managed group. outcomes were excellent, however in the non-operatively managed (grade iv-v) cases, / ( . %) normotensive patients had a non-functioning kidney within one year of follow up. conclusion: non-surgical management of high grade blunt renal injury can be safely undertaken and also recommended unless the patient is haemodynamically unstable. accurate grading is sometimes imprecise in multi-trauma patients, where instability is not always due to renal injury. drainage of extravasation is necessary to reduce morbidity. abdominal exploration does not mandate concomitant renal exploration, which is indicated in selected instances, otherwise it is an aggressive decision with a triple incidence nephrectomy rate. management of grade iv renal trauma: a revision of the aast renal injury grading scale is mandatory chiron p , hornez e , , boddaert g , dusaud m , bayoud y , molimard b , desfemmes f , durand x introduction and objective: th e aast (american association for the surgery of trauma) injury grading scale for renal trauma is currently the most important variable predicting the need for kidney repair or removal, for morbidity and mortality aft er blunt or penetrating injuries of the kidney. th e revision included the renal pelvis, the uretero pelvic junction and the segmental vascular injuries as grade iv, limiting grade v to severe hilar injuries. however, this revision does not permit the identifi cation of the group of patients who will require surgery because of hemodynamic instability due to grade iv renal injuries. th is study aims to propose an add-on for the grade iv of aast renal injury scale, in order to improve the management of these patients. we searched the following electronic databases: medline and scopus database. searches were not restricted by date, language or publication status. searches were last conducted in september . paediatric studies were excluded. results: seventy-one articles were found, were pertinent, including directly related to the topic. th ree risk factors were identifi ed to be associated with surgery for hemodynamic instability: peri-renal hematoma > . cm, intravascular contrast extravasation, medial renal laceration. presence of two or more of these criteria has been validated by others studies to predict the need for intervention. patients with > % devascularized fragments also present a poor prognosis and should be treated more aggressively. conclusion: th ese data should be incorporated into a future reassessment of the classifi cation, in order to better determine the need and time for surgery in grade iv renal traumas, generally leading to a nephrectomy. single panurethral reconstruction can be a surgical challenge. techniques include staged urethroplasty, augmented anastomosis with buccal mucosa graft (bmg) onlay via penile and/or transperineal, skin fl aps, or combinations of these. we report our experience of single stage modifi ed transperineal urethroplasty using a dorsal bmg in treatment of panurethral stricture. aft er obtaining irb approval, we performed a retrospective review of our urethral stricture database and identifi ed patients having undergone single stage transperineal urethroplasty using dorsal bmg as treatment of pan-anterior urethral stricture. patient characteristics, operative, and post-operative outcomes were studied. failure was defi ned as a need to any intervention during the follow-up period. results: th irteen patients underwent complete anterior urethra dorsal urethrotomy with dorsal bmg onlay between september and january . mean age was . years (sd: +/- . ). urethral stricture etiology was lichen sclerosis in patients ( . %), idiopathic in ( . %), hypospadias in ( . %) and infection in ( . %). previous treatments of dilatation and dviu were noted in patients ( . %) and previous urethroplasty in ( . %). mean operative time was . minutes (sd: +/- . ). mean estimated blood loss was . cc (sd: +/- . ). th ere were no intraoperative complications. early postoperative complications were buccal donor site bleed in patients ( . %) one treated with digital compression and other with hemostatic stitch, one patient ( . %) presented a perineal abscess and secondary urethroperineal fi stula. late complications was observed in patients who had postoperatory dribbling ( %). at mean follow up of . +/- . months, had recurrence ( . %) requiring dviu without new recurrence aft er a mean follow-up of . months (range - ) and one had meatal stenosis treated with dilatation ( . %) without recurrence aft er . month of follow-up. conclusion: in this small cohort, reconstruction of panurethral strictures may be safely and eff ective-introduction and objective: we present a novel technique for reconstruction of bulbo-membranous urethral strictures aft er surgery for bph with external sphincter sparing to preserve continence. anatomical studies have shown that the rhabdosphincter is separated from the membranous urethra by a sheath of connective tissue. by meticulous dissection of this sheath we separated the muscle from the urethral wall preserving the sphincteric function. patients with bulbo-membranous strictures aft er turp or open prostatectomy (op) who failed dilation and/or internal urethrotomy were reconstructed with a bulbo-prostatic anastomosis with preservation of the fi bers of the external sphincter. th e bulbo-membranous junction is approached dorsally, the inter-crural space is opened on the midline and the bulb is mobilized only from one side, without detachment from the perineal body. th e bulbo-membranous junction and membranous urethra are exposed and secured with vessel loops. th e membranous urethra sheath is opened circumferentially, carefully refl ecting the circular muscle fibers until exposure of the urethral wall. gentle blunt proximal dissection allows separating the muscle away from the urethra up to the prostatic apex, where healthy urethra is found to perform the anastomosis. results: from january to march we operated patients ( aft er turp and aft er op). all had membranous or bulbo-membranous strictures; bladder neck contractions were excluded. mean age was years ( - ). fourteen patients have been treated with either dilation and/or dviu; seven were with a suprapubic tube. mean length of stricture was cm ( - . ) , mean time from surgery to reconstruction was months ( - ) and mean follow-up was months ( - ) . two patients were not evaluable due to insuffi cient follow up. of the remaining , twelve were completely dry or using one security pad ( . % success). th ere were two clavien complications (both scrotal hematomas) and no stricture recurrence. conclusion: excision and bulbo-prostatic anastomosis with sphincter sparing for strictures aft er surgery for bph is feasible and safe. our technique allows preserving continence in most patients. to our knowledge this technique has not been described before. a larger series and reproduction in other centers will help to validate its therapeutic role. introduction and objective: panurethral strictures are complex and extensive strictures that involve the penile and bulbar urethra. management of these patients is challenging. in the last two decades, oral mucosal graft s have gained widespread popularity as the most versatile substitute tissue for urethral reconstruction. th e aim of this paper to present the shortterm outcome of our experience in the use of oral mucosal graft s in one-stage urethroplasty in patients with panurethral strictures. materials and methods: between april and october , men were evaluated and had one-stage oral mucosa urethroplasty for panurethral strictures. results: th ere were patients age range of - years with a mean of . years. aetiological factors identifi ed were poorly treated urethritis ( . %), post-urethral catheterization ( %) and lichen sclerosis ( . %). th e commonest cause of catheter-associated panurethral strictures was part of intra-operative patient monitoring in ( %), following spinal cord injury ( %). preliminary suprapubic cystostomy was done in patients ( . %). graft length ranged from - cm with a mean of . cm. oral mucosa donor sites were buccal in ( . %), labial ( . %), combined buccal and labial ( . %) and ( . %) for combined buccal/lingual and buccal/labial/penile skin fl ap respectively. twenty eight patients ( . %) had satisfactory voiding on removal of the urethral catheter and subsequent follow-up whereas patients ( . %) experienced diffi culty. of these , one patient had bladder outlet obstruction due to benign prostatic hyperplasia which was the reason for previous repeated urethral catheterization that had resulted in the stricture. oral mucosa donor site complications were present in patients ( . %) and consisted mainly pain and numbness in the mouth. duration of follow-up ranged from - months and there was no mortality among the patients. conclusion: panurethral strictures are common in our practice mainly resulting as complication of prolonged urethral catheterization. urethral reconstruction by one-stage oral mucosa graft urethroplasty is feasible, has good outcome though it may be associated with minor donor site complications. larger number of patients and longer-term follow-up are needed to assess durability of the procedure. missed and delayed ureteral injuries in hasan sadikin hospital, bandung, indonesia introduction and objective: to review our experience with delayed and missed traumatic ureteral injuries. materials and methods: genitourinary trauma database was retrospectively reviewed from - . variables such as time to diagnosis, imaging modalitites, location of missed or delay injuries, management, duration of operation, length of stay and complications were noted. introduction and objective: traumatic urethral stricture as the result of straddle injury or pelvic fracture urethral injury (pfui) is associated with long term morbidity and reduce the quality of life. most patients will end with long life urethral dilatation even aft er endoscopic treatment. anastomotic urethroplasty at present is the answer of defi nitive treatment. general principles of urethroplasty are to defi ne healthy urethra above and below the site of surrounding fi brosis and to perform a spatulated end-to-end anastomosis. prior to the year of , most urethral stricture cases including traumatic anterior and posterior urethral stricture was managed mostly with direct vision internal urethrotomy (dviu) in our institution. we present our experience with transperineal anastomotic urethroplasty. to our knowledge this is the fi rst indonesian local centre report of the changing defi nitive treatment of traumatic urethral stricture in a series of patients. we retrospectively reviewed traumatic urethral stricture due to straddle injury and pfui that had been treated with urethral reconstructive surgery by transperineal anastomotic urethroplasty approach. th e data cases from january -december were analyzed; which were the age of patients, location, length of gap, previous operations, and treatments. th e clinical outcome was evaluated with urofl owmetry aft er , , , and months aft er the surgery. results: a total of patients came with traumatic urethral stricture to hasan sadikin hospital during , which consist of patients with pfui and patients with traumatic anterior urethral stricture due to straddle injury. th e median age was . and . for pfui and straddle injury, respectively. twenty four percent of pfui patients had distraction length > cm and % had distraction length < cm. meanwhile, % of straddle injuries had stricture length < cm and % had distraction length > cm. in order to achieve tension free of anastomotic urethroplasty, % of pfui patients underwent crural separation, % patients underwent inferior pubectomy and only one patient for supracrural re-routing. sixteen percent of patient of pfui are redo case urethroplasty. success rate aft er transperineal anastomotic urethroplasty of pfui cases was %, % for redo case pfui and % for straddle injury cases. mean q max rates at , , , and months aft er catheter removal of pfui patients was , , , and ml/s whereas for straddle injury patients was , , , and . conclusions: in short term follow up, transperineal anastomotic urethroplasty achieved a signifi cant good result for traumatic urethral stricture treatment at our institution. recurrence after urethroplasty in a tertiary care centre in sub-saharan africa: an analysis of preoperative factors introduction and objective: urethral strictures disease remains very common in sub-saharan africa but despite this, there are no available reconstructive urology trainings / fellowships outside the formal urology residency programmes of the region. we reviewed the outcomes of urethroplasties at a tertiary urology centre in nigeria, sub-saharan africa which typically off ers general urology service. preoperative independent predictors of recurrence post-urethroplasty were determined. th e records of a total of men who had urethroplasty for proven anterior urethral stricture disease between february and january were retrospectively analyzed. age, social status, aetiology of strictures, stricture location, length of strictures and type of urethroplasty were assessed. appropriate inferential statistics were performed to determine independent predictors of stricture recurrence. results: mean patient age was years (range to ) and majority of the patients were of low income status ( . %). iatrogenic strictures due to urethral instrumentations and catheterization ( . %) and post infl ammatory strictures ( . %) were more common. isolated penile and long segment peno-bulbar strictures accounted for over two-thirds of all patients ( . %). mean stricture length was . cm (range to cm). most patients had quartey's urethroplasty ( . %), others had buccal mucosal graft ( . %), orandi ( . %) and anastomotic bulbar urethroplasty ( . %). for a mean follow up of . ± months, the overall recurrence rate was . % with mean time to recurrence of . months. of the evaluated preoperative factors (age, p= . ; social status, p= . ; aetiology, p= . ; stricture location, p= . ; type of urethroplasty, p= . ; stric-ture length, p= . ), only stricture length (p= . ) was a signifi cant predictor of recurrence. roc analysis was done and stricture length > cm signifi cantly predicted recurrence (auc of . , p= . ). conclusion: stricture length > cm are a signifi cant cause of recurrence following urethroplasty in the setting of prevalent general urology practice in sub-saharan africa. th e introduction of formal reconstructive urology fellowship or training may help improve skills and outcomes. introduction and objective: males with hypospadias are likely at increased risk for future urologic complications as adults. however, it is unclear how childhood surgery modifi es this risk. th e purpose of this study is to describe the spectrum of adult presentations with hypospadias-related complications and examine the eff ect of childhood surgery on these complications. a retrospective chart review over a year period, from august -december , demonstrated adult patients who presented to an adult reconstructive urologist with urologic complications related to hypospadias. patients were divided into two groups: those with no prior hypospadias surgery (group , n= ) and those who underwent surgical correction as a child (group , n= ). charts were reviewed for age at presentation, initial complaints, history of repair, and surgical intervention required. results: overall, the mean age at presentation was . years old. meatal location was not statistically diff erent between groups and , respectively: glans ( . % vs. . %), subcoronal ( . % vs. . %), coronal ( . % vs. . %), distal penile ( . % vs. . %), midshaft ( . % vs. . %), and penoscrotal ( . % vs. . %). overall, luts ( . %) was the most common presenting complaint, followed by spraying ( . %), urethrocutaneous fi stula ( . %), recurrent uti's ( . %), and chordee ( %). comparison demonstrated group patients were more likely to present with luts ( . % vs. . %, p= . ) and recurrent uti's ( . % vs. %, p= . ). contrastingly, group patients presented more commonly with cosmetic dissatisfaction ( . % vs. . %, p= . ). urethral stricture disease was demonstrated in more patients who had previous hypospadias repair, than those who had not ( . % vs. . % p= . ). of these, strictures were signifi cantly longer in the previous surgery group ( . cm vs. . cm, p= . ). surgical intervention was required in . % of group and . % of group (p= . ). conclusion: correction of hypospadias as a child likely increases the future risk of urethral stricture, recurrent uti's, and subsequent luts, but improves patient satisfaction with cosmesis. follow-up of hypospadias repair patients should extend into adulthood, as a signifi cant portion of adult presentations ultimately require surgical intervention. introduction and objective: during male to female gender confi rming surgery with vaginoplasty, a space is created for the neovagina within the potential space between the prostate anteriorly, and denonvillier's fascia and rectum posteriorly. entry to this plane is challenging, and to date, the only surgical approaches to this space describe blunt and sharp dissection along the ventral surface of the urethra. th e likely trauma to perirectal vasculature muscle-laden connective associated with this approach may account for the observed recto-vaginal fi stula rate associated with vaginoplasty. we describe an alternative, never before published approach using a male urethral sound upon the apex of the prostate to enter this plane with sharp dissection in a reliable and effi cient fashion. we describe our surgical technique, wherein we use a male urethral sound during the dissection to help expose denonvillier's fascia over the apex of the prostate. we dissected a block of tissue containing prostate, denonvillier's fascia and rectum from human cadavers, to describe (using ihc) the location and relative abundance of blood vessels (factor viii ab.), nerves (nf & s- ab.), and connective tissue (h&e and masson's trichrome), to support the sharp surgical approach we describe over the traditional approach to this plane. we describe clinical outcomes and the recto-neovaginal fi stula rate utilizing this approach in our institutions. results: immunohistochemistry results showed that the sharp dissection we describe is associated with incision through signifi cantly fewer blood vessels and sensory-motor nerves as compared to the traditional surgical approach. use of the sharp dissection we describe resulted in, at our institutions, a signifi cant decrease in recto-neovaginal fi stula in the peri-operative period. conclusion: th e surgical technique we describe for dissection of the plane between prostate and denonvillier's fascia during vaginoplasty is well supported by the anatomic studies we performed, and, is associated with lower morbidity. th is surgical approach and technique is also likely useful for gaining access to this same plane for repair of recto-vesical and recto-urethral fi stulas. introduction and objective: mitrofi noff procedure is commonly employed as bladder draining tool in patients who are unable to do clean intermittent self-catheterization through native urethera. it preserves renal function in small capacity and high pressure bladders and to improve quality of life. here we want to share our single centre experience of patients undergoing mitroffi noff procedure. a retrospective study of patients who underwent mitrofi noff procedure from january till december with a median age of (range = to ). twenty eight patients were males while female. indications for catheterizable stoma formation included neurogenic bladder in patients, small bladder in , bladder tumor in , uretheral stricture in one and interstitial cystitis in one patient. median follow-up was month to years. stoma was made from appendix in cases, from tapered ileum in cases and from ureter in cases. stoma location was lower right quadrant in cases, left lower quadrant in cases and at umbilicus in cases. augmentation accompanied by mitrofanoff was done in patients while mitrofanoff alone was done in patients. augmentation was done by using ileum in patients and cecum in one and illeocecum in one patient. data was entered from chart review and analyzed on spss. sixteen patients were analyzed in terms of complications and stoma revision. results: post-operative complications included uti in ( . %) patients, stones formed in ( . %), fistula was seen in ( . %) patient (augmentation cystoplasty + mitrofanoff ), stoma stenosis seen in ( . %), stoma revision done in ( . %). one female ( . %) patient had dribbling urine through urethera (incontinence), she underwent bladder neck closure. metabolic complications were not seen based on serum electrolytes follow-up records. we concluded that aft er mitrofanoff procedure renal function was preserved in most of the patients while no metabolic complications were seen in patients aft er undergoing mitrofanoff +bladder augmentation. stone risk was . % which was not very high. quality of patients was improved aft er mitrofanoff procedure. results: sesfm has higher porosity and larger pore size compared with bam (p< . ). at weeks, the presence of vesical calculus was evident in / rabbits. histological analysis showed that sesfm and bam promoted similar degree of urothelium regeneration (p> . ), and sesfm promoted a higher degree of smooth muscle and vessel regeneration compared to bam at each time point (p< . ). in addition, muscle strips supported by sesfm displayed higher contractile responses to carbachol, kcl, and phenylephrine compared with bam. at weeks, both matrices elicited similar mild acute and chronic infl ammatory reactions. conclusion: our results demonstrated that sesfm has greater ability to promote bladder tissue regeneration with structural and functional properties compared to bam, and with similar biocompatibility. introduction and objective: ureteral access sheaths (uas) can aid ureteroscopy by facilitating multiple passes of the ureteroscope, maximizing irrigation drainage, and reducing intra-renal pressures. however insertion of the access sheath may induce ureteral ischemia, cause iatrogenic ureteric injury, and could ultimately lead to ureteric stricture. in this study, we aim to evaluate the stricture rate following ureteroscopy both with and without the use of uas. we performed a retrospective chart review of consecutive ureteroscopies performed at our center (a tertiary referral center for endourology) between april and april to treat ureteric and renal calculi. th e primary outcome was the development of new hydronephrosis three months following successful ureteroscopy, not due to an obstructing stone. patients without follow-up renal ultrasound (us) or ct scan months post-ureteroscopy were excluded. data on age, sex, size of the stone, location of the stone, stone density, stone-free rate (sfr), time of the procedure, pre-op stenting, postop stenting, use of the uas, size of the uas, length of the uas, stone analysis, and imaging details were recorded. baseline and outcome variables were compared with anova and chi-square analysis where appropriate using spss statistical soft ware. results: a total of patients were eligible. a uas was used in ( . %) patients; ( . %) for renal stones and for proximal ureteric stones. th ere was no signifi cant diff erence in baseline or demographic data. none of the patients developed new hydronephrosis or developed a ureteric stricture, and none required endoureterotomy. conclusions: uas use during ureteroscopy for renal and ureteric stones is both safe and eff ective. even with routine use of . f and f uas, ureteric stricture rates are very low (zero in this series), suggesting that signifi cant ureteric injury is rare with proper technique and case selection. to evaluate the value of fl exible ureteroscopy for the treatment of the upper urinary tract calculi in children. a total of children, males and females, were identifi ed in this study. th e median age was . years, range months to years. among them, patients had the upper ureteral calculi ( with calculi in situ, with middle/fi stal ureteral calculi shift ing to upper ureteral aft er rigid ureteroscopic lithotripsy) and had renal calculi. ipsilateral mild to moderate hydronephrosis was found in all of the cases. four children had melamine-induced stones ( with upper ureteral calculi and with renal calculi). th e calculi were found on left side in cases, on right side in , and on both sides in (upper ureteral calculi). th e median stone size was . (range . to . ) cm. retrograde fl exible ureteroscopy and anterograde fl exible ureteroscopy in mini-percutaneous nephrolithotomy was performed. results: twenty eight cases were performed retrograde fl exible ureteroscopic procedure. one case was conversed to mini-percutaneous nephrolithotomy because the fl exible ureteroscope could not be inserted into the upper ureter. th e fl exible ureteral access sheath was failed to insert into the upper ureter in cases, and the fl exible ureteroscope was inserted into ureter directly. th e successful rate of stone search was % in cases. th irty cases were successfully performed in one stage. th e stones were successfully fragmented aft er two stages in two cases. th e success rate of stone fragmentation was . % with the holmium laser lithotripsy in one stage. th ree anterograde fl exible ureteroscopy with mini-percutaneous nephrolithotomy were successfully performed, and the stones were successfully found and fragmented aft er a single holmium laser lithotripsy. th e median operative time was (range to ) mins. th ere was no major perioperative complication. th e patients were discharged from hospital aft er a median of . days (range to ). double-j stent was removed aft er to weeks when no residual stones more than . mm in size were found. no recurred stones, no urethra stricture, no ureter stricture, no urinary incontinence and no vesicoureteral refl ux were found during the to -months follow-up. conclusion: flexible ureteroscopy is a safe and feasible method for the treatment of the upper urinary tract calculi in children. it is suitable for the stones in the pelvis and calyceal where the rigid ureteroscopy could not reach. introduction and objective: laparoscopic ureterolithotomy is an alternative to open ureterolithotomy for the primary treatment of large, impacted, proximal or mid ureteral stone. transperitoneal and retroperitoneal approaches are the basic techniques and each has its own advantages and disadvantages. th e aim of this study is to compare retroperitoneal versus transperitoneal laparoscopic ureterolithotomy in eff ectivity, pain scale and early complications. in this prospective comparison study from january to december , patients with proximal and mid ureteral stones underwent retroperitoneal laparoscopic ureterolithotomy or transperitoneal laparoscopic ureterolithotomy. th e randomization occurred on consecutive sampling on a : basis. groups and consisted of patients who underwent retroperitoneal laparoscopic ureterolithotomy and transperitoneal laparoscopic ureterolithotomy, respectively. demographic and clinical variable, operative time, length of stay, ureteral suturing, pain scale according to visual analog scale (vas) and early complications data were collected and analyzed. statistical analysis was performed with spss® version . using student t-test and mann-whitney u tests with p value< . considered statistically signifi cant. results: vas on day between the groups was statistically signifi cant, and was higher in group (p< . ). according to the clavien-dindo classification of surgical complication all the patients were in grade classifi cation. th e diff erences in operative time, length of stay, ureteral suturing, visual pain analog score on day , and early complications between the groups were not statistically signifi cant. ionising radiation is commonly used in urological practice in the form of fl ouroscopy. to date there is a relative dearth of information regarding patient exposure during the urological procedures and the subsequent risk of development of a lethal malignancy due to the radiation exposure. objectives: to determine the radiation exposure for a patient for the most commonly performed urological procedures and determine the lifetime additional risk of fatal cancer per procedure. data was collected prospectively in two institutions on endoscopic urological operations. procedures were classifi ed as retro-graphic, semi-rigid ureteroscopic (urs) and fl exible ureterorenscopic (furs). data collected included procure type and diffi culty, dose are product [dap (gy*cm )]). th e eff ective dose (ed) as measured in millisievert was determined from the dap by using the monte carlo calculation. results: a total of consecutive operations from two institutions were assessed. th e mean ed for all procedures in this study was . msev, irq ( . - . ). th e maximum ed was . msev. th e radiation exposure for all procedures was relatively small, for diagnostic retrographic procedures the median ed was . msev. for retrograde procedures that involved a stent insertion the median ed was . msev. th e median ed for all ureteroscopic surgeries was . msev, and the median ed for all furs procedures is . . th e fi ndings of this study are reassuring. endoscopic urological procedures appear to expose patients to relatively small radiation compared to other procedures requiring fl uoroscopy and a very low lifetime additional risk of fatal cancer per procedure. five during the follow no local recurrence was noted and two patients presented with distant metastasis. th e actual -year overall and cancer specifi c survival was . % and . %, respectively. on multivariable cox regression analysis, acci was the only factor associated with increased risk of overall mortality (hr . ; % ci ( . - . )). conclusion: rpn achieves excellent long-term oncological outcomes. age and comorbidities are associated with increased risk of overall mortality. to our knowledge, this is the fi rst series of long-term follow up aft er rpn reported to date. introduction and objective: partial nephrectomy provides equivalent oncologic and superior functional outcome compared with radical nephrectomy over the short and long term. with the development of laparoscopic techniques and increasing laparoscopic surgical experiences, laparoscopic partial nephrectomy (lpn) has become an acceptable alternative to radical nephrectomy for expert laparoscopic urologists to treat small renal mass. it was reported that using barbed suture can reduce warm ischemia time during lpn. we designed a single blind randomized controlled trial to fi nd whether the barbed suture can materials and methods: from july to march , forty-six patients with renal score less than were enrolled for this study. patients were randomized into two groups: control and v-loc group. all patients were evaluated before surgery including performance status, asa score, liver and renal function, abdominal ct, lung function, and cardiac function etc. during the surgeries, standard ports were placed. aft er the renal artery was clamped by bulldog, tumor resection was performed using a cold scissor. th en the inner layer deep vessels and collecting system, and outer layer were sutured with v-loctm respectively in v-loc group. in control group, inner layer was sutured with - absorbable sutures, and the outer layer renal parenchyma was sutured with absorbable sutures. operative characteristics and complications were compared between groups. results: laparoscopic partial nephrectomy was successfully completed in all forty-six patients without open conversion. control and v-loc groups were equivalent in demographic and tumor characteristics. no signifi cant diff erence was seen between control and v-loc groups in operative time ( vs. min, p = . ), estimated blood loss ( vs. , p = . ), warm ischemia time ( vs. min, p = . ), and complication rate ( % vs. . %, p = . ). conclusion: lpn with v-loc sutures for renorrhaphy is safe and feasible. however, using v-loc suture for renorrhaphy doesn't show any superiority in patients with low and moderate complexity renal tumors in our randomized control trial. small th e local recurrence free survival was signifi cantly better in the combined us/ct-guided group than in the us-guided group (p= . ). recurrences were found in % with us/ct-group and in % in usgroup. th e overall complication rate was similar (us/ ct % versus us %) in both groups. th e mean percentage decrease in the estimated glomerular fi ltration rate (egfr) aft er the treatment was . ± . % with us/ct, compared to . ± . % mean decrease in egfr aft er treatment in the us-guided group (p= . ). conclusion: th e use of combined us/ct-guidance when performing renal rfa resulted in superior primary and short term outcome compared to the use of us-guidance alone in patients treated at the same institution. increased experience with rfa treatment probably also contributed to the results. introduction and objective: to present our initial experience in female patients undergoing transvaginal notes-assisted laparoscopic partial nephrectomy (pn). between august and january , a prospective analysis of the initial ten patients who underwent transvaginal notes-assisted pn was entered into an institutional review board (irb)-approved database. th e procedure was performed using two umbilical trocars and one trocar through the vaginal wall. th e main renal artery clamping, segmental renal artery clamping and unclamped pn were performed depending on the circumstances of the tumour. some perioperative parameters including operative time, warm ischemic time, blood loss, and perioperative complications were recorded. sexual function was assessed with the female sexual function index (fsfi) questionnaire before and aft er surgery. th e cosmetic results were investigated by administering patient scar assessment questionnaire and scoring system (psaq). results: nine transvaginal notes-assisted pns were completed successfully. one patient with a right anterior upper-pole tumor was converted to radical nephrectomy because of persistent bleeding from the parenchymal defect. th e median (range) operating time was ( - ) mins and the median (range) estimated blood loss was ( - ) ml. th e median (range) warm ischaemia time (wit) was ( - ) mins. th e median (range) postoperative hospital stay was ( - ) days. all surgical margins were negative. eight patients completed the fsfi questionnaire, and analysis did not show diff erences in fsfi scores before and aft er surgery. th e better cosmesis results were confi rmed by the psaq score. transvaginal notes-assisted pn is a safe and feasible surgical procedure in the treatment of small renal mass with excellent cosmesis results. more prospective studies with long follow-up are needed to investigate the oncologic safety. introduction and objective: to analyze the complications of urologic transvaginal natural orifi ce transluminal endoscopic surgery (tv-notes), and to explore eff ective measures for its prevention and management. materials and methods: from may to february , a total of cases underwent tv-notes in our institute. intraoperative and postoperative complications were graded according to satava and clavien-dindo grade classifi cations system. th e major complications and their treatments were most importantly analyzed. results: among the tv-notes procedures, case conversion to open surgery and one case conversion to suprapubic-assisted laparoendoscopic single-site surgery (sa-less). th irty-one ( . %) patients had intraoperative complications, the minor and major was ( . %) and ( . %), respectively. th e intraoperative complications include cases of pneumoderm, cases of skin ecchymosis, cases of pleural damage, cases of liver injury, case of adrenal central vein injury, cases of spleen injury, cases of inferior vena cava injury, cases of renal veins injury, case of right iliac vein injury, case of bladder injury, case of renal collecting system injury, cases of colon injury, case of rectum injury. th e proportion of patients incurring minor and major postoperative complications undergoing tv-notes was . % (n = ) and . % (n = ), respectively. th e postoperative complications include case of adrenal crisis, cases of incision infection, cases of postoperative fever, cases of postoperative bleeding, case of the right external iliac artery thrombosis and case of urinary leakage. no intraoperative and postoperative deaths occurred. conclusion: tv-notes operation is safe and feasible surgical technique in urology, and does not increase the incidence of complications. but there is a potential risk of major complications occurring, which should be paid more attention to prevent. introduction and objective: knotless barbed suture, a relatively innovative type of suture, can eliminate knot tying, speed the placement of the sutures, and create the possibility of improved scar cosmoses. th e minimally invasive radical prostatectomy (mirp), as one of the earliest surgeries that adopted this advanced technique, was reported about diverse eff ects on the patients and the surgeons. our objective is to present the available evidence about the effi cacy and safety of barbed sutures in minimally invasive radical prostatectomy. we searched pubmed, em-base, and cochrane library for published studies and clinicaltrials.gov for additional information to identify randomized controlled trials (rcts) and cohort studies addressing the application of barbed and conventional sutures in mirp (until feb. ) . quality assessment was performed according to cochrane recommendations. th e data were analyzed using review manager (version . ), and sensitivity analysis was performed by sequentially omitting each study. hemi-pelvises, . % had the periprostatic plexus (ppp) as the largest vein of the dvc. th is was followed by the obturator vein (ov) ( . %), which originates from the lateral part of the plexus and runs laterally. next was the internal pudendal vein (ipv) ( . %), which originates lateral to the posterior part and runs postero-laterally. in the rp group, the dvc bunching stump was an average of . mm from the origin of the cavernous vein. no complications occurred while performing examinations. conclusion: d-ct pelvic venography depicted the dvc and its related veins in all cases. venous systems making up the dvc diff ered among patients. in . %, the main venous system was the ppp, which can be controlled by conventional dvc ligation technique. however, in the remaining % of hemi-pelvises, the ipv and the ov were the main venous systems. th ese will need wider ligation because of existing outside and to the back of pathways. we believe that a better understanding of dvc will lead to refi ned rp. introduction and objective: bladder pheochromocytoma and carcinoid tumors are rare neuroendocrine tumors of the bladder. presenting a series of cases of these rare bladder tumors which were managed laparoscopically. materials and methods: case was a years lady who presented with symptom of giddiness following micturition. ultrasound revealed a . cm bladder mass at the bladder base. twenty four hour urinary biochemical evaluation and mibg scan did not reveal any abnormalities. cystoscopy revealed a submucosal sessile mass above the trigone. on cystoscopic bladder distension a spike in blood pressure ( / ) was noticed which fell rapidly on emptying. patient underwent laparoscopic partial cystectomy aft er weeks of alpha blockade with phenoxybenzamine. case was a years old gentleman who presented with episodes of severe headache following micturition. despite antihypertensives his blood pressures were not under control. ultrasound revealed a cm bladder mass in the left lateral wall encroaching close to the left ureteric orifi ce. twenty four hour urinary biochemistry and mibg scan was suggestive of bladder pheochromocytoma. aft er weeks of alpha blockade he underwent cystoscopy followed by laparoscopic partial cystectomy with left ureteric reimplantation. case was a years old gentleman a hypertensive who underwent an attempted turbt and subsequent hypertensive crisis and bleeding for a bladder mass in a peripheral hospital. he was stabilized and referred to our center for further management. ultrasound revealed a cm anterior wall mass. twenty four hour urinary biochemistry and mibg scan was suggestive of bladder pheochromocytoma. aft er weeks of alpha blockade he underwent laparoscopic partial cystectomy. mri has shown to be accurate in diagnosing index tumours in prostate cancer. a variety of focal therapies has been explored in treating these lesions. th is study aims to compare the detection rate, grade and location of non-index lesions found in radical prostatectomy specimens with their initial mpmri. a prospective database of all men undergoing mpmri for suspicion of prostate cancer in our group practice was kept. ethics approval was obtained from epworth healthcare. of these men, all who had a -d summary diagram including pirads score for each mpmri and who then underwent radical prostatectomy were assessed. volumetric studies were performed for all prostatectomy specimens and compared to each corresponding mpmri -d summary diagram. analysis of non-index lesions was performed. conclusion: a signifi cant amount of patients who underwent radical prostatectomy in treatment for prostate cancer were identifi ed to have non-index tumours in their volumetric analysis. in our cohort of patients, the majority of low grade disease was undiagnosed on mpmri. however, a signifi cant amount of moderate grade non-index tumours were also missed on initial mpmri. th is questions the safety and appropriateness of focal therapy. ongoing research is warranted and we will continue to report our prospective mp-mri database as our experience with this modality grows. eligibility for active surveillance of prostate cancer and functional outcomes after prostatectomy shepherd a , , o'callaghan m , , introduction and objective: we aimed to compare the outcomes following radical prostatectomy (rp) of active surveillance (as) and non-as candidates. we hypothesised that as eligibility at diagnosis would be associated with favourable pathological, surgical and also functional outcomes. using a prospectively maintained database, all patients with a primary treatment of rp conducted prior to were identifi ed, including those who were initially eligible for as. men defi ned as eligible for as were those: diagnosed between and years of age; with gleason score ≤ ; psa ≤ ; clinical stage ≤ a; and with percentage of positive cores ≤ %. we compared the histopathological and functional outcomes of the two groups. results: of patients with a primary treatment of rp, met the criteria for as. pre-operative tumour characteristics of the patients meeting criteria for as were favourable compared with those ineligible (lower psas and less cancer in the biopsies; p< . ). functionally, the groups had similar pre-operative continence ( % vs. %) and potency rates ( % vs. %). histologic characteristics of the prostate specimen in patients qualifying for as were more favourable, with lower rates of positive surgical margins and extracapsular extension observed in this group (p< . ). following rp, at -, -and -month follow-up, there were no signifi cant diff erences in the proportion of men who were continent between as and non-as candidate groups ( months: % vs. %; months: % vs. %; months: % vs. %; p> . ). similarly, no signifi cant diff erences between groups were observed in the proportion of men who were potent at -and -month follow-up ( months: % vs. %; months: % vs. %; p> . ). aft er -month follow-up, however, potency appeared to be higher for the as candidates ( % vs. %; p= . ). were assessed pre-implant as well as at , , and months aft er seed implantation, and every months thereaft er. we evaluated clinical factors, including prostate volume (pv), neoadjuvant combined androgen blockade (cad), radiation dose to % of the prostate volume (d ), and to % of the urethral volume (ud ) to predict urinary disorders aft er brachytherapy using multivariate analysis. results: th e mean pre-implant ipss was . , with the greatest mean score of . at month aft er seed implantation. at , , , , and months, the mean ipss had decreased to . , . , . , . , . and, . respectively. th e mean pre-implant prostate volume (pv) was . g, followed by . g at months and . g at months aft er brachytherapy. in cases with pv more than g, d more than gy, and ud more than gy, ipss levels were signifi cantly high-er even years aft er treatment. on multivariate analysis, d more than gy (p< . ) and ud more than gy (p= . ) were independent predictors for ipss increases of more than points at years aft er brachytherapy. only d was an independent predictor at (p< . ) and years (p= . ) aft er brachytherapy. introduction and objective: metformin has been shown to be protective in prostate cancer (pc). we aimed to assess the eff ects of metformin on pc outcomes in men treated with external beam radiotherapy (ebrt) and/or androgen deprivation th erapy (adt). we also aimed to investigate the eff ects of metformin on the above outcome measures in type diabetic men with pc. th e outcome measures of time to biochemical failure (bf), metastasis, pc specifi c mortality and overall mortality were analysed in men on metformin using a competing risk model and a cox proportional regression model. a total of eligible cases, of whom were on metformin, were identifi ed with a median follow-up of . months. th ere were no diff erences in age, initial psa, gleason scores, t stage, d' amico risk or duration of adt between men who were on metformin and those not on metformin. treatment with metformin did not result in any apparent improvement in time to bf, time to metastases or overall survival but there was an increase of . fold in pc-specifi c deaths (p< . ) in men on metformin and adt when adjusted for cancer risk and co-morbidities. on a subgroup analysis of the men with type diabetes, similar fi ndings were seen with metformin being associated with a . fold increase in pc-specifi c deaths (p < . ). th ese adverse eff ects were lost in men on metformin and statins. conclusions: th e use of metformin did not improve time to metastases, time to bf or overall survival in men undergoing ebrt +/-adt for pc with curative intent. however, in type diabetic men on high doses of metformin there was an increased risk of pc-specifi c mortality. further studies are needed to investigate these fi ndings. th e objective of this study is to assess ire eff ects in prostate tissue and to correlate ire treatment planning with the d-histopathology of radical prostatectomy (rp) specimens that essential structures will be spared. sixteen patients, scheduled for rp, ire procedures were performed weeks before rp. ablation was performed according to two protocols: focal or extended ablation. th e electrode probes were inserted transperineally under ultrasound guidance. th e locations of the electrodes were used as input for the plannings soft ware. following rp, the specimens were processed into whole-mount sections, were histopathologically (pa) assessed and ablation zones were delineated. th e volumes of tissue alteration were determined by adding the delineated areas. th e planned and pa ablation volumes were compared using the pearson correlation coeffi cient. results: th e d volumes of the ablation zones follow the planned lesions volumes with a pearson correlation index r= . with a slope of . ( figure ). th e focally planned ablations results in a volumetric smaller histopathological ablation zone than predicted whereas the extended ablations result in volumetric larger ablation. pa showed sharply demarcated fi brotic and necrotic areas with mild infl ammation. th e urethra was aff ected by the ire treatment in nine mp- . , figure . correlation of ablation volumes t -weighted mri and ceus with h&e pathology (pa) mp- . , figure . scatterplot of planned ablation zone volumes compared with volumes in histopathology patients were observed throughout the neurovascular bundle in thirteen prostates and extended beyond the prostatic capsule in twelve cases. conclusion: ) ire in prostates results in sharply demarcated lesions with fi brotic and necrotic features, but may damage essential structures as urethra, capsule and nerves. ) th e actual ablation zones on d-histopathology follow reasonably the planned ablation zones. ) focal ablation protocols lead to a smaller ablation zone than extended ablation protocols. therapeutic all patients treated at our institution with primary pca t - , n , m were included provided they did not present with a long history of adt. patients were stratifi ed into groups according to their psa nadir occurring between - weeks following hifu. group a (n= : nadir < . ng/ml), group b (n= : nadir > . - ng/ml ng/ml), group c (n= : nadir > ng/ml). th e primary endpoint of our analysis was the onset of any salvage therapy other than hifu. repeat hifu can be performed without undue additional morbidity and is standardly not considered as salvage therapy but rather an adjuvant to the index hifu. multivariate analysis was performed to determine what predicts onset of salvage therapy. results: at inclusion: . % of patients were t and . % were t . outcomes are summarized in table . conclusion: group a (nadir < . ) showed % salvage treatment free survival without adt; preoperative high gleason, high initial psa and "no turp" were negative predictive factors for outcome; % of the patients had nd hifu treatments in follow-up; in case of salvage therapy most patients opted for adt. metastasis-free survival of % at and % at years excludes turp in pca as potential metastasis-inducing factor. combined "turp and hifu" showed its oncological effi cacy, postponing / avoiding classical salvage therapies (rad/adt) and their potential side eff ects. laparoscopic radical prostatectomy (lrp): changing trends in practice introduction and objective: we audited our lrp outcomes in order to evaluate outcomes and how our practice has evolved over the years. we evaluate pathological and margin status outcomes and determine whether there has been a shift towards treatment of higher risk disease and the impact of this practice on margin status. a total of patients underwent lrp performed by one surgeon at our institution from june to september . we divided the cohort into early period from - (group , n= ) and - (group , n= ). results: mean age was yrs. mean preoperative psa ( . ) and gleason score (gs, ) did not diff er between groups. however, preoperative stage ≥t c increased from ( %) to ( %) for groups and respectively. postoperatively, diagnosis of gs ≥ increased from ( %) in group to ( %) in group . similarly, % of group was staged as pt compared to % of group . th ere were more extracapsular extension in group ( %) compared to group ( %). overall positive surgical margin (psm) rate was % (group , % vs. group , %). when stratifi ed according to pathological stage, psm was identifi ed in more men with pt ( %) compared to pt ( %). th e commonest site of psm was at the apex. seminal vesicle invasion rate was similar ( %). results: mean operation time and length of hospital stay for rarp and lrp were . ± . min and . ± . min, and . ± . days and . ± . days, respectively (p = . and p = . ). aft er cases, the mean operation time for rarp was similar to lrp (less than h). positive surgical margins in localized cancer were seen in . % and . % of cases in rarp an lrp, respectively (p = . ). at postoperative months, sexual intercourse was reported in % and %, and pad-free continence in % and % in patients with rarp and lrp, respectively (p = . and p = . ). conclusion: previous large-volume experience of lrps may shorten the learning curve for rarp in terms of oncological outcome. additionally, previous experience with laparoscopy may improve the functional outcomes of rarp. introduction and objective: signifi cant prostate cancer is increasingly diagnosed in younger men. th is patient group has high expectations regarding oncological and functional outcomes at robotic radical prostatectomy (rarp). we reviewed a prospective database ( rarps) at a single tertiary referral centre and obtained erectile dysfunction rates/treatment and continence pre-and post-operatively, positive margins, metastases and death. median follow-up was years. male sprague-dawley rat aged weeks were used. a total of rats were divided into two groups. one group was used as a control and other group received intramuscular injections of testosterone propionate ( mg/kg) plus β-estradiol ( . mg/kg) for weeks to induce bph. th e prostate and genitourinary organ weights, histopathologic change and serum hormones were evaluated. we compared the eff ects of ldd ( mg/kg) with tamsulosin ( μg/kg) in intraurethral pressure responses induced by es of the hypogastric nerves. we performed western blotting for alpha a and d receptor of adrenergic nerve. results: bph-induced rats showed signifi cantly increased absolute prostate weight and prostatic index (prostate weight/body weight x ), increased testosterone, free testosterone and estradiol levels in the serum. histomorphology also showed that epithelial cell layers in the prostates of bph-induced rats were larger than control groups. ldd and tamsulosin signifi cantly inhibited the intraurethral pressure elevation induced by es of the hypogastric nerves. alpha d and alpha a adrenergic receptors in bph rat model were expressed more than control. ldd decreased expression of alpha d adrenergic receptor than control. conclusions: th is study suggested that ldd could be an alternative medicine to treat bph inducing lower urinary tract symptoms. does according to recent studies, atherosclerosis has a key role in the pathogenesis of bph. th erefore, we evaluate the correlation between prostate volume and intima-media thickness (imt) of carotid artery in diabetic bph. from january to august , patients with dm were analyzed, retrospectively. baseline characteristics and diabetic profi le were collected. mean intima-media thicknesses (imt) were collected using carotid doppler ultrasound. and prostate volume (pv) was measured by transrectal ultrasound. two groups were analyzed using lineal regression analysis. results: th e patients were classifi ed into group (n= , . %) and into group (n= , . %) based on the presence of bph. th ere were statistically signifi cant diff erences on bmi, waist circumference and hba c between the two groups (table ) . th ere is a signifi cant correlations between imt and pv and imt and transition zone (tz) (p= . , p= . , figure ). porting symptoms listed on the otc label as reasons for not using the product; traces of glucose, leukocyte, and/or blood in their urine; or an aua-si score ≥ . conclusion: pvp has demonstrated acceptable complication rates compared to traditional turp in treating bph in a cohort of men having a greater frequency of comorbidities and in those having to remain on oral anticoagulation. th is makes pvp an attractive alternative to turp in such men particularly if symptomatic relief and re-treatment rate in the longer term is demonstrated to be equivalent. prospective study of high-risk patients undergoing photovaporisation of prostate (pvp) without cessation of oral anticoagulants ow d , papa n , sengupta s , , lawrentschuk n , , , bolton d introduction and objective: greenlight laser photovaporisation of the prostate (pvp) is suggested to be safe to perform on high risk patients requiring surgical intervention in the management of benign prostatic hyperplasia (bph), where cessation of oral anticoagulation is not possible due to medical comorbidities. we prospectively evaluated the outcomes of patients who underwent pvp with ongoing oral anticoagulant therapy. materials and methods: between january and december , patients with ongoing oral anticoagulant therapy were treated with pvp. types of oral anticoagulants were recorded and perioperative outcomes were collected. th ese metrics included transfusion rate, duration of hospital stay and laser treatment variables. ninety-day readmissions also were recorded as were complications of treatment. results: sixty-two patients were treated by greenlight laser pvp while taking oral anticoagulants. out of this total, patients ( . %) were on warfarin while ( . %) had ongoing clopidogrel. th e remaining were either taking one or a combination of other (non-asprin) oral anticoagulants. nine out of ( . %) patients required readmission post pvp, and all of these readmissions were for management of complications related to haematuria. five of this group of patients ( . % of total cohort) had undergone pvp without cessation of warfarin, while of patients ( . % of total cohort) had undergone treatment without cessation of clopidogrel. th ree patients ( . %) required blood transfusion. conclusions: despite continuation of oral anticoagulants in these high risk patients, the readmission rate is low and transfusion rate is similar to what has previously been reported for conventional turp in patients without anticoagulation. greenlight laser pvp is a viable option for surgical management of bph in patients for whom cessation of oral anticoagulant therapy is contraindicated. introduction and objective: cystinuria is a rare, chronic condition characterised by recurrent urolithiasis. th e condition is due to a variety of genetic mutations in an amino acid transporter and accounts for between . - percent of urinary tract stones. cystine urolithiasis may be treated by preventative medical therapy or therapeutic urological intervention. it is the authors' experience that patients tend to shy away from long-term medical treatment, possibly due to a perceived lack of effi cacy or poorly tolerated side-eff ects. as with all chronic conditions, quality of life for cystinuric patients is expected to be diminished. sub-optimal medical therapy and the need for repeated urological intervention is expected to have a further impact on quality of life. th e authors seek to describe the natural history and quality of life in patients with cystine urolithiasis. th is in turn allows further improvements to the standard-of-care off ered to such patients. a cohort study was carried out involving participants recruited from a single surgeon's case mix. participants suff ering from cystinuria and related urolithiasis were invited to complete a questionnaire involving demographic information, use of medical treatment, surgical interventions and the sf- quality of life survey. attitudes towards the use of current and potential future medical treatments were also explored. results: fourteen participants completed the survey. th e sf- survey showed lower quality of life than the general public in of domains. th e mean interventional rate in patients with cystinuria was . procedures per patient. most patients reported previ-ous use of d-penicillamine and urinary alkalinisation medications, with most ceasing due to side-eff ects or lack of perceived effi cacy. conclusion: cystinuria is associated with a high rate of surgical intervention and lower quality of life than the general public. individuals with this condition report that medical management is either ineff ective or poorly tolerated. th ere is a need for further improvements in medical management of cystinuria, to reduce the rate of operative intervention. recommendations to guide clinical practice, based on patients' experience of cystinuria management can be made. dipstick results: a total patients were retrospectively reviewed for the ph results. th e mean diff erence in ph between spot urine value and the -hr collection values was . ± . ph. higher ph was associated with lower accuracy (p < . ). th e accuracy of spot urine samples to predict -hour ph values of < . was . %, . % for . to . and % for > . . samples taken more than days apart had only % the accuracy of more recent samples (p < . ). th e overall accuracy is lower than % (p < . ). infl uence of diurnal variation was not signifi cant (p = . ). conclusions: spot urine ph by dipstick is not an accurate method for evaluation of the patients with urolithiasis. patients with alkaline urine are more prone to error with reliance on spot urine ph. relationship is the fi rst lithotripter on the market with a unique design that allows for a dual focus system with the option of either a narrow or wide focal zone. ex vivo data on the slk-f lithotripter shows that the disintegration capacity and the renal vascular injury are independent of the focal diameter of the sw generator at the same peak positive pressure and disintegration power. th e objective of this study is to compare the single-treatment success rates of narrow and wide focal zones for the shock wave lithotripsy of renal stones. a total of patients with previously untreated radio-opaque solitary stone located within the renal collecting system, measuring at least mm, were randomized to receive narrow or wide focus lithotripsy while maintaining a constant overall energy level. patients were followed with kub x-rays and renal ultrasound at and weeks post lithotripsy to assess stone area and stone free status. urinary markers indicating the degree of renal cellular damage (microalbulin and beta microglobulin) were measured pre and post swl, hours post swl and days post-treatment. primary outcome was success rate, defi ned as stone-free or adequate fragmentation (sand and asymptomatic fragments <= mm) at months post-treatment. mp- . , figure . introduction and objective: despite being uncommon, infantile kidney stone remains a major health problem due to its higher recurrence rate and morbidity. th e parents usually notice that their infants have recurrent fever and failure to thrive of unknown origin. th ose patients comprise a big challenge for the urologist in management. th erefore, this study aimed to evaluate the outcome of shockwave lithotripsy (swl) in management of renal stones in infants. a retrospective analysis of prospectively collected data performed between january and december for infants underwent swl for single radio-opaque renal stones ≤ mm at a single stone center. swl was performed with dorneir s lithotripter with a maximum of shocks per session. a single session was indicated for each infant, but a second session was performed when satisfactory disintegration was not achieved. follow-up based on urinalysis, urine culture and sensitivity, plain x-ray kidney ureter bladder (kub) and abdominal ultrasonography (us) was carried out weeks post swl and monthly for successive months. multislice computed tomography (msct) was performed -months post-swl to confi rm the stone-free status. results: a total of infants, less than months of age were enrolled in this research. swl success was defi ned as absence of any residual fragments on msct months aft er the last session. stone free rate was . % aft er the fi rst swl session and reached % aft er the second session. rate of retreatment with second session of swl was . %. urinary tract infection (uti) was detected in . %, transient renal obstruction with low grade fever in . % of infants and no major complication had been recorded. conclusion: th e new generation of swl technology with a precise focal area seems to be safe and eff ective in management of kidney calculi in infants. stone introduction and objective: th e incidence of abdominal discomfort is frequent during pregnancy, but renal colic is infrequent. one of the main causes of renal colic during pregnancy is urolithiasis. managements of urolithiasis during pregnancy are hydration, antibiotics, ureteral stent insertion, percutaneous nephrostomy, and ureteroscopic stone removal. in this study, we assessed the reliability and stability of ureteral stent insertion to pregnant patients with renal colic. results: th e overall mean patient age ( years), male to female ratio ( . : ) and mean asa score ( . ) did not vary signifi cantly between years. admissions for elective renal stone procedures, adjusted for population, increased % over the study period. th is growth was entirely in the last years, corresponding with a -fold increase in the use of pyeloscopy (from to cases per year). from the fi rst to last year, there was a % reduction in eswl (from to cases per year) and a % increase in pcnl (from to cases per year). nephrolithotomy ranged from to cases per year. th ere has been an increase in the proportion of associated ureteric stent insertions from % to %. th e proportion of day-only admissions has decreased from % to %. th e average government assigned cost per admission has increased %. conclusion: victorian public hospitals have seen a rapid expansion in the use of pyeloscopy and laser for treatment of renal stones. th is corresponds with a signifi cant increase in admissions for elective renal stone treatment, relatively fewer day-case admissions, higher treatment costs and more associated stent isertions. introduction and objective: th is retrospective study assessed the semirigid ureteroscopy approach coupled with ballistic or ho:yag laser lithotripsy for the treatment of proximal ureteral stones. patients with a single lower calyceal stone with an evidence of a ct diameter between and cm were enrolled in this multicentric study. exclusion criteria were the presence of coagulation impairments, age less than or more than , presence of acute infection, presence of cardiovascular or pulmonary comorbidities. patients were randomized into three groups: group a: patients treated with swl; group b: patients treated with rirs; group c: patients treated with pcnl. patients were controlled with abdomen x-ray and ct scan aft er months. a negative x-ray or an asymptomatic patient with stone fragments less than mm big and a negative urinary colture were the criteria to assess the stone-free status. a statistical analysis was carried out to assess patients' data, success and complications rates, re-treatment rate and need for auxiliary treatment. radiotherapy is an eff ective and common treatment for the prostate cancer. however, there is still an historic deep rooted fear of its use due to the existence of late genitourinary toxicities such as the radiation cystitis. nowadays these toxicities may pose less of a threat due to the use of newer radiotherapy techniques and the reduction of radiation doses applied to the tissues adjacent to the tumor. th e objective of our study is to fi nd predictive factors and determine the cumulative incidence of overall and severe radiation cystitis. conclusion: radiation cystitis is a feared complication of the use of radiation therapy in prostate cancer which occurs infrequently, and the severe cases requiring hospitalization are very rare. th e characteristics of the tumor, purpose of radiotherapy used or radiation dose applied do not seem to infl uence the incidence of radiation cystitis. introduction and objective: th e aim of the study was to assess prognostic factors of biochemical and radiological disease progression (dp) in subgroup of lymph node (ln) positive prostate cancer (pc) pts. evaluation of detection rate of ga-psma pet/ct for biochemical recurrence after radical prostatectomy introduction and objective: prostate specifi c membrane antigen (psma) is overexpressed in more than % of all prostate cancers (pca). since the introduction of pet-imaging with gallium-labelled psma, this method is regarded as a signifi cant step forward in the diagnosis for recurrent pca. from the patients that were scanned for detection of recurrent pca aft er radical prostatectomy between august and december , were evaluable for retrospective analysis. patients underwent pet/ct aft er injection with the ga-hbed-psma. th e potential infl uence of psa-level, primary gleason score (gsc) and psa-doubling time (psa-dt) on the detection rate were evaluated. results: a total of ( %) patients had pathological fi ndings on the ga-psma pet/ct, with an average psa-level of . ng/ml (range . - ng/ ml). detection rates were %, %, % and % for psa-levels < . , . - , > - . and > . respectively. if recurrent pca was detected, oligometastatic disease ( metastasis or less) was most commonly seen ( %). th e detection effi cacy was signifi cantly infl uenced (p< . ) by higher gsc ( % and %, for gsc ≤ and ≥ respectively). for the patients that were evaluated for the infl uence of psa-dt on detection rate, no signifi cant diff erence was found (p= . ) for psa-dt < months and ≥ months (detection rate % and % respectively). conclusion: ga-psma pet/ct has a high detection rate compared to prior studies of conventional imaging modalities, especially in lower range psa-levels. further research is needed to determine to assess whether localization of small volume disease on ga-psma pet/ct can improve diagnostic algorithms and outcomes in patients with recurrent pca. introduction and objective: to assess long-term results of salvage pelvic lymph node dissection (plnd) in prostate cancer (pc) patients (pts) with biochemical recurrence aft er primary local treatment and confi rmed solitary lymph node (ln) metastases. results: a total of , abstracts were screened, full-text papers were considered, and articles were included ( rct, comparative studies, and case series). th is abstract focuses on the comparative studies. primary therapy was prostatectomy in , radiation therapy in , and studies included both therapies. diff erent defi nitions of recurrence were applied among mostly retrospective studies and the adt strategy oft en not specifi ed. factors associated with unfavorable outcomes (overall, pc-specifi c, or metastasis-free survival) included higher age, higher psa nadir, higher gleason score, higher psa-dt, and early start of adt at recurrence. contradictory results were reported on the role of the length of adt aft er ebrt, partly explained by a selection of high risk cases. most patients with disease relapse aft er primary therapy seem not to benefi t from adt while side eff ects are known to be harmful. selected highrisk patients (short psa doubling time, high gleason score) however may have benefi t, and early start of adt may be preferable in this group. an intermittent adt strategy in this setting may be feasible. a rct is indicated, although diffi cult to perform. a personalized approach is warranted, taking disease characteristics, side eff ects, and quality of life into account. adt may only be given in patients with pc recurrence who have high risk characteristics. introduction and objective: locally radio-recurrent prostate cancer (rr-pca) can off er a chance of cure albeit with potential morbidities. current salvage treatment options include radical surgery and minimally-invasive ablative modalities such as hifu and cryosurgery (s-cryo). current data suggests that s-cryo can achieve disease-free survival (dfs) rates up to % at years. however, the majority of data is based on retrospective analysis with mid-term follow-up and there is still paucity of data on longterm outcomes. th e aim of this study was to analyze morbidity and oncological outcomes, with median follow-up years, of s-cryo on rr-pca patients at an academic center. figure ). adverse events were similar between the treatment arms. figure . th ese analyses demonstrates that, during the fi rst year of treatment, men treated with degarelix had a reduced risk of disease-related adverse events. th ere was also a lower risk of death, likely due to the higher incidence of cv events in lhrh agonist patients. introduction and objective: androgen-deprivation therapy (adt) appears to increase cardiovascular (cv) morbidity and mortality in men with prostate cancer, particularly in those with a history of cv disease (cvd). however, the risk is lower with the gonadotropin-releasing hormone (gnrh) antagonist, degarelix, compared with lhrh agonists. here we evaluate regional diff erences in baseline cv status in men with prostate cancer treated with degarelix or lhrh agonists and their subsequent risk of cv events. th is was a pooled analysis of data from three phase studies with a duration > months. individual patient level data on baseline cv status and subsequent cv events over year were summarized by geographic region (usa/canada vs. europe). cv event data were compared using cumulative incidence functions (with all-cause mortality as the competing risk) and cox regression analyses. canada had more severe disease and a higher cv risk (p< . ) ( table ). in men with baseline cvd, cumulative incidence ( % ci) of a cv event was . ( . - . ) in usa/canada vs. . ( . - . ) in europe (p= . ). at baseline, cv status was similar in the degarelix and lhrh agonist groups (table ) . however, in those with baseline cvd, degarelix was associated with a lower risk of subsequent cv events vs. lhrh agonists in both regions (hazard ratio [ % ci]: . [ . - . ]; p= . ). conclusions: men in the usa/canada with prostate cancer and cvd and who were treated with adt were more likely to experience a cv event than their counterparts in europe. th is likely refl ects the greater severity of baseline cvd and higher cv risk in these patients. degarelix reduced the risk of cv events compared with lhrh agonists in both regions. introduction and objective: androgendeprivation therapy (adt) decreases bone mineral density and may increase skeletal complications in metastatic prostate cancer. however, lhrh agonists and gnrh antagonists have diff erential eff ects on follicle-stimulating hormone (fsh), which regulates bone resorption. th e current analysis compared the eff ect of lhrh agonists and the gnrh antagonist, degarelix, on serum alkaline phosphatase (salp), a marker of bone turnover, and the incidence of skeletal adverse events (aes). conclusions: degarelix suppressed s-alp more quickly and for longer than lhrh agonists. it also reduced bone pain and was associated with a lower incidence of fractures. collectively, these data indicate that degarelix provides better control of skeletal disease in men with metastatic prostate cancer, an eff ect that may be mediated by its diff erential eff ect on fsh. prognostic introduction and objective: testosterone (t) regulates nitric oxide synthase and is necessary to achieve an optimum response to pde inhibitors for erectile dysfunction. recently, tadalafi l was found to be eff ective for treating lower urinary tract symptoms (luts) secondary to benign prostatic hyperplasia (bph). we studied the relative importance of the t level in patients with luts and determined whether the t level predicts the response to tadalafi l mg once daily for luts/bph. aft er a -week washout period, men older than years without (n= , t level ≥ ng/dl) and with (n= , t level < ng/dl) hypogonadism were given tadalafi l mg once daily for weeks. we assessed its impact and the severity of luts/bph using the international prostate symptom score (ipss) and bph impact index (bii) and ipss quality-of-life (ipss-qol) subscores. safety was assessed using treatment-emergent adverse events. introduction and objective: diabetes has been reported as a major cause in patients who complain of erectile dysfunction and is frequent in the comorbidity of severe erectile dysfunction. also, patients with diabetes are oft en poor response to treatment for erectile dysfunction. in such patients, according to the mirodenafi l (mvix ) use of the odf (oral decomposition fi lm) mg and mg was to compare the therapeutic eff ects of the treatment period. of the patients with erectile dysfunction were enrolled in a patient with diabetes. and the patients were classifi ed into two groups by randomized double blind controlled trial. th e fi rst group was to take the mirodenafi l odf mg once a daily and the second group was to take a mg at least twice one week, depending on the need to have sexual intercourse. international index of erectile function- (iief- ), international prostate symptom score(ipss) were examined for each time of initial visit, weeks, weeks, weeks. th e questionnaire items of two groups were analyzed at each time point. total of patients were included in the study. th e patients who were taking once a daily were and the patients taking when needed were . th ere was no signifi cant diff erence between age, iief- score, and ipss of each groups on initial visit. ipss score and quality of life score was lowered gradually all aspects in the two groups. iief- score was a tendency to increase in all categories. in comparing the two groups at weeks, once a day group showed a signifi cantly higher score than the group taking when needed for the questionnaire of erection confi dence, erection times, iief- total score(p< . ). th ere was no diff erence between two groups at weeks, weeks. in addition, this study showed the similar therapeutic eff ect between the two groups at end point of continued treatment during the weeks. conclusion: aft er daily dose method weeks, at least twice weekly dosing method and daily dose method is determined to exhibit the same eff ect. th erefore, we think that it is possible to change the intermittent dosing from daily regimen aft er two months. introduction introduction and objective: phosphodiesterase inhibitors (pde i) are the established fi rst line therapy for most cases of erectile dysfunction(ed). it is estimated that - % of ed patients may drop out and discontinue the usage of these drugs. th is study aims to evaluate the patient perspective of discontinuation of on-demand tadalafi l mgm and switching to daily tadalafi l mgm for ed. th e study comprises men with median age years suff ering from ed of average . years duration. co-morbidities included: hypertension ( %), diabetes ( %), dyslipidemia ( %) and smoking ( %). th e primary indication for usage of on-demand tadalafi l mgm was ed. all the patients had used mgm tadalafi l on demand on more than occasions over the last months. results: th irty-eight out of men opted to discontinue on-demand mgm tadalafi l and switch to daily dose mgm tadalafi l. a detailed interview was conducted to identify the reasons for this switch over. th e salient factors were: ) unsatisfactory clinical response to on-demand dose ( %), ) adverse eff ects with on-demand dose ( %), ) concomitant improvement in luts ( %), ) economic factors-daily dose therapy is cheaper than on-demand ( %), ) freedom of spontaneous sexual activity with daily dose ( %), ) patient perception of daily dose as a long-term cure for ed ( %), ) combination of above factors ( %). overall % of patients planned to continue daily dose tadalafi l mgm. conclusion: daily dose tadalafi l mgm appears to be preferred by patients over on-demand mgm tadalafi l for ed treatment. and plateaued aft er two years. in % of men, iief-ef improved by category, in % by and in % by categories. five men remained within the same category despite slight improvements in score, man's score dropped from to changing from "no ed" to "mild ed". fift y six percent men achieved normal erectile function. conclusions: improvements in erectile function were clinically meaningful and signifi cant during the fi rst to years of t therapy and sustained during the full treatment duration. th ey were independent of obesity class. it may be necessary to continue t therapy for to years before an optimal response is achieved. hypogonadal conclusion: all changes were clinically meaningful and sustained for the full observation period, despite the fact that patients' age increased by years. t therapy seems to be highly eff ective in hypogonadal men with t dm, improving both erectile function and glycemic control. needle-free delivery of intracavernosal injections: proof of concept introduction and objective: intracavernosal injection is a well-established second line therapy for the treatment of erectile dysfunction (ed) and has shown very high success rates. despite this, intracavernosal injection is not a therapy suited to all patients for a number of reasons including needle phobia (trypanophobia), pain, and anxiety with self-needling. th e development of needle-free injectable devices has been heralded as a promising advance in the administration of certain vaccines and parenteral medications. initial research into the use of these devices in the delivery of intracavernosal injections however showed inferiority to needle-tipped injectors in terms of efficacy and pain scores. th e use of needle-free injection devices is not currently recognised for the administration of intracavernosal injections. it was the aim of our study to investigate the ability of contemporary needle-free injection devices to successfully deliver intracavernosal injections. two diff erent needle-free injection devices were used to inject . mls of methylene-blue solution into the corporal bodies of a number of australian brangus bullock penises; the bioject®ze-tajet™(spring-loaded fi ring system) and biojector® (pressurized co fi ring system) were used. both products are produced by bioject medical technologies inc., california, usa. all the available syringe depths were used for each device, and compared with the injection of the same volume of methylene-blue with an insulin syringe as a control. following injection, a cross-section of the penis was taken, and the depth of penetration observed macroscopically. results: despite the comparatively thicker and denser tunica albuginia of the bullock penis, the pressurized co device successfully delivered the solution into the corporal body, through the tunica. none of the syringes from the spring-loaded device penetrated the tunica. we have shown that contemporary needle-free injectable devices can in theory be used to administer intracavernosal injections successfully. th e bullock penis model may not be the ideal model for the human penis but we are currently in the process of performing human cadaveric experiments with these devices. needle-free injection devices may be very useful in the administration of intracavernosal injections in the future and extend the use of these therapies to a wider population of patients. penile linear shock wave therapy for poor responders to prior erectile dysfunction therapy ( ), ici with alprostadil ( ), vcd ( ) and muse ( ) . all these patients opted to discontinue these regimen due to unsatisfactory erectile improvement or side eff ects. th ese patients were treated with lswt by renova device with four weekly outpatient sessions without any analgesia or preparation. lswt was applied to four anatomical sites (right, left crura, and right, left corpus cavernosum) at shocks per minute, total shocks per session. patients were followed up at and months aft er the last session. results: at one month follow up statistically significant improvement in iief was recorded in patients ( %) from mean score of . at baseline to . .th e improvement was maintained at months .no side eff ect was noted. overall % patients expressed satisfaction with lswt irrespective of the clinical outcome. conclusion: lswt appears to be a safe and eff ective noninvasive, offi ce based therapy in the management of diffi cult to treat poor responders to prior treatment of ed. introduction and objective: hypogonadism and sexual dysfunction are common clinical presentation in male liver transplant candidate. th e aim of the study was to evaluate the eff ects of living donor liver transplantation (ldlt) on testosterone, sex hormone-binding globulin (shbg), free androgen index (fai) and erectile function in ldlt recipient. introduction and objective: penile size has been a source of major concern and anxiety to the male population since several years. diff erent methods for increasing penile size have been described in the literature, such as, pubopelvic liposuction, lipectomy, suspensory ligament dissection, z-plasty, v-yplasty and injections. combining some of these techniques may be more eff ective to improve the length of the penis. in this study, patients were underwent the combination of z-plasty and suprapubic lipectomy for increasing penile size. between and , patients who complained decreased penile size were underwent surgery. z plasty and suprapubic lipectomy were performed to each patient. informed consent was provided by all participants. th e outcomes were assessed based on the preoperative and postoperative penile length in the fl accid state at maximal stretch and patient-partner satisfaction. th e paired student t test was used for statistical analysis. results: median age of the patients was . ( - ) years. th e etiologies were congenital micropenis in ( %), concealed penis in ( %), previous penile surgery in ( %) and epispadias in ( %) patient. mean preoperative and postoperative penile lengths were . cm ( - cm) and . cm ( . - cm) respectively. th e mean increase in stretched penile length was . ± . cm (minimum . cm, maximum cm) (p< . ). th e patient and partner satisfaction rates were . % ( / ) and . % ( / ) respectively. only one postoperative complication was detected. th is was a wound infection at suprapubic incision site. conclusions: based on our results, the combining of the penoscrotal z-plasty and suprapubic lipectomy is a safety, eff ective and satisfactory procedure for lengthening of the penis in selected cases. corporal lengthening with infl atable penile implants : - ( ) ). recently, we have developed a new technique that combines key aspects of these approaches to create a minimally invasive, no-touch ("mint") technique for penile prosthesis insertion. we theorized that the mint technique would take advantage of the benefi ts that each of these established approaches off ered and therefore our aims were to assess feasibility, safety, post-operative hematoma and infection rate and percentage of patients cycling the prosthesis by weeks. th e principles of the mint technique involve a small infrapubic incision approach combined with a no-touch technique facilitated by using standard surgical drapes ( x clear non-adhesive drape and x ioban® drape) and an alexis® wound retractor. we present results for our fi rst consecutive patients undergoing primary prosthesis implantation from may -july with at least months follow-up. patients having revision surgery, or with complex surgery necessitating > incision were excluded. data was collected using a prospective database. results: average age (±sd) was . (± . ) years. median follow-up was . months. patients had one or more of the following etiologies for erectile dysfunction: vascular disease (n= ), post-radical prostatectomy (n= ), diabetes (n= ), peyronies disease (n= ), venous leak (n= ) and priapism fi brosis (n= ). seventy percent had used intracavernosal injections. implant used: coloplast titan (n= ), american medical systems (lgx; n = ), (cx; n = ). th e average (±sd) cylinder and rear tip extender length was . (± . ) and . (± . ) cms respectively. all operations were completed successfully and there were no peri-operative complications necessitating intervention or re-operation. th ere were post-operative hematomas (treated conservatively). sixty-fi ve percent could cycle prosthesis by weeks. th ere were no post-operative infections. conclusion: th e mint technique for penile implant surgery is a safe and feasible procedure with a zero infection rate in our fi rst patients. effi cacy and safety of botulinum th e initial number of patients to be recruited were twenty-six, but actual patient enrolment was eleven (six control and fi ve botulinum toxin a). all of the patients had a history of vulvar pain for more than six months despite proper medical treatments. patients were randomly assigned to two groups: control -saline injection, toxin -botulinum toxin a (meditoxin® injection, meditox, inc., korea). in both groups, areas of pain were mapped on the vestibule and injections were performed at fi ve sites to cover the entire painful area. th e dosage of each injection was - ml with a maximum cumulative total of ml. at baseline, two, four, and eight weeks aft er the injection, visual analogue scale (vas) and sf- questionnaires were scored. data was analyzed and p value was considered to be signifi cant at < . according to the mann-whitney test. results: th e mean age of patients was . ( - ) years old in the control group and . ( - ) years old in the toxin group. aft er breaking of the blinding, two of the toxin group had iu of botulinum injection, and the others had iu injections. two patients from the control group dropped out because of aggravated pain. th eir vas were and respectively at their drop-out point (baseline and , respectively). at week eight, vas was signifi cantly decreased in toxin group when compared with baseline (table ) . th ere were no drug related adverse reactions. introduction and objective: congenital anomalies of uro-genital system have increased globally as a consequence of higher maternal age at pregnancy and developments in assisted reproductive techniques in the last few decades. aim of the study was to determine the incidence of apparent congenital uro-genital anomalies in north indian newborns and factors associated with them. a prospective study was conducted to collect data of all newborns delivered at our institute between september and august . th e predetermined format included newborn's birth weight and gestational age, maternal age, parity and infertility treatment if any. newborns weighing less than gm or born before weeks of gestation were excluded from the study. results: th ere were , deliveries with , males and females. a total of apparent uro-genital congenital anomalies were recorded with an incidence of . per newborns. th e most common anomaly was cryptorchidism found in newborns, amongst others hypospadias was noted in , ambiguous genitalia in , congenital hernia/hydrocele in , exstrophy-epispadias complex in and prune belly syndrome in newborn. newborns weighing less than , grams had a higher proportion of anomalies ( . %) in comparison to those weighing over , grams having . % (p = . ). maternal age (> yrs), parity (> ) and infertility treatment were recorded in . %, . % and . % respectively and all were independently associated with increased risk of uro-genital anomalies (p= . ). conclusions: incidence of apparent congenital uro-genital anomalies was . %. infertility treatment, parity (> ) and maternal age (> years) were independently associated with increased risk of congenital uro-genital anomalies. comparison conclusions: double-breasting spongioplasty is very good method to decrease complications in hypospadias repair, so it is recommended an as interposing tissue in tipu. advantages of the double breasting spongioplasty are that avoiding of suture line and adding two layers of spongiosum over neourethra decreases the chances of urethral fi stula and gives cylindrical shape to neo-urethra. use stretched penile length (spl) is the standard measurement used in reconstructive penile surgery (rps), but is associated with high inter-rater variability, and is seldom reported. furthermore, ruler-based measurements require that all measurements be made intraoperatively; post-hoc measurements are diffi cult to impossible. we used a novel smartphone application to assess the correlation of post-op digital-photo based length measurements to intra-operative ruler measurements. th congress of the sociÉtÉ internationale d'urologie -siu abstract book materials and methods: intra-operative spl was measured in a consecutive series of pediatric patients undergoing rps who agreed to participate in this study. spl was measured intra-operatively (spl-io), and a picture was taken, with the ruler and from a true lateral view, as proof. a second digital picture was taken at the same time, with a reference object (obj) (object whose dimensions are known and constant). post-op, spl was later measured using the medmeasure! app for iphone and ios android, using the picture with obj, by two diff erent surgeons blinded to intra-op measurements. th e three diff erent measurements (intra-op spl (spl-io), and post-op using the app (spl-s -spl-s ) were then compared to assess overall correlation and correlation to ruler measurements using spss . statistical soft ware package. results: twenty consecutive patients underwent surgery for hypospadias (n= ), buried penis (n= ), epispadias (n= ) and circumcision accident (n= ). median age at surgery was months [ - ]. median penile spl-io was . cm [ . - . ]. when ruler-based measurements (spl-io) and app-photo based measurements were treated as independent measurements (students t test), there was no statistical diff erence between any of the three groups (p . - . ). even with spl-io measurements were treated as the gold standard, by bland-altman limits of agreement analysis, the correlation factor of spl-ip to spl-s & spl-s was > %. conclusions: when compared with intraoperative measurements, digital measurements using medmeasure! are reliable and precise, provided that the picture is taken from a true anterior-posterior or lateral view. because measurements are made based on captured images, a limitless number of length measurements (within the same plane as the reference object) can be made post-hoc. use of digital photography and this smartphone app has the potential to aid in surgical planning, improve documentation, and, facilitate clinical research. aseel's technique for distal penile and coronal hypospadius repair (simple, easy with less complications) introduction and objective: th is technique is modification of the old operation of arab that makes it very simple, easy to learn and even in cases of failure there will be no problem of redoing it or other operation because of the minimal tissue dissection. th is technique was applied in patients. first a transverse ventral incision is done parallel to the circumcision incision and cm proximal to the urethral meatus, figure ( ) . th en proximal and distal skin dissection is done, figure ( ). a longitudinal incision across the urethra plate extending through the meatus is done, figure ( ) and closed transversely that leads to urethral advancement, figure ( ). th en aided by skin hooks the distal skin edge is pulled downwards to create a roof for the advanced urethra, figure ( ) followed by closure of the skin incision, no catheter or stent is left , figure ( ). th is is a -minute operation and the patient is discharged as a day case. results: th irty-eight patients passed without complications and had loss of the skin stitches either partial in cases or complete in cases that were repaired by reapplication of the stitches, no meatal stenosis or fi stula were reported. th is is a very easy technique that can be applied as an outpatient or day case, and done in minutes, with no catheter or stent per urethra left or complications such as urethral meatus stenosis or fi stula formation. th e remained boys ( ) underwent transinguinal laparoscopy during ipsilateral herniorrhaphy. all data were collected prospectively. results: th e incidence of cppv confi rmed by transinguinal laparoscopy was . % ( / ). th e width of hernia sac and mother's age at birth were signifi cant risk factors in the univariate analysis. however, in the multivariate analysis the width of hernia (> cm) sac was only an independent risk factor for cppv (odds ratio . ; p= . ). th e laterality, type of hernia, age, preterm, low birth weight, twin, blood type, father's and mother's age at birth, and the type of delivery were insignifi cant. in this study the width of hernia sac was the independent risk factor for cppv. th is result suggests that the transinguinal laparoscopic examination is benefi cial for the detection of cppv in boys with this risk factor. however, it should be considered in the clinical practice that the one-third of boys with cppv has a narrowed width of hernia sac (< cm). low introduction and objective: traditionally bladder exstrophy complex is managed by staged repair, however now there is trend towards single stage repair. to achieve a satisfactory level of continence, secure abdominal wall closure and preservation of renal functions in patients with bladder exstrophy remains an elusive goal. objective of the study was to assess continence and functional outcome of single stage repair pediatric and adults. materials and methods: th irteen patients, boys and girls with classic bladder exstrophy were treated from to . aft er proper evaluation patients under went complete primary repair of exstrophy repair (ureteric re-implantation, bladder closure with or without cystoplasty, iliac osteotomy, neck reconstruction and epispadias repair). bladder and urethral plate was mobilized as single unit and bladder closure was done to create an adequate capacity bladder. epispadias repair was done by separating the two corpora; tubularization of urethral plate and ventral transposition of neo-urethra to create an orthotopic neomeatus. th en bilateral anterior iliac osteotomies were performed and external fi xators were applied to approximate the pubic symphysis which helps in sphincteroplasty. bladder neck was reconstructed using young dees technique and placed deep within the pelvis; sphincteroplasty was done followed by abdominal wall closure. voiding cysto-urethrography was obtained at months and at one year. continence was defi ned as dry intervals of hours or more. patients were followed-up at , , , months and annually. results: age of patients varied from days to years (mean . years). pre-operative symphyseal gap varied between - cm and post operatively the average diastasis was . cm with the range of cm to cm. in a follow-up period was months to years, patients had good results ( girl and boys) minor supra-pubic leak was present in patients which was managed conservatively, all being able to hold urine for - hours with no leaking at night. colo-cystoplasty was needed in cases with small bladder plate. overall continence rate was . % in single stage. two male incontinent patients were continent aft er second surgery. conclusions: single stage complete bladder exstrophy repair is safe and viable option for both pediatric and adult cases. augmentation enterocystoplasty is required in small bladder capacity cases. anterior iliac osteotomy with approximation of pubic symphysis improves continence and allows tension free closure of abdominal wall and sphincter. long wilms tumor (wt) represents approximately six to seven percent of all pediatric cancers and accounts for more than percent of all tumors of the kidney in the pediatric age group. recently some centers have explored the role of nephron sparing procedures in children with unilateral wilms tumors because of the concern about late occurrence of renal dysfunction aft er unilateral nephrectomy. we assessed the long-term renal functional outcome aft er parenchymal-sparing procedure for non-syndromic unilateral wilms tumor at our center. we retrospectively reviewed the records of all children with unilateral wilms tumor who had undergone nephron sparing surgery at our center. patient's long-term renal function, tumor recurrence, and survival, were determined from a review of each patient's medical record. results: a total of eight patients underwent partial nephrectomy (pn) and the remaining three with polar tumors underwent hemi-nephrectomy (hn) following chemotherapy. smaller tumor volumes were associated with not only preservation of renal function but also increase in egfr during the follow-up period. th e median preoperative egfr was ± . and median egfr at the last follow-up was . ± . . in properly selected children with non-syndromic unilateral wilms tumor, nephron sparing surgery provides excellent renal function preservation. introduction introduction and objective: hyperbaric oxygen (hbo) therapy, which increases the amount of oxygen dissolved in the blood and that carried to tissues, is used in the treatment of several disorders. hbo therapy may be a useful adjunctive treatment in the management of some of challenging conditions encountered in pediatric urology practice. in this paper, we report our experience on the use of hbo therapy in children with urologic problems. we reviewed our department's records to identify pediatric patients who received hbo therapy between and . all patients were evaluated at the department of underwater and hyperbaric medicine and informed consent was obtained from the patient or his parents. total number of hbo sessions was determined based on patient's clinical response to hbo therapy. results: eleven patients received hbo therapy during the study period. all of them were male. th e mean age was . ± . ( - years) . indications of hbo therapy were necrosis aft er hypospadias and epispadias repair, penile glans necrosis, circumcision caused penile skin necrosis, sickle cell crisis induced priapism, and testicular torsion. th e average number of hbo sessions was . ± . ( - ). nine patients ( %) healed aft er hbo therapy, but ( %) patients did not (table ) . . th e essential parameters of kegel exercise are duration of contraction and active relaxation, and, frequency of exercises. to date, exercise duration times could only be captured during in-clinic biofeedback. we hypothesized that a smartphone-based app that provides users biofeedback -and reports mean duration of contraction and relaxation, could help return to continence aft er rp. we designed/made a working prototype of such an app, and validated it. our novel app (ios) was programmed to allow users to record the duration of kegel active pfm contraction and relaxation. it also allows users to record urinary frequency, urgency, voiding, and leakage events, and number of pads used-on a daily basis. it contains a -q visual analog scale questionnaire that queries satisfaction (urinary, sexual, erectile), pain control, depression, sleep quality, and quality of life. data from the app can be "pushed" automatically by the user to a queryable custom database on a hipaa-secure server (ucsf). we provided the app to non-medical colleagues ( women/ men age - ) for evaluation. all completed mock kegel exercises using the app to measure contraction/relaxation duration, which were timed using a stopwatch. measured times were compared to duration times recorded in our database for each user. a -point likert scale was used to query the following items: ) user reported ease of use; ) privacy related anxiety related to use of such an app to submit study data wirelessly; and ) perceived usefulness of the app to improve kegel performance. results: th e pfm contraction and relaxation times recorded by the app within the wireless database disagreed with stop-watch measured duration times by mean +/-< second for all subjects. mean likert scores: . "overall ease of use" score = . (sd . ), "privacy related anxiety" score = . (sd . ), and "usefulness"= . (sd . ). conclusions: our novel smartphone app appears to allow users to accurately record key kegel exercise parameters: duration and progress. th e platform also allows collection of key patient data during daily life. a randomized controlled clinical study is warranted to further assess clinical utility, and, possible means to further enhance utility and research. safety and effi cacy of reduced dose of botulinum toxin-a for patients with detrusor overactivity place j, vyas l, watcyn-jones t, lupton b, miah s, darrad j, kumar v introduction and objective: th is prospective study was carried out to look at the response of a lower dose of botulinum toxin-a for treatment of symptoms of oab, its tolerability and side-eff ects. materials and methods: following due counselling and consenting, all newly diagnosed patients with confi rmed detrusor overactivity on uds (n= , with a mean age of . years (range= - )) were given iu of trigone-sparing, intra-detrusor botulinum toxin-a. of the total of patients, ( . %) were males and ( . %) were females. of this cohort, . % stopped anticholinergic medications because of lack of benefi t. th e rest ( . %) could not tolerate the side eff ects. th e procedure was performed in outpatient department using a fl exible cystoscope under local anaesthetic. th ese patients fi lled up a pre-treatment iciq-sf for oab as well as ui and follow-up scores at week , and . th e per-procedural pain score and follow-up urinary residual volumes were recorded. results: two ( . %) patients did not respond to the treatment at all. in the responders, average scores from the iciq-sf questionnaire fell from the pre-treatment level of . ( - ) to . ( - ) at week , . ( - ) at week and . ( - ) at week (p< . ). th e urgency incontinence scores fell from an average pre-treatment level of . ( - ) to . ( - ) at week follow-up. th e average daytime urinary frequency scores fell from . to . and nocturia scores fell from . to . . five patients went into urinary retention following intra-detrusor botulinum toxin-a injections. in the rest of the cohort, post void residuals remained largely unchanged with pre-procedure fi gure of . mls ( - ) to . mls ( - ) (p=ns). average pain score was . ( - ) on a scale of to . no symptomatic uti was found in post procedural patients. conclusions: th ese results albeit with a small number of cases, have suggested a signifi cant clinical response in over % patients with proven detrusor overactivity with a reduced dose of intra-detrusor botulinum toxin-a injections, thereby maintaining the clinical eff ectiveness of the drug and at the same time reducing the cost of delivery with possibly reduced incidence of urinary retention. prior to the initiation of intravesical onabotulinumtoxina treatment, all patients had an assessment of mid-stream urine for culture and sensitivity, renal tract ultrasound scan, subjective and objective assessments of symptoms (including iciq-ui and iciq-oab questionnaires) and conventional urodynamic study. all patients had proven overactive bladder. onabotulinumtoxina effi cacy and durability was assessed by subjective and objective assessments of symptoms. results: duration of effi cacy of onabotulinumtoxi-na injections is well maintained in the idoa group in comparison with noab group. th ese trends are shown in figure . four injections out of administered in total to the idoa group were unsuccessful ( . %) and brought no relief of symptoms to the patient. th ere were no unsuccessful treatments in the ndoa group ( / total injections administered). results: from the general practitioner's records, none of the non-traceable patients were on botulinum toxin-a treatment elsewhere. of the total number of traceable patients (n= ), ( %) stayed on mirabegron alone. of these % were satisfi ed ( / ). as a whole . % ( / ) were satisfi ed and continued with mirabegron only. one patient moved to combined mirabegron with an anticholinergic. of the patients on mirabegron iciq-sf scores fell from . ( - ) to . ( - ) at months. eighteen of ( %) patients progressed requiring botulinum toxin a treatment. side-eff ects included-palpitations ( ), vomiting ( ), rashes ( ), lethargy ( ) and yellow urine ( ) . th is study showed that % of patient with refractory oab symptoms awaiting fi rst or subsequent treatment with intra-detrusor botulinum toxin a injections will respond to mirabegron and % of these responders ( . % of total) are able to come off botulinum toxin a at months, reducing the burden of the waiting list; with a cost reduction mirabegron= £ vs cost of botulinum toxin a= £ /year/patient. th is is a small study but provides a medium-term option for patients on long waiting list for botulinum toxin a thereby helping to limit use of botulinum toxin-a for patients with detrusor overactivity. introduction and objective: patients that fail to achieve symptom improvements with sacral neuromodulation (snm) may benefi t from increased aff erent stimulation via tined lead placement at the pudendal nerve. we evaluated −year outcomes of chronic pudendal neuromodulation (cpn) in patients that had failed sacral neuromodulation (snm). adults enrolled in our prospective observational neuromodulation study that had a pudendal lead placed were evaluated. medical records were reviewed. outcomes were measured at , , and months with interstitial cystitis symptom/problem indices (icsi−pi), overactive bladder questionnaire (oabq) symptom severity (ss) and quality of life (qol), voiding diaries, and global response assessments (gra analysis of voiding dysfunction after transobturator tape procedure for stress urinary incontinence introduction and objective: voiding dysfunction is common complication of midurethral sling surgery (mus) for stress urinary incontinence. however, the defi nition of post-mus voiding dysfunction is inconsistent in the literature. subjective feeling of slow stream, signifi cant postvoid residual (pvr), additional procedure for bladder emptying, or objective fl ow rates can be a yardstick of voiding dysfunction. in this study we retrospectively investigated the risk factors for post transobturator tape procedure (tot) voiding dysfunction applying various defi nitions in one cohort. four hundred fi ft een patients were evaluated who underwent tot. preoperative urodynamic study were performed and urofl owmetry and international prostate symptom score questionnaire were investigated pre and post-operatively. several postoperatively parameters representing voiding dysfunction were adopted for analysis. acute urinary retention requiring catheterization (aur), subjective feeling of voiding diffi culty during follow-up (vd), and signifi cant postoperative pvr greater than ml or more than % of voided volume (pvr) were adopted for categorization of the defi nition of voiding dysfunction. results: sixteen patients ( . %) required catheterization, ( . %) experienced post-operative voiding diffi culty, ( . %) and ( . %) showed low fl ow rate and signifi cant pvr. in the aur and vd category, concomitant co-operation and general anesthesia were signifi cant parameters, especially anteroposterior repair of vagina. older and menopaused patients complained subjective voiding diffi culty. th e patients in vd category showed lower fl ow rates and larger pvrs. patients in pvr category had old age and low preoperative fl ow rates. th e patients with vd tend to be prescribed alpha blocker during postoperative follow-up period. th ere were no signifi cant urodynamic parameters attributing for various voiding dysfunction categories. with logistic regression analysis aur, vd and pvr category had concomitant co-operation and preoperative retention history as risk factors. conclusion: several factors including preoperative voiding symptoms and intraoperative parameters such as co-operation may aff ect postoperative voiding dysfunction. th e diversity in clinical presentation underscores the importance of a high clinical suspicion with an appropriate diagnostic evaluation. subjective and objective voiding dysfunction should be evaluated aft er midurethral sling operation. introduction and objective: some have hypothesized that patients with lower functional bladder capacity (fbc) experience less improvement in symptoms after staged neuromodulation procedures. th erefore, we evaluated the impact of baseline fbc on generator implant rate and symptom changes. adults enrolled in our prospective observational neuromodulation study were evaluated. functional bladder capacity (fbc) was defi ned as average volume per void on day voiding diary. data were collected from medical records, and validated interstitial cystitis symptom/problem indices (icsi−pi) and overactive bladder questionnaire (oabq) symptom severity and health related quality of life (hrqol) domains, and examined with descriptive statistics, wilcoxon rank sum tests, logistic regression, and spearman correlation coeffi cients. results: of patients (mean age . ± . years; % female), most had urinary urgency/frequency with or without urge incontinence ( %) and a sacral lead placed ( %); % had the lead placed at the pudendal nerve. mean fbc at baseline was . ± . ml. among the , ( %) had ≥ % improvement in overall symptoms aft er lead placement with subsequent generator implant. baseline fbc was similar between implanted/not implanted patients (p= . ), however implanted patients had a median . % increase in fbc aft er lead placement compared to explanted patients whose fbc decreased by median . % (p= . ). logistic regression identifi ed a strong relationship between percent change in fbc aft er lead placement and generator implant (p= . ) but there was no relationship between baseline fbc (ml) and subsequent generator implant. at months, a lower pre-implant fbc weakly predicted a greater improvement in oab-q hrqol from baseline (p= . ; r = - . ). fbc (ml) at baseline, or percent change in fbc aft er lead placement, had no relationship with achieving at least % improvement in icsi−pi or oab−q symptom severity scores at months. conclusions: lower baseline fbc should not be a contraindication to neuromodulation since there was no impact on outcomes. improved fbc aft er lead placement may have contributed to overall improvements in symptoms leading to generator implant. improvement in fbc was equal to or greater than that seen in medical treatment trials for oab. introduction and objective: to present our preliminary experience with the sars (sacral anterior root stimulator) in spinal cord-injury patients with hyperactive bladder at our center. th e sars is an implantable electronic device that allows patients with spinal cord injury to assume voluntary control of micturition, defecation and erectile function. it involves a s -s dorsal (sensitive) rhizotomy and placement of electrodes around those roots, which are connected to a subcutaneous receiver antenna. by transcutaneous radiofrequency stimulation of that antenna the patient can selectively use stimulation programs to activate the diff erent functions: program for micturition, program for defecation and program for erection. results: between january and november nine sars implants (eight men and one woman) were performed in patients with spinal cord injury-related overactive bladder refractory to standard conservative treatment. average age was years and mean follow-up was months (range - ). bladder function: eight of the nine patients exhibit an increase of the bladder capacity and use the device - times daily, voiding - cc with ≤ cc residual urine. one of these patients showed de-novo postoperative stress incontinence due to sphincter incompetence that was solved with placement of a suburethral sling. th e ninth case had a poor compliance and low capacity bladder; despite sars, he failed to increase capacity and persisted incontinent so aft er months he underwent a continent urinary reservoir. voiding objectives were therefore achieved in / patients ( % success). defecation: all patients use the device once a day. erectile function: of the eight male patients, seven achieved erection with sars. however, this erection was not always reliable for intercourse; patients associate sildenafi l and eventually requested a penile prosthesis implantation. complications: th ere were no postoperative complications or failure of the internal components. one patient showed a transient s neurapraxia, which resolved spontaneously aft er months. conclusion: in selected spinal cord injury patients, sars is an excellent option for urinary and defecatory control, being also useful for erectile function in some of them. how to determine the complication rate of urolastic (vinyl dimethyl polydimethylsiloxane, pdms), a bulking agent for female stress urinary incontinence. twenty-eight females with stress urinary incontinence were treated with pdms. th e group mainly consisted of secondary patients (n= ), with extensive comorbidity. six patients had one previous surgical procedure for sui; nine underwent two procedures and ten received three or more interventions. an amount of . - . ml of pdms was injected at - positions paraurethrally at the midurethra. procedures were performed on the outpatient department, with local anaesthesia. th e clavien dindo score was determined aft er months, to assess the severity of the complications encountered. results: aft er six months, % ( / ) of the patients reported a % improvement, % ( / ) a - % improvement and % ( / ) a - % improvement, % ( / ) reported % improvement and % ( / ) was % improved. six patients ( %) had no improvement aft er six months, four of which had also not shown initial improvement. in one patient the implants were removed during surgery, so no follow-up was available. of twenty-eight patients treated, % ( / ) had no complications. in % ( / ) complications were seen, which were classifi ed following the clavien dindo-classifi cation. a score of i was appointed to % ( / ) of the patients. reasons were: implant-exposure, minor pain, anti-emetics use or de novo retention. th ree patients had a score of ii, because of more severe complaints of pain or urge. th ey were treated pharmacologically. in % ( / ) one or more implants were removed, mostly due to exposure, erosion or pain. removal under local anaesthesia was performed in % ( / ) of the patients and this resulted in a iiia-score. th ree patients ( %) had a iiib-score, which meant the implant(s) were removed under general anaesthesia. in the fi rst twenty-eight diffi cult to treat patients receiving pdms, in ten cases a clavien dindo grade ii-iiib is scored, mainly because of surgical removal of implants. in spite of the seemingly high complication rate, this remains a useful therapeutical option for female stress urinary incontinence. magnetic stimulation for stress urinary incontinence: a randomized, double-blind, sham-controlled trial introduction and objective: we conducted a multicenter, randomized, double-blind, sham-controlled trial to evaluate the effi cacy of magnetic stimulation (ms) for stress urinary incontinence (sui). a total of sui subjects were randomized : to active or sham ms for eight weeks (twice weekly). th e primary criterion for response was a reduction of points or more in the international consultation on incontinence questionnaire for urinary incontinence-short form (iciq-ui sf). th e secondary outcomes included objective (leakage of less than gram on -hour pad test) and subjective cure (a 'never' response to 'how oft en do you leak urine?), incontinence diary, pelvic fl oor muscle strength, urofl owmetry, patient global impression of improvement (pgi-i) and international consultation on incontinence questionnaire-lower urinary tract symptoms quality of life (iciq-lutsqol). results: using the primary criterion, ( . %) of subjects were treatment responders in the active group compared to ( . %) of subjects in the sham group (relative risk (rr) . , % ci . - . , p< . ). based on objective cure, ( . %) subjects in the active group were dry versus ( . %) subjects in the sham group (rr . , % ci . - . , p< . ). nineteen ( . %) in the active group and ( %) subjects in the sham group perceived themselves as dry (rr . , % ci . - . , p< . ). th e active group had greater reductions (p< . ) in incontinence frequency than the sham group. changes in pelvic fl oor muscle strength and urofl owmetry parameters were not statistically signifi cant between groups (p> . ). th irty-nine ( %) subjects in the active group reported signifi cant benefi ts (much/very much better) for pgi-i rating compared to ( . %) subjects in the sham group (p< . ). all item scores in iciq-lutsqol were not statistically diff erent (p> . ) except 'eff ect on friends' , 'smell' , feeling of embarrassment' and 'overall impact' in the active group. of all evaluable subjects, ( . %) of subjects in the active group and ( . %) of subjects in the sham group experienced adverse events (p= . ). conclusions: modifi ed tvt abbrevo is a simple, safe and eff ective procedure with comparable short-midterm cure rates to standard tvt abbrevo. th e modifi cations of avoiding the tunnelling device and groin exit helped to minimize the groin pain and analgesic requirements. evaluation of standard practice for artifi cial urinary sphincter implantation auckland dhb, auckland, new zealand; ucd medical center, sacramento, usa introduction and objective: th e artifi cial urinary sphincter (aus) has been available since and over this time it has established itself as the gold standard in management of post prostatectomy incontinence. th e successes, failures and diffi culties are well documented, however little is published regarding the standard implantation practice of the aus. our objective was to review the standard practice for implantation of the aus within a group of high volume implanters. aft er obtaining institutional review board ethical approval a web-based questionnaire was designed using survey monkey soft ware. an email was sent to the current members of the society of genitourinary reconstructive surgeons (gurs) explaining the aims of the confi dential questionnaire with a web link to the aforementioned questionnaire. all results were collected via survey monkey and were then analyzed. results: one hundred and twenty gurs members were contacted by email, members replied. th is group averaged aus placements a year (range to ). pre-operative assessment utilized routinely included pad weights in . %, pad numbers in . % and urodynamic studies in % of participants. additionally % of participants surveyed would routinely perform a cystoscopy in the pre-operative assessment ninety four percent of those surveyed used greater than one pre-operative antibiotic; most commonly gentamicin with either vancomycin or cefazolin. th e antibiotic most commonly utilized alone was levofl oxacin. post-operatively % continue antibiotics anywhere between hours and month, with % continuing intravenous antibiotics for a minimum of days. intra-operatively % have aus componentry prepared on a separate set up stand. th e single cuff aus, size . and . cm cuff were the most commonly placed cuff s, with the - cm reservoirs. radio-opaque contrast is used by % of participants in the aus reservoir. only % of participants would recommend a medical alert bracelet in the post-operative period, and % encourage pump traction. conclusion: despite a uniform technique recommended for the implantation of the aus by american medical systems in order to improve success and decrease complications, there is great heterogeneity in pre-operative assessment, surgical placement and post-operative management of the aus in a cohort of high volume implanters. patients presenting to a multi-disciplinary stone clinic were administered a survey. th ey were asked to elect a treatment modality from shock wave lithotripsy (swl), ureteroscopy (urs) or percutaneous nephrolithotomy (pcnl) for a hypothetical mm kidney stone. th e success rates ( % swl, % urs and % pcnl), morbidity and the risks associated with each treatment options were explained. patients were also to elect whether personal or doctors' decision of treatment is most preferred and the most important variable in deciding a choice of treatment modality. results: of the respondents with mean age . ± . , female/male ratio was : ( figure ). majority of the subjects ( %) elected urs as their treatment choice (table ) . previous experience with urs (p= . ) and pcnl (p= . ) impacted the choice of urs. th e respondents were equally distributed in their primary concern being success rate ( %) versus risks ( %) associated with the procedure of choice (p= . ). age and gender has no infl uence on treatment choice (p= . and p= . ) and on whether the primary concern is success or risk (p= . and p= . respectively). majority ( %) of the surveyed population would prefer the physician recommend the appropriate treatment. conclusion: th ough patients prefer the physician to recommend the appropriate treatment for a medium-sized renal stone, it is important for the physician to consider the patient's priorities of minimizing risk versus maximizing success. as such, majority of patients selected ureteroscopy as a procedure with a balance of moderate risk and moderate success. solo introduction and objective: sonography has been brought in percutaneous nephrolithotripsy (pcnl) as an adjunct to x-ray to restrict radiation exposure. th is study was designed to respond this question that "is sonography proper enough to supersede x-ray in pcnl under spinal anesthesia?" moreover, we investigated possible predictors of success. tract infection were excluded from study. th e intraand post-operative surgical outcomes were evaluated. results: th e mean age of the patients was . ± . years. mean stone size was . ± . cm. mean access and operative time were . ± . and ± . minutes respectively. superior calyx was selected for access in % of patients. th e patients were categorized in following groups; history of more than one section previously open stone surgery ( %), horseshoe kidney ( %), major lumbosacral deformity ( %), failed standard pcnl ( %), children under years old ( %), pregnancy ( %). th e primary complete stone free rate was %, and aft er ancillary procedures (urs, swl), raised to %. th e mean hemoglobin drop was . ± . gr/dl. transfusion needs in patients. signifi cant prolonged or delay hemorrhage was not shown in any cases. pneumothorax was detected in one patient that managed with chest tube insertion. visceral or solid abdominal organ injury was not occurred. conclusion: with some attention, the outcomes of ultrasonography-guided pcnl for challenging renal stones are comparable with standard fl uoroscopic approach, and in some situation, fl ank position contain benefi ts rather than standard prone position. study of ten cases of p.c.n.l in "previously operated kidney stone with incisional hernia" conclusions: p.c.n.l in incision hernia patient is a safe procedure with excellent results. c.t. urogram is necessary tool for puncture. st puncture in virgin fi eld (out of incisional hernia site) and avoiding colonic gas shadow on fl uoroscopy is key point. bowel injury is the concern -which should be taken care during puncture. daycare pcnl: now a reality! introduction and objective: pcnl as a therapy for renal stones is an established modality. th e use of holmium laser has led to miniaturisation of instruments and sheaths and has thus made the procedure less morbid. a stage has come for the patient to now leave hospital on the same day of the procedure. materials and methods: all cases were done under spinal anaesthesia and prone position. aft er placing a retrograde ureteric catheter, pcs was accessed through the appropriate calyx, and a french sheath with suction capability was used. holmium laser was the energy used. aft er fragmentation, clearance was achieved by a combination of suction and retrograde wash and confi rmed radiologically and visually. clots were fl ushed out through the sheath which was then removed having retained the guide wire. finger pressure on the puncture site achieved haemostasis. th e guide wire and the retrograde catheter were fi nally removed. no urethral catheter was kept. a total tubeless procedure in the real sense. all patients were counselled about haematuria and pain. results: from january to march , a total of cases are included comprising renal and upper ureteric stones. stone size ranged from . to . cms. age ranged from to yrs. th e m/f ratio was : . operative time ranged from to mins. th ere was no signifi cant blood loss. all patients received dose of a parenteral analgesic hrs post procedure, were ambulant hours postopt and were allowed oral liquids. patient had leak at puncture site lasting for hours .all had haematuria which cleared completely within to hours. all were off ered discharge on the same day without any major event. one patient had clot retention on the th po day requiring clot evacuation. conclusion: pcnl as a day care procedure has been achieved by the above described method. patient acceptance is fair though most showed apprehension of going home the same day aft er a major procedure. whether it can be accepted universally remains to be seen. initial experience in ultraminiperc we have reviewed our initial experience of ultra-miniperc-ump in patients. between june and march , total patients underwent ultra-miniperc. puncture and dilatation were done under fl uoroscopy in prone position. we used and fr ump amplatz. stones were fragmented by holmium laser and removed by whirlpool eff ect. post-operative stone-free status was confi rmed by ultrasonography and x-ray aft er week. results: mean patient age was years ( to years) and male to female ratio was . : . in % the procedure was bilateral simultaneous and in % in solitary kidney. stone locations were lower calyx ( %); upper calyx ( %), middle calyx ( %), renal pelvis ( %), upper ureter ( %) and rest were at multiple sites. calyx punctures were lower ( %), upper ( %), middle ( %) and multiple in rest. eight punctures were supracostal. mean operative time from puncture to amplatz removal was minutes (range to minutes). signifi cant bleeding (hb drop more than . gm/dl) was in %. all were managed conservatively without transfusion. dj stents were kept in patients. nephrostomy-tube was not kept in any patient. eleven percent of patients had minor complications like pleural eff usion ( %), uti-fever ( %), and mild hematuria ( %). all were managed conservatively. one patient required conversion to miniperc- fr track due to intraoperative poor vision. mean hospital stay was days ( - days). th ree patients required readmission for fever or clot colic. stone-free rate was %. eight percent had small fragments that were treated by oral hydrotherapy. two patients were treated by eswl. introduction and objective: a prospective randomized controlled study was executed to compare minipercutaneous nephrolithotomy (miniperc) and retrograde intrarenal surgery (rirs) in the management of renal stones larger than mm in a single session. between june and february , patients presenting with renal stones > mm were randomized to a miniperc or a rirs group in a ratio of : . randomization was performed by a biostatistician and opened to the surgeon at the time of the patient's admission on the day before surgery. patient and stone characteristics, perioperative outcomes, and complications were compared between the two groups. th e primary end point was "stonefree", which was defi ned as no residual stone or stones < mm on computed tomography within months postoperatively. results: th irty-fi ve patients (miniperc) and (rirs) were included in the fi nal analysis. th ere were no statistically signifi cant diff erences in stone size ( . ± . versus . ± . mm, p= . ) and stone number ( . ± . versus . ± . , p= . ) between the miniperc and rirs groups. laterality, mean hounsfi eld units, stone location, presence of staghorn stone, and stone composition were similar between the both groups (p> . ). miniperc and rirs had stone free rates of . % and . %, respectively (p= . ). operation time ( . ± . versus . ± . minutes, p= . ), hemoglobin drop ( . ± . versus . ± . g/dl, p= . ), and hospital stay ( . ± . versus . ± . days, p= . ) were similar between the two groups. pain visual analogue score at hour postoperatively ( . ± . versus . ± . , p= . ) and analgesic requirement ( . % versus . %, p= . ) were lower in the miniperc group. two patients in the miniperc group and in the rirs group had minor pelvic or ureter perforation. one patient in each of both groups had hypertension and urinary tract infection. miniperc and rirs are safe and feasible surgical options for managing renal stones larger than mm. rirs had a little higher stone free rates, but more immediate postoperative pain and higher analgesic requirement compared with miniperc. colonic perforation during percutaneous nephrolithotomy darabi mahboub m, aslzare m, shakiba b introduction and objective: percutaneous nephrolithotomy (pcnl) is the treatment of choice for large, extracorporeal lithotripsy failure stones and those in the inferior calyx. despite the development of new techniques and the increasing experience in recent decades, complications may still occur. colonic perforation is one of the most dangerous and rare complications of pcnl, which may lead to peritonitis and sepsis. we present our -year experience on the diagnosis and management of colonic perforation during pcnl. we retrospectively reviewed the data of pcnl procedures performed between may and august . preoperative and operative factors, such as age, sex, history of previous ipsilateral stone intervention, stone side, stone location, site of skin puncture and punctured calyx, were reviewed in patients with colonic injury. results: colonic perforation was found in patients ( males and females) and the mean age was . ± . years (range: to ). all injuries were retroperitoneal. th e left side was aff ected in patients and the right side was injured in cases. conservative management was the treatment planned for all patients. it included withdrawal of the nephrostomy tube outside the kidney to the colon as a percutaneous colostomy, insertion of a double-j ureteral stent, intravenous broad-spectrum antibiotics, bowel rest and total parenteral nutrition. under this conservative management, complete healing of the colon was achieved in all patients. early diagnosis and conservative management of colonic perforation can minimize patient morbidity and mortality and result in excellent healing of the fi stulous tract without any serious complications. colon materials and methods: during ten years, pnl procedures performed in our center. extraperitoneal colonic perforation complicated procedures. all cases were managed without any tube in the colon. we took a retroperitoneal drain through pnl tract and a double-j stent inserted in all cases. we reported the results of our cases that managed without colostomy tube. results: male to female ratio was / . th e diagnosis was established aft er nephrostomy tract dilation and nephroscope insertion before lithotripsy in two cases and in other cases, at the end of nephrolithotomy during amplatz sheath removal. conservative treatment was successful in all cases. mean hospital stay was / days. th ere wasn't any fever or other major complication. conclusions: it seems that management of retroperitoneal colonic perforation when diagnosed intraoperatively during tubeless pnl without colostomy tube is safe and eff ective. does intercostals nerve block and peritubal nerve block with bupivacaine reduce post-operative pain after percutaneous nephrolithomy? introduction and objective: to fi nd the most eff ective post-operative analgesia method aft er percutaneous nephrolithotomy (pcnl). in a prospective, -months duration study all patients undergoing pcnl (tubeless or with -f nephrostomy) were divided into groups. group (pcnl in fi rst- -months) had no intervention; group (pcnl between and months) received intercostal block (icb) with . % bupivacaine; group (pcnl in last -months of study) had peritubal track infi ltration (pti) with . % bupivacaine at end of procedure. visual analog pain scores and rescue analgesia requirements at , , and hours in the arms were compared. results: see table . conclusions: peritubular tract infi ltration with bupivacaine established its superiority over both intercostal block and standard pcnl for post-operative analgesia and rescue analgesic requirements. the post-operative fever was defi ned as body temperature above . within hospital stay. relationship between clinical factors and sirs or post-operation fever was assessed using logistic regression analysis. results: a total of male ( . %) and female ( . %) were enrolled in our study (table ) . forty-fi ve cases ( . %) developed sirs and fever was observed in cases ( . %). shock was observed in ( . %) cases. in univariate analysis, stone size (p = . ) and urine wbc (p = . ) were found to be the predictors of sirs. in multivariate logistic analysis, stone size (or= . , p= . ) and urine wbc (or= . , p= . ) were signifi cantly related to the development of sirs (table ). in univariate analysis, post-operative fever was found to be associated with the location of stones (p= . ), stone size (p= . ), urine wbc (p< . ) and albumin (p= . ). by multivariate logistic regression analysis, only stone size (or= . , p= . ), urine wbc (or= . , p= . ) and serum albumin (or= . , p= . ) were associated with post-operative fever (table ) . conclusion: patients with larger stone size and urinary tract infection before surgery might have higher risk of developing sirs and fever, while a normal serum albumin was found to be the protective factors of fever development. introduction and objective: perioperative hemorrhage owing to high vascularity in bph is the fearsome complication of turp that leads to clot retention, reoperation and oft en requiring blood transfusion. finasteride, a type α-reductase inhibitor, by interacting with vascular endothelial growth factor (vegf), reduces prostatic angiogenesis. microvessel density (mvd) is a histological measurement of angiogenesis and thus a marker of bleeding. we aim to determine the eff ect of two weeks preoperative fi nasteride therapy in reducing prostate vascularity in terms of mean microvessel density (mvd) and expression of vegf in prostate urothelium among patients of bph by comparing with controls. trial has been conducted in department of urology at shifa international hospital islamabad from jan to jan . total patients of benign prostatic hyperplasia (bph) planned for transurethral resection of prostate (turp) having prostate sized of more than grams on trans-abdominal ultrasonography were randomized into two groups each group having patients. th e finasteride group (group a) was prescribed oral mg of fi nasteride daily for weeks before surgery. th e control group (group b) didn't receive any drug. aft er weeks, turp was performed and prostate chips were sent for histopathological determination of mvd and expression of vegf. results: mean age . ± . years, ranging from minimum of years to years. th e mean prostate gland size was comparable in both groups ( ± . grams vs. . ± . grams). mean mvd in fi nasteride group was . ± . whereas in control group mean mvd was . ± . . when compared the mean mvd in both group, the mean mvd was signifi cantly low in fi nasteride group as compared to control group with a p= < . . similarly mean expression of vegf was % in fi nasteride group compared to % in control group. th is expression of vegf was also signifi cantly lower in fi nasteride group as compared to control group (p= . ). also mean mvd was clearly correlated with size of prostate gland and the correlation was found statistically signifi cant on pearson correlation test ( -tailed) with p= . . conclusion: finasteride reduces microvessel density and hence prostate vascularity with only week therapy and the mean mvd is clearly correlated with size of prostate. characteristics -alpha reductase inhibitor induced prostate volume reductions yun j , yang h , kim d , jeon y , lee c introduction and objective: benign prostatic hyperplasia develops in the transition zone of the prostate and α-reductase inhibitors ( -aris) reduce prostate volume. we investigated whether oral treatment with the -aris dutasteride and fi nasteride more significantly aff ected volume reduction in the transition zone or in the entire prostate. total prostate and transition zone volumes (tpv and tzv) were measured at baseline using a transrectal ultrasound (trus) and then at yr aft er the commencement of dutasteride ( . mg) or fi nasteride ( . mg). th e ratio of tpv to tzv was used to determine the transition zone index (tzi). volume reduction (%) was calculated as the ratio of volume reduction to baseline prostate volume. additionally, serum prostate specifi c antigen (psa) concentrations were measured at baseline and then at yr aft er the -ari were commenced. results: all of the patients (mean age, . yr ± . ; range, - yr) with clinical lower urinary tract symptoms suggestive of benign prostatic hyperplasia and who were -ari naïve were prescribed dutasteride ( . mg, . %, / ) or fi nasteride ( . mg, . %, / ) for more than yr ( . ± . mos). at baseline, the mean tpv, tzv, and tzi values were . ± . cm , . ± . cm , and . ± . , respectively. at yr aft er the commencement of the -ari, the mean tpv, tzv, and tzi were . ± . cm , . ± . cm , and . ± . , respectively. th e tzi value is not signifi cantly diff erent at yr compared with baseline (p > . ), while the tpv and tzv reductions are . ± . % and . ± . %, respectively; there is no signifi cant diff erence between the tpv and tzv volume reductions (p> . ). conclusion: th ese results show that prostate volume reduction induced by -aris occurs in the entire prostate universally, rather than in the transition zone specifi cally. russo g, favilla v, privitera s, castelli t, fragalà e, cimino s, morgia g introduction and objective: combination therapy with of -alpha reductase inhibitors ( -ari) and alpha-blockers (ab) is the gold standard for the treatment of moderate-severe secondary to benign prostatic hyperplasia (bph). several clinical trials have already analyzed the overall impact of the medical treatment of luts/bph on sexual sphere, but any one investigated the overall impact on erectile dysfunction (ed) and libido alterations (la). th e aim of this this systematic review and meta-analysis was to evaluate the impact of combination therapy on ed and la from randomized clinical trial (rct). we performed a search of the cochrane central register of controlled trials, pubmed, embase, cochrane database of systematic review, and web of science, until december . we conducted a meta-analysis to determine the impact of combination therapy ( ari + ab) in determining the onset of ed or la. a p value < . was used to denote the presence of heterogeneity. of the studies reviewed, only fi ve rct were included, involving participants. th e overall prevalence of erectile dysfunction was of . %, . % and . % in patients treated with combination therapy, ari and ab respectively. th e overall prevalence of altered libido was of . %, . % and . % in patients treated with combination therapy, ari and ab respectively. combination therapy ari + ab was found to be associated with increased risk of ed (or = . ; p < . ) and la (or = : ; p = . ) compared to monotherapy with ab. th e combination therapy was found to increase the risk of ed (or = . ; p = . ) compared to monotherapy with ari, but not the risk of la (or = : ; p = . ). analyzing the individual monotherapies, therapy with alpha-blockers signifi cantly reduces the risk of ed (or = . ; p < . ) and la (or = . ; p = . ) compared to treatment with ari. conclusions: combination therapy ari + ab is associated with a higher risk of ed. in addition, ari monotherapy has the same risk of the combination of having la. th ese results could be taken into account during the counseling therapy in patients with luts/ bph. mladenov b, mariyanovski v introduction and objective: bph bleeding is one of the common causes of gross hematuria in older men. -alpha reductase inhibitor ( ari) treatment has been showed to reduce prostate tissue microvascularity and to prevent bph-associated hematuria. alpha-blockers are oft en prescribed, where their eff ect on hematuria is not well evaluated. th e aim of this study was to investigate the impact and effi cacy of the current used drugs for bph for treatment and prevention of bph-caused hematuria. a total of men with median age of were enrolled for a period of years. all were presented with bph-caused macrospopic hematuria, diagnosed according to an adopted investigation protocol. detailed history was obtained, including usage of alpha-blockers and/or -ari prior to the hematuria episode. patients were released or immediately hospitalized and catheterized according to their status. all patients were followed up for year for recurrent bleeding and were divided into groups -with an alpha-blocker, -ari, or without therapy. in this study patients were sent home and treated conservatively, other with severe bleeding and/or clot retention necessitated catheterization and hospitalization. from patients ( %) were taking alpha-blockers, ( %) -ari, and ( %) had no medications for the bph prior to the hematuria. patients were followed up for recurrent bleeding for year in medication groups. were given alpha-blockers, - -ari and were released without medication for the bph. within year bph-bleeding occur respectively in , , and cases. th ere was a statistically signifi cant diff erence between the group with -ari therapy and the group without therapy (p= . ). no statistically signifi cant diff erence (p= . ) was found between the groups with an alpha-blocker and without therapy. in all cases with medication the hematuria episodes were lighter according to blood loss and/or hospital stay (in days) than the initial one. conclusions: according to our study, bph-associated hematuria can be eff ectively controlled and reduced with ari. although as per our data alpha-blockers have a positive eff ect on the intensity of the recurrent hematuria, much more signifi cant results in treating and controlling bph-bleeding are shown with -ari. effi overactive bladder syndrome (oab) is a common condition with a negative impact on quality of life. botulinum toxin is commonly used. despite the favorable outcomes seen using botulinum toxin a, the method of injection and side eff ects still need to be solved. our aim is to use botulinium toxin with simple method and check its safety and effi cacy. a total of patients with refractory oab were included in this study. inclusion criteria was refractory non neurogenic oab not responding to conservative management for at least months. aft er written consent, patients were randomly divided into two groups. group a ( patients) received botulinium toxin a unit intravesical instillation diluted in cc normal saline, group b ( patients) received placebo in the form of cc normal saline by the same method. patients were evaluated initially by history, physical examination, overactive bladder symptom score (oabss), quality of life symptom score (qolss), urine analysis, routine laboratory investigations, kub, pelviabdominal ultrasound and urodynamics. patients were followed up at one, and two month post instillation for effi cacy and safety by oabss, qol score, side eff ects and postvoid residual urine. introduction and objective: th e authors evaluate the safety and effi cacy of the prostatic urethral lift when performed in conjunction with a second procedure. in this retrospective study, patients underwent the prostatic urethral lift between january and november . sixteen patients received the prostatic urethral lift as a single procedure and the mean patient age for this group was years (range to ). in the remaining patients, a second procedure was performed in conjunction with the prostatic urethral lift . th ese procedures were: th ulium laser enucleation of the middle lobe, optical urethrotomy and bladder neck incision. results: in patients who were treated with the prostatic urethral lift as a single procedure the mean international prostate symptom score was . (range to ) and mean maximum urine fl ow rate was . mls- (range to ). th e average prostate volume was cc (range to ) and mean quality of life rating was . points (range to ). at months aft er the procedure, the mean international prostate symptom score improved by . points ( %), mean maximum urine fl ow rate by . mls- ( %) and mean quality of life rating by . ( %). th e improvements achieved in the combined procedures were greater than the patients who underwent the prostatic urethral lift as a single procedure. th ere was one case ( %) of postoperative moderate pelvic pain which was managed conservatively with a nonsteroidal anti-infl ammatory drug. a urinary tract infection occurred in one case ( %) and resolved aft er treatment with an antibiotic. th ere were no complications in the combined procedure cases. no patients reported any decline in erectile function, retrograde ejaculation or dysejaculation. conclusion: th e prostatic urethral lift is a safe and eff ective treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia while preserving sexual function. in carefully selected patients, the performing the prostatic urethral lift in conjunction with a second procedure may achieve superior results with no major complications. evaluation . we sought to evaluate the effi cien-cy, safety and outcome parameters between green-light pvp and vit. data of xps cases were retrospectively collected from experienced surgeons at high volume greenlight xps centers. preoperative, operative and post-operative parameters were collected and compared between groups. pvp was defi ned as pure vaporization only while vit included techniques to incise into adenoma and allow tissue resection and removal. results: as summarized in table , men undergoing vit (n= ) had larger prostate size, higher ipss∕qol and retention preoperatively than those undergoing pvp (n= ). while vit allowed greater delivery of energy ( . vs. . kj∕g), operative time was longer and had greater need for > fi bres. th ere were no diff erences in intra and post-operative adverse events. while no diff erences were observed in ipss∕qol at months post-operatively, more favorable qmax and pvr were observed at months, along with greater psa reduction, in the vit group. preoperative patient characteristics introduction and objective: to prospectively evaluate at two years, the quality of life (qol) and satisfaction of subjects randomized to either gl-xps or turp for luts/bpo. a total of patients at sites in european countries who were candidates for surgical relief of bpo were randomised : to undergo gl-xps or turp. subjects had ipss scores > and prostate volumes < mls. multiple self-administered patient questionnaires were assessed from baseline to years via: ) a general health status eq- d- l questionnaire (index score and visual scale); ) physical and mental health (sf- physical health and sf- mental health scores); ) erectile function and ejaculatory status (iief- questionnaire); ) urinary continence via oabq-sf symptoms, oabq-sf health and iciq-ui sf; ) overall satisfaction: willingness to undergo the procedure gain or ) recommend to a friend. table and subject satisfaction at years is shown in figure . conclusions: th ere is a statistically similar improvement in qol with gl-xps and turp at years. erectile function is not aff ected by gl-xps or turp and both result in a % risk of retrograde ejaculation at years. functional introduction and objective: technology for photoselective vaporisation of the prostate (pvp) has evolved in recent years. we report our early experience of pvp with the greenlight™ -w xps and assess our institutional learning curve for this technique. we performed a retrospectively analysis of our fi rst patients undergoing pvp using the greenlight™ -w xps over a twoyear period. data was collected on demographics, prostate volume, length of stay, time to trial of void, and complications. complications were graded according to the clavien classifi cation system. th e operative learning curve was analysed via various intra-operative lasering variables including the total delivered energy, total vapourisation time (vt), and vapourisation time/operation time (vt/ot). th e study population was divided into three consecutive equal groups and the three groups were compared. results: mean age was . mean length of stay was . days. mean prostate volume was cc. twenty-fi ve percent were on some form of anticoagulation. twenty-one percent were in-dwelling catheter-dependent preoperatively. th e median duration to removal of in-dwelling catheter was day. seventy-six percent had a successful trial of void on day . th e overall complication rate was %, the vast majority of which were clavien grade i or ii. th ere were no statistically signifi cant diff erences between the groups in terms of age or prostate size. over time, there was a statistically signifi cant decrease in ot and increase in vt/ot but no diff erences in complication rates, time to trial of void or length of stay as experience increased. conclusion: greenlight laser pvp using the -w xps is a safe and effi cient treatment option for benign prostatic hyperplasia, with minimal bleeding and low complication rates. our data suggests that a learning curve exists for this procedure in terms of intra-operative lasering variables with no statistically signifi cant increase in post-operative complications or length of hospital stay during this period. tillou x, le gal s, chahwan c, oitchayomi a, doerfl er a introduction and objective: to compare results of pvp (photoselective vaporisation of the prostate) in elderly patients to those observed in younger male patients taking into account the presence of an indwelling bladder catheter. we performed a review of our prospectively maintained database between december and march . a total of patients were operated for luts related to hbp. th ree groups were fi rst established to compare results of pvp in elderly male patients. we then analyzed the impact of an indwelling bladder catheter by comparing two groups of patients under and above year-old. results: th ere were no diff erences between groups for bmi, neurological disorder or hypertension history, aspirin treatment, ipss, qol and preoperative pvr (post void residual). patients above years old had statistically more heart diseases (p= . ) and had more anticoagulant treatments (p= . ). prostate volume increased with aging (p= . ), which resulted in an increased procedure time (p= . ) and an increased amount of energy delivered (p= . ). for postoperative outcomes, there were no diff erences between groups for bladder catheter removal time, ipss, qol, pvr, and surgical complications. postoperative qmax was statistically lower for patients above years old (p= . ) but with a decreased diff erence compared to preoperative measurements (p= . ). in the group without an indwelling catheter, postoperative catheter time was signifi cantly longer in patients over years (p= . ) with a greater pvr (p= . ). urofl owmetry and ipss voiding were signifi cantly improved in both groups without diff erences. th ere was no diff erence for early or late postoperative complications. for patients with an indwelling catheter, for all parameters studied, no statistically signifi cant diff erences were found except higher post-operative pvr in patients older than year-old. conclusions: pvp is an effi cient and safe procedure in elderly male patients despite more heart diseases and anticoagulant treatments. with or without a previous indwelling bladder catheter, functional outcomes were identical whatever age. introduction and objective: th e procedure of holep has steep learning curve and more than cases are needed for overcoming the curve. th e objective of our study is for identifying the detailed steps in improving skills during learning curve. total patients who underwent holep in single center were included in the study. th e operation was performed by surgeons who were experienced tur-p more than cases. patients were divided into groups. groups were initial cases (group ), mid cases (group ), and later cases (group ) in each surgeons. th e enucleation time, morcellation time, the amount of energy use, diff erential count of hemoglobin between pre-and post-operation, post-operative urofl owmetry parameter were compared between each group. especially, enucleation time was divided into diff erent steps, which was action time that was actual use of laser energy or dissecting prostate tissue using cystoscopy and identifi cation time was time for identifying anatomical structure without any procedure. results: mean ages was . years old and mean bmi was . kg/m . mean psa was . ng/ml and mean prostate volume was . cc. th ere were no signifi cant diff erences in baseline characteristics in preoperative data. aft er cases (group ), there was less use of laser energy, less time consuming for morcellation and identifi cation compared to group . identifi cation time was signifi cantly improved than group and more shortening feature as cases added but had no signifi cant diff erence. aft er cases (in groups ), there was more signifi cant diff erence in all operative parameter. especially morcellation time was signifi cantly improved aft er cases. th ere was no signifi cant diff erence in post-operative urofl owmetric parameters. conclusion: in initial experience, it seemed to be overcoming one step about identifying surgical anatomy in learning curve aft er cases. especially, cases were optimal cases for overcoming learning curve for morcellation. aft er cases, we did not overcome the learning curve but all operative parameter was improved. transrectal ultrasound as an intraoperative tool in the identifi cation of the plane of dissection during holep procedure introduction and objective: holmium laser enuclation of the prostate (holep) has been named since as the potential gold standard of treatment for bladder outlet obstruction as a consequence of benign prostatic hiperplasia. one of the most important steps during procedure is to identify the plane of dissection between the adenoma and periferic zone. in this study we demonstrated the utility of transrectal ultrasound in the identifi cation of this surgical plane during ho-lep for novel surgeons. materials and methods: previews informed concerned, we preform transrectal ultrasound during holep of patients, using the proved of the flex focus ultrasound system of bk medical, obtaining images of the prostate as a method to simplify the identifi cation of the surgical plane. we preformed holep as a standard method with storz endoscopic instruments using fr resectoscope with a kunts element and with the watts holium laser power suite from lumenis, we obtained images of the fi ve patients in real time with axial and sagital planes simultaneously, clearly helping the surgeon to identify the surgical dissection plane between the adenoma and the peripherical zone. conclusions: transrectal ultrasound could be a useful tool during the training of novel surgeons in holep technique. introduction and objective: th e aristolochia family of herbaceous plants has been used worldwide for traditional medicinal purposes for more than two centuries. th ese plants contain aristolochic acid (aa), a powerful nephrotoxin and human carcinogen, which, in susceptible individuals, causes chronic kidney disease and/or upper urinary tract urothelial carcinoma (utuc). bioactivation of aa yields a reactive intermediate that binds covalently with dna to form aristolactam (al)-dna adducts. in the urothelium, these adducts give rise to a unique mutational signature. as there are several reports of renal dysfunction in japan associated with the use of aa-containing chinese herbs, we hypothesize that a fraction of utuc cases in this country may result from past use of aristolochia herbs. patients with histologically confi rmed utuc who underwent nephroureterectomy in kyushu university aft er august were eligible for this study. informed consent was provided by each participant prior to surgery. surgical specimens of tumor and renal cortex were snap-frozen following nephroureterectomy. dna was isolated from renal cortex and analyzed for the presence of al-dna adducts using either mass spectrometry or a p-postlabelling method. dna isolated from matched tumor samples was subjected to mutational analysis of the tumor suppressor gene tp . results: th irty three utuc patients were enrolled in this study between august and march , males and females, with a mean age of years. al-dna adducts were detected in of renal cortex samples ( . %) analyzed; adduct levels were . and . per deoxynucelotides. sequencing analysis of tp in tumor dna revealed the absence of the unique mutational signature associated with aa. conclusion: aa exposure was confi rmed in two utuc patients; however, in these two cases, the mutational profi le of tp in tumor dna was not consistent with aa-induced carcinogenesis. further accrual and analysis of utuc cases are needed to estimate the prevalence of aa exposure in japan, to evaluate the role of aa exposure to utuc in this country, and to confi rm the public health implications of these fi ndings. preoperative introduction and objective: our aims are to assess the association between upper urinary tract urothelial carcinoma (uutuc) development and the polymorphisms in the aurora kinase a (aurka) phe ile (rs ) and survivin rs c>t genes. a total of patients with uutuc and hospital controls with bladder stones were recruited in this study. clinical records, demographic data, and possible confounding factors were collected using a standardized questionnaire. genotyping was determined using a real-time polymerase chain reaction using taqman probe. results: signifi cantly more controls than patients with uutuc drank alcohol and tea, but there were no diff erences in the frequencies of cigarette smokers and coff ee drinkers. aurka phe ile gene polymorphisms, but not survivin rs c>t gene polymorphisms, were associated with uutuc development (χ test and multivariate logistic regression) (χ = . , p= . ; crude or= . , % ci= . - . ; adjusted or= . , % ci = . - . ). stratifi cation analysis and multivariate logistic regression analysis showed that only the association between aurka phe ile gene polymorphisms and uutuc development were diff erentiated between those with and without the habits of smoking, tea drinking, or coff ee drinking. conclusion: our major fi ndings supported that aur-ka phe ile gene polymorphisms, but not survivin rs c>t gene polymorphisms, increase genetic susceptibility to uutuc. metastatic and has thereaft er stabilized around %. th ere was a regional variation in the proportion of patients who underwent cn between % and %. th e relative survival at fi ve years was % aft er cn compared to % in patients who did not undergo cn (p< . ). th e median age of the m patients who underwent cn was years compared to years in patients who did not undergo cn. tumor recurrence, aft er initial treatment with curative intention in primary m patients, was % aft er fi ve years. th e location of the metastases were: lung %, bone %, lymph nodes %, liver %, adrenal % and brain metastases in % of the patients. th irteen percent of the patients suff ered local recurrence in the renal fossa aft er nephrectomy. th e most common treatment for patients with a recurrence was oncological medical treatment ( %). metastasectomy was performed in % of the patients with recurrence and in % of the patients the surgery had a curative intention. conclusions: th e incidence of metastases in renal cell carcinoma in sweden is decreasing and is lower than in historical materials. th e patients with synchronous metastases who undergo cn have a signifi cantly better survival than patients who do not undergo cn, but constitute a highly selected group. recurrence after initial treatment with curative intention is treated surgically in % and oncologically in %. immediate introduction and objective: pretreatment characterization of renal masses (rm) remain suboptimal with overtreatment being a signifi cant concern. we examined the ability of preoperative clinical characteristics to predict histological features of rms. in the global renal mass study conducted by the clinical research offi ce of endourology society (croes), data were collected for consecutive patients with renal masses who underwent surgery for clinical stage i renal mass between - . based on surgical histology, tumors were categorized as benign, low aggressiveness cancer, and high aggressiveness cancer. we assessed the ability of clinical (patient gender, age, smoking history, bmi), laboratory (preoperative hemoglobin and c-reactive protein) and radiographic (tumor diameter, location, exophytic rate and enhancement) characteristics to discriminate between benign and cancer (low + high aggressiveness) and between highly aggressive tumors and others (benign + low aggressiveness cancer). multivariate logistic regression was used to estimate the probability of the histological group by clinical and radiographic features in the entire cohort and a sub group of ct a tumor. th e performance of the models was consequently studied by calibration, nagelkerke's r , and discrimination (roc area under the curve). results: th e study cohort included patients with clinical stage i renal mass of which ( %) had ct a mass. benign lesions were found in ( . %), low aggressiveness tumors in ( %) and high aggressiveness tumors in ( . %). male gender, smoking history, increased tumor size, and lower exophytic rate were associated with malignancy and high aggressiveness features (all p-values < . ). models developed based on these characteristics had the ability to discriminate benign from malignant (bootstrap corrected c-index of . ) and high aggressiveness tumors from benign and low aggressiveness tumors (bootstrap corrected c-index of . ). similar results were achieved in the ct a subgroup. th e c-index of tumor diameter as a single predictor of malignancy and high aggressiveness tumors in the entire cohort was . and . , respectively. conclusions: although older age, male gender, smoking history, increased tumor diameter and reduced exophytic rate are associated with malignancy and high aggressiveness of renal mass, models incorporating these characteristics have modest discriminating power, slightly better than the predictive ability of tumor size alone in clinical stage i tumors. could surgery be prevented in the management of small renal masses? introduction and objective: th e diagnosis, characterization and management of small renal masses (srms) remains an important clinical issue. a proportion of srms may be benign or have low malignant potential. th ese lesions could arguably be managed non-operatively. strategies such as renal mass biopsy may be valuable in reducing the rate of unnecessary surgery. we evaluated a large contemporary surgical series of resected srms in a tertiary center with a very low biopsy rate to determine the number of procedures that could have been prevented for benign and low malignant potential lesions. conclusion: sbrt is a safe and effi cacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with rcc. cyberknife can deliver complex treatment plans to multiple lesions while minimizing irradiation to the surrounding healthy tissue, thereby decreasing the risk of complications. cyberknife has the potential to be an excellent treatment modality for renal cancer patients with renal cell carcinomas or patients with bilateral renal cell carcinoma who refuse surgery or are medically inoperable. introduction and objective: th e introduction of the robotic surgical systems has changed the way both surgeons and patients view urological surgical procedures. we tested the same theoretical and tangible benefi ts for partial nephrectomy with tele-lap alf-x system. we review our technique of robot-assisted laparoscopic partial nephrectomy performed using a new robotic telesurgical device (alf-x) on swine large white/landrace model. we set up an operating theatre to test alf-x on partial nephrectomy procedure to be performed on swine large white/landrace in total anesthesia. th e console incorporates the following main components: an ergonomic seat, the laparoscopic teleoperation master (ltm) with haptic handles, a d-hd monitor, an eye-tracking system (ets), a keyboard and a touchpad, and one foot pedal. th e ets is an infrared-based eye tracking system that detects which point the surgeon is looking at. th ere was one surgeon placed at computer-console and one surgeon placed at the surgical table. a random decision on the kidney to be tested is performed before the operation. once the trocars are placed and the kidney isolated a period of warm ischemia is due to perform the partial nephrectomy on the lower or upper pole (random choice). th e haptic sensation can be used for palpation, pushing or pulling to estimate elasticity and consistency of tissues and controlling the tensility of the sutures when tying. low-cost disposable or reusable instruments were used. results: to date, we performed partial nephrectomy with alf-x robot on swine large white/landrace (pigs) models. th ree robot's arms were used. five partial nephrectomies were on the right kidney, while were on the left one. th e mean surgical time was . minutes (range - min). th e mean warm ischemia time was . min (range . - min). th e mean blood loss was . ml (range - ml). conclusions: according to these experimental experiences on pig models, we may assume that robot-assisted laparoscopic partial nephrectomy, using tele-lap alf-x system, is safe, feasible and reproducible procedure. moreover it off ers a good perception when instruments touch each other avoiding collision between robotic arms. we believe that robot-assisted tele surgery approach could be reasonable an innovative contribution in the near future also in humans. it also off ers a reduction of costs per intervention. preoperative chronic kidney disease to reduce the eff ects of selection bias and potential confounding factors, patients in non-ckd group were selected by propensity score matching. results: th e median age of all patients was . years (range, - years) and the median follow-up was . months (range, - months). comparisons of the propensity score-matched cohorts showed that t and n stages were more advanced and the tumor size was larger in the ckd than in the non-ckd group (p < . each). kaplan-meier analyses showed that recurrence-free survival (rfs), cancer-specifi c survival (css), and overall survival (os) were signifi cantly lower in the ckd group (p < . each). multivariate regression analysis showed that preoperative ckd status was an independent predictor of css and os in patients with rcc (p < . each). conclusion: preoperative ckd may be associated with more aggressive features and poorer prognosis in patients with rcc. rcc patients with preoperative ckd should be followed up frequently and carefully aft er nephrectomy. . ) were independent prognostic factors. bone-modifying agents (zoledronic acid and denosumab) were not associated with os. th e median os of patients receiving molecular-targeted therapy aft er diagnosis of bone metastasis was signifi cantly better than that of those who did not receive targeted therapy ( . vs. . months, p= . ). our study suggests that molecular-targeted therapy prolongs survival of rcc patients with bone metastasis. th us, molecular-targeted therapy, nephrectomy and surgery for bone metastasis should be considered for these patients. introduction and objective: ureteric stenting for urinary tract obstruction secondary to malignancy may off er a survival benefi t and buy time for oncological management. since the introduction of the ureteral stent symptom questionnaire (ussq), studies have revealed that up to % of patients with ureteric stents for benign conditions experience stent related symptoms that interfere with daily activities and reduce quality of life. our aim was to evaluate stent symptoms in patients with malignant obstruction and their impact on health related quality of life. patients with indwelling ureteric stents for malignant obstruction were identifi ed from the departmental stent register during a march to june . telephone interviews and face to face interviews at the time of stent change were conducted using the validated ussq. results were analysed according to the questionnaire scoring system. results: twenty patients with a mean age of years completed the ussq. of these patients - % reported bothersome urinary symptoms that included storage symptoms, incontinence and haematuria. fifty percent of patients experienced stent related pain in the fl ank ( / ), suprapubic ( / ) and groin area ( / ). fift y percent of these patients required regular analgesia and - % experienced pain interfered with activities and daily life. seventy percent of patients experienced diffi culty in performing physical activities, with a negative impact on social life. one out of patients reported sexual dysfunction. eighty fi ve percent experienced urinary tract infection (uti) with % having a uti most or all of the time and % requiring admission to hospital. mortality within one year of stent insertion was %. conclusion: ureteric stents are associated with signifi cant debilitating symptoms and reduced quality of life in patients with malignant obstruction. th is has signifi cant implications for management of cancer patients and patient counselling. ureteric stenting can prevent death from malignant obstruction, but may result in prolonged suff ering due to stent symptoms without benefi t in overall survival. introduction and objective: management pheochromocytoma laparoscopic was initially controversial because of the possibility of adrenergic discharge with the generation of the pneumoperitoneum. th e work of a proper medical preparation and anesthetic precise control obvious that circumstance and allows more precise surgery and a better image as it gives the laparoscopy to get with much less aggressive surgical removal. our goal is to present the preparation and the key points in its approach. we present -year-old male with recent diagnosis prostate cancer and high pressure treated with drugs. discovery of left adrenal mass of cm. in ct and mri and scintography with mibg suggestive focus of pheochromocytoma in the adrenal gland. twenty-four-hours urine: total catecholamines: . ug/ ( - ) adrenaline: . ug/ hours ( d- ); normetanephrines ug/ ( - ), metanephrines: ug/ ( - ). vanilvandelico . ug/ ( - ). preparing medical / anaesthetic consisted: entry days before surgery and control alpha-blockers with doxazosin every hours. treatment with beta-blockers with propranolol. expansion of intravascular volume with intravenous fl uid therapy hours before surgery. and control of blood glucose levels. intraoperatively crisis were treated with nitroprusiate. results: aft er adrenalectomy laparoscopic left with a length of minutes and adequate control pressure intraoperative the pathology diagnosis was of pheochromocytoma. postoperative attended without incident (clavien i) and went out hospital to the hours. th e presence a pheochromocytoma should not be a contraindication to laparoscopic approach of the adrenal gland in services experienced laparoscopic, and must be an exhaustive control of anesthetic, as well as a careful dissection of the gland trying to avoid excessive manipulation of the same. robotic assisted "davinci" adrenalectomy al-ansari a, younes n, al-rumaihi k, al-jalham k, gul t, badawi a, kamkoum h introduction and objective: adrenal mass could be challenging, especially when it is large in size or cystic, adrenal had short and variable vasculature, in addition to functional adenoma, adrenal surgery require minimal handling. robotic assisted adrenalectomy (ra) had been proven to be safe and eff ective. objectives: to describe robotic adrenalectomy (ra), to ensure a safe and eff ective removal of complex adrenal mass. we reviewed the record of consecutive patients who underwent ra performed by a single surgeon, between january and january , fi ve were right and fi ve were left , were solid and were cystic, none were functional adenoma patients position and port placement were similar to renal surgery, aft er control of the renal vein the gland was dissected, small arteries were clipped and the gland were removed. results: patients were females and males, age range between to years mean tumor size was . cm range ( . - cm), mean hospital stay was days, no perioperative complications, all masses were intact, one postoperative addisonian crisis pathology was benign cyst, adenoma, ganglionuroma, neuroendocine, adrenal hyperplasia, adrenocortical neoplasm of low malignant potential. conclusion: robotic adrenalectomy is safe and feasible in the management of complex adrenal mass. robotic materials and methods: th e girl was in a good general health and came walking to our out-patients department. she was admitted and her investigations reviewed. she had a right renal mass with cavo-atrial extension with an isolated embolus in the pulmonary artery. she was planned for a complete excision under cardio-pulmonary bypass with deep hypothermic circulatory arrest. under general anaesthesia, aft er establishing complete monitoring, she was opened by long midline laparotomy and mid-sternotomy. mid-sternotomy extension was done up-front in-view of the pulmonary embolus. an incision was made in the posterior peritoneum medial to the inferior mesenteric vein. th e right renal artery was dissected posterior to the left renal vein, ligated and divided. suddenly her end tidal carbon-di-oxide fell. th e video demonstrates the trans-esophageal echo-cardiography confi rming fragmentation of the cavo-atrial thrombus and its migration into the right ventricle and main pulmonary artery. th e patient was immediately put on cardio-pulmonary bypass. initially the venous return was low. she was rapidly cooled to degrees centigrade and aorta cross clamped just above the diaphragm. arterial infl ow was reduced to litre per minute to main blood fl ow to the brain. th e video demonstrates opening, clearing and repairing of the right atrium, right ventricle and main pulmonary artery in a step by step approach. th e branches of the pulmonary artery were cleared with fogarty's catheter. right radical nephrectomy was completed and ivc cleared and repaired. th e total circulatory arrest time was minutes. she was slowly re-warmed and taken off cardio-pulmonary bypass. results: her post-op recovery was uneventful. th e fi nal histo-pathology report showed a primitive neuro-ectodermal tumor. she received adjuvant chemotherapy for cycles and is well at months of follow-up. in an appropriate case pulmonary artery embolectomy along with excision of cavo-atrial tumor thrombus is acceptable in experienced centers. an up-front mid-sternotomy should be contemplated in patients where the risk of embolisation of tumor thrombus is high. a total of consecutive patients who underwent a turbts were identifi ed from january to february by a single surgeon at our institution. we excluded patients as they had a known history of bladder cancer that previously underwent treatment. via rigid cystoscopy, tumors were resected en bloc using a polypectomy snare with electro-cautery and retrieved transurethrally. following turbts, the base of the tumor was either biopsied and fulgurize or a formal turbt was performed. results: nineteen consecutive patients (median age , range - ) underwent an initial turbts for the initial staging and management of bladder tumor. median number of tumors found was (range - ). median tumor size was cm (range cm- cm). median follow-up was months (range - months). tumors sites were: posterior wall, trigone, lateral wall, anterior wall. immediate aft er snaring of the tumor, patients underwent biopsy and fulguration while underwent a turbt in the same operative setting. patient from the turbt group experienced an obturator refl ex. muscle was visualized on of pathology specimens. patients required subsequent redo procedure to obtain muscle for tissue diagnosis and staging. recurrence occurred in patients (median . months, range . - months). conclusion: turbts is a feasible technique for pedunculated bladder tumors. it provides a bloodless fi eld with maximal visibility for the surgeon and may be an adjunct in turbt. dilep-diode laser ( nm technical aspects for overcoming the holep learning curve omori y, matsumoto s, matsumoto s introduction and objective: holep is an excellent surgical procedure and alternative to turp and open prostatectomy for bladder outlet obstruction due to benign prostatic hyperplasia. it has been widely accepted and performed, for its safety and eff ectiveness. however, it may not be considered an option for the majority of worldwide urologists, because of its steep learning curve. our objective is to help beginners and operators who are interested in learning holep to get familiarized with it, and feel confi dent about opting for this procedure. in this video we demonstrate a case of holep using watt holmium laser in a -year-old male with ml prostate. th e operative fl ow is described as follow: ) downward dissection of the left lobe and longitudinal incision; ) downward dissection of the right lobe and longitudinal incision; ) enucleation of the medium lobe; ) lateral side dissection of the both lobes; ) o' clock incision and bladder neck ablation at between and o' clock ) diagonal longitudinal incision of apical lobes; ) enucleation of the both lobes; ) hemostasis; ) morcellation. results: in this video operative time was min (enucleation time: min) and resected tissue weight was g. our procedure has some modifi cations compared to the surgical technique from original procedure of gilling, separating lobes and dissecting in a retrograde fashion. conclusion: holep is a safe and eff ective surgical procedure. we hope our procedure will become the reference for beginners and urologists who are wishing to master it, but are worried about methods and complications. and also we hope holep will become the new gold standard for the treatment of benign prostatic hyperplasia. to obliterate the circular fi bers of bladder neck to the level of proximal urethra, carefully avoiding the external striated sphincter. laser power is reduced to w to prior to vaporization of any pseudomembranous trigonitis, which is commonly found in pbno or recurrent cystitis cases. results: laser vaporization is successful in relieving voiding diffi culties. th is procedure opens the bladder neck and allows for optimal post-operative urine fl ow. th e patient had improvement in both objective and subjective voiding functions immediately aft er treatment. during -months follow-up urofl owmetry, the maximum fl ow rate increased from to ml/s. th e postvoid residual urine decreased from ml to less than ml. conclusion: primary bladder neck obstruction in female can be eff ectively and safely treated with laser photoselective vaporization of the bladder neck. bilateral retroperitoneal laparoscopic nephrectomy using mm instruments introduction and objective: laparoscopy has become the standard nephrectomy approach. it has been shown that th e retroperitoneal approach is comparable to the transperitoneal approach when it comes to safety and results, even more, it can present advantages in selected patients, as in patients with prior abdominal surgery. th e use of mm instruments is gaining acceptance as a safe way to improve aesthetic results and minimize abdominal wall trauma while maintaining the principles of standard laparoscopy. we present the case of a -year-old woman with a history of radical hysterectomy and radiotherapy, aft er which she presents: ) bilateral ureteral obstruction that produces terminal renal insuffi ciency, and, ) vesico-vaginal fi stula, refractory to conservative treatment. th e decision is made to perform a bilateral retroperitoneal laparoscopic radical nephrectomy as a defi nitive treatment of the vaginal fi stula and as preparation for the kidney transplant. results: th e right nephrectomy is performed fi rst. classic retroperitoneal technique is used, using mm trocars (with an mm trocar to create the retroperitoneal space). on the left side, a previously produced nephrostomy catheter tract is used to insert a mm trocar. no relevant intraoperatory complications were observed. preoperative haemoglobin was g/l and the postoperative was g/l aft er transfusion of one bag of packed red blood cells. th e only postoperative complication was the infection of the mm left side trocar tract (where the previous nephrostomy catheter was placed). th e total hospital stay was days. th e pathological anatomy for both kidneys was: chronic pyelonephritis with extended interstitial fi brosis and tubular atrophy. conclusions: retroperitoneal laparoscopic nephrectomy is an effi cient and safe approach, comparable to transperitoneal laparoscopic nephrectomy, and even superior to this one in patients with previous abdominal surgery. th e use of mm instruments (in this case in a combined fashion), allows performing the surgery in a safe way, with superior aesthetic results. pure aft er complete mobilization of the renal artery three hem-o-lok clips were applied and the artery was transected. th e ivc was isolated upwards as far as possible, and intraoperative laparoscopic ultrasound was employed to identify the extent of the thrombus. aft er the inferior vena cava ivc was blocked using tourniquet loops above and below the thrombus and the contralateral renal vein was blocked, the ivc was opened and the tumor thrombus was extracted entirely. th e ivc was stitched with a running - polypropylene suture. th e specimen was extracted in an endoscopic extraction bag through a gibson incision. results: from february to june , fi ve patients underwent pure conventional retroperitoneal laparoscopic nephrectomy and tumor thrombectomy. th e mean patient age was yr ( - yr). th e mean operative time was min ( - min), and the mean estimated blood loss was ml ( - ml). th e mean length of tumor thrombus was . cm ( - cm). with a mean follow-up of . mo ( - mo), one patient was identifi ed lung metastasis four months postoperatively. introduction and objective: partial nephrectomy provides equivalent oncologic and superior functional outcome compared with radical nephrectomy over the short-and long-term. with the development of laparoscopic techniques and increasing laparoscopic surgical experiences, laparoscopic partial nephrectomy has become an acceptable alternative to radical nephrectomy for expert laparoscopic urologists to treat small renal mass. however, higher complexity tumors are associated with more resection of normal tissue, a longer warm ischemia time, and postoperative morbidity, especially entirely endophytic hilar tumor. in order to reduce normal tissue resected during laparoscopic partial nephrectomy for entirely endophytic hilar tumor, we develop a novel technique to deal with the higher complexity tumors. subject is a -year-old female with t a clear cell carcinoma with a diameter of . cm. th e tumor is entirely endophytic hilar tumor. renal nephrometry score is . she underwent laparoscopic partial nephrectomy in retroperitoneal approach. standard ports were placed. th e surgeon opened gerota's fascia and dissects along the renal capsule mobilizing the kidney from within gerota's fascia. th e resection line was marked using the laparoscopic ultrasound probe. aft er the renal artery was clamped by bulldog, tumor enucleation was performed using a cold scissor. one incision above the tumor was made, and careful dissection was performed to approach the tumor. th e tumor was completely mobilized outside its margin. th en the inner layer renal parenchyma and collecting system was sutured with - absorbable sutures and the outer layer renal parenchyma was sutured with absorbable suture. results: th e procedure was successfully accomplished without open conversion and transfusion. th e operative time was min, and the estimated blood loss was ml. th e warm ischemia time was min. histology revealed that the tumor was chromophobe renal cell carcinoma, and the surgical margin was negative. conclusion: laparoscopic partial nephrectomy for entirely endophytic tumor is challenging. tumor enucleation with one resection line can reserve more normal renal tissue during the procedure. more cases are needed to evaluate the effi ciency of the technique. introduction and objective: laparoscopic adrenalectomy by posterior approach carries high recovery and shorter operative time. children with metastatic high risk neuroblastoma arising from the suprarenal gland should undergo local surgical excision of the primary tumor before further intensifi cation of chemotherapy and possible bone marrow transplantation. herein, we report a video of left laparoscopic adrenalectomy showing the diff erent steps of the procedure. th congress of the sociÉtÉ internationale d'urologie -siu abstract book materials and methods: a . -year-old boy with left metastatic suprarenal neuroblastoma, received chemotherapy according to high risk european protocol. child positioned in prone position, fi rst trocar at the tip of the last rib by open introduction, two mm trocars one in costovertebral angle and the other is lateral. balloon development of the space, gerota fascia opened, the upper pole of kidney identifi ed, mass dissected, suprarenal vein is clipped during dissection, extraction in bag. results: oral feeding is begun aft er hours, discharge from hospital in the second day postoperatively, rapid convalescence, rapid resumption of chemotherapy. conclusion: laparoscopic adrenalectomy using posterior approach gives direct access to the adrenal gland, no peritoneal violation, rapid intestinal movement recovery, short hospital stay and rapid recovery. all advantages that might facilitate the early start of adjuvant chemotherapy in children with neuroblastoma, however, oncological outcome should be proven by long-term follow-up, larger number of patients, and good selection of small tumor facilitates surgical extirpation. introduction and objective: robotic multiplex partial nephrectomy (rmxpnx) is minimally invasive partial nephrectomy for three or more tumors in a single kidney. rmxpnx has been previously shown feasible with excellent preservation of renal function. we present our technique of off -clamp robotic transperitoneal multiplex partial nephrectomy in the treatment of multifocal and hereditary renal tumors. a prospectively maintained database was retrospectively queried to identify all patients who underwent rmxpnx from to . rmxpnx is defi ned a resection of or more masses from a single kidney. patients underwent rmxpnx when the largest tumor reached cm in size. tumors were excised using enucleation techniques. from the data of eligible patients, a representative patient was identifi ed and surgical video was edited to demonstrate the important aspects of the surgical technique. results: th e patient is a -year-old white male with von hippel lindau diagnosed with bilateral multifocal renal tumors with several tumors > cm in size. he underwent bilateral robotic multiplex partial nephrectomy separated by weeks with no operative complications. th irty fi ve tumors were excised from the right kidney. fift y two lesions were then resected from the left kidney. his preoperative creatinine was . and at year postop from bilateral multiplex partial nephrectomies his creatinine is . . in the hands of an experienced surgeon, off -clamp robotic transperitoneal multiplex partial nephrectomy is feasible, safe and eff ective in the treatment of multifocal and hereditary renal tumors. th is technique provides exceptional renal functional preservation and decreases technical diffi culty of reoperation. louie-johnsun m introduction and objective: th e advantages of minimally invasive laparoscopic surgery are well documented. as there are few urological emergencies suitable for a laparoscopic approach, the increased use of robotic surgery for elective procedures that can be performed equally as well laparoscopically threatens the acquisition of skills that can be transferred from these elective procedures (e.g. laparoscopic radical prostatectomy, pyeloplasty and partial nephrectomy) to emergency cases. in emergency situations, a robotic approach may not be feasible or practical. we highlight this with three recent cases. materials and methods/results: a video presentation of three of our recent urological emergency cases managed successfully laparoscopically which includes: ( ) a -year-old girl with neurogenic bladder presenting with urinary peritonitis aft er spontaneous rupture of an augmentation cystoplasty: laparoscopic adhesolysis and repair of perforated augmented bladder. ( ) an -year-old woman with intraoperative mid ureteric injury during laparoscopic right hemicolectomy: laparoscopic ureteroureterostomy and insertion of ureteric stent. ( ) a -year-old woman with ureterovaginal fi stula post laparoscopic hysterectomy: laparoscopic ureteric reimplantation with psoas hitch and insertion of stent. conclusion: despite the increasing use of robotic surgery in urology we encourage the continued training and dissemination of advanced laparoscopic skills in the elective setting to allow for the advantages of laparoscopy to be transferred to the less common urological emergency setting. robotic ureteric catheter placement; ) port placement with patient in lateral position; ) bowel mobilization; ) localization of lower calyx by intra-operative ultra sound probe; ) lower segmental nephrectomy; ) anastomosis (ureterocalicostomy) with - v-lock sutures over a pre placed f ureteric catheter and drain placement; ) changing of ureteric catheter to dj-stent on rd day post-operatively. results: th e procedure was completed successfully without any intra operative complications in all the cases. mean operative time was ± minutes and analgesic requirement of ± milligram of tramadol. none of the patients required blood transfusion. urethral catheter was removed on th and drain on th post-operative day and stent aft er weeks. one patient had clavien grade (pyrexia) complication. conclusions: robot-assisted laparoscopic ureterocalicostomy for secondary upjo is safe and feasible in expert hands. apart from the short recovery times, early mobilization, decreased analgesic requirements; robotic approach provides the added advantage of technical ease and precision of suturing. laparoscopic dismembered pyeloplasty for upjo in pelvic ectopic kidney apollo bgs hospital, mysore, india introduction and objective: renal ectopia is a rare anomaly and may be associated with pelvic ureteric junction obstruction (pujo). we report such a case with an ectopic pelvic kidney (l-type) with pujo and its successful laparoscopic management. th rough this report we emphasize the importance of adequate preoperative imaging and intraoperative details to avoid mishaps. a -year-old male was admitted with complaints of right-side lower abdominal pain of a dull aching type lasting months. ultrasonography revealed left pelvic kidney. th ese fi ndings were confi rmed with an intravenous pyelogram, which showed the left kidney low lying in the pelvic region with features of hydronephrosis and upjo. ct angiography revealed no crossing vessel as the cause of pujo. results: th e patient was taken up for transperitoneal laparoscopic pyeloplasty under general anesthesia. aft er creation of the pneumoperitoneum and with the ports in place, dissection was started and the dilated pelvis could be visualized through the peritoneal window. th e peritoneum was incised and the dilated pelvis on the left side was reached. aft er further dissection, the classic anderson-hynes dismembered laparoscopic pyeloplasty was done by using - vicryl. minimal excision of the redundant pelvis was required and because the kidney was not mobilized, nephropexy was not required. care was taken to avoid injury to the right ureter, which was coursing in close proximity to the left renal pelvis. preoperatively placed stent was retained and repositioned during the pyeloplasty. estimated blood loss during the procedure was around ml, and the procedure was completed in minutes without any intraoperative complications. th e patient could tolerate oral feeding on the evening of the same day. conclusion: th e upjo in ectopic pelvic kidneys presents a large spectrum of presentation. th e laparoscopic approach provides good surgical exposure, and operative times are compared to those of laparoscopic procedure in anatomically normal kidneys. laparoscopic we present laparoscopic radical cystectomy (lrc) and intracorporeal orthotopic ileal neobladder with two isoperistaltic aff erent limbs. a -year-old male patient with recurrent urothelial bladder carcinoma. ct demonstrates bulky bladder tumor in right lateral wall. lrc and intracorporeal urinary diversion were performed. six trocars were used in the procedure. aft er lrc and extended pelvic lymph node dissection were accomplished, a cm ileal segment cm proximal to the ileocecum was harvested, of which a cm proximal ileal segment was moved to anastomose with the end of the harvested segment which was right isoperistaltic aff erent limb. th en cm ileal segment was detubularisated leaving cm intact proximal ileum for left isoperistaltic aff erent limb. th e harvested ileal segment was symmetrically folded with identical limb lengths. th e posterior wall of the neobladder was sutured, and ileoureteral stents were delivered into the two isoperistaltic limbs and passed up the ureter and coiled into the renal pelvis, and one foley catheter was delivered into the neobladder at the same time. bilateral ureteroileal anastomoses were performed in a continuous manner respectively. th e anterior wall of the neobladder was closed and the posterior urethra was anastomosed with the neobladder. we have performed cases with this technique. all procedures were completed without open conversion. th e mean operative time was min with a blood loss of ml. th e construction time of the neobladder was min. th e time to orally allow was postoperative day in all. th e mean hospital stay was d. foley catheter and dj stents were removed on postoperative day . no major complication was occurred. conclusion: laparoscopic radical cystectomy and intracorporeal orthotopic ileal neobladder with two isoperistaltic limbs were a safe and feasible for experienced laparoscopic surgeons. however, more cases and long follow-up were required to evaluate the function of the novel neobladder. all in this video, we wanted to share our robotics augmentation ileosistoplasty experience in -year-old male patient with a diagnosis of neurogenic bladder. an -year-old male patient treated with clean intermittent catheterization and anti-cholinergic therapy for neurogenic bladder. bladder capacity was detected cc, the irregularities in the bladder contour and left grade vur was detected in control video urodynamics. so we decided to implement robotic augmentation ileocystoplasty to the patients. results: th e transperitoneal approach is performed by using veress needle to access the peritoneal cavity. th e abdomen was insuffl ated using co and trocars placed under direct vision ( of camera port ( mm), of da vinci ports ( mm) was placed and of mm and of mm assistant ports were placed). a cm segment of ileum with mesentery was incised with about cm proximal from the ileocecal valve and this segment was suspended. intestinal anastomosis was performed with - vicril and - monocril sutures and created a u-shaped ileal pouch. th e bladder was released from the surrounding tissue. about cm, longitudinal incision was made to the bladder. a single-j catheters were placed to the left ureter and bladder for the left ureteral catheter and cystostomy. th e bowel prepared for bladder augmentation and it was sutured with . pds with wate tight anastomosis. operation was terminated by placing the drainage catheter. introduction and objective: although their numerous indications make double-j stents frequently preferred in the armamentarium of the urological practice, serious complications can arise, if they are not used correctly. in endourological surgeries, due to type and stuff of material the breakage or fracture risk of the equipment is more. th ere are various types of surgical procedures for the removal of the foreign bodies. shock wave lithotomy (swl) and ureteroscopy (urs) are the fi rst step in the removal encrusted ureteral stent. th is report presents a case of successful forgotten ureteral stent removal by means of fl exible ureterorenoscope (furs) and fl uoroscopic imaging. a -year-old male patient was admitted to our clinic with the complaint of recurrent urinary tract infection. in his medical history he said that he had an open kidney stone surgery in and aft er months d-j catheter removal had been performed. aft er radiologic imaging it is determined that there are two d-j catheter pieces in the right kidney collecting system. furs and removal of foreign body was performed successfully. postoperative fi rst day patient discharged with no complication. results: various materials and coatings have been developed to avoid ureteral stent complications such as encrustation and infections. th e incidence of encrustation increases with the duration that the stent remains in place. th ere are numerous types of removal techniques for foreign body removal, however furs seems to be the better one with the minimal postoperative rates. our technique was performed easily and in a short surgery time. conclusion: flexible urs modifi ed with fl uoroscopy has particular advantages for treating encrusted ureteral stents. th is procedure is least invasive and is thus considered to be most suitable surgery for encrusted ureteral stents or foreign body materials in the kidney. results: we outline strategies to prevent diffi culties with urethro-ileal anastomosis during rarc iucd neobladder formation. furthermore we off er some key technical points that can be benefi cial in overcoming challenging urethro-ileal anastomosis. conclusions: due to the technically complex nature of rarc icud neobladder formation, the awareness of potential pitfalls during each step of the process is essential. issues and solutions discussed in this video provide a valuable resource for clinicians performing this procedure. robotic in this video we present a patient presenting with concomitant renal neoplasm and a large calculus in the renal pelvis that what was managed with robotic pyelolithotomy at the time of partial nephrectomy. results: aft er exposure of kidney the ureter was identifi ed. th e renal pelvis was exposed and pyelolithotomy was performed. aft er this hilum was clamped and partial nephrectomy and renorrhaphy followed. th e warm ischemia time was minutes. th e procedure was completed without any complications. patient was discharged on the second postoperative day. conclusions: although uncommon, the presence of concomitant stone and renal neoplasm can make the decision of optimal patient care more challenging. using robotic platform simultaneous management of both conditions can be accomplished in appropriately selected cases. single introduction and objective: female epispadias is a rare congenital anomaly and is classifi ed, into vestibular, subsymphyseal, and retro-symphyseal. historically treatment consists of staged repairs with urethral and vulvar reconstruction in fi rst stage followed by bladder neck reconstruction at a later age. in addition, staged procedures require multiple sessions of surgery and anesthesia, and are associated with relatively higher morbidity. recently single stage perineal urethroplasty has been used for epispadias repair. objective of the study is to evaluate the results of single-stage perineal urethroplasty with double breasting of the urethra and bladder neck and sphincteroplasty in female epispadias. we treated patients with severe female epispadias since to . age varied from to years (mean years). perineal urethroplasty with double breasting, sphincteroplasty, and genitoplasty was done in cases. th e urethral plate and bladder neck was mobilized from the surrounding tissue till bladder neck. a urethral mucosal strip of about to mm was denuded from the bladder neck to the end of urethral plate on one lateral edge, and tubularized over a f catheter. urethroplasty was done with double breasting of the urethral muscle margins starting from inside the bladder neck downward to the neo-meatus with corporoplasty, sphincteroplasty, and genital reconstruction. results: all patients were satisfi ed and happy about cosmesis. of the patients, were fully continent with a dry interval of to hours, one of them had occasional night wetting was put on anticholinergic. one was partially continent with dry interval of hours required anticholinergic. conclusions: perineal urethroplasty with double breasting of urethra, from inside the bladder neck to the neomeatus, resulted in continence in most cases because it increased the urethral and bladder neck resistance, as well as bladder capacity, all were important factors in continence. we advocate this procedure as a fi rst choice in all patients with female epispadias, because it is simple, safe, and eff ective for continence. single we had partial penile disassembly to have the advantage of both technique. so objective of the study was to evaluate the functional and cosmetic outcome of single stage partial penile disassembly repair in isolated male epispadias. a retrospective analysis of cases of primary epispadias repair, performed during july to july at our institution. patients were classifi ed on the basis of type of epispadias, urinary incontinence, presence/degree of chordee and penile rotation. exstrophy epispadias complex and secondary repair were excluded. surgical technique: penile de-gloving with mobilization of urethral plate from ventral to dorsal aspect with preservation of blood supply at both ends, distally up to the level of midglans and proximally up to pubic symphysis with division of penopubic ligament to lengthen the penis and position the urethra ventrally. tubularization of urethral plate followed by spongioplasty, corporoplasty with medial rotation of corporeal bodies (without any corporotomy) and glanuloplasty with meatoplasty to bring the meatus ventrally. skin cover with rotation of ventral fl aps and z-plasty when required. results: age of the patients varied from months to years with a mean of years. forty patients ( %) had excellent cosmetic outcome while three patients ( %) had minimal residual chordee/torque but didn't require any surgery in a follow-up to - years. all seven partially incontinent patients in the study group achieved continence aft er surgery. none of the patients developed complications like fi stula or stricture. all the patients in the post pubertal group reported normal erections and successful ejaculations aft er the surgery. post-operative follow-up ranged from - years with a mean of years. conclusions: th e technique incorporates all the benefi ts of cantwell ransley repair, needs less extensive dissection than total penile disassembly. both functional and cosmetic results are good with low complication rate. spongioplasty reconstructs near normal urethra and corporoplasty with spongioplasty also helps in prevention of urethral fi stula. introduction and objective: to introduce a unique technique, single port laparoscopic assisted extraperitoneal closure of patent processus vaginalis using j shaped bended spinal needle. materials and methods: a . -mm -degree laparoscope was inserted through an umbilical incision. th e scope could view both inguinal ring. j shaped bended g spinal needle was inserted just mm lateral to the internal inguinal ring. th e needle was introduced to the extraperitoneal space over the vas deferens and spermatic vessels, injecting of saline for the preperitoneal hydrodilation. a - polyester suture was threaded through an g spinal needle. same - polyester suture was threaded through a g spinal needle from the tip. along the guidance of the suture and g needle, j shaped bended g spinal needle was reintroduced to extraperitoneal space. g spinal needle traveled through the upper margin of internal ring, g needle tip was pulled out of the initial g needle punctured opening. - polyester suture was pulled outside from the g needle tip and then g needle is also withdrawn. aft er all these procedure, internal inguinal ring was completely encircled and tied extracorporeally. th e knot was buried in the subcutaneous area within the punctured needle hole. results: sixteen children underwent laparoscopic transcutaneous extraperitoneal (lte) repair of hydrocele by using j shaped bended spinal needle. all patients were discharged on the same day aft er surgery without any complication. during a mean follow-up period of months (range - mo), no recurrence has been observed except fi rst cases. th is lte technique is simple, fast, safe and cosmetic procedure for pediatric hydrocele. robot assisted laparoscopic ureteral reimplantation for girl and boy patients: differences and similarities introduction and objective: nowadays robot assisted laparoscopic extravesical ureteral reimplantation is getting famous and in the literature is being an alternative for gold standard open surgery. in our clinic we have performed ralur procedures in our clinic for vesicoureteral refl ux and ureterovesical stricture and with this video-abstract we would like to share our experience on ralur in girl and boy patients; diff erences and similarities of procedure. we have performed ral-ur cases in our clinic between july -april for pediatric and adult patients. technique: all procedures have been performed under general anesthesia. nasogastric tube and urethral catheter placed to all patients. for all procedures -port confi guration is used: two robotic mm trocar, one mm camera trocar and one mm (including mm cover) assistant trocar. following docking robotic working arms of robot is placed. in all procedures one monopolar curved scissors, one needle holder and one maryland bipolar forceps is used as the working arms. all procedures performed transperitoneally and extravesically. in the working area of the procedure girls have more structures compared to boys. uterus, fallopian tubes and ovaries are the risky structures for girls while the vas deferens in boys. as seen in the video fallopian tubes, uterus and vas deferens are extraperitoneal organs, but ovary is intraperitoneal organ. we create a peritoneal window to reach the retroperioneal space and to dissect the ureter. dissecting the ureter we have been very careful not to harm vas deferens in boys and fallopian tubes in girls. protecting this structures we open one peritoneal window in boys and two windows in girls to fi nd and to work with the distal part of the ureter. vessel tape is used to hang the ureters. th e bladder is elevated with a - straight needle vicryl suture through the abdominal wall. aft er that the ureter was clipped with a hemoloc clip and sutured with a - vicryl suture in watertight fashion (if necessary). aft er suturing the distal ureter tailoring for the dilated distal rest ureter is performed (if necessary). following detrusorotomy, mucosa is cut for the anastomosis (if necessary). before the ureterovesical anastomosis f nelaton or a dj catheter was placed inside the ureter (if necessary). ureterovesical anastomosis is made with a - monocryl suture (if necessary). in the cases that ureter and mucosa are not cut, realignment suture is used. detrusorraphy is performed by a - barbed suture. following detrusorraphy we repaired the parietal peritoneum to close the peritoneal window one line and two lines in boys and girls, respectively. results: ralur procedure has been used successfully in girls and boys by considering the anatomical differences. bleeding was minimal in all patients. all patients discharged at the nd or rd postoperative days. conclusion: while using ralur procedures in pediatric patients, surgeon must be aware of the anatomy. mistakes during the procedure may damage the reproductive system components. performing this procedure in children, compared in adult patients, there are diffi culties due to the small size of the abdominal cavity. with the appropriate trocar placement this problem can be solved. robot assisted laparoscopic left ureteral reimplantation for ureterovesical stricture introduction and objective: extravesical robot-assisted laparoscopic ureteral reimplantation (ralur) for vesicoureteral refl ux (vur), ureterovesical strictures (uvs) and ureteral pathologies are alternative to the gold standard open repair in the literature. with this video presentation we want to share our initial experience with robot-assisted laparoscopic extravesical ureteral reimplantation using the ureteral advancement technique for a -year-old boy patient who is the youngest patient received this intervention in turkey. we have performed ral-ur procedure for adult and pediatric patients in our clinic. th is patient explained in the video was a -yearold boy who has had recurrent infections due to this condition. when the patient applied to our clinic he had already grade left ureterohydronephrosis. we performed left sided ralur procedure for this patient. technique: th e davinci si system was used via a transperitoneal approach. we used a port confi guration for the procedure; one -mm trochar for optic, two -mm trochars for robotic working arms and one -mm trochar for assistance. th e patient was placed in a modifi ed trendelenburg (approximately °) position. aft er docking the robotic arms, the ureter is identifi ed closed to the vas deferens. th e ureter is dissected distal to the vas and tented up with a tape. th e bladder is elevated with a - straight needle vicryl suture through the abdominal wall. a cm detrusorotomy is performed". aft er that left ureter was clipped with a hemoloc clip and sutured with a - vicryl suture in watertight fashion. aft er suturing the distal ureter tailoring for the dilated distal rest ureter is performed. before the ureterovesical anastomosis f nelaton catheter is placed thorough urethra and bladder inside the left tailored ureter. following this application nelaton catheter is binded to the urethral catheter. ureterovesical anastomosis is made with a - monocryl suture. detrusorraphy is performed by a - barbed suture. following detrusorraphy we repaired the parietal peritoneum and fi nished the procedure. foley catheter, nelaton catheter and drain are left at the end of the procedure. rectourethral fi stula is a morbid complication that can occur post trauma, radical prostatectomy, radiation, or pelvic surgery. th e management of these cases can be challenging and might require multiple procedures to achieve cure. th e use of omentum fl ap between the rectum and the urethra is recommended for its potential benefi ts in prevention of fi stula recurrence. we aim to illustrate the feasibility and safety of a new laparoscopic surgical technique for interposition of omentum in patients with complex pelvic fractures urethral injury (pfui) and rectourethral fi stula (ruf). we performed prospective case series of patients with pfui and ruf from september till october . th e initial approach is perineal with continued dissection until urethral transaction. laparoscopic team mobilises omentum and enters retroperitoneum lateral to bladder. a tvt needle is passed from perineum hugging the posterior wall of pubic symphysis and enters peritoneal cavity. th is tract is dilated and omentum transposed in to perineum. th is omentum is used as interposition between urethral anastomosis and rectum. th e clinical outcome was considered a failure when any instrumentation was needed or the recurrence of ruf. th congress of the sociÉtÉ internationale d'urologie -siu abstract book results: median age is years (range - ). all patients had complex pfui with ruf. th ey all had an attempt of perineal anastomotic urethroplasty with ruf repair that failed outside our center and were referred to us subsequently. all the patients had supra pubic catheters and of the three patients were passing urine through the rectum and the urethral meatus. one of the patients had a loop colostomy that was closed during the fi rst failed surgery. no intra-operative or post-operative complications occurred. patients were discharged home on post-operative day . all patients had the urethral catheter removed aft er weeks. th ree-month follow-up shows no fi stula recurrence with good urine fl ow. conclusion: using our new technique of laparoscopic omentoplasty for interposition of omentum in patients with ruf post pfui is a viable and safe option. th is allows us to perform a perineal surgery with the benefi t of omental interposition using a minimally invasive technique. further studies with larger number of patients as well as longer follow-up would be needed. introduction and objective: to test the hypothesis that a new surgical technique using elaborated perineal anastomotic urethroplasty combined with laparoscopic omentoplasty for patients with complex and prior failed pelvic fracture urethral defect repair was feasible, safe, and eff ective. we performed a prospective, observational, stage a study to observe treatment outcomes of combined perineal and laparoscopic approach for urethroplasty in patients with pelvic fracture urethral defect at a single center in pune, india, between january and february . complex and redo patients with pelvic fracture urethral defect occurring aft er pelvic fracture urethral injury were included in the study. anterior urethral strictures were excluded. th e primary study outcome was the success rate of the surgical technique, and the secondary outcome was to evaluate feasibility and safety of the procedure. th e clinical outcome was considered a failure when any postoperative instrumentation was needed. results: fift een male patients with a median age of years were included in the study. seven patients were adolescents ( - years) and patients ( . %) were adults ( - years). th e mean number of prior urethroplasties was . (range, - ). all patients underwent elaborated bulbomembranous anastomosis using a perineal approach with inferior pubectomy combined with laparoscopic mobilization of the omentum into the perineum to envelope the anastomosis and to fi ll the perineal dead space. of patients, ( . %) were successful and ( . %) failed. one adolescent boy years old developed a recurrent stricture months aft er the procedure and was managed using internal urethrotomy. median follow-up was months (range, - months). conclusion: combining a laparoscopic omentoplasty to a membranobulbar anastomosis for complex and redo pelvic fracture urethral injury is successful, feasible, safe, and with minimal additional morbidity to the patient. th e technique has the advantage of a perineal incision and the ability to use the omentum to support the anastomosis. dorsal results: buccal mucosal graft urethroplasty was done in all the patients with the graft being harvested from the buccal mucosa of the oral cavity. postoperative evaluation was done with voiding cystourethrogram at the time of catheter removal during the th postoperative week. mean peak urinary fl ow rate increased from . ml/sec to . ml/sec with normal fl ow curve stabilised at months to a mean of . ml/sec. patients were followed at , , and months in the fi rst year and then monthly thereaft er with urofl owmetry and ultrasonogram. mean follow-up period is around months. two patients required urethral dilatation for recurrence of symptoms. none of the patients developed stress urinary incontinence during follow-up. conclusions: female urethral stricture disease is under diagnosed and bmg urethroplasty is underutilised. our study adds to the limited evidence base, that bmg urethroplasty can be done safely with good results in females. a introduction and objective: ureteral fi stula's treatment oft en includes long and complex surgical and endoscopic therapies and represent a challenge for the urologist oft en with disappointing results. uventa® stent placement could represent a new option of conservative treatment for ureteral fi stulas. materials and methods: uventa® self-expanding ureteral stent are able to restore urinary fl ow in ureteral stenosis and to facilitate the closure of ureteral fi stulas thanks to its triple layer structure made of two layers of metal mesh with interposed a ptfe membrane. uventa® stents are available in diff erent lengths and diameters, and allow the coaxial overlap of the ends of multiple stents, providing a lumen of large caliber able to ensure the proper urinary fl ow and the possibility of further endoscopic procedures. we show the case of -year-old man that in september , undergone to pelvic surgery for an adenocarcinoma of the sigma in advanced stage. th e postoperative period revealed a urinary leakage, dealt initially in conservative way by the general surgeon. due to unsatisfactory results, the patient was then evaluated by the urologist and subjected to bilateral ascending pyelography highlighting the presence of a high fl ow left ureteral fi stula in pelvic tract; he case was managed immediately with bilateral ureteral stenting prior to placement of a uventa® stent. th e subsequent step was a retrograde pyelography through the left stent, used to identify the site of the ureteral fi stula. aft er hydrophilic guidewire positioning and mono-j stent removal, the delivery system of the uventa® stent is advanced coaxially to the guidewire under radiologia control. once reached the desired position the stent is released from its delivery system whit pull-back technique playing a uventa® stent fr x cm allowing its simultaneous self-expansion. th e next ureteroscopic control has shown the need to placement of an additional uventa® stent to complete fi stula's coverage. following the insertion of a hydrophilic nitinol guidewire a new uventa® stent fr x cm has been positioned further in order that the ends of the two stent's overlap for a length of at least cm. results: intraoperative retrograde pyelography showed that the stent have eff ectively excluded the fi stula. th e absence of contrast medium leakage was also documented by retrograde cystography performed after days from stents positioning. conclusions: in our experience, the application of uventa® stent has proven to be an eff ective option in the conservative treatment of minimally invasive ureteral fi stulas. robotic we performed fi ve robotic ureteroplasties using a buccal mucosal onlay between september and march . th e graft was procured by our otolaryngology colleague (jcl). th e graft onlay was performed using - pds suture and stent was placed robotically. stent was left in place for - weeks, and imaging repeated aft er removal. results: table describes each case and the outcomes observed. th e three patients who have undergone stent removal and reimaging had complete success and resolution of obstruction. th ere were post-operative complications, and none were higher than grade iii (table ) . table shows the demographic and perioperative variables of the patients undergoing this procedure. conclusion: our technique of robotic buccal mucosal ureteroplasty is safe and eff ective. we believe this is a relatively simple technique which is easily replicated. long-term data will be important to prove the validity of this procedure. primary endoscopic realignment of rupture urethra introduction and objective: pelvic fracture urethral injury (pfui) is more common in india and subcontinent. th ere is no consensus on the initial management of this injury. th ere are two schools of thoughts in all cases of suspected or confi rmed urethral rupture: a) initial supra-pubic catheterization (spc) followed by urethral reconstruction of inevitable stricture; and b) realignment of urethra. we demonstrate method of primary endoscopic realignment of rupture urethra and review the literature comparing these two procedures. a /m-presented with retention of urine and bleeding per urethra. he had sustained pelvic trauma when he was crushed between a tank and a wall. aft er initial resuscitation he had x ray pelvis, ct abdomen, rgu. he then underwent spc under ultrasound guidance. on th day aft er spc he underwent primary endoscopic realignment of the rupture urethra. we have shown a technique and reviewed the relevant literature emphasizing advantages of realignment. results: we used a two endoscopes technique one each from the spc route and per-urethral route. intra-operative contrast study was done to see extent of injury and also to see possible patency and continuity of the urethra. additionally methylene blue study was also done. a ptfe guide wire (gw) was passed from below. at the fi rst site of the gw from above it was apparent that further manoeuvers such as "going for light" would not be required. th e gw was carefully pulled in suprapubically. a silicon foley catheter ( f) was gently passed perurethrally over it. th e position of catheter was confi rmed suprapubically. patient had no major or minor complication. catheter was placed in for weeks and removed. post catheter removal patient voided well. th ese results correlated well with other studies in the literature. conclusion: ) technically not a challenging procedure. ) low risk and low complication rate. ) one failure of procedure does not preclude further attempts. ) adequate experience and instrumentation are essential. ) level evidence in favor of this approach over spc alone and further urethroplasty. neourethra with penile skin flap after total amputation of the penis kulkarni s, joshi p, batra v, sharour w, hunter c, surana s, kulkarni j introduction and objective: urethral carcinoma is a rare oncological entity. th e standard treatment for invasive urethral squamous cell carcinoma is radical penectomy, prostatectomy, cystectomy and ileal conduit. in our technique, we describe a palliative surgery that avoids the ileal diversion and perineal urethrostomy through the use of dorsal penile skin tubularization. th is video represents a detailed, step-by-step technique for retro auricular graft harvesting that we have found facilitates resident and general urologist teaching. ears were prepped and draped. th e grafted was areas were marked bilaterally. diluted lidocaine with epinephrine was injected subcutaneously. th e graft was harvested using sharp scissors. donor site was closed in two layers with minimal aesthetic changes. conclusions: our technique to harvest retroauricular graft is a simple and reproducible. it is useful in patients with lack of bmg. th is step-by-step video could be a useful resource for residents and general urologist who wish to learn an alternative graft . hand combined antegrade and retrograde intraureteric surgery in re-implanted ureter introduction and objective: we review a case of re-implanted ureter complicated with stricture and stone impaction. a -year-old gentleman was following the urology department at hmc. between the year until he was managed by the same urology team for his multiple urological complaints. diff erent open and endourological approaches were conducted. at the year of , this gentleman was complaining of colicky pain due to a cm impacted stone in the left lower ureter, sessions of eswl failed to break it. ivu showed left ureteric stricture, cystoscopy with trial of ureteroscopy was unsuccessful because the left ureteric orifi ce couldn't be identifi ed, so left percutaneous nephrostomy access inserted and followed by antegrade fl exible ureteroscopy, small opening found at the lower part of mid ureter and opened widely by laser, then followed by antegrade double j stenting. retrograde rigid ureteroscopy french identifi ed the stone at mid ureter in a later session and fragmented by laser. a double j stent was reinserted and removed later with smooth recovery. results: management of stones, in the male urethra, is a challenge, more so in a reconstructed urethra. th e dilemma always is whether it is worth incising an otherwise normal or reconstructed urethra, to extract a calculus, especially in this minimally invasive era. th e point to note is the 'painting' technique used to powder the stone, rather than fragmenting the stone into large fragments, which are then diffi cult to remove. high frequency and low energy laser setting is the order of the day. conclusion: laser lithotripsy using a high frequency low energy setting, is a good option for urethral calculi in a reconstructed urethra. retrograd introduction and objective: uretery duplication is a most common congenital anomaly of upper urinary system. th e incidence of it, in autopsy and intravenous pyelography (ivp) series, is . % and - % respectively. it is two-fold more frequent in women than men. retrograde intrarenal surgery (rirs) is a new technology in stone surgery with the fl exibility and most eff ective visualing. in patients who suff er from kidney or uretery with ureter duplication, rirs become the best surgery choice with its advantages. in this case, we present a patient who have the symptoms of kidney stone and ureter duplication. a -year-old male patient applied our clinic with the left fl ank pain. in his intravenous pyelography (ivp) and computerized tomography, it was clearly seen left ureter duplication of which both ureteropelvic junction and duplicated ureters obstructed by two kidney stones. other laboratory tests were normal. rirs surgery was performed the patient successfully. postoperative fi rst day patient was discharged without any complication. results: ureter duplication is a rare congenital anomaly of upper urinary system but the rarest thing is that the obstruction of both duplicated ureters with upj by kidney stones. in our case this kind of case successfully treated by rirs. in this surgery a new technique of access sheet entering for rirs was applied. to our knowledge it is the fi rst case in literature. surgical procedures in patients with urinary tract abnormalities are more diffi cult than the normal anatomy. th e development of new technologies is changing approach to such cases. rirs fi eld of use is gradually increasing in urologic practice. rirs in is a preferable method in duplicated ureter with stone formation. a introduction and objective: nephron-sparing surgery is now the standard of management of small renal mass and is increasingly performed for larger and more challenging lesions. th e aim of this study is to report our experience with robotic partial nephrectomy (rpn) and lapascopic partial nephrectomy (lpn) in patient's surgical outcome (blood loss, wit los renal function, complication). ( )) aml (rpn ( ) lpn ( )), oncocytoma (rpn ( ) lpn ( )) and simple cyst (lpn ( )). th e positive surgical margin rate were both % in rpn and lpn group. th e decline in glomerular fi ltration rate at the last available follow-up was similar in both groups. laparoscopy training at home guijarro a, ascencios j, morales s, huertas j, fernández b, navarro f, paniagua p introduction and objective: th e increasing use of laparoscopic surgery makes training fundamental to acquisition of the basics techniques of endourology. unfortunately, laparoscopic fi eld requires high ability and a long learning curve so it's needed simulators to practice. traditional pelvitrainers improve the laparoscopic skills of a trainee but don't simulate the real conditions of the human body. we present a homemade training surgical model that may help to achieve the skills needed and simulates the abdominal space. it is called simulated environment for laparoscopic training (selt). we have developed a laparoscopic training system based in a simulated environment. we modifi ed a dummy who represents a human trunk, this model it easy to fi nd in hardware stores. th en, we performed several orifi ces in order to place traditional laparoscopic ports in pelvic surgery disposition and two additional for our camera. inside the dummy we placed three screws and developed another hole for attaching a cork panel. also, we used a wardrobe fl ashlight as lighting system. as optical system we have used a inch tablet or a photographic camera linked to the tv. finally, for reproducing a vesicourethral model we use two balloons in order to create an anastomosis between them. final price for the selt model, excluding optical system and disposables (we used discarded ports) was euros, what is signifi cantly lower than the commercial pelvitrainers. time needed for installing all the devices is about minutes. results: th e level of simulation is high, it is more realistic, being harder and diffi cult than "traditional" pelvitrainers. th e degree of movements is limited by the real placement of the ports, distance until exercise is similar and we have to be able to work without results: nine patients underwent tmc left pyeloplasty. th ere were female and male patients with age ranging from - years .operating time ranged from - minutes with mean of minutes. per-operative blood loss was minimal ranging from - ml. return of bowel movement was within - days. all patients were discharged within days and drain removed with - days. two patients were discharged on nd day but drain was removed on rd day in outdoor. follow-up of patients showed improvement in their pain status and ivu showed no re-stricture or stenosis. our last patient is yet to come for the fi rst follow-up. conclusion: tranmesocolic approach for left puj obstruction is feasible and seems to have low morbidity with shorter hospital stay. comparison with colon-refl ecting pyeloplasty and larger number of cases are needed for better statistical evaluation. transperitoneal conclusion: th e overall cdr ( %) for our cohort was comparable to results from mri in-gantry biopsy. in volumes > cm , the cdr was % which was signifi cantly higher than that achieved by historical trus controls. th is study reinforces the benefi t of fusion biopsy in prostates in all volumes, but this utility is further enhanced in large volume glands without the potential toxicity associated with increased number of biopsies. fusion mim-transperineal fusion biopsy has the greatest impact in the biopsy naive population results: during the above mentioned period patients underwent radical prostatectomy. in ( . %) cases erp was preceded by mpmri and psm was detected in of them ( . %). in the majority of patients ( / ; . %) with positive margins pca was locally advanced or gleason score was greater than . th e margin was focal in ( . %) cases. th e most frequent location of psm was the prostate apex. it occurred in patients ( . %) and in of them the right side was involved. in ( . %) patients psm was detected in a location in which mpmri did not reveal the presence of pca. in of them, cancer invaded periprostatic tissues. macroscopic evaluation of the specimen performed directly aft er the erp indicated the possibility of psm presence only in patients but in both cases histological evaluation of the prostate specimen revealed extensive psm. the peri-prostate fat seen on mri. prostate volume was calculated using (height x width x length x π)/ . peri-prostatic fat density was then calculated using peri-prostatic fat volume/ (peri-prostatic fat volume + prostate volume). peri-prostatic fat ratio was calculated using (peri-prostatic fat volume / prostate volume). intervention includes cryoablation, brachytherapy, prostatectomy, external beam radiation with or without androgen deprivation therapy. results: a higher periprostatic fat density is signifi cantly associated with a higher gleason score, p= . , odds ratio . . a higher periprostatic fat ratio is also associated with a higher gleason score, p= . odds ratio . .patients with a higher prostate fat density (p= . , odds ratio . ) and higher peri-prostatic fat ratio (p= . , odds ratio . ) was also more likely to undergo intervention for prostate cancer (table ). psa has no correlation between periprostatic fat and periprostatic fat ratio. a higher prostate fat density and fat ratio is signifi cantly associated with a higher gleason score and a higher likelihood of patient undergoing an intervention for prostate cancer. peri-prostatic fat density and fat ratio may be an important risk factor in diagnosing patients higher grade prostate cancer. laparoscopic . th e mean urinary ph among the diabetics was . ± . and among the non-diabetics was . ± . , which was signifi cantly lower (p< . ). conclusions: th ere is a strong association between type diabetes and uric acid stone formation. th ere is also a strong association between diabetes mellitus, bmi, and also with lower urinary ph. the most patients ( %) were discharged on good condition while one patient died post-operatively. majority of patients ( %) stayed in the ward more than days post operation, the long-term post-operative outcome is yet to be assessed. conclusion: usd in our local setting seem to aff ect people of low social economic status whose daily activities in the fi elds, livestock keeping etc. mean survival; therefore longer stay in the hospital has a detrimental economic impact. outdated diagnostic, treatment equipment and technology lead to prolonged hospital stay. th ere is a need therefore for administrators and urologists in tanzania to improve quality of management of usd by acquiring aff ordable equipment and technologies. percutaneous nephrolithotomy in an ambulatory setting introduction and objective: percutaneous nephrolithotomy (pcnl) is the gold standard for the surgical management of large renal stones. various modifi cations have been done over a period of time to bring down the morbidity of this procedure. ambulatory pcnl (a-pcnl) aims at short hospital stay which is less than hours with faster recovery aft er pcnl. th is study aimed at exploring the feasibility and safety of short stay ambulatory pcnl. : th e number of pcnl procedure done at our institute annually ranges between - . hence, carefully selected patients with single renal calculus, size< cm, bmi < kg/m , favorable anatomy, no medical co-morbidities and moreover patients staying within a radius of km to the hospital with a supportive well informed family were given the option of a-pcnl. a total of patients underwent a-pcnl from april to june . all patients underwent totally tubeless pcnl with single puncture, amplatz size < f, minimal saline irrigation and puncture site infi ltration with . % bupivacaine. postoperatively narcotic analgesics were given; catheter was removed in the post-operative ward and patient was discharged within hrs. patients were explained regarding the complications of the procedure and need for homecare management. results: ten out of patients had insignifi cant post-operative period. one patient returned aft er hrs with loin pain which was evaluated and managed with injectable nsaid. another patient had hematuria which resolved aft er hours with conservative management. introduction and objective: chronic kidney disease (ckd) is associated with increased cardiovascular (cv) disease, independent of other risk factors. it is unclear whether anaemia develops in the setting of nephrectomy induced ckd, and whether it leads to an increased risk of cv morbidity. we assessed the impact nephrectomy has on renal function and evaluated our cohort for the presence of anaemia in relation to ckd stage and cardiac specifi c morbidity. pre-operative, post-operative, and yearly creatinine, hb and hct (up to years) was collected from nephrectomy patients between and . th e cohort was stratifi ed by cardiac risk factors and the prevalence of anaemia was stratifi ed by each ckd stage. we collected all-cause mortality and cv morbidity and mortality data. statistical tests were two-sided. where data was non-normally distributed median values and non-parametric tests were used. results: th e eff ect of nephrectomy on renal function is immediate (pre-operative vs. post-operative cr: p= . ) but not progressive (post-operative vs. -year cr: p= . ). elderly patients, patients with ≥ risk factors, bmi≥ or hypertension had signifi cantly higher post-operative cr (p= . ; p= . ; p= . ; p= . ). advanced age and mild ckd were important risk factors for ckd stage progression. th e prevalence of anaemia increased as ckd stage increased. at one year, the prevalence of anaemia was highest in ckd- patients ( . %), compared to ckd- ( . %) and ckd- ( . %) patients. fift een percent of patients experienced a new cv event; % of these patients were anaemic. conclusion: nephrectomy leads to immediate renal function deterioration but with no progression over time. th e clinical impact of nephrectomy is especially important in elderly patients and in patients with mild pre-operative renal impairment. th e prevalence of anaemia is more common in patients who have a higher ckd stage aft er nephrectomy, and may be a key risk factor for cv morbidity in nephrectomy patients. we believe that it is important to be able to predict who will progress to clinically signifi cant ckd, in order to optimise comorbidities and aggressively treat complications of ckd, such as anaemia. renal results: urological complication were observed in . % of all transplants. in an early phase we found that . % of patients showed problems related to the ureterovesical suture (loosening of the suture or attaching the double-j stent in the suture). suspicion of leakage with the formation of a urinoma was noted in . % of cases. more frequent were the late urological complications: hydronephrosis was seen in . % of cases. when further analyzing this group we discovered a distal ureteral stenosis in . % of all transplants. persistent hydronephrosis was resolved by reimplantation ( . %), permanent nephrostomy ( . %) or placement of a double-j stent ( . %). a large group of late complications consisted of infectious pathology. th us . % suff ered from complicated urinary tract infections which slightly more than a quarter of this population presenting with hydronephrosis. recurrent urinary tract infections without complications were found in . % of transplanted patients. conclusion: currently, the urological team mainly plays a role in the pre-and post-operative phase of renal transplantation. given the signifi cant compli-cations associated with the ureterimplantation performed during kidney transplantation, we advocate a place for the urologist in the perioperative phase as well. since the majority of the complications could be related to refl ux pathology, we propose a ureterimplantation with anti-refl ux mechanism. and october , patients were prospectively randomised into two groups. all patients presented with a simple renal cyst underwent ultrasonographic aspiration and injection of a sclerosing agent. in group , patients had the cyst injected with eo, and in group , were treated with ae. one injection was used in cysts of < ml and two injections were used in larger cysts. complete and partial success were defi ned as complete cyst ablation or a > % reduction in cyst volume with symptomatic relief, respectively. patients were followed up using semi-annual ultrasonography and computed tomography for years. results: sclerotherapy was technically successful in all patients. th ere was no signifi cant diff erence in cyst volume between the groups. aft er years of follow-up there was complete symptomatic relief in both groups, and the overall radiological success rate was % of both groups, at % complete and % partial in group , and % complete and % partial in group . th e frequency of transient complications in the form of microscopic haematuria was % and %, and of low-grade fever was % and % in groups and , respectively. a composite outcome parameter, known as "trifecta", has been recently proposed as measure of the surgical quality for partial nephrectomy (pn) procedures. we aim to validate the value of "trifecta" as a predictor of operated kidney functional preservation in a multi-institutional cohort of patients undergoing minimally invasive pn. we retrospectively reviewed records of consecutive cases of minimally invasive (laparoscopic and robotic) pn performed for ct renal masses in centres from usa and europe from to . inclusion criteria consisted of availability of a renal scan obtained within two weeks prior to surgery and follow-up renal scan - months aft er the surgery. trifecta was defi ned as a combination of negative surgical margin, zero perioperative complications and warm ischemia of less than minutes. th e primary endpoint of the study was to compare the degree of ipsilateral renal function preservation in relation to achievement of trifecta. renal function preservation was defi ned as a proportion of post-operative to pre-operative split renal function assessed by mag renal scan. a multivariable linear regression model was used to determine the independent value of several factors (surgical modality, charlson comorbidity score, achievement of trifecta, r.e.n.a.l score) to predict ipsilateral split function preservation. th e logic was that pnet is chemo-responsive and remaining are not. results: a total of patients were identifi ed. th e various histo-pathologies are shown in table . group had and group had patients. mean age in group was . yrs ( - yrs) with ( %) males and ( %) females. tumor was right-sided in ( %) and left -sided in ( %) cases. th e mean tumor size was . ( - ) cm. necrosis was noted in ( %). level of thrombus was level i in , level ii in , level iii in and level iv in . mean age in group was . yrs ( - yrs) with ( %) males and ( %) females. tumor was right-sided in ( . %) and left -sided in ( . %) cases. th e mean tumor size was . ( - ) cm. necrosis was noted in ( %). level of thrombus was level i in , level ii in , level iii in and level iv in . one of these was diagnosed pre-operatively by a biopsy and had received chemotherapy with partial tumor shrinkage. remaining received adjuvant chemotherapy. of relevance is that the youngest patient in group was years whereas the oldest patient in group was years. in patients with renal tumors and venous thrombus who are younger than years, pre-operative biopsy should be contemplated. in patients with a diagnosis of pnet, neo-adjuvant chemotherapy can be studied. introduction and objective: th e use of nephrectomy in emergency is increasingly rare due to the improved critical care urinary sepsis and development of radio-embolization. few series have been reported on this subject. th e aim of our study was to evaluate current indications, morbidity and mortality and results of nephrectomies performed in our hospital in emergency. a single-center retrospective study was conducted from january to december . twenty patients were operated in emergency from total nephrectomy. results: nine women and men with a mean age . ( . to . ) were treated for sepsis on emphysematous pyelonephritis or renal abscess, trauma with haemorrhagic shock, acute bleeding on renal tumours with haemorrhagic shock. one patient required critical care for multiple organ failure. th e time between the initial care and surgery was . days ( . - ). ten patients were referred to the emergency room by their physician and by a peripheral hospital. all these nephrectomies concerned native kidneys ( left kidneys). surgical approach was a lumbotomy for patients and a median laparotomy for patients. one patient died of multiple organ failure following urinary sepsis. one patient required dialysis following nephrectomy. th e mean follow-up aft er surgery was . months ( . to . ). conclusion: th e nephrectomy in emergency remains anecdotal. uncontrolled urinary sepsis were the main indications. th e identifi cation of populations at risk of progression to septic shock is essential for faster and reduced mortality in sepsis care. experiences of adrenalectomy for the incidentally discovered adrenal masses introduction and objective: a diagnosis of urinary tract obstruction (upjo) results in a functionally signifi cant impairment of the urinary transport from the renal pelvis to the ureter. options for the surgical management of upjo include ureteral stent placement, balloon dilation (antegrade, retrograde or cutting balloon), endopyelotomy, and open or laparoscopic pyeloplasty. however, in some cases, surgery is not eff ective, or too invasive for a particular patient. we herein report ten cases of treatment using bethanecol chloride. we retrospectively reviewed the record of patients, men and women, aged - years (mean . ) whose diagnosis was upjo ( cases of hydronephrosis on the left , on the right). th e chief complaints were back pain ( cases) and urinary tract infection ( cases). one patient had no complaint. all patients took mg of bethanecol chloride times a day for two weeks. aft er two weeks, kidney condition was evaluated using ultrasonography. results: five cases of hydronephrosis decreased or disappeared. five cases showed no improvement. among the latter, one had pyelonephritis, two had received laparoscopic pyeloplasty (one of whom had a non-functioning kidney and a pyelonephritis), and another had a non-functioning kidney. guzman martinez-valls p, sanchez rodriguez c, doñate iñiguez g, maluff torres a, honrubia vilchez b introduction and objective: we present man -yearold, hypertensive, diagnosed incidentally of intrathoracic renal ectopia during a constitutional syndrome study. intrathoracic renal ectopia is a very rare fi nd, with an incidence of less than of every , , which mainly aff ects left kidney since the liver protects the right diaphragm from pressure changes. a literature review of incidence, source, clinic, diagnostic and treatment of this type of renal ectopia occurs and we present the case diagnosed in our service. : chest x-ray shows a mass back in mediastinum so it was decided to ask for tomography computer (ct) that shows a hernia left postero-lateral difragmatic with promotion to the thoracic cavity of upper pole and half of the left kidney. since the patient is asymptomatic and the hernia is extrapleural does not need repairing surgical treatment. annual checks will be. intrathoracic renal ectopia is a very uncommon, usually asymptomatic, fi nding oft en diagnosed incidentally and which does not usually require treatment. surgical ( ), non-clamp zero ischemia ( ). th e average blood loss was ml (range ml - ml) and patients ( %) required blood transfusion. postoperatively patients ( %) had surgical complications: severe haemorrhage requiring emergency completion nephrectomy ( ), post-operative urinoma formation requiring ureteric stenting ( ), pneumothorax requiring tube thoracostomy ( ) . early day mortality occurred in one patient with pre-existing stage chronic kidney disease who died of acute on chronic renal failure. th e r.e.n.a.l. score of those with and without surgical complications was . and . respectively. th e complication rate of low (score - ), intermediate (score - ), and high (score - ) r.e.n.a.l. category was . %, . % and % respectively. statistically, blood loss, transfusion rate and surgical complication rate were not signifi cantly associated with medical co-morbidity, r.e.n.a.l. score or mode of ischemia, although more complex mass apparently resulted in more surgical complications. our study suggested that partial nephrectomy is a safe operation with acceptable bleeding risk and low complication rate. further larger scale study is needed to analyze the correlation of complications with renal mass complexity. introduction and objective: th e sound of running water has been eff ectively used for toilet training during the toddler period. however the eff ect of the sound of running water (srw) on voiding function for adult male with lower urinary tract symptoms (luts) has not been evaluated yet. to determine the eff ect of the srw on urination of male patients with luts, multiple voiding parameters of urofl owmetry with postvoid residual urine (pvr) were assessed according to the presence of the srw played by mobile application. a statistically pre-calculated numbers of consecutive male patients with luts were prospectively enrolled between march and april , excluding patients with hearing impairment, disability for movement, neurologic disease, urology deformity, and recent history of urinary tract infection or urethral stricture. urofl owmetry with pvr measured by bladder scan were randomly performed once a week for two consecutive weeks with and without srw in a completely sealed room away from exterior noise aft er pre-checking bladder volume scanned to be more than cc. th e srw was played with river water sound among relax melodies recorded in the smart-mobile application. results: th e mean age of enrolled patients and their mean ipss were . ± . years (range: - ) and . ± . . all patients have not been prescribed any medications including alpha-blocker or anti-muscarinic agents in the last three months. a signifi cant increase in mean peak fl ow rate (pfr) with srw was detected in comparison with pfr without srw ( . ml/s vs. . ml/s, p = . ). however, there were no diff erences in other urofl owmetric parameters including pvr. materials and methods: over a two-year period, men underwent lumbar spinal fusion by a single neurosurgeon. we excluded men with previous prostate or urethral surgery, a history of urinary retention, men taking alpha-blockers or fi ve alpha-reductase inhibitors, and men with prolonged hospital stay, leaving men evaluable. all men left the operating room with a foley catheter in place and were given a void trial on the day of anticipated discharge. twenty-three men were unable to void aft er eight hours and had their foley catheters replaced; they were discharged next day with an appointment for urologic follow-up. th ese men were compared to successful voiders with respect to comorbid medical conditions, age, surgical placement of hardware, operative time, lumbar level, multiple level fusion, and surgical approach. results: using multivariable analysis, successful postoperative voiders were compared with men who failed the initial voiding trial. only insulin-dependent diabetes mellitus (p-value less than . ) and multiple lumbar level surgery (p-value less than . ) were predictive of initial postoperative failure of voiding trial. conclusion: men scheduled to undergo lumbar fusion who have insulin-dependent diabetes or who will require multiple level intervention may benefi t from preoperative initiation of alpha blockade at the time of scheduling, as well as an inpatient postoperative urologic consultation. introduction and objective: heart rate variability (hrv) is a tool to measure autonomic nervous function, however there is no evidence that it is able to defi ne sympathetic hyperactivity in men with luts. we suppose that luts is diff erent between sympathetic hyperactive and hypoactive patients. th erefore we measured their hrv, divided luts patients into two groups, sympathetic hyperactive group and sympathetic hypoactive group according to the lf/hf ratio, and then compared their clinical situations. a total of symptomatic luts patients (ipss> ) and healthy volunteers were enrolled. all subjects had no disease which can aff ect autonomic nervous system, such as diabetes, hypertension and so on. electrocardiographic signals were obtained from subjects in resting state and calculated the hrv indices with spectral analyses. we divided luts patients into two groups by lf/hf ratio . which was mean value in healthy volunteer and compared the diff erence of clinical characteristics, ipss, psa and trus results. th e parameters were compared by independent sample t-test using spss version . results: th ere was no diff erence in age, serum psa and volume of prostate. th e comparative results of pa-rameters of hrv between groups (mean ± standard error) are in the table . conclusions: as most investigators believe that lf and hf represent sympathetic and parasympathetic nervous system activity, respectively, our results may suggest that luts patients with relatively sympathetic hypoactivity suff er from nocturia more than those with sympathetic hyperactivity. we suggest that the imbalance of the autonomic nervous system activity may be a factor that evokes varieties of symptoms in men with luts. introduction and objective: women presenting with urogenital pain oft en have lower urinary tract symptoms (luts). pelvic fl oor dysfunction and hypertonicity is thought to contribute to these symptoms. physical therapy and myofascial release are eff ective for both conditions, suggesting a common underlying pathophysiology. we aim to investigate the association among pelvic fl oor tone, luts, and pelvic organ distress. th ere was a tendency of lower hemoblobin decrease in ari group, however, this results was not statistically signifi cant. th ere were also no significant diff erences in improvement of ipss, qol and urodynamic fi ndings between the two groups. conclusion: preoperative use of ari does not compromise, but rather increase the effi ciency of surgery. th e use of ari is not a contraindication to th ulium laser vapoenucleation. age-specifi c relationships between lower urinary tract symptoms and late-onset hypogonadism symptoms in the japanese general population introduction and objective: aging is known to aff ect sexual, psychological and physiological functions including lower urinary tract symptoms (luts). recent data suggested that severity of luts was associated with that of late-onset hypogonadism (loh) in elderly men. however, information on the association in young adults is limited. in this study, we evaluated the relationship between luts and loh symptoms in young and middle-aged adults. results: th e mean ages of the patient and control groups were . ± . years and . ± . years, respectively (p= . ). th e mean ifsf-total and all of the ifsf sub scales (except pain) in the patient group were signifi cantly lower than those of the control group. th e mean udi- score of the patients was signifi cantly higher than the controls (p= . ). th e mean iiq- scores of the patients was higher than controls, however this increase was not statistically signifi cant (p= . ). introduction and objective: sav is one of the core components of hippo pathway, and this pathway plays a role for cell proliferation, apoptosis and migration through regulation of yes-associated protein (yap ). yap is known as an oncogenic protein in many human cancers, but only a few studies demonstrated that yap acts as an oncogene in renal cell carcinoma (rcc). in our previous study, we identifi ed sav was downregulated in high grade clear cell renal cell carcinoma (ccrcc) cases compared with low grade ccrcc cases and re-expression of sav inhibited rcc cell proliferation in vitro. to evaluate a role of sav in vivo, we created a murine xenograft model of human rcc. a total of -o cells with stable sav re-expression (sav - ) and control cells (control) were subcutaneously injected into the fl anks of mice, respectively. th ese two cell lines were also injected into subrenal capsule. tumor size, histological appearance and proliferation rate were evaluated. furthermore, transcriptome analysis was performed using a whole-genome microarray, in order to identify functional pathway by ingenuity pathway analysis (ipa) soft ware. to explore whether the identifi ed pathway was involved in hippo signaling pathway, western blotting was performed using antibodies against downstream proteins. in addition, the luciferase reporter assay was performed to explore whether the promoter activity is regulated by hippo signaling. results: tumors injected with sav - showed a decrease of tumor size and growth rate, compared with those of control. by immunohistochemical analysis, it was shown that re-expression of sav caused yap to localize in the cytoplasm. pathway analysis revealed that tgfβ signaling was found to be inhibited in tumors with sav - . in sav re-expression cells, protein levels of tgfβ were lower than those in control cells. when yap and tead were introduced, reporter activity of tgfβ promoter was increased. attached to a linear motion stage with a stepper motor. shaft buckling was determined by measuring the peak force to compress a cm section of the shaft a distance of cm. lubricity was measured by extracting each wire through simulated tissue at a constant speed, measuring average force over a second period. tip fl exibility was determined by isolating the distal cm portion of each guidewire and measuring the peak force required to compress a distance . cm while securing the tip in a small hole in a wooden block. perforation force was evaluated by stabilizing each wire in the dilator of a ureteral access sheath and measuring peak force required to perforate aluminum foil. up. , table . th e results showed that kh- protected tm cells against h o -induced oxdidative stress in a dose-dependent manner. it improved signifi cantly both the decline of semen parameters and decrease of testicular weight of androgen-defi cient rats at a dose of mg/kg. also it inhibited the activities of aromatase with and then increase the serum testosterone levels. conclusion: th ese results suggested that the aromatase inhibitory activity of kh- may contribute to the improvement of serum testosterone levels in androgen-defi cient male rats. introduction and objective: although several theories have been suggested, the pathophysiology of interstitial cystitis/bladder pain syndrome (ic/bps) is unclear. disruption of the bladder epithelial barrier is an important pathophysiologic theory of ic/bps, and uroplakin is known to have an important role in the bladder epithelial barrier. th e change in expression of uroplakin subtypes in the bladder could be related to ic/bps. we investigated the change in expression of uroplakin ib and iii in the bladders of patients with ulcerative ic/bps. bladder tissue samples were obtained from patients with ulcerative ic/bps who were treated with augmentation ileocystoplasty. samples for the control were obtained from normal bladder tissue apart from the malignant lesions of patients with bladder cancer who needed radical cystectomy. a voiding diary, the pain visual analogue scale (vas), and the o'leary-sant interstitial cystitis symptom index (icsi), and problem index (icpi) were used to assess patients with ic/bps before operation. expressions of uroplakin ib and iii were compared between the ulcerative ic/bps and control groups by immunofl uorescence staining and western blotting. results: in total, patients with ic/bps (mean age . ± . years, women and men) were evaluated. th e mean symptom duration was . ± . years. preoperative voiding frequency, nocturia, and functional bladder capacity documented in the voiding diary were . ± . , . ± . , and . ± . ml (mean ± sd), respectively. pain vas score, icsi, and icpi were . ± . , . ± . , and . ± . (mean ± sd), respectively. th e mean anesthetic bladder capacity was . ± . ml. immunofl uorescence staining showed that uroplakin ib and iii were localized in the urothelium. in western blot analysis, immunoreactive bands indicating expression of uroplakin iii were signifi cantly increased in the ic/bps group compared with the control group. however, uroplakin ib expression was not diff erent between the ic/bps and control groups. green fl uorescence protein cassette, and the infectivity of kshv was assessed using fl ow cytometry. to investigate viral replication, the levels of expression of representative kshv latent and lytic proteins were analyzed by immunofl uorescence assay. in addition, cell cycle and proliferation following kshv infection was analyzed. finally, cdna microarray was performed to identify gene changes by infection of kshv in bc. results: four bc cell lines, except rt , showed levels of infection similar to or higher than those of hu-vecs. infectivity of kshv in tccsup and huvec cells was similar, but t , , and ht- cells showed signifi cantly higher infectivity than huvec. our tested kshv-infected bc cells were latently infected by kshv. interestingly, a subset of kshv-infected bc cells showed higher brdu incorporation and proliferation rate than non-infected cells. furthermore, in soft agar colony formation assay, the numbers and sizes of colonies of kshv-infected cells were signifi cantly greater and larger, respectively, than non-infected cells. cdna microarray analysis showed that many proliferation and cancer development-related genes were simultaneously up-regulated in kshv-infected cells. introduction and objective: bladder cancer (bca) is the second common genitourinary tumor, and especially muscle-invasive bca (mibc) is poor prognosis. th erefore, it is important to clarify the mechanism of invasion in mibc is useful for the strategy of appropriate treatment. previously, we have showed hgf-met signaling is correlated with invasion in bca cells. here, we investigate the eff ects of met inhibitor, cabozantinib (xl ), in bca cells to investigate the significance of met upregulation in rt , , j , t , um-uc- cells, we conducted western blot analysis. next, we examined eff ect of cabozantinib on proliferation and invasion abilities using mtt and matrigel invasion assays. invasion assays were performed by the xcelligence system. moreover, to investigate biological function of hgf-met signaling, we analyzed gene expression profi le and real time pcr of cells which cultivated with or without hgf stimulation. . th e mechanical properties of scaff olds were measured to compare tensile strength between two types. for in vitro cell study, scaff olds were seeded with human fi broblast cell at x cells and were cultured for up to weeks. th e ability of these scaffolds to support fi broblast cell growth was also investigated in vitro. results: d strand-deposited scaff olds were characterized by sem images and porosity measurement. sem images showed the surface morphology of pcl scaff olds. th e young's modulus of °pcl was . ± . mpa, and °pcl was . ± . mpa, respectively. human fi broblast cells covered well the surface of the scaff olds. immunofl uorescent staining of α-er-tr on fi broblast cells/scaff olds confi rmed that the cells remained viable and proliferated throughout the time course of the culture. th is is a preliminary study to investigate the possibility of using d bioprinting technique for tissue engineered tunica albuginea. introduction and objective: aft er - years at people the decrease in a pool of pluripotent stem cells resulting in insuffi ciency of replenishment of cellular structure of cambial zones and, as a result, to incomplete replacement of the perishing old cells is observed. in reply surrounding epithelial and endothelial cells, and also the macrophages, attracted with death of old cells, stimulate cells division of growth zones by the cellular growth factors (pechersky a.v. et al., ) . to patients aged from till years with a cancer of a kidney, bladder, prostate gland of a stage of t -t the chemotherapy or target therapy was carried out. to patients of - years for restoration of regeneration it was carried out from to transfusions of mononuclear fraction of peripheral blood, same-gender and blood types with recipients. results: in month aft er carrying out chemotherapy or target therapy aft er development of a leukopenia in patients the level of the basic fi broblast growth factor (bfgf) increased on average by . times, at patients from them the increase in level of the human vascular-endothelial growth factor (human vegf-a) on average by . times was observed, the rd of them had an increase in the human epidermal growth factor (human egf) on average by . times. in - months aft er the last transfusion of mononuclear fraction of peripheral blood the maintenance of hemopoietic cells predecessors of cd + in peripheral blood increased on average by . times (at patients with to - cells in mcl). at patients the level of the basic fi broblast growth factor (bfgf) decreased on average by . times, at patients from them reduction of level of the human vascular-endothelial growth factor (human vegf-a) on average by . times was observed, the rd of them had a reduction an human epidermal growth factor (human egf) on average by . times. decrease in levels of cellular growth factors naturally brought at all patients in a buccal epithelium to decrease in an expression of p on average by . times, at the rd of them to decrease in an expression of bcl- on average by . times. excess stimulation of mitotic activity at people years are more senior it is possible to lower to normal level by means of restoration of number of a pool of pluripotent stem cells by transfusion of mononuclear fraction of the peripheral blood from young donors of - years of one with the recipient blood types and a sex. mashhadi r to compare the expression rate of sex steroid hormone receptors of estrogen (er), progesterone (pr) and androgen (ar) in normal urothelium and urothelial bladder cancer (ubc) and to evaluate the possible associations of these receptors expression with cancer progression and patient's survival. we evaluated the clinical data and tumor specimens of patients with patho-logically confi rmed primary ubc with normal healthy controls. both patients and controls selected from list of subjects who have been referred to sina urology clinic, and had a minimum of one year follow-up duration. data collected from medical cords. for evaluation of expression, immunohistochemistry was performed on paraffi n-embedded tissue sections using a monoclonal antibody for androgen, estrogen and progesterone receptors. presence of at least % positive cells defi ned as positive expression. results: none of the control subjects showed ar expression, while % of the patients were ar-positive. er/pr expressions were observed in . %/ and . % of the cases and in . % and . % of the controls, respectively. a statistically signifi cant correlation was found between ar expression and tumor stage and grade (p < . ). ar-positive patients showed a signifi cantly poorer prognosis than ar-negative cases (log-rank test, p = . , hazard ratio = . ; % confidence interval: . - . ). conclusion: ar expression was signifi cantly associated with higher grade and poorly diff erentiated tumors with unfavorable outcome. ar expression test might be useful as a diagnostic tool for determining the malignancy and outcome of ubc patients. park s, park w, yoon s introduction and objective: previous researchers consider interaction roles of ampk and ros as a regulator of cancer cell apoptosis and cancer invasiveness in hypoxia and oxidative stress. th e aim of this study was to fi nd out the other aspect of invasion and cell death mechanisms as a new treatment option in urothelial cancer. we performed western blot analysis to determine association between ampk regulator (compound c, aicar) and ros scavenger (nac and tempol) as cytotoxic eff ectors. using gelatin zymography to measure mmp- , activity, we evaluated the cancer invasion. pathway activation analysis was also determined by western blot. cell survival was investigated by mtt analysis. results: ros scavenger like nac and tempol treated cells showed no change of expressions of phospho-ampk. aicar, compound c and tempol treated cells showed no change of mmp- and mmp- expressions. however, nac treated cells showed decreased expressions of mmp- and mmp- . ai-car and compound c treated cells with or without added nac and tempol showed no change of mtor and phospho-mtor expressions. aicar treated cells only showed decreased expression of phospho-p s k. compound c and tempol treated cells did not showed statistically any change in cell counts. however, aicar and nac treated with or without added compound c and tempol showed increased cell death signifi cantly. conclusions: activator of ampk and ros scavenger like nac decrease t invasion activity and increase t cell death. so, we demonstrate that the cytotoxic mechanism of bladder cancer remains to be further investigated. epigenetic bladder cancer is still one of common human malignancies which some environmental agents play important role in the process of carcinogenesis, such as aromatic amines or chronic arsenism, and easy to be recurrent and progressive despite of therapy. it is continuing to search some novel genetic or epigenetic biomarkers and to investigate their signifi cance in bladder urothelial carcinoma. doc- /dab (diff erentially expressed in ovarian carcinoma- /disabled- ) interacting protein (dab ip), a novel family of ras gtpase-activating protein family, is a potent tumor suppressor gene. th e objectives of this study are to explore the prognostic values of dab ip expression and the possible regulatory mechanism in superfi cial bladder cancer. with irb consent and patient permit, eight human urothelial cancer cell lines and superfi cial bladder cancer tissues were available for exploring dab ip expression using western blotting and immunohistochemical staining, respectively. th e prognostic signifi cance of dab ip expression in term of recurrence and progression were analyzed with log-rank test. aft er treated with demethylizing agents trichostatin a (tsa) and -aza ' deoxycytidine (aza) separately and together, urothelial carcinoma cell lines were then tested with dab ip mrna expression using quantitative rtpcr. data mining was also done using published mrna diff erential array (dataset gse ). th irty patients with non-muscle invasive bladder cancer and agematched healthy controls were included in the study. peripheral blood samples were obtained from the patients before transurethral resection of bladder tumor (turbt), twenty days aft er the operation (fi rst control) and at the end of intravesical immunotherapy (second control). vegf- , mmp- , es and tsp- were measured by enzyme-linked immunosorbent assay (elisa). th e mean marker levels of the patients and controls were statistically compared. th e mean marker levels of the patients before turbt, in the fi rst and second control were also compared. results: th e mean age of the patients ( females and males) and controls ( females and males) were found to be . ± . and . ± . , respectively (p= . ). although the mean vegf and mmp levels in the patients before turbt were signifi cantly higher than the controls (p< . and p< . , respectively), there were no diff erences between the mean es and tps- levels (p= . and p= . , respectively). th e wegf- and mmp- levels signifi cantly decreased aft er turbt (p< . and p< . , respectively). th ese reductions continued aft er intravesical immunotherapy, but these diff erences between fi rst and second control were statistically insignifi cant. th is study showed that elevated angionenic factors in the patients with bladder cancer decreased aft er the treatment. we think that vegf and mmp may be used for the follow-up and therapy of non-muscle invasive bladder cancer. prognostic results: nitrose oxide level and bfgf expression were signifi cally elevated in patients with urothelial carcinoma associated with chronic bladder infection, normal urothelium showed low levels of no and low expression of bfgf. conclusion: th e association of elevated levels of nitrose oxide and over-expression of bfgf indicated that the angiogenic peptide bfgf had been modulated by nitrose oxide. th ese results would indicate an anti-angiogenisis target therapy in urothelial carcinoma associated with chronic bladder infection. the relationships between increase of serum creatinine and recurrence of nonmuscle invasive bladder cancer after transurethral resection of bladder tumor introduction and objective: while impaired renal function had a negative impact on the prognosis of invasive bladder cancer by infl uencing stage of tumor and selection of treatment modality, the relationships between the change of renal function and prognosis of non-muscle invasive bladder cancer (nmibc) have not yet been studied. preliminarily, we investigated the impact of increased serum creatinine and recurrence of nmibc. a total of patients who underwent transurethral resection of bladder tumor (turbt) with minimum follow-up of months were divided into two groups based on with (n= ) or without recurrence (n= ). th e changes of serum creatinine from the preoperative baseline to the time of recurrence were evaluated (Δ creatinine). for subjects without recurrence, serum creatinine was measured at months aft er turbt. th e impact of variables including characteristics of host (age, sex, past medical history, bmi, and smoking history), tumor (location, size, and grade), and laboratory data on recurrence of nmibc were then analyzed. tsai y , jou y , tsai y , liu b , lin h , wei c , chen s , tsai h , tzai t introduction and objective: bladder cancer is a common human malignancy and exhibits a life-long risk of disease recurrence and progression. it is continuing to search some simple, innovative biomarker to monitor the disease status in order to diminish the suff ering during cystoscopic follow-up. th e metabolite of tryptophan aft er indoleamine , -dioxygenase (ido) digestion, -hydroxyanthranilic acid ( -haa) is conventionally thought to be a potential biomarker for bladder cancer occurrence. th e aim to study is to investigate the diagnostic potential of an integrated a -haa-based biosensor for urothelial carcinoma of the upper tract and urinary bladder. human urothelial cancer cell lines and human urothelial carcinoma tissues as well as adjacent benign tissues were available for exploring ido expression, including western blotting and immunohistochemical staining. patients who received urological surgery were enrolled for urine -haa testing using an integrating biosensor for -haa. some of urine specimens were investigated with high performance liquid chromatography (hplc) assay. results: from western blotting assays, eight human urothelial carcinoma cell lines exhibited more ido expression than the immortalized cell sv-huc. both of urothelial carcinoma of urinary bladder and upper urinary tract exhibited more ido immunoreactivity than those of the adjacent benign bladder, ureteral or cortical tissues (chi-square test, p= . ). th ere is a moderate correlation for urine -haa measurement based on between hplc and the biosensor assays (r = . , p= . ). besides, the -haa content within the cultured media of tccsup and bftc measured with biosensors signifi cantly increased with incubation time (p < . ). finally, patients with urothelial carcinoma of bladder and upper tract have higher urine -haa levels than those without recurrence or benign urological disease, such as bph, or hernia (unpaired t-test, p= . ), except for urolithiasis. conclusion: th e integrated biosensor exhibited a modest accuracy in urine -haa detection. both of urothelial carcinoma of urinary bladder and upper tract exhibited higher ido expression and its metabolite -haa in urine. how a cancer spreads: public awareness of genitourinary cancer introduction and objective: patients' perceptions of disease can aff ect the diagnosis and treatment of the disease. it is diffi cult to give a defi nite answer to the questions; "can genitourinary cancers be spread around during coitus or in public bathtub?". doctors know that there is no evidence that cancers can be spread in this way, however many people don't know that. th e objective of this study was to investigate the public awareness of genitourinary cancer. one hundred and forty nine patients who have visited outpatient department of urology completed a self-administered questionnaire from june to july . th e questionnaires included epidemiologic information about age, gender, residential area, level of education and yearly income and the questions whether prostate cancer and bladder tumor could spread out during coitus or bathing. returned responses to questions were analyzed. results: a total of of ( %) patients completed the questionnaires. mean age was years, and ( %) men and ( %) women were included. th e residential area were metropolitan in ( %), urban in ( %), and suburban in ( %), respectively. th e level of education were middle school graduates in ( %), high school graduates in ( %), and college graduates in ( %), respectively. th e yearly incomes were under , dollars in ( %), , ~ , in ( %), and over , in ( %), respectively. seventeen ( %) and ( %) patients answered that they thought that bladder tumor could spread during coitus and bathing, respectively. likewise ( %) and ( %) patients answered that they believed that prostate cancer could spread during coitus and bathing, respectively. moreover, young patients (< years) reported that they have the opinions that coitus spreads prostate cancer ( %) and bladder tumor ( %). of college graduates, % and % reported that they thought coitus spreads prostate cancer and bladder tumor, respectively. conclusion: a signifi cant proportion of patients believed that prostate cancer and bladder tumor could spread during coitus. furthermore, even young and highly educated people also tended to have this misbelief. protoporphyrin we evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples aft er extracorporeal treatment with -aminolevulinic acid (ala). further, we investigate the protein that plays a key role in increased accumulation of protoporphyrin ix in bladder cancer cells. sixty-one patients with bladder cancer, confi rmed histologically aft er the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and outpatients without history of urothelial carcinoma were recruited as the control group. half of the voided urine sample was incubated with ala, and the rest was incubated without treatment. intensity of the samples at the excitation wavelength of nm was measured using a spectrophotometer. th e diff erence between the intensity of the ala-treated and ala-untreated samples at nm was calculated for photodynamic diagnosis of bladder cancer. immunohistochemistry was used to estimate the expression of peptide transporter , hydroxymethylbilane synthase, ferrochelatase, atp-binding cassette , and heme oxygenase- in samples from patients who underwent transurethral resection of bladder tumors. th e correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin ix in bladder cancer cells in voided urine was evaluated using pearson's correlation analysis. results: th e area under the curve was . . sensitivity and specifi city of the method were % and % respectively. th e expression of peptide transporter (p < . , r = . ), heme oxygenase- (p < . , r = . ), and ferrochelatase (p < . , r = . ) was correlated with the accumulation of protoporphyrin ix in bladder cancer cells in voided urine. we demonstrated that protoporphyrin ix levels in urinary cells treated with ala could be quantitatively detected by spectrophotometer in patients with bladder cancer. th e expression of ferrochelatase plays a key role in the accumulation of protoporphyrin ix in photodynamic diagnosis of bladder cancer. assessment of visual inspection as a tool to determine pelvic drain fluid type following radical cystectomy crozier j, papa n, lawrentschuk n introduction and objective: following radical cystectomy, patients generally spend a period of days under observation on a urology ward. during that time, staff closely monitor pelvic drain output to assess for the possibility of a urine leak. we aim to investigate the ability of medical and nursing staff to correctly identify pelvic drain fl uid type using visual inspection alone. investigators collected a series of de-identifi ed images showing pelvic drain fl uid in patients post radical cystectomy. th e fl uid type in each image was confi rmed by measuring creatinine level. investigators then attended a victorian public hospital urology meeting and a victorian gp conference. attendees were invited to participate in a study. present staff included consultant urologists, urology registrars, urology residents, urology nurses, medical oncologists, radiation oncologists, general practitioners and medical students. participants were then provided with a survey. th ey were asked to indicate their level of experience working on a urology ward, the number of years since graduation from their primary medical or nursing degree. participants were then shown the series of pelvic drain fl uid images on a project. th ey were asked to correctly identifying the fl uid type in each image. using the survey, participants had the option of choosing either urine or peritoneal fl uid. results: all groups poorly identifi ed fl uid type. no individual staff group was signifi cantly better at identifying fl uid type. level of experience on a urology ward and years since graduation do not infl uence ability to determine fl uid type. conclusion: visual inspection of pelvic drain fl uid is a poor determinant of fl uid type. chang y, hsiao p, chen g, lee s, huang c, wu h, yang c, chang c introduction and objective: muscle invasive bladder urothelial cell carcinoma occasionally mixed with squamous diff erentiation. we conducted this study to investigate the incidence and treatment outcome of bladder urothelial cell carcinoma with squamous component. we enrolled patients muscle invasion bladder cancer who received radical cystectomy with bilateral pelvic lymph node dissection during to . patients' characteristics, chemotherapy record, and pathological report were retrospectively reviewed. th e following endpoints were assessed: overall survival (os) and recurrence-free survival (rfs). response of neoadjuvant chemotherapy subgroup was also analyzed. all survival data were analyzed by the kaplan-meier method using a log-rank test and multivariate analysis was carried out using a cox proportional hazards regression model. results: it was very clear that more than one third of these cases coming from the south of saudi arabia ( . %). th e bilharzia infestation found in ( . %) of the cases most of them are the southern patients. th e t staging turn to be high in most of our cases ( . % are t b). squamous cells carcinomas was also a striking feature of our result and found in ( . %). lymph node involvement found in one fourth of these cases ( . %). a total of ( . %) had local or lymph node recurrence and ( . %) got distant metastasis. around % ( cases) of our result showing that these cases having high grade and around % ( cases) had a hydronephrosis upon presentation. bladder cancer as a cause of death because of its advancement or recurrence account for ( . %) of deaths happened in these cases. th e survival of these cases severely aff ected by the fact that cases ( . %) could not know there survival status because they stop to show up in our institute for follow-up in spite the fact that there are some of them followed for more than years. arabia showing that the bilharzia infestation is quit high especially in the south and the squamous cell cancer is not as low as we expected. finding of hydronephrosis, lymph node involvement, high t and high recurrence in high percentage of our cases indicating that the bladder cancer aggressiveness behavior is not changing over years. introduction and objective: th is is an observational retrospective study utilising long-term patient follow-up for years (ys). to determine the survival and quality of life in women with age range - years, who had been treated for carcinoma of the bladder with radical cystectomy with preservation of genital organs. materials and methods: study included women patients with invasive urothelial carcinoma of the bladder treated with genital sparring radical cystectomy during the period from to . th ey had orthotopic ileal neobladder. follow-up included recurrence-free survival, metastases-free survival, overall survival, continence, and sexual function. results: overall survival up to - ys was in / women ( . %). survivors up to ys were in / ( . %). survival from to ys was in / patients ( . %). tumours stage of t were / patients, t were / patients, and t a were / patients. tumour grade was g in / , g in / , and g in / . age range of - ys were patients, range of - ys was patients, range of - ys was patients. continence was good in / patients; three patients / needed cic. sexual function tested by fsfi over< - was ( . %). conclusion: th e study provide evidence of safety and effi cacy of radical cystectomy with sparing of genital organs in women aged to with low grade, low stage invasive urothelial carcinoma of the bladder. oncological outcome for - years was good; continence and sexual function were very good. th is procedure should be considered when surgical approach appears to be feasible. tan w, sherer b, nehra a, deane l introduction and objective: radical cystectomy for bladder cancer has been the surgical gold standard for decades. increasingly, experience with robotic assisted techniques has become more common in select centers. in the majority of instances, the urinary diversion has been performed extracorporeally and with the use of stents. herein, we report our center's initial experience with robotic radical cystectomy and stentless totally intracorporeal urinary diversion. a retrospective review of the medical records of all patients undergoing robotic cystectomy and intracorporeal diversion was conducted at rumc from - . specifi cally, attention was focused on perioperative parameters. results: a total of patients were identifi ed (male= , female= ) in the sample. four patients underwent intracorporeal ileal conduit reconstruction and one patient underwent totally intracorporeal ileal neobladder reconstruction. no patients received a pre op bowel preparation, post op pca or epidural and all were allowed oral intake early. no patient received a transfusion for operative blood loss. one patient was readmitted for dehydration. see table for details. conclusion: robotic assisted radical cystectomy with stentless intracorporeal diversion is safe and feasible. eliminating bowel preparation, pca and epidural, and incorporating early refeeding and ambulation may result in a shortened length of stay. a rigorous post-operative plan to optimize return of bowel function, permit rapid reintroduction of diet without restrictions and facilitate early ambulation is critical in improving outcomes for this patient population. computed up. , table . and hypermethylation of these two gene promoters. in order to investigate clinical usefulness for noninvasive bladder cancer detection, we further analyzed the methylation status in urine samples of bladder cancer patients. methylation of the tested genes in urine sediment dna was detected in the majority of cases that were hypermethylated in tumor samples ( . %) and the frequencies were . % . % and . % for apc, rarβ and survivin, respectively. our results indicate that methylation of apc, rarβ and survivin gene promoters is a common fi nding in patients with bladder carcinoma. th e ability to detect methylation not only in bladder tissue, but also in urine sediments, suggests that methylation markers are promising tools for noninvasive detection of bladder cancer. usefulness of the all cases were followed for over year. th e procedure is ) point marking; ) circular incision; ) level incision; and ) specimen retrieval using a needle electrode in accordance with the ukai's method. we investigated pathological fi ndings (margin situation), operation time, complications and recurrence. results: it is possible to diagnose the precise pathological fi ndings by turbo. we judged the width and depth ew in sequential section. th ere were few complications during and aft er the operation. operation time of turbo ( - min) was longer than conventional turbt. urethral catheter holding period and hospitalization period aft er turbo was the same as turbt. turbo is a relatively safe procedure even for beginners. twenty cases had a recurrence in cases. eleven cases had a recurrence in under year, but the same place recurrence was cases. th ere were few cases of same place recurrence in under year among margin-negative cases. th erefore we judged that ew-negative cases had no residual cancers. conclusion: turbo is a safe and useful procedure that provides precise pathological fi ndings with minimal complications. second tur is not necessary for turbo. turbo has a possibility to be gold standard of the treatment for non-muscle invasive bladder cancer (nmibc). the risks of bladder-preserving bacillus calmette-guérin therapy in high-grade non-muscle-invasive bladder cancer continuous physical activity has many eff ects on human body. it doesn't only strengthen the skeleton or muscles; it also affects cardiovascular system, nervous system and etc. in this research we wanted to fi gure out if continuous physical activity (cpa) eff ects the lower urinary tract symptoms in retired military offi cers or not. th is is a retrospective study. retired offi cers attending to urology clinic for annual prostate control and not using any drugs for prostate were enrolled in this study. aft er the patients' permission were taken for the study they were asked for cpa or not and their international prostate symptom scale (ipss) answers were compared. results: th ere were patients in cpa group and patients in non-cpa group. th e mean age is ( - ) in cpa group and . ( - ) in non-cpa group. answers of questions in ipss: incomplete emptying (p= . ), frequency (p= . ), urgency (p= . ), and straining (p= . ) were detected statistically rare in cpa group (table ) . although they were not statistically signifi cant, intermittency (p= . ), weak stream (p= . ) and nocturia (p= . ) were rare in cpa group too (table ) . in order to maintain a better lower urinary tract function, elderly men should continue their physical activity aft er retirement. conclusions: th e number of nocturia episodes was signifi cantly and linearly correlated with ipss total score, voiding, storage, qol and nih-cpsi voiding scores. however, other risk factors, including bmi, body fat percentage, blood pressure, bun, creatinine, lipid panel, ck, t , free t , prostate-specifi c antigen, serum testosterone levels, urine fl ow (assessed using urofl owmetry) and prostate size (assessed using transrectal ultrasound and digital rectal examinations) were not associated with the number of nocturia episodes, despite an a priori assumption that they all infl uence nocturia risk. risk results: symptom prevalence increased to . %, and the mean international prostate symptom score increased by . points during years. aft er adjusting for confounders, smoking history of ≥ pack-years was an independent risk factor for symptom deterioration and storage sub-symptoms, compared with non-smokers ( . and . odds, respectively). physical activity had a protective eff ect for voiding sub-symptoms. high daily protein intake exacerbated the storage symptoms. however, alcohol intake was not associated with symptom deterioration. conclusions: th e symptom prevalence among elderly men living in a suburban area increased to . %, and the international prostate symptom score increased by . points during years. smoking history, physical activity, and protein intake were associated with symptom deterioration. however, there was no signifi cant association with alcohol intake and symptom deterioration. russo g, castelli t, urzì d, privitera s, fragalà e, favilla v, cimino s, morgia g introduction and objective: a signifi cant amount of epidemiological evidences have underlined an emerging link between mets, benign prostatic enlargement (bpe) secondary to benign prostatic hyperplasia (bph) and related lower urinary tract symptoms (luts). we aimed to assess the connections between lower urinary tract symptoms (luts) related to benign prostatic enlargement (bpe) and metabolic syndrome (mets) with its components. is increased prostatic urethral angle related to lower urinary symptoms in male without prostatic obstruction? introduction and objective: th e prostatic urethra is a bent tube, and the clinical signifi cance of the prostatic urethral angle (pua) was recently reported. we investigated the statistical signifi cance of an increased pua on the international prostate symptom score (ipss), with luts/bph. a prospective analysis was made of patients ( . ± . years) with luts and/or bph. patient underwent an evaluation including the ipss, psa, transrectal ultrasonography, urofl owmetry, and measurement of post-void residual. pua were measured by cystourethroscopy ( figure ). in order to minimize the eff ect of prostate, patients with prostatic obstruction under cystourethroscopy were excluded. th e minimum pua degree of symptoms change was constructed as a predictor of the eff ect of medication. all patients received tamsulosin . mg during the fi rst weeks and . mg during the next weeks. results: th e psa, prostate volume and pua were . ± . ng/ml, . ± . ml and . ± . °, respectively. th e area under the roc curve was . at the degrees with a sensitivity of . % and a specifi city of . %. comparing a higher pua (over degree, group a) with a lower pua (under degree, group b), patient with a higher pua had a longer luts period (p= . ), an improvement of symptoms aft er medication (p= . ) and an increase of average fl ow rate (p= . ). however, there was no signifi cant diff erence in age, psa, post-voided volume between the two groups. conclusion: pua showed signifi cantly correlated with the improvement of ipss, the eff ect of medication, and urofl owmetry. our fi ndings suggest that pua under cystourethroscopy may be one method to assess the presence of luts in men and help in the treatment of individuals by better predicting their likely classifi cation from ipss, urofl owmetry, and prostate volume. however, further studies are needed to explore the mechanisms and the eff ects of pua under cystourethroscopy. introduction and objective: th e prevalence of lower urinary tract symptoms increased with age. it is known that irritable bladder symptoms such as urinary frequency, urgency, nocturia increased with age in many studies. recently it was reported that vascular calcifi cation was one of the cause of lower urinary tract symptoms. we studied to evaluate the association between lower urinary tract symptoms of vascular calcifi cation in the abdominal ct using by agar score. th e records were obtained from a retrospective database who underwent abdominal ct due abdominal pain, hematuria. sex, age, height, weight, prostatic size, calcifi cation of aorta and internal iliac artery, amount of subcutaneous fat and visceral fat in the umbilicus level, international prostate symptom score, overactive symptoms score and urofl owmetry were assessed. calcifi cation of aorta was estimated from renal artery bifurcation to iliac artery bifurcation level. and internal iliac artery calcifi cation was calculated from bifurcation of iliac artery to bladder. we scanned each subject of . cm interval on the ct scan. th e calcifi cation of blood vessels was measured as agar score using abdominal ct aft er our explaining about each contents of nih-cp-si and iief- , the paper was checked by volunteers in person, and then we collected it. th e subjects were limited to - s korean male. we analyzed the collected questionnaires, and considered men who have perineal and/or ejaculatory pain or discomfort and a total nih-cpsi pain score of ≥ as having prostatitis-like symptoms, and categorized to four groups by iief- score, mild ( - ), mild-moderate ( - ), moderate ( - ), severe ( - ). results: an average age of volunteers was years old ( - ). th e iief- category was divided to fi ve groups. among total volunteers, persons were chronic prostatitis like symptom patients ( . %), and whose nih-cpsi average of pain score, voiding score, quality of life score and total score were . ± . , . ± . , . ± . , and . ± . , respective-up. , figure . ly. th ere were a little correlations among pain score, voiding score, quality life score, but not signifi cant. an average of total iief- scores in chronic prostatitis like symptom patients was . ± . , it was signifi cantly lower than absent group. th ere were all negative correlations of between iief- and pain score (t=- . , r = . , p= . ), voiding score (t=- . , r = . , p= . ), qol score (t=- . , r = . , p= . ), and total score (t=- . , r = . , p= . ). conclusion: th e higher total nih-cpsi score, especially pain score plays a larger role, adversely aff ects erectile function of chronic prostatitis like symptom patients in - s korean male. a antimuscarinic agent is the mainstay of treatment, but it have side eff ects such as dry mouth, constipation. th ese eff ects resulted in cessation of medication in many cases. th e authors therefore assessed the impact of side eff ects on health-related quality of life (hr-qol) through an analysis of questionnaires. th is study was designed to investigate the patients' satisfaction by quality weight (utility weight) of health status as aff ected by the side eff ects of oab medications in tertiary hospitals in korea. patients who had oab symptoms lasting longer than months and side eff ects aft er any antimuscarinic treatment fi lled in the eq- d. th e questionnaire and vas score for two diff erent health statuses, presence or absence of side eff ects, were analyzed. quality weight was calculated using the score of ed- d health status. results: one hundred patients were enrolled. th e most prevalent side eff ect was dry mouth ( %), followed by constipation ( %). twenty-eight percent of the patients had dry mouth and constipation concurrently. most of the patients with side eff ects tried to overcome these side eff ects ( %), but % desired a change in medication, and % stopped medication altogether. fift y-fi ve patients replied that they consider side eff ects to be an important factor in deciding on the continuation of medication. th e quality weight of eq- d without side eff ects was . , while the quality weight with side eff ects was . (p= . ). th e vas score was in patient without side eff ects and in those with side eff ects, supporting the results of quality weight assessment. th e same trend was observed when stratifi ed according to age and sex. as for the overall distribution of ed- d, the patients with side eff ects were less healthy in terms of daily life, pain/discomfort, and anxiety/depression. introduction and objective: treatment of men with large prostates is challenging with greater risk of complication and retreatment. while photo-vaporization (pvp) has been well described for greenlight w-xps, vapor resection techniques have been described to help improve tissue resection, including vapour-incision techniques (vit). we sought to evaluate the effi ciency, safety and outcome parameters between greenlight pvp and vit specifi cally for men with prostate volumes > . among xps cases retrospectively collected from experienced surgeons at high-volume greenlight xps centers, had large prostates. preoperative, operative and post-operative parameters were collected and compared between groups. results: as summarized in table , men undergoing vit (n= ) had comparable preoperative parameters to those undergoing pvp (n= ). while vit allowed greater delivery of energy ( . vs . kj/g), operative time was longer and there was greater need for > fi bres. th ere were no diff erences in intra-and day post-operative adverse events. both vit and pvp demonstrated comparable marked improvements in ipss/qol at months post-operatively. however, despite greater urinary retention and pvr preoperatively, men with vit demonstrated signifi cantly lower post-operative pvr and greater qmax at moths. no signifi cant diff erence in retreatment rates was noted between vit and pvp follow-up. conclusions: both greenlight pvp and vit techniques can be safely used to treat men with large prostates. both techniques off er signifi cant and durable relief of symptom relief with comparable complication rates at years. longer follow-up is necessary to assess durability. open within two years, one-hundred patients were prospectively randomized into two equal groups. all patients underwent tvp whereas rb was used in group- . rb is a balloon fi xed to -way foley catheter tip by blaster strip making it air tight. we placed it in the rectum opposing prostate and infl ate (pressure controlled) for min. hemoglobin (hg) levels have been assessed pre-and postoperation. blood transfusion, amount of saline for irrigation, catheter duration, hospital stay, and rectal complain were recorded. follow-up was and -mo, postoperatively. results: enucleated adenoma weight was gm in g- and gm in g- . th ere is signifi cant diff erence between both group for hg-loss within fi rst h post-operative and total hg-loss . gm in g- and . gm in g- (p, . ) and . gm vs. gm (p, . ) respectively. also there is signifi cant diff erence between both group in relation to the saline/l for irrigation ( . vs. . l), catheter duration ( . vs. . day), and hospital stay ( . vs. . day), with favorable results to the rb group. blood transfusion was in g- and one in g- . th ere is no rectal complain. conclusion: rb infl ation post-tvp is simple and safe procedure without operative technique, reduces post-operative blood loss, blood transfusion incidence, saline for irrigation, and shortens the catheterization period and hospital stay, without rectal complication. conclusion: th ough this was not a head-to-head study and there were a number of dissimilarities in the study design, we demonstrated a non-inferiority of our study and a signifi cantly shorter median length of catheterization, time until stable health, and hospitalization relative to the goliath study. introduction and objective: th ulium laser enucleation of the prostate (th ulep) has been introduced as a minimally invasive treatment for benign prostatic obstruction (bpo). th e aim of the study is to assess what are the intraoperative key points and possible complications of the morcellation procedure aft er th ulep. to assess whether this events have any eff ect on hospitalization length. a cooperation between the university of milan and moscow was settled. prospective study that analyzes events that prolonged the morcellation process aft er completing thullium laser enucleation procedure in a group of consecutive patients was performed. events related to the morcellation procedure were recorded. patients' hospitalization length were evaluated aft er discharge only considering patients that were not re-admitted because of a surgical related issue. statistical analysis was performed by the student t and chi-square test and logistic regression analysis. for all statistical comparisons signifi cance was considered at p< . . results: mean age was . years. five groups of reasons for prolonged morcellation were recorded. bladder suction with wall damage, bleeding due to "ex vacuo" fast empting, suction problem, morcellation impairment and prolonged morcellation time due to enlarged prostate. each group of issues was related to a signifi cant prolonged operative time (p< . ). th e table shows the key points rate and their correlation with a prolonged hospital stay. a statistical significance between the event and the prolonged hospital stay found only for bladder suction. conclusions: issues related to the morcellation procedure aft er laser enucleation of the prostate (th ulep) causes prolonged hospitalization length only in the case of bladder suction. other events, even if related to a slower operative time, do not mean a prolonged hospitalization. suprapubic cystostomy makes turp more effective and safer introduction and objective: a recent survey found turp the commonest performed procedure in bph, despite the rising popularity of laser prostatectomy. th e reasons for popularity in laser are ease of performance, lesser complications, and good results. it is the complications factor that makes it look attractive. th e onus is therefore to make turp safer. th is is more applicable in india, where the cost of laser excludes - % of patients. numerous innovative procedures have been tried to make turp safer. continuous outfl ow has been described as innovation, the means to achieve it not described. introduction and objective: prophylactic peri-vesical drain placement during suprapubic prostatectomy remains a widespread surgical practice. however the surgical technique of suprapubic prostatectomy has signifi cantly improved and as such the contemporary role of prophylactic surgical drains needs reevaluation. it has been traditionally assumed that prophylactic drains helps prevent fl uid collection (blood, serum, urine) which if not drained can lead to surgical wound complications. th is paper investigates the incidence of surgical wound complications aft er a series of suprapubic prostatectomy done without placement of surgical drains but in the context of modifi cations to the surgical technique. prostatic hyperplasia (bph) were operated upon between and -all using a modifi ed suprapubic prostatectomy technique that includes meticulous dissection, hemostatic suturing that covers the main areas of anatomic distribution of the urethral arterial branches of the inferior vesical artery, non-placement of drains and suprapubic catheter, and also routine irrigation of the surgical wound with normal saline among other modifi cations. pre-and post-operative blood hemoglobin levels, prostate specimen weights and presence of surgical wound complications if any were recorded. th e main outcome measure was to determine the presence of early surgical wound complication defi ned as clinical evidence of hematoma/ seroma, infection, drainage or wound dehiscence. results: th e mean age of the patients was . (range of to years). th e mean prostate weight was . gm-(range of to gm). th e mean hemoglobin diff erence was . mg/dl (range of . mg/dl to . mg/dl). on a minimum days observation of the surgical wounds, there was only one case of superficial wound infection ( . %) that healed with wound dressing. th ere was no mortality and none of the patients received blood transfusion. in the context of an improved surgical technique, suprapubic prostatectomy for bph can be safely performed without the placement of prophylactic peri-vesical drain. non-placement of prophylactic surgical drains in this series was not associated with increased wound complication rate. effects of detrusor underactivity conclusions: according to detrusor activity, there were not diff erent in diff erences between preoperative or postoperative ipss. abnormal detrusor contractility (esp. dua) cannot be a contraindication for tur-p, and turp should be a defi nite therapeutic option in abnormal detrusor activity. geavlete p, dragutescu m, multescu r, georgescu d, geavlete p introduction and objective: th is long-term retrospective study aimed to analyze the re-intervention necessities aft er bipolar plasma vaporization of the prostate (bpvp) in patients with medium sized benign prostatic hyperplasia (bph). materials and methods: th ere were followed patients who underwent bpvp for prostates sized between and ml. th e re-intervention rates were analyzed during a follow-up period of at least months. results: additional interventions consisted of immediate reoperation for secondary hematuria, endoscopic re-intervention for urethral stricture or blad-der neck sclerosis and transurethral resection of the prostate (turp) for residual bph bulk. endoscopic hemostasis during hospitalization was required in cases ( . %) and in discharged patients in other cases ( . %). during the follow-up period, patients ( . %) with bladder neck sclerosis underwent the plasma vaporization approach. urethral stricture was diagnosed in patients ( . %), of them receiving internal optical urethrotomy while urethroplasty was performed in cases. residual adenoma was present in patients ( . %), thus requiring and secondary turp. conclusion: bpvp is a valuable endoscopic treatment alternative for medium size bph cases with higher effi ciency and a satisfactory rate of reoperation. diode laser nm for the treatment of bph: long-term comparison of the enucleation vs. vaporization introduction and objective: to report -years follow-up results of clinical trial comparing diode laser enucleation of the prostate (dilep) with diode laser vaporisation of the prostate (dlvap). a total of consecutive patients were included in the prospective study who had received laser treatment for bph. patients were assigned to two groups based on the type of procedure: to dilep group and to dlvap group. patients with a history of neurogenic bladder dysfunction, chronic prostatitis or bladder cancer were excluded from evaluation. standard follow-up examinations were performed in both study groups in predefi ned time points (in the perioperative period, at month and month , and month , and then every year). primary endpoints included: lower urinary tract symptoms (luts) as measured by the international prostate symptom score (ipss), urinary fl ow rates and post-void residual urinary volume. complications were assessed. an additional endpoint was to review video records to precisely determine the timeframes for individual surgical procedures and to plot the learning curve. results: all the remaining patients had undergone the -year follow-up assessment. measurements were performed at , , , , , , and months. th ere were no statistically signifi cant differences in baseline characteristics between the two groups. no signifi cant intraoperative and early postoperative bleeding was observed. hospital stay aft er surgical intervention covered day that was equal to average time of urethral catheter indwelling. th e improvement rates, calculated based on the ipss scores at years aft er surgery, were . % and . % in the dilep and dlvap group, respectively. th e results indicate signifi cant decrease in severity of luts. th e sustained treatment eff ect was in favor of dilep intervention group. also treatment effi cacy was better in the dilep group compared to the dvlap group, as regards the maximum urinary fl ow rate (qmax). th e diff erence was statistically signifi cant. conclusions: diode laser enucleation and vaporisation of the prostate are low-risk minimally-invasive treatment option of treatment of patients with bph. both methods may be safely performed even in high risk and patients on ongoing oral anticoagulation. treatment eff ects are better and more sustained with laser enucleation than with laser vaporization of the prostate. dilep is a true endourological alternative to turp. changes in urination according to the sound of running water using a mobile phone application introduction and objective: th e sound of running water (srw) has been eff ectively used for toilet training during toddlerhood. however, the eff ect of srw on voiding functions in adult males with lower urinary tract symptoms (luts) has not been evaluated. to determine the eff ect of srw on urination in male patients with luts, multiple voiding parameters of urofl owmetry with postvoid residual urine (pvr) were assessed according to the presence of srw played by a mobile application. eighteen consecutive male patients with luts were prospectively enrolled between march and april . urofl owmetry with pvr measured by a bladder scan was randomly performed once weekly for two consecutive weeks with and without srw in a completely sealed room aft er pre-checked bladder volume was scanned to be more than cc. srw was played with river water sounds amongst relaxed melodies from a smartphone mobile application. results: th e mean age of enrolled patients and their mean international prostate symptom score (ipss) were . ± . years (range: - ) and . ± . , respectively. all patients had not been prescribed any medications, including alpha-blockers or anti-muscarinic agents, in the last months. th ere was a signifi cant increase in mean peak fl ow rate (pfr) with srw in comparison to without srw ( . ml/s vs. . ml/s, respectively, p = . ). however, there were no diff erences in other urofl owmetric parameters, including pvr. th e study showed that srw from a mobile phone application may be helpful in facilitating voiding functions by increasing pfr in male luts patients. th is study aims to analyse how bladder outlet obstruction index (booi) and bladder contractility index (bci) aff ect surgical outcome for bph patients who were treated homium laser enucleation of the prostate (holep). we classifi ed the patients, who were treated holep and observed more than months, into group i (booi≥ and bci≥ , n= ), group ii (booi≥ and bci< , n= ), group iii ( °. results: all female patients (mean age, ± years; range, - ) who complained of urinary incontinence were assessed using the q-tip angle. th e pelvic organ prolapse quantifi cation stages of all patients were ≤ stage . mean q-tip angle with an empty bladder was . ± . ° in the supine position and . ± . ° in the ° reclining position (p = . ). mean q-tip angle during the fi lling bladder state was . ± . ° in the supine position and . ± . ° in the ° reclining position (p = . ). th e urethral hypermobility rate during the bladder emptying state was . % ( / ) in the supine position and . % ( / ) in the ° reclining position. th e relative positive ratio of the reclining to the supine position is . . th e urethral hypermobility rate during the bladder fi lling state was . % ( / ) in the supine position and . % ( / ) in the ° reclining position. th e positive rate was higher in the ° reclining position during bladder emptying than that in the other position during bladder fi lling. conclusion: th e outcome of the q-tip angle measurement and the rate of urethral hypermobility changed in relation to patient position. th e reclining position during bladder emptying increased the q-tip angle, resulting in positive urethral hypermobility. rotational th ere was no mortality from the surgical procedure, whereas pain and catheter blockage was main complication. all patients were followed at , , and weeks respectively. our success rate was %. vesicovaginal fi stula is the most common urogenital fi stula. obstructed labor and its complications are still the leading cause of its development, whereas iatrogenic fi stula is also up-coming warning for all health care professional. the effi cacy of combination therapy of alpha blocker with anticholinergic in adult women with overactive bladder introduction and objective: overactive bladder (oab) is associated with symptoms including urgency, with or without urge incontinence, usually with frequency and nocturia. anticholinergics are mainly used for the treatment of patients with oab, especially women. other than anticholinergics, alpha blockers have been shown in several clinical reports to be useful in treating detrusor overactivity caused by neurological diseases. th e aim of the study is to evaluate the effi cacy of alpha blocker in combination with anticholinergics to treat women suff ering from oab. th is prospective study enrolled female patients with oab. patients have been randomised into two groups. th e interventions for the -week treatment period included solifenacin daily for the group and combination of both solifenacin and tamsulosin daily for the group . at baseline and weeks aft er treatment, patients completed a -day bladder diary, international prostate symptom score (ipss), quality of life (qol) index, overactive bladder symptom score (oabss), maximum fl ow rate (qmax) and postvoid residual urine volume (pvr). results: a total of women were randomised and completed this study (group ; , group ; ). statistically signifi cant improvements in terms of urgency and frequency were observed in both groups at weeks aft er treatment as compared with baseline (p< . and < . ), while no inter-group diff erence was observed between the two groups. although group showed improvement of ipss voiding subscore, qol and qmax than group but not statistically signifi cant (p= . , p= . , p= . ) . no signifi cant diff erence was observed in terms of toxic events between the two groups. conclusion: th e combination of alpha blocker and anticholinergic for weeks was noninferior to anticholinergic alone in effi cacy, and there was no evidence of benefi t of alpha blocker in treating female oab. further studies are needed to assess the role of combined therapy of alpha blocker and anticholinergic in the treatment of female oab. conclusion: advancement of cystoscopy will continue undoubtedly. th is report emphasizes the key people whom contributions will always be a corner stone in the fi eld of urology. "gleason" in a nutshell unusual urogenital disorders introduction and objective: to present some aspects of unusual urogenital disorders, congenital malformations, and syndromes, sometimes occurring in eminent personalities or having been described by famous scientists. th e review of historical sources and biographies of famous suff erers and the study of modern medical literature about all these rare urogenital diseases. results: penile deformities such as hypospadias (the most known representative was henry ii of france - , suff ering also from chordee) and the rare epispadias (respectively the most known was the byzantine emperor heraclius, - ) were recorded by historians because of the infertility consequences or the bizarre urination habits (heraclius needed protective measures to avoid getting wet). historians also were attracted by spectacular and dramatic urological emergencies, such as fournier gangrene, known by the case of the prominent suff erer herod. referring to famous researchers, françois gigot de la peyronie ( - ), founder of the royal academy of surgery of france, described the homonymous disorder ( ), consisting of penile deformity due to induration of the corpora cavernosa of the penis. th e above disease, called also induratio penis plastica (ipp) is one of the extraordinary urogenital problems together with the strongly psychologically and non-physically induced syndromes koro (genital retraction syndrome) and castration anxiety (the latter described by freud). belief that genitals have disappear and fear of damage or loss of the penis characterize them both. much of the research has been done on the two above topics, although still relevant today. conclusions: unusual urological disorders are broadly known when happening on famous personalities or when described by famous physicians or when attract the common opinion as extraordinary events (called mirabilia by historians). koutsiaris e , drettas p , oikonomou a , poulakou-rebelakou e , rempelakos a introduction and objective: th e loss of a testis represents a psychologically traumatic experience in males of any age. testicular loss is commonly the result of torsion, trauma, infection or malignancy. th e patients who experience orchiectomy request the implantation of an artifi cial testis for psychological or cosmetic reasons. testicular prostheses are one of the most commonly implanted devices and we present the evolution of these devices. review of the medical literature regarding the history of testicular prostheses and the various materials that have been used during the decades. results: th e fi rst testicular prosthesis was an alloy of molybdenium, cobalt and chromium and was used in . during the s, other materials were used such as plexiglass and polyethylene without much success. it was then suggested by the scientifi c community that the ideal testicular prosthesis should not produce any infl ammatory reaction and that should be also made by a proven non carcinogen material. it was also suggested that the material of the prosthesis should also resist mechanical press and take and hold the desired form. as a result, solid silicone rubber prostheses were introduced and used in the s. th e demand for more natural feeling implants lead to gel fi lled silicone devices appearing in . in , fi rmer silicone coated prosthesis became the "gold" standard. in the us in , the food and drug administration (fda) halted the use of gel fi lled breast implants due to the risks of autoimmune disorders and the possibility of tumor development. as a consequence, in there was a voluntary withdrawal of silicone gel fi lled testicular prostheses and replacement with saline fi lled prostheses. nowadays both silicone and saline fi lled testicular implants are used worldwide which are safe and eff ective. conclusions: testicular prostheses reduce the psychological impact that results from loss or absence of a testicle and should be off ered to male patients of any age. introduction and objective: we investigated population-based management trends of urinary stone disease in the use of extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy during the recent years in a korean population. we conducted this retrospective study by reviewing the medical records of patients diagnosed with acute ureteric colic in the emergency room and in the urology outpatient from january to december . nine hundred patients were diagnosed with ureteric stone and all of them underwent ultrasound as the primary imaging modality. sensitivity, specifi city, positive and negative predictive value in determining the size, position of the stone in the ureter by ultrasound has been documented. results: out of patients, there were males ( %) and females ( %). age range was - years. our study found that color doppler ultrasound with twinkling sign, diagnosis was made with confi dence in cases ( . %). sixty-fi ve patients who failed the ultrasound, the stones were confi rmed by helical ct, failure to detect the stone was mainly due to poor visualization (due to bowel gases and obesity) and smaller size of stone. right side stones were seen in ( . %) patients while left side stones were seen in ( . %). stones were detected bilaterally in cases ( . %). th e range of stones size was - . mm. th ere were ( . %), ( . %) and ( . %) upper, middle and lower ureteral stones. conclusion: th ere is no doubt that spiral ct is superior in the demonstrating of ureteral calculi. th e present study emphasized that utilization of color doppler ultrasound with twinkling in trained hands can provide an excellent alternative modality with high sensitivity and specifi city in diagnosis of acute ureteric colic and with confi dence can be used as fi rst imaging modality, hence we could avoid high cost, higher radiation dose and high workload. contemporary imaging practice patterns following ureteroscopy for stone disease cleveland clinic, cleveland, usa introduction and objective: routine imaging following ureteroscopy for treatment of renal/ureteral calculi continues to be a topic of debate. however, with the increasing focus on healthcare costs and quality, judicious use of diagnostic imaging to optimize outcomes while minimizing resource utilization is a priority. we sought to identify post-ureteroscopy imaging practices amongst experienced urologists. a redcap questionnaire was sent to urologists in north america. th e questionnaire surveyed demographic data, clinical volume, and imaging preferences post-ureteroscopy. additionally, we surveyed the extent to which stone, anatomic, and procedure-related factors infl uenced these preferences. th e likelihood of altering clinical practice and the desire for specifi c imaging guidelines were also assessed. th e interquartile range (iqr) was utilized as a measure of median consensus, with a lower iqr denoting increased agreement. results: th ree hundred twenty two urologists completed the questionnaire. th e mean number of years in practice was ± ; % of respondents performed more than ureteroscopic stone procedures monthly. routine postoperative imaging was obtained by % of participants as follows: us ( %), kub ( %), ct ( %), ivp ( %), and kub + us ( %). urologists who did not routinely image patients were more concerned about cost ( % vs. %, p= < . ), radiation exposure ( % vs. %, p= < . ), and diagnostic inaccuracy of us ( % vs. %, p= < . ). th ese urologists were also less likely to have completed an endourology fellowship ( % vs. %, p= < . ). th e most compelling predictors of obtaining postoperative imaging were post-op pain and fever (median , iqr ), residual stones (median , iqr ), ureteral perforation (median , iqr ), and presence of a solitary kidney (median . , iqr ). conclusions: currently, about % of urologists who regularly perform ureteroscopic stone procedures obtain post-op imaging. imaging preferences were guided by the presence of residual fragments, ureteral perforation, solitary kidney, and postoperative pain or fever. introduction and objective: ct scans expose patients to ionizing radiation which is associated with risks of secondary malignancy. we sought to evaluate the performance of reduced dose ct scans in patients evaluated for renal colic in the emergency room. up. , figure . introduction and objective: intraoperative exposure to ionizing radiation is a growing concern for the safety of both patient and or staff . eff orts to reduce the amount of radiation during ureteroscopic procedures oft en result in decreased image quality. lessray™ is a device used to digitally enhance images obtained from a c-arm using a low-dose pulse setting allowing for reduction in radiation dose while maintaining image quality. a randomized prospective trial of patients was performed comparing ureteroscopic cases for unilateral obstructing ureteral stones using standard fl uoroscopy compared to lessray™. patient demographics, stone parameters, and operative characteristics were recorded in addition to total radiation dose, total fl uoroscopy time and images obtained ( (table ) . a statistically signifi cant reduction in radiation exposure to the surgeon was also noted (p = . ). image quality was not compromised and no conversion from less-ray™ to standard fl uoroscopy was needed in any case. a nearly threefold reduction in patient radiation exposure was achieved using the lessray™ digital enhancement device compared to standard fl uoroscopy. th is novel technology has not previously been used in urologic surgery and off ers a promising alternative to standard fl uoroscopy while ameliorating risks to both the patient and surgeon. bilateral results: in the cases of cn patients, accepted retroperitoneal laparoscopic cyst unroofi ng, accepted retroperitoneal laparoscopic partial nephrectomy, patient with a preoperative diagnosis of cystic renal cell carcinoma, the maximum diameter of cm and located in the center of the kidney got retroperitoneal laparoscopic radical nephrectomy. one patient recurred yrs later aft er retroperitoneal laparoscopic cyst unroofi ng, and underwent open partial nephrectomy at last. six mestk patients underwent retroperitoneal laparoscopic radical nephrectomy and accepted retroperitoneal laparoscopic partial nephrectomy. twelve cases were followed up for months to years, no recurrence. conclusion: cn and mestk are rare benign tumors of the kidney. preoperative misdiagnosis is high. multi-cystic lesions with no mural nodules should take cn/mestk into consideration, especially when the lesions convex to the pelvis, should be highly suspected for cn diagnosis, and to assess the possibility of partial nephrectomy. cyst unroofi ng for cn has recurrence risk. the value of -t multiparametric mri for detecting prostate cancer of t stage introduction and objective: th e objective of this study was to prospectively determine the value of -t multiparametric (mp) mri with pelvic -phased array coil for prostate cancer of t stage. december , patients underwent -t mpm-ri with pelvic -phased array coil, transrectal ultrasound-guided biopsy and radical prostatectomy for adenocarcinoma. mr images were evaluated by three experienced radiologists with regard to extracapsular extension and seminal vesicle involvement and compared with whole-mount histopathological sections as a gold standard. we estimated the sensitivity, specifi city, positive, and negative predictive value and overall accuracy of mpmri for t disease. introduction and objective: prostate cancer (pca) imaging has undergone a revolution in the past fi ve years with the rise of multiparametric magnetic resonance imaging (mri) for cancer detection and the evolution of positron emission tomography-computed tomography (pet-ct) for staging. initially, choline pet-ct was considered the new standard for detecting metastatic disease where biochemical recurrence (bcr) occurs aft er primary treatment, but a newer agent based on prostate-specifi c membrane antigen (psma) has emerged. despite the reported promising results with this novel imaging modality few reports correlating psma pet-ct with pca histology have been documented. we present the case of a fi t year old gentleman, where psma pet-ct was used to accurately detect pca pelvic lymph node (ln) metastasis in the setting of bcr following primary radiation treatment. results: th e positive psma pet result was confi rmed with histological examination of the involved pelvic lns following robotic-assisted laparoscopic pelvic ln dissection (plnd). larger studies are required to document accurately the role of psma pet-ct but it is likely it will usher in a new era of surgical and even radiation treatment of oligometastatic disease, aiming for cure or prolonged deferring of systemic treatment. introduction and objective: imaged guided radiotherapy has been shown to improve the outcome of pelvic radiotherapy, notably with prostate gold seed fi ducials. lipiodol has been utilized for radiotherapy bladder fi ducials, but can be technically diffi cult to inject as discrete fi ducial markers, particularly in the post-prostatectomy setting. th e objective is to investigate contrast agent/tissue glue mixtures as radiotherapy bladder fi ducials with respect to deliverability and visualisation for radiotherapy verifi cation. two radiopaque contrast agents, lipiodol and urograffi n were investigated. th ese were mixed with a three tissue glues: histoac-ryl™, tisseel™ and glubran™. to simulate the clinical procedure, the mixtures were injected ex-vivo into the submucosa of fl uid fi lled pigs' bladders using a cystoscope and williams needle. th e aim was to produce a small, medium and large fi ducial. th e bladders were transferred to a pigs' pelvis to provide realistic tissue densities for radiotherapy imaging. visualisation of the pelvis was performed in accordance with radiotherapy procedures. th e initial imaging was done on a radiotherapy ct simulator. radiotherapy verifi cation was performed by radiation therapists using widely accepted protocols including cone beam ct (cbct) and kilovoltage (kv) & megavoltage (mv) d planar images. results: delivery: urograffi n glue mixtures were diffi cult to deliver as it polymerized rapidly in the catheter. consequently it was only possible to produce a single fi ducial. th e lipiodol glue combinations were all deliverable. visibility: th e urograffi n glue combinations were only able to produce a single fi ducial that was visible on ct and cbct but were not visible with kv or mv verifi cation. all of the lipiodol glue combinations produced multiple fi ducials that could be satisfactorily visualised on ct and cbct. lipiodol with either hystoacryl or glubran produced visible fi ducials on kv imaging, however the lipiodol tisseel combinations could not be seen. no combination produced suffi cient contrast with mv planar imaging. introduction and objective: th e fl exible urethrocystoscopy is a procedure that is performed routinely in urology for monitoring bladder tumors and diagnosis in patients with lower urinary tract symptoms and hematuria. th e aim of this study is to analyze whether the use or not of antibiotic prophylaxis is indicated in this outpatient procedure. prospective nonrandomized observational study in which patients were divided into two groups: -group : patients with prophylaxis with ciprofl oxacin mg h before urethrocystoscopy; -group : patients without antibiotic prophylaxis. prior to inclusion in the study absence of urinary tract infection is checked by urine culture obtained three days before the procedure. indication of cystoscopy, cystoscopy results, presence of comorbidities, urine culture aft er days, urinary symptoms over the next seven days were analyzed. statistical analysis with spss . with signifi cance diff erences p≤ . . results: th e mean age of patients in group was . ± . years versus . ± . years in group (p= . ). no diff erences in the percentage of men / women included among the groups. fourteen percent of patients in group had bacteriuria compared with % in group , no signifi cant diff erence. in the multivariate analysis, it appears that neither age, diabetes, smoking, lower urinary tract symptoms or immunosuppression were associated with the onset of bacteriuria between groups. conclusion: th e use of ciprofl oxacin prophylaxis in fl exible cystoscopy is not indicated in our health area, because does not diminish the presence of urinary tract infection or bacteriuria. minimal inhibitory concentrations for a novel anti-bacterial peptide eluting urethral catheter introduction and objective: catheter associated urinary tract infection is a serious prevalent medical problem. several strategies have been developed to suppress the seemingly inevitable ascent of foreign pathogens through the urethra. th e primary strategy has been to coat the surface of the catheter with repellant agents, such as silver alloy hydrogels or anti-biotics. anti-bacterial peptides, such as human beta defensing (hbd- ) or cathelicidine are naturally produced peptides from the urothelium, acting to inhibit bacterial attachment and infi ltration as part of the innate immunity of the host. we have recently been able to engineer anti-bacterial peptide elution through gelatin coated catheters. th is study investigates the effi cacy of this strategy in deterring common uti pathogens. materials and methods: e. coli and p. aeruginosa, bacteria commonly associated with uti, were inoculated in tryptic soy broth, and then were aliquoted into each well of plates. anti-bacterial peptides, either recombinant hbd- or cathelicidine, were diluted and added to each well at increasing concentrations, where microorganisms were exposed for hours or for the indicated times following antimicrobial challenge and determination of the planktonic mics. bacteria were then enumerated by serial dilution plating. time-kill studies were performed. bactericidal activities of the antimicrobial agents were defi ned as a log decrease in the cfu/ml over hours relative to cell counts in the starting inoculum. results: th e standard inoculant of e. coli and p. aeruginosa commonly required an mic of μg/ml hbd- , and μg/ml for cathelicidine. time kill studies estimated bactericidal eff ect for hbd- on e. coli and p. aeruginosa both at hours, while for cathelicidine it was and hours, respectively. conclusion: th e current study demonstrates the efficacy and feasibility of a controlled release elution of anti-bacterial peptides, hbd- and cathelicidine, in inhibiting growth of common uti pathogens. the conclusion: co-infections of ng with ct appear less frequently. and mpcr method is rapid and accurate for identifi cation of stp. th e mpcr should be conducted in advance prior to antibiotic treatment as well as it will be better to give suitable antibiotics rather than empirical combination antibiotics for ng with ct in patient with urethritis. introduction and objective: th e prevalence of multi-drug resistant extended-spectrum beta-lactamase-producing (esbl) bacteria in normal gut fl ora in the australian community is increasing. current prophylactic antibiotic regimes for trans-rectal ultrasound (trus) prostate biopsies do not have activity against esbl organisms leaving some men at risk of esbl sepsis. our objective is to determine the prevalence of esbl in gut fl ora in northern tasmanian men and to identify risk factors for colonisation. patients were recruited into two groups. group were volunteers from the urology pre-operative clinic or the general community. group were men undergoing trus prostate biopsies. all patients were assessed via an enrolment questionnaire for the presence of known esbl risk factors. further procedural data were collected for those who had trus biopsies. all patients were assessed for esbl via a faecal culture, prior to any antibiotic prophylaxis. fisher's two-tailed test was used for comparative analysis. patients with ic/pbs were assessed with the o'leary-sant interstitial cystitis index score and global response assessment questionnaire prior to commencing treatment. assessment with these questionnaires was performed aft er treatments ( weeks) and again aft er treatments ( weeks). assessment end points were pain, urgency, symptom score and problem score. results: data was collected on patients, female and male. six patients had failed rimso- dimethyl sulphoxide (dmso) % w/w treatment prior. at baseline the mean pain score was . , urgency score . , symptom score . and problem score . . aft er weeks the mean pain score fell to . , urgency score to . , symptom score to . and problem score to . . at weeks the global response to treatment was %. nocturia was the fi rst symptom to improve with urgency and pain following. no side eff ects were noted no was reported during instillation and all patients tolerated the treatments. conclusion: ic is a diffi cult disease to treat. it requires a multimodal approach. we found that intravesical chondroitin sulphate reduced pain, urgency and o'leary-sant symptom and problem scores in patients with ic/pbs. all patients tolerated the treatment and no side eff ects were reported. introduction and objective: extended spectrum beta-lactamase (esbl) producing enterobacteriaceae are an increasing concern in an era of antibiotic resistance as they cause infections ranging from community acquired urinary tract infection (uti) to life threatening sepsis. we retrospectively reviewed the incidence and antibiotic susceptibility profi le of all esbl producing enterobacteriaceae at a university hospital in the united kingdom. patient gender, age and catheter specimen were assessed as risk factors. patient age, gender and specimen type were recorded in the database. urine samples received from outside our institution (including community isolates) were excluded from the analysis. urine was processed by calibrated loop sampling on to chromogenic clear media (oxoid ltd, basingstoke, uk). a positive culture was defi ned as ≥ cfu/ml except for samples from children and pregnant women where a cut-off value of > cfu/ml was used. susceptibility testing was performed by bsac (british society of antimicrobial chemotherapy) disc diff usion testing and reported for ampicillin, co-amoxiclav, piperacillin-tazobactam, carbapenems (ertapenem, meropenem), nitrofurantoin, pivmecillinam, trimethoprim, cephalexin, fosfomycin, third generation cephalosporins (ceft riaxone, ceft azidime) quinolones (norfl oxacin or ciprofl oxacin), aminoglycosides (gentamicin, amikacin) and others. cultures of more than two organisms (heavy mixed growth) were considered contamination and excluded. other exclusion criteria included missing data such as gender, age or susceptibility results, age < years old or an unusual specimen type such as an ileal conduit, nephrostomy, prostatic secretion, bag specimen or a suprapubic aspirate. results: our initial database included , samples which was reduced to , samples from , unique patients aft er exclusion criteria were applied. causative organisms were found to predominantly be e. coli, enterococcus, klebsiella, pseudomonas and proteus species. th e proportion of causative organisms was largely stable across the ten year period. antibiotic resistance was demonstrated to have increased, particularly across fi rst line agents. male gender and catheter use were associated with multi-resistance. in the modern era of antibiotic resistance we demonstrate that antibiotic resistance in hospital urinary tract infections is increasing. our results may be used to guide empirical treatment of hospital urinary tract infection. chronic pyelonephritis is a risk factor for renal dysfunction after urinary diversion in bladder cancer uehara s , , murao w , otsuki h , shimizu t , yoshioka t , , fujio k okayama university, okayama, japan; abiko toho hospital, abiko, japan introduction and objective: several reports showed that acute pyelonephritis is a risk factor for renal dysfunction in bladder cancer aft er urinary diversion, but the impact of chronic pyelonephritis fer renal dysfunction was unclear. materials and methods: from to , patients underwent radical cystectomy in our institute. among those patients, who showed hydronephrosis (more than grade ) or did not have enough data were excluded in this retrospective study. finally patients were enrolled. th e urinary diversions were divided into types: ileal neobladder (ib), ileal conduit (ic), ureterocutaneostomy without stent (uc) and ureterocutaneostomy with stent (ucws). ureteral stents were indwelled because of the ureteral stenosis aft er ureterocutaneostomy. because the cases of ucws generally showed pyuria and bacteriuria, ucws was determined as the chronic pyelonephritis model, and the estimated serum creatinine-based glomerular fi ltration rate (egfr) was calculated and compared with other urinary diversion. results: median follow-up period was . months (range - months) and median egfr was . ml/ min/ . m before surgery and . ml/min/ . m at the last follow-up. th e median decrease of egfr during the period between pre-surgery and the last follow-up in ib, ic, uc and ucws was . , . , . and . ml/min/ . m respectively. renal function was signifi cantly impaired in ucws cases than other urinay diversion. conclusion: chronic pyelonephritis may be a risk factor for renal dysfunction aft er urinary diversion. to avoid the renal dysfunction, ureteral stents should not be indwelled permanently. comparison of antibiotic susceptibility of escherichia coli between community-acquired and post-biopsy acute prostatitis introduction and objective: th e etiology of acute prostatitis aft er transrectal-ultrasound-guided-prostate-biopsy (pbx-ap) seems to be diff erent from that of community-acquired acute prostatitis (ca-ap). recent studies suggested that pbx-ap should be considered a separate category of prostatitis, distinct from spontaneous acute prostatitis. th us, we aimed to compare antibiotic susceptibility of escherichia coli between ca-ap and pbx-ap. of , patients who underwent transrectal-ultrasound-guided-prostate-biopsy, a total of patients had pbx-ap. in among these, escherichia coli was isolated on urine or blood culture. in of the patients with ca-ap, escherichia coli was identifi ed on urine or blood culture test. th us, a total of patients with ca-ap (n = ) or pbx-ap (n = ) caused by escherichia coli were included in this retrospective study. we compared demographic variables, data on clinical laboratory tests or transrectal ultrasound and antibiotic sensitivity data between the two types of prostatitis. results: in comparison to the ca-ap group, the pbx-ap group showed signifi cantly higher incidence of bacteremia and lower count of white blood cell. th ere was no signifi cant diff erence between the two, regarding to other clinical or laboratory parameters including age, body mass index, serum psa, prostate volume and percentage of patients with ebsl-positive escherichia coli. th e percentages of patients with quinolone-resistant escherichia coli in the ca-ap and pbx-ap groups were . % and . %, respectively, while those with nd or rd cephalosporin-resistant escherichia coli were . % - . % and . % - . %, respectively (table ). in both groups, the percentage of patients with amikacin-resistant escherichia coli were . %. our data suggest that a combination therapy of cephalosporin and amikacin can be recommended for treatment of pbx-ap while quinolone alone may be a feasible treatment option for ca-ap. the effectiveness of prostatic massage in treating chronic prostatitis (cp) tanabalan c, panah a, kabir m, masood j, pati j, nargund v introduction and objective: we review the eff ectiveness of prostatic massage under general anaesthesia (ga) for persistent symptoms aft er failure of antibiotic therapy. th e mainstay of treating cp is empirical antibacterial therapy with varying results. prostatic massage has been used to treat cp with mixed results. retrospective study of patients that were seen in urology outpatient clinics from june to july with symptoms of chronic prostatitis. all patients had a full clinical evaluation and urinary samples were sent for culture/microscopy on their visit. patients were treated initially with a course of -aminoquinolone and doxycycline in combination with lifestyle advice. if initial antibiotic therapy failed and no abnormal results detected in the work-up, a prostatic massage was off ered. th is involved a rigid cystoscopy followed by a -minute prostatic massage under anaesthesia. post-operatively patients received a further course of antibiotics. patients were followed up aft er the procedure and were assessed for improvement in symptoms. a total of patients ( %) commented on an improvement in some or all of their cp symptoms for a mean length of time of . (range . to . weeks). mean psa was . (range . to . ). one bladder tumour and one urethral stricture were detected on cystoscopy with one prostate cancer following prostate biopsies. if voiding urinary symptoms present men were given an alpha-blocker, there was no signifi cant improvement in pain symptoms post-operatively between the two groups (p= . ). th ere were no adverse eff ects from having the procedure with no complications noted. prostatic massage under ga is a safe and eff ective therapy in the treatment of refractory cp in select patients. th e issues of long-term surveillance and assessment of response to treatment remains a challenge. th ere seems little role for alpha-blockers, psa testing and mri prostate in the management of cp. oral antibiotic therapy and lifestyle modifi cations should remain as a fi rst-line treatment option. th e eff ect of stress, lifestyle and ethnicity has not been demonstrated in this study and further research will need to be undertaken. intravesical hyaluronic acid and chondroitin sulfate therapy for interstitial cystitis and painful bladder syndrome shin b, hwang e, chung h, kim s, jung s, kang t, park k, kwon d introduction and objective: damage to the urothelial glycosaminoglycan (gag) barrier layer may underlie the pathogenesis of several chronic bladder pathologies, including interstitial cystitis/painful bladder syndrome (ic/pbs). th is study evaluated the eff ect of intravesical hyaluronic acid (ha) in ic/pbs. twenty patients received intravesical ha mg and chondroitin sulfate (cs) g (ialuril®) in ml saline solutions once weekly for weeks, once every weeks for the next month, then once every month for the next months. results: a signifi cant improvement in urinary symptoms was evident on voiding diaries (number of voids and mean void volume; p= . and . , respectively). th e interstitial cystitis symptom index and interstitial cystitis problem index resulted in a significant improvement in both scores (p= . and . , respectively). th e storage symptom score (ipps) decreased from . to . (p= . ). th e quality of life to urinary symptom reduced from . to . (p= . ). th ere was no statistical signifi cant change in the voiding symptom score of ipps aft er ialuril instillation (p= . ). conclusions: th is promising experience seems to offer an additional therapeutic option in patients with refractory ic/pbs. prevention of surgical site infection: new approach alexander e , , hulda t , edna d introduction and objective: until the middle of the th century, when ignaz semmelweis and joseph lister became the pioneers of infection control by introducing antiseptic surgery, most wounds became infected. in cases of deep or extensive infection this resulted in a mortality rate of - %. most surgical site infections (ssi) are superfi cial, but even so they contribute greatly to the morbidity and mortality associated with surgery. th e aim of this study is to fi nd out rate of surgical site infection by single change of wound dressing. th e study is prospective in two hospitals (ba regional hospital, tophill hospital in kumasi). surgically clean cases are selected for operation. wounds are not opened till the seventh day or when soaked. window is left for wound inspection. results: results are shown in table . table , patients with diff erent surgical conditions were operated. average post-surgery change of dressing was days. ssi= / ( . %). single post-surgery change of dressing is eff ective ssi prevention method. effects of semen cuscutae on the fertilization ability in varicocele-induced rat introduction and objective: th ere is no specifi c medication to improve the sperm motility and count yet. th is study aimed to evaluate the favorable eff ects of purifi ed fl avonoid, semen cuscutae extract (sce) against oxidative stress injuries and other homeostatic imbalances in reproductive organs in adolescent rat with varicocele and to develop the new herbal medication to treat the male fertility. materials and methods: seventy-two rats were divided into groups: control (ctr) + hydroxypropyl-methyl cellulose (hpmc) (ctr + hpmc), ctr + mg/kg sce and ctr + mg/kg sce, varicocele (vc) + hpmc, vc + mg/kg sce and vc + mg/kg sce. in ctr group, they were started with medication for days from weeks aft er environmental stabilization. for the vc groups, they were given medications for days aft er weeks of operation. blood was collected before sacrifi ce for the testosterone test. sperm motility, daily sperm production (dsp), sperm count, and sperm transit time were calculated. th e seminiferous tubules were graded according to johnsen scoring. th e mrna expression of glutathione peroxidase (gpx ) and . nmol/mg protein, respectively) than vc group ( . ± . u/mg protein and . ± . nmol/mg protein, respectively). also, the testosterone, johnsen score were signifi cantly increased in the dose of mg/kg sce group than other groups. th ese results suggest that purifi ed fl avonoid semen cuscutae extract could be an alternative medicine for the infertility patients by inhibition of oxidative stress by favorable mechanisms. the relationship between pregnancy rate and semen quality improvement after varicocelectomy varicocele is the most common cause of male infertility and is generally correctable via surgery. in some reports, pregnancy rates were improved aft er varicocelectomy in male patients with poor semen quality. th e aim of this study was to determine the relationship between semen improvement and pregnancy rate. patients who underwent microsurgical varicocelectomy from jan. to jun. were enrolled. all patients had history of infertility (> year) and confi rmed varicocele on physical examination. th e abnormality of semen analysis results was based on who guidelines. varicocelectomy was performed in patients with poor semen quality in a series of two semen analysis where the female partner was normal in spontaneous pregnancy, as evaluated gynecologically. microsurgical varicocelectomy was performed by single surgeon. follow-up semen analysis was performed months aft er operation. improvement in semen quality was defi ned as > % improvement in total motile sperm compared with pre-operation semen analysis. pregnancy rate, method of pregnancy, and time to pregnancy were investigated. results: a total of male patients were included in this study, ( . %) in the improvement group (ig) and ( . %) in the non-improvement (nig). th e pregnancy rate was % ( / ) in the ig group and % ( / ) in the nig group; there was no significant diff erence between groups. pregnancy methods between the two groups were similar (table ) . introduction and objective: to review the learning curve, complications and outcomes of the fi rst cases of microsurgical vasectomy reversal performed in a developing country. th e fi rst dedicated service in male infertility microsurgery in south africa was established in . between january and december , a total of patients underwent microsurgical vasectomy reversal by a single surgeon (amir d zarrabi). mean patient age was years (range to ), mean age at vasectomy years (range to ), mean number of children for the male partner . and mean age of the female partner years (range to ). th e mean time interval between vasectomy and reversal was . years (range . to . ). five patients had previous failed vasectomy reversals and in patients the indication for reversal was post-vasectomy pain syndrome. a total of % of patients travelled from other countries for their surgery. results: mean surgical time per testicular unit was . minutes (range to ) and total operative time minutes (range to ). sperm motility (intra-operative light microscopy) was good in . %, average in . % and poor in . %. vasovasostomy was required in . % of testicular units and vaso-epididymostomy in . %. in patients sperm was harvested at the time of reversal for cryopreservation. complications occurred in % of patients and were managed conservatively in all but , who required an additional surgical procedure. for patients with adequate follow-up the overall surgical success rate was %. mean post-operative sperm count was . million. nine pregnancies and live births have been recorded during the limited follow-up. comparing the fi rst cases with the last cases revealed no signifi cant diff erences in surgical time, complications or patency rates. th e mean post-operative sperm count was % higher for the last cases. although microsurgical vasectomy reversal is technically demanding and requires specialized equipment and instruments, it can be successfully implemented in a developing country. infl uence of unilateral iatrogenic torsin on contralateral testis in rat, prepubertal and postpubertal introduction and objective: th e present study was conducted to investigate the infl uence of hemicastration and age at hemicastration on the subsequent contralateral testis. sixty-four wistar-derived male rats divided randomly in groups. group named immature intervention, group immature control, group mature intervention and group mature control. in group , rats hemicastrated at days of age (prepubertal). in group , sham surgery (midscrotal incision) was done at same age. in group , rats hemicastrated at days of age (postpubertal) and in group sham surgery was done at same age. twenty days aft er fi rst surgery, in intervention groups contralateral orchiectomy was done and in control groups random orchiectomy (left or right) was done. blood sampling for evaluation of serum testosterone was performed just before second surgery. results: testis weight and the mean testicular weight per g of body weight was greater in hemicastrated rats. th ese parameters was greater in prepubertal group than postpubertal hemicastrated rats. th ere was no appreciable diff erence in serum testosterone levels in groups. our research demonstrated that hemicastration resulted in compensatory hypertrophy of the remaining testis and it decreased as the animals aged. hemicastration does not lead to reduction in serum testosterone levels and remaining testis can retrieve a normal serum testosterone level. role of antibiotic in the treatment of semen hyperviscosity: a single institution study introduction and objective: th e prevalence of semen hyperviscosity is estimated to be between - % and can lead to male factor infertility both in vivo and in vitro. semen is composed of fl uids secreted by the male accessory glands, which contain proteins essential to the coagulation and liquefaction of semen. hypofunction of the prostate or seminal vesicles causes' abnormal viscosity of seminal fl uid. hyperviscosity can impair normal sperm movement in the female reproductive tract, and can lead to decreased sperm count. multiple factors have been predicated which result in the development of semen hyperviscosity, of this infection is considered to be one of the main contributor. aim of the study was to predict the eff ect of antibiotic in the treatment of hyperviscosity. th is is a single institution study, patients (age range - years) were recruited who were diagnosed with semen hyperviscosity (failure to liquefy aft er min). medical, sexual, and family history were documented. all the patients semen were kept for culture and they all got levofl oxacin for days and patient who had positive culture were changed to appropriate antibiotics. all the patients underwent repeat semen analysis aft er weeks. results: seventy seven percent patient had previous history of prostatitis, % patient had past history of sexual transmitted diseases. seventy fi ve percent patient are suff ering from infertility, of this % patient had a family history. th irty seven percent patients had positive culture and of this only % patient had liquefaction post treatment. culture negative patients, % patient had liquefaction post treatment. conclusions: semen hyperviscosity is associated with infertility and exact cause is considered to be multifactorial, of this infection is considered to be the main factor. in our study we did found that most of the patients has infection but antibiotic treatment even for culture positive patients showed minimal eff ect. treatment with antibiotic along to treat hyperviscosity cannot be considered curative since in our study the eff ect was only %. further research is needed to better understand the contributors to semen hyperviscosity and the treatments that can be used for infertile males with hyperviscous semen. modifi ed microsurgical subinguinal varicocelectomy: bundle ligation technique hong y, lee s, choi k, park d, hong j introduction and objective: microsurgical varicocelectomy has become the gold standard because of low recurrence and postoperative complication rate. during the procedure, isvs should be carefully dissected, cut and suture-ligated one by one. however, it is not easy to divide all isvs in a horizontal line, which can result in some uncertainty whether every single isv was divided or the same vein was unnecessarily divided multiple times. th erefore, we have developed a modifi ed technique, so called bundle ligation technique (blt), to make the procedure more reliable and simpler. a total of cases of microsurgical subinguinal varicocelectomy performed from to were grouped as conventional varicocelectomy (cv, n= , age: ± . ) and blt (n= , age: ± . ). mean follow-up time was . ± . months. blt is a simpler procedure because isvs are ligated as a whole, however, it is possible only aft er dissecting and securing the testicular artery fi rst. we compared operation time, resolution of palpable varicocele or pain, recurrence rate and complications. results: mean operation time was . ± . in cv group and . ± . in blt group (p= . ). resolution rates months aft er surgery were . % (cv) and . % (blt) in each group. recurrence aft er surgery during the mean follow-up time was . % (cv) and . % (blt). th e aim of the study is to evaluate the eff ect of hbo on the level of sperm dnaf and on the content of reactive oxygen species (ros) in semen. th e study included men with idiopathic infertility, the level of sperm dnaf was above % and the content of ros in the sperm was above . mv/sec. in the main group (n= ) sessions of hbo were performed and in vitro fertilization (ivf) was carried out months later. in the control group (n= ) ivf was performed without preceding hbo. th e age of patients ranged from to years (median - . years). sperm dnaf was determined by tunel, the level of ros in semen was studied by chemiluminescence. th e assessment was made at the time of entry into the study and aft er months (in the main group - months aft er hbo). in the main group, average sperm dnaf aft er hbo decreased from . ± . % to . ± . % (p< . ), the median level of ros in semen decreased from . mv/sec to . mv/sec (p< . ), whereas in the control group of patients these fi gures have remained almost at the same level - . ± . % and . ± . % (p> . ), . mv/sec and . mv/sec (p> . ). pregnancy resulting from ivf occurred in . % ( / ) of the cases in the study group and in . % ( / ) -in the control group (p< . ). conclusion: hbo is an eff ective method to reduce the number of sperm with dnaf, which can potentially lead to an increased fertility in patients with idiopathic male infertility. to evaluate the natural history and growth kinetics between sporadic clear cell renal cell carcinoma (ccrcc) and ccrcc in von hippel-lindau disease (vhl). we reviewed patients with sporadic ccrccs and patients with vhl ccrccs all confi rmed by delayed surgery aft er at least months active surveillance. th e growth rate was calculated. th e growth kinetics between sporadic and vhl ccrcc were compared. th e initial tumor diameter and pathological grade were reviewed, and their correlation with the growth rate were analyzed. results: th e mean growth rate of sporadic ccrcc was . cm/yr (range, - . cm/yr). th e mean growth rate of vhl ccrcc was . cm/yr (range, . - . cm/yr). th e growth rate of vhl ccrcc was lower than that of sporadic ccrcc (p= . ). for vhl ccrcc, the initial tumor diameter aff ect the growth rate (r= . , p< . ), while the pathological grade not (p= . ). for sporadic ccrcc, the pathological grade aff ect the growth rate (p< . ), while the initial tumor diameter not (r=- . , p= . ). conclusion: th e growth kinetics of vhl ccrcc is more indolent than that of sporadic ccrcc. for ccrcc with aggressive growth kinetics, its growth rate might correlates with the pathological grade, for those with slow growth kinetics, the growth rate might correlates with the initial tumor diameter. effects of trpm silencing on the proliferation, migration, and invasiveness of renal cell carcinoma (rcc) cells proliferation, migration, and invasiveness of human rcc following trpm knockdown. we constructed sirna sequences targeting the trpm gene and then transfected them into rcc cells mediated by liposome. th e potency of nm trpm sirnas was detected trpm mrna measurement by rt-pcr. th e eff ect of trpm sirna on cell viability was determined by wst- assay. cell motility and invasiveness were evaluated by wound healing assays and a matrigel migration and invasion assay. transfected rcc cells were cultured in eagle's minimum essential media supplemented with % fetal bovine serum. all measurements were done hours aft er trpm blocking. results: trpm sirna weakly inhibited the gene transcription of trpm . it was for nothing in the proliferation of human rcc cells. compared with vehicle control, the migration and invasion of human rcc cells were suppressed signifi cantly by trpm sirna until aft er hours. in addition, although protein levels of mmp- were not changed signifi cantly, we found that the protein levels of matrix metalloproteinase (mmp)- were diminished markedly by trpm sirna. th ese results suggest that trpm may have a role in the rcc progression including migration and invasion through upregulation of mmp . role of tnf-and cd in resistance to sunitinib treatment in clear cell renal cell carcinomas introduction and objective: tumor necrosis factor-α (tnf-α) was originally reported as a cytokine to induce apoptotic cell death and cachexia. recent studies have indicated that tnf-α also enhances tumor progression by inducing epithelial-mesenchymal transition (emt). tnf-α is also known as a modulator of cd expression, which belongs to cancer stem cell marker in several cancers. in this study we clarifi ed the signifi cance of tnf-α as well as cd in clear cell renal cell carcinomas (ccrccs). protein expression of tnf-α and cd was examined by immunohistochemistry in primary ccrccs, untreated metastatic ccrccs, and metastatic ccrccs treated with sunitinib, and its association with the clinicopathological parameters and prognosis was analyzed. involvement of tnf-α in emt and induction of cd was analyzed by comparing expression of emt-related genes and cd , and migration and invasion in cultured ccrcc cell lines. results: tnf-α and cd were predominantly expressed in carcinoma cells of high-grade ccrccs with positive correlations with primary tumor stage and distant metastasis. th ere was a positive correlation between tnf-α and cd expression, and elevated expression of tnf-α and cd was a poor predictor of prognosis. tnf-α enhanced migration and invasion of ccrcc cells together with down-regulation of e-cadherin expression and up-regulation of matrix metalloproteinase and cd expression. tnf-α also up-regulated the expression of tnf-α itself in ccrcc cells. twenty-fi ve patients were treated with sunitinib for metastasis, and the patients with cd -high tumors showed a shorter time to treatment failure compared to those with cd -low tumors. furthermore, residual carcinoma cells in the sunitinib-treated metastatic ccrccs were strongly positive for cd , and the cd expression was signifi cantly higher in tumors from the sunitinib-treated patients than in those from untreated ones. conclusions: tnf-α seemed to play an important role in progression of ccrccs by inducing emt, and suggested that tnf-α-induced cd might be involved in the resistance to sunitinib treatment. although further experimental studies on the relations between cd expression and cancer stem cells in ccrccs are needed, our data suggest that therapy targeting tnf-α and/or cd may provide a clue for improving the prognosis of patients with sunitinib-resistant ccrcc. introduction and objective: th e aim of this study was to investigate the relationship between the immunohistochemical expression of hypoxia-inducible factor- α (hif- α) with histological parameters such as tumor size; presence of tumor necrosis and hemorrhage; nuclear grade and pathological stage in patients with clear cell renal cell carcinoma (ccrcc). specimens from cases of rcc patients treated with radical prostatectomy were formalin-fi xed, paraffi n embedded, and stained with h&e. additional sections from each case were stained for hif- α. hif- α immunohistochemical expression was estimated as negative ( ), weak positive (+ ), moderate positive (+ ), and intense positive (+ ). th e statistical package "in stat " was used for data processing. results: immunohistochemical expression of hif- α in crcc was signifi cantly higher than in normal kidney tissue at statistically signifi cant level (hif- α: x -test = . , p= . ). a positive non-signifi cant correlation was found between hif- α and the tumor nuclear grade (r= . , p= . ); between hif- α and presence of hemorrhage (r= . , p= . ); whereas, a negative non-signifi cant correlation of a very weak scale was observed comparing hif- α and tumor size (r = - . , p= . ); hif- α and pathological stage (r=- . , p= . ), as well as hif- α and tumor necrosis (r=- . , p= . ). conclusion: our data showed heterogeneity in angiogenic activity, which might have an impact on biological behavior and anti-angiogenic, anti-vegf therapy of ccrcc patients. th is study suggests that there should be taken more than one tissue biomarkers into the consideration in predicting the biological behavior of ccrcc. introduction and objective: clear cell renal carcinoma (ccrcc) is the most frequent rcc subtype and is characterized by high mortality of %, due to late diagnosis and distant metastases found in % of rcc patients. although the involvement of vhl (von hippel-lindau), hif a (hypoxia-inducible factor -alpha) and vegf-a (vascular endothelial growth factor a) genes in development and progression of ccrcc is widely analyzed, our objective was to perform the common study of those factors in clinical samples of matched tumor-normal kidney biopsies of ccrcc cases. materials and methods: vhl, hif a and vegf-a mrna levels in samples were assessed by quantitative polymerase chain reaction (qpcr); rna was extracted from matched tumor-normal (t, c) kidney samples of ccrcc patients (mean age . ± . , median age ); ccrcc cases were characterized by local or distant metastasis; sunitinib was administrated to patients. vhl, hif α and vegf-a proteins were localized in matched tumor-kidney tissue of patients with the use of immunohistochemistry (ihc). molecular data was statistically calculated with clinical and follow-up data. introduction and objective: to identify tissue biomarker that are predictive of the therapeutic eff ect of sunitinib in treatment of metastatic clear cell renal cell carcinoma (mcrcc). our study included patients with mcrcc; these were selected from patients who received sunitinib in our hospital between the years - according to inclusion criteria of the study. patients were stratifi ed into two groups based on their response to sunitinib treatment; non-responders (progression), and responders (stable disease, regression). th e eff ect of treatment was measured by comparing imaging studies performed before the initiation of treatment with those done between rd and th months of treatment. histological samples of tumour tissue and healthy renal parenchyma, acquired during surgery of the primary tumour, were examined with immunohistochemistry to detect tissue biomarkers (mtor, p , vegf, hif , hif , caix). th e comparison between the two groups of patients was based on comparing the average levels of biomarker expression in both tumour tissue, as well as in healthy renal parenchyma. results were evaluated using student's t-test. results: when considering the results of the group of responders, statistically signifi cant diff erences in marker expression in tumour tissue versus healthy parenchyma were found for mtor ( %/ . %;p= . ), p ( %/ . %;p= . ), vegf ( . %/ %;p= . ) and caix ( %/ . %;p= . ). as for the group without response (non-responders), a statistically signifi cant diff erence was also evident in p a vegf expression in tumour versus healthy tissue ( %/ . %;p= . resp. . %/ %;p= . ). in the responders, a further signifi cant diff erence was found in the frequency of high expression (more than %) between tumour tissue and healthy parenchyma in vegf ( %/ %;p= . ) and caix ( %/ %;p= . ). caix shows high levels of expression in the tumour tissue, in both of the evaluated groups. when comparing the expression levels in the same type of tissue, between the group of responders and non-responders, no signifi cant diff erence in any biomarker was found. conclusion: a signifi cantly higher expression of vegf in crcc in comparison to healthy parenchyma, can predict a better response to sunitinib. on the other hand, the high expression of vegf in healthy renal parenchyma can predict worse response to treatment. the impact of preoperative retrograde pyelography before radical nephroureterectomy for upper urinary tract urothelial carcinoma on intravesical tumor recurrence song p , ko y , choi j , moon k , jung h , kim t introduction and objective: despite its diagnostic role in identifi cation of upper urinary tract urothelial carcinoma (uut-uc), approach to ipsilateral ureteral potentially aggravates spread of tumor, as reported in preoperative ureteroscopy before nephroureterectomy. we thus assessed the impact of preoperative retrograde pyelography (rgp) on intravesical recurrence aft er radical nephroureterectomy for uut-uc. of a total of patients who underwent nephroureterectomy for uut-uc from january to june in our institution, patients who did not undergo preoperative ureteroscopy were selectively enrolled. computed tomography and urine cytology as a basic diagnostic modality were performed in all subjects. th e impact of preoperative rgp and the other variables (age, sex, operating time, clinicopathological factors, and hematological factors) on intravesical recurrence were analyzed by multivariate cox regression model. during a mean follow-up period of . months, ( . %) patients had intravesical recurrence aft er rnu, and subjects ( . %) underwent preoperative rgp. th e mean duration from preoperative rgp to rnu was . ± . days and mean interval of intravesical recurrence was . ± . months. multivariable analysis showed that rgp and pathologic stage over t were independent factors for intravesical tumor recurrence (p= . and p= . , respectively, table ). regarding the duration from preoperative rgp to rnu, no signifi cant diff erence was observed between the recurrence group and the non-recurrence group (p> . ). as with preoperative ureteroscopy, our data demonstrated that preoperative rgp is an independent factor associated with intravesical recurrence of uut-uc aft er rnu. introduction and objective: axitinib which is tyrosine kinase inhibitor is standard nd-line treatment for metastatic renal cell carcinoma (mrcc). th e neutrophil-to-lymphocyte ratio (nlr), an index of systemic infl ammation, is associated with outcome in several cancer types. to assess the relation of pretreatment nlr with progression-free survival (pfs) and overall survival (os) of patients treated with axitinib. twenty-two patients with mrcc were treated with axitinib between october and january . patients were stratifi ed in two groups with nlr > (group a: n= ) vs. < (group b: n= ). pfs and os were estimated using kaplan-meier method. results: median os and pfs were . and . months, respectively. median os was . and . months in group a and group b, respectively (p= . ). median pfs was . and . months in group a and group b, respectively (p< . ). multivariate analysis showed that nlr > was an independent predictor of os (hr . . ; p= . ). in patients with mrcc treated with axitinib, pretreatment nlr might be an independent predictor for the outcome. th e aim of this study was to evaluate whether preoperative neutrophil-to-lymphocyte ratio (nlr) predict the prognosis in patients with upper urinary tract urothelial carcinoma (uu-tuc). a cohort of patients diagnosed with uutuc from to at tokyo metropolitan tama medical center was enrolled in this retrospective study. log-rank test and cox proportional hazards regression models were used for univariate and multivariate analyses. results: on univariate analysis, pathologic t stage, grade, lymphovascular invasion, c-reactive protein (crp) level, and nlr were signifi cantly associated with recurrence-free survival (rfs) and cancer-specifi c survival (css). th e rfs rates for an nlr < . and for one ≥ . at years were . % and . %, respectively. th e css rates for an nlr < . and for one ≥ . at years were . % and . %, respectively. th e multivariate cox proportional hazards regression models showed that the nlr could be an independent predictor for rfs and css. based on the results of multivariate analysis, the scoring model was developed. rfs and css rates at years were as follows: risk factor, . % and . %, respectively; risk factor, . % and . %, respectively; risk factors, . % and . %, respectively; risk factors, . % and . %, respectively; and risk factors, . % and . %, respectively. conclusion: th e preoperative nlr is an independent prognostic predictor. th e model based on the nlr and pathologic factors can be useful in clinical practice. clinicopathological outcome of small cell carcinoma of upper urinary tract: one starting point, diverging paths lu k, wang h, lin v, yu t introduction and objective: primary small cell carcinoma of upper urinary tract (uut-scc) is an extremely rare disease entity with distinct histological and biological behavior, representing less than . % of urinary tract tumor. th e rarity of these neoplasms poses a diagnostic and therapeutic challenge. little is known about uut-scc and the current knowledge of this disease is based on case reports or small series. our aim of study was to characterize the patients with uut-scc and to evaluate patient outcomes with the available treatment modalities. th is was a single-institute retrospective observational cohort study of patients with small cell carcinoma of upper urinary tract followed at e-da hospital, kaohsiung city, taiwan be-tween january , and october , . patient and tumor data were analyzed using descriptive statistical methods. results: six patients with primary uut-scc were identifi ed, consisting of arising from renal pelvis and from upper ureter. th e median age at diagnosis was years with male-to-female ration of : . th e most common presenting symptoms were painless gross hematuria, followed by fl ank pain. th e morphological appearance of the tumor cells and their immunohistochemical reactivity for neuroendocrine markers and cytokeratin helped establish the diagnosis. in of cases, scc coexisted with urothelial carcinoma. surgery was standard treatment given to all patients. of all cases, of patients received chemotherapy, including one receiving neoadjuvant chemotherapy and administering adjuvant chemotherapy. overall median survival was months. conclusion: primary small cell carcinoma of the upper urinary tract is characterized by an aggressive clinical course with early metastatic spread and relatively short overall survival. although high response rate to cytotoxic chemotherapy, its duration of response is limited and the prognosis remains dismal. as there is no standard of care for patients with uut-scc, further eff orts should be directed at its early detection and made to develop more eff ective therapeutic approach for this high-risk lethal disease. prognostic introduction and objective: th e aim of this study was to evaluate the impact of body mass index (bmi) on survival in patients with non-metastatic renal cell carcinoma (rcc) treated with radical or partial nephrectomy. between june and july , patients with rcc underwent radical or partial nephrectomy at two hospitals. among these patients, patients with lymph node or distant metastasis were excluded. th us, the medical records of the remaining patients ( men and women, mean age of . years) were retrospectively reviewed. th e median follow-up duration was months (range to months). th e patients were classifi ed into groups according to their bmi based on the asia-pacifi c criteria for obesity: normal ( . to < kg/m ), overweight ( to < kg/m ), and obese (≥ kg/ m ). th e prognostic signifi cance of various clinicopathological variables including bmi was analyzed using univariate and multivariate analysis. results: of the total patients, patients ( . %) were categorized as normal, ( . %) as overweight, and ( . %) as obese. forty-six patients ( . %) developed local recurrence or distant metastasis and patients ( . %) died of disease during the follow-up period. in the univariate analysis, bmi, tumor size, t stage, fuhrman's nuclear grade, coag-ulative tumor necrosis, and lymphovascular invasion were signifi cant predictors of recurrence-free survival. also, bmi, tumor size, t stage, fuhrman's nuclear grade, and lymphovascular invasion were signifi cant predictors of cancer-specifi c survival. in the multivariate analysis, bmi (p= . ), tumor size (p= . ), t stage (p< . ), fuhrman's nuclear grade (p= . ), and lymphovascular invasion (p= . ) were independent predictors of recurrence-free survival. also, bmi (p= . ), tumor size (p= . ), t stage (p= . ), and lymphovascular invasion (p= . ) were independent predictors of cancer-specifi c survival. our results suggest that bmi is an independent prognostic factor for recurrence-free and cancer-specifi c survival in patients with non-metastatic rcc treated with radical or partial nephrectomy. th ese fi ndings indicate that bmi could be an eff ective tool for predicting recurrence or survival in patients undergoing nephrectomy for non-metastatic rcc. phase i/ii study of multipeptide-based cancer vaccine ima after single-dose cyclophosphamide in japanese patients with advanced renal cell cancer hongo f , ueda t , nakamura t , naya y , okihara k , tamada s , schoor o , singh-jasuja h , nakatani t , miki t introduction and objective: ima is the fi rst therapeutic vaccine for renal cell cancer (rcc) consisting of multiple tumor-associated peptides (tumaps) confi rmed to be naturally presented in human cancer tissue. objective was to assess the safety and tolerability of ima vaccination. in this phase i/ii study in japan, we treated a total of japanese patients with advanced rcc with human leukocyte antigen a (hla-a)* + subjects in - . each of the vaccinations consisted of an i.d. injection of gm-csf ( μg) followed within - minutes by an i.d. injection of ima ( μg of each peptide). th e vaccine therapy was a monotherapy, i.e. no other anti-tumor therapies were concomitantly administered during the study course. no treatment with either anti-cancer agents or immunosuppressants was allowed within weeks before entering the trial. patients were to receive vaccinations in the fi rst weeks of treatment (induction period) followed by further vaccinations at weeks intervals for up to weeks (maintenance period). th e primary endpoint was safety and tolerability. th e secondary endpoints were pfs, os, immunogenicity. results: no treatment-related serious adverse events (saes) or deaths were observed during the study period. at follow-up at months, all cases were assessed for treatment response. ten percent of patients had partial response (pr), % with stable disease (sd), % of patients had progressive disease (pd). median pfs was . months and median os was . months. among all patients analyzed for t-cell response, fi ve showed vaccine-induced (vi) t-cell responses against at least one hla class i-restricted tumap and two patients with responses to multiple tumaps. interestingly, two of the immune responders were of hla-a* phenotype, a hla suballele rarely occurring in europe and us but common in japan. we evaluate the patients who underwent robot-assisted laparoscopic partial nephrectomy (ralpn), laparoscopic partial nephrectomy (lapn), or open partial nephrectomy (opn) in terms of perioperative outcomes. all patients with ct a renal masses who underwent ralpn (n= ), lapn (n= ), or opn (n= ) between november and may at our institute were compared in terms of perioperative outcomes, including the mean operative time, ischemia time, estimated blood loss, change in the estimated glomerular fi ltration rate (egfr), surgical margins, and complications. intraoperative and early postoperative data were collected retrospectively. conclusion: ralpn was signifi cantly associated with shorter ischemia time. any methods of partial nephrectomy preserved renal function at three months postoperatively and showed good oncological outcomes. laparoscopic nephrectomy: does patient obesity affect outcome? introduction and objective: th e prevalence of obesity worldwide is increasing, up to % of men and % of women are now obese. th ere are various means to assess obesity, waist circumference (wc) has emerged as a superior determinant of obesity and then body mass index (bmi). th is study evaluates wc on the outcome of laparoscopic nephrectomy. data was obtained on consecutive patients. a wc of > cm for women and > cm for men is considered obese. data collected includes age, gender, asa score, wc, anaesthetic duration, operative approach, surgery duration, blood loss, renal function, complication rate and duration of hospital stay. overall, patients underwent laparoscopic nephrectomy, were male and female. seventy three ( . %) patients had wc above normal for their gender. mean anaesthetic duration was longer in obese patients . minutes vs. . minutes, (p= . ). operative duration in obese patients was also longer, . minutes vs. . minutes, (p= . ). th ere was no diff erence between groups for conversion, number of ports, intra-operative complications, blood loss, or post-operative complications. however, obese patients had a longer in-patient stay; . days versus . days. conclusion: laparoscopic nephrectomy is safe in obese patients. however, obese patients should be warned that their obesity may be associated with increased anaesthetic and surgical ties and prolonged recovery. the long-term oncologic results of radiofrequency ablation for small renal tumors sung g , bae y , kim s introduction and objective: th e aim of this study was to retrospectively evaluate the long-term oncologic results of radiofrequency ablation (rfa) of small renal masses (srms). : th e patients who had been followed over years aft er percutaneous or laparoscopic rfa for small renal mass were included in this study. a total of patients and renal tumors were included. th e follow-up study included physical examination, chest radiography, creatinine, and contrast-enhanced ct or mri. recurrence was defi ned as contrast enhancement aft er months or lesion growth at subsequent imaging or viable cancer cells on follow-up biopsy. results: th e mean tumor size was . cm and the mean follow-up period was . months. technical success was achieved in / renal tumors ( . %). repeated rfa was necessary in tumors due to incomplete ablation. th e overall complication (oc) occurred in . % of which the low-grade complications accounted for . % of oc. a relevant deterioration of renal function aft er rfa was very rare. th e -year local recurrence-free survival rates, cancer-specific survival rates, and overall survival rates are %, . %, and . % respectively. conclusion: rfa is considered useful treatment for selected patients with srms and also for nephron-sparing. our long-term follow-up results suggest excellent therapeutic outcome with rfa, while achieving eff ective local tumor control. introduction and objective: endoscopic approach of the terminal ureter was proposed as a complementary fi rst step in nephroureterectomy with perimetal cystectomy in order to obviate the low abdominal incision. we aimed to establish the value of a novel method of endoscopic distal ureteral management: pluck technique using bipolar plasma vaporization. during the last years, we performed nephroureterectomy involving plasma-button uretreal desinsertion by bipolar vaporization in upper urinary tract transitional cell carcinoma (uuttcc) cases (pta - cases; pt - cases; pt - cases; pt - cases). th e tumor was pyelocaliceal in cases, ureteral in cases and both ureteral and pyelocaliceal in cases. th e follow-up protocol included cystoscopy with urinary cytology, abdominal ultrasound and ct. th e mean follow-up period was months (range to months). results: all procedures were successfully completed. th e mean duration of the endoscopic procedure was minutes. in cases, aft er the completion of the nephroureterectomy, endoscopic haemostasis of the desinsetion area and margins was necessary. th e postoperative complications' rate was . %: cases of hematuria, one imposing endoscopic approach and another treated conservatively. during the follow-up period, patients presented bladder recurrences, had renal fossa tumor and had secondary lymphnode invasion. th e disease-specifi c mortality rate was %. conclusion: th e endoscopic detachment of the terminal ureter using bipolar plasma vaporization as part of one-step nephroureterectomy is a safe and eff ective method. mid-term evaluation demonstrated good oncologic outcomes. th congress of the sociÉtÉ internationale d'urologie -siu abstract book introduction and objective: we thought that combining open and laparoscopic surgery for partial nephrectomy would be less invasive than open method, easier and expend shorter time to clamp renal artery than pure laparoscopic approach. and combining approach would lead to introduce pure laparoscopic approach safely from open method. we reviewed the records of patients with renal mass treated with partial nephrectomy from to at our hospital. a total of patients underwent partial nephrectomy. of these, patients underwent pure laparoscopic procedures. seventy-seven patients underwent combining method, and two patients of these with solitary kidney and one patient with chronic nephritis were excluded. we compared these two groups in terms of perioperative outcomes, including the mean operative time, ischemic time, change in the glomerulofi ltration rate (egfr), and adverse events. conclusion: th is nonrandomized, comparative study suggests that pure laparoscopic approach had longer cold ischemic time but lower postoperative egfr change. complication rates were almost equivalent for both approaches. th erefore, we might shift safely to pure laparoscopic approach through the combined approach in the way of partial nephrectomy. nephron th irty-four ( . %) had bilateral suspected malignant tumors and were used as material for this study. twenty-fi ve were men and were women. results: eighteen patients ( %) had the same type of tumor in both kidneys. ten of them had clear cell carcinoma and had papillary renal cell cancer. four patients had bilateral oncocytomas. in patients ( %) the lesions diff ered between the kidneys (table ). in all patients only one kidney was operated on one occasion. in two patients treated with radical nephrectomy (rn) over years ago for renal cancer the subtype of the fi rst tumor was unknown. ten patients were treated with nss -nss, with rn -nss, with nss -rn, with nss -observation and with nss -radiofrequency ablation. two of the patients had von hippel-lindaus disease and one had birt-hogg-dubé syndrome. conclusion: bilateral renal masses were found in % of the patients in a material of patients treated with nss. over % of them had the same type of tumor on both sides but % of these were benign. th e combination of diff erent malignant and benign lesions occurred in %. th ese fi ndings are strong arguments for tumor biopsy before surgery is decided. preoperative oita red cross hospital, oita, japan introduction and objective: approximately % to % of patients who underwent total nephroureterectomy for upper urinary tract (uut) urothelial carcinoma (uc) developed recurrence in the bladder during the follow-up period. last year, we presented a risk factor for intravesical recurrence aft er laparoscopic radical nephroureterectomy (lrnu) in patients with uut-uc in siu congress. th is time, we will report the result of analysis of a multi-center study. a total of patients with uut-uc received lrnu between january and december in oita university hospital and affi liated institutions that were enrolled in this study. patients with concomitant bladder cancer or a history of bladder cancer were excluded from this study. postoperative cystoscopy and urine cytology were performed every months for to years, and postoperative intravesical recurrence was evaluated pathologically. th e signifi cance of each variable was analyzed univariately by log-rank test. multivariate analyses by cox proportion hazards regression model was used to estimate simultaneous eff ects of multiple risk factors. statistical signifi cance was defi ned as a p value of < . . results: median follow-up aft er lrnu was months (range - ). of the patients, postoperative intravesical recurrences were shown in / ( %). average time to fi rst intravesical recurrence was . months. in univariate analysis, there were two signifi cant risk factors of intravesical recurrences. one was for patients who did not receive postoperative adjuvant chemotherapy (p= . ). th e other was for patients with preoperative positive urine cytology indicating class iv and v (p= . ). multivarite analysis revealed that preoperative positive urine cytology indicating class iv and class v was a signifi cant risk factor for intravesical recurrence (hr . % ci . - . p= . ). in this multi-center retrospective study, preoperative positive urine cytology was a significant risk factor for intravesical recurrence. th erefore, adjuvant chemotherapy such as intravesical instillation therapy can be eff ective to prevent intravesical recurrence in patients with preoperative positive urine cytology. retroperitoneal laparoscopic nephron-sparing surgery for complicated renal cysts introduction and objective: to evaluate the feasibility, effi cacy and safety of laparoscopic partial nephrectomy for complex renal cystic lesions. a retrospective cohort study on clinical data of patients with complex renal cystic lesions treated by laparoscopic partial nephrectomy from may to april in peking university th ird hospital. according to the bosniak classifi cation, cases were lesions of grade iif, were grade iii, and were grade iv. th e mean diameter of cystic lesions was ( . ± . ) cm, and lesions were larger than . cm. results: all procedures were performed through retroperitoneal approach and successful. th e mean operative time was ( . ± . ) min, ranged from min to min, and the mean renal warm ischemia time was ( . ± . ) min, ranged from min to min. blood loss in operations was from ml to ml, and the mean was ( . ± . ) ml. th e postoperative hospital stay was ~ days, and the mean was ( . ± . ) day. postoperative pathological results included simple renal cysts ( . %), cases of adult cystic nephroma ( . %), mixed epithelial and stromal tumor ( . %), cases of renal cell carcinoma with cystic change ( . %), and multilocular cystic renal cell carcinoma ( . %). th e results showed . % of cystic lesions of grade iif, . % of grade iii and . % of grade iv were malignant. in the follow-up ranged from to months (median months), there was no case of recurrence. conclusion: th e diff erentiation between benign and malignant renal cystic lesions before surgery remains diffi cult. according to the bosniak classifi cation, radiological diagnostic fi ndings are standard but still limit to the accuracy to determine the dignity of pathological entity. laparoscopic partial nephrectomy is feasible to treat complex renal cystic lesions, and is a safe and eff ective minimally invasive option. introduction and objective: th e aim of the study was to evaluate the value of metastasectomy in patients with metastatic renal cell carcinoma (mrcc) in the targeted therapy era. we reviewed the medical records of patients who presented with mrcc and received no systemic therapy before enrollment. of them, underwent complete metastasectomy followed by targeted therapy (complete metastasectomy group), underwent partial metastasectomy followed by targeted therapy (partial metastasectomy group), and treated with targeted therapy alone (non-metastasectomy group). we estimated progression-free and overall survival using kaplan-meier curves. a cox proportional hazards regression model was used to estimate the prognostic signifi cance of metastasectomy. results: clinicopathological variables did not diff er among the groups except for history of nephrectomy, bone metastasis, number of metastatic sites, and time from diagnosis to treatment. th e median progression-free survival was . , . , and . months in the complete, partial, and non-metastasectomy groups (p = . ). karnofsky performance status (hr . , p < . ), cell type (hr . , p = . ), sarcomatoid or rhabdoid features (hr . , p < . ), retroperitoneal lymphadenopathy (hr . , p < . ), number of metastatic sites (hr . , p = . ), lactate dehydrogenase (hr . , p = . ), and time from diagnosis to treatment (hr . , p = . ) were independent predictors of progression-free survival. th e median overall survival was . , . , and . months in the complete, partial, and non-metastasectomy groups (p < . ). complete metastasectomy (hr . , p = . ) was an independent predictor of overall survival, along with age (hr . , p = . ), karnofsky performance status (hr . , p < . ), sarcomatoid or rhabdoid features (hr . , p = . ), bone metastasis (hr . , p = . ), retroperitoneal lymphadenopathy (hr . , p < . ), number of metastatic sites (hr . , p = . ), hemoglobin (hr . , p = . ), neutrophil (hr . , p = . ), corrected calcium (hr . , p = . ), and time from diagnosis to treatment (hr . , p = . ). conclusion: complete metastasectomy performed before targeted therapy signifi cantly increased overall survival in patients with mrcc. if surgically resectable, aggressive metastasectomy should be considered. guideline results: prominent international guidelines and strategies varied signifi cantly in relation to follow-up practice. th e mode and frequency of radiological imaging was signifi cantly diff erent across the guidelines for low and intermediate risk disease. although there is currently no consensus within the literature regarding surveillance protocols, various guidelines and strategies have been developed using both patient and tumour characteristics. th is information raises questions regarding the follow-up practice in australia due to both the lack of guidelines and the fi nancial. introduction and objective: nephrectomy is the cornerstone therapy for renal cell carcinoma (rcc) and its continued refi nement through research may enhance patient outcomes. medical registries are used domestically and internationally to aid research, assess trends and help guide future practice of many medical disciplines. th ere is currently no national australian nephrectomy registry. th is review aimed to explore possible defi ciencies within the australian rcc nephrectomy fi eld and through assessment of literature from established registries, determine if a national nephrectomy registry is appropriate and justifi ed to address these issues. a pubmed search identifi ed records pertaining to rcc nephrectomy in australia. a similar search identifi ed records relating to established nephrectomy registries internationally as well as other surgical registries of clinical importance. th ese records were reviewed to address the stated aims of this article. results: australian rcc nephrectomy fi eld lacks population-based data: resulting key issues identifi ed ) diffi culty benchmarking individual and institutional outcomes; ) small sample sizes and reduced power of studies; ) assessment of regional and nationwide outcome trends: diffi cult to achieve and oft en done years in retrospect with no ongoing monitoring; ) care centralisation debate: can small volume centres provide comparable outcomes to high volume centres? ) best practice guidelines: patterns of adherence to existing protocols is uncertain; and ) limited platform for large scale prospective studies -restricting potential research. review of established international registries demonstrated the registry model can eff ectively address issues comparable to those identifi ed in the australian literature. a centrally held, de-identifi ed national nephrectomy registry could provide a means of ad-dressing defi ciencies identifi ed in the australian rcc nephrectomy fi eld. th e model is supported by evidence from comparable international examples and will provide population-based data needed for studies at the institutional, regional and national level. th e development of a confi dential and non-threatening escalation policy to be implemented should trends in the data emerge is a future possibility. scope exists for possible integration with current or future registries/ databases to develop a more encompassing urological, cancer or surgical registry. need remains for continued exploration of the feasibility and practicalities of initiating such a registry. new technologies of identifi cation of renal artery in retroperitoneal laparoscopic renal surgery hao y, xiao c, liu y, ma l introduction and objective: th e objective of this study was to evaluate the feasibility of a new method to identify renal vessels during retroperitoneal laparoscopic nephrectomy. a total of patients underwent transperitoneal radical laparoscopic nephrectomies from january to august . in the fi rst consecutive patients (group ) we located renal artery with the standard technique; in the last consecutive patients (group ) the medial arcuate ligament (mal)-psoas muscle fat complex was used as an anatomic landmark to identify renal vessels. comparative analysis was carried out between the two groups, including mean hilar exposure time, mean blood loss, duration of hospital stay, conversion rate and complication rate. no diff erences were noted in gender, age, mean body mass index, tumor side and size of the lesions in the two groups (p> . ). mean hilar exposure times were . ± . minutes in group versus . ± . minutes in group (p< . ). mean blood loss was . ± . ml in group versus . ± . ml in group (p< . ). no signifi cant diff erences were detected regarding duration of hospital stay, complication rate and conversion rate between the two groups (p > . ). no complications and no recurrence of disease at ct evaluation were recorded neither in group nor in group . conclusion: radical laparoscopic nephrectomy in use of the mal-psoas muscle fat complex as an anatomic landmark is technically feasible and safe. in conclusion, the mal-psoas muscle fat complex can serve as an objective and belt-and-braces anatomic landmark for the identifi cation of the renal vessels in retroperitoneal laparoscopies. kalpinskiy a, alekseev b, kaprin a, nyushko k, vorobyev n, vokach d introduction and objective: th e aim of our study is to evaluate the results of percutaneous radiofrequency ablation (rfa) of renal tumors in elderly patients with severe comorbidities and a high risk of surgical intervention. th e aim of this study was to evaluate the expression of cd and microvessel density (mvd) in clear cell renal cell carcinoma (ccrcc) as well as the relationship between mvd and possible prognostic markers like tumor size, degree of tumor necrosis and degree of tumor hemorrhage. expression of cd was detected in patients with ccrcc and cases with benign kidney tissue using immunohistochemical staining. th e mvd was studied by weidner's method. results: th e expression of cd in the clear cell renal cell carcinoma (ccrcc) ( . (ds± . ), varied from to .) were signifi cantly higher than the expression of cd in the benign kidney tissue, as the control group, was . (ds± . ) (u= , p< . ). th e mvd values marked by cd were negatively correlated with degree of tumor necrosis (r=- . , p= . ), tumor size (r=- . , p= . ), but no association was found between mvd values and degree of tumor hemorrhage (r=- . , p= . ) in crcc. our results show that mvd in crcc were signifi cantly higher than mvd in the benign kidney tissue. th ere was a negative non signifi cant correlation between the mvd and presence of tumor necrosis as well as between mvd and tumor size. on the other hand, there was no correlation between mvd and degree of tumor hemorrhage in ccrcc. conclusion: expression of hif- α and vegf in crcc was signifi cantly higher than in normal kidney tissue. th e expression of hif- α and vegf may be responsible for angiogenesis in ccrcc, however these angiogenic factors play an important role in the prognosis of ccrcc patients. transvaginal hybrid notes nephrectomy in a low resource setting firaza p, lorenzo e, bardelosa j, reyes e, patron n introduction and objective: hybrid notes decreases the invasiveness of conventional laparoscopic surgery and overcomes the limitation of pure notes especially in the absence of angulated instruments. th e patients are , and -year-old females with complaints of recurrent fl ank pain and urinary tract infection due to an obstructed non-functioning kidney. materials and methods: materials used include standard laparoscopic instrumentations and a endoscope. under general anesthesia the patient was placed in a lithotomy position with the aff ected side up at degrees. veress needle was initially inserted thru the umbilicus and was later replaced with a mm laparoscopic port with additional mm port also inserted at the aff ected lower quadrant site. pa-tient was then positioned in a steep trendelenberg and mm port was inserted thru the posterior vaginal wall under direct vision from the abdominal cavity that was later used for the endoscope. nephrectomy proceeded despite noted severe adhesions and the kidney was placed in the specimen retrieval bag. th e vaginal port site was enlarged to cm for extraction of the specimen. th e vaginal wound was repaired using running - absorbable sutures. results: th ree cases of transvaginal hybrid notes nephrectomy were successfully completed. th e median operative time was minutes (range: - ). th e mean estimated blood loss was ml for the three cases. median renal dimensions (cm) were as follows: craniocaudal . (range: . - ), laterolateral . (range: - . ), and anteroposterior . (range: . - . ). th e patient resumed regular diet as early as day post operatively. drain was removed prior to discharge. th e mean date of discharge was rd day post-operatively. th ere were no noted surgical complications according to clavien-dindo grading system. conclusion: hybrid notes transvaginal nephrectomy is a feasible and reproducible procedure in selected patients regardless of laterality for better cosmesis, reduced post-operative pain and early recovery. however, the view was challenging because it was from the pelvis. th e left side procedure proved to be more diffi cult due to the gonadal vein obstructing the view, which is usually larger in young females. introduction and objective: to summarize our clinical experiences of laparoendoscopic single-site surgery (less) in urology. results: all procedure underwent successfully using single trocar x cone (storz) without any major complications. early recovery with minimal scar is the hallmark of less surgery. duration of time ( - mns), blood loss ( - ml), mobilization ( - hrs), hospital stay ( - days). no intraoperative complication without any conversion to other surgery (multi port laparoscopic surgery) and uneventful post-operative period was the fi nal outcome. introduction and objective: th e use of fl exible cystoscopy to study bladder is usually perform in urology departments using diff erent types of lubricant to reduce pain. th e objective is to compare the use of lubricant gel with lidocaine versus lubricant gel without anesthetic in fl exible cystoscopy in terms of pain and tolerability. materials and methods: seventy two patients are divided in two groups in this observational not randomized study. group : patients with lidocaine gel % and group : patients with lubricant gel without anesthetic. th e main variables analyzed are score in visual analogue scale (vas) and score in spanish pain questionnaire (spq). t-student test and chi-square test are used to compare diff erences using spss program and signifi cant statistical diff erences is considered p≤ . . results: mean age of patients in group is . ± . years and . ± . years in group (p= . ). th e distribution according to sex was men: women in group and men: women in group (p= . ). th e main pain score in vas was . ± . in group versus . ± . in group (p= . ). in the spq, the current intensity value was . ± . in group versus . ± . in group (p= . ), and the total intensity value was . ± . in group versus . ± . in group (p= . ). th e cost of gel with lidocaine is . euro and gel without anaesthetic . euro. conclusion: th e use of lidocaine gel do not produce benefi t in the fl exible cystoscopy and expensive the procedure. new laparoscopic surgery using water filled laparo-endoscopic surgery systems introduction and objective: urologist usual operated under water fi lled condition, such as transurethral surgery, percutaneous renal surgery. however, laparoscopic surgery was done under co . water fi lled condition has several merits. water pressure is suppressing venous bleeding and prevent from co embolism in venous injury condition. to keep water temperature as same as body temperature was useful to avoid low body temperature. simultaneous observation of ultrasound image from the surface of the body and laparoscopic view is possible during surgery. th us we conduct to develop the water fi lled laparo-endoscopic surgery systems (wafles). first problem is dispersion of blood aft er bleeding. it interrupts the laparoscopic view. we solved this problem to control the fl ow of irrigation, aff ording the continuous observation of bleeding point and it is easy to control the bleeding by vessel sealing system or coagulation. second problem is managing fl oating organs such as intestine or nets. th ese are disturbed the operating view and space. to keep the operating space, we use sheath and single port devices. however, obtaining wide view was still hard in the water because fl oating organs disturb the fi eld. to solve this problem, we use -d tracking navigation system. results: using young male pig, we performed partial nephrectomy and radical cystectomy using this new system. wafles is now developing. we will be present the update of this research soon. comparison of safety, effi cacy and cosmetic outcomes between standard laparoscopic live donor nephrectomy and mini-laparoscopic donor nephrectomy: a randomized clinical trial introduction and objective: th is study was conducted to compare safety, effi cacy and cosmetic outcome between standard laparoscopic live donor nephrectomy (sldn) and mini-laparoscopic donor nephrectomy (mldn) in a randomized clinical trial. from march to june , consecutive kidney donors were randomly assigned to two equal groups for laparoscopic donor nephrectomy. from march to june , consecutive kidney donors were randomly assigned to two equal groups for laparoscopic donor nephrectomy. mldn: six to eight centimeters pfannenstiel incision was made slightly above pubis symphysis and millimeters trocar was fi xed through exposed fascia using open technique. five mm port was placed under direct vision at the umbilicus for camera insertion and two . mm ports were placed in subxiphoid and paraumbilical area. sldn: ten mm port was placed at umbilicus using open access technique for camera insertion. five mm trocar for grasping and mm trocar for vascular clipping were placed at subxiphoid and paraumbilical areas under direct vision, respectively. th e second mm trocar was placed in suprapubic area. cosmetic appearance was assessed three months aft er surgery by using the modifi ed patient scar assessment questionnaire (psaq). conclusion: our experience in this study revealed that peri and postoperative fi ndings were comparable between sldn and mldn but mldn has signifi cant better cosmetic appearance than standard laparoscopic approach. qiu m, ma l, lu j introduction and objective: to report our experience and outcomes with retroperitoneal laparoscopic anderson-hynes dismembered pyeloplasty for the repair of ureteropelvic junction obstruction (upjo). we performed retroperitoneal laparoscopic anderson-hynes dismembered pyeloplasty between june and december . ureter was found in the lower pole of the kidney psoas front, then ureteropelvic junction stenosis was dissociated. ureter was cut at about cm distal ureter beyond the part of stenosis, then stenosis was resected. posterior wall was continuous sutured, and double j tube was antegrade placed. at last, anterior wall was continuous sutured. patient characteristics and perioperative outcomes were analyzed. perioperative parameters including operative time, estimated blood loss, postoperative length of hospital stay, and complication. results: th e procedure was successfully accomplished in all patients, and no patient required conversion to open surgery. th e mean operation time was . min ( - min), mean estimated blood loss was ml ( - ml), mean postoperative length of hospital stay was . d ( - d), and mean time of keep drainage tube was . d ( - d) . patients were followed up for ~ months (average . months). eighteen cases were followed up in years, and an- renal cyst ( ) other patients were followed up for - years. th e total remission rate was . %. conclusion: retroperitoneal laparoscopic dismembered pyeloplasty is a safe and effi cacious procedure for upjo in a long time follow-up. positioning-related complications of robot-assisted radical prostatectomy (rarp) in a steep trendelenberg position with physique fixation appliance by the negative pressure takeda h, nakano y, narita h introduction and objective: because of recent advances in minimally invasive surgical techniques, robot-assisted radical prostatectomy (rarp) has become the primary treatment option in prostate cancer. rarp, however, necessitates patients to be placed in a steep trendelenberg position, which presents multiple opportunities for complications relating to the positioning of the patient. our study aims to study the prevalence and demographic predictors of these positioning complications. we included patients who underwent rp from to using data extracted from our hospital database. all patients (n= ) had trendelenberg position with physique fi xation appliance by the negative pressure, hug-u-vac and film dressings. positioning complications (skin, eye, nerve, compartment syndrome/rhabdomyolysis) were identifi ed using patient-level diagnosis and procedural international classifi cation of disease, th edition, clinical modifi cation codes. we analyzed body pressure by portable interface pressure sensor. results: positioning complications occurred in . % of cases with shoulder complications contributing the most to this frequency. rubefaction occurred in cases, without bedsore. having positioning complications not increased a patient's odds of having increased age, bmi, operation time, body pressure, insignifi cantly. conclusion: th e steep trendelenberg position used in rarp was not shown to be associated with patient positioning-related complications in this sample. physique fi xation appliance by the negative pressure is safety and useful. evaluation of nasogastric tube (ngt) suction for evacuation of large bladder blood clot introduction and objective: blood clot formation in the urinary bladder can be caused by many etiologies such as postoperative bleeding, tumor bleeding, radiation cystitis and etc. acute urinary retention may disclose and a large three way catheter with irrigation is placed conventionally to prevent further formation of blood clot and manually remove the blood clot. when this failed an endoscopic procedure takes place to con-trol the bleeding and to relief the bladder. urologists may fi nd it diffi cult to remove a large, thick and bulky clot using ellik evacuator. here we introduce using nasogastric tube as an alternative to procure a safe and effi cient way to remove these bothersome clots. aim: to introduce a novel method to successfully remove large, troublesome blood clots during cystoscopy. we prospectively perform blood clot evacuation on patients within month (september -february ) in hasan sadikin hospital. th e patient, preoperatively have at least ½ of bladder volume with blood clot using ultrasonography. a fr ngt inserted into the bladder through the resectoscope sheath fr and connected to suction unit with a mmhg negative pressure. a calibration of the ngt tip does not exceed more than cm from the cystoscopy beak was made. backward and forward movement was set in motion during the procedure to facilitate blood clot removal. cystoscopy evaluation was performed in the end of the procedure to evaluate any complication. a total cystoscopy time, ngt suction time, and the volume of blood clot were documented. results: a total patients was all successfully managed with this method without any complications such as bladder laceration/perforation. th e mean age was years old with male predominance. most common etiologies of blood clots retention were postoperative bleeding ( %). th e average time for clot removal time was ( - ) minutes. th e average volume of blood clots removed was grams. conclusion: evacuation using ngt suction is eff ective, safe and an effi cient way to remove of large bothersome clot. learning curve assessment of robot-assisted radical prostatectomy in the oncological and functional outcomes takeda h, nakano y, narita h introduction and objective: th is study aims to compare the oncological, safety and functional outcomes between fi rst-step rarp and second-step rarp. th e study was conducted on a total of patients having undergone robot-assisted radical prostatectomy from to . th e fi rst patients (group ) were compared with the second (group ) to evaluate the learning curve eff ects. results: both groups were similar with respect to age, prostate-specifi c antigen level, body mass index, gleason score, and distribution of the clinical stage. th e operative time was minutes for group , and minutes for group (p= . ). individual times of various stages of the procedure (dissection of the seminal vesicles, entering the extraperitoneal space and dissection of the endopelvic fascia, incision of the bladder neck, division of the prostatic pedicles and preservation of the neurovascular bundle, and urethrovesical anastomosis) decreased signifi cantly over time. estimated blood loss was ml for group , ml for group . th e length of stay was . days for group , . days for group . positive surgical margin rates were % for group , % for group . while one patient in group had biochemical recur-rence, no patient in group had biochemical recurrence. continence rates at months were . %, and . % in groups and . conclusion: surgical, oncologic, and functional outcomes of rarp improve with increasing experience. outcomes similar to the published series by high-volume centers could be achieved aft er to rarp cases. possibility of d modeling and intraoperative navigation during procedures in the retroperitoneal space introduction and objective: application of d modeling allows you to get more information about the spatial imaging of the disease. intraoperative navigation in the retroperitoneal space is an innovative minimally invasive procedure, the surgeon improves orientation in retroperitoneal space. we present the method of intraoperative navigation based on virtual simulation during videoendoscopic partial nephrectomy for kidney's tumors. special computer program has been developed, that created three-dimensional image of operative space on the basis of preoperational tomographic data of a concrete patient. we used hardware-soft ware complex (hsc) for virtual modeling of the surgery zone. th e complex consists of a pc, original soft ware and mechanical d digitizer. th e hsc allowing to form virtual d model of a patient according to the results of tomography examination. th e original method of matching the system of coordinates of a virtual model with the patient was off ered. th e procedure was conducted under the conditions warm ischemia, aft er mobilization of the kidney, partial nephrectomy was performed by observing the image of d organ model agreed with the video image of the kidney tumor. th e method was originally performed for the patients with small renal tumors, who needed in surgical treatment, their average age was . (in the range from to ) years, men - ( . %), women - ( . %). size of the tumors were . ( . - . ) cm, they were located in the lower poles of the kidneys. average time of an operation performed with the use of the computerized choice of the surgical approach was . ( - ) minutes. warm ischemia time was . ( - min). th ere were no complications during the operation and in the post-operative period. th ere were no cases of positive surgical margins. conclusions: usage of the introduced computer program allows the surgeon to determine compliance with the contours of the d models of the body shown in the video monitor. th e technique provides additional possibilities for the surgeon in selecting borders in partial nephrectomy. th is method is particularly perspective for teaching beginner surgeons, it can help them acquire skills in minimally invasive surgery. possible impact of continuous drainage after minimally invasive partial nephrectomy introduction and objective: postoperative management of partial nephrectomy without drain placement is common, but the specifi c eff ects on patients are unclear. we investigated the impact of no drain placement aft er minimally invasive partial nephrectomy (mipn). we retrospectively studied consecutive patients who underwent laparoscopic and robotic partial nephrectomy at a single academic center. th e study group included evaluable patients without drain placement. th e quantity of postoperative fl uid collection in the perirenal space was calculated using computed tomography. th e pre-and postoperative serum concentrations of total protein and albumin, in addition to neutrophils, lymphocytes, monocytes numbers and c-reactive protein (crp) levels in the blood were compared. results: drain was placed in ( . %) patients who underwent mipn. th e remaining ( . %) patients were not provided with drain placement. although the average total quantity of fl uid discharged from the drain was ml, the average fl uid remaining in the perirenal space was not signifi cantly diff erent with or without drain placement ( . ml vs. . ml, p= . ). decrease in serum total protein and albumin with drain placement was signifi cantly greater than without drain placement (total protein; . % vs. . % p< . and albumin; . % vs. % p= . ). no drain placement also caused markedly greater decreases in lymphocytes and monocytes than drain placement, while neutrophils and crp were not different. a mipn population was necessary by design, which may limit the ability to generalize these results. conclusion: analysis of the quantity of fl uid collection showed little need for routine drain placement. no drain aft er mipn prevents serum protein loss and might aff ect wound-healing immune responses. initial experiences of laparoscopic radical cystectomy introduction and objective: simultaneous treatment of bilateral lesions is an interesting application of laparoscopy. our goal was to present our experience with simultaneous bilateral laparoscopic pyeloplasty using three midline ports in two adult patients. two adult patients (one male and one female) underwent bilateral laparoscopic dismembered pyeloplasty in one session. one of the patients had horseshoe kidneys. a -mm trocar was placed through the umbilicus, and two -mm trocars were placed midline - cm superior and inferior to the umbilicus. results: intra-and postoperative periods were uneventful. operation time was and minutes in the fi rst and second patient, respectively. obstruction was relieved in both patients bilaterally on a -month follow-up. conclusions: simultaneous bilateral laparoscopic pyeloplasty using three midline ports is safe and feasible in adult patients with bilateral ureteropelvic junction obstruction. introduction and objective: radical cystectomy is considered to be the most eff ective treatment for patients with muscle-invasive bladder cancer. most urinary diversions are performed extracorporeally because of complex procedure time consuming. however, with the development of minimally invasive radical cystectomy techniques, increasing attention has been focused on intracorporeal urinary diversions, including both ileal conduit and orthotopic neobladder. we reviewed cases of laparoscopic radical cystectomy with intracorporeal ileal conduit in our medical center. ten patients with bladder cancer who underwent laparoscopic radical cystectomy and intracorporeal ileal conduit were retrospectively reviewed. with the cystoprostatectomy and lymphadenectomy completed, a - cm segment of ileum was identifi ed cm from the ileocecal junction. division of the isolated segment of bowel and the mesentery was performed using the endo-gia stapler. ileo-ileal continuity was reestablished by creating a generous side-to-side anastomosis with endo-gia stapler. th e left ureter was passed to the right side of the abdomen. aft er placement of single-j stent, the ureters were spatulated and the ureteroileal anastomis was performed with a running suture. results: laparoscopic radical cystectomy and intracorporeal ileal conduit were performed successfully in all ten patients from jan to dec . th e mean operating time was min ( - min), and the mean ileal conduit construction time was min ( - min). th e mean blood loss was ml ( - ml), and no patient received transfusion. th e time to orally allow was postoperative day ( - ). th e mean hospital stay was d. no major complication occurred. results: all the procedures were successfully completed without additional trocars except for one patient who was immediately converted to suprapubic-assisted laparoendoscopic single-site surgery (sa-less) nephrectomy for rectal injury during the placement of the zou-port. in our initial cases, tri-port was used. in the subsequent procedures, zou-port was used. th ere were no other intraoperative complications occurred. postoperative complications included a right external iliac artery thrombosis in one patient who underwent pure transvaginal notes simple nephrectomy. th e mean operative time was (range to ) mins and the mean estimated blood loss was (range to ) ml for pure transvaginal notes renal cyst decortication. th e mean operative time was (range to ) mins and the mean estimated blood loss was (range to ) ml for pure transvaginal notes nephrectomy. th e mean visual analog scale (vas) pain score was . (range - ) on postoperative day . th e mean time for ambulation was . (range - ) d. th e mean time for oral feeding was . (range ~ ) d. th e mean postoperative hospitalization stay was . (range ~ ) d. during the to -month follow-up period, all the patients were in good condition. th e posterior colpotomy incision healed well. th ere was no scar on the abdominal wall. th ere was no retrograde infection of pelvic and abdominal cavity, umbilical hernia, or uterine prolapse. conclusion: th e application of zou-port in pure notes transvaginal eff ectively reduces the diffi culty of operation and avoids the abdominal and pelvic organ injury, which is worthy of clinical application. lower ureter stricture. all the cases presented only one abdominal scar before surgery, including cases with the history of caesarean section, cases with the history of birth control surgery, cases with the history of appendectomy, cases with the history of inguinal hernia repair, cases with the history of ureterolithotomy, one case with the history of bladder lithotomy, and cases with the history of laparotomy surgery. th e mean length of scar is . ( . to . ) cm. under general anesthesia, the patients were positioned in lithotomy with aff ected side elevated at °. two trocars ( mm or mm) were introduced into abdominal cavity from the incisions at the right and left medial margin of umbilicus. a -or -mm trocar was inserted into the abdominal cavity through the abdominal scar under the direct vision. our technique for the transabdominal scar-assisted u-less is similar to that of standard laparoscopy, using conventional operating apparatus placed in the umbilical trocars, under direct vision achieved by a fl exible-tip ° laparoscope placed through the trocar at the abdominal scar. th e specimen was placed inside a homemade bag and removed under direct vision through an extended incision at the abdominal scar. to explore the application of three-dimensional ( d) laparoscopic technique in hybrid transvaginal notes nephrectomy. a total of female patients underwent hybrid transvaginal notes nephrectomy using d laparoscopy system. th ose included cases of hydronephrosis, cases of renal empyema, and cases of renal atrophy. th e median age was (range to ) years, and body mass index was . ( . ~ . ) kg/m . all patients were with unilateral disease and normal contralateral kidney. th e perioperative data including operative time, estimated blood loss, and surgical outcome were analyzed. results: th e procedures were successfully completed. th e median operative time was ( to ) mins. th e median estimated blood loss was ( to ) ml. th e patients were recover ambulation on postoperative day to , and tolerated diet on postoperative day to . th e patients were discharged on postoperative day to . th ere were no intraoperative or postoperative complications. during the -to -month follow-up period, all the patients were in good condition. th e posterior colpotomy incision healed up well. th ere were two hidden umbilicus scars. and p= . , respectively). mean incision length was shorter ( . vs. . cm, p< . ) and the scar satisfaction score was higher ( . vs. . , p= . ) in ldn with fl ank incision group. th e postoperative pain scores were higher (p= . ) in ldn with fl ank incision group but analgesic requirements were similar in both groups (p= . ). conclusion: ldn with fl ank incision had cosmetic satisfaction and comparable graft function, although challenging to the surgeon with longer warm ischemia time and higher postoperative pain. the effect of caudal block on postoperative analgesia in robotic assisted laparoscopic prostatectomy: a prospective study in a national referral centre introduction and objective: caudal block is widely used in paediatric surgery. it provides satisfactory postoperative pain relief in lower abdominal operations with minimal complications. th is pilot study explores its eff ect on postoperative pain control and its safety in patients who underwent robotic assisted laparoscopic prostatectomy (ralp). from to , consecutive patients were randomised into groups of patients. th e intervention group received caudal block using ropivacaine immediately aft er operation, while the control group only received analgesia consisting of paracetamol, nsaids, and opioids. both groups were assessed using verbalised pain scores in recovery room, and , , , , hours aft er the operation. additional analgesic requirements were recorded in the intervention group. opioid-related adverse events and the time to passage of fl atus were also recorded. introduction and objective: th e dorsal venous complex (dvc) ligation and vesicourethral anastomosis (vua) are the most challenging parts during laparoscopic radical prostatectomy (lrp). th is study will introduce a unique technique without any knots for the dvc ligation and vua using the unidirectional single running self-retaining suture. th is study is to examine the eff ectiveness of our knotless laparoscopic radical prostatectomy compared with the conventional technique. materials and methods: from december to december , lrp were separated into groups: group of knotless lrp and group of conventional single-knot lrp. during knotless lrp, the dvc is sutured using a - / circle self-retaining suture with bites at the same place, and the vua is performed with a -cm - / circle barbed self-retaining suture with one needle driver. retroperitonoscopic pyeloplasty is a feasible approach in the management of pelviureteric junction obstruction with a crossing vessel. anterior transposition using the posterior approach demands a good experience. herein, we present a case with complex vascular anatomy representing a real surgical challenge for a retroperitonoscopic approach. in the period from - , cases with a crossing vessel were operated by a single surgeon using both transperitoneal and retroperitoneal approaches. we report here a y old girl with left sided pelviureteric junction obstruction presenting with recurrent loin pain. lateral retroperitoneal laparoscopic approach was used with trocars; mm optic trocar and two mm working trocars. th e pelviureteric junction was tightly pushed anteriorly and close proximity to complex crossing vessels. dissection from the crossing vessels was performed followed by anterior transposition of the pelviureteric junction and a diffi cult anastomosis was performed with antegrade dj insertion. smooth postoperative recovery, no leakage, dj is removed aft er . month; follow-up ultrasound revealed decompression of the pelvis with no recurrence of the symptoms during the follow-up period. conclusion: retroperitonoscopic lateral approach is feasible for the management of pelviureteric junction obstruction with crossing vessel even in the most diffi cult cases in well trained hands. robotic assisted laparoscopic reimplantation for iatrogenic ureteral injury franklin a, jones c, pokala n, cummings j introduction and objective: ureteral injuries are a source of morbidity in pelvic surgery. robotic approaches to these injuries have been proposed. we reviewed our experience with this approach to examine the outcomes in patients undergoing robotic assisted laparoscopic reimplantation (ralr) for iatrogenic ureteral injury. oncological outcomes of robotic prostatectomy in the victorian public sector basto m , , sathianathen n , te marvelde l , landau a , , graves r , , everaerts w , , birch e , lawrentchuk n , goad j , moon d , murphy d , , , , introduction and objective: following the installation of the davinci s at peter maccallum cancer centre in , we aim to report medium-term oncological outcomes of patients undergoing robot-assisted radical prostatectomy (rarp) and to identify factors that act as predictors for biochemical recurrence (bcr) and oncological failure (of). a prospective cohort of consecutive men who underwent rarp in a single victorian public hospital were followed up for a median time of . and . months for bcr and of respectively. of was defi ned as bcr (psa≥ . ng/ml) or the start of adjuvant therapy. however, longer-term data is still required to better evaluate oncological success. functional outcomes of robotic prostatectomy: the victorian public sector experience basto m , , sathianathen n , te marvelde l , landau a , , graves r , , everaerts w , , birch e , lawrentchuk n , goad j , moon d , declan murphy d , , , , introduction and objective: to report medium-term functional outcomes of men aft er undergoing robotic assisted radical prostatectomy (rarp). furthermore, the impact of the procedure on quality of life will also be analysed. a cohort of consecutive men who underwent rarp in a single victorian public institution was assessed post-operatively for continence and potency status. a 'prostate cancer research survey' that was distributed pre-operatively and at , , , and months post-rarp, in combination with hospital medical records were utilized to collect data. th e following validated questionnaires were included in the survey: expanded prostate cancer index composite for clinical practice (epic-cp), sexual health inventory for men (shim) and prostate cancer related quality of life scale (pcar-qols). th e latter primarily evaluated the impact of surgery on quality of life. results: utilising hospital medical records, of the ( %) men that had follow-up post-operatively, % ( / ) were fully continent at months using a zero pad defi nition and % ( / ) were continent using a zero or security pad defi nition. of those who completed the epic-cp questionnaire, preoperatively (n= responders), . % and . % were continent using a zero and security pad defi nition respectively. at -months (n= responders), . % of patients were fully continent using zero pads per day and . % of patients were continent using none or security pad per day. regarding erectile function, shim scores were available for men pre-rarp, of which % were considered to be potent. of this subset of men, only %, % and % are considered post-operatively potent at , and -months. none of the patients that were pre-operatively impotent regained their erectile function at months. sexual confi dence was the facet of life that was most impacted by rarp. other quality of life subdomains showed no signifi cant diff erences aft er robotic prostatectomy. conclusion: th ere has been satisfactory recovery of continence post-rarp, however, erectile dysfunction still remains an important adverse sequela of surgery. overall, robotic prostatectomy has been successfully implemented in the victorian public sector with satis-introduction and objective: to compare patterns of care and perioperative outcomes of robotic prostatectomy to other surgical approaches, and create an economic model to assess the viability of robotic prostatectomy in the case-mix public health funding system. we retrospectively reviewed all radical prostatectomies (rp) performed for localised prostate cancer in victoria, australia, between july and april from the victorian admitted episode dataset (vaed), a large administrative database that records all hospital inpatient episodes in victoria, australia's second most populous state. patterns of care, length of hospital stay (los) and blood transfusion rates (btr) were compared by surgical approach. we then created an economic model to evaluate the incremental cost of robotic assisted radical prostatectomy (rarp) over open radical prostatectomy (orp) and laparoscopic radical prostatectomy (lrp) incorporating the cost off set from diff erences in length of hospital stay and blood transfusion rates. th e economic model constructs estimates of the diagnosis related group (drg) costs of orp and lrp, adds the gross cost of the surgical robot (capital, consumables, maintenance and repairs), and manipulates these drg costs to obtain a drg cost per day which can be used to estimate the cost off set associated with rarp in comparison with orp and lrp. economic modelling was performed around a base-case scenario, assuming a -year robot lifespan and robotic cases performed per fi nancial year, and one and twoway sensitivity analyses performed for the -arm da vinci shd, si and si dual surgical systems (intuitive surgical ltd, sunnyvale, ca, usa). both situations present a challenge to the surgeon contemplating a radical prostatectomy for prostate cancer, due to surgical access and anomalous vascular and ureteric anatomy. open radical prostatectomy has been reported in transplant recipients, but very little has been described using a robot-assisted laparoscopic approach. a case series will be described, illustrating the challenges and techniques required to successfully perform transperitoneal robot-assisted radical prostatectomy in patients with a congenital pelvic kidney or renal transplant within the pelvis. operations were performed using the da-vinci surgical system. we will describe a series of patients between and who underwent transperitoneal ro-bot-assisted radical prostatectomy, including patients with a congenital pelvic kidney and a redo renal transplant within the pelvis. prostatectomy was performed using a partial nerve spare in all cases, and pelvic lymph node dissection was not performed. th ere was a mean console time of minutes with a mean estimated blood loss of ml. histopathology confi rmed gleason sum - disease confi ned to the prostate with no extraprostatic extension or seminal vesicle invasion (pt c), and surgical margins were free of tumour in all cases. th e tumour volume ranged from . to . cubic centimetres. th e psa became undetectable postoperatively and remained undetectable without further therapy. careful perioperative review of imaging and placement of ports under direct vision was essential in avoiding complications. stay suture is applied at glans. circumcision incision is applied leaving at least mm tissue of inner mucosal collar. penile skin is denuded down to the penoscrotal junction. minor degree of chordee is corrected by this procedure. a fr feeding tube in the urethra adds to identify the distal urethra which is just underneath the skin in these case, which removed at the end of procedure. mucosa is defi cient ventrally and is replaced by a triangular patch of skin. th is skin patch is excised and mucosal edges are approximated in the midline. th is simple maneuver gives glans penis an upward tilt and meatus appears almost on the tip of glans. redundant preputial skin is excised and mucocutaneous approximation is done with / pds. no dressing is required. we operated cases of glanular hypospadias between december and january . mean age of children was . ± . years. all cases were day cases. th ere was no need for catheterization and dressing. we used temporary dressing for mild bleeding immediate post op in cases only which were removed in recovery room. th ere was no immediate post-operative complication like urinary retention, severe pain, fever or urinary tract infection. th ere was no complication of meatal stenosis in follow-up ( - month follow-up). urine stream was good and cosmesis was satisfactory to parents. we had low complications in our set up and success of glanular hypospadias by our technique was good in terms of good urine stream and cosmesis. conclusions: th e goal of modern hypospadias surgery is a functional neourethra that appears to be normally circumcised penis. tubularized incised plate urethroplasty is a widely applicable technique for distal hypospadias repair. but our current series shows that modifi ed tubularized incised plate technique has low complication rate and excellent cosmetic results superior to tubularized incised plate urethroplasty for primary distal hypospadias repair. however, these results must be further evaluated by comparison study of large series. the impact (catalona, ) was performed in patients. occult metastatic disease was found in two patients ( groins) at the time of diagnosis and subsequently developed in patients during follow-up. th erefore, a total of ( %) of the patients developed metastatic disease. conclusions: current management protocols place moderately diff erentiated t penile scc without vascular invasion in a low risk group for lymph node metastases. for this reason a primary option for these patients expectant approach is currently recommended. our experience has shown that patients in this group are really at higher risk for metastatic disease, and we suggest early modifi ed groin dissection instead of expectant observation. introduction and objective: penile cancers are rare. in ghana, they account for less than % of all genitourinary cancers. data on penile cancers in ghana is scanty. we report on cases of penile cancers seen over the last years at the komfo anokye teaching hospital (kath). th e aim of the study was to describe the clinicopathological presentation and the mode of treatment of penile cancers in our setting. th is was a retrospective study of histologically confi rmed cases of penile cancers seen at kath from january to december . information gathered included age, the clinicopathological features and mode of treatment using a structured proforma. results: th ere were cases of histologically confi rmed penile cancers over the period. th e age range was from - years with a median age of years. eight were uncircumcised and were married. in only one did the lesion not originate from the glans penis rather aff ecting the base and upper part of the left of hemi-scrotum. in patients, the lesion was restricted to the glans penis, it had involved the distal penis in , midshaft in , proximal penile in and base of penis in one of whom had auto amputation. all were squamous cell carcinoma with majority being moderately well diff erentiated ( %). seven had ulcerative lesions and were caulifl ower-like. majority were advanced (t ) involving the corpora ( %). only one patient reported with a t lesion. eleven patients ( . %) had lymph node involvement and two had distant metastasis at presentation. only one patient had a penile sparing surgery with of them having partial penectomy at various levels with ure-throstomy at the stump ends. one had total penectomy with suprapubic urinary diversion whiles the one with auto amputation had radiotherapy as the primary treatment. eleven of the patients had lymph node dissection. four had adjuvant radiotherapy. conclusion: most patients present with advanced disease making any hope of achieving a functional and cosmetically acceptable penis aft er treatment impossible. further education is needed to ensure early detection and treatment. how does partial penectomy due to penile cancer affect the sexual life? even though the high incidence of penile cancer in brazil, the sexual life of its patients, as well as their partners, has never been evaluated before. th e aim of this study is to evaluate erectile function in patients who underwent partial penectomy due to penile cancer, describe the socio-demographic and clinical data as well as to assess the patient's partners' sexual function. we performed a prospective analysis in patients between and at pernambuco state cancer hospital in brazil. th e sample consisted of patients who were submitted to partial penectomy for the treatment of penile cancer. control group included volunteer couples from the general population with similar socio-demographic features. th e assessment of erectile function and female sexual dysfunction were evaluated with iief- and fsfi respectively. results: th e prevalence of erectile dysfunction (ed) in the group of individuals subjected to partial penectomy was . %, including severe ed in %, moderate ed in %, mild-to-moderate in %, mild ed in . %, and no ed in . % of the participants. th e prevalence of ed in men of the control group was . % and was typically characterized as mild ed (p < . ). between partners of partial penectomy and control groups, % and % reported sexual dysfunction, respectively (p = . ). a comparative analysis of the risk factors for the ed showed that there were not diff erences between both groups (body mass index (bmi); tabagism; diabetes; hypertension; dyslipidemia and hypogonadism). conclusion: th e actual incidence of erectile dysfunction in patients submitted to partial penectomy for penile cancer is . %. comparative analysis between patients who underwent partial penectomy and general population showed a higher dysfunction rate in addition to more severe ed. in despite of that, their partner's sexual function was similar between the analysed groups. the introduction and objective: androgens are essential for the development and growth of the genitalia. th ey regulate the erectile physiology by multiple mechanisms. several studies have examined associations among sex hormones' serum levels, erectile function and sex drive. we sought to identify a protocol for using testosterone in men with erectile dysfunction and late-onset hypogonadism (loh). during a -month period, men with erectile dysfunction who presented to the andrology clinic were selected. th ey underwent a complete physical examination and fi lled out the international index of erectile function- questionnaire. serum luteinizing hormone (lh) and testosterone levels were evaluated. patients received a single intramuscular injection of mg testosterone. th ereaft er, serum levels of lh and testosterone were measured weeks later. results: th e mean age was years old. aft er treating patients with testosterone, ( %) showed improvement in loh symptoms including libido, loss of energy, irritability and quality of life. th e mean international index of erectile function was and . , prior to and aft er treatment respectively. mean serum testosterone levels before and aft er treatment were . and . ng ml_ respectively (p = . ). mean serum lh revealed a signifi cant decrease aft er the study (p = . ) ( . and . ng ml_ , before and aft er the study respectively). our fi ndings suggested that testosterone replacement therapy improves libido and loh symptoms in individuals with almost normal or lower limit normal value of serum testosterone levels. does l-carnitine therapy add any extra benefi t to standard inguinal varicocelectomy in terms of deoxyribonucleic acid damage or sperm quality factor indices: a randomized study to evaluate if addition of l-carnitine therapy to standard varicocelectomy adds any extra benefi t in terms of improvement in semen parameters or deoxyribonucleic acid (dna) damage. one hundred patients enrolled in this study and were randomly divided into groups ( patients in each group). in group , standard inguinal varicocelectomy and, in group , standard inguinal varicocelectomy plus oral antioxidant therapy (oral l-carnitine, mg times a day) were performed for months. for all patients, routine semen analysis and dna damage test of spermatozoa (by methods of terminal deoxynucleotidyl transferase dutp nick end labeling and protamine damage assay) were performed at baseline and at and months postoperatively. results: in both groups, the improvement in semen analysis parameters and dna damage was observed, but there was not any statistically signifi cant diff erence between the groups in these parameters, although the slope of improvement in dna damage was slightly better in group (that was not statistically signifi cant). we observed that addition of mg of l-carnitine orally daily to standard inguinal varicocelectomy does not add any extra benefi t in terms of improvement in semen analysis parameters or dna damage. serum uric acid as a risk predictor for erectile dysfunction introduction and objective: testicular torsion is one of the few urological emergencies that require prompt diagnosis and treatment, since its delay leads to testicular ischemia inevitably leads to testicular necrosis and atrophy. we aimed to determine the pattern of presentation and early outcome of patients with testicular torsion managed at kcmc. th is was a hospital based descriptive retrospective and prospective study involving patients who were managed for testicular torsion between january and january . eighty three ( %) were at the age of years with a mean . and a standard deviation of . . results: left side was more aff ected by . %. th irty two ( . %) patients arrived at kcmc within six hours from the onset of symptoms. scrotal pain was the main complaint. seventy two ( %) patients were misdiagnosed at the peripheral health facilities and treated empirically with antibiotics. ninety six point nine percent of those with more than degrees of rotation and duration of arrival to kcmc beyond six hours were found with missed torsion compared to . % of those with a degree of rotation less than and less than six hours on arrival to kcmc (p-value . ). orchiectomy of the aff ected testis and fi xation of the viable was the mostly adopted treatment option by . %. eighty four percent of our clients had fi rm and smooth testis at follow-up of three months with % having atrophic testis at three months in both groups (retrospective and prospective arms). conclusion: testicular torsion aff ects more young adolescent males. all patients with testicular torsion presented with scrotal pain. most patients arrived to kcmc hospital beyond six hours majority of them being treated empirically with antibiotics at the peripheral health facilities. missed torsion is a common sequel to our patients outcome at three months is promising by having viable testis. ho:yag laser ablation for ulcerative interstitial cystitis tokyo women's medical university aoyama hospital, tokyo, japan introduction and objective: in cases of ulcerative interstitial cystitis are usually treated by tur or by electrocautery, resulting in improvement of pain. efficacy of electrocautery using laser remains unclear because of a very few number of case reports. we treated this time ulcers of interstitial cystitis by cautery using ho:yag laser to evaluate its effi cacy as well as safety. materials and methods: eight cases with hunner's ulcers whose pains were hardly controlled aft er drug therapy and/or hydrodistention were treated with ho:yag laser. patients were evaluated with interstitial cystitis symptom index (icsi), interstitial cystitis problem index (icpi), international prostate symptom score (ipss), quality of life (qol) index and a visual analog pain scale (vas) at base line, one, three and six months post operatively. statistical analysis was performed using the paired t test, in which p< . was considered statistically signifi cant. results: patients were all females aged to years. half of them were treated more than two times. scores obtained by the questionnaire survey were improved aft er the laser therapy. scores of icsi, icpi, ipss, qol index and vas were statistically signifi cantly decreased at one and three months. only vas was statistically signifi cantly decreased at six months. th ere was no severe complication associated by the therapy. conclusion: ho:yag laser therapy for ulcerative interstitial cystitis is effi cacious at least for three months. also this treatment is safe for aged patients. introduction and objective: th e use of methylene blue (mb) to highlight anatomic structures in urology is a well-established practice. a narrow urethral plate can be diffi cult to properly locate intraoperatively, particularly in panurethral strictures. our objective is to assess the value of intraurethral injection of mb during urethroplasty. th ere is cc of mb ( mg/ ml) diluted in cc of normal saline. th e mb is gently injected retrograde into the urethra. a penile clamp is applied for minutes to increase the contact time of the mb with the urethra. th e urethroplasty commenced and the urethra was opened. th e impact of the mb on the anatomy of the urethra was by subjective assessment of a single surgeon (s.b.k.). results: a total of consecutive cases were prospectively evaluated from - . precise staining of the narrow lumen was successfully observed in ( %). in these cases, the diseased urethral strictured portion of the urethra was subjectively stained blue with mb. th e grossly normal appearing urothelium remained pink and did not take up signifi cant mb stain. in ( %) cases minimal or no staining was observed. extravasation in to the spongiosa was seen in ( %) cases. in ( %) cases there was dense staining distal to the narrow lumen. th ere were no known allergic complications. conclusion: normal urothelium does not appear to be stained by mb. mb readily stains diseased and strictured urotheilum. intraurethral injection of mb is a useful tool in urethroplasty. it helps in delineation of stricture and identifying lumen. it guides us to the exact area of urethra to be augmented. it is a simple, non-costly and non-invasive tool. in our high volume tertiary referral unit, it is now standard to inject methylene blue in urethra immediately prior to urethroplasty. demography, preoperative imaging and surgical outcome in penile fracture results: condition was occurred in . % of patients during an abnormal sex such as masturbation, aggressive sex and also taghaandan. all patients except one that refused intervention were treated surgically. only four cases involved bilateral corporal injury. two involved unilateral corporal injury with an associated urethral injury, and one involved bilateral corporal injury with an associated urethral injury that all were repaired primary. urine analysis was performed for . % of patients. gross hematuria was seen in one and microscopic in two patients of urethral injury and did not see in others. retrograde urethrogram were not taken of patients with urethral injuries. diagnostic cavernosography or magnetic resonance imaging was not used in any of the patients. cystoscopy was performed in case of gross hematuria with complete urethral transection. no complications occurred in the patients in early follow-up. we are interested in that report entire result of this study such as longterm surgical outcome at congress. conclusion: based on islam promotion for early and inexpensive marriage, avoiding from abnormal sex can signifi cantly decrease penile fracture. in addition, we recommended immediate surgical exploration and repair of tunica albuginea without any preoperative diagnostic imaging. introduction and objective: cowper's glands are two exocrine glands, which are located in the perineal pouch between the fascia layers of the urogenital diaphragm. th ey excrete pre-ejaculate into the urethra to lubricate it and neutralize acid to enable sperm to pass through the urethra. th e glands form two ducts that are . to cm long. although anatomic variations exist, the majority of ducts combine to make one confl uent passage that opens at the posterior part of the bulbar urethra. cowper's gland collecting ducts dilatation is called syringocele, an uncommon and under-diagnosed anomaly in adults. in pediatric patients there are . % and . % found on autopsy studies. we are presenting case of an adult -year-old male, whose symptoms were unrecognized by many physicians, even experienced urologists. th e patient had diff erent treatments with antibiotics and other diff erent medications without success. results: th e patient's chief complaint was dribbling aft er voiding few drops of urine when smiling, coughing, sneezing, crouching and any kind of eff ort. he received treatment as an outpatient by family physician and dermatologist. a bulging on the perineum was found by palpation, hard to elastic consistency, walnut size formation in the corpus spongiosum, easily movable from the perineal skin. urethroscopy was performed and the fi nding in the bulbar urethra was a cystic formation, gray to white color with very thin blood vessels. it fi lled the lumen of the bulbar urethra, but with pressure very easily passed the urethra and verumontanum to the bladder. voiding and retrograde urethrography showed fi lling defects in the bulbar urethra. th is cystic formation was fi xed to the fl oor of the urethra. an incision and deroofi ng of the cystic wall by resection was done. th e patient aft er this procedure was without dribbling aft er voiding. introduction and objective: th e use of methylene blue (mb) to highlight anatomic structures in urology is a well-established practice. th ere are diff ering opinions regarding the management of short atraumatic bulbar strictures. some favor augmentation with buccal mucosal graft (bmg) while others favor excision and primary anastamosis (epa). th e divergence of opinion is unifi ed toward epa in the face of signifi cant spongiofi brosis. our objective is to determine if mb can be used to assess the degree of spongiofi brosis in short atraumatic bulbar strictures. we term the procedure methylene blue spongiography. five cc of methylene blue ( mg/ml) is diluted in cc of normal saline. th e dissection for the urethroplasty continues until the bulbar urethra is exposed. th e location of the stricture is identifi ed. insulin needles are inserted in three locations. one needle is placed in the sponge proximal to the stricture. another needle is placed in the sponge at level of stricture. th e third needle is placed in the sponge distal to the stricture. large atraumatic clamp is place at the most proximal extent of the bulb to limit the confounding blood fl ow from the bulbar artery. methylene blue is gently injected via distal needle. th e two remaining needles are then observed for mb effl ux. presence of mb effl ux in needle proximal to stricture implies a defi ciency of signifi cant spongiofi brosis and urethral transection with epa is not performed. absence of effl ux of methylene blue in proximal needle implies signifi cant spongiofibrosis and epa is performed. we performed mb spongiosography in short bulbar idiopathic strictures. mean length of the stricture was . (range to . ). in ( %) cases methylene blue was seen across the stricture and transecting urethra was avoided. in ( %) cases where no mb went across primary excision and anastomosis was performed. no patients had adverse reaction or complication of methylene blue. conclusions: methylene blue spongiography can be performed to guide the method of urethroplasty performed. it is a simple, cost eff ective, and time effi cient method to further evaluate the degree of spongiofibrosis. effi . th e allium bulbar urethral stent is a fully covered, self-expandable, large caliber metal stent, specially designed for the treatment of bulbar urethral strictures. th e indwelling time for the stents was planned to be months. all men underwent an internal uretrotomy procedure followed by an endoscopic stent placement. progressive decreasing of the urinary peak fl ow rate, recurrent urinary infection and stent migration were the early removal criteria. th e success criteria aft er the stent removal were: no evidence of stricture on urethrogram or endoscopy, urinary peak fl ow greater than ml/sec and no recurrent urinary tract infection. results: five stents were replaced since very early migration not more than one month period. none of the patients reported discomfort at the stent site. five patients complained of mild urinary incontinence which was resolved aft er stent explantation. all stents were removed very easily without any complication to months (mean . months) aft er implantation. follow-up period was meanly months ( to ) after stent explantation. clinical success was achieved in patients ( %). conclusion: based on our results, temporary placement of allium bulbar urethral stent, for management of the recurrent urethral strictures, is noninvasive, safe and eff ective procedure. the impact of testicular loss on the psychopathology we also compared the results of long-term treatment group and short-term treatment group. th is study showed that cases of long-term continuous administration of doc consisting of or more cycles among patients of castration-resistant prostate cancer (crpc) treated with doc from october to september at our institution, retrospectively. nineteen patients who had treated with doc or less cycles were defi ned as short-term dose group, and both groups were compared. doc was administered every to weeks at to mg/m , and was treated with prednisolone at mg/day as a general. results: th e median number of treatment cycles was (range to ), and the median age of patients was (range to ) years old. th e median psa levels at start of doc based chemotherapy was . (range . to . ) ng/ml. th irteen cases ( %) showed a decrease in psa levels and cases ( %) showed a decrease in psa levels of % or more, the -year survival rate of long-term dose and short-term dose group were % and %. adverse eff ects of grade or lower consisted of leukocytopenia in % and thrombocytopenia in %, stomatitis and general fatigue in some cases, however, grade or higher were not observed in long-term dose group. in multivariable analysis of parameters, long-term treatment was related to psa levels at start of treatment and alp levels. pattern of use of androgen deprivation therapy in prostate cancer: an italian multicenter cross-sectional analysis introduction and objective: androgen deprivation therapy (adt) for prostate cancer (pca) is widely used with diff erent indications, however, some discrepancies exist between clinical practice and the recommendations of the international guidelines. th e aim of this cross-sectional study was to evaluate patterns of use of adt in patients with pca in italy. we also aimed to measure the adherence of adt prescriptions to the recommendations of the eau guidelines. materials and methods: th e choice study was an italian multicenter cross-sectional studying conducted from december to january on patients treated with adt for pca (fi rst prescription or renewal of therapy). th e project involved radiotherapy departments and urology centers. inclusion criteria were: age ≥ years, previous diagnosis of pca and current adt. at baseline all the following information were included: charlson comorbidity index (cci), clinical stage, psa level at the time of the diagnosis, total prostate volume and gleason score; gleason score and pathological stage from radical prostatectomy (rp) when available. we subdivided the cohort into three risk categories for each treatment group, based on d' amico classifi cation. patients were categorized according to primary treatment into rp, radiotherapy (rt), rp + rt and adt only. radiotherapy comprised external beam therapy and brachytherapy. adt included bilateral orchiectomy, gnrh agonists or anti-androgens. th ree geographical areas were considered: northern, central and southern italy. adt change (adt-c) was defi ned as any modifi cation of therapy between previous adt and treatment prescribed aft er enrolment. the prevalence and outcomes of pt disease after neoadjuvant hormonal therapy plus radical prostatectomy in high-risk prostate cancer introduction and objective: to identify the prevalence and clinical outcomes of pt disease following neoadjuvant hormonal therapy (nht) and radical prostatectomy (rp) in high-risk prostate cancer. we retrospectively included patients who had received nht and rp for the treatment of high-risk prostate cancer. we classifi ed the patients into two groups, the pt group and the non-pt group depending on whether a residual tumor was observed or not. we identifi ed cases ( . %) with pt disease aft er reviewing all slides of the patients. th ere was no recurrence of disease in the pt group during a median follow-up of months. among the patients in the non-pt group, biochemical recurrence (bcr) developed in patients ( . %), with the median time to bcr being months. conclusions: among the patients with high-risk prostate cancer, we found cases that showed a pathologic complete response aft er nht and no recurrence of disease during the follow-up, which means that the androgen-deprivation therapy could potentially eradicate high-risk prostate cancer. th is is one of the largest studies demonstrating the prevalence of pt disease and its outcomes aft er nht among patients with high-risk prostate cancer. introduction and objective: in metastatic castration-resistant prostate cancer (mcrpc), data are limited regarding optimal combinatorial or sequential use of available treatments. p - (stride; nct ) is an ongoing, randomized, open-label, phase study evaluating concurrent vs. sequential administration of the androgen receptor inhibitor enzalutamide (enz) with the autologous cellular immunotherapy sipuleucel (sip-t). fift y-two patients (pts) with asymptomatic or minimally symptomatic mcrpc were randomized : to receive sip-t infusions with enz starting weeks before (n= , concurrent arm a) or weeks aft er (n= , sequential arm b) sip-t initiation. th e primary endpoint is peripheral t cell proliferation response to pa , the sip-t immunizing antigen. secondary endpoints include interferon (ifn)-γ elispot and humoral immune responses to pa and prostatic acid phosphatase (pap), product release parameters (total nucleated cell count, cd + cell counts, and antigen presenting cell activation [as measured by cd upregulation]), cytokine production, and adverse events (aes). results through week are described. results: pa -specifi c t cell proliferative response was signifi cantly elevated at all post-baseline time points (p< . ) and was sustained through week , including a > -fold increase at week in both arms. th is pa -specifi c response was observed in nearly all pts, . % in arm a vs. . % in arm b. both arms showed a signifi cant and sustained increase in humoral responses to pa and pap as well as ifn-γ elispot response to pa . sip-t product parameters were similar between arms. cytokines indicative of immune activation (such as ifn-γ, interleukin- , and tumor necrosis factor-α) were also elevated in both arms. aes were observed in % (arm a) and % (arm b) of pts. th e incidence of grade ≥ aes was similar between arms. materials and methods: tur specimens without hormonal use ( cases), specimens aft er three weeks of chlormadinone acetate (cma) ( cases), specimens aft er average six months of dutasteride ( cases), and specimens two weeks aft er initial use of degarelix ( cases) were studied using he and immunohistochemical staining with prostate specifi c antigen (psa), prostatic stem cell markers such as cd , cd , and vimentin. results: specimens treated with cma showed acinar dilatation and atrophy of glandular cells. specimens treated with dutasteride showed marked decrease of gland and increase of fi bromuscular tissue. specimens treated with degarelix showed prominent decrease of gland and glandular cells. psa was stained all of the prostatic glandular cells in all specimens. cd was stained at basal cells in normal prostatic tissue without hormones, however in hormone treated specimens, basal cells elongate and some glandular cells were also stained by cd , especially in cma treated specimens. cd was stained in many glandular cells without special patterns. vimentin was stained in all mesenchymal interstitial cells and a part of basal cells, and not stained in glandular cells. conclusion: elongation of basal cells and increased sensitivity to cd in glandular cells, especially treated with cma, were thought to the result of emt of prostatic glandular cells. th ree weeks use of cma might be a good model to observe emt of prostatic cells among these three hormone models, presumably because six months use of dutasteride is long enough to alter the structure of prostatic tissue, and degarelix has strong apoptotic activity to prostate cells in a short period. aryl plays an important role in normal physiologic responses such as development, cell cycle regulation, and immune function in various tissues. th e strong nuclear ahr expression was observed in the invasive phenotype and an elevated nuclear ahr expression was associated with a poor prognosis of human prostate. on the other hand, the ahr defi ciency results in a smaller volume and in increased susceptibility to prostate tumors in mouse model. in the present study, we investigated ahr expression and its role in the growth and invasiveness of human prostate cancer cells. we checked ahr proteins expression in prostate cancer cell lines and in human prostate cancer specimens by immunoblotting and immunohistochemistry respectively. we used a small interfering rna targeting ahr, constitutive active ahr expression vector, and ahr agonist and antagonist were used to moderate its expression and signaling to examine growth and invasion in prostate cancer cells. introduction and objective: androgen deprivation therapy (adt) has been increasingly used in patient with prostate cancer (pca). it has been considered that adt is associated with greater risk of incident cardiovascular disease (cvd). th e one of the reason is that hyperlipidemia was caused by adt may contribute to greater cvd risk. but the evidence remains inconclusive and sometimes contradictory. in our present study, we investigated an eff ect of adt on arterial atherosclerotic changes assessed by cardio-ankle vascular index (cavi) in pca patients. th e present study was participated in patients with prostate cancer before initiate adt. we recorded and statistically analyzed the data of the patients before adt and at months, months, and months aft er adt. and the patients' arterial atherosclerotic changes was evaluated by cavi at baseline. correlation between the degree of infl ammation and gleason score in prostate cancer patients alexandrescu e, geavlete p, georgescu d, geavlete b introduction and objective: hypothesis regarding the involvement of infl ammatory processes in prostate cancer has been the subject of several recent studies. chronic infl ammation generates the appearance of morphological changes of atrophic type, lesions located predominantly in the periphery of the gland, as well as prostate cancer (pca). th e aim of the study was to assess the possible infl uence of associated infl ammation on the gleason score in pca patients. results: th e gleason score - was detected in patients ( . %), score - in patients ( . %) and score - in patients ( . %). cases of aggressive disease (gleason score - ) were detected by prostate biopsy, while high-grade infl ammation has been mostly associated with pca cases incidentally detected by turp. no signifi cant correlations were found between the presence and degree of histologically proved infl ammation and the gleason score or the presence of pca. identifi cation of n -methyladenosine methylated mrnas in prostate cancer pang k , , cumberbatch m , , catto j , introduction and objective: rna methylation is a common epigenetic event in oncogenesis, and the most common form is the methylation of n -adenosine (m a). th e recent identifi cation of > , m a-methylated human mrnas from > human genes point towards novel epigenetic mechanisms. however, the distribution of m a in the prostate transcriptome is unknown. we aimed to predict the mrnas susceptible to m a-methyation in primary prostate cancer (pca) and castrate-resistant pca (crpc), and identify the functions of these mrnas. th e aim of this study was to assess the contribution of multiparametric mri and pca in pre-decision of initial biopsy in patients with serum psa level - ng/ml and normal digital rectal examination. th e study is planned as prospective and single-centered. patients whose serum psa level - ng/ml with normal digital rectal examination scheduled for initial prostate biopsy were included in the study between february and march . each patient underwent multiparametric mri (diff usion, spectroscopy, dynamic-contrast, t ) one week prior to biopsy. th e lesion seen at least in two mri was accepted as multiparametric mri lesion. twenty to thirty ml initial urine samples were taken aft er minutes prostate massage for pca examination before biopsy. pca score over was considered as signifi cant. guided biopsies were taken according to lesions seen in multiparametric mri. patients with high psa levels were separated into two groups as high pca scores and normal pca scores. each group, then, was separated into two groups due to mri results as lesion positive and negative. tumor incidence and positive predictive values were calculated in patients with high psa and pca scores with positive multiparametric mri lesion. tumor incidence and negative predictive value were also calculated in patients with high psa level but low pca score with negative multiparametric mri lesion. up. , figure . a biopsy-induced hemorrhage was defi ned as a case in which a subject complained of bleeding from the rectum and excretion of blood clots was confi rmed. we categorized signifi cant rectal bleeding into two grades for hemostasis management, including mild and severe. when the bleeding was classifi ed as mild, we inserted the gelatin sponge into the participants in either group b or reinserted it into those participants in group a. if the bleeding could not be stopped by this approach, we additionally used index fi nger pressure for ten minutes or more to promote hemostasis. in the severe cases, an endoscopic clipping was performed to control the bleeding because arterial bleeding was suspected. a blood test and a questionnaire survey, and pain related to biopsy was performed before and aft er biopsy. th e diff erence in background factors between groups a and b was assessed. to identify the independent predictive factors for rectal bleeding for all participants, background factors, including insertion of a gelatin sponge into the rectum were analyzed by logistic regression analysis. results: signifi cantly fewer patients in group a required hemostasis aft er biopsy compared to group b ( ( . %) vs. ( . %), p= . ). th e results of blood tests performed before and aft er biopsy and the results from the questionnaire did not diff er signifi cantly between the two groups. in multivariate analysis, only "insertion of a gelatin sponge into the rectum" emerged as a signifi cant predictor of hemostasis. our results suggest that the tissue elastic modulus of prostate cancer may increase with an increase in the gleason score and that the diff erence in the stiff ness between low-grade lesions and prostate hyperplasia may be slight. th ese basic fi ndings will contribute to the development of quantitative elastography technique. the results: th e median ipss was , the mean psa was . ng/ml; the mean size of prostate was . cc. of the total subjects, prostate cancer was detected in ( . %) patients. among subscores refl ecting specific luts, the nocturia was only symptom score predict the cancer detection. th e detection rate of patient with nocturia more than time a day was . %, but the cancer detection rate of patient without nocturia was only . %. at multivariate analysis adjusting infl uence of covariate of age, psa, prostate size and transitional zone size, frequency and nocturia scores were the two only factor predicting cancer detection. at the roc curve analysis measuring the benefi t of the additional consideration of the severity of nocturia and frequency, the additional consideration induced . % prediction accuracy elevation (from . to . ). conclusions: men with frequency or nocturia have lesser chance of prostate cancer detection rate than the men without luts. however, the infl uence of these storage symptoms seems not strong enough to change current consensus of indication to biopsy the prostate. routine in the discontinuing group were %, %, - . %, - . % and - . %, respectively (p= . ). th e median Δegfr at baseline, , , and months in the continuing group were %, %, - . %, - . % and - . %, respectively (p= . ). th e continuing group decreased months later. however, the renal function in the discontinuing group had a tendency to improve at months aft er treatment insignifi cantly. th ere was not statistical signifi cant diff erence in various factors between discontinuing group and continuing group. conclusions: it was possible that the recovery of testosterone was associated with the improvement of the renal function. it has been reported that the discontinuation of adt recovered the level of testosterone. namely, the discontinuation of adt for prostate cancer might revive the renal function. th erefore, it was suggested that intermittent adt might recover the renal function. introduction and objective: as more and more patients are getting diagnosed as carcinoma of prostate (cap), we would like to look into how prostate cancers are presented at the early age of forties and how they were treated. as cap is more popularised in the media, more and more people are asking gps for psa measurements. introduction and objective: irreversible electroporation (ire) is a novel ablative therapy for prostate cancer, with reported advantages of sparing surrounding essential structures. th ese properties could potentially help to reduce or avoid side eff ects. th e objective is to determine quality of life outcomes (qol) and side-eff ects of ire treatment. sixteen patients planned for radical prostatectomy (rp), were asked to participate in the study. all patients underwent an ire treatment one month before rp, using a focal or extended ablation protocol. th e safety was measured by the number of adverse events graded by the common terminology criteria for adverse events (ctcae). to determine qol validated questionnaires (expanded prostate cancer index composite (epic), the fi ve-item version of the international index of erectile function (iief- ) and international prostate symptom score (ipss)) were used. results: five developed a urinary retention (ctcae grade ) solved by an indwelling catheter or self-catheterisation. two patients developed a urinary tract infection (ctcae grade ), one progressed to urosepsis (ctcae grade ), both resolved without sequelae. mild haematuria (ctcae grade ) was noted in ten patients, spontaneously resolved within days. five patients experienced temporary incontinence with duration of - days, three suff ered from total incontinence and needed pads and pelvic fl oor training (ctcae grade ). two patients reported mild hematospermia, lasting one and thirty days. ipss showed no signifi cant diff erence between baseline (average of (avg) ± ) and four weeks postoperatively (avg ± ). iief showed no signifi cant diff erence between baseline (avg ± ) and four weeks postoperatively (avg ± ). epic outcomes, shown in figure , were not signifi cantly diff erent at baseline, one and four weeks aft er ire, regardless of the used ablation protocol. conclusion: ire treatment for prostate cancer is safe and shows only adverse events that lie within the range of what was expected and shows promising rates of genito-urinary functional preservation. introduction and objective: mri-guided transurethral ultrasound ablation (tulsa) is a novel minimally-invasive technology for treatment of prostate cancer aiming to provide local disease control with low morbidity. th e ultrasound device generates conformal volume of thermal ablation, shaped precisely to the prostate using real-time mri thermometry feedback control. aim of this prospective, multi-national phase i study is to determine safety and feasibility of mri-guided tulsa. biochemical recurrence (bcr) was defi ned using phoenix criteria (psa nadir + ng/dl) and positive biopsy in the treated area was considered recurrence. we compared the perioperative and oncologic outcomes following fc in patients with gs vs. gs ( + ) at initial trus biopsy. th e complications were reported using the clavien-dindo classifi cation. we found patients with gs and with gs ( + ). clinical and operative characteristics were similar (table ) . th e mean follow-up was . (± . ) months. th ere was no signifi cant diff erence noted between gs vs. gs in the biopsy recurrence ( % vs. %, p= . ) and bcr rates. th ere were complications in ( . %) patients. all were low grade, except two patients who had iii b complications (table ) . conclusion: th e perioperative and oncologic outcomes of fc -hemiablation for unilateral, organ confi ned pca appears to similar between gs and gs ( + ) disease. pentafecta in the evaluation of surgical results after open radical prostatectomy de la rosa h, rios s, martinez n introduction and objective: "pentafecta" has been used to evaluate the oncological and functional results in patients with prostate cancer treated with minimal invasive radical surgical techniques. in this study we evaluate, with this quality tool, the outcomes in a group of patients undergoing open radical prostatectomy. we analyzed retrospectively the database of surgeries performed at the urology department of the military hospital of guadalajara and the clinical fi les of patients with localized prostate cancer treated with radical prostatectomy. we describe the patients' characteristics including the charlson comorbidity index (cci) and identify the parameters that conform pentafecta as well as the variables that can infl uence the oncological and functional results using the fisher´s exact test. results: fift y four patients were treated with radical prostatectomy between and , fi nding in their fi les a minimum of months of follow-up. seven patients were discarded of the study because they undergo laparoscopic radical prostatectomy, and more because missing information at their fi les. th e average age was ( - ) and the cci average was . ( . - . ). mean operative time was min ( - ) and intraoperative bleeding cc ( - ). th e presence of potency, continence, biochemical recurrence-free survival, negative surgical margins and no perioperative complications were %, %, %, % and % respectively. seven ( %) patients achieved pentafecta, and patients ( %) failed to achieve. statistical analysis confi rmed the surgeon's experience as the only factor associated with achieving pentafecta. conclusions: th e fi rst cause of failure to achieve pentafecta in our study group was impotence, second were positive surgical margins and third surgical complications mainly intraoperative bleeding. pentafecta is a useful tool for objective assessment of oncological and functional outcomes of patients treated with open radical prostatectomy. plasma introduction and objective: hepatocyte growth factor (hgf) is a well-known multifunctional growth factor, the amount of evidence has accumulated suggesting that the hgf/met (hgf receptor) signaling axis is involved in cancer progression. macrophage stimulating protein (msp) is also known as a growth factor which activates not only macrophages but also cancer cells and osteoclasts through the activation of the specifi c receptor d' origine nantais (ron). hgf and msp are secreted as an inactive single-chain precursor (pro-hgf, pro-msp), which lacks biological activity and, therefore, requires proteolytic activation for conversion to an active two-chain form by hgf activator (hgfa). although, there have been reported a lot of study for hgf/met signaling with castration-resistant (cr) pc and bone metastasis, the report for examination of plasma protein is rare. in addition, msp/ron signaling axis is not well evaluated in pc. here, we analyzed the associations between pc progression and plasma levels of hgf and a closely related molecule, msp. conclusion: dehydroepiandrosterone (dhea) concentrations in blood were examined by newly developed ultra-sensitive quantifying method, lc-ms/ms. we confi rmed that low serum dhea levels in men with prostate were related to high gleason score and advanced clinical stage. th ese results suggest that serum dhea level may be useful as a prognostic factor in men with prostate cancer. introduction and objective: androgen/androgen receptor (ar) signal is known as a powerful driver of prostate cancer (pca) progression. previously we reported the limitation of prostate-specifi c antigen (psa), which is an ar-regulated protein, at diagnosis as a prognostic biomarker of pca. paradoxically pca patients with low psa < . ng/ml had a more advanced stage of cancer compared with those with psa between . and ng/ml. although serum total testosterone (tt) has also been reported as a pca prognostic biomarker, its usability is still controversial. we examine the potential and the character of tt as a biomarker, comparing to psa. serum tt level of patients who underwent prostate biopsy at kanazawa university hospital between and were measured and pca-specifi c survival (pcass), overall survival (os), and the correlation between tnm stage and tt level were analyzed. results: of total biopsied patients, were diagnosed with pca. median tt was . ng/ml (range: . - . ). when patients were divided into groups according to their tt at diagnosis, patients with tt < and ≥ ng/ml had worse pcass than those with ≤ tt < , ≤ tt < , and ≤ tt < ng/ml. os in patients with tt < and ≥ ng/ml also was worse than that in other groups. moreover, tt < and ≥ ng/ml showed worse pcass even in patients with advanced stage (t or n or m ). higher tnm stage was observed in patients with tt < and ≥ ng/ml than those with ≤ tt < ng/ml. low tt level has been reported as a predictive biomarker indicating worse outcomes in pca patients. th is study showed not only low but also high tt level may indicate poor prognosis. th ese data are consistent with our previous studies showing low psa (< . ng/ml) also might indicate poor prognosis as well as high psa. although poor prognosis of high tt and high psa strongly depends on androgen/ar signal, poor prognosis of low tt and low psa patients may be due to other signals than androgen/ar. usefulness of psa as a marker of prostate cancer in men treated with dutasteride takeda h, nakano y, narita h introduction and objective: to analyse whether the use of treatment-specifi c criteria for repeat biopsy maintains the usefulness of prostate-specifi c antigen (psa) level for detecting prostate cancers. th is study was a retrospective investigation to assess the eff ects of dutasteride on psa in asymptomatic men aft er negative st biopsy and on repeat prostate biopsy decision. th e usefulness of psa was evaluated using biopsy thresholds defi ned by three times consecutive rises and . ng/ml up in psa from nadir (the lowest psa level achieved while in the study) in the dutasteride group. prostate cancer pathological characteristics were compared. results: of men, (dutasteride) underwent at least one prostate biopsy during the study and were included in the analysis. mean follow-up (month) was . , ipsa was . ng/ml, mean prostate volume(cc) was . , psad was . ng/ml/cc. nine of ( %) were detected prostate cancer, % ( / ) of gleason and % ( / ) of gleason - cancers were detected in the dutasteride group. in the study, the incidence of gleason and gleason - cancers generally increased with greater rises in psa. sensitivity of psa kinetics with dutasteride was high as usual. conclusion: using treatment-specifi c biopsy thresholds, the present study shows that the ability of psa kinetics to detect prostate cancer is maintained with dutasteride in men with a previous negative biopsy. biopsy decisions based on three times consecutive increased and . ng/ml psa measurement from nadir in the dutasteride group are useful, indicating the importance of confi rmation of psa measurements. our goal was to develop a fi t-for-purpose assay that could be performed on rna from diagnostic needle biopsies, and provide improved risk stratifi cation in early-stage pca. to date, development and validation studies have included > , patients from four academic centers. in these studies, archival tissues were assayed following prospectively designed protocols with pre-specifi ed methods and statistical analysis plans. results: feasibility and development studies confi rmed gene expression and identifi ed genes whose expression was predictive of clinical recurrence, biochemical recurrence (bcr), prostate cancer death, and adverse pathology (ap) at surgery in the face of tumor heterogeneity and multifocality. analytic validation studies showed that the assay provided robust, reproducible results over a wide range of rna inputs, diff erent operators, instruments, and reagent lots. th e fi rst clinical validation study established gps as an independent predictor of ap in men with nccn verylow to intermediate-risk pca. exploratory analyses showed that gps is a robust predictor of ap despite inter-observer diff erences in pathologic grade and stage assessment. a second clinical validation study in a racially diverse population confi rmed the assay as a predictor of ap and validated the assay as a strong predictor of bcr (hr/ gps units= . ; p< . ). gps was also signifi cantly associated with metastatic disease (hr/ units= . ; p= . ). other exploratory analyses showed that the assay can predict ) likelihood of clinical recurrence aft er bcr, regardless of salvage therapy, and ) tumor aggressiveness when assessed in adjacent normal-appearing tissue. all four gene groups contribute to the predictive value of the assay. conclusions: th e development program for the assay addressed challenges of small sample size, tumor heterogeneity, multifocality, and biopsy under-sampling. validation in two large contemporary cohorts of men with pca in two prospectively designed studies provides level ib clinical evidence for gps as a predictor of ap. clinical and therapeutic implications of neuroendocrine prostate cancer: a long winding road to cure lu k, wang h, lin v, yu t introduction and objective: primary neuroendocrine cancer of prostate is an extremely rare variant of prostate cancer, comprising . % to % of prostate malignancies. th is entity encompasses various clinical contexts, ranging from the de novo small cell carcinoma (scc) to a treatment-emergent transformed phenotype that arising from typical adenocarcinoma (ad) of the prostate. th e rarity of these neoplasms poses a diagnostic and therapeutic challenge. little is known about neuroendocrine prostate cancer and the current knowledge of this disease is based on case reports or small series. our purpose was to characterize the cases treated at a tertiary academic center and to evaluate patient outcomes with the available treatment modalities. th is was a single-institute retrospective observational cohort study of patients with neuroendocrine prostate cancer followed at e-da hospital, kaohsiung city, taiwan between january , and october , . patient and tumor data were analyzed using descriptive statistical methods. results: among prostate cancers, six patients were identifi ed with primary neuroendocrine prostate cancer, comprising from de novo mixed variety (scc and ad) and from transformed phenotype (pure scc). th e median age at diagnosis was . years. th e most common presenting symptoms were obstructive symptoms (weak stream, incomplete empty and urine retention). th e morphological appearance of the tumor cells and their immunohistochemical reactivity for neuroendocrine markers, and prostate specifi c antigen (psa) helped establish the diagnosis. overall median survival was months from diagnosis of neuroendocrine prostate cancer/ prostate small cell carcinoma. conclusion: primary neuroendocrine prostate cancer is characterized by an aggressive clinical course with relatively short lifespan. although high response rate to cytotoxic chemotherapy, overall prognosis is poor. as there is no standard of care for patients with neuroendocrine prostate cancer, further eff orts should be directed at its early detection and made to develop more eff ective therapeutic strategy. association th e mean duration for the side eff ect to occur was months (range - months), the mean duration between the onset of side eff ect and beginning of hbo therapy was months (range - months). th e patient with both hemorrhagic proctitis and cystitis completely recovered, and the remaining patients had improvement of side-eff ects. conclusion: hbo therapy can be a choice of treatment for radiation induced side-eff ects. a treatment trend of the prostate cancer in japanese provincial hospital introduction and objective: th e prostate cancer patients can choose various treatment options for cancer. however, the choice is limited by a diff erence in the scale and/or the location of each medical institution. we examined a treatment trend of the prostate cancer in our japanese provincial hospital. we evaluated patients who had a diagnosis of prostate cancer between and . th ey were classifi ed four groups, cases of the middle-aged generation (range - years old), cases of the early advanced-aged generation (range - ), cases of the middle advanced-aged generation (range - ) and cases of the latter advanced-aged generation (range -). we sorted each groups using the d' amico risk classifi cation system. in the middle-aged generation, patients, except for metastatic cases, underwent radical prostatectomy or radiotherapy. in the early advanced-aged generation, of low-very high risk group patients ( %) chose radical prostatectomy or radiotherapy. on the other hand, in the same generation, of intermediate risk group cases ( %) were treated with hormonal therapy. in the middle advanced-aged generation, only of low-very high risk group patients ( %) underwent radical prostatectomy or radiotherapy, which was fewer compared with the early advanced-aged generation. th at means, they oft en chose hormonal therapy. in the latter advanced-aged generation, all patients, except for cases, were treated with hormonal therapy. th e cases belong to the low-intermediate risk group, chose watchful waiting (psa monitoring). introduction and objective: robot-assisted radical prostatectomy (rarp) has emerged as an excellent treatment option for men with localised prostate cancer. as with other surgical treatment options, urinary incontinence remains a signifi cant side eff ect of the procedure and has been associated with weak pelvic fl oor muscle (pfm) strength. we aimed to assess pfm strength preand post-rarp, its relevance to incontinence and relevant predictors of poor outcomes post-op. we conducted a retrospective analysis of a prospectively collected database of men undergoing rarp by urologists over a -month period. each man had a pelvic fl oor strength assessment pre-operatively and at week and weeks post-operatively. pfm strength was recorded as strong (grade ), moderate (grade ) or weak (grade ). continence rates were recorded at weeks post-op, with continence defi ned as no requirement for pads or continence aids. basic demographic data and histological data were also collected. introduction and objective: urethral trauma is reported to occur in . % of patients undergoing catheterisation but, in practice, seems to be more common than this. we have investigated its incidence retrospectively and prospectively and have evaluated a new approach to catheterisation to reduce the incidence of catheter-related trauma and its consequences, which has led to the development of a novel urethral catheterisation device (ucd) produced by urethrotech™. a total of patients being catheterised for cardiac surgery were reviewed retrospectively and studied prospectively to determine the incidence of urethral trauma due to urethral catheterisation. one hundred similar patients were then studied prospectively to trial a ucd to see if it reduced the incidence of trauma. ( ) lavh ( ) myomectomy ( ) lap. ovarian cyst excision ( ) ( ) nephrectomy ( ) ileal ureter substitution ( ) ureterolithotomy ( ) angioembolization ( ) urs c d-j stent ( ) ureteroneocystostomy ( ) ureteroureterostomy ( ) . hospitalization ( notes. none had documented consent and none had been counselled about potential complications. one hundred and forty-six were successfully catheterised. four ( . %) required a suprapubic catheter for traumatic and unsuccessful urethral catheterisation. no other adverse events were recorded. seventy-four consecutive patients were studied prospectively aft er counselling and consenting. th e incidence of urethral trauma was out of ( . %). five had urethral or perineal pain and urethral bleeding ( . %) and ( . %) additionally required a suprapubic catheter. having developed a practice of passing a urethral catheter over a guide wire in patients undergoing reconstructive urethral surgery in our unit we subsequently trialled the urethrotech™ ucd for routine urethral catheterisation. th is ucd was used for catheterisation in consecutive patients without complications. we conclude that urethral catheterisation has a signifi cant risk of trauma -ten times the reported incidence -and to reduce that risk the catheter should be passed over a guide wire, as with the ure-throtech™ ucd, as is the practice for passing catheters and similar tubes into other anatomical structures. th is should particularly apply in high risk patients, such as those being catheterised for cardiac surgery who are about to be heparinised, and in higher risk circumstances such as when catheterisation is being performed by junior medical or nursing staff . results: mean age at the time of transplantation was . ± . years with male to female ratio of . : . etiology of esrd included renal parenchymal diseases ( %), o vesicoureteric refl ux ( %) and o vesicoureteric refl ux due to posterior urethral valve ( %), urolithiasis ( %) and neurogenic bladder ( %). pre-transplant bilateral nephroureterectomies were performed in patients, augmentation ileocystoplasty with mitrofanoff conduit in patients while posterior urethral valve fulguration in patients. mean serum creatinine post-transplantation was . mg/dl and . mg/dl at week and months respectively. surgical complications occurred only in two patients; one developed lymphocele while other presented with febrile uti due to ureteric refl ux in the early postoperative period and was managed by doing a new ureteral reimplantation. th e mean graft and patient survival rates at one year were % and % respectively. one patient lost her graft at months which was turned out case of hyperoxaluria. acute rejection was seen in ( %) patients. all of these were successfully reversed with pulse therapy. none of the patients developed cytomegalovirus (cmv) infections or lympho-proliferative disease. symptomatic urinary tract infections aft er transplantation occurred in ( %) patients including pyelonephritis in ( . %) patients. two of these patients with pyelonephritis had prior bladder augmentation. ureteric stenosis is a well recognised major urological complication of renal transplantation. following initial antegrade decompression, defi nitive treatment options include long-term ureteric stenting, endoscopic stricture dilatation/division or ureteric re-implantation. th ere is minimal current data in the literature to help guide patient choice. we aimed to characterise the outcomes following management of ureteric stenosis at a large european regional transplant centre. a retrospective cohort study was performed for all patients following renal transplantation who required treatment for ureteric stenosis between august and august . case identifi cation was via a prospectively maintained database on all renal transplant patients and international classifi cation of disease procedure codes. results: of renal transplants performed during the study time period, patients developed ureteric stenosis requiring intervention ( . %). eleven patients underwent initial open ureteric re-implantation, had endoscopic management and had longterm ureteric stents. mean length of time between elective stent changes was . months (range - months). one patient opted for open re-implantation aft er a period of stenting with a good outcome. one experienced graft failure due to non-compliance with immunosuppression, otherwise renal function was preserved. of the patients having open re-implantation only one experienced re-stenosis -managed with long-term ureteric stenting and . % had satisfactory renal function at follow-up. two patients received successful balloon dilatation and patient had upper tract stenosis managed with pyeloureteroplasty. all patients have experienced no decline in graft function since. endoscopic, open reconstruction and long-term stenting can all provide satisfactory outcomes for the majority of renal transplant patients aff ected by this problem. medium-term graft function was well preserved. in recent years approximately half of patients have proceeded to open re-implantation. surgical and clinical factors impact the choice of treatment. however, patient choice also plays a significant role. th is study has provided up to date information to aid counselling patients. further prospective study is warranted to assess what variables infl uence patient choice and cost effi ciency of open re-implantation versus long-term ureteric stenting. the angiogenic mechanisms of endothelial progenitor cells in kidney transplantation patients introduction and objective: th e blood fl ow blocking during kidney transplantation oft en results in renal ischemic injury. in this process, endothelial cells and endothelial progenitor cells (epcs) are activated to participate in angiogenesis. epcs and endothelial cells participate in angiogenesis and tissue repair through diff erent signaling pathway. prostaglandin e (pge ) is a kind of metabolites of arachidonic acid, and is a mediator of infl ammation and ischemia. pge took part in angiogenesis and epcs diff erentiation according to our previous study. in this study we will demonstrate the angiogenic function of epcs of kidney transplantation patients and reveal the molecular mechanisms of angiogenesis. materials and methods: epcs from peripheral blood aft er kidney transplantation were isolated by density-gradient centrifugation. facs was used to identify the epcs. th e aa metabolites pge in epcs cultured medium was measured by liquid chromatography-tandem mass spectrometry (lc-ms/ms). q-pcr and wb were used to detect the expression of endothelial markers in human umbilical vein endothelial cells (huvecs) cultured with epcs conditional medium. tube formation assay was performed to elucidate the angiogenic ability of huvecs. results: epcs from kidney transplantation expressed c-kit and cd by facs analysis. multiple types of aa metabolites was detected in the conditional medium by lc-ms/ms and pge was increased to more than -fold aft er kidney transplantation. huvecs cultured with conditional medium highly expressed cd and ve-cadherin and also formed more tubes compared with control. huvecs given pge had the same biological characteristics like the conditional culture. conclusion: pge paracrine of epcs from kidney transplantation enhanced the capacity of angiogenesis in huvecs. graft survival, proteinuria and kidney growth: challenges between pediatric and adult deceased kidney donation basiri a , , , zare s introduction and objective: th e presence of widening discrepancy between supply and demand of donor and recipient in the fi eld of renal transplantation, has led us to compare the graft and patient survivals, post transplantation complications, rate and severity of proteinuria secondary to hyperfi ltration injury and the kidney growth of recipients who underwent transplantation from pediatric (group ) and adult deceased donors (group ). each groups contains patients. outcome measures included, patient and graft survivals, quality of graft function as assessed by serum creatinine (scr) and estimated gfr (egfr), surgical complications, proteinuria that was detected by routine urinalysis and then confi rmed by a -h urine protein > mg, and kidney length that measured by early and following ultrasonography. results: th e mean donor age in groups and were . (range . to y/o) and ( to y/o) respectively. th e nine kidneys ( %) from pediatric donors (group ) were off ered en-block. mean follow-up was month (range to ). th ere were no statistical differences in the incidence of dgf between two groups ( % versus %) (p= . ). group had a slightly higher incidence of acute rejection than group ( versus %), but the diff erence was not statistically signifi cant (p= . ). one year's graft survival were similar between two groups ( % and %). serum cre-atinine (scr) and estimated gfr (egfr) th ere were no statistically diff erences between two groups ( . versus . mg/dl and versus cc/min respectively) (p= . ). th e incidences of surgical complications that required surgical intervention (urinary leakage, ureteral stenosis, lymphocele, vascular thrombosis) were similar in both groups ( versus %) (p= . ). development of proteinuria was not diff erent between two groups ( % versus %) (p= . ). early kidney length within one week was signifi cantly lower in group than in group ( ± mm versus ± mm) (p< . ), but the rate of increase of kidney length in group was signifi cantly greater than group ( ± mm versus ± mm) (p< . ) under follow-up period. conclusion: although in this study, median-term outcomes and complications of single and en-block kidney transplantation from pediatric donors are acceptable and same as those from older donors. but assessment of functional and hemodynamic adaptation of small pediatric kidneys in adult recipients and subsequent hyperfi ltration eff ects requires the study with more cases and greater follow-up periods. george a, singh c, devasia a introduction and objective: th e need for vascular access for hemodialysis (hd) increases with the increasing number of patients with end stage renal disease (esrd) requiring hd, with increasing life span, and with more available facilities especially in developing countries. when the usual accesses (radiocephalic and brachiocephalic) have been utilised or failed, a ptfe graft is usually considered. we present here a 'bridging' option of a basilic vein transposition, as a doable, cost eff ective procedure before av graft ing. patients with end stage renal disease were included. th ey all either had poor cephalic veins at the wrist and cubital fossa, or had previously used and failed fi stulae. anasthesia: regional block (local anaesthetic). technique: th e basilic vein was exposed using three small incisions: cm above cubital fossa, mid arm (medial aspect), and upper arm (medial aspect up to axilla). th e vein was completely freed off surrounding structures, tributaries tied, distal end ligated, patency ensured and vein delivered out of the uppermost incision. using a tunneller, the vein was rerouted subcutaneously, anteriorly to reach the cubital fossa incision. th e brachial artery was identifi ed and looped. arteriovenous anastomosis was done using 'o' prolene, continuous sutures. (images in the poster). results: out of a total of venous access surgeries done during the study period, seven basilic vein transpositions were done. all had pre-operative doppler evaluation to assess size and patency of veins. all fi stulae created were functional at the time of discharge. th e fi stula is used for hemodialysis at - weeks, when the fi stula matures (arterialization of the vein implying good/suffi cient fl ow for dialysis). one patient needed exploration for a venous thrombus, hours later, which was removed with a venotomy and th congress of the sociÉtÉ internationale d'urologie -siu abstract book using a fogarty catheter. subsequently with anticoagulation for hours, the fi stula continued to function and is being used for access. th e second patient had exploration on the th post-operative day for evacuating a subcutaneous hematoma. th e fi stula is patent and will be used once it has matured. five of the seven done were uneventful and are being used for hemodialysis access. conclusion: basilic vein transposition, is the preferred option of vascular access over a ptfe graft , as it is cost eff ective, autologous and doable under regional anaesthesia. retrospective results: a total of renal transplants have been performed since . th e transplants were performed via an extraperitoneal approach with a modifi ed lich-gregoir ureteric anastamosis in most cases. jj-stents were not routinely used. th irty two urological complications were noted in transplants ( %). th ere were boys and girls with ages ranging from . to . yrs (mean . ). th e most common complication was vesico-ureteric refl ux (vur) occurring in patients ( %). all those with vur presented with recurrent urinary tract infections and bladder dysfunction was present in % (none were augmented). vur was managed successfully with reimplant in six and submucosal injection of defl ux in three; eight patients were managed conservatively. post-operative urine leaks occurred in patients ( %) and were managed with reimplant in two, uretero-ureterostomy in one, jj-stent in one and conservatively in two. ureteric stenoses presented in patients ( %) with hydronephrosis and worsening renal function and were managed initially with either percutaneous nephrostomy or jj-stent placement. surgical management was performed in four patients (three reimplants and one uretero-ureterostomy); two patients were managed conservatively with transient jj-stent placement. th ree patients ( %) developed unexplained hydronephrosis -one with worsening renal function due to chronic rejection and two with stable renal function. loss of graft occurred in patients ( %) as a direct result of their urological complication. th ere were deaths -two due to chronic rejection and one due to overwhelming sepsis immediately post uretero-ureterostomy for ureteric stenosis. conclusion: urological complications following paediatric renal transplantation are common and can cause signifi cant morbidity and even mortality. vur was the most frequently observed and, if presenting with recurrent utis, can be managed successfully with surgery. other urological complications observed included urine leaks, ureteric stenoses and unexplained hydronephrosis. kidney transplantation in abnormal bladder: analysis of outcome kumar a, gulia a, chauhan u, sharma a, yadav r, dassi v introduction and objective: kidney transplantation in abnormal bladder is a challenging situation and associated with poor outcome. we have analyzed outcome of our data of last years. materials and methods: from to , patients who had abnormal bladder had undergone kidney tx. average age at the time of transplant was years. average age at bladder reconstruction was years. four patients had neurogenic bladder who were practicing cic, using native urethra and one had appendix as a mirofenof procedure. two patients had bilateral nephrectomy for grade vur and their lower ureters were used for augmentation and other two had ileocystoplasty. four patients of grade vur refl ux had subsequent transplant in the bladder. four patients with puv had bladder augmentation and mitrofenof procedure due to poor compliance. one child with puv had augmentation by stomach patch when he was year old. one patient had cystectomy in the past and ileal conduit reconstruction where transplant ureter was implanted. all patients had very trabeculated and thick bladder during ureteric reimplantations. all patients had extravesical ureteroneocystostomy with stents. urethral catheter was kept on average of days. no patients had any ureteric leak or stricture in postoperative period. all four patients with cic through native urethra had recurrent uti in the postoperative period and required long-term chemoprophylaxis. one patient who had ileocystoplasty before transplant, died due to sepsis just before his transplant. incidence of uti was % in this group. six patients also had pyelonephritis, which was controlled by injectable antibiotic. rejection rate was % in this group in fi rst month which was higher than our normal bladder group. average serum creatinine was . mg% at months and . mg% at year which was high than normal bladder population. average follow-up is . years where serum creatine was . mg%. mean hospital admission was . times. conclusion: kidney transplant in abnormal bladder is a good option but long-term results are inferior. recurrent uti and pyelonephritis are still a troublesome problem. various techniques and procedures are required to overcome these diffi cult situations. analysis of results: th e mean operative time, warm ischemia time and blood loos were minutes, . minutes. ml respectively. th ere were major complications including hemorrhage and injury to organs like bowel, spleen and pancreas. fourteen of these patients required exploration to control bleeding or repair. two patients were explored for adhesive obstruction. th ere were minor complications which were managed conservatively. one patient died in immediate postoperative period due to slippage of a single hemolock clip. all patients have adequate vascular and ureteric length. th ere were cases of multiple vessels. th ere were two urinary fi stulae and one ureteric obstruction. mild atn was noticed in patients. no graft was lost. hospital stay was . days. operative time has also come down to from minutes. th e average cost of the laparoscopic donor nephrectomy is us$ . conclusion: lap donor nephrectomy is a safe and minimally invasive procedure. it is a cost eff ective procedures even for the developing country. prostate carcinoma in solid organ transplant recipients tillou x , guleryuz k , bouvier n , belin a , chiche l , bensadoun h , doerfl er a introduction and objective: improvements in immunosuppression and anti-infection drugs in solid organ transplantation have led to a signifi cant survival increase for patients and graft s. prostate cancer (pc), being the most common tumor in men and given the increasing number of old male recipients, should show an increasing incidence in solid organ transplant recipients (sotr). th e aim of this study was to analyze retrospectively our liver (ltr), kidney (ktr) and cardiac transplant recipients (ctr) treated for a pc. between january and december , we found pc in male sotr ( %): pc in ltr, in ktr and in ctr. a ge at diagnosis was . ± . ( . - . ) years old and the interval from transplantation to diagnosis was . ± . ( . - . ) months. mean psa level was . ± . ( . - ) ng/ml. clinical stages were t , t and t in respectively , and patients. diagnosis was suspected during screening, because of prostatitis or bone pain in respectively , and patients. th ree pc were discovered aft er prostate transurethral resection. results: th irty-one patients ( ktr and ltr) with a localized disease underwent radical prostatectomy (rp). histological fi ndings were pt c and pt tumors, with positive surgical margins. gleason score (gs) was in case, in cases, in cases and in case. one patient with positive pelvic lymph nodes was given hormonotherapy. another had a biochemical recurrence at months and was treated with salvage radiotherapy. with a mean follow-up of . ± . ( . - . ) months, two ktr died from kp, and years aft er hormonotherapy and rp respectively. conclusions: prevalence of pc in sotr remains controversial, even though a signifi cant increase can be expected in the coming decades. it is therefore recommended to systematically screen male transplant recipients aft er years of age because outcome is much better if pc is diagnosed and treated early. radical prostatectomy is feasible in ktr as well as in ltr. conservative introduction and objective: conservative surgery results in the transplanted population remain unknown because they are only presented in small series or case reports. our objective was to study renal conservative surgery for kidney graft renal cell carcinomas (rcc) in a multicenter cohort. nephron sparing surgery (nss), radiofrequency ablation (rf) and cryoablation (ca) were studied. iiib) . none of the patients treated by radiofrequency ablation or cryoablation had complications. th e mean time of follow-up was . months ( . - ). fift y-nine ( . %) patients had a functional kidney graft , without dialysis and no long-term complications. specifi c survival was % at the last time of follow-up. conclusion: nss has proven its effi ciency for treatment of small tumors of transplanted kidneys with good long-term functional and oncological outcomes, which prevent patients from returning to dialysis. cryoablation and radiofrequency ablation seem to be alternative therapies that can be chosen with good results, in selected patients. ureteric implantation into introduction and objective: conventional technique recommends ureteric anastomosis to the bladder during kidney transplantation in patients with bladder augmentation. we report our experience of kidney transplantation in augmented bladders with the transplant ureter implanted into the bowel portion of the cystoplasty. a total of patients (mean age, . years (range - years), female, deceased donors) with augmented cystoplasty and subsequent kidney transplantation by a single surgeon between and was reviewed. following standard arterial and venous anastomosis and reperfusion of the transplanted kidney, ureteric implantation involved continuous pds / anastomosis between the spatulated ureter and full thickness bowel portion of the cystoplasty over a size fr dj stent. a second layer of bowel plication was performed around the anastomosis to prevent refl ux using interrupted / vicryl sutures. chart review was performed to evaluate the short-term urological and kidney function outcomes. results: th e cause of renal failure was bilateral vesicoureteric refl ux in patients, posterior urethral valve with refl ux nephropathy in patients, tuberculosis of the urinary tract with infl ammatory ureteric stricture in patient, and lumbosacral agenesis with neurogenic bladder in patient. bladder reconstruction was performed at a median duration of months ( - months) before transplantation. gastrocystoplasty was performed in patients, while the colon and/or ileum were used in the remaining patients. all reconstructed bladders except had a mitrofanoff created for clean intermittent self-catheter drainage aft er transplantation between to x / day. aft er surgery, th e dose fi nding study, toxicokinetics of human bone marrow-derived mesenchymal stem cells, and study deciding timing and number of cell injection were conducted in order. results: from the dose fi nding study, × was selected as dose per an injection of human bone marrow-derived mesenchymal stem cells. from the toxicokinetics of human bone marrow-derived mesenchymal stem cells, days was selected as interval between repeat treatments. in the third study, the ratio of maximal intracavernous pressure to mean arterial pressure was signifi cantly lower in the control group than in the sham group ( . % vs. . %, p< . ). immediate single injection of human bone marrow-derived mesenchymal stem cells ( . %, p= . ) signifi cantly improved erectile function compared to that in the control group, whereas delayed single injection ( . %, p= . ) showed marginally signifi cant improvement. all histomorphometric changes were signifi cantly improved in the up. , figure . immediate or delayed single injection groups than in the control group. repeat treatments did not provide any incremental eff ect on recovery of erectile function and histomorphometric changes. conclusion: intracavernous injection of × human bone marrow-derived mesenchymal stem cells results in recovery of penile erection along with histomorphometric changes in a rat model of cavernous nerve injury, even when treatment was delayed by weeks following cavernous nerve injury. any incremental eff ect aff orded by repeat treatments remains to be undefi ned. relationship between metabolic syndrome, erectile dysfunction and hypogonadism abou farha m, el-abd s, el-gharbawy m, abou farha o introduction and objective: a strong association between erectile dysfunction (ed) and metabolic syndrome (ms) and hypogonadism was determined. aim of the work: to investigate the relationship between (ms), (ed) and the incidence of hypogonadism. th e correlation between hypogonadism and the metabolic risk factors was also determined. a total of patients with ed were included in the study, patients meet the criteria of ms were estimated. ed was classifi ed based on iief- domain score and the relation between severity of symptoms and the number of metabolic risk factors was determined. th e incidence of hypogonadism in ms patients was determined and the correlation between hypogonadism and metabolic risk factors was identifi ed. introduction and objective: peyronie's disease (pd) is a fi brotic disorder aff ecting the tunica albuginea of the corpora cavernosa. erectile dysfunction (ed) due to pd may be secondary to the penile deformity and the resultant changes in the hemodynamic parameters. th e aim of this study is to defi ne color doppler duplex ultrasound (cddu) characteristics in pd, with specifi c attention to describing the presence and etiology of ed in these patients. introduction and objective: th e cause of peyronie's disease (pd) is unknown. th e most accepted causative theory is trauma to tunica albuginea. because prevalence varies ( . - %), the potential for contributory cofactors have been proposed. we hypothesized that metabolic syndrome and other comorbidities may be found at higher rates in pd. retrospective chart review of patients presenting to a men's health clinic with a variety of complaints: erectile dysfunction (ed), premature ejaculation (pe), premarital checkup, small penis, decreased libido, lower urinary tract symptoms (luts) were screened for pd. variables collected: presence/absence of diabetes mellitus (dm), hypertension(htn), dyslipidemia (dl), body mass index (bmi), total testosterone (t), penile peak systolic velocity (psv) and end diastolic volume (edv), smoking, and glycosolated hemoglobin level (a c) in patients with dm. results: a total of patients, with a mean age of years (range - ) were analyzed. pd incidence ranged widely within individual clinics ( - %, average %). hypertension, bmi, t level, total number of comorbidities, low psv, abnormal edv, and mean a c were not associated with the presence of pd. th congress of the sociÉtÉ internationale d'urologie -siu abstract book diabetes was associated with pd (p= . ) and dm patients had a % higher incidence. patients with the highest a c levels (> . ) had an increased incidence of pd [or . (p= . , ci . - . )]. increased age was correlated with pd (p= . ); for each year of life, the likelihood increases by an or of . (~ % per year) (p= . , ci . - . ). dyslipidemia (p= . ) and smoking (p= . ) were associated with - % lower incidences of pd. conclusion: peyronies disease is found in about % of patients seen for other complaints. diabetes, particularly poorly controlled diabetes, is associated with an increased incidence. several other clinical factors appeared noncontributory. a decreased incidence of pd in smokers and patients with dyslipidemia is seen, but does not necessarily refl ect a protective role, but likely increased levels of erectile dysfunction in these groups--patients with inability to achieve erection are unlikely to complain of peyronies' disease. further research into the interaction of pd and dm are warranted. kim j, park j, chae j, oh m, park h, kim j, moon d introduction and objective: limited data are available concerning sexual behavior of korean men. th is study aimed to perform the national sex survey and to collect the basic data for establishment of the prevention strategies of sexually transmitted infections (stis) and hiv/aids. th is is a national survey performed on a sample of , individuals ( , men and , women) aged - years old. th e online surveys were carried out on a national scale in south korea. subjects were randomly selected from resident registration. a structured questionnaire was developed which elicited information concerning: demographic information, information on their sexual behavior, sexual identity, prostitution, experience of stis, and experience of sex education. results: th e majority of the subjects were either married or living with a partner. mean number of sexual intercourse is . ± . times a month. mean sexual satisfaction score using visual analog scale is . ± . . eighty-four percent had a fi xed sex partner; . % ( . % of men; . % of women) had experience through a speed dating or prostitution; . % of men and . % of women were sexually attracted to the same gender only, . % of men and . % of women were sexually attracted to both gender; . % of participants had the experience of the stis. only . % of the respondents had received sex education in the past year. we performed the national sex survey according to the nationwide distribution of population. it would be useful for establishment of the prevention strategies of stis and hiv/aids. to control stis and hiv/aids, powerful policies containing sex education and medical services will be needed. the introduction and objective: erectile function evaluated by international index of erectile function- (iief- ) tends to decrease in aging, obesity and hypogonadism, but the importance of body composition is unclear. in the present study, we evaluated associations between iief- , body composition and testosterone level (tt) in middle-aged men. design was a population-based cross-sectional study in middle-aged men. between march and september , police officers aged - years who had participated in a health examination were included. total , men underwent a detailed clinical evaluation using the validated international index of erectile function- (iief- ) questionnaires and body composition (measured by bioelectrical impedance analysis). weight, body mass index (bmi), waist-hip ratio (whr), and serum testosterone level were also established. results: data from men were analyzed. th e median age was . years, and median value of iief- score was . th e iief- score was inversely associated with age, whr, and body fat percentage (bfp) (r=- . ; p< . , r=- . ; p< . , r=- . ; p= . , respectively), and positively associated with body muscle percentage (bmp) and body skeletal muscle percentage (bsp) (r=- . ; p= . , r=- . ; p= . , respectively). testosterone level had no correlation with iief- score (p= . ). using logistic regression analyses, age, whr, bfp, and bsp predict moderate to severe erectile dysfunction (ed) in univariate analysis. age, whr, and bfp were independent predictive factors for moderate to severe ed in multivariate analysis (p< . , or . , % ci . - . ; p= . , or . , % ci . - . ; p= . , or . , % ci . - . , respectively). our data showed that erectile function in middle-aged men was closely associated with whr and bfp than with testosterone level and body muscle percentage. however, whr was identifi ed as a negative predictive factor for ed. further studies for the unique form of obesity pattern in korean men will be needed. in order to estimate the magnitude and outline the main components of adult male genital organs "dysmorphophobia" in greece, we surveyed the beliefs of men about parameters potentially aff ecting their sexual performance and activity as they relate with self-perceptions regarding adequacy of their external genitalia image. herein, we present preliminary results of this questionnaire based cross-sectional study. a specially designed self-administered questionnaire, consisting of demographic characteristics and main outcome measure questions aiming at defi ning whether and how beliefs regarding men's sexual image adequacy aff ect their sexual confi dence and function (answers scored - ), was fi lled in by males (aged - ) who consulted a single urology clinical setting, for symptoms unrelated to genital area pathology. statistical analysis was performed using spss- , p< . . results: th e majority of subjects ( . %) were highly satisfi ed of their sex organs image, while only one in seven ( . %) reported moderate to low levels of satisfaction. small penile size in the fl accid state was the most frequent ( . %) complaint followed by small erect penis dimensions ( %). in one out of two men ( . %), sex image inadequacy impression was based on self-assessment, in . % on sexual partner comments and in only . % on expert medical examination. nine out of ten men ( . %) considered external genitalia appearance the most signifi cant determinant of a man's sexual confi dence with . % believing they strongly fulfi l this requirement, while most of them ( . %) were highly satisfi ed with their whole body image. in only one in ten men ( . %) the impression of the sexual partner regarding sex image aff ects signifi cantly his sexual performance. most men ( . %) argued against resorting to surgical techniques to improve their sex image, % considered this option imperative for their well-being, while one in four ( . %) would consider surgery if a spectacular cosmetic result was guaranteed. various statistically signifi cant correlations between demographic and main outcome measures variables were recorded. conclusions: symptoms of genital organs dysmorphophobia, are expressed by one in seven men of the general population, in most cases complaints focus mainly at small penile size, while most frequently impression of inadequate sex image originates from self-assessment and negative sexual partner's comments. th e majority of men consider genital image a strong determining factor for sexual performance, while very few experience sexual relationships difficulties due to feelings of genital inadequacy. only a small minority of men would be strongly willing to undergo external genitalia surgery, which they consider imperative treatment for sexual image inadequacy. abou farha m, el-abd s, el-gharbawy m, abou farha o introduction and objective: metabolic syndrome is a public health problem associated with increased incidence of erectile dysfunction (ed). erectile dysfunction in patients with metabolic syndrome is diffi cult introduction and objective: erectile dysfunction (ed) and lower urinary tract symptom/ benign prostatic hyperplasia (luts/bph) has common pathophysiology. and phosphodiesterase type inhibitor (pde -i) partially reverses the prostatic tissue contraction, and increases cyclic guanosine monophos- phate to show antiproliferative eff ects in the prostatic smooth muscle cells and consequently, voiding symptoms were suggested to be improved. however, there was no defi nite mechanism of the eff ectiveness of pde -i on luts/bph. some previous study has reported the hypothesis which is pde -i improve the blood fl ow rate of prostate and it may improve the luts. in present study, by transrectal ultrasonography (trus), evaluated the change of blood fl ow rate of prostate aft er pde -i administration. materials and methods: total patients were included in this study. among enrolled patients, patients had once daily administrated mirodenafi l (mvix®, sk chemical, korea) mg for week, other patients had administrated placebo daily. peak systolic velocity (psv) and end diastolic velocity (edv) were estimated by trus at before medication and a day aft er last administration. results: baseline characteristics were no signifi cant diff erence between two groups. in mirodenafi l group showed . cm/sec increase of psv and placebo group showed . cm/sec increase of psv (p= . ). moreover, mirodenafi l group showed . cm/sec increase of edv and placebo group showed . cm/sec decrease of edv (p= . ). once daily administration of mirodenafi l mg showed improvement of blood fl ow rate of prostate. factors predicting outcomes of penile rehabilitation with udenafi l mg following radical prostatectomy introduction and objective: udenafi l is a selective phosphodiesterase type inhibitor (pde i) made available in recent years for the treatment of erectile dysfunction (ed). penile rehabilitation using pde is following radical prostatectomy (rp) has been advocated; however, there are no previous reports on the role of udenafi l for potency recovery aft er rp. herein, we evaluated independent predictors of potency recovery in rp patients who underwent penile rehabilitation with udenafi l mg. between january and december , a total of patients underwent rp at a single institute. among them, men were enrolled in a penile rehabilitation program using udenafi l mg every other day. uni-and multivariable cox regression analyses were used to determine independent predictive factors for potency recovery. results: th e overall potency rate was . % during the mean follow-up of . months. on the multivariate cox analyses, preoperative international index of erectile function (iief)- scores (hazard ratio [hr], . ; p = . ), alcohol consumption (hr, . ; p = . ), and gleason biopsy score (hr, . ; p = . ) were independent preoperative predictors for potency recovery. among post-rp variables, the use of robotic procedures (hr, . ; p = . ) and pathologic stage (hr, . ; p = . ) were significantly associated with potency recovery. conclusion: th is study identifi ed predictive factors for the recovery of potency in patients undergoing penile rehabilitation with udenafi l following rp. our results provide physicians with useful information for counseling rp patients and selecting optimal candidates for penile rehabilitation. introduction and objective: androgen replacement therapy (art) effi cacy on late-onset hypogonadism (loh) has been widely investigated in western countries; however, it remains controversial whether art can improve health and prolong active lifestyles. we prospectively assessed long-term art eff ects on the physical and mental statuses of aging men with loh in japan. of volunteers eligible patients > years with loh were randomly assigned to either the art (n= ) or the control groups (n= ). art was conducted with intramuscular injection of testosterone enanthate mg each time every four weeks up to times. th e primary endpoint was health-related quality of life assessed by questionnaires. secondary endpoints included glycemic control, lipid parameters, blood pressure, waist circumference, body mass index (bmi), body composition, muscular strength, bone mineral density (bmd), international prostate symptom scores (ipss), international index of erectile function (iief)- scores, and serum prostate-specifi c antigen levels. th e safety and tolerability of long-term art were also examined in these populations. results: fift y-two weeks aft er the initial treatment, art signifi cantly aff ected the role physical subdomain of the short form- health survey (sf- ) scale (p = . ). art was also associated with signifi cant decreases in waist circumstance (p = . ) and serum triglyceride (tg) (p = . ) and with signifi cant increases in whole-body and leg muscle mass volumes (p = . and . , respectively), serum hemoglobin (p < . ), ipss voiding subscore (p = . ), and the second question on iief- (p = . ). th ere was no signifi cant deference between the groups in terms of bmi, bmd, isometric handgrip strength, serum fasting blood sugar and hemoglobin a c, serum psa, and the incidence of sever adverse events. conclusion: long-term art for patients with loh have the benefi cial eff ects on role physical subdomain of the sf- scale, serum tg, waist circumstance, muscle mass volume, voiding subscore of ipss, and the second question of iief- . we hope our study will contribute to the future development of this area. introduction and objective: hyperoxaluria is characterised by a high urinary oxalate level. super-saturation of urine with oxalate will lead to nucleation, aggregation and the formation of calcium oxalate crystals leading to renal calculi. patients with hyperoxaluria are at increased risk of recurrent urolithiasis. objectives: to analysis the interventions and outcomes of new patients with enteric and dietary hyperoxaluria referred to a metabolic stone clinic. an analysis of patients with hyperoxaluria was performed. data examined included; age, sex, metabolic abnormalities, malabsorptive syndromes, previous treatments, stone composition, medical and life style interventions. all patients had or more hr collections of urine performed at median of months apart. twenty-four-month follow-up was performed to assess need of further stone treatment. results: a total of patients were identifi ed for study. twenty-fi ve were male, were female. th e median age is years, iqr ( - ). first median urinary oxalate level is . mm, iqr ( . - . ). patients that reduced their oxalate intake and increased their fl uid intake were signifi cantly less likely to need further long-term stone treatment. th e arr of increased urinary output and decreased urinary oxalate on the need for further stone surgery is th congress of the sociÉtÉ internationale d'urologie -siu abstract book . %, ci (- . - . ) . th e rrr for the need of stone surgery is . %, ci (- . - . ) . th e nnt to prevent one patient needed further stone treatment is . , ci ( . -- . ) . conclusion: hyperoxaluria is important cause of recurrent stone formation that requires management in a dedicated metabolic stone clinic. compliance with fl uid, dietary and medical management is limited. in compliant patients, urine parameters and stone recurrence rates can be altered. clinical using specifi c diagnosis codes from billing data, patients were identifi ed that met criteria for urosepsis secondary to an obstructive ureteral calculi. data was analyzed in the following areas: demographics, admitting hospital of origin, duration of admission before transfer, need for higher level of care, need for invasive procedures, and length of hospital stay. results: using the screening criteria patients were identifi ed. th e average age was ; % were female versus % male. patients transferred from an outside hospital made up % of the patients and overall hospital admission lasted . days. of the patients transferred % went to the icu for an average duration of . days. of the transferred patients % needed vasopressor/ionotropic therapy, and % required intubation. overall, over % needed urologic intervention; % had ureteral stent placement and % underwent nephrostomy tube placement. patients admitted from the ed made up % of the patients and had an average admission of . days. of these patients % went to the icu for an average of . days. only % and % needed vasopressor/ionotropic therapy and intubation respectively. also, % had ureteral stent placement and only % had a nephrostomy tube placed. conclusion: urospesis in the setting of an obstructive ureteral stone is a medical emergency that merits urgent relief of the obstruction. once this condition is identifi ed, any facility without the resources for prompt intervention should transfer these patients immediately to a center with these capabilities. th is is supported by our data, as transferred patients on average had a longer icu and hospital stay, and needed more aggressive interventions. clinical signifi cance of ureteral wall thickness adjacent to the stone in abdomen-pelvis ct in the patients treated with extracorporeal shock wave lithotripsy park m, yeo j, cho d introduction and objective: although, ivp was standard diagnostic tool for years, the use of abdomen-pelvis ct (apct) without contrast, particularly in an acute setting, is becoming increasingly common. th is study was planned to know the clinical signifi cance of ureteral wall thickness adjacent to the stone in apct in the patients treated with extracorporeal shock wave lithotripsy (eswl). : th e data of patients who took ap-ct to diagnose ureter stone and were treated with eswl was reviewed. aft er maximum zoom of the ap-ct image showing the longest diameter of stone, the ureteral wall thickness adjacent to the stone was measured by same physician. th e baseline characteristics of patients, the parameters related to ureter stone and effi cacy of eswl were investigated. th e correlation between ureteral wall thickness and those parameters was statistically analyzed. th en, the patients were divided into two groups by the median value of ureteral wall thickness and the diff erence of those parameters between two groups was also investigated. additionally, cut-off value of ureteral wall thickness contributing to the diff erence in the effi cacy of eswl was determined. in simple correlation analysis, bmi, stone length at kub, stone diameter in ct, number of eswl, and time to stone removal showed signifi cant positive correlation with ureteral wall thickness. th e median value of ureteral wall thickness was . mm and the patients were divided into two groups. in comparison of baseline characteristics between two groups, group ii showed more incidence of pyuria than group i and stone burden at kub and ct also showed statistical diff erence between two groups. in comparison of effi cacy of eswl, group ii showed more number of eswl and longer time to stone removal than group i. th e cut off value of ureteral wall thickness contributing to the diff erence in the effi cacy of eswl was . mm. conclusions: in addition to actual size of stone, ureteral wall thickness of ct also aff ects the treatment effi cacy of eswl. especially, the ureteral wall thickness greater than . mm has an impact on the results of the eswl. the introduction and objective: th e treatment of large volume bladder stones by current equipment continues to be a management problem in both developing and developed countries. ah- stone removal system (srs) invented by us is primarily used to crush and retrieve bladder stones. th is study evaluated the safety and effi ciency of transurethral cystolitholapaxy with srs to treat the large volume bladder stone. materials and methods: srs, which was invented by aihua li in , composed by endoscope, continuous-fl ow component, a jaw for stone handling and retrieving, lithotripsy tube, handle, inner sheath and outer sheath. a total of patients with bladder stones were performed by transurethral cystolitholapaxy with srs since . th ese patients were divided into four groups by the stone size. fift y nine patients with stone size < cm were in group a, patients with stone size from to . cm were in group b, patients with stone size from to . cm were in group c, and patients with stone size ≥ cm were in group d and the largest stone was . cm. results: characteristics of patients and stone removal time in variable size were evaluated. to patients with single stone, stone size was . ± . cm and the operating time was . ± . min in group a. stone introduction and objective: eswl has emerged as a primary modality of treatment for solitary renal calculi in modern era. th e size of calculus is a major factor for consideration before subjecting a patient to eswl procedure. stone size less than two centimetre is considered ideal for eswl. other factors like obesity, position of calculus, renal infundibular anatomy and stone composition etc. also determine clearance rates. given a choice patients in india still prefer one time clearance by pcnl than multiple eswl sittings for similar sized calculus. our study reiterates the benefi ts of eswl in developing world with multivariate data supporting it. th e objective of this study was to evaluate the feasibility and safety of minimally invasive percutaneous nephrolithotomy combined with fl exible ureteroscopy for upper urethral calculus aft er radical cystectomy urinary diversion. a total of patients underwent minimally invasive percutaneous nephrolithotomy combined with fl exible ureteroscopy from january to august . th ere were cases that were diagnosed urinary stones aft er bricker urinary diversion of radical cystectomy, case of studer orthotopic ileal neobladder, and case of cutaneous ureterostomy. th ere were cases with left side calculi and cases with right side ones, including renal calculus, ureteral calculus and ureterointestinal anastomotic calculus. th e upper urethral calculi were identifi ed by urinary tract ultrasound and the multiplanar ct. all of cases underwent minimally invasive percutaneous nephrolithotomy combined with fl exible ureteroscopy. th e ureteral stent was indwelled for weeks routinely. th e kidney ureter and bladder x-ray or a ct scan was examined weeks aft er the procedure to evaluate the clinical outcomes. any residual calculus larger than mm was taken as signifi cant. results: th e combined lithotripsy was carried out successfully in all the cases. th e mean operative time was ( ± . ) min. th e nephrostomic catheter was removed days aft er the surgery. th e average blood loss was less than ml. no residual calculus was found during the weeks' follow-up. th e average follow-up was months. one case had recurrent calculus months aft er the fi rst procedure, which was successfully managed by the fl exible ureteroscopy again. minimally invasive percutaneous nephrolithotomy combined with fl exible ureteroscopy for upper urethral calculus secondary to urinary diversion aft er radical cystectomy is technically feasible introduction and objective: th e main goal of any intervention for urolithiasis is complete stone removal in order to achieve a stone free status. complete stone removal assures resolution of the immediate adverse outcomes of the stone disease, and prevents possible long-term complications such as pain, obstruction and stone growth. percutaneous nephrolithotomy is an eff ective procedure which is being considered as the gold standard in the treatment of large/complex renal calculi. reported stone free rates are up to %, probably refl ecting the level of experience, stone properties and equipment employed in the procedure. it is well established that higher incidence of residual fragments increases the complication rates and needs further interventions. th e main reason for failure of complete radiolucent stone clearance is inability to visualize the residual stones either by nephroscope or by fl uoroscopy. th e use of intraoperative ultrasound for assessment of residual radiolucent stones during percutaneous nephrolithotomy, will help to increase stone free rate. materials and methods: between sept. and sept. intraoperative ultrasound was used in cases of large complex radiolucent renal stones. results: it showed stone free rate % in patients, false negative in patients ( %) and there was diffi cult scanning in patients ( %). conclusions: th e use of intraoperative ultrasound for assessment of residual radiolucent stones during percutaneous nephrolithotomy, it will help to increase stone free rate. intravenous acetaminophen decreases sedation requirements during extracorporeal shockwave lithotripsy conclusion: th ere is benefi t in pre-operative administration of intravenous acetaminophen in reducing the dose requirements of sedative analgesic for satisfactory pain control during the procedure of swl under conscious sedation. introduction and objective: while most of the bleeding associated with pcnl can be managed conservatively, few need angioembolisation. th ere are diff erent technical methods of embolisation with risk of varying degree of parenchymal damage. we present case of ultrasonography guided embolisation. materials and methods: right lower calyx pcnl was performed successfully in year female with mm renal stone in solitary kidney. she came back on th postoperative day with gross hematuria, with cm by cm clot in renal pelvis and mm arterio-venous fi stula at pcnl puncture site. patient was managed with iv higher antibiotics, strict bed rest, blood transfusion and iv tranexamic acid. but her renal function deteriorated (creatinine- . mg/dl). one haemodialysis was done and patient was explored by sub costal approach, with idea of removal of blood clots and suture ligation of av fi stula. renal pelvis was opened and clots were removed. during operation av fi stula was located with doppler usg and deep suture by - vicryl was attempted to close av fi stula, but due to oedematous kidney suture closure was not possible. so under usg guidance gauze lumber puncture needle was inserted into av fi stula, its position was confi rmed by saline jet on real time usg and cc histoacryl tissue adhesive (monomeric n-butyl- -cyanoacrylate) was injected into av fi stula. intraoperative embolisation of av fi stula was confi rmed by colour doppler. results: renal functions became normal in hours and patient was discharged on th postoperative day. aft er days ivp was done which demonstrated normally excreting whole kidney, showing successful superselective embolisation in solitary kidney. conclusions: usg guided procedure avoids the side eff ects of contrast media in case of acute renal failure. it avoids hazards of radiation and complications of angiographic catheterisation. th e main importance of this procedure is preserving maximum renal tissue, especially in case of renal insuffi ciency and in solitary kidney. th is procedure gives a new vision to do percutaneous usg guided embolisation by thin gauze needle without need of angiography, iv contrast, radiation and minimum morbidity. ultrasound th ree pregnant women in the th, th and th week of pregnancy presented with a symptomatic large renal stone in the fi rst and multiple renal stones in the second and third which were unresponsive to conventional medical therapy. th ey required defi nitive stone treatment. th e operations were done in nov , jun and feb . data was gathered prospectively. all steps of gaining access to the pyelocalyceal system including needle insertion, tract dilation, and amplatz sheath placement were performed under ultrasonography guidance. tract was dilated with single shot technique. th e fi rst two procedures were performed in supine position and the third procedure was performed in lateral fl ank position. results: two patients were stone-free postoperatively and one patient had only an asymptomatic mm residual stone. th ey were discharged on the nd postoperative day and had an uneventful postoperative course. no fever, bleeding or renal colic was noticed during postoperative hospitalization. th e fi rst two patients delivered their fetuses at term without any abnormality reported by the examining pediatric specialist aft er their birth. th e third patient was followed until week of pregnancy without any obstetric complication. conclusion: ultrasonography can be used as an imaging modality guiding all steps of obtaining percutaneous access in pregnant women. supine or fl ank ultrasound guided percutaneous nephrolithotomy can be off ered to pregnant women in whom conservative measures fail to the patient's well-being. introduction and objective: acute ureteral obstruction in pregnancy may result in severe pain, hematuria and serious complications like upper urinary track infection with consecutive sepsis. th e ureteral stenting has been usual in recent years. we evaluated the usefulness of ureteral stenting for ureteral obstruction with symptoms in pregnancy. fift y-three pregnant women participated in this study. abdominal ultrasonography, serum creatinine levels, white blood cell (wbc) counts, urinalysis and urine culture were done in all patients. of these pregnant women, women were treated by ureteral stenting because of not improving with conservative management (positioning, analgesia, antibiotics, etc.). th ey were completely followed-up to removal of ureteral stent. results: of these pregnant women, women who were treated by ureteral stenting, experienced signifi cant relief of pain at least for days. in abdominal ultrasound, patients ( %) had resolution of hydronephrosis. twelve of patients ( %) continued to have problems post-therapeutically irritative voiding symptoms with dysuria, urgency, frequency, and hematuria, but patients experienced relief of symptoms for days. a patient was taken remove of stent due to continuous complaint irritative voiding symptoms. aft er delivery, patients were taken ivp. of patients, were normal fi nding with ivp. four patients were diagnosed ureter stone (upper , mid , lower ). th ree patients were treated by extracoporeal shock-wave lithotripsy for the stone in upper and lower urinary tract. a patient was treated ureteroscopic lithotripsy. conclusions: since the ureteral stents were usually placed without any major problems and well tolerated with only minor and short post-therapeutic discomfort. we concluded that the ureteral stenting was a simple, safe and eff ective method of internal upper tract drainage in case of symptomatic ureteral obstruction during pregnancy. safety introduction and objective: to evaluate objective and subjective outcomes of retrograde intrarenal surgery (rirs) for the treatment of radiopaque - mm renal calculi. a retrospective analysis was performed for patients who underwent rirs to treat renal calculi sized with - mm between april and december . operative and postoperative data were collected for each patient such as stone burden, stone location, number of sessions, and auxiliary procedures. th e term of follow-up was one year at least. surgery was usually performed under general anaesthesia. flexible ureteroscopy with ureteral access sheath and holmium-yag laser were employed. patients were evaluated with simple radiography, abdominal ultrasonography, or ct without contrast. surgery success was determined as stone free rate (sfr) at three months aft er last session. re-treatment rates were also calculated. results: mean age was . ± . years old. th e highest-frequency location was pelvis ( %). single stones were described in % of patients although multiple urolithiasis were detected in the %, mainly located in the lower calyceal. average surgery time was . ± . min. th e auxiliary procedure rate and the re-treatment rate were . % and . %, respectively. th e overall sfr and sfr aft er a single session were . % and . %, respectively. although no serious complications were noted in all of patients (above clavien-dindo classifi cation level iii), clavien level i to ii complications were identifi ed in two-patients ( . %). all these patients were successfully treated conservatively. conclusion: our fi nding suggest that rirs represents a valuable treatment option of - mm radiopaque renal calculi for selected patients. rirs would be also a good therapeutic alternative to extracorporeal shock wave lithotripsy (eswl) and percutaneous nephrolithotomy (pnl). rirs should be considered as fi rst line treatment. prospective analysis is required to be corroborated these fi ndings. ureteroscopic lithotripsy for extremely old patients yoshioka t , uehara s , otsuki h , shimizu t , murao w , fujio k , kikuchi h , fujio k , wada k , araki m , ebara s , watanabe t , nasu y introduction and objective: one of the biggest problems in st century is an aging society. in , the number of old people (≥ years old) in japan was , , . th at is about % of all japanese population. japanese society is becoming not an "aging" society, but an "aged" society, and we have to prepare for this society. on the other hand, upper urinary stone is a common disease, and oft en occurs not only young people but also aged people. however, there are no standard treatments for aged patients of upper urinary stones, especially extremely old patients who are more than years old. in this study, we investigate the safety and effi cacy of ureteroscopic lithotripsy of upper urinary calculi for these patients. between january and october , ureteroscopic lithotripsy (urs) underwent in abiko toho hospital. of these cases, cases are for the extremely old patients (≥ years old). we retrospectively reviewed gender, age, body mass index (bmi), american society of anesthesiology (asa) physical score, stone size, reasons for operation (whether symptomatic or not), operative duration, and stone free rate (sfr) of all cases. all data were reviewed by one urologist, and asa physical scores were evaluated by one anesthesiologist. results: all cases were bedridden female. mean age was . (range to ), bmi was . kg/ m^ (range . to . ), asa physical score was . (range to ). cases had preoperative complicated pyelonephritis, and out of these cases were indwelled preoperative unilateral ureteral catheters. mean stone size was . mm (range . to . ), and operative duration was . minutes (range to ). postoperative complication was pyelonephritis (clavien grade ), and sfr was % ( / cases). in all cases, postoperative unilateral ureteral catheters were indwelled, and were withdrawn weeks later. th ere have been no recurrent stones and/or pyelonephritis (median observation time: . months). conclusion: although sfr was low, urs for extremely old patients can prevent recurrent complicated pyelonephritis even on infected stones. th ere were . % of patients who had a single urinary stone and . % (n = ) had or more. one hundred and nine stones were treated. sixty-three percent of stones were intrarenal. th ere were ( . %) postoperative complications: two stage clavien classifi cation infections (prostatitis at day and two pyelonephritis hours aft er the procedure); three stage b complications (two renal colics requiring ureteral stenting hours aft er discharge and symptomatic perirenal urinoma hours aft er discharge). th ere was one intraoperative complication ( . %): a ureteral wound with contrast leakage. th e rate of transfer to conventional hospitalization was . %. stone size infl uenced the stone-free status and the need for more than one sessions (p < . ). th ere was a signifi cant correlation between operative time and stone size above mm (p= . ). conclusions: flexible and rigid ureteroscopy are safe and effi cient procedures for upper urinary tract stones, and can easily be carried out in an outpatient introduction and objective: renal stone disease is one of commonest urological disorders. pakistan is located in stone belt region with high incidence of urolithiasis. th ere have been innovations and improvement in stone treatment modalities. eswl is one of them. here we share experience of single centre in terms of stone free rate and effi cacy in adults. a retrospective study in which we included adults (age above years old) who underwent eswl from january to december . eswl was done by standard technique. we used modulith sl x lithotripter th generation storz medical. number of shocks per session for kidney and for ureter. energy level for kidney is set at and for ureter at . rate of shock wave delivery is shocks/minute. we followed patients for to months aft er last eswl session done. stone free status was defi ned as residual stone not more than mm in size. we reviewed data charts of patients for diff erent variables mentioned in results. introduction and objective: yolk-sac tumor (yst) is formed almost % germ cell tumors of infant and children. yst is the most common type of testis tumors in prepubertal period, but adult pure yst is extremely rare. in this case we aim to share our surgical experience with an adult pure yst in the right testis. a year-old man was referred to our clinic from cardiovascular surgery department for right testicular mass which is detected during the evaluation of his deep vein thrombosis. th e patient stated having a slowly progressive increase in size of his right gonad. th ere is no history about testicular trauma or epididymoorchitis. physical examination revealed a painful right testis which was uniformly increased in size and presented a smooth surface. usg showed a volumetric increase in the right testis. mass size was detected as . x . x cm, which was characterized by cystic components in heterogeneous echogenicity. serum chemistry revealed a marked increase in afp while β-hcg and ldh levels were within the normal limits. results: a right radical inguinal orchiectomy was performed. during the orchiectomy, because of the invasion to scrotum skin, scrotum skin was removed. th e surgical specimen was rigid, its surface was smooth and necrotic areas were observed ( figure ). pathologic examination revealed a pure yst with positive spermatic cord, tunica albugea, tunica vaginalis and scrotum skin invasion and in light microscopy tumor cells with large hyperchromatic nuclei arranging concentrically around a small vessel were seen (schiller-duval or glomeruloid body). metastasis of lung adenocarcinoma to the testis is an extremely rare occurrence and very few cases have been reported to date. th e authors aim to review the current literature in regard to incidence, clinical manifestation, sources of primary tumour and mechanism of metastasis, in addition to retrospective ten year review of testicular pathology at a single institution. we report an unusual case of a -year-old non-smoking australian gentleman who presented with a six month history of cough and dyspnoea. a physical examination, complete laboratory and radiological work up was performed. a palpable left testicular mass was identifi ed, ct scan revealed multiple bilateral lung nodules and mediastinal lymphadenopathy, however testicular tumour markers were negative. th e patient underwent a radical left inguinal orchidectomy and endobronchial hilar lymph node biopsy with bronchial washings. medical records and pathology results for patients undergoing radical orchidectomy over the past ten years at our institution were obtained and analysed. results: histopathological examination of the left testis and lung biopsy revealed features of a moderately to poorly diff erentiated adenocarcinoma, with morphological and immunohistochemical appearances consistent with lung origin. th e prognosis is extremely poor. a total of patients underwent radical orchidectomy at our institution between january and february . th e mean patient age was ( - ). histopathology is summarised in table . cur-up. , figure . th congress of the sociÉtÉ internationale d'urologie -siu abstract book rent literature review confi rms testicular metastases are rare and may be discovered incidentally at autopsy or following diagnostic orchidectomy. autopsy series revealed testicular metastases in . to . % of specimens. th e most common primaries, excluding lymphoma and leukaemia, include prostate, melanoma, sarcoma, gastrointestinal tract, kidney and lung, with most testicular metastases being a fi nal manifestation of widespread tumours. conclusions: testicular metastases from lung adenocarcinoma origin are scarcely encountered in clinical practice and may create a diagnostic dilemma by mimicking primary testicular neoplasms. extensive pathologic evaluation and specifi c immunohistochemical staining is essential. in patients presenting with a testicular mass, the diff erential diagnosis must include metastatic carcinoma. by . on average compared to only . by non-users (p= . ). many of these fi ndings were only present with recent vge; heavy users from high school and middle school did not show similar trends (table ; figure ). conclusion: th is study shows that subjects with heavy vge perform better on the da vinci skills simulator than subjects who report no vge. th e improvements seen with recent vge are not apparent if stratifying for frequency of use during high school and middle school. th ese fi ndings may have important implications for the future of surgical training. 'virtual urology clinic': a feasibility study in a busy uk teaching hospital introduction and objective: urology is an advancing surgical specialty with a parallel increase in demands from health service commissioners to meet national targets and patients' needs. th is has been refl ected on the outpatient urology service with a rising burden and delays in patients' outpatients' assessments. in our busy tertiary unit, we estimated a total of overdue outpatient appointment (by months or more). th us we designed this virtual clinic feasibility study aiming to: prioritise patients according to their clini- cal needs, enhance their care and decrease the burden by assigning patients to our novel computer based follow-up models. we used the hospital information system to identify one urologist overdue appointments (by months or more). all included cases had thorough review of their medical notes, investigations and treatment before being stratifi ed according to their diagnosis then assigned one of outcomes: urology, cancer nurse specialist (cns) and gp follow-up. results: a total of cases were reviewed in this virtual clinic over a period equivalent to full working days. even though they were all waiting to see one urology cancer surgeon, only % had a primary diagnosis of cancer with the rest being diagnosed with a benign urological condition. th e clinical investigator recommended for only % of all patients to have a urology follow-up with % and % discharged to the gp and computer based follow-up respectively. all patients received a letter explaining the procedure of this clinic along with a tailored management plan. th ere was an evident gap between the dynamic changes in service provision with new available tools and our current practice. th is virtual clinic allowed bridging this gap by categorising the urological priorities and utilising existing resources such as our novel computer based follow-up models. over the last year more than patients' visits have been registered on our computer based clinic which is potentially a cost eff ective model. patients' perspectives of accessibility introduction and objective: patients undergoing major lower abdo/pelvic operations are oft en catheterised (idc) at the start of the procedure to monitor urine output and decompress the bladder to avoid bladder injury. early removal of urinary catheters aft er surgery has been associated with a decrease in urinary tract infections though increasing failure of trial of void (tov), thus being discharged with idc or prolonged admissions. th e aim of this study is to determine the optimal time for tov. th is is a retrospective study looking at patients undergoing abdominal or pelvic procedures due to colorectal/pelvic pathology in the townsville base hospital surgical unit from jan -dec . pre-procedure idc and the deceased were excluded. data was collected from the operating theatre database (ormis). results: out of the total, were female while male, abdominal and pelvic procedures. sixteen male patients had documented prostatic history which include bph, prostate cancer and prostatitis post radiation. four were discharged with an idc failing tov. fift y-seven percent of the patients had their catheters removed on day post-op; . % on day , % on day , . % on day and % > days. th ree patients developed a urinary tract infec-tion (uti) ( . %). patients with good pre morbid function and female tend to pass their trial of void on day post op for pelvic procedures. th e majority of patients had comorbidities and failed tov on day . th ere was no signifi cant diff erence between day and day in uti rates (increasing day onwards). conclusions: idc's should be removed in a timely manner to reduce complications, balanced with monitoring fl uid balance. we proposed that patients should have tov on day , due to increased rates of failed tov day in patients with comorbidities and no diff erence in uti rates between days and . th e limitation of this study is the lack of documentation of preoperative urinary function. to further this study, we can analyse the data to state diff erences between bladder dysfunction as well as tov in groups with various comorbidities. international urology journal club on twitter: a growing educational forum introduction and objective: urologists use urinary and thoracostomy drainage collection systems regularly. pleural and urine fl uid pools at the bottom of dependent loops of both thoracostomy and urinary drainage tubing systems, respectively. we hypothesized that fl uid pooled in a dependent loop ) diminishes the expected negative pressure-head delivered to the pleural space by a chest-tube, and ) obstructs antegrade catheterized urine drainage. we created an ex-vivo thocacostomy tube model, and, performed two separate clinical trials to test our hypothesis. a pleur-evac chest drainage system was connected to - cmh o wall-suction. a digital pressure transducer was connected to the drainage tubing close to the insertion of connection to a chest-tube. model: to simulate dependent loops observed in hospital patients, we created , , and cm-high dependent loops (distance between the bottom of loop and the highest-point en-route to the drainage box). th e pressure close to the (blind-ending) chest-tube was measured as the drainage tube was fi lled in ml. increments. fitted linear regression of pressure and loop-height was performed. clinical trials # . pressure within the drainage tube was measured in six icu patients with thoracostomy tubes in place following cabg surgery. clinical trial # : we performed early-morning hospital icu bedside bladder-scan us on patients with an indwelling urinary catheter and clear urine, to assess for un-drained residual urine. results: with an empty dependent loop, thoracostomy tube pressure equaled the suction pressure (- cm h o). pooled of fl uid within the dependent loop diminished proximal negative pressure (p< . ) in a volume (i.e. loop-height) dependent fashion. th e net range of proximal drainage tube pressure ranged from - to + cmh o. in icu patients, an identical relationship between loops and chest-tube pressure was observed. bladder scan of catheterized ward patients revealed high urine residuals (mean ml) with a dependent loop present, and ~zero residual when no loop present. conclusions: th oracostomy-tube negative-pressure is steadily diminished as a dependent loop fi lls with fl uid. th e resulting air-lock opposes antegrade drainage. th e weight of the fl uid column accounts for positive thoracic pressures, and could account for why many patients fail water seal trials. similarly, urinary tubing dependent-loops result in air-locks that prevent gravity dependent drainage. th oracostomy and urinary drainage tubing should always be positioned without dependent loops. single incision mid-urethral sling (miniarctm) and tension-free vaginal tape (tvt) procedure in women with stress urinary incontinence (sui) at months. a total women with sui were randomized to receive miniarc and tvt. th e primary outcomes were objective and subjective cure rates at a -month follow-up visit. objective and subjective cure of sui were defi ned as a negative cough stress test and absence of self-reported sui symptoms. cure rates of the two groups were compared at -month follow-up. results: a total of ( %) of women originally included in the study (miniarc: , tvt: ) were evaluated at -month follow-up. th ere were no signifi cant diff erences found in demographic and clinical preoperative parameters. objective cure rates for miniarc and tvt groups were % and % while subjective cure rates were % and %. th ere was no statistically signifi cant diff erence between groups (p> . ). conclusions: our -month randomized clinical trial showed that miniarc single incision sling is not inferior to tvt procedure with respect to objective and subjective cures at -month follow-up. introduction and objective: male sui is a debilitating and challenging problem to manage. insertion of transobturator sling off ers less invasive treatment than aus insertion. published data demonstrate cure rates of % but are limited by short follow-up. th e aim of our study was to report long-term outcomes for male transobturator slings for sui with a mean year (minimum year) follow-up. a single-centre retrospective audit of outcomes in male patients who underwent transobturator sling insertion for sui. follow-up was conducted via telephone or in outpatient clinic. incontinence was classifi ed as mild (≤ pads/day), moderate ( - pads/day) or severe (≥ pads/day). classifications post-surgery were: cured -dry; improved -≤ pads/day and ≥ % less pad use; failure -no change or worsened. results: in patients with mild/moderate incontinence, / patients (= . %) were cured/improved with tot. success rates were poor in severely incontinent patients, regardless of radiotherapy history ( %; n= ). of 'cured'/'improved' patients, ( . %) maintained that degree of continence for the duration of follow-up. one patient was lost to follow-up. th ree patients reported a later decline in continence; patients had had previous pelvic radiotherapy. one patient had progression of underlying prostate cancer. conclusion: durable success rates of . % are achievable in men with mild/moderate sui who have not had pelvic radiotherapy. pelvic radiotherapy may play a role in delayed failure of tots with % of patients with mild/moderate sui who were initially cured/improved declining in the second or third year aft er surgery. the mesh wallstent (urolume) in the treatment of detrusor external sphincter dyssynergia in men with spinal cord injury dept. of surgery, div. of urology, king saud university faculty of medicine, riyadh, saudi arabia introduction and objective: to evaluate the longterm effi cacy and safety of the urolume stent for the treatment of detrusor sphincter dyssynergia (dsd) in spinal cord injured (sci) patients. twenty-four spinal cord injured patients with neurogenic bladder and dsd associated with high detrusor pressures and incomplete emptying on pre-operative video-cystometrograms (vcmg) were retrospectively reviewed. twenty-one patients had cervical level injury whilst had a thoracic injury. eleven patients were on clean intermittent catheterization (cic) and with indwelling foley's catheter. all patients underwent urolume stent insertion according to standardized protocol. follow-up assessment included blood chemistry, ultrasound scan (upper tracts and residual urine) at one and three months aft er insertion, and a follow-up vcmg at six months. residual urine volume, autonomic dysrefl exia, catheter need, and presence of bladder stones and hydronephrosis were compared before and aft er treatment. post-operative patient and physician satisfaction, complications and re-obstruction rates were also analyzed. paired t-test is used and p value < . was taken as signifi cant. results: th e twenty-four patients had a mean (range) follow-up of . ( . - ) years. th e mean age was introduction and objective: at present, sacral neuromodulation (snm) with interstim® therapy is indicated for non obstructive urinary retention and overactive bladder, including urinary urge incontinence and signifi cant symptoms of urgency-frequency alone or in combination, in subjects who have failed or could not tolerate more conservative treatments and do not have any neurological disorder. th ere are also reports of the use of interstim® in the treatment of chronic pelvic pain and other conditions. we report our experience with the use of this device in patients with post-traumatic brain injury damage without anatomical anomalies and with severe urinary voiding dysfunction who had failed intensive medical and behavioral therapies. materials and methods: from november to november , patients underwent interstim® placement ( male and female). all had severe voiding dysfunction secondary to post-traumatic brain injury damage; ten of them had also defecatory disturbances ( a chronic constipation and fecal incontinence). th e main goal was to evaluate the improvement of the urinary symptoms and the second goal the improvement of the intestinal symptoms. success was defi ned as a ≥ % improvement in any of the two variables evaluated. results: with a mean follow-up of months, / patients reported ≥ % improvement in their urinary voiding symptoms ( %), in these patients urinary frequency decreased from to episodes per day, mean voided volume increased from cc to cc, incontinence disappeared in of patients and urgency disappeared in all patients. of patients with intestinal disturbances, showed a signifi cant improvement ( %). one patient showed a clavien iii complication (seroma and partial dehiscence of the surgical wound managed with conservative surgical treatment). conclusion: snm in post-traumatic brain injury patients is an eff ective and safe option for urinary and defecatory dysfunction when other conservative therapies have failed. to our knowledge the use of inters-tim® in this scenario has not been reported previously. a larger series and a longer follow-up are needed to validate this indication. introduction and objective: th ere were some reports that in the patients who have stress incontinence (sui) with detrusor underactivity, voiding symptoms aggravated aft er mid-urethral sling operation (mus). we report our experiences of mus cases on the patients who have sui with detrusor underactivity. conclusion: urethral sphincter and bladder function worsen immediately aft er rarp and recover over time. th e bladder storage function aft er rarp returns to almost the same level before rarp, the voiding function improves compared with the condition inserted into the rabbit bladder through the urethra and saline solution is infused using a disposable syringe into the bladder through the end cap. conventional cystometry was performed and the intravesical pressure was measured by prototype intravesical pressure sensor at the same time. we also evaluated the biocompatibility of ecofl ex® by checking changes in the levels of macrophages, macrophage migratory inhibitory factor, and infl ammatory cytokines in the bladder tissue and urine. cape town, south africa th congress of the sociÉtÉ internationale d'urologie -siu abstract book and urgency incontinence are signifi cantly detected luts in children with vur the -gene genomic prostate score assay: initial commercial experience of , patients th congress of the sociÉtÉ internationale d'urologie -siu abstract book th congress of the sociÉtÉ internationale d'urologie -siu abstract book pelvic strength physiotherapy percutaneous treatment of bladder stones in children: -year experience; is blind access safe? extirpative treatment of upper urinary tract urothelial carcinoma: an -year comprehensive review paik l th e overall complication rate was %. no hydronephrosis were seen thought the follow-up period. stricture rate was low, only one patient ( %) at one year, and none at years had urethral stricture. patients ( %) required re-stenting due to stent migration ( patients, %), or stricture ( patient, %), all of which happened during the fi rst year of surgery. patients ( %) required alpha-blockers to control bladder neck dyssynergia post operatively. stents ( %) were removed due to exacerbation of autonomic dysrefl exia symptoms (n = ); encrustation and stone formation (n = ). overall, % of patients and % of physicians felt there was improvement in urination at year. conclusions: th e treatment of detrusor sphincter dyssynergia in spinal cord injured patients with urolome stent is safe and eff ective sacral neuromodulation with interstim® therapy for urinary voiding dysfunctions in post-traumatic brain injury patients: a new therapeutic indication? hospital pablo tobon uribe, medellin, colombia th congress of the sociÉtÉ internationale d'urologie -siu abstract book between pre-and post-operative qmax abstract book before rarp; however, the urethral sphincter func male ( . %) ( %) . ** introduction and objective: we evaluated the clinical eff ect of alternative fl utamide therapy for metastatic prostate cancer that relapsed aft er initial maximum androgen blockade (mab), and investigated the relationship between the eff ectiveness of alternative fl utamide therapy and the eff ectiveness of initial mab. and december , patients with metastatic prostate cancer that relapsed aft er initial surgical or medical castration along with bicalutamide for mab were treated with fl utamide therapy ( mg daily). importantly, patients who had discontinued bicalutamide because of adverse events were excluded.results: of the patients treated with alternative fl utamide therapy, prostate-specifi c antigen (psa) levels decreased by > % (group a) in patients ( %), by - % (group b) in patients ( %), and by - % (group c) in patients ( %), but increased by > % in patients ( %). th e median duration of response was . , . , and . months for groups a, b and c, respectively. th e duration of response for patients ( %) was more than months. aft er alternative fl utamide therapy, decreased psa levels of > % were achieved in of patients ( %) with mab nadir psa levels of < . ng/ ml, in of patients ( %) with mab nadir psa levels of . to ng/ml, and in of patients ( %) with mab nadir psa levels of > ng/ml. during the observation period there were no severe side eff ects.conclusion: approximately % of patients with metastatic prostate cancer who relapsed aft er mab with bicalutamide achieved a decrease in their psa level with no severe side eff ects. th e nadir psa level during mab, however, was not a predictor for the eff ectiveness of alternative fl utamide therapy. th us, alternative fl utamide therapy is a reasonable treatment option for metastatic castration resistant prostate cancer. nevertheless, changing to another therapy should be considered in patients who achieve decreases in psa levels of < % with alternative fl utamide therapy, as the duration of response was relatively short in these patients. association of renal function and androgen deprivation therapy with prostate cancermasuda h, kanesaka m, sugiura m, hou k, araki k, kojima s, naya y introduction and objective: we evaluated the change of renal function by androgen deprivation therapy (adt) and examined the association of the occurrence of renal dysfunction and concomitant diseases. between january and april , patients who could measure estimated glomerular fi ltration rate (egfr) at pretreatment, , and months were evaluated retrospectively. all of them were diagnosed prostate cancer by prostate biopsy pathologically and had taken adt for at least months. we assessed the renal function of prostate cancer patients by using the egfr and investigated the time-independent change rate of the egfr (Δegfr) aft er adt. th e Δegfr was calculated by (post treatment egfr-pretreatment egfr)/pretreatment egfr × ). univariate and multivariate logistic analyses were carried out to identify clinical covariates signifi cantly associated with the risk factors for renal dysfunction at months later.results: th e incidence of the renal dysfunction at months was % ( / ). th e mean Δegfr at , , months were - . %, - . % and - . %, respectively (p= . ). th e incidence of the renal dysfunction at months was signifi cantly associated with the renal dysfunction at month (p< . ), at months (p< . ), hypertension (p= . ) and dyslipidemia (p= . ). th e renal dysfunction at pretreatment with adt did not aff ect the renal function months later (p= . ). th e renal dysfunction at months (odds ratio [or] . , p= . ), renal dysfunction at months ([or] . , p= . ), hypertension ([or] . , p= . ) and hyperlipidemia ([or] . , p= . ) were independent predictors of the renal dysfunction at months in the multivariate analysis.conclusions: it was suggested that the renal dysfunction with adt occurred relatively early. th e earlier renal dysfunction may cause the renal dysfunction at months later. so, when the treatment of adt began, it was thought that an examination of periodical renal function was necessary. th e present results suggested that it was necessary to control the blood pressure and lipid for receiving adt with prostate cancer. immune (pc) and isolated lymph node metastases aft er curative therapy are usually treated with an anti-androgen therapy. th e choline pet-ct is the method of choice in diagnostic of the recurrent psa. controver-sial in the latest debate is the oncological eff ectiveness of the local salvage therapy of isolated lymph node metastases. th e aim of this study is to compare the oncologic outcome of the salvage lymphadenectomy (la) alone versus the la in combination with adjuvant radiotherapy (ar) and androgen deprivation therapy (adt).materials and methods: th erefore we randomized patients with biochemical recurrence of a pc (psa: ≥ , ng/ml) aft er curative local therapy and detection of at least one lymph node metastasis. we applied two treatment arms. a (n= ): single la; b (n= ): la plus ar/adt (bicalutamide) over years. we determined the biochemical recurrence-free survival (bfs) and the time-to-treat (ttt) until complete androgen blockade. conclusion: compared for both treatment arms, the combination of la plus adt/ar is superior to la alone. however, both methods are to be seen as individual decisions in highly selected patients. th e oncological long-term eff ectiveness is questionable. stem cell transformation of prostatic cells after hormonal therapy we reviewed consecutive patients who underwent transperineal mri-trus fusion target biopsy followed by conventional transrectal systematic core biopsy between july and mar in our institution. in all patients, t low region was detected by prostate mri image and target biopsy was conducted for region of interest (roi) of the mri image utilizing biojet system. baseline characteristics and pathological outcome were analyzed.results: in analyzed cohort, mean age was . ± . years, median initial psa was . ng/ml (range, . - . ), median prostate volume (pv) was . ml (range, . - . ) , and median volume of roi was . ml (range . - . ). of patients, prostate cancer was detected in ( %) patients by target biopsy and ( %) patients by systematic biopsy. patients with positive biopsy was likely to be higher psa than men with negative biopsy (p= . ). median roi/pv was not signifi cant between them ( . vs. . : positive vs. negative, p= . ). cancer detection rates per core between target and systematic biopsy were . and . %, respectively (p= . ).regarding pathological results, mean gleason score of target biopsy was . compared with . of systematic biopsy, although which is not statistically signifi cant (p= . ).conclusion: mri-trus fusion target biopsy is gradually spreading in japan, since its higher cancer detection rate compared with conventional systematic biopsy. in our institution, substantial detection ability of prostate cancer by mri-trus fusion target biopsy was confi rmed, which encouraged future clinical trial for prostate focal therapy. multiparametric introduction and objective: sepsis has always been a concern in the traditional transrectal ultrasound (trus) guided biopsy of the prostate. however, rates of sepsis following trus biopsy have shown to be increasing around the world in addition to the emergence of multiresistant organisms found in rec-tal fl ora. as a result, our practice of seven urologists has switched to transperineal (tp) biopsy. we aim to determine the rate of hospital re-admission in our patients undergoing tp biopsy. an ethics approved prospective database of all men undergoing tp biopsy at our practice has been kept including antibiotics used as well as re-admission for infection. introduction and objective: robot-assisted radical prostatectomy (rarp) has become one of standard treatments for localized prostate cancer. however, a feasibility of rarp in elderly patients has not been clear yet. we performed a comparative analysis of peri-surgical / oncological outcomes for younger and elder patients underwent rarp. we reviewed and compared our initial consecutive patients who underwent rarp from / to / for peri-surgical outcomes, including surgical times, blood loss, complications, pathological fi ndings, continence recovery, and oncological outcomes stratifi ed by age less than and over years.results: in our cohort, men were age less than and men were ≥ . preoperative parameters (age, psa, gleason score) were similar in both younger and elder groups. operative time (mean: vs. minutes) and estimated blood loss were similar in both groups. one of elder patients ( . %) needed transfusion. peri/post-operative complications in both groups appeared to be minimal with no cases of intra-operative open conversion. one of younger patients needed a surgical settlement for port site herniation. surgical positive margin rates in organ-confi ned (pt ) disease were also similar ( . %, younger vs. . %, elder). continence at months was % in elder patients as opposed to % in younger patients. biochemical recurrences in short follow-up period (median vs. months) were observed . % in elder patients as opposed . % in younger patients.conclusions: in our study, although urinary continence recovery in elderly patients might show a short delay, rarp in elderly patients was relatively safe and yielded good oncologic results. rarp is feasible eve in elderly patients. quality in the fi rst study, community-based urologists ordering at least assays from / to / participated. clinicopathologic data, the gps and treatment were abstracted from medical records of gps patients and a clinically similar baseline group. th e proportion of men recommended and pursuing active surveillance (as) before and aft er the availability of the gps were computed. in the second prospective study, urologists at centers (academic and community) recorded tr on pre-and post-gps questionnaires, including changes in treatment intensity.results: fift een urologists completed the chart review study on men ( gps; baseline). th e relative increase in tr for as was %, ( % baseline, % gps; absolute diff erence of %). gps pts chose as more than baseline pts ( % gps; % baseline, absolute increase of %, relative increase of %). of men recommended as, % of gps and % of baseline pts chose it. in men in the prospective study, the relative increase in recommendation for as was % and absolute tr increase for as was also % ( % to %). % of tr changed post-gps and tr modality and/or intensity occurred in % of men ( decreased; increased; equivocal).conclusions: both studies, conducted with diff erent methodologies, demonstrate that use of gps provides meaningful change in tr and decisions in men with newly diagnosed pca and results in a net increase in recommendation and/or adoption of as. in the chart review study, tr changes appear to underestimate changes in actual treatment received and more gps patients than baseline patients were assigned to as supporting the clinical utility of gps in the initial assessment and management of men with low risk pca. comparison we prospectively evaluated in patients with clinically localized prostate cancer, the possible association between hce (≥ . mmol/l) and aggressive prostate cancer. pre-operative serum cholesterol levels (ch), triglycerides (tr), were prospectively assessed in men treated consecutively with radical prostatectomy from feb. to oct. . th e results were related to patient specifi c and clinico-pathologic data.results: patients with hce (n= ) had a more aggressive grade gleason score (gs) ≥ b, p< . )), a locally more advanced stage (≥pt a, p< . ), and lymph node metastasis (n+, p< . ). hce was also associated more frequent with a positive surgical resection margin (r , p< . ). in multivariate regression analysis hce is associated with a high-risk pc (hr . , % ci . to . , p < . ) -adjusted for psa, dre, age and poor biopsy score (gs ≥ ).conclusion: th e results indicate that hca is associated with high-grade and metastatic disease in men diagnosed with clinically localized pc. our fi ndings suggest that ch can be used as an additional predictive marker in therapy. conclusion: th e incidence of bs-positive tumours is low in men being staged for radical treatment except in high-risk disease. pelvic/prostate mpmri alone cannot be relied upon to exclude bone metastases in this group. hyperbaric oxygen therapy for radiation induced side-effects introduction and objective: to evaluate the effi cacy of hyperbaric oxygen (hbo) th erapy for prostate conclusions: in our japanese provincial hospital, the comparatively young patients chose a treatment according to treatment algorithm. however, according to aging, the patients tended to choose hormonal therapy regardless of algorithm. as for one of the reasons, it is thought as follows: even if the patients chose operation or radiotherapy, it may be diffi cult to visit the institutions that have such a treatment because public transport does not develop in our prefecture. nurse-led telephone follow-up for prostate cancer surveillanceturner b, tanabalan c, nargund v, pati j, wells p introduction and objective: we review the patients' experience of a nurse-led, telephone follow-up service for men with 'stable' prostate cancer, to measure satisfaction and quality. th e telephone follow-up service is based on the premise that psa measurement can be used as a surrogate for outpatient attendance. telephone follow-up service serves to reduce the number of patients attending hospital appointments. th is has led to increased clinic capacity and reduced waiting times, ensuring urgent care is available for patients who need it. a nurse-led, protocol based telephone follow-up service was set up for patients deemed to have 'stable' disease. questionnaires were sent to all patients. survey was voluntary and anonymous. we addressed a variety of aspects of the service, including time, duration and content of the telephone appointments, patients' preference for type of follow-up (telephone vs. hospital follow-up) and overall satisfaction with the service.results: response rate of %. reported high satisfaction with telephone follow-up ( % were either satisfi ed or very satisfi ed). majority of patients found the length of the conversations to be 'just right' ( %) with a lesser majority expressing that the calls were always at times convenient to them ( %) and that they were always called when they were told they would be called ( %). patients felt that the information given to them over the phone was always easy enough to understand ( %) and the majority felt that they always had the opportunity to ask questions during the conversations ( %). when asked whether they would prefer telephone follow-up or hospital follow-up, % of respondents reported that they would prefer telephone follow-up, citing convenience, time and privacy as the reasons for their preference. twenty-one percent of patients would prefer hospital follow-up, reporting ease of understanding, not liking the telephone and preference for face to face contact.conclusions: telephone follow-up relieves pressure on the outpatient department, increases capacity, reduces waiting times and brings care closer to home. patients perceive the service as a valuable addition to their care and report high levels of satisfaction with the service. prostate ' th e target sample sizes of australasian trials 'currently recruiting' ranged from to men (median= ), the majority of trials investigating medical and radiation oncological interventions. five of the trials 'currently recruiting' were recorded as single-centre studies in new south wales, victoria and queensland. of the remaining trials, % (n= ) were recorded as international, industry sponsored, multi-centre studies with australian and/ or new zealand recruitment sites.conclusion: australasian prostate cancer clinical trial activity (though likely under-recognised in this study, due to trial registration limitations) represents a relatively small fraction of international eff ort. continued investment will ensure that the talented and world-leading scientists and medical professionals across both nations can tackle the big challenges in prostate cancer through working collaboratively. assessment modifi ed laparoscopic intravesical nonrefl uxing ureteral reimplantation with psoas hitch using a submucosal tunneling introduction and objective: we aimed to study the safety and effi cacy of the cystoscopy-assisted nonrefl uxing ureteral reimplantation technique using sub-mucosal tunneling during laparoscopic ureteroneocystostomy (unc) with a psoas hitch in patients with distal ureter stricture aft er gynecologic surgery. we reviewed six female patients who underwent gynecological surgeries. all patients showed persistent postoperative distal ureter stricture or obstruction. th ese patients underwent laparoscopic nonrefl uxing unc with a psoas hitch using a submucosal tunneling technique combined with cystoscopy at our institute.results: th ey had corrective surgery at an average of . weeks aft er ureteral injury. th e short-term success was confi rmed either by voiding cystourethrography (vcu) or by diuretic isotope renal scan (mag- ) conducted months aft er the operation. none of the patients showed evidence of postoperative stricture at the reimplanted site and refl ux on either mag- renal scan or vcu. none of the patients showed major or minor complications during follow-up. it is safe and feasible to perform the laparoscopic nonrefl uxing unc with a psoas hitch using a submucosal tunneling technique combined with cystoscopy for ureteral stricture. upper ureteral injuries were more frequent in the urological surgery group than in the non-urological surgery group ( % vs. . %). complications or serious injuries were more frequent in the urological surgery group. th ere were no signifi cant diff erences in the mean durations of hospitalization and indwelling times between the groups. conclusion: th e occurrence of a ureteral injury during urological surgery is an infrequent but serious complication may occur. urologists should pay attention to the potential for ureteral injury, especially during a ureteroscopic ureterolithotomy for the treatment of an upper ureter stone. reducing the risks of trauma due to urethral catheterisation mundy a, yim i, tamini a, roberts n conclusion: isolated ureteric trauma can be managed successfully using minimally invasive endoscopic and radiological approach. a pcn initially helps in minimizing extravasation and ureteral wall edema subsequently facilitating stent placement. medium-and long- university of sydney, sydney, australia introduction and objective: urethral stricture is a common urological presentation for obstructive lower urinary tract symptoms. th e treatment of choice for a durable outcome is usually substitution urethroplasty using buccal mucosal graft . graft failure is not uncommonly encountered. we present the mediumand long-term outcomes of ventral buccal mucosal graft urethroplasty using spongio fl ap technique. a retrospective review of a single surgeons experience was reviewed for a period of years. data was collected from medical records, surgeon's notes and operation reports. inclusion criteria included reconstruction of anterior urethral stricture using bm graft positioned ventrally and graft support using spongio fl ap technique. patients who were lost to follow-up were excluded from analysis. graft patency was defi ned as having a lumen greater than fr. th is was assessed via cystoscopic examinations at , and months intervals post procedure.results: a total of male patients identifi ed with age ranging from to years and mean age of years. average length of bm graft used was . cm. total of ( %) achieved long-term successful outcome. of these ( . %) patients had successful outcomes with no further interventions, and ( . %) required gentle urethral dilatation at fi rst cystoscopy and subsequently achieved long-term patency. sixteen ( . %) of this cohort formed recurrent stricture at initial cystoscopy, and ( . %) of patients formed urethral stricture formed delayed stricture, despite the initial cystoscopic examination and urethral dilatation.conclusion: ventral buccal mucosal graft urethroplasty using spongio fl ap technique has very good short-term and long-term graft patency outcomes. outcome of paediatric kidney transplantation: single center experience nawaz g, jamil i, athar khawaja m, muhammad s, shohab d, ur rehman a, ali khan i, khan a, hussain i, akhter s introduction and objective: renal transplantation is the treatment of choice for children with end-stage renal disease (esrd) because in addition to making them off dialysis it also improves growth and development of the child. about - % of children have a lower urinary tract dysfunction due to congenital or acquired genitourinary anomaly as the etiology of esrd and they need a diversion or augmentation procedure prior to transplantation. we aim to deter-mine the outcome of paediatric renal transplant at year in term of graft survival and complications. we retrospectively reviewed the record of consecutive children underwent living related renal transplant between jan to jan . all were primary renal transplants and had living related renal donors. patient characteristics, causes of esrd and pre transplant surgical procedure were recorded. patients with lower tract abnormalities as cause of renal failure underwent reconstructive procedure prior to transplant. induction immunosuppression consisted of triple therapy with antithymocytic globulin (atg), prednisone and mycophenolate mofetil (mmf). cyclosporine was introduced when creatinine came down to > % of normal. all patients were treated as cmv positive with either acyclovir or ganciclovir and received daily dose of trimethoprim-sulfamethoxazole as prophylaxis for pneumocystis carnii pneumonia aft er transplantation. post transplant surgical and medical complication, graft and patient survival were recorded.conclusion: ureteric implantation into the bowel portion of augmented bladders appears safe in this population of patients with previously reported increased risk of ureteric complications and urinary tract infections aft er transplantation. transition of cavernous function after radical prostatectomy materials and methods: study subjects were ed patients with a history of rp (median age: ). intervals between rp and examination diff ered among patients (range: to months). we also performed doppler penile ultrasound examination using intracavernous injection of micrograms of prostaglandin e . we adopted an infusion rate of less than ml/min at mmhg of intracavernous pressure as the normal cavernous function limit for dicc.results: arterial velocity in ultrasonic examinations showed a tendency to decrease. cavernous function aft er rp clearly diff erentiated according to phospho-diesterase inhibitors (pde is) response ( figure ). in the pde is responder patient group ( cases), the rate of normal cavernous function was % at month, months, and months, but the rate increased to % at months, and % at months. a diff erent transition was seen in the pde is non-responder patient group ( cases). in this group, the rate of normal cavernous function was also % at month. however, from here, the rate increased to % at months, and then aft er this point, it decreased to % at months. sixteen -week-old sprague-dawley rats were induced diabetes by a onetime intraperitoneal injection of streptozocin ( mg/ kg). one week later, the diabetic rats were randomly divided into groups including a normal control, dm control and two uu treated group ( , and mg/kg/d). th e latter rats were fed uu by intragastric administration for weeks. aft er weeks, penile hemodynamic function was evaluated by measuring the intracavernosal pressure aft er electrostimulating cavernous nerve. we measured nitric oxide (no) and cyclic guanosine monophosphate (cgmp) activity. endothelial nitric oxide synthase (enos) and neuronal nos (nnos) protein expression was determined by western blot. masson's trichrome staining was also assessed.results: serum glucose level in dm +uu group was signifi cant lower than in that of the dm control groups. maximum intracavernosal pressure in dm control rats decreased signifi cantly compared to normal control rats and increased signifi cantly compared to untreated dm rats aft er uu supplementation. dm + uu group had signifi cantly increased no and cgmp level compared with the dm control group. decreased activity and expression enos and nnos were found in the dm groups compare with normal control group. decreased enos and nnos in diabetic rats were improved by uu administration. decreased the cavernous smooth muscle to collagen ratio was improved in dm + uu groups in the masson's trichrome staining.conclusions: uu eff ectively ameliorated erectile function in a streptozocin induced diabetic rat model of erectile dysfunction. you d , jung s , jang m , kim b , lee c , song g , choi k , shin h , suh n , kim y , ahn t , kim c the etiology and management of erectile dysfunction (ed) in patients with metabolic syndrome (ms). eighty-six patients suff ering from erectile dysfunction and metabolic syndrome were included in the study, patients were classifi ed based on iief- domain into three groups: mild ed (n= ), moderate ed (n= ) and severe ed (n= ). th ese patients were treated using upgraded regimen protocol (changing of the life style for months, on demand use of pde- inhibitors for months, chronic dosing with long acting pde- inhibitors for months and combination therapy of pde- inhibitors and intracavernosal injection for months) re-evaluation of the patients was done at the end of each stage by (iief-ef, waist circumference and laboratory investigations).results: aft er months of lifestyle modifi cation there was increase in the iief-ef but this change was not signifi cant the overall improvement was ( %), aft er on demand pde- inhibitors for months( . %) of patients with mild ed were improved, ( %) with moderate ed and ( . %) with severe ed were improved. non-improved patients in each group aft er on demand pde- inhibitors received pde- inhibitors chronic dosing for another months then re-evaluated ( . %) of patients with mild ed were improved, ( . %) with moderate ed and ( . %) with severe ed were improved, combination therapy in the form of tadalafi l mg daily and pge μg on demand were off ered to patient whom reported failure of pde- inhibitors chronic dosing patients with mild symptoms reported the maximum improvement ( %), patients with moderate symptoms reported fair improvement ( . %); however patient with severe symptoms reported no improvement at all.conclusion: pde inhibitors should be considered as the fi rst line phamaco-therapy in treatment of ed in metabolic syndrome patients. non-responders to pde inhibitors may have a benefi t from daily dosing of long acting pde- inhibitors. combination therapy of pde- inhibitors chronic dosing associated with intracavernosal injection of pge may play a role as a salvage therapy aft er failure of monotherapy. following this upgraded regimen case with ms and ed can have overall successful results in . %. comorbidity of premature ejaculation and erectile dysfunction: are they inseparable in chinese adult men?tang y, yang j, jiang x introduction and objective: premature ejaculation (pe) and erectile dysfunction (ed) are usually regarded as a symbol of incompetence. but in china for the inconsistent defi nitions of pe, some of them cannot correctly distinguish pe from ed. th erefore, to fi nd out the real relationship between pe and ed, a detailed investigation was implemented. were enrolled. all the subjects were evaluated by the face-to-face questionnaires of premature ejaculation diagnostic tool (pedt) and the international index of erectile function (iief- ). a professional urologist was invited to measure their lengths of penis and volumes of testes. all the data were analyzed by spss version . soft ware.results: a total of men aged from to years ( . ± . ) were categorized into lifelong pe (lpe) ( men), acquired premature ejaculation (ape) ( men), variable pe (vpe) ( men) and subjective pe (spe) ( men), respectively. th ere was no signifi cant diff erence among the four pe subtypes except for the ielts and the iief- . th e self-estimated ielt of spe was signifi cant longer than that of other subtypes, and the similar case could be seen in iief- . th e highest percentage was found in ape ( . %) for chronic prostatitis (cp) and in lpe ( . %) for ed.conclusion: vpe was the most common subtype, next ape, thirdly spe and the least one is lpe. consistent with the previous reports, we found that the incidence of cp in ape was the highest among all the four subtypes of pe, and cp was a signifi cant risk factor of ape but not for other subtypes. th ere has always been controversial about the relationship between pe and ed. th e results from our multinomial logistic regression analysis showed that ed was not only associated with pe, but also could be regarded as a risk factor of pe. introduction and objective: depression oft en overlapped with late-onset hypogonadism (loh) syndrome. clinically, many loh patients who have depressive symptom were treated with testosterone replacement therapy (trt). however, treatment efficacy of trt for these patients is unclear. in this study, we aimed to identify characteristics of loh patients on trt who had medical history of ongoing mental health treatment for depression syndrome. we reviewed consecutive patients who visited men's health clinic and underwent trt in our institution during june and december . prior to trt, patients received a physical examination and full hormonal evaluation including free testosterone (ft), lutenzing hormone (lh), and follicle-stimulating hormone (fsh). th e aging males' symptoms (ams) score was also evaluated. trt was conducted by mg monthly testosterone injection. effi cacy of trt was noted when diff erential of ams score between pre-and post-treatment was more than points. in the entire cohort of patients, the mean age was . ± . years and pre-trt ams score was . ± . . pre-trt ft, lh, and fsh were . ± . ng/ml, . ± . miu/ml, and . ± . miu/ml, respectively. of total patients, cases ( . %) had diagnosis of depression by psychiatrist and ongoing mental health treatment. patients with positive medical history of mental health treatment were found to be younger ( . vs. . years, p = . ), higher pre-trt ams score ( . vs. . , p < . ), lower lh ( . vs. . %, p = . ), and lower fsh ( . vs. . %, p = . ) compared to patients with negative medical history of mental health treatment. effi cacy of trt was greater in men who have mental treatment history ( . vs. . %, p = . ) based on ams improvements. while, there were no signifi cant diff erence in ft ( . vs. . ng/ml, p = . ), trt duration ( vs. days, p = . ), and trt discontinuation rate ( . vs. . %, p = . ) between two groups.conclusion: even though, loh patients who had diagnosis of depression and underwent medical treatment such as antidepressant, trt can be feasible approach for those patients. majority of those loh patients underwent mental health treatment at the same moment with trt, which may not harm treatment effi cacy of trt. the effect on blood flow rate of prostate in daily administration of mirodenafi l mg for benign prostatic hyperplasia patients: randomized paroxetine is the most eff ective ssris. in few studies, tramadol has been used to treat pe. considering the high incidence of pe in men and lack of consensus on its treatment, we decided to compare the therapeutic eff ects of tramadol, paroxetine and placebo in the treatment of primary pe. in this randomized, double-blind, placebo-controlled clinical trial, patients were randomly divided into groups. one group was treated with tramadol mg, the other group took paroxetine mg and the third group was treated with placebo. before starting treatment and aft er weeks, patients were asked to measure their average intravaginal ejaculation latency time (ielt) and fi ll the pep (premature ejaculation profi le) questionnaire. aft er collecting the data, they were recorded in spss version and were analyzed.results: patients in the groups in baseline characteristics, including mean age, ielt and pep were similar at the beginning of the study and there was no clinically signifi cant diff erence in the groups (p> . ). a total of patients completed the study period. at the end of the th week, the mean ielt and average of pep scores increased in all groups. th ese changes in tramadol group were signifi cantly higher than the paroxetine and placebo groups (p< . ). th ere were no signifi cant diff erences in terms of side eff ects between the groups. th e results showed that despite an increase in mean ielt and pep scores in all groups, the rate of improvement in tramadol group was considerably more than the other groups. th us, tramadol may be considered as an appropriate alternative therapeutic for long-life pe. the effi cacy and safety of tadalafi l mg once daily for the treatment of erectile dysfunction related to the vascular causes after robot-assisted radical prostatectomy: -year follow-updong-a university hospital, busan, south korea; jeil hospital, ulsan, south korea introduction and objective: to evaluate the effi cacy and safety of tadalafi l mg once daily use in the treatment of erectile dysfunction (ed) based on the vascular cause aft er robot-assisted radical prostatectomy (rarp). th e study retrospectively evaluated patients who underwent rarp and had a penile rehabilitation by tadalafi l mg once daily use at our medical center. th e patients were surveyed based on the abridged fi ve-item version of the international index of erectile function (iief- ) questionnaire, which was self-administered before the surgery, and at months, year and years aft er the surgery. th e patients were classifi ed into the tadalafi l group (n= ) and the non-tadalafi l group (n= ). each group was then classifi ed depending on the nerve-sparing (ns) procedure: bilateral ns and unilateral ns. additionally, patients who underwent a penile color-duplex u/s study to evaluate the cause of erectile dysfunction were also analysed.results: at months, year, and years, the total iief score of the tadalafi l group and that of the non-tadalafi l group were . ± . vs. . ± . , . ± . vs. . ± . , and . ± . vs. . ± . , respectively. statistically signifi cant improvements (p< . ) were observed in the tadalafi l group for all domains of iief- score, while in the non-tadalafi l group there was no signifi cant improvement in any of the domains at and years. fift y three patients had a penile color-duplex u/s study. arteriogenic and venogenic ed was seen in patients ( . %) and patients ( . %). fift een patients ( . %) showed unremarkable fi ndings. venogenic ed patients had little response compared to arteriogeinc ed patients by tadalafi l mg once daily use ( % vs. . %). th e overall side eff ects were hot fl ushing in . %, headache in . %, and dizziness in . %. in ed patients aft er ns ralp, a once daily dosage of tadalafi l mg was well tolerated and signifi cantly improved ef compared with the non-tadalafi l group until two years. but in the venogenic ed patients, response to a once daily dosage of tadalafi l mg was relatively limited compared to the arteriogenic ed patients. effects of long-term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism (earth): a randomized phase trial in japan introduction and objective: to determine the role of stone density and skin-to-stone distance (ssd) by non-contrast computed tomography of the kidneys, ureters and bladder (ct-kub) in predicting the success of extracorporeal shock wave lithotripsy (eswl). we evaluated patients who received eswl for renal and upper ureteric calculi measuring - mm, over a month period. mean stone density in hounsfi eld units (hu) and mean ssd in millimeters (mm) was determined on pre-treatment ct-kub at the ct workstation. eswl was successful if post-treatment residual stone fragments were ≤ mm.results: e wl success was observed in . % of the patients. mean stone densities were ± and ± hu in e wl successful and failure groups, respectively; this was statistically signifi cant (p < . , student's t-test). mean ssd were . ± . and . ± . cm in eswl successful and failure groups, respectively, this was not statistically signifi cant.conclusions: th is study shows that stone density can help in predicting the out-come of eswl. we propose that stone densities < hu are highly likely to result in successful eswl. conversely, stone densities > hu are less likely to do . th is should be accounted for when considering eswl. assessment th is prospective study was conducted upon children with mean age . ± . years. patients underwent retrograde intrarenal surgery (rirs) under general anesthesia as monotherapy. th e procedure was initially started by the semi-rigid ureteroscope (storz . f) and holmium laser and was completed by the fl exible ureterorenoscope (fl ex x ) for other parts of the stone which were not accessible by the semi-rigid ureteroscope. ureteral access sheath was not used and only hydrodilation was performed. patients were evaluated preoperatively by ultrasound and plain x-ray of the abdomen and pelvis. pre-intervention sterilization of urine was performed in all patients using culture guided antibiotics. follow-up lasted for months.results: stone-free rate aft er a single session treatment was % and % aft er second session. mean operative time was . ± . minutes. th e mean fl uoroscopy exposure time was . ± . seconds. mean hospital stay was . ± . days. all patients had jj stent inserted. no major complications (clavien iii-v) occurred. none of the children received blood transfusion. th ree patients needed a second session of rirs, patient required a pnl session.conclusions: retrograde intra renal surgery using combined semi-rigid and fl exible ureteroscope off ers eff ective and safe option for treatment of medium sized renal stones children with comparable results to shock wave lithotripsy (swl) and percutaneous nephrolithotomy (pnl). introduction and objective: calcium stones are associated with osteoporosis and manifested mainly by elevated fasting urinary calcium/creatinine ratio. th e objective of this study is to demonstrate the presence of abnormal metabolism of calcium and calciuria in women with osteoporotic fracture with no previous-ly known renal lithiasis compared to women without osteoporosis and without renal lithiasis. eighty-seven women were included in the study and divided into two groups: group : postmenopausal women with osteoporotic fracture and without renal lithiasis; group : postmenopausal women without osteoporosis and without history of renal lithiasis. th e following parameters of phospho-calcium metabolism were analyzed: calciuria h, oxaluria h, uricosuria h and citraturia h. th e presence of hypercalciuria, hyperoxaluria, hyperuricosuria and hypocitraturia was compared between the two groups. statistical signifi cance was determined as p≤ . . results: th e mean age was . ± . years in group and . ± . years in group (p = . ). women in group had higher levels of serum alkaline phosphatise (p< . ) and fasting urinary calcium/ creatinine ratio (p< . ) than women in group . th e percentage of women with hypercalciuria in group ( %) was higher compared to women in group ( . %) and statistically signifi cant (p = . ). th ere were no statistically signifi cant diff erences in the percentage of hyperoxaluria, hyperuricosuria and hypocitraturia between the two groups. th is paper has the limitations of cross sectional study in a unique center and with a low number of patients. dept. of urology, ulster hospital, dundonald, uk introduction and objective: bladder stones are more common found in children from developing countries. open cystolithotomy or transurethral cystolithalopaxy are the traditional treatment but a percutaneous approach has been advocated. we present our experience with percutaneous cystolithotomy in children with bladder stones without any ultrasonic or fl uoroscopic guidance. from april to october , a total of children ( boys and girls) with a mean (range) age of . ( - . ) years underwent percutaneous cystolithotripsy (pccl). th e mean (range) stone diameter was . ( . - ) cm. one hundred thirty-eight children ( %) had a solitary stone while nine ( %) had more than one stone. th e main component of the stones were calcium oxalate in patients ( . %).results: all children were stone-free aft er one pccl; no recurrent stones developed. th e mean (range) pccl procedure time was . ( to ) min and intraoperative blood loss was scant. perioperative complications were few. th e mean (range) hospital stay was . ( - ) days.conclusions: blind access pccl (without any ultrasonic or fl uoroscopic guidance) is a facile and safe approach for removing stones in the pediatric bladder stones. advantages include the lack of ionizing radiation, no need for opacifi cation by iodine contrast media and low relative cost. we recommend this minimally invasive technique for management of large bladder stones (larger than cm) in children. to our knowledge, this is the largest single center series re-ported on percutaneous cystolithotripsy of endemic bladder stones in children. retrograde intrarenal surgery (rirs) in an unusual kidney ( ), polycystic kidney ( )]; who underwent rirs for stone management was evaluated. stone size was less than mm in all the cases. bleeding being the commonest complication, hemoglobin drop was measured to fi nd out the blood loss. all patients were assessed by x-ray and usg on the fi rst postoperative day and month follow-up. th e other parameter of focus was operative time, hospital stay, stone free rate and the auxiliary procedure. th e auxiliary procedure was divided as (staged, follow-up ( month) or other-pcnl/swl) so that stone free was the main target for the patients. conclusion: urolithiasis occurs in an abnormal kidney, indeed challenging, but rirs can also be performed successfully. proper handling of instrument can increase the longevity of the instrument for cost eff ectiveness. although complete stone clearance cannot be achieved, but meritorious achievement is less morbidity, early recovery, minimal bleeding with less complication. th us, rirs can be performed effi ciently, effi caciously and successfully in an unusual kidney with prior exposure of rirs. value of intraoperative ultrasound in decreasing of the risk of residual radiolucent stone post-pcnl al shareef j, aboelmagd m introduction and objective: hemorrhage is the most concerning complication aft er tubeless percutaneous nephrolithotomy (pcnl). we compressed the access tract of the kidney with oxidized regenerated cellulose (surgicele) aft er pcnl to facilitate homeostasis for tubeless pcnl. since april to september , pcnl was performed at our hospital. all patients received one stage procedure with metal dilator. aft er the end of stone extraction, the access tract was cauterized and an f foley catheter was inserted to the renal pelvis through the working sheath then infl ated and gently retracted. th e working sheath was withdrawn to the renal capsule and the access tract of the renal parenchyma was packed with surgicele and compressed with small sized dilators through the working sheath for minutes. a bloodless tract usually could be obtained in nearly every patient and all patients underwent tubeless modifi cation. th e results of these patients were analyzed with retrospective chart review.results: th e age of these patients ranged from to (mean . ) years old. th e average stone size was . ( . - . ) cm and the average operation time was . ( - ) minutes. th e target stones had been removed in all patients and the overall stone free rate was . %. th e postoperative blood transfusion rate was . % with no patient underwent angiographic intervention or other management for severe hemorrhage. postoperative fever was noted in . % patients and sepsis was noted in . % patients. th is study was designed to evaluate the adverse eff ects of swl on the metal devices for spine fi xation and the hemoclips for hemostasis. a total of cases who underwent swl for treatment of upper ureteral and renal stones were investigated. th eir ages were from ~ years (mean . ± . ). male patient was one and female patients were . th e piezolith (wolf, germany) was used as the lithotripter. th e metal devices were hemoclips for cholecystectomy in one, and pedicle screw in fi ve patients and bone cement (polymethylmethacrylate) in one patient for spinal fi xation through l to s . th e locations of the stones were the kidneys in and the upper ureter in patients and their sizes were from . cm to . cm (mean, . ± . ) . th e numbers of the swl were . ~ . times (median, ) . th e distances between the stones and metal devices were . ~ . cm (mean, . ± . ). th ey were followed-up for . ~ . months ( . ± . ). th e complications were investigated in terms of pain, fever, damage of the devices (change of morphology and location in simple x-ray fi lm and their function). no patient showed fever and pain in sites of the devices requiring medication, injection or other management during or aft er swl. one patient was admitted for acute colick fl ank pain with tenderness in costovertebral angle caused by acute ureteral obstruction by a crumbled small piece of the stone. th ere was no complication concerning with the eff ect of the swl on metal devices. even though swl is one of the safe treatment modality in various clinical fi elds, it can't be said that swl is always safe without complication. however, it can be said that it would be safe when it being done following the instruction. a prospective study to identify risk factors of pleural injury during percutaneous nephrolithotomy a total of patients with renal/upper ureteric stones, undergoing pcnl between january and june were evaluated for pleural injury. an erect chest x-ray antero-posterior view on inspiration was done within -hours of pcnl. th e patients were divided into groups a and b depending on whether they developed or did not develop pleural injury. patient-, stone-, renal-and procedure-related factors were compared between the two groups. patients with any known disease of lungs or pleura, patients undergoing simultaneous bilateral pcnl, relook nephroscopy, concomitant other procedures such as endo-pyelotomy or retrograde ureterorenoscopy were excluded from study. tract dilatation up to -f was done using alken metal dilators and an amplatz sheath was placed into system. nephroscopy was done with rigid nephroscope and stones were fragmented with pneumatic lithoclast.results: pleural complications occurred in patients ( %). out of patients, had supra-costal puncture and ( . %) developed pleural injury; patients had infra-costal puncture and pleural injury occurred in ( % on multivariate analysis, only low bmi and mean age < -years was associated with higher risk of pleural injury. th e limitation is the small number of patients (as pleural injury is not common a very large number is needed to show signifi cance).conclusions: higher incidence of pleural injury was noted in patients with low bmi and younger age. large multicenter study can provide a true picture. flexible and rigid ureteroscopy in th e success rate was defi ned as radiopacities less than mm on plain fi lm at one month follow-up aft er the fl exible ureteronoscopic procedure. our tips included: tip , moving technique, refers to move the lower pole stones to the upper pole or middle pole depending on the convenient site for fragmenting the stones with the escape basket. if the stones were large or the lower pole orifi ce is narrow, we fragmented the stones into two or more pieces, trapped and moved the stones into the convenient pole. tip , holding technique, refers to hold the stones in the renal pelvis and insert a laser fi ber through the escape to fragment the stones. tip , sheath technique, refers to extract the large stones and pull the stones to the sheath distal side, the stone was too large to pull out, a laser fi ber was inserted though the escape, fragmented the stones. all the videos were recorded.results: overall success rate was . %. th e success rate in the renal pelvis stone, upper pole, middle pole and lower pole was %, . %, . %, . % respectively. th e operating time was . minutes on the average. th ree patients had fever over °c aft er the procedures. no urosepsis occurred.conclusion: our tips are feasible in the treatment of kidney stones with fl exible ureteronoscopy. satisfactory success rate, shortening operating time, less fl exible ureteronoscopy consuming and less complication were obtained in the procedures of fl exible ureteronoscopy with escape. ureteroscopic introduction and objective: patients with underlying diseases, especially in old-aged, the urinary tract obstruction with the ureter stone would progress to the severe condition like renal failure or sepsis. prompt urinary diversion like percutaneous nephrostomy or removal of the stone via ureteroscope is necessary for these patients. however, most of them have poor general conditions to endure regional or general an-esthesia. so, we tried to implement the ureteroscopic removal of stone (urs) without anesthesia for the patients with ureter stone who were in septic conditions or severe urinary tract infections (uti). fift een patients ( males and females) included this study and all of them had serious problems like sepsis, heart problems or lung problems which were diffi cult to endure anesthesia. most of them were inserted pre-operative percutaneous nephrostomy catheter (pcn) due to impending septic shock. all of the stones were impacted in the ureter and urs were successfully performed with painkiller like pethidine mg iv. success rate of stone removal, pain perception during operation using a visual analog pain scale were done. results: th e mean age of the patients was . (± . ). th e position of the stones was as follows; upper ureter, mid-ureter and lower ureter stones. and there was no patient that had to stop the operation because of intolerable pain. th e mean of vas (visual analogue pain scale) was . (± . ). overall success rate was %. however, % of cases were unable to fi nd the impacted calculi but stone debris and blood clots. th e general condition of the patients except one was improved quickly aft er operation and discharged aft er . (± . ) days.conclusion: most obstructive uropathy due to calculi was in serious conditions to need immediate procedures and urs were safely and successfully performed under intravenous analgesics. in some of female patients, urs is well-tolerated even without analgesics. prompt urs procedure with intravenous analgesics can recover these conditions with minimal morbidity. geavlete p, georgescu d, multescu r, geavlete b introduction and objective: percutaneous nephrolithotomy (pcnl) is nowadays a widely practiced procedure. despite the good stone-free rates, it still has a specifi c morbidity. our goal was to describe the complications of this method on a signifi cant series of patients. between january and january , patients (age between and years) underwent pcnl ( procedures). we used f rigid nephroscopes and f fl exible ones ( procedures). th e mean follow-up period was months (range to months).results: intraoperative incidents were encountered during procedures ( . %): losing the percutaneous traject ( cases), poor visibility due to bleeding and imposing the termination of the procedure ( cases) and descendant stone fragments' migration imposing antegrade ureteroscopic removal ( cases). th e overall complications' rate was % ( cases): signifi cant bleeding requiring blood transfusions ( cases), emobolisation ( cases) nephrectomy ( cases) or open surgical hemostasis ( cases), sepsis ( cases), fever ( cases), pyelocaliceal perforations ( cases), hemoperitoneum ( case), persistent lumbar uri-nary fi stulae requiring retrograde jj ureteral stenting ( cases) and extra-renal stone fragments migration ( cases). however, the majority of these complications were minor. th e mortality rate related to pcnl procedures was %.conclusion: according to our experience, pcnl is a safe and eff ective technique. most of the intraoperative incidents or complications are minor and easy to solve. however, an adequate training is imperative in order to reduce the associated morbidity. is spinal anesthesia adequate for percutaneous nephrolithotomy? introduction and objective: to evaluate the adequacy of spinal anesthesia in terms of patient and surgeon satisfaction and convenience during percutaneous nephrolithotomy. patients who were candidates for percutaneous nephrolithotomy and operated by two endourology fellows during july -september were enrolled. spinal anesthesia was performed using an injection of . mg/kg bupivacaine . % in the intrathecal space; no opium (fentanyl) agent was used. all procedures were performed with the patient in the prone position. access was achieved by fl uoroscopic guidance, and the tract was dilated using a single-stage technique. anestheisa duration was defi ned from injection of anesthetic medication to fi xation of nephrostomy tube. operation duration was defi ned from start of cystoscopy to fi xation of nephrostomy tube. patient pain and satisfaction during operation and surgeon satisfaction was measured by an ordinal likert-type scale and collected by an examiner blinded to the study objectives.results: a total of patients (mean±sd age, . ± . years; male) were enrolled during the study period. th e mean±sd of anesthesia and operation duration were . ± . and . ± . minutes respectively. severe pain causing signifi cant discomfort to the patient and surgeon was observed in patients ( %). in three patients the operation was prematurely terminated because of excessive pain and/ or agitation of the patient. mild-moderate pain was observed in eight patients ( %). vomiting and headache was observed in another two patients. the african : our experience of stenting ureters in outpatients without screening or ga introduction and objective: to review ureteric catheters/dj stents placed under local anaesthetic, with antibiotic coverage, without the use of screening, at groote schuur hospital (gsh) over the last years. a prospectively collected database exists from july until present. all patients signed informed consent and received pre-procedural oral antibiotics. a post-procedural abdominal kub radiograph was obtained to ensure correct placement. demographic data and variables (stent/catheter, indication, side, success/failure -including reasons for failure) were collected. patients were asked to subjectively rate the level of pain at the end of the procedure.th e data has been collected and tabulated into an ex-cel® worksheet.results: a total of procedures (average . per year) were performed with age range from to years (average: . years). th e average time taken was minutes (median: minutes). th e shortest procedure recorded was minutes, and longest was minutes (with a failure). th e failure rate totals . % and further inspection shows that . % of failures were with bilateral stents, . % right sided and . % left sided. stated diff erently, % ( / ) of bilateral stents failed, . % ( / ) of right sided stents failed, and . % ( / ) left sided stents failed. th ere was a success rate of . % with stenting under local anaesthetic. th e average subjective pain score was . , which is tolerable. sivalingam et al ( , urology : - ) showed the average cost for stenting under general anaesthetic was almost times more expensive than under local. th eir local group had a failure rate of . %, which was lower than our . %, but we had a larger group ( in years vs. in years).conclusion: flexible cystoscopy and stenting under local anaesthetic without screening is useful and feasible, with minimal morbidity, discomfort and failures. it can be practiced as a cost eff ective, offi ce-based procedure and is suitable for the third world environment. introduction and objective: urolithiasis is an ancient disease with global distribution and is an important health problem all over the world. th ere are diff erent results for stone clearance rate in diff erent renal and ureteric locations aft er eswl. here we share our experience of the comparison of stone free rates and complications in diff erent renal locations. a retrospective study in which we included adults (age above years old) who underwent eswl from january to december . eswl was done by standard technique. we used modulith sl x lithotripter th generation storz medical. we followed patients for to months aft er last eswl session done. stone free status was defi ned as residual stone not more than mm in size. we reviewed data charts of patients for diff erent variables mentioned in results. introduction and objective: tubeless percutaneous nephrolithotomy (pcnl) for staghorn calculi has been reported to be safe and eff ective in select patients. although outpatient pcnl has been recently been shown to be safe and eff ective in a series of patients, it requires further study before urologists embrace same day discharge following pcnl. th e objective of this study is to report our early experience in treating staghorn calculi with pcnl on a completely outpatient basis, assessing its safety and effi cacy. a review of all outpatient tubeless pcnl cases between march and may at two canadian centres was performed, including collection of preoperative, intraoperative and postoperative data. strict preoperative, intraoperative and postoperative criteria were used in the selection of candidates for outpatient pcnl: no intraoperative complications including signifi cant bleeding or collecting system perforation; postoperative hemodynamic stability; adequate pain control; reliable patient with supportive family.results: fift y patients underwent ambulatory pcnl during the study period. staghorn calculi were treated in patients including cases of bilateral staghorn calculi, resulting in a total of staghorn renal units treated by ambulatory pcnl. all patients were discharged home uneventfully - hours postoperatively. th ere were no major postoperative complications, emergency room visits, hospital readmissions or deaths. th e stone-free rate was %, with of the renal units being stone-free at follow-up.conclusion: th is small series represents the largest series of ambulatory pcnl for staghorn calculi to date. in very carefully selected patients, pcnl for staghorn calculi on a completely outpatient basis appears safe and may be feasible. further research on ambulatory pcnl for staghorn calculi is required prior to widespread adoption by urologists. introduction and objective: th e most diffi cult aspect of percutaneous nephrolithotomy (pcnl) is frequently the renal puncture. most are performed under fl uoroscopic control. parallax, the assessment of the displacement of an object when viewed along two lines of sight, is the concept which allows the surgeon to gauge the d relationship of the needle to the kidney from a d fl uoroscopic image. whilst most urologists appreciate successful access correlates with both kidney and stone images moving in unison on rotation of the c arm (or "reverse parallax"), confusion oft en arises with unsuccessful attempts in relating how to amend the puncture with the radiological fi ndings. we create a model to describe visual observation of parallax. by way of a short video we outline how it can be implemented seamlessly into routine pcnl.results: visualization of the theory followed by its application in theatre clearly demonstrates a failsafe technique to allow operators to reliably detect when their puncture needle is deep or superfi cial to the stone.conclusions: parallax, as an adjunct to routine fl uoroscopy during pcnl, allows the operating urologist to rapidly gauge depth of needle in relation to the collecting system in diffi cult access scenarios. familiarity with this technique is important to minimize radiation exposure, ensure satisfactory access to the collecting system and improve operating times. the signifi cance of non-enhanced compute tomography for renal colic has been overestimated in absence of pyuria kim t , ahn s , kang j , kim j , myung s , moon y , kim k , chang i introduction and objective: th e study was undertaken to compare clinical utility in patients undergoing non-enhanced computed tomography (nect) and intravenous urography (ivu) in patient with classic symptoms of renal colic without evidence of urine infection and to determine the clinical importance. th is was a retrospective observational analysis of all adult patients between and . all nect and ivu were reviewed and categorized as the cause of symptoms. non-urolithiasis cause were further categorized as "acutely important", "follow-up recommended", and "other unimportant cause". full record review blinding to imaging fi nding was underwent including demographics, diagnosis, and management. we compared stone characteristics on imaging study, and demographic, exact diagnosis, and management methods between nect and ivu groups.results: a total of , patients were available inclusion criteria and ( . %) patients were underwent ivu and patients were nect. th e incidence of nect was . % at , but . % at . nect group was older ( . ± . vs. . ± . years old, p< . ), less hematuria in urine analysis ( . vs. . %, p< . ) and more admit ( . vs. . %, p< . ) than ivu group. urinary stones were detected ( . %) patients. nect group showed higher proportion of renal stone, mid ureteral stone and multiple stones ( . vs. . %, p< . , . vs. . %, p< . , . vs. . %, p< . , respectively), and smaller stone ( . ± . vs. . ± . mm, p< . ), and more radiolucent stone ( . vs. . %, p< . ) comparing to ivu group. th e incidence of urolithiasis more than mm were no diff erence between nect and ivu groups ( . vs. . %, p= . on radiologic fi nding, and . vs. . %, p= . on full chart record). moreover, the incidence of "acutely important" among non-urolithiasis cause was similar between nect and ivu groups on full record review ( . vs. . %, p= . ) . th e incidence of the active management including surgery and extracorporal shock wave therapy (eswl) were not diff erence between nect and ivu group ( . vs. . %, p= . ).conclusions: nect is a rapid and accurate diagnosis test for suspected renal colic, and nowadays almost renal colic patients in our hospital underwent nect in ed. however, it did not show better advantage for the detection of clinically signifi cant urolithiasis and acutely signifi cant cause of renal colic in patient with renal colic and absence of pyuria. from january to july we reviewed the scrotal ultrasound images of all patients diagnosed with leydig cell tumor and treated with conservative surgery (group a). we considered only patients that were fi rst diagnosed at one of the participating centers. we create a random homogenous control group of patients (group b), in term of age and presentation, diff erent from the group a just for the defi nitive malignant histology. all the images were collected and we analyzed ultrasound features of the lesions classifi ed in terms of length, us lesion homogeneity, shape, presence of hypervascularization. th e collected data were analysed by an online regression (student's t-test, chi-square test, and logistic regression analysis).results: th irty fi ve patients with leydig cell tumor underwent conservative surgery at our centers. a random group b of patients was also considered. pa-tient mean age was . years (range to ) for the fi rst group and . years for the second one (range to ). patients presented either with a palpable testicular nodule ( patients group a, . % - patients . % group b) or a nodule diagnosed by ultrasound ( patients group a, . % - patients . % group b). mean ultrasound size was . cm and . cm for the two groups respectively (range . to . cm and . to cm). both groups had hypervascularization of the lesions with no signifi cant diff erences. patients presenting with lct (group a) had an homogenous ultrasound intralesional aspect and the shape is defi ned with an elliptic or spheroid mold while patients from group b had dis-homogenous intralesional aspect and non-defi ned margins (p> . ).conclusion: although most focal lesions will be malignant and require an orchiectomy, recognition of the benign entity may be challenging. in a small lesion mainly not palpable the presence of a well-defi ned shape with an homogenous intralesional ultrasound aspect do correlate with a lct. adult testicular pure yolk-sac tumor the association of torsion with testicular cancer: a retrospective study introduction and objective: testicular torsion is a medical emergency that usually requires surgical exploration of scrotum to allow reperfusion of the aff ected testis. nonetheless, such surgeries can be frequently resulted in orchiectomy due to tissue ischemia and necrosis. however, testicular malignancy has been anecdotally reported with the association of torsion in the surgical specimens and the literature remains scant on the association of torsion with testicular tumors. th is retrospective study was set to explore the association of torsion with testicular cancer in cases of testicular torsion undergoing orchiectomy during scrotal exploration. a chart review was performed for patients who admitted to our clinic and had a diagnosis of testicular torsion between january and february . data of patients' characteristics, the laterality of the torsion, time and type of intervention and pathological examination were recorded. results: overall, patients with a diagnosis of testicular torsion were identifi ed. th e mean age was . years (ranges from to years). all the patients had unilateral intravaginal testicular torsion aff ecting the left side in cases ( . %) and on the right side in cases ( . %). manual detorsion was successful in patients ( . %) all of whom underwent bilateral testicular fi xation surgery within hours via scrotal incision. twenty-six ( . %) patients underwent emergency surgery with a testicular detorsion and fi xation surgery in ( . %) cases (bilaterally in and right-sided in ) and orchiectomy in ( . %) cases ( in right side and in left side). th e type of incision was scrotal in cases, inguinal in cases and unspecifi ed in surgeries. pathological examination of specimens revealed ischemia and necrosis in cases, while patients underwent testicular removal via inguinal incision had malignancy including seminoma and malign mixed germ cell tumor.conclusion: our retrospective study, as the largest case series in the current literature, showed the association of intravaginal torsion with testicular cancer to be . %. further high-level evidences are needed to establish the optimal incision type in testicular torsion cases with surgical exploration to avoid scrotal violation resulted from suboptimal approaches. wong l , , dickson b , catton c , yap s , , alkasab t , van der kwast t , hamilton r , jewett m st vincent 's hospital, melbourne, australia; princess margaret hospital, toronto, canada; university of california davis, davis, usa introduction and objective: paratesticular sarcoma (pts) is an uncommon disease and the literature is mostly confi ned to small case series with short follow-up. herein we present an update on our institution's experience in the management of patients with pts. fift y-one men with pts at princess margaret cancer center, between and were identifi ed from retrospective chart review. important relevant clinical pathological variables were collected with study endpoints being local recurrence, metastasis and overall survival. univariate analysis of variables associated with survival end points was performed with cox proportional hazards regression.results: median follow-up of our cohort was . years (iqr . - . ) with a median overall survival of . years. at presentation . % (n= ) of men had localized disease. interval completion hemiscrotectomy (performed aft er initial unplanned diagnostic surgery) was done in men, in which % (n= ) had residual disease present. local recurrence (lr) occurred in patients ( . %). median time from diagnosis to lr was months. univariate analysis showed presence of positive margins at diagnostic surgery (hr . , p= . ) and upfront/ completion hemiscrotectomy (hr . , p= . ) to be signifi cant variables. at last follow-up, / men ( . %) with lr were alive and disease free, developed metastatic disease with pts-related mortalities, and deceased of other cancer type. metastasis was present in men ( . %), with median time to metastasis mo, and median to from metastasis to death . mo. at last follow-up, . % (n= ) of the patients were deceased with cases attributable to pts. on univariate analysis, there were no significant variables for metastatic disease, and age (hr . , ci . - . , p= . ) and non-localized disease at presentation (hr . , p= . ) were signifi cant for overall survival.conclusion: in our cohort of pts patients with median years follow-up, aggressive treatment of local recurrence ( . %) resulted in good disease free survival for of men. completion hemiscrotectomy, particularly for positive margin disease, may decrease local recurrence. a rare case of testicular metastasis from primary lung adenocarcinoma: case report and ten-year review of testicular pathology at a single institution demkiw s , jackett l , goad j , wong l introduction and objective: health care websites provide a valuable resource of health information to online consumers, especially patients. offi cial surgical and medical society websites should be a reliable fi rst point of contact. th e primary aim of this study was to quantitatively assess medical and surgical society websites for content and highlight the essential features required for a high-quality, user-friendly society website. twenty specialty association websites from each of the regions, australia, uk, canada, europe, and the usa were selected for a total of websites. medical and surgical specialities were consistent across each region. each website was systematically and critically analysed for content and usability.results: th e average points scored per website was . out of . of the total (n= ) websites, scored at least out of points and scored out of . as well, % ( . / ) of the websites had an infor-mation tab for patients on their respective homepages while % ( . / ) had download access to patient information. a minority of the websites included different forms of multimedia such as pictures and diagrams ( . / , %) and videos ( . / , %). we found that most society websites did not meet an adequate standard for delivery of information. half of the websites were not patient accessible, with the primary focus being for health professionals. as well, most required logins for information access. specialty health care societies should create patient-friendly websites that would be benefi cial to all online consumers. application materials and methods: students were selected by sampling in pbl group (n = ) and pbl-ebm group (n = ), and the two groups received clinical teaching of urology by pbl and pbl-ebm model respectively. at the end of the study, each student received objective and subjective evaluation.results: th ere was no signifi cant diff erence in results of the baseline on evidence-based medicine between two groups (p> . ), but the percentage of high-recommended-level research evidence obtained by the students in the pbl-ebm group was signifi cantly higher than that in pbl group (p< . ). and questionnaire showed more students in pbl-ebm group believed that this teaching model improved their ability of comprehensive analysis and application of medical evidence, and developed their skills in solving problem and obtaining information on various subjects (p< . ).conclusions: th e model of problem-based learning combined with evidence-based medicine is feasible and eff ective in clinical teaching of urology and optimize the outcomes from pbl education. by the pbl-ebm model teaching, students improve the ability to advantage in managing evidence from medical studies, analyzing and solving problem, obtaining and applying medical information. incidence (dvt) or pulmonary embolism (pe), is recognized as one of the most serious complications of surgery. in urologic surgery, this has not been well reported thus the objective of this study is to access the risk factors for the development of vte among patients undergoing major pelvic surgery for prostate and bladder cancer in an australian tertiary referral center. consecutive patients undergoing major pelvic uro-oncologic surgery, namely radical cystectomy and radical prostatectomy over a fi ve-year period ( - ) were identifi ed. patient variables, types of surgery, types of thromboprophylaxis (pharmacological and/or mechanical) used in this patient cohort were collected for analyses as predictive factors.results: an overall incidence of vte was . %. patients undergoing radical cystectomy were more likely to suff er a vte event compared to patients having radical prostatectomy. in this cohort, the risk factors for vte include, prolonged operative time of greater than hours, lymph node dissection (lnd) and patients requiring blood transfusions.conclusion: patient undergoing major pelvic uro-oncologic surgery have a % risk of developing vte. risk factors identifi ed in this study should be used to guide the use of early and prolonged thromboprophylaxis. optimal trial of void after idc insertion for pelvic surgery th am c , ho p introduction and objective: in , we pioneered the fi rst international twitter-based journal club (#urojc) to discuss urology articles on a monthly basis with diverse global participation. since that time, this model of an international twitter-based journal club has been adopted by several other medical specialties including general surgery, respiratory medicine and nephrology. th e objective of this study is to examine the development of the urology journal club into an innovative and thriving forum for exchange of ideas, information and opinions since its conception two years ago. monthly twitter analyses such as number of users, tweets and impressions for the journal club were obtained via a third-party service called symplur using the hashtag #urojc. qualitative analysis was also performed of each individual tweet to assess for relevance to the discussion. comparisons were made between data from the fi rst and second year of operation of the journal club, including the number and geographic location of participants, as well as the quantity and quality of tweets.results: see table for summary statistics. th e total number of unique users of #urojc almost doubled from year one to year two. th e mean number of total participants increased by seven per month, and mean number of total countries represented increased by three per month. while the number of tweets per month also increased from year one to year two, the proportion of content-relevant tweets remained stably high at approximately %. meanwhile, there was a greater degree of participation from authors of the study being discussed over time. journal club continues to draw robust participation from a global audience, and serves as a benchmark for twitter-based journal clubs in other specialties. th e majority of tweets are relevant to the content of the article, providing a novel forum to discuss new research fi ndings with a global audience. prognostic impact of perinephric fat stranding on computed tomography in ureteral urothelial carcinoma introduction and objective: ureteral urothelial carcinoma causes gradual ureteral obstruction. perinephric fat stranding is defi ned as linear areas of soft tissue attenuation in the perinephric space, which can result from any acute process or injury to the kidney. we analyzed the prognostic impact of perinephric fat standing as well as secondary signs of upper urinary obstruction on the oncologic outcomes of patients with ureteral urothleial carcinoma. a total of patients who were evaluated by abdominal-pelvic computed tomography (ct) preoperatively and were diagnosed with ureteral urothelial carcinoma aft er nephroureterectomy conducted between january and december were enrolled in this retrospective study. we analyzed the association between oncologic outcomes and clinical-pathologic fi ndings, including secondary signs of upper urinary obstruction on preoperative ct such as hydronephrosis grade, perinephric fat stranding, renal enlargement, kidney density diff erence, renal cortical thinning, periureteral fat stranding.results: preoperatively patients ( . %) had perinephric fat stranding on preoperative ct. multivariate analysis showed that perinephric fat stranding, higher pt stage (≥ t ), lymph node involvement of cancer, and positive surgical margin were independent prognostic factors of cancer-specifi c survival (p = . , p = . , p < . and p = . , respec-tively). and perinephric fat stranding, higher pt stage (≥ t ), lymphovascular invasion, and lymph node involvement of cancer were identifi ed as independent prognostic factors of recurrence-free survival in ureteral urothelial carcinoma (p = . , p = . , p = . and p = . , respectively).conclusion: perinephric fat stranding on preoperative ct in ureteral urothelial carcinoma was found to be an independent prognostic factor of disease recurrence and cancer-specifi c mortality. our fi ndings indicate that immediate radical surgery and adjuvant therapy should be considered in patients with perinephric fat stranding preoperatively. lower increased urinary tract malignancy in end-stage renal disease (esrd) has been reported. however, little is known in chronic kidney disease (ckd). th is study is designed to explore the association between ckd and upper urinary tract urothelial carcinoma (uut-uc). health insurance database, we included ckd patients between january and december . th e non-ckd controls were selected with the ratio : and frequency matched with gender, age group and index date. chi-square test and t-test were used to inspect sociodemographic information and comorbidities. logistic regression analysis was used to calculate hazard ratio (hr) and % confi dence interval (ci). a year-old man with a strong family history of various cancers presented with haematuria and was subsequently found to have a mass in the right pelviureteric junction suggestive of urothelial carcinoma. work-up confi rmed the diagnosis without evidence of metastatic disease and the patient went on to have an open transperitoneal nephroureterectomy. laparoscopic approach was initially attempted but abandoned due to dense adhesions thought secondary to previous open bowel resection for colorectal cancer. a fl ank incision was used; there were no specifi c operative complications and the specimen was easily retrieved without manipulation or rupture. post-operative recovery was unremarkable and histological analysis of the tumour revealed a non-invasive high-grade papillary urothelial carcinoma at the right pelviureteric junction with clear resection margins. approximately months post-operatively the patient re-presented with a rapidly enlarging mass at the fl ank incision. imaging demonstrated a circumscribed hypodense mass within the muscle layers at the site of the scar and biopsy revealed poorly diff erentiated carcinoma. surgery to excise the mass was subsequently performed and immunohistochemical analysis revealed a lack of staining for msh .results: abdominal wall metastasis following open nephroureterectomy for upper tract urothelial carcinoma is rare, with only one case reported previously. given patient's previous history of colorectal cancer, strong family history and immunohistochemical fi ndings are highly suggestive of lynch syndrome. incisional site tumour recurrence following surgery for urological malignancy is a very rare complication, with only a handful of case reports existing, mostly relating to port-site metastasis following laparoscopic surgery. wound recurrence following open surgery is an extremely uncommon but recognised event, more frequent in certain gynaecological and general surgical malignancies. ls involves inherited defects in the dna mismatch repair system, resulting in predisposition to a number of malignancies. urologists should consider the possibility of lynch syndrome in any patient with de-novo upper tract urothelial carcinoma, and strongly recommend genetic testing where patients meet the amsterdam ii criteria or are diagnosed under the age of . prognostic ) developed recurrent bladder cancer within years aft er nephroureterectomy, and the median interval between surgery and intravesical recurrence was . months (range to months). multifocal tumors, native aristolochic acid nephropathy and distal ureter invasion were determined as risk factors for intravesical recurrence by univariate analysis. however, by multivariate analyses, multifocality (hazard ratio = . , % ci = . - . , p = . ) and native aristolochic acid nephropathy (hazard ratio = . , % ci = . - . , p = . ) were identifi ed as independent predictors for the development of recurrent bladder cancer aft er surgery for uut-uc in renal transplant recipients.conclusions: th e incidence of intravesical recurrence aft er laparoscopic nephroureterectomy for uut-uc in renal transplant recipients is high, and most subsequent bladder cancers recur within years aft er surgery. tumor multifocality and native aristolochic acid nephropathy are signifi cant independent risk factors in developing initial intravesical recurrence aft er laparoscopic surgery for primary upper urinary tract urothelial carcinoma aft er renal transplantation.introduction and objective: transient urinary incontinence may occur in up to % of patients aft er holmium laser enucleation of the prostate (holep). however, there are few published data concerning the factors associated with de novo urinary incontinence (ui). th e aim of this study was to investigate the associated factors of de novo ui aft er holep. our study included patients who underwent holep. enrolled patients were divided into two groups according to the presence of ui. independent t test was used to compare between two groups. logistic regression was performed to analyze a correlation between de novo ui and other factors such as age, prostate volume, retrieved tissue weight, operative time, and the fi rst post-void residual (pvr) urine volume immediately aft er removing postoperative urethral catheter. urethral catheter was removed aft er bladder instillation with a ml normal saline via urethral catheter, and pvr urine volume was estimated immediately aft er the fi rst postoperative self-voiding. all defi nitions of ui corresponded to recommendations of the international continence society.results: aft er holep, patients ( . %) had de novo ui, most of which resolved within - months; had stress ui, had urgency ui, and had mixed ui. age and pvr urine volume were signifi cantly higher in ui group than non-ui group ( . ± . vs. . ± . years; p = . , . ± . vs. . ± . ml, p < . ). in a logistic linear regression analysis, only pvr urine volume was an independent predictor of de novo ui aft er holep. th e most optimal cut-off value of pvr urine volume for predicting de novo ui was defi ned as . ml in the receiver operating characteristics curve analysis (sensitivity, . %; specifi city, . %; auc, . ; p < . ).conclusion: about one-third of patients might undergo de novo ui following holep, and most of them might have been resolved within - months. high pvr urine volume aft er removal of postoperative urethral catheter is associated with de novo ui aft er holep, and could be used a practical tool to predict postoperative de novo ui. concomitant transurethral and introduction and objective: stress urinary incontinence is a common medical problem among women. th e urethral closure complex and/or the support mechanisms are responsible for incontinence in the majority of patients. several surgical procedures with diff erent degrees of invasiveness and outcomes have been reported to treat the problem. although many are reasonably eff ective, a general trend towards study of natural and biocompatible tissues is emerging over popular synthetic materials. here we report our experience with injection of autologous adipose-derived stem cells to the periurethral region as a new method of stress urinary incontinence treatment. ten women with symptoms of stress urinary incontinence were treated by injections of autologous adipose-derived stem cells into the periurethral region via transurethral and transvaginal approach under urethroscopic observation. th is report presents the short-term outcome of the patients. th e outcome measured by pad test results, iciq-sf scores and qmax.results: th e mean age of the participants was . ± . years. urinary incontinence signifi cantly decreased through the fi rst two, and weeks aft er the injection therapy. th e diff erence was signifi cant in pad test results (p< . ) and iciq-sf scores (p< . ), especially comparing results between and weeks and among and weeks, but not for and weeks compared to each other. surprisingly, qmax showed improvement aft er the study period (means . vs. . ; p= . ). th is study showed that injection of the autologous adipose-derived stem cells to periurethral region is a safe, yet shot-term eff ective treatment option for stress urinary incontinence. further studies with longer follow-up are needed to confi rm its longterm effi cacy. sparc sling system for treatment of female stress and mixed urinary incontinence in the elderly sung l, noh c, chung j, yoo j introduction and objective: th e aim of this study was to investigate the safety and effi cacy of the suprapubic arch (sparc) sling procedure for the management of urinary incontinence in elderly versus younger women. a total of women underwent the sparc procedure for female urinary incontinence. of these patients, were classifi ed younger women (sui, . mui, ) and (sui, . mui, ) were elderly (more than year). th e preoperative evaluations included a complete medical history, a female bladder questionnaires, urogynecological examination and urodynamic test with valsalva leak point pressure (vlpp). th e main outcome measures were perioperative morbidity, postoperative sui, persistent or de novo urge incontinence, postoperative complication and voiding dysfunction. th e objective and subjective success rate were evaluated by visual analogue score and global patient impression questionnaire at , , months. th e mean follow-up period was ± mo (range, - mo).results: th e incidence of sparc related morbidity was similar in both groups. for the operation outcome results, in younger group ( patients) there were cases of cure ( . %), cases of improvement ( . %), and cases of fail ( . %) and in elderly group ( patients) there were cases of cure ( . %), cases of improvement ( . %), a case of fail ( . %) (p> . ). th e operation satisfaction rate of patients was . % in the younger group and . % in the elderly group (p> . ). a total of patients ( . %) would like to recommend the sparc procedure to others. th e objective success rate and operation satisfaction rate of the younger group did not diff er from elderly group. no severe intraoperative or postoperative complications occurred in both groups.conclusions: th e sparc procedure is eff ective and off ers a satisfactory cure rate without signifi cant morbidity in elderly women. validity introduction and objective: urinary incontinence secondary to surgery or trauma is a debilitating condition for the patient, and for the urologist a diffi cult situation to manage. because of the complexity of reconstructive surgical techniques and the cost of the prosthetic devices used, there is a need for a simple procedure. aims: we here in report our experience in managing urinary incontinence secondary to sphincteric incompetence in patients using a modifi ed bulbar urethral sling procedure over a period of years. results: all patients were continent postoperatively, with only mild stress leakage in the erect posture in two patients, during a mean follow-up of . months (range - months) and required one or some time two pads per day to remain continent during the daytime. one patient required clean intermittent catheterization for a short period postoperatively. conclusions: th e male bulbourethral sling procedure using a polypropilene mesh is economical and safe but further experience is needed to establish this procedure as an alternative for the treatment of male urinary incontinence. investigation of a teikyo university, tokyo, japan; juntendou university, tokyo, japan introduction and objective: th is study compares the safety and benefi ts of administering anticholinergic agent propiverine hydrochloride in combination with adrenergic alpha- receptor antagonist silodosin (sp group) as therapy for patients diagnosed with benign prostatic hyperplasia with overactive bladder, as opposed to administering silodosin alone (s group). th is study included male patients aged or above who had an international prostate symptom score (i-pss) of or more, an overactive bladder, a qol index of or greater, an overactive bladder syndrome score (oabss) of or more along with an oabss urgency score of or greater, and a maximum urinary fl ow rate of < ml/s. at random, patients were assigned to the sp group, and to the s group. th e sp group was administered mg/day of silodosin along with mg/day of propiverine hydrochloride and the s group mg/day of silodosin only, for weeks respectively. i-pss, qol index, oabss urofl owmetry results, and residual urine were evaluated prior to therapy and , , and weeks post-therapy.results: th ere were no statistically signifi cant diff erences in patient background between the two groups. statistically signifi cant improvements were seen in i-pss total score, qol index, and oabss weeks post-therapy, but there were no statistically signifi cant diff erences between the two groups. both groups refl ected statistically signifi cant improvements in i-pss storage symptom scores and voiding symptom scores, but there were no diff erences between the two groups. analyzing by prostate volume, among those with lower prostate volume (average . ± . mm ), the sp group showed a statistically signifi cant improvement in i-pss total score and oabss as compared to the s "monotherapy" group. no serious side eff ects were shown in either group.conclusion: among benign prostatic hyperplasia patients with overactive bladder, those treated with silodosin alone showed statistically signifi cant improvements in both storage and voiding symptoms, as did those additionally treated with propiverine hydrochloride. results were even more benefi cial when both silodosin and propiverine hydrochloride treatment were used for patients with lower prostate volumes. the effi cacy and safety of fesoterodine in vulnerable elderly patients with overactive bladder takeda h, nakano y, narita h introduction and objective: we evaluated the efficacy and safety of fesoterodine in medically complex vulnerable elderly patients with overactive bladder. in this -week, patients were community dwelling men and women years old or older. patients with oab had scores of less or more on the ves- by nccn (vulnerable elders survey). we evaluated the changes of each parameter before and to weeks aft er the administration of fesoterodine mg per day. th e overactive bladder symptoms score (oabss), ipss were used as a subjective questionnaire for overactive bladder symptoms. we compare between vulnerable elderly group and no-vulnerable elderly groups. statistical comparisons before and aft er the administration were made using the wilcoxon signed-rank test. to examine the relation between oabss and ipss, spearman's testing was used for correlations between independent variables and p< . was considered statistically significant. safety evaluations included self-reported symptoms and post-void residual volume.results: a total of patients were enrolled (mean age . years, . % age years or greater). th e vulnerable elderly patients had high rates of comorbidities, polypharmacy and functional impairment. at week both group had insignifi cantly greater improvements in oabss (p= . ) and ipss (p= . ). adverse eff ects were generally similar.conclusions: fesoterodine improved overactive bladder symptoms not only in no-vulnerable elderly patients, but also in vulnerable elderly patients. the effectiveness and tolerability of fesoterodine mg in "real world" outpatient clinical settings the benefi cial effect of a combination of solifenacin and mirabegron on oab patients persu c, paraianu b, nita g, geavlete p introduction and objective: th e development of a new drug class intended for the treatment of oab patients opened a new and promising era for our patients. th e current study aims to evaluate the eff ects of a combination therapy using an antimuscarinic and mirabegron. we designed a prospective study including oab patients with or without wet episodes. treatment was started with two months of solifenacin mg, then mirabegron mg was added for the next two months. th e patients were evaluated using a bladder diary for three consecutive days at the end of each treatment period. we compared the total number of voidings, the number of urgency episodes and the number of urge incontinence episodes. th e statistical analysis included only the patients who fi nished the whole four month period. a total of fourteen female sprague-dawley® rats weighing - g were used, which were randomly divided into two groups. both the experimental group and the control group, fourteen rats were inserted intrathecal catheter in the spinal l -s segment. seven days later, all rats were catheterized through the bladder dome for saline-fi lling cystometry. in experimental group, seven rats were given intrathecal diff erent concentration ketanserin ( . - . mg/kg) dose-response curves for ketanserin were followed by doi ( . mg/kg) test.in control group, seven rats were given intrathecal normal saline. all rats were intravascularly perfused with % paraformaldehyde aft er the completion of the urodynamic recordings. th e l -s spinal cord were removed and pathological sections and immunohistochemical staining were made. meanwhile, we observed and recorded the distribution of -ht a receptors in the spinal motor neuron. results: th irty-four patients were included in the study. twenty-four of them completed the follow-up. twenty-one were female and were male with an average age of . years ( - years). detrusor sphincter dyssynegia was the most common abnormal urodynamic fi ndings in these patients. th ere was an improvement in bladder capacity, detrusor and sphincter action following de-tethering surgery.conclusion: urodynamics should be considered as a part of preoperative evaluation in all patients with primary tethered cord syndrome to decide the urological aspect of management. urinary bladder reinnervation with creation of a "somato-autonomic" refl ex pathway in rabbits -s ) and detrusor muscle (recipient, s -s ) were located. aft er their resection, intradural anastomosis of donor root to the recipient distal root stub was performed. th ose roots whose stimulation elicited the largest response were always selected. aft er - months (mean months), the artifi cial refl ex arc's function was examined (to date in rabbits). under general anaesthesia, skin segments l -s were peripherally stimulated and then the spinal root above the anastomosis was stimulated. detrusor response was measured using an emg strip electrode and intravesical pressure (pves) monitoring and sphincter response using an emg needle electrode. a root sample from under the anastomosis was resected for histology.results: electromyography confi rmed detrusor response to peripheral skin stimulation in ( %) animals and sphincter response in ( %). five ( %) animals displayed elevated intravesical pressure (pves) up to cm h o. root stimulation induced detrusor and sphincter emg response in ( %) and ( %) rabbits, respectively, and ( %) animals displayed increased pves up to cm h o. micturition was not induced in any animals. with confi rmed detrusor contraction (emg, elevated pves), external sphincter activity was never inhibited. somatic-to-autonomic anastomosis creation was histologically confi rmed in all samples. hind limb paresis occurred in ( %) animals and spinal lesion in ( %).conclusion: lumbar-to-sacral-nerve rerouting is a technically manageable method with donor root fibres verifi ably joining recipient roots. only in a limited percentage of cases, however, can the method achieve positive functional results, i.e. demonstrable detrusor contractions and elevated intravesical pressure. physiological micturition without detrusorsphincter dyssynergia as described in the literature did not occur in our experiment. development in this study, we evaluate the effi cacy of the prototype intravesical pressure sensor integrated into a catheter-like tube and in the rabbit and biocompatibility of ecofl ex® as a packing materials in the rats. th e catheter type wireless pressure sensor is manufactured by direct inserting the prototype sensor into the port split from the feeding tube between the sensor and the port so the tube could hold the bladder pressure. th e tip of the tube is results: th e measured resonance frequencies and the pressure data converted from those signals were compared to the reference pressure data obtained from a conventional cystometry. th e scale factor of the sensor to correlate the prototype sensor resonance frequencies to the reference pressure data is - . kpa/ mhz (=- . mhz/kpa), comparable to the result of its in-vitro measurement, a pressure responsivity of - . mhz/kpa. increased macrophage activity and mif in the bladder were revealed in the early phase aft er implantation of ecofl ex®. however, decreased macrophage activity and mif in the bladder were observed in the later aft er implantation. furthermore, decreased infl ammatory cytokines were also observed at that time. in this study, we demonstrated the feasibility of the catheter type which is non-invasive method and easy to apply to patients in actual examination. further investigation to overcome the limitation of the prototype intravesical pressure sensor is necessary for the application to the real life practice. in addition, ecofl ex is biocompatible materials for the implanted medical devices in the bladder. introduction and objective: urethral pressure profi le (upp) is a primary method for evaluating urethral continence function in human beings. however, upp recording in female rat, a widely used animal model, has been challenging because of the animal's small body size. th is study reports a novel method for recording upp in female rats. seventeen anesthetized female rats were studied. leak-point pressure (lpp) data of rats were included; the other rats were excluded due to animal die or abnormal urogenital organ. upp curves were recorded using a modifi ed method of water-perfusion catheter system, with the lateral hole facing -, -, -, -o' clock positions respectively in a randomized sequence. lpp, functional urethral length (ful), and maximum urethral close pressure (mucp) were the analysis parameters. in the era of aging society, an easy-to-use screening tool for voiding dysfunction refl ecting to activity of daily life is much-needed. bladder diary (frequency volume chart) is gold standard to check urine storage status, but diffi cult for elderly to measure and record all the time. urofl owmetry is useful to check voiding status, but limited to clinics or hospitals. we developed a portable device, p-urofl owdiary®, which records every urine fl ow with bladder diary at home. we elucidate the feasibility and the usefulness of this device. materials and methods: p-urofl owdiary® records voiding time and date, length of voiding, voided volume, fl ow rate and self-evaluation of every urination for a couple of days with gravimetric determination method. th e device consists of a disposable urine cup, a load cell and the circuit board on which microcomputer, clock, acceleration sensor, audio guidance, bluetooth and sd card mounted. self-evaluation of every urination is recorded by pushing one of the four buttons on the body-side, which represent "very good", "good", "bad" and "very bad". th e data in sd card are analyzed using the dedicated soft ware. accuracy of the measurement has been approved in a comparative study of the device and an existing urofl owmeter. th e infl uences of hand shaking are canceled by acceleration sensor and are smoothed by the soft ware.results: th e feasibility study were done under the approval of irb of nara medical university. first semester study in healthy volunteers focused on user-friendliness. th e results were almost acceptable except for female volunteers, especially in elderly. th e urine volume and peak fl ow rate as well as self-evaluation were linearly related in volunteers who measured multiple sessions. a clinical trial in patients with voiding dysfunction is in operation in seven institutions, and summarized data will be reported.conclusion: p-urofl owdiary® is light and small and easy-to-use at home even in elderly. although its practical usefulness as voiding diary have been proved, the usefulness as urofl owmetry and self-evaluation of every urination is not clarifi ed yet. however, p-urofl owdiary® seems to be a useful tool for screening of voiding dysfunction as well as assessment of therapeutic performance. to determine the continence position and the contributory factors in the female canine urethra. materials and methods: by using adult female dogs, we determined the continence function of each mm intervals of the urethra when we excluded these segments by progressively inserting a fr catheter and recording the abdominal leak-point pressure (alpp). th e urethral pressure profi le (upp) and alpp were determined before and min aft er occlusion of the abdominal aorta. each urethra specimen was split into segments averagely and the histological components were determined. th e relationship between the histological components and the urodynamic parameters were analyzed.results: th e striated muscle confi ned to the distal / urethra. th e anatomic structure of the proximal / urethra was found to be quite homogenous, which surrounded by circular smooth muscle. th e connective tissue constituted with abundant collagen fi bers and vascular plexus was most voluminous in the distal / urethra, and relatively richer near the bladder neck. upp had pressure zones: high pressure zone corresponding to the distal / urethra and low pressure zone corresponding to the proximal / urethra. alpp decreased sharply when exclusion progressed over the distal / urethra. alpp and mucp decreased about % and % aft er occlusion of aorta, respectively. th e distribution of the urethral pressure or pressure change is in accordance with the location of the striated muscle sphincter; there is no linear correlation with any other particular tissue component in the diff erent urethral segments.conclusion: th e strongest continence function locates at the distal / urethra with striated muscle layer; the remaining / proximal urethra lacking striated muscle has only weak continence function. striated muscle is the predominant contributory factor to continence and the other components like vascular sinusoids, smooth muscle, collagen fi bers are minor contributory factors. urodynamics in children: a -year experience persu c, mirciulescu v, geavlete p introduction and objective: urodynamics, in the modern defi nition of the term, developed rapidly from a state of the art gadget into an extremely useful tool in the armamentarium of the modern practitioner, who is no longer accepting the clinical exam as the mainstay of the diagnosis, but requires more and more in-depth data from paraclinical investigations.our study aims to review the particular aspects of the urodynamic examination in children. we retrospectively reviewed the data from our archive in patients aged less than years old, examined in our department in the last years. for analysis purposes, patients were divided into two groups, less than years old and more than years old, considering that compliance during the examination improves greatly with age. a total of children were evaluated, in the fi rst group and in the second. we noticed changes in the procedure over time, due to the lack of standardization.results: th e main conditions behind the urinary symptoms were spina bifi da, myelomeningocele, cerebral palsy, spinal cord injury, frontal dementia. children with chronic conditions showed a signifi cantly better compliance during the examination, providing "cleaner" traces and shorter examination times. in cases ( %), the results of the exam were considered unreliable. in the fi rst group, sensations are recorded in only cases ( %), the other traces are marked as pain or crying. in the second group, the sensations are reported by children ( %). in six cases ( %), more than one examination was available, and the intra-individual variability was higher than in adult patients. urodynamics in children is a challenging, yet useful investigation, which requires both a state-of-the-art equipment and dedicated and highly professional staff . th e main question when thinking about urodynamic testing in children is not whether it can be done, but if it is really needed for the management of the patient, keeping in mind not only the benefi ts but also the potential harm that it can do. the underactive bladder syndrome: a single center experience persu c, geavlete p introduction and objective: detrusor underactivity (uab syndrome) is defi ned as a contraction of reduced strength or duration, leading to obstructive symptoms of the lower urinary tract. our study aims to review our clinical experience with such cases. we reviewed the electronic fi les of the patients diagnosed with uab aft er urodynamics in the past years. our review focused on the referral diagnosis and other associated conditions, as well as on the symptoms reported by the patient during history taking or the examination itself. we tried to correlate symptoms with the parameters obtained during urodynamics. th e initial treatment offered was also recorded.results: a total of patients ( males, females) were analyzed. th e most common referral diagnosis was bladder outlet obstruction ( pts - %), followed by oab syndrome ( pts - %) and other conditions ( pts - %). most patients reported signifi cant dysuria ( pts - %), sensation of incomplete voiding ( pts - %) and the need for straining in order to void ( pts - %). other reported symptoms include recurrent utis ( pts - %), urgency ( pts - %), frequency ( pts - %) and urinary incontinence ( pts - %). th e initial treatment consisted of self-catheterization ( pts - %), α blockers ( pts - %), suprapubic cystostomy ( pts - %), double voiding ( pts - %) and neurostimulation ( pts - %).conclusion: th e most common causes for uab include neurogenic conditions and obstructive symptoms associated with aging. th ere are no specifi c symptoms to support this diagnosis but some might suggest it stronger than others. urodynamic evaluation is mandatory to assess the parameters of this condition. underactive bladder: clinical features, urodynamic parameters, and treatmenthoag n, gani j introduction and objective: underactive bladder is a complex clinical condition that remains poorly defi ned in the available literature. we aim to determine its prevalence among those with voiding dysfunction, presenting symptoms, risk factors, urodynamic fi ndings, and treatment undertaken. a retrospective chart review was conducted on consecutive urodynamic studies performed for voiding dysfunction between and , to identify patients with detrusor underactivity. underactive bladder was defi ned as bladder contractility index less than . charts and urodynamic tracing were examined for patient demographics, suspected risk factors, presenting symptoms, urodynamic parameters, and treatment undertaken.results: th e prevalence of underactive bladder in this series was % ( / ). average age was . (range - ). women represented . % ( / ) of patients. th e most common reported symptoms were: urinary urgency ( . %), weak stream ( . %), straining ( . %), nocturia ( . %), and urinary frequency ( . %). prior pelvic surgery and prior back surgery was noted in . % and . %, respectively. most common management was intermittent self-catheterization at . %, followed by observation/conservative treatment at . %, and sacral neuromodulation at . %.conclusion: underactive bladder is common, yet precise diagnosis and treatment remains nebulous. th ere exists signifi cant overlap in symptoms compared to other bladder disorders, and urodynamic evaluation is useful in determining those patients with impaired detrusor contractility. th is will help prevent mismanagement of these patients with surgery or medical therapy that may worsen their condition. th ere remains much work to be done to better understand this condition, and establish optimal management for patients. what is the relationship between the size of a patient's medical notes and their fitness?birring a, jelski j, burns-cox n introduction and objective: assessment of patients' co-morbidities is necessary when considering treatment options. comorbidity tools exist but aren't always used outside of studies. clinicians may infer a patient's fi tness from the size of their notes. th is is particularly apparent in multidisciplinary meetings when the patient, and sometimes the referring clinician, is absent. we aim to establish if any correlation exists between the thickness and weight of medical notes and patient comorbidity. th ickness and weight of medical notes was measured for consecutive patients admitted to a urology/surgical ward. comorbidity was assessed using the charlston comorbidity index (cci).results: mean (and range): age ( - ) years; thickness . ( . - . ) cm; weight ( - ) g; cci . ( - ). male to female ratio : . pearson's correlation (r) between thickness and cci was . (p= . ). th e correlation between weight and cci was . (p= . ). regression analysis showed, an . cm increase in thickness gives in a -point increase in cci (p= . ); and a g increase in weight gives a -point increase in cci (p= . ).conclusion: th ere is a statistically signifi cant relationship between the thickness and weight of a patient's notes and their cci (p= . ), but the strength of this relationship is extremely weak (r= . and . ). on average, an . cm or kg diff erence in size has only a -point diff erence in cci. th is change may reduce the -year survival of a patient by as little as %. size of notes is a highly misleading indicator of fi tness. patients should have a formal comorbidity assessment before deciding treatment options.did you know? siu academy... the endorsed event programme allows approved webcasts from high-quality meetings around the world to be presented and shared on the portal.off ers a wide range of content eligible for selflearning cme credits non-accredited content is eligible for self-learning credits. 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equal voice in this influential organization. we believe that each member can contribute the knowledge and experience needed to forge valuable links between urologists, and between developed and developing nations. by working together, our members carry on the tradition of creating positive change in a changing world. as a new member, you will be a partner in the one urological association dedicated to creating sustainable educational projects and providing and improving urological resources worldwide.members are able to vote for siu leadership, organize siu-endorsed educational activities, become involved in the congress scientific programme, as well as contribute to various siu academy programmes. we strive to make each member feel valued, respected, and supported.the siu network, both virtual and live, is an unparalleled pool of global contacts. siu brings urologists together. key: cord- -v m l wz authors: nan title: neurocritical care society (th) annual meeting date: - - journal: neurocrit care doi: . /s - - - sha: doc_id: cord_uid: v m l wz nan in this exploratory analysis, csf levels in the progesterone treated group were variable and not as supratheraputic compared to serum levels. this study highlights an additional factor that needs to be considered in the designing of clinical trials in tbi. not only does the heterogeneity of the injury and subsequent outcome measures need to be refined, but the biomarker of pk levels also needs to be analyzed in csf as well as serum to determine if the treatment is reaching the target organ, the brain. arctic ground squirrels (ags) are extreme hibernators capable of withstanding months of freezing temperatures by suppressing metabolic rate. hibernation is characterized by hypoxia and low cerebral blood flow and interrupted by bouts of arousal in which perfusion is quickly restored. curiously, ags do not experience reperfusion injury which is hypothesized to be reflected in altered transcriptional signatures in an in vitro model of reperfusion injury. to investigate the influence of ischemia/reperfusion on ags neuronal stem and neural progenitor cells (nsc/npcs), we exposed ags and murine nsc/npcs to control conditions, hypoxia, oxygen and glucose deprivation or glucose deprivation alone or following return to normal conditions to model reperfusion. cell viability and cell cycle state were assessed by automated cytometry; metabolic phenotype by in vitro oxygen consumption and extracellular acidification rate. to determine novel genes involved in ags resilience to reperfusion injury, a cdna library was constructed in a mammalian expression vector and introduced into murine nscs that were then assayed for viability after ischemia/reperfusion. ags nsc/npcs demonstrated marked resistance to ischemia/reperfusion injury compared to murine nsc/npcs. this survival phenotype is associated with suppressed mitochondrial oxidation and altered cell cycle regulation. ags genes regulating mitochondrial function strongly modulated murine nsc/npc viability following ischemia/reperfusion injury. a dynamic ability to suppress mitochondrial oxidation may underlie resilience to reperfusion injury in ags by promoting a quiescent cell cycle phenotype. development of therapeutic agents suppressing mitochondrial oxidation may induce a protective phenotype and promote survival following reperfusion injury. high throughput imaging of motor system connectivity in the mouse brain. stroke results in profound alterations to architecture in the brain, particularly the corticospinal tract (cst). some plasticity may contribute to functional recovery, while other changes may be maladaptive. studies of cst connectivity have been limited by standard imaging methods which do not allow visualization and analysis of global axonal connectivity in the brain. we employed two novel imaging methods to visualize axonal projections to forelimb musculature. first, a pseudorabies viral (prv) vector carrying green fluorescent protein (gfp) was injected into the left forelimb flexor in naïve - week-old c mice. prv was transported retrogradely and transynaptically, labeling neurons in the motor cortex and other regions of interest. whole slide imaging was performed using an automated slide scanner (nanozoomer, hamamatsu photonics k.k., hamamatsu city, japan) producing images of serial coronal sections, allowing visualization of multiple levels of the brain in a single slide image. for serial two-photon tomography (stpt), utsw whole brain microscopy facility used a tissuecyte imaging system (tissue vision, somerville, ma) which uniquely performs automated sectioning and fluorescent imaging of the brain to produce -dimensional images with micronlevel resolution. this allows for unprecedented visualization of axonal connectivity in the whole brain. we have imaged motor systems in the brain of uninjured mice using two different methods, each with distinct benefits. whole slide imaging allows for quantification of regions of interest in the brain on a single slide, while stpt produces a highly detailed image that improves our understanding motor systems in -d space. future directions will investigate changes in connectivity following stroke injury and during recovery, allowing a greater understanding of the complexity of plasticity and how it contributes to beneficial and pathological circuit remodeling after injury. andexanet alfa (anxa) is a modified recombinant factor xa (fxa) derivative that sequesters direct fxa inhibitors and reverses their anticoagulation effects. non-specific prothrombin complex concentrates (pccs) have been proposed as potential reversal strategies. the objective of these studies was to compare -factor (bebulin) and -factor (kcentra®) pccs, approved for reversal of warfarin, with anxa in reversing anticoagulation effects of rivaroxaban in a rabbit model of bleeding. nzw rabbits were treated with rivaroxaban (iv, mg/kg) and min later, either pccs ( -factor pcc: or mg/kg; -factor pcc: , , or iu/kg) or anxa ( or mg/rabbit) was administered iv. liver injury was then induced with -cm incisions following laparotomy, and blood loss was measured for min. plasma concentrations of unbound (active) and total rivaroxaban, as well as pharmacodynamic (pd) parameters (anti-fxa activity, pt, and aptt) were determined. anxa reduced blood loss in rivaroxaban-anticoagulated rabbits to levels seen in non-anticoagulated rabbits. in rabbits treated with anxa, anti-fxa activity and unbound rivaroxaban were reduced dosedependently by > % and > %, respectively, within minutes, and both parameters correlated with reduction in blood loss. in contrast, -factor or -factor pccs had no significant effect on any of these markers in rivaroxaban-anticoagulated rabbits. anxa effectively reversed the anticoagulation activity of rivaroxaban in a rabbit model of bleeding. in contrast, pccs showed no reversal activity as assessed by blood loss or pd markers. these results suggest that use of non-specific pccs as reversal agents for direct fxa inhibitors are not likely to be as effective as specific reversal agents that target fxa inhibitors. investigation of anxa vs. pcc to reduce hematoma expansion in models of intracranial hemorrhage is warranted. outcomes after resuscitation from cardiac arrest (ca) remain poor. preventable secondary injury from ongoing brain tissue hypoxia (bth) may worsen injury burden. unfortunately, markers to allow individualized, real-time care optimization are lacking. we performed a randomized crossover trial in a swine model of opioid-induced ca to ) determine the prevalence of bth with standard care (stdc), and ) test whether neuromonitor-guided goal-directed care (ngdc) can prevent bth. female swine ( - kg) were anesthetized with propofol and fentanyl. we placed femoral arterial and venous sheaths, a continuous cardiac output pulmonary artery catheter (edwards lifescience) and a right frontal intracranial access bolt (hemedex) with probes for brain tissue oxygen (pbto ), pressure (raumedic), microdialysis (mdialysis ), cerebral blood flow (cbf) (hemedex), and an -contact electroencephalographic depth electrode (adtech). we induced apnea with mcg/kg fentanyl, extubated the animal and began acls min after apnea. after h stabilization, animals with return of spontaneous circulation (rosc) were randomized to three alternating h care blocks: stdc (mean arterial pressure> mmhg, oxygen saturation - %, cardiac output> % baseline) or ngdc (pbto > mmhg, cbf> ml/ g/min). animals were euthanized at h post-rosc. our primary outcome was the effect of care block on pbto , which we analyzed at min resolution using generalized estimating equations with robust standard errors. overall, of animals achieved rosc after ± min. pbto was higher during ngdc than stdc (p< . ) and did not differ during ngdc from pre-arrest. pbto was < mmhg more during stdc than ngdc ( % of minutes vs %, p< . ). cbf was lower during ngdc than stdc (p< . ), and lower in both arms than pre-arrest (both p< . ). brain tissue hypoxia was common in this cardiac arrest model and prevented by neuromonitor-guided goal-directed care. lower cbf and higher pbto during goal-directed care implies preserved hypoxic cerebral vasodilation and diffusion-limited oxygen delivery. future work will incorporate electroencephalographic and metabolic injury markers. sage- is a proprietary formulation of the endogenous neurosteroid allopregnanolone, being studied as a potential adjunctive therapy for the treatment of super-refractory status epilepticus (srse) . srse refers to a condition of persistent seizures that have failed treatment with first-, second-and third-line treatments. in preclinical models, prolonged seizures reduce the surface expression of synaptic gabaa receptors, exacerbating neuronal excitability and limiting target sites for gabaergic treatments (eg. benzodiazepines). here we present preclinical data describing the pharmacological properties of sage- that support its further development as a potential treatment for srse. gaba-evoked currents were examined in vitro with whole cell patch clamp recordings in cells expressing -pilocarpine model of refractory status epilepticus (pouliot ) was used to examine in vivo anticonvulsant activity. sage- or pentobarbital was administered intravenously minutes after the onset of pilocarpine-induced seizures, a time point when benzodiazepines are ineffective in animal models (pouliot ). sage- potentiated both synaptic-vitro, with ec s of nm and nm, respectively. the concentration-gabaa receptors by sage- was , -fold more potent than that observed with pentobarbital alone. when sages were also observed in the rat model of rse. when sub-active doses of sage- and pentobarbital were combined, electrographic seizure activity was significantly reduced. in vitro, sage- potently modulated both synaptic-type and extrasynaptic-type gabaa receptors, and the maximal potentiation at these receptors was further augmented by the co-application of pentobarbital. this enhanced in vitro potency and maximal effect at gabaa receptors provides further support for the development of sage- as a potential treatment for srse. vasospasm has long been considered the primary mechanism underlying delayed cerebral ischemia (dci) in subarachnoid hemorrhage (sah), but increasing evidence shows that other processes such as cortical spreading depressions and inflammation. we propose that abnormal neural activity in the form of epileptiform abnormalities, we term ictal-interictal continuum abnormalities (iicas), may contribute to dci. these abnormalities may increase metabolic demands in injured brain tissue, thereby contributing to metabolic crisis and secondary neuronal injury. here, we investigate whether the presence of iicas predict dci development. we analyzed eeg reports from icu patients with moderate-severe non-traumatic sah. continuous eeg data was recorded with daily review to identify electrographic seizures and interictal patterns. we tallied daily seizures, sporadic epileptiform discharges, lateralized or generalized periodic discharges (lpds and gpds), and lateralized or generalized rhythmic delta activity (lrda and grda). delayed cerebral ischemic events were also marked. cumulative distribution curves and iica-to-dci time plots were calculated. iicas are more prevalent in patients who develop dci, especially when they begin several days after the onset of sah. all iica types except generalized rhythmic delta activity occur more commonly in patients who develop dci. in particular, iicas that begin later in hospitalization correlate with increased risk of dci (lrda day , ed day , lpds day , gpds day ) most iicas also precede the onset of dci. we next trend features of discharges to identify those most closely associated with dci and will present our preliminary findings. iicas represent a new marker for identifying early patients at increased risk for dci. moreover, iicas might contribute mechanistically to dci and therefore represent a new potential target for intervention to prevent secondary cerebral injury following sah. up to % of patients resuscitated from cardiac arrest remain in a coma, and the ability to predict longterm neurologic recovery in these patients is limited. quantitative analysis of electroencephalography (qeeg) is objective and may facilitate outcome prediction. consecutive patients with hypoxic-ischemic coma were enrolled. continuous eeg was obtained on all patients. eeg was post-processed and analyzed by fourier transform. spectral analysis was conducted on artifact-free contiguous -minute eeg epochs from each hour. whole band ( -- hz) --suppression ratio were computed as quantitative metrics of eeg for the entire eeg recording, and then statistically compared during the last hours of eeg. sedation, level of arousal, and body temperature were also analyzed. good outcome (good neurologic outcome, gno) was defined as consciousness recovery at any point in the acute hospitalization. ten subjects were included in the study, with ceeg durations ranging from - hours of recording. the mean age was . years ( - ). there were significant differences in alpha power ( . ( . - . ) vs . ( . - . ), median (iqr), p< . , gno vs poor neurologic outcome [pno] ), delta power ( . ( . - . ) vs . ( . - . ), median (iqr), p= . , gno vs pno), burst suppression ratio ( . ( . - . ) vs . ( . - . ), median (iqr), p= . , gno vs pno), and multiple measures of variability between gno and pno patients. quantitative spectral analysis of continuous eeg may be predictive of consciousness recovery in patients with hypoxic-ischemic coma. higher alpha power, lower burst suppression ratio, and higher variability were all correlated with good outcome. because the media plays an important role in educating the public and impacting public perception on medical topics, we sought to evaluate whether mainstream media provides education or misinformation to the public about brain death through review of articles on two recent highly publicized brain death cases: ) the jahi mcmath case, in which a teenage girl was declared brain dead and her family refused to allow organ support to be discontinued; and ) the marlise muñoz case, in which a pregnant woman was declared brain dead and the hospital refused to terminate organ support until they were ordered to do so by a judge. media websites of using the search terms, "jahi mcmath" and "marlise muñoz." each article was evaluated to determine whether it contained ) teaching points, or ) misinformation, defined as misleading, incomplete, or incorrect information. we reviewed unique articles. the subject was referred to as being "alive" or on "life support" in % ( ) of the articles, % ( ) of which also described the subject as being brain dead. a definition of brain death was provided in % ( ) of the articles. only % ( ) of the articles noted that organ support should be discontinued after brain death declaration unless a family has agreed to organ donation. reference was made to wellarticles and % ( ) of these implied both patients were in the same clinical state. mainstream media provides poor education to the public on brain death. because public understanding of brain death impacts organ and tissue donation, it is important for physicians, organ procurement organizations, and transplant coordinators to improve public education on this topic. neurocrit care ( ) :s -s post-operative hemorrhage: a possible predictor of delirium in brain tumor patients post-operative delirium after brain tumor resection is frequent, difficult to manage, and may increase chart review of patients admitted to the neurologic intensive care unit (nicu) after brain tumor resection. we also evaluated the effect of agitated delirium on length of stay. medical records of nicu admissions form - were reviewed to identify cases and controls. cases were defined as patients with no pre-existing neuropsychiatric history who experienced significant agitated delirium post-operatively, defined by requirement for treatment with neuroleptics (quetiapine or dexmedetomidine) < hours after surgical resection. we compared these patients to a control group comprised of randomly selected patients admitted after brain tumor resection who did not experience agitated delirium. in a multifactors: sex, age, tumor location, pathology, postpost-operative hemorrhage, use of steroids and prophylactic anti-epileptics, particularly levetiracetam. there were cases and controls. multivariate analysis revealed male sex (o.r . ; % ci . - . ; p= . ) and a post-operative course complicated by hemorrhage within the resection cavity (o.r . ; % ci . - . ; p< . ) as significant predictors of agitated delirium. the icu length of stay was significantly longer in those with agitated delirium ( . ± . days vs. . ± . days; p< . ). neurointensivists caring for post-operative patients with brain tumor may consider resection site ctor for developing agitated delirium. future studies may investigate -operative bleeding and delirium and the long term outcome of these patients. cardiac arrest is a leading cause of death and disability, and predicting outcome in these patients is a challenge. optic nerve sheath diameter (onsd) on brain ct correlates closely with intracranial pressure. therefore in this study we studied correlation between onsd measured on the initial brain ct in patients after cardiac arrest and outcome. this is a retrospective study of patients with cardiac arrest admitted to the medical intensive care unit at our hospital between and . pati arrest were included. demographics, neurological status on arrival and day and outcomes were collected. onsd on brain ct was measured bilaterally mm behind the optic nerve head and averaged for each patient. a total of patients were included. mean age was ± . years, patients ( %) were male. patients ( %) suffered out-of-hospital cardiac arrest. mean glasgow coma scale (gcs) on admission was . ± . (range - ; median ). return of spontaneous circulation (rosc) time was . ± . intervention. patients ( . %) underwent therapeutic hypothermia. patients ( . %) had seizures. average modified ( . %) had a good outcome (mrs - ). average duration from rosc to ct was . ± . days. mean onsd in patients with gcs - at day was . ± . mm, while in those with gcs - at day , onsd was . ± . mm (p= . ). mean onsd in patients with mrs - at discharge was . ± . mm, while in those with mrs - was . ± . (p= . ). there does not appear to be a significant correlation between the onsd o cardiac arrest and outcome at day . traumatic brain injury (tbi) is a major public health problem. while the association between subarachnoid hemorrhage and systolic dysfunction (sd) has been established, the effect of tbi on the incidence of early sd in previously healthy patients following moderate-severe tbi, and ) to describe the longitudinal change in we conducted a prospective cohort study among mild and moderate-severe tbi patients admitted to a level trauma center with these inclusion criteria: ) age < years, ) no severe non-tbi injuries, ) no prior cardiac disease, and ) minimal comorbidities. transthoracic echocardiograms were performed at < hours, - days, and - days following tbi. systolic function was assessed using fractional shortening (fs), and sd was defined as fs< %. descriptive statistics were used to compare the mild and moderate-severe tbi groups. multivariable linear regression was used to compare fractional shortening between groups. patients were studied ( mild tbi and moderate-severe tbi). both groups were young ( . years mild tbi and . years moderate-severe tbi) and mostly male ( % mild tbi and % moderatesevere tbi). early sd was present in ( %) moderate-severe tbi patients and ( %) mild tbi patients (p< . ). on multivariable regression, moderate-severe tbi was associated with an absolute . % reduced fs compared to mild tbi ( % ci . % - . %, p= . ). all patients with early sd recovered to normal systolic function by - days injury ( figure ). sd is common early after moderatehospitalization. tbi severity is independently associated with worse systolic function. early echocardiography is a safe, applicable, and feasible procedure following tbi and may aid clinicians with hemodynamic management post tbi. sophie samuel. department of pharmacy. memorial hermann medical center, houston, tx, usa. paroxysmal sympathetic hyperactivity (psh) is a neurological condition that occurs most frequently after traumatic brain injury (tbi). sympathetic hyperactivity can manifest as increased heart rate, blood pressure, respiratory rate, temperature, sweating and posturing activity. in , a consensus statement and probability of diagnosis. the objective of this study is to report the incidence, frequency and severity of psh symptoms in the acute setting after tbi using the new diagnostic criteria. this was a retrospective study from july -august . included were all adult patients admitted to a tertiary care intensive care unit with a primary diagnosis of tbi and a length of stay longer than days. symptoms were recorded. the most frequent symptom was tachycardia ( %), followed by tachypnea ( %), hypertension ( %), symptoms occurring simultaneously and % had symptom - ) vs ( - ); p= . ] and at day ; [ ( - ) vs ( - ); p< . .] medications often used to control symptoms included, anti-pyretics, opioids, beta--- ) vs ( - ); p= . ], but no difference in mortality. symptoms of sympathetic hyperactivity were seen commonly after tbi in the acute setting. using a admitted with a hospital length of stay greater than days. hypertonic saline (hts) appears to be more effective than mannitol in reducing raised intracranial pressure (icp) after severe traumatic brain injury (tbi). in this study we investigated which agent had superior combined effects on icp and cerebral perfusion pressure (cpp). the brain trauma foundation tbi-patients who received only hts were identified and matched with patients who received mannitol only ( : and : match). the two groups were matched for age, pupillary reactivity, glasgow coma scale (gcs), ct abnormality, craniotomy and occurrence of hypotension on day . univariate analysis was performed to compare combined average and duration of icp> mmhg (icphigh) and cpp< mmhg a total of patients with severe tbi, who received only hts were identified and matched with ( : ) and ( : ) patients who received mannitol only. in the : group hts patient was excluded, as there was no corresponding match in mannitol group. the mean age, gcs, incidence of abnormal pupils, hypotension, abnormal ct, craniotomy and day of icp insertion were similar in the groups. there was no difference in number of days of icp monitoring (p= . , . ; : , : groups). osmolar doses were comparable; all patients in hts group received % hts except one who received . %. in : match, number of days with cpplow ( . ± . vs. . ± . , p= . ) was significantly lower in the hts group. in p= . ) were significantly lower in the hts group. these results were reproduced in the : analyses. hts is superior in its combined effect on icp and cpp after severe tbi when compared to mannitol. statins constitute a class of medications commonly used in the treatment of elevated cholesterol. however, in experimental studies statins also have other non-cholesterol mediated mechanisms of action, which may have neuroprotective effects. the purpose of this study was to determine if administration of atorvastatin for days after injury would improve neurological recovery in patients with mild traumatic brain injury (mtbi). the hypothesis was that atorvastatin administration would reduce post-concussion symptoms and also -injury would be safe. patients with mtbi were placebo for days starting within hours of injury. assessments of post-concussion syndrome, postthe rivermead post-concussion symptoms questionnaire at months was the primary outcome. enrollment in the trial was stopped early because of difficulty in recruiting sufficient numbers of subjects. patients with mtbi were enrolled; patients received atorvastatin and received placebo. the mean rivermead score was . for the atorvastatin group compared to . for the placebo group at months post-injury [f( , ) = . , p=. )]. the change in the rivermead score between baseline and months was also analyzed. the mean change in score was a decrease of . for the atorvastatin group and . for the placebo group [f( , )=. , p=. ]. no serious adverse events occurred, and there was no significant difference in the incidence of adverse events in the two treatment groups. atorvastatin administration for days post-injury was safe, but there were no significant differences in neurological recovery after mtbi with atorvastatin. association between comorbidities, nutritional status, and anticlotting drugs and neurological outcomes in geriatric patients with traumatic brain injury an essential part of the management of traumatic brain injury (tbi) is the mitigation of secondary insults to the brain such as sustained increases in intracranial pressure (icp). it would be beneficial to be able to predict increased icp so as to facilitate safe transport of patients. given the role of neuro-inflammation in increases in icp. after admission. receiver operating characteristic (roc) curves were used to compare the predictive elevation of icp above or mmhg for min or more in the following hours. serum samples from patients were matched to subsequent hour periods of monitoring.. ni-vs the predictive capacity of a combined model of ni-vs and il level over ni-vs alone in predicting icp elevation to > mmhg ( . vs . , p mmhg ( . vs . p < . ). levels when combined with physiological data. even without invasive monitoring, predictions about measurements. head injury neuroworsening (nw) after traumatic brain injury (tbi) is a major cause of added morbidity, however, there is no reliable way to predict nw. we hypothesized that autonomic nervous system dysfunction (ans) measured by analysis of plethysmograph variability (ppgv) in the first hour after presentation may predict nw in the initial hours after tbi. and head abbreviated injury score(ais)> . patients with systemic trauma were excluded. nw was defined as any of the following occurring in the first hours: new asymmetric pupillary dilatation (> mm), point gcs decline, interval worsening of ct scan as assessed by the marshall score, or requirement for neurosurgical intervention. the beat-to-beat variation of the ppg, and ppg morphologic features were calculated to quantify the ans impact on the physiological status. multivariate stepwise logistic regression was used to develop predictive models of nw. there were patients (mean age years old, gcs , iss , % women) who met criteria between december and may . nw occurred in ( %) patients. ppgv analysis at (ppg ) and (ppg ) minutes post-admission demonstrated predictive capability for nw(p< . ). ppgv was able to better discriminate nw as compared to a baseline model of age, sex, initial vs (roc . v. . , p= . ). ppgv better discriminated future nw as compared to the model of age, sex, admission vs and gcs (roc . v . ,p= . ), and marginally better than a model combining admission vs, gcs, and marshall score on ct(roc . v . ,p= . ). ans dysfunction assessed by continuous ppg waveform analysis in the first hour represents a nonclinical factors to more accurately predict nw, potentially leading to automated algorithms for earlier therapeutic interventions. tanzania severe traumatic brain injury (tbi) is the number one cause of death and disability among young adults worldwide. formulation and subsequent adherence to the brain trauma foundation (btf) guidelines has been associated with reduced mortality after severe tbi. in this study we studied epidemiology and treatment of severe tbi at a tertiary referral hospital in tanzania in reference to the btf guidelines. patients with tbi hospitalized at bugando medical centre, a tanzanian tertiary referral hospital were recorded in a prospective registry. demographics, cause of trauma, clinical characteristics, hospital care, and mortality were recorded for days and on the day of discharge. between september and october , of patient . %) were hospit pressure (icp) monitoring were not performed for any patient. thirty-eigh - pre-hospital and routine icu care, ct imaging, blood pressure and icp monitoring are underutilized or unavailable in the management of severe tbi in the tertiary referral hospital setting. tbi associated mortality is significantly higher than that in high-income countries. improving outcomes after severe tbi will require concerted investment in pre-hospital care as well as improvement in availability of neuroimaging, icu resources and expertise in multidisciplinary care. establishment of comprehensive traum elevated intracranial pressure (icp) is thought to mediate secondary brain injury by decreasing cerebral perfusion pressure (cpp) and reducing cerebral blood flow. clinical trials targeting icp thresholds have not demonstrated benefit. we hypothesized that stratifying elevations in icp based on their effect on cpp would be feasible with the use of continuous, time-resolute neuromonitoring data. we studied a convenience sample of five patients undergoing intracranial neuromonitoring after severe traumatic brain injury per our institutional protocol. patients had a parenchymal icp monitor time-synced with continuous arterial blood pressure. waveform data were recorded into moberg cns monitors, and second-bywere identified and their duration was measured along with cpp. elevations were stratified into those that exhibited a reciprocal decrease in cpp (icp[neg] ) and those with stable or elevated cpp (icp [preserved] ). the mean patient age was ; three were male. a total of individual elevations in intracranial pressure were observed over a monitoring duration of , minutes. we found icp elevations that reciprocally decreased cpp (icpneg) were identifiable using bedside neuromonitoring devices, and that these elevations resulted in a cpp drop of nearly mmhg, despite a similar maximum icp despite a shorter duration. the majority of these icp elevations occurred in patients with poor outcome, and may represent a target for aggressive icp lowering therapy. mild traumatic brain injury (mtbi) is defined as an initial glasgow coma scale (gcs) - . current recommendations include a follow-up computed tomography (ct) scan of the head prior to discharge. often, imaging and neurological exam remains stable, questioning the role of routine repeat imaging. a retrospective chart review was completed on tbi patients evaluated at a level trauma center between august and december . inclusion criteria included: initial gcs - , blunt head injury, and available repeat imaging. exclusion criteria included gcs < , penetrating trauma, those that required immediate surgery, or those without repeat imaging. a total of patients were included in the analysis. statistics were done with mann-u whitney or chi-square testing. age was . ± years. there were males and females. the most common mechanism was falls ( . %), followed by motor-vehicle collision ( . %), motor-cycle accident ( . %), assault ( . %), pedestrian--related ( . %). polytrauma occurred in . %, better, . % were stable, . % were worse. only patients ( . %) exhibited neuro-exam changes, where patients received repeat imaging which ultimately demonstrated stable findings. ultimately, only one patient required a neurosurgical procedure, an external ventricular drain, due to significant decline. age, gender, mechan neuro-exam changes. on the other hand, neuro-exam changes significantly correlated with ct changes (p = . ). repeat imaging tend to show worse findings when associated with neurological changes. on the other hand, results for repeat imaging were variable without neurological changes and generally did not alter repeat imaging is only warranted for neurological changes that may necessitate a neurosurgical procedure. create a meaningful tool, we explored family members' and physicians' perspectives on prognosis communication during goals-of-care discussions for citbi patients employing mixed-methods. we conducted semi-structured interviews with citbi surrogate decision-- trauma centers, and attending physicians representing geographic (northeast,mid-atlantic,south,west,midwest] and subspecialty diversity (neurocritical care,neurosurgery,trauma,palliative care). two independent reviewers analyzed transcribed interviews using deductive and inductive approaches (nvivo-software). the sample size was determined by theme saturation. prognosticated outcomes expressed as percentages, and % preferred prognosis in a "more direct" manner. surrogates favored percentages because they were "more clear, more concise, and less confusing". in contrast, % of physicians stated that they do not use precise percentages when discussing prognosis in citbi due to distrust in the predictive accuracy of existing data: "better have damn good data to do that with, and most often, we do not." physicians also voiced concern over families' judgment…they become simplified and [these numbers are] used against you later." the dissimilar preferences for the use of percentages and numbers during prognostication represent an important difference between surrogates and physicians. these findings have a direct impact on the design of a goals-of-care sdm tool for citbi. a future goals-of-care decision aid will require iterative decompressive craniectomy (dc) is not a new procedure, however, it has gained momentum in recent years, in the management of refractory intracranial hypertension. however, the timing of dc has not been -based guidelines for the optimal timing of dc has resulted in a wide variability in practice patterns. in most instances, dc has been performed based on neurosurgical evaluation of the patient with or without intracranial pressure (icp) monitoring and evidence of increased shown variable outcomes in emergency (within hours of injury) neurosurgical procedure in traumatic brain injury (tbi). the purpose of this study was to evaluate the impact of emergency dc on in-hospital mortality following blunt tbi. craniectomies performed on patients with a blunt mechanism of head injury within twenty-four hours of admission, were included in the study. in-hospital mortality was the main outcome of interest. patients qualified for the study. patients ( %) underwent a craniectomy within hours (emergency group)and patients ( %) had craniectomy performed between > hours hours to hours following hospital arrival (late group). propensity matched analysis identified pairs of patients in both groups. the mean standardized differences were less than % after matching. there were no significant differences in mortality [odd ratio . , ci ( . [ . , % ci (- . , . ), p= . ] and length of stay between the groups [hazard ratio, . , % ci ( . , . ], p= . ]. no difference was seen on in-hospital mortality between patients operated within hours versus patients operated between and hours of admission. spreading depolarizations (sds) are pathological waves of neuronal depolarization that occur in % of patients with traumatic brain injury (tbi) who require surgical treatment of focal lesions. the incidence of sds in non-surgical tbi i (deeg) placed at bedside via burrhole. we hypothesized that the incidence of sds recorded using deeg in non-surgical patients would be similar to that documented in surgical tbi. -penetrating tbi who did not require urgent neurosurgery on admission. all patients underwent bedside burrhole placement of intracranial pressure, tissue oxygen, regional blood flow and deeg monitors via a single quad-lumen bolt per institutional protocol. data were recorded on moberg cns with dc-coupled amplifiers. over a -- ; % male; gcs range - ) underwent monitoring for a mea - . hours, beginning . hours (median, quartiles: . -( %) monitoring devices were placed in nonpatients had focal pathology in the monitored lobe, w died, including those with sds. there were no significant hematomas or infections related to invasive neuromonitoring. the incidence of sds detected with deeg placed in non-dominant frontal lobe was lower than previously reported with injury-targeted placement of subdural strips in surgical tbi patients. this may be due to targeting to injured periinnate incidence of sd in patients with non-surgical or more diffuse injuries. targeted placement of subdural electrodes through burr holes may be warranted in non-surgical tbi patients. university of utah general surgery, salt lake city, ut, usa. traumatic brain injury (tbi) is a prevalent condition that is responsible for a significant amount of disability and healthcare expenditures. clinicians can and do use the impact prognostic calculations to inform o examine self-reported individual and institutional use of the impact prognostic calculations in an effort to identify trends and effects on treatment. we conducted an international and multidisciplinary survey examining self-reported awareness and use of the impact prognostic calculator. factors associated with awareness and use of the calculator including provider specialty, years in practice, personal and institutional volume of tbi patients treated, and institutional trauma level were als voluntary and anonymous survey in an email. study data was collected and managed using redcap. respondents ( . %) were aware of the calculator, only . % ( ) said that they often, and . % ( ) said they sometimes used it. volume of tbi cases and specialty both were positively associated with awareness and use of the calculator. providers often or sometimes used calculator, . % ( ) stated that it had some influence on their care for the patients. . % used the information to better of care and % used it to provide more aggressive care. of those aware, still only slightly more than half ( %) used it. the use of the impact calculator was mainly to better communicate with patient family, but a portion, . % and % of providers, said it influenced their care in other ways. these results provide direction to increase awareness and use of the impact prognostic calculations. the brain trauma foundation guidelines suggest individualizing cerebral perfusion pressure (cpp) goals based on tissue oxygenation (pbto ), pressure reactivity (index; prx), and metabolism (lactate-pyruvate ratio; lpr). our objectives were to investigate practices pertaining to bedside hemodynamic and neuromonitoring in tbi patients, and to analyze differences among "neurointensivists" (nis; defined as clinical electronic survey of items including a tbi case-scenario; endorsed by sccm ( , recipients) and esicm (on-line newsletter) in . chi-square test was used to compare proportions of responses between nis and ois with a significance p< . . there were responders ( % completion rate); ( %) were classified as ois and ( %) as nis. use of neuromonitoring-derived variables to optimize cpp in patients with severe tbi, for the entire cohort: pbto ( %), transcranial doppler(tcd) ( %), jugular venous bulb ( %), ct perfusion(ctp) ( %), prx ( %), and lpr ( %). nis use more pbto ( % vs. %, p= . ) and ctp ( . % vs. . %, p= . ). more nis have a hemodynamic protocol ( . % vs. . %, p= . ) for tbi, use more arterial waveform analysis ( % vs. %, p= . ), and bedside ultrasound ( % vs. . %, p= . ), while more ois monitor mixed venous oxygen saturation ( . % vs. %, p= . ). in the case scenario of raised icp, low pbto , and preserved pressure autoregula (vasopressor use . % nis vs. % ois, p= . ). "neurointensivists" employ more hemodynamic and neuromonitoring to patients with tbi. intracranial pressure and cpp remain cornerstones of management, however the use of other physiologic variables -specific pp goals. the predominant experience of penetrating traumatic brain injury (ptbi) derives from battlefield settings, but the civilian experience in western settings in patients treated after is limited to only small and single-center studies. as a result, outcome predictors of civilian ptbi in modern trauma and neurocritical care settings are poorly defined. the aim of this study was to identify predictors associated with survival in a contemporary, large, diverse two-center ptbi cohort, and to develop a parsimonious survival prediction score for civilian ptbi. our cohort comprised ptbi patients retrospectively identified from the local trauma registries at two u.s. level- trauma centers, of which one was predominantly urban and the other predominantly rural. predictors of in-hospital and -month survival identified in univariate and multivariable logistic regression were used to develop the simple surviving penetrating injury to the brain (spin) score. at hospital discharge and -months post ptbi was . %. motor glasgow coma sub-score, pupillary reactivity, self-inflicted injury, transfer from other hospital, female sex, injury severity score and inr were independently associated with survival (all p< . ; area-under-the-curve . ). important radiological factors associated with survival were also identified but their addition to the full multivariable would have resulted in model overfitting without much gain in the area-under-the-curve. we developed the spin score, a logistic regressionafter ptbi. while external validation is warranted, this clinical survival prediction tool may provide important information to guide families and physicians during intervention-and goals-of-care decision- real-time visualization of the cumulative pressure and time dose of intracranial pressure in individual traumatic brain injured patients. the 'dose' of intracranial hypertension, a summary measure of duration and intensity of elevated intracranial pressure (icp) episodes, is associated with worse outcome in traumatic brain injury ( retrospective analysis of minute-by-minute icp monitoring data from a large multicenter database of tbi population-based color-coded plots by güiza et al, where 'bad' icp episodes are red, and 'good' icp episodes are blue. the icp insult currently experienced by the patient, together with his icp episodes of the previous hours, and the cumulative icp burden since icu admission, are shown. when playing these minute-by-minute snapshots consecutively, an animation is created showing the current and cumulative burden of icp of the patient. we present the clinical course of patients, with good outcome (gos ), and who died (gos ). clinical trials aiming at aggressively treating icp below a fixed threshold of mmhg have given thresholds, could present a new way to define secondary injury by icp, and a future target for therapy. the proposed method visualizes the current and cumulative time and pressure burden of icp for individual patients, which could help a neuro-intensivist in identifying when a patient is currently in a state of potentially harmful elevated icp, or when his outcome is at a turning point. acute blood pressure variation and mortality in severe traumatic brain injury we retrospectively evaluate temperations ( hematomas) from april to march operated by one young neurosurgeon. during the operation, we made sure to put the burr hole the highest, not to drainage tube into the right position. we scaled the amount of hematoma by hand free roi using head ct before operation and also the next day to evaluate the improvement rate. the recurrence rate was . % ( cases). the average amount of air contaminated was . ml and the improvement rate was . %, both of which didn't relate to the recurrence. no relevance among the recurrence rate, the amount of air contaminated and the hematoma improvement rate could be found. though the amount of air contaminated during temperation doesn't relate to the recurrence rate, it was useful to scale the hematoma improvement rate and the amount of air in order to objectively assess the d recurrence became less, which suggest that we need to investigate the operation for chronic sundial hematoma further after we operate more. the aim of this prospective observational study was to evaluate if trans-cranial doppler (tcd) ultrasonography can be used as an inference tool of cerebral hypoxic episodes in patients with moderate to severe traumatic brain injury. recruited patients had serial tcd studies to assess blood flow velocity of the middle cerebral artery (mca). measurements were done on bilateral mcas as soon as logistically possible after the insertion of pbto monitoring, once a day for a total of days, and during dynamic challenge tests when feasible. multiple physiologic parameters were registered concomitantly with each tcd measurement, with a particular focus on determinants of pbto and potential confounding factors. we studied consecutive patients with a total of tcd studies, of which ( %) were performed - . h) after tbi. when considering all readings, we found no correlation between pbto and mca's readings > h. for value level, icp, and cpp. to correlate with brain tissue hypoxia and could be use as a screening tool to help minimise timesensitive secondary injury during that period. otherwise, vmean is not correlated to pbto . a precise assessment of brain condition after severe traumatic brain injury (tbi) is crucial to reduce secondary injuries and sequelae. multimodal neuromonitoring permits to assess multiple systemic and brain parameters, but these data are complex to interpret continuously, especially in the overwhelmed environment of intensive care unit (icu). computerized decision support systems (cdss) can assist the clinicians in optimizing care. this study aims to evaluate an algorithm for classifying the cerebral condition, as a first step in the development of a cdss. the study was approved by the local research ethics committee. patients with severe tbi (glasgow coma score < ) with a monitoring of intracranial pressure and brain tissue oxygenation pressure were eligible. data were extracted from the existing icu electronical medical records (semi solutions médicales). an incremental learning fuzzy minparameters online was implemented. the different cerebral status categories included: control condition, ntracranial hypertension. previously validated and published datasets were used to train the system. the system was then tested with the patients' data and compared to a classification made by two clinical experts. eight -hour recording periods from adults with severe tbi were analyzed. the pathophysiological status was appropriately classified by the cdss in (median) % (interquartile: - %) of time. every critical event was detected, but brief misclassifications were frequently observed during the transition periods. in this preliminary cohort of patients with severe tbi, the cdss was able to adequately classify the brain condition in a large proportion of time, but some errors occurred during brief transitional periods. further training of the cdss with a larger dataset may improve the system accuracy, which should be tested in a larger patient population. mild traumatic brain injury (tbi) is a commonly seen pathology at trauma centers. neurosurgical consultation is a routine practice; however, the vast majority do not require surgical intervention or invasive monitoring during the entirety of their hospital stay. in certain trauma centers, neurologycentered neurocritical care solely evaluate and manage mild tbi. we provide a retrospective analysis of this practice at our level trauma center. a retrospective chart review was completed on tbi patients evaluated at a level trauma center between september and december . inclusion criteria included; initial gcs - , blunt head injury, available repeat imaging, and management by neurology-centered neuro-intensivists. exclusion criteria included gcs < , penetrating trauma, those that needed immediate surgery, those with neurosurgical consultation, and those without available imaging. a total of patients were included in the final analysis. age was . ± years. there were males and females. the most common mechanism was falls ( . %), followed by motor-vehicle collision ( . %), motor--related ( . %), assault ( . %), and pedestrian- . % were stable, . % were worse. only patients ( . %) exhibited neuro-exam changes, where patients received repeat imaging which ultimately demonstrated stable findings. no patients required a neurosurgical procedure. average hospital stay was . ± . days. neurology-centered neuro-intensivists can manage mild tbi appropriately without official neurosurgical consultation. this practice can streamline tbi management and potentially reduce hospital costs. bulic, natasha n. renda, may m. kim-tenser, gene g. sung, benjamin b. emanuel. usc, los angeles, ca, usa. measurements of optic nerve sheath diameter (onsd) using bedside ultrasound (us) have been shown to correlate with clinical and radiologic signs and symptoms of increased intracranial pressure (icp). eleven patients ( males, females) with traumatic brain injury (tbi) and gcs< were evaluated. all patients had extraventricular drainage (evd) monitors, right and left. three patients had right decompressive hemicraniectomy, had left hemicraniectomy, had suboccipital craniectomy and did not have decompression. a total of examinations were obtained with invasive icp measurements, pulsatility indices (p balance were recorded. twenty-nine ocular uss were performed on individual patients. in ons assessments, bilateral onsd was . mm, while icp was mmhg, however, later developed icp mmhg within hours. another patient had bilateral ons . mm, while icp was mmhg, however, later developed icp of > mmhg within hours. two patients had bilateral ons measurement> . mm with corresponding icp > mmhg all patients with onsd mmhg had ons > . mm. although, patients with ons > . mm and icp mmhg within the next h. there was no correlation between pi on tcd, thus tcd was not useful in this dataset. there was no correlation between increased temperature or elevated blood pressure with icp> mmhg. this small sample size suggests that onsd may predict future icp elevations, however, a larger sample size is needed to confirm these results. the precise threshold differentiating normal and elevated intracranial pressure (icp) is variable among individuals. in the context of several pathophysiologic conditions, elevated icp leads to abnormalities in global cerebral functioning and impacts the function of cranial nerves (cns), either or both which may contribute to ocular dysmotility. the purpose of this study is to assess the impact of elevated icp on eye watching a -second continuously playing video moving around the perimeter of a viewing monitor. pupil position was recorded at hz and metrics associated with each eye individually and both eyes together were calculated. linear regression with generalized estimating equations was performed to test performed at icp levels ranging from - to mm hg in twenty-three patients (twelve female, eleven male, mean age . years) on fiftycorrelating with cranial nerve function linearly decreased with increasing icp (p-value mm hg was . . intracranial pressure. increasingly elevated icp was associated with increasingly abnormal eye tr physiologic impact of elevated intracranial pressure. this represents a new non-invasive automatable means for assessing the physiologic impact of elevated icp. use of shared decision--of-care decisions in critically-ill traumatic brain injury (citbi) offers the hope to decrease variation and bias in goals-of-care discussions. sdm guidelines demand the inclusion of an evidenceand acceptance of the "international-mission-for-prognosis-and-analysis-of-clinical-trials-in-tbi"(impact)-model by physicians holding such discussions with citbi families. we conducted a mixed-methods study with semi-structured interviews in attending physicians representing geographic (northeast,mid-atlantic,south,west,midwest) and subspecialty diversity (neurocritical care, neurosurgery, trauma, palliative care). we explored methods of prognosis derivation and communication, citbi outcome model use, and, specifically, awareness and perceived utility of the impact-model. we analyzed transcripts in nvivo-software with the investigator-triangulated-inductive--approach. theme saturation determined the final sample size. overall, % of physicians use the impact-model, % were not aware of it, and % don't rely on any tbi outcome models. positive impact-model views included: "helpful in getting an idea where your confidence should be"; "to ground physicians a little bit"; "reduces the variability of prognosis that a large some participants "do not thin only"; "those calculators are about populations; they're not about individuals, use of those calculators for this purpose is a perversion of the original construct". we identified substantial physician variability in the awareness of, use, and attitude toward the impactmodel, which crucially informs the development and successful implementation of future goals-of-care sdm tools in citbi. the analyses of acute subdural hematoma using acute subdural hematoma (asdh) is associated with cerebral contusion and laceration of bridging veins following a head injury, however a few cases of asdh without head injury had been reported. the purpose of this study was to detect the difference of traumatic asdh and non-traumatic one. cases of asdh hospitalized at our institute from march to march were retrospectively reviewed. traumatic groups were patients ( . %), and non-traumatic groups were patients ( . %). the results were statistically analyzed by logistic regression to use the various factors: age, gender, glasgow coma scale (gcs) score, the presence of light reflection, danti--coagulation agents, neurological outcome and so on. neurological outcome was evaluated using glasgow outcome scale, and it was classified into two groups: the good prognosis group (gr, md) and the poor prognosis group (sd, vs, d). traumatic groups were mean age . ± . years, and were comprised of males and females. non-traumatic groups were mean age . ± . years, and were comprised of male and females. there were significant difference in patients` characteristics, the presence of light reflection, d-dimer and neurological outcome (p < . ). non-we will be described the detail of them and collect further cases in the future. traumatic brain injuries (tbi) are of significant importance due to increased morbidity and mortality. we retrospectively analysed tbis to assess clinical profile and factors predicting in-hospital mortality. electronic database at a private, urban tertiary care centre was screened ( to ) to include all tbi -hospital mortality outcome were assessed. mean age of population was . ± . years with . % being males. most injuries ( %) resulted from road traffic accidents (rtas). bleeding from either ear, nose or throat (ent) was most common presentation ( . %) followed by vomiting ( . %) and convulsions ( . %). on presentation, severe brain d subdural ( . %) haematoma was most common followed by sub-arachnoid ( . %), extradural ( . %) and intracerebral ( . %). threatened airway was observed only in . % cases. bony trauma ( %) followed by face ( . %) ,chest ( . %), and spine injuries ( . %) were associated injuries. in-hospital in-hospital mo . , . ; p< . ), tachycardia (or . , % ci . , . ; p= . ) and with development of hyponatremia (or . , % ci . , . ; p< . ) or fever (or . , % ci . , . ; p= . ) during hospitalization. ventilator support was necessary in ( %) cases out of which ( %) died. hospital stay (days) did not vary significantly in survivors and non-survivors ( . ± . vs . ± . , p= . ). development of hyponatremia or fever and requirement of assisted ventilation were associated with -hospital mortality. casey we established a team that included attending physicians, fellows, advanced practice providers (app), specific guidelines. we surveyed staff regarding team communication and discussion of qsis during rounds. we designed a dgt that defined team member roles, structured communication patterns, and prompted standard discussion of qsis. following implementation, we evaluated team compliance with the dgt, as well as rates of catheter-associated urinary tract infections (cauti) and ventilatorassociated pneumonias (vap). % respiratory therapists). for most qsis, a minority of staff reported that these were always addressed during morning rounds (% staff indicating qsi "always" addressed: % pressure ulcers, % code status, % cam icu, % mobility goal, % central line catheter removal, % urinary catheter removal, % dvt prophylaxis plan, % ventilator weaning). shared understanding of daily goals between nurses and physicians was reported by % of staff, with a significant difference between nurse %), p = . . dgt audits spanning patient days demonstrated median compliance greater than % for discussion of all qsis. there was an % reduction in cautis ( % ci %, %), p = . , and a trend towards reduction in vap that was not significant. team discussion of qsis can be enhanced by dgts. by promoting adherence to evidence-based best practice, dgts may reduce hospital-associated infections. follow-up is ongoing to determine the impact of dgts on clinical outcomes and team communication. catheter-associated urinary tract infection (cauti) is the most common health-care associated infection accounting for > , nosocomial infections annually (gould, ) . according to the center for disease control, cautis are also a leading cause of secondary blood stream infection resulting in development related to cognitive, motor, and sensory deficits. neuroicu's goal was to eliminate cautis, defined as a rate of zero. with initial efforts ( ( catheter days (titsworth et al, . in february, neuroicu launched a patient-centered quality improvement effort to further reduce cautis. the neuroicu interdisciplinary comprehensive unit safety program (cusp) performed an extensive literature review of evidence based best practices specific to urinary catheter management. a preexisting, staff nurse driven urinary catheter management protocol was revised to better fit the needs of the neurocritical care population, including assessment of and interventions for acute and chronic scan assessments to every hrs, revision of urinary d-ofconducted daily rounds to evaluate the necessity and management of indwelling urinary catheters. after three months of implementation, compliance with use of the neuroicu's urinary catheter management algorithm (ucma) was greater than %, urinary catheter utilization was reduced from % to %, and cauti rates were reduced to zero. implementing a neurocritical care patient-centered, interdisciplinary approach to urinary catheter management significantly impacted urinary catheter utilization, cauti rates, and unit culture. dedicated neurointensivists have previously been shown to improve various outcome measurements in patient and family satisfaction. the purpose of this study is to evaluate the impact of newly appointed neurointensivists on quality outcome measures in a nsicu. this is an observational cohort study of adult patients (> years) in a -bed nsicu at an academic, tertiary care center evaluating quality outcome measures pre-and post-neurointensivists. outcome measurements include catheter associated urinary tract infection (cauti), central line blood stream infection (clabsi), ventilator associated pneumonia (vap), patient acuity, mortality, and length of stay (los). patient satisfaction questionnaires from discharged patients were compared to historical controls. tentiveness of doctors; ) recommend the hospital to others. statistics include -sample binomial and n- chi-squared (categorical) and t-test (continuous). for questionnaire data, considered significant. total patient days occurred pre-and days post-neurointensivist coverage. patient acuity decreased . % (p= . ). cauti ( %, p= . ), clabsi ( %, p= . ), central line days ( . %, p< . ), ventilator days ( . %, p= . ), and vap ( %, p= . ) also decreased. these saved the hospital an estimated $ , based on health services advisory group data. questionnaires were returned. patient satisf on physicians' attentiveness (p= . ). patients recommending the hospital to others increased % (p= . ). dedicated neurointensivists positively impact quality outcome metrics, particularly significantly improving patient satisfaction. future studies should evaluate the direct impact of neurointensivists on medicare reimbursement from improved patient satisfaction. bertan hallacoglu, tanmayi t. oruganti, chandran c. seshagiri. research & development, boston, ma, usa. cephalogics has developed a wearable diffuse optical tomography (dot) imaging device to help clinicians monitor perfusion and oxygenation from multiple brain regions on the bedside in disease states the system to changes in cerebral tissue oxygenation (scto ) induced by hyperventilation in a pig and human subjects. dot sensor was positioned on the pig's head along the sagittal line, and the second sensor was positioned on the hind leg muscle for monitoring systemic tissue oxygenation (ssto ). dot measurements were performed continuously during baseline ( mins, paco = mmhg), transient hypercapnia ( mins, paco = mmhg), and recovery ( min, paco = mmhg) periods controlled by the respiratory rate of the ventilator. dot data were recorded to a laptop for off-line analysis. sto -sd) were computed for comparison of results across measurements. the approach was also investigated in three human volunteers, who were instructed to hyperventilate during dot recordings. -- %), consistent with reports of reduced cerebral blood flow during hypocapnia. in contrast, ssto estimates - %), indicating elevated systemic perfusion. both parameters fully recovered to baseline values during the recovery period. scto response to hyperventilation in human volunteers were consistent with the results in pig. hypercapnia induced reduction in scto was noninvasively imaged in human subjects and a pig despite the large scalp-cortex distance in pig. the results of this study demonstrate the sensitivity of the cephalogics' dot system to scto values and its ability to separate scto from systemic perfusion. brittany doyle, michael m. rogers, daiwai d. olson, venkatesh v. aiyagari. ut southwestern, depts. of neurological surgery, neurology and neurotherapeutic, dallas, usa. multidisciplinary rounds play a pivotal role in optimizing care in the neurosciences critical care unit (nccu). care providers were frustrated with inconsistency and the need for manual data entry to conduct multidisciplinary rounds. the purpose of this project was to develop an integrated computerized form that incorporated "smart" features within epictm. the nccu nursing council collaborated with the physicians to design a standardized system-based approach to multidisciplinary rounds, and the elements that would be addressed within each system. input was collated from nursing, neurology, neurosurgery, pharmacy, and critical care into a paper version which was beta tested before the epic tool was officially rolled out. the rounds template is now a perpetually editable note with fields that include drop-down menus, copy--populate with up-to-date data (e.g., icp values, lab values). while there was a learning curve to the use and un -led rounds became much more efficient, comprehensive, and less frustrating for the entire healthcare team. within four months, nursing management saw the benefit of such a standardized tool for clear communication and the tool also became the standard for nurse-to-nurse handover at change of shift. efficient and orderly presentation of information during multidisciplinary rounds is greatly assisted by the use of a standardized electronic tool. having all of the current, relevant data available in a single location has greatly improved the quality of nurse-led neurocritical care rounds. this tool can be replicated and customized to the needs and patient populations of other units and hospitals. the degree of burst suppression on continuous critical care eeg (cceeg) monitoring is used to guide dosing of intravenous anesthetic drugs (ivads) in the treatment of refractory elevated intracranial pressure (icp) and refractory status epilepticus (se). however, medication titration is performed only as frequently as cceeg review (potentially as little as - times a day). quantitative eeg (qeeg) may provide a continuous, objective assessment of the level of burst suppression that would allow for more precise and rapid titration of ivads. compared software-generated qeeg burst suppression ratio (qeeg bsr) with three raw eeg variables as determined by two board-certified neurophysiologists (r and r ): bursts per minute (bpm), total burst duration per minute (bd) and average inter-burst interval (ibi) for one minute segments per patient. a total of eeg segments were analyzed. agreement between readers was very high for the three raw eeg variables: bpm, bd and ibi (correlation coefficient . , . , and . , respectively). the best correlation was observed between bd and qeeg bsr (- . for both r and r ). the correlation between bpm and qeeg bsr (- . r and - . r ) and ibi and qeeg bsr ( . r and . r ) was not as strong. left and right hemispheric qeeg bsr did not differ statistically from the generalized qeeg bsr (p= . and . , respectively) despite the presence of focal intracranial pathology. the depth of therapeutic burst suppression can be accurately assessed by generalized qeeg bsr. although cceeg bursts per minute is the most commonly used cceeg metric of burst suppression, it shows a lesser correlation with qeeg bsr than total burst duration per minute. there is little operational data on optimal neuro-icu physician staffing. this prospective study evaluated the introduction of night-time in-hospital neurocritical care fellows (ncfs) in an urban academic hospital. the goal was to determine if the new staffing model enhances patient care and provider and patient satisfaction. irb approval was obtained. the new staffing model was rolled out on - - . providers (ncfs; neurology residents and attendings; neurosurgery residents, physician assistants, advanced practice nurses and attendings; neuro-icu nurses) were surveyed. a pre-roll out survey of providers' perceptions of the existing model (night-time ncf coverage from home with on-call in-hospital neurology residents and neurosurgery physician assistants or residents, not dedicated to the neuro-icu) was administered prior to new model roll-out. two follow-up surveys, a separate night-shift nurses survey, and patient (or surrogate) surveys were administered between - - and - - . surveys were electronic and responses were voluntary and anonymous except for the night-shift nurses survey which was paper, required, and anonymous. response rates were % (pre-roll out), % (first follow-up), and % (second follow-up). % of providers indicated pre-roll out that night-time in-hospital ncfs would be beneficial; % (first follow-up) and % (second follow-up) indicated satisfaction with the new staffing model. major reasons for satisfaction included: physician response to emergencies, physician -nurse communication, and patient outcome. the reason for dissatisfaction was decreased educational opportunity for residents. % of night-shift nurses reported preference for the new model. % of patients (or surrogates) agreed to participate: % reported satisfaction with the care they received in the icu; dissatisfaction was not more than % of providers were satisfied with a new staffing model featuring night-time in-hospital ncfs. additional studies are necessary to determine optimal neuro-icu physician staffing with increasing patient and treatment complexity and decreasing resources. therapeutic plasma exchange (tpe) is a first-line therapy for guillain-barre syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy and polyneuropathy associated with paraproteinemias. tpe is also a second-line therapy for neuromyelitis optica, chronic focal encephalitis, and acute multiple sclerosis. the therapy is also used in autoimmune encephalopathies, refractory status care service has provided a neurointensivist run tpe program using membrane-based technology with the gambro® prismaflex system. a benefit of a neurointensivist managed membrane -based service is lower direct costs compared to centrifugal-based therapies. since a consultation to another service (often available during business hours) is avoided, delays in therapy can be reduced (potentially further decreasing costs) and the therapy is also available for emerging indications such as refractory status epilepticus. this review is of the initial patients treated with tpe in our neurocritical care unit between april and may . all patients were treated with % albumin with a targeted exchange of . to . plasma volumes. overall dosing, timing, indications as well complication were reviewed. indications for therapy included guillain-barre syndrome, myasthenia gravis, autoimmune encephalitis, refractory status epilepticus, autoimmune vasculitis, and parainfectious transverse myelitis. all patients received a minimum prescription of . plasma volumes and had the therapy started sooner than historical controls. no changes in nurse staffing were required for the therapies and we report no bleeding, infectious or access related complications. mild coagulopathy was seen in most patients after previously not available. a neuro-intensivist lead tpe program is feasible and safe. the therapy can be delivered more timely and can be offered for a wider variety of indications. a cost analysis of the program is now underway. specialty neurocritical care improves hospital length of stay and mortality in patients with critical neurologic illness. however, clinical practices are often informed by studies focused on mortality or gross functional outcome. both staff and family members face uncertainty about neurological outcome, which performing detailed followup for all patients admitted to the university of cincinnati neurosciences intensive care unit (nsicu). all patients admitted during a twotrained outcome scale-extended (gose), cognitive outcome using the teleph and quality-of-life using the euro-qol. we assessed the duration of each follow-up call in order to determine feasibility. n= patients were admitted to the nsicu; mean age was ; % were male. overall follow-up was obtained in %; % of survivors were contacted. disposition from nsicu included: home ( %), acute rehab ( %), long-term care ( %), hospice ( %). in-hospital mortality was %. median gose (iqr) was ( - ) and median mrs (iqr) was ( -- . an average of : (mm:ss) was required for each assessment; comprehensive assessments required : . overall, a total time of approximately hours was required for patients. our pilot study demonstrated feasibility of following patients admitted to the nsicu. these findings have the potential to guide in-hospital care and out-of-hospital resources when used as a quality improvement metric, and to provide valuable information for retrospective research. our neurocritical care unit restructuring provided an opportunity to revise our staffing model. the prior model ratio of : resulted in at least one nurse experiencing a : ratio when high acuity patients -specific data to support a higher staffing. prospective observational study of nursing time using the -item therapeutic intervention scoring system (tiss- ) and manual timing of discrete nursing interventions including off-unit transport. baseline data was obtained to include measures of nursing experience. measures of central tendency and regression analysis was performed using sas v . . the average time to complete a neurologic assessment was . minutes; the average time to chart a neurologic assessment was . minutes. for time spent off the unit the average time spent traveling to ct was < minutes, average time spent in mri was minutes twice a day, average time in ir was . minutes. we found that nursing experience was not associated with patient acuity, duration of assessment, nor time spent doc ents. assessment time was associated with documentation time. moreover, higher acuity was a predictor of both assessment time and documentation time. the data were used to support an increased acuity model with nurses having planned : ratio. neurologic critical are patients require more hands on nursing care and time spent in diagnostic testing than an average critical care patient. neurocritical care units staffing ratios should be adjusted to provide time to ensure nursing care is complete. melissa panter, sonja s. stutzman, daiwai d. olson, venkatesh v. aiyagari. utsouthwestern/neurocritical care, dallas, usa. venous access is a basic yet critical component of care. determining which venous access devices (vad) to use depends on the type, duration, and frequency of infusion. prolonged continuous infusion of drugs or fluids, benefit from midline peripheral catheter (midline) or a peripherally inserted central catheters (picc). midlines are safe and effective but use is declining in favor of piccs, which have similar insertion costs and added benefits, such as the delivery of toxic drugs harmful to peripheral veins. however, an infection associated with a picc is classified as a central line associated blood stream infection which has important financial implications for the hospital. therefore, it is important that the type of vad be specifically tailored based on -physician collaborative study to design and test a decision support tool to assist clinicians in determining the appropriateness of the piccs vs midlines for patients. this study has three phases. first, a retrospective chart review of vad decisionexamine the current degree of appropriateness for each type of vad for each specific patient scenario. next, we will design a decision support tool to help decide which vad should be used. the tool will be developed based on expert clinician, pharmacist review and a review of the literature. finally, we will their patients. the first phase of the study is ongoing and we will present the results of the retrospective part of the study and the decision support tool at the annual neurocritical care society meeting. a decision support tool to guide clinicians choosing between different types of vad will help improve current clinical practice and patient outcomes. clinical trials in neurocritical care require a predictable set of baseline, monitoring, treatment, and clinical outcomes data. however, interoperability standards restrict automated real-time streaming of this data, resulting in inefficiencies performing clinical trials, preventing real-time clinical trial oversight and constraining collaborative research. we investigated available data systems and developed a conceptual e. examining current traumatic brain injury interventional trials, we considered technical interoperability -based clinical trial oversight and collaborative analytic research. we elaborated a vendor-neutral interoperability schema for data extraction, repositories, analysis, annotation, and visualization. the proposed conceptual solution is described. nodes of data acquisition include: ) continuously streaming devices including physiologic monitors and infusion pumps; ) discrete data from highpenetrance ehr and laboratory platforms; and ) biospecimen, radiology, and clinical outcomes repositories. an application program interface performs function calls to utilize individual episodes of data. a data management system queries and manages multiple patient records for batch processing of ondemand or prefor real-time or post-hoc assessment of raw and derived parameters (e.g., percent time in target range or on-protocol compliance). we enumerate the variety of current nodes requiring interoperability interfaces, and propose an open standard to promote a highly efficient platform for n -based clinical research, featuring automated case report form data extraction, a programmable interface for oversight and early warning detection, and a platform for annotation and crowdsourcing of novel algorithms. this conceptual architecture for a modular, vendor-neutral, data collection and management system for -based clinical trials in neurocritical care and offer new functionality for real-time oversight and collaborative analytics. improving cancer is a devastating illness; with a rise in brain and spine tumors specialized care is more important that ever. with advances in technology and treatment strategy, those too ill to previously receive care reased acuity has translated to the need for higher levels of hospital care. recognizing the unique expertise required to care for this emerging population, the decision was made to merge neurology and oncology specialties within critical care. the purpose of this poster is to describe the admission criteria, patient population, utilized technology, staffing model, and patient outcomes of a newly created neuro-oncology critical care unit (nccu). in january , a bed neurocritical care unit was opened in a midwestern academic medical center. six of the beds housed within this bed unit were designated and budgeted to the oncology medical center. separate nursing staff and management teams were created to support the care within the unit while maintaining close collaboration with university hospital nccu nursing teams. while nursing teams are distinct, nurse practitioners, neurointensivist, and other multidisciplinary team members are shared between both services. to evaluate the benefit of patient diagnosis, care needs, nccu length of stay (los), number of ventilator acquired pneumonias (vaps), urinary tract infections (utis), and central line acquired bloodstream infections (clabsis). at the time of this submission, specific results are still being tabulated. merging access to academic research trials and oncologic and neurointensive specialists, this has created an environment that promotes care reflective of the most up to date evidence based practice. through the utilization of creative staffing and focused onboarding, this unit has been able to treat this subspecialized population holistically utilizing a multidisciplinary approach to minimize hospital acquired complications and los. in , the neurocritical care society (ncs) published a consensus statement in support of multimodal neuromonitoring, emphasizing the essential need for systems to integrate data in meaningful ways to t barrier to the integration of data from multiple group on neurocritical care informatics was established in ; it includes experts from the clinical and research side of neurocritical care and representatives from medical device manufacturers. through an open meeting and continued discussion, a recommendation document "medical device connectivity" was produced. its objective is to provide guidance to medical device manufacturers desiring to design a communication protocol that allows external systems to acquire data from their devices. our research on this project uncovered a high percentage of errors in medical device protocols as well as undocumented characteristics and safety issues. the group developed recommendations for providing robust communications as well as address usability and safety concerns. the document outlines the content that should be transmitted which includes device identification, protocol version identification, patient identifier, events, alarm conditions, system status, data labels, and units. finally, it must be thoroughly documented and validated by the manufacturer. multimodal monitoring (which requires medical device connectivity) reportedly improves quality of care through reduction of errors and increased detection of adverse events. however, widely adopted connectivity are on the horizon. in the meantime, the document created in this project will provide guidance for manufacturers in their communications protocol development. in doing so, they will then further the ncs's recommendations on device connectivity for multimodal monitoring. warfarin-related intracranial hemorrhage (ich) is associated with increased mortality due to higher rates of hematoma expansion. current guidelines recommend rapid anticoagulation reversal using intravenous vitamin k and prothrombin complex concentrate (pcc). previous studies show high prevalence of incomplete anticoagulation reversal with -factor pcc. we therefore sought to assess the impact of pcc type in reversing warfarin in ich patients. this was a retrospective study of ich patients ( traumatic and non-traumatic) with warfarinassociated coagulopathy who were admitted to a level ii trauma center between january and september and received at least one dose of -factor or -factor pcc. post-pcc inr of £ . was considered successful inr reversal. multivariable model using logistic regression was performed to assess the impact of pcc type on successful inr reversal after adjusting for age, sex, bmi, and baseline inr. overall, the prevalence of successful inr reversal was . %. there was a higher proportion of patients with successful inr reversal in those who received -factor pcc than -factor pcc ( . % vs. . %, respectively, p= . ). in the multivariable model, -factor pcc (or . ; % ci: . to . ) and baseline inr (or per unit of inr . ; % ci: . - . ) were independent predictors of successful inr reversal. the change in inr post-pcc was significantly greater in those who received -factor pcc than -factor pcc ( . ± . vs. . ± . respectively, p< . ). -factor pcc more reliably reversed warfarin in ich patients compared to -factor pcc. cortical spreading depolarizations (csds) as highly active metabolic event commonly occur in patients with intracerebral hemorrhage (ich) and may contribute to secondary brain injury. fever is an independent predictor for unfavorable outcome after ich and may trigger csds. here, we investigated the dynamics of brain-temperature (tbrain) relative to csds and core-temperature (tcore). twenty comatose patients with ich and multimodal electrocorticograpy (ecog) monitoring were prospectively enrolled. a subdural ecog strip was placed adjacent to the evacuated ich. a combined intracranial pressure (icp) and tbrain probe was inserted in the white matter ipsilateral to the ich. monitoring data were averaged to -minute-means for longitudinal analysis and to one-hour-means. -burden was defined as % of temperature > . ° c per -hours. data were analyzed using gee-models and are presented as median and interquartile range (iqr). during hours ( hours [ -csds occurred in clusters. baseline tcore and tbrain were . °c ( . - . ) and . °c ( . - . ), respectively. tbrain but not tcore significantly increased minutes preceding the csds by a median of . °c ( . -- . ]; p< . ) but not tcore (p= . ) was higher during clusters compared to episodes of single csds. csds probability was highes or= . per %; tcore: p< . ; or= . per %) independent of map and icp. csds were triggered during episodes of fever. our data suggest an association between csds and cerebral heat production, especially during clusters. integration of ecog monitoring in trials investigating prophylactic normothermia after ich may help to understand the potential beneficial effect of this intervention. anticoagulation reversal is recommended for patients with intracerebral hemorrhage (ich) on vitamin k antagonists. we propose a window for reversal of vitamin k antagonists, in which ich volume remains below the average growth in a control population on follow up imaging a retrospective review of neuro icu patients at henry ford from - was conducted on patients with the icd code for diagnosis of ich. inclusion criteria: brought to ed at onset of symptoms, either not on anticoagulation or were on warfarin with therapeutic inr, and had received pcc administration. fifty eight total patients were identified. patients were approximately matched for gcs on admission, ich w - cc difference in volume estimation. forty-seven control patients were identified: mean age ( - ), gcs on admission ( - ), sbp , ich volume on admission . cc, ich volume on repeat scan . cc, change in ich volume . %, and mean time between initial and stability scans was minutes. eleven patients on vkas were identified who underwent reversal with -factor pcc. mean age ( - ), gcs on admission ( - ), sbp , ich volume on admission . cc, ich volume on repeat scan . cc, and time between scans was minutes. average inr on presentation was . . all patients on warfarin patients who had pcc administered before minutes ( ) had a mean change in ich volume of . %. patients who had reversal completed after the minutes ( ) had a mean change in ich volume of . %. (p value= . ). we propose a potential "recommended reversal time" of less than minutes for vitamin k antagonists in our institution. limitations of study include small sample size. the full outline of unresponsiveness (four score) is a validated scale that provides the essentials of a coma examination by incorporating motor response, eye opening and eye movements, brainstem reflexes, and respiratory pattern. we incorporated the four score into the existing ich score and consecutive patients admitted to our institution from - with spontaneous ich were reviewed. using patient age, hemorrhage location, hemorrhage volume, evidence of intraventricular extension and gcs, the ich score was calculated. the four score was then incorporated into the ich score as a substitution for the gcs (ich-four score). the ability of the two scores to predict mortality at month was then compared. in total, patients met inclusion criteria. the median age was years (iqr - ) and ( . %) were male. overall mortality at one month was . % (n= ). the area under the roc curve was . ( % ci . - . ) for the ich score, and . ( % ci . - . ) for the ich-four score. for ich scores of , , and , one-month mortality was . %, . %, . % and . %. in the ich-four score model, mortality was . %, . %, . % and . % for scores of , , and , respectively. the ich score and the ich-four score predict -month mortality with comparable accuracy. as the four score provides additional clinical information regarding patient status, it may be a reasonable substitute for the gcs into the ich score. depressive symptoms in patients with intracerebral hemorrhage (ich) are common and are associated with worse outcomes. it is not well described how often depressive symptoms are appropriately ascertained and treated in a multicenter cohort, and whether this is a potential target for improving outcomes. we retrieved diagnostic codes from four university health systems across chicago (multicenter cohort). separately, we prospectively screened for depressive symptoms (nih patient reported outcomes measurement information system, promis, t score ), in patients at one prospectively assessed cohort center at one, three and twelve months after ich onset. we compared detection rates of depressive symptoms between the two samples. diagnostic codes for depressive symptoms up to three months after ich onset were recorded in of ( . %) of the multicenter cohort versus of ( . %) in the prospectively screened cohort (or . , % ci . - . , p < . ). results were similar considering depressive symptoms up to months after ich, of patients in the multicenter ( . %) versus of prospective patients ( . %; or . , % ci . - . , p < . ). in the multicenter cohort less than % of patients months of ich onset. the prevalence of depressive symptoms in survivors of ich is more common than would be suggested treated and ssris may be an under-utilized therapeutic option. vitamin k antagonist (vka)are associated with higher mortality than primary ich. prompt reversal of international normalized ratio (inr) with prothrombin complex concentrate (pcc) may promote hemostasis and decrease hematoma impact of an electronic order set designed to standardize and facilitate more timely reversal of coagulopathy in vka-associated ich. we identified all adults that received pcc for vka-associated ich from june to march at ucsf medical center, which included a period before and after an electronic order set became available in . we abstracted baseline demographics and clinical data from electronic medical records. the primary outcome was time from radiographic identification of ich to administration of pcc. secondary outcomes included pcc dosing accuracy based on actual weight and baseline inr as well as time from pcc order to follow-up inr. we identified patients that received pcc for vka-associated ich, including patients before and patients after the order set became available. baseline demographics and clinical features were similar. order set use was associated with a significant decrease in the time from identification of ich on imaging to the administration of pcc (median vs. minutes; p= . ), more accurate doses delivered ( . % vs . %; p< . ), and a shorter time from the pcc order to follow-up inr (median vs minutes, -hospital mortality were similar in the two groups. an electronic order set for administering pcc for vka-associated ich was associated with significantly faster time to pcc administration and increased accuracy in dose administered. andrew naidech, alan a. long, kathryn k. muldoon, rajbeer r. sangha. northwestern medicine, chicago, il, usa. crucial to identify patients. both active contrast extravasation ("spot sign") and lower platelet activity have been associated with hematoma growth. we tested the hypothesis that patients with a spot sign had lower platelet activity. we prospectively identified patients with acute ich, measured platelet activity on admission, routinely obtained ct angiography and graded the presence or absence of a spot sign. we limited the analysis to patients who underwent ct angiography within hours of ich symptom onset. platelet activity was measured with the verifynow-asa (accumetrics, ca). non-normally distributed data were compared with the mann-whitney test, and binary variables with chi-squared or logistic regression. - . years, % were women and % had a history of hypertension. sixteen ( . %) had a positive spot sign. a spot sign was associated with lower platelet activity ( [ - ] vs. [ - ] aru, p= . , where <= aru indicates an aspirin effect). of patients with a spot sign, had platelet activity <= aru. platelet activity <= aru was associated with increased odds of a spot sign (or . , % ci . - . , p= . ). the presence of a spot sign on ct angiography was associated with lower platelet activity, suggesting a hematoma growth. introduction: clot dissolution is a biochemical process catalyzed by enzymatic proteins, requiring a specific temperature range for optimal function. clear iii, a randomized, double-blinded, placebocontrolled trial tested whether extraventricular drainage (evd) plus intraventricular alteplase improved outcome by removing ivh compared to evd plus saline. methods: retrospective assessment of prospectively collected temperature data q h over first days post randomization. blinded assessment o functional outcome (mrs - ). results: median (interquartile range) daily temperature was . ( . , . )°c and did not differ between - (vs. at days [ . ( . , . ) vs. . ( . , . ), p . °c was significantly associated with faster ivh clot lysis rate (spearmans rho . ; p= . ), but despite significantly higher temperatures, patients with mrs - (vs. mrs - ) had significantly lower average percentage ivh removal at day ( . ± . %vs. . ± . %, p< . ) and ( . ± . % vs. . ± . %, p= . ). temperature functional outcome of . ( %ci: . - . ) and . ( %ci: . - . ) at and days respectively, and was an independent predictor of poor functional outcome at day , but not after adjustment for early infection and other severity predictors. associated with faster clot lysis rate, but also with poor functional outcome. negative associations with of ich patients, patients ( %) had waich and received kcentra. the inr ranges were: . - . in patients ( %), . - . in ( %), . - . in ( %) and > . in patients ( %). within minutes of -minute repeat inr ranges were . - . and . - . , respectively. ffp was administered to ( %), ( %), ( %) and ( %) patient in each group for a persistently elevated inr. at h post-pcc, inr reversal occurred in %, % (rest had inr . ), %, and %, respectively. at h and one had dic following pcc administration. in this small case series of waich patients, inr correction with kcentra was adequate except for those with inr . - prevalence of stroke following craniotomy or craniectomy for spontaneously intracranial hemorrhage intensive care resources, particularly, neuroscience intensive care resources are limited and costly. in most institutions in the country, all intracerebral hemorrhage (ich) patients are admitted to the neuroscience intensive care unit. we sought to identify what criteria will allow us to determine which primary intracerebral hemorrhage patients will not need admission to an intensive care unit (icu). we studied retrospectively patients with primary ich from january to the end of dec . we reviewed multiple admitting characteristics: demographics, hematoma volume, location of hemorrhage, any brain compression, blood pressure, respiratory status, inr, glasgow coma score (gcs). the reasons for neuroscience intensive care unit admission requirements are the need for mechanical ventilation, hydrocephalus, increased intracranial pressure, low gcs score, hematoma expansion, or the unit, and who did not require any icu care intervention. this group had the following characteristics: supratentorial ich, ich volume . we called this criteria the "non-admission criteria for patients with primary intracerebral hemorrhage". patients were identified as primary ich. patients ( . %) fulfilled the non-admission criteria to the neuro-intensive care unit. of patients patients ( . %) discharged home, patients to acute rehab facility ( . %), patients discharged to snf ( . %), patient died ( . %); elderly patient with existing dnr comfort care orders. none of the patients had to be readmitted to neuroscience intensive care unit, and none required neurosurgical procedure. we propose that ich patients that fulfill the non-admission criteria do not have to be admitted to an icu and can safely be monitored in a step down unit this represented about % of ich patients at our tertiary academic medical center. future prospective studies are required to validate the criteria. joseph r. blunck, justin j. shewmaker. saint lukes hospital / pharmacy, kansas city, mo, usa. current guidelines recommend the use of -factor prothrombin complex concentrate (pcc) rather than fresh frozen plasma for reversal of warfarin-related intracranial hemorrhage (wrich). there is no consensus regarding an optimal pcc dosing strategy, but limited data suggest that pcc dosing should be based on weight and international normalized ratio (inr). in november of , our health system implemented a wrich reversal protocol with a -factor pcc dosing nomogram that utilized fixed-dose options of , above or below . the purpose of this study is to evaluate the effectiveness and safety of this simplified -factor pcc dosing protocol. patients given -factor pcc for wrich reversal in our health system were retrospectively identified with billing codes. chart review was completed to evaluate the primary endpoint of achieving a post treatment evidence of a venous thromboembolic event, time to goal -hospital mortality. we identified wrich patients from november through april that were reversed with our simplified -factor pcc dosing protocol. seventy-seven ( . %) patients achieved a post reversal goal -six ( . %) patients received a pcc dose equivalent to rounded pi dosing and the mean (sd) dose difference between groups was ( ) units vs. ( ) units, protocol vs. pi dosing, respectively. one patient ( . %) had a thromboembolic event that occurred days post reversal. a simplified -factor pcc dosing protocol is a safe and effective strategy for wrich reversal. -hospital, year and year mortality, and has been influences functional outcomes. we sought to evaluate the association between cci and outcomes in patients with primary intracerebral hemorrhage (ich). patients admitted to our center with primary-ich from - were included. demographic and clinical data were collected. the primary outcome measures were the proportion of patients with discharge mrs (dmrs) of - , death and poor discharge disposition (any disposition other than home or inpatient-rehabilitation). crude and adjusted logistic regression were used to evaluate the association between cci and outcomes. patients were identified. there were ( . %) patients with a cci of or , ( . %) patients with a cci of - , and ( . %) with a cci of or greater. while the continuous cci was not significantly associated with a dmrs of - (or . , % ci . - . , p= . ), it was associated with disposition. the odds of poor disposition increased % with each increase in cci (or . , % ci . - . , p= . ). the odds of death increases % with each point increase in cci (or . , % ci . - . , p= . ). after adjusting for baseline ich score, cci remains significantly associated with poor disposition (or . , % ci . - . , p= . ), however the association between cci and death was not statistically significant (or . , % ci . - . , p= . ). in contrast to previous studies, cci was not associated with poor short-term functional outcome or inhospital mortality in ich patients after adjusting for ich score. however, it was significantly associated with poor discharge disposition. this suggests that cumulative comorbidities only predict disposition in ich, because the ich score strongly impacts poor functional outcome and in-hospital mortality. accurate assessment of renal function remains a unique challenge in patients with intracerebral hemorrhage (ich). mathematical estimates of creatinine clearance (crcl) routinely used are often inaccurate in this setting. subsets of critically ill patients have been shown to exhibit a hyperdynamic response leading to an enhanced renal clearance. no studies exist evaluating the directly measured creatinine clearance of patients with ich. this was a single-center prospective observational study of adult patients with ich admitted to the nsicu between january and july . eight-hour urinary creatinine clearances were performed daily to directly measure crcl until the patient no longer had a foley catheter or the patient left the nsicu. urinary -gault equation. statistical significance was defined as p-value < . . thirty patients with ich were enrolled in the study. the study sample was % male with a mean age of ± . years. the median admission ich score was (iqr - ) with a mean ich volume of ± . ml. the median admission gcs was . (iqr - ) and median admission sofa score was . (iqr -additionally, the mean urinary crcl was significantly higher than the estimated crcl each individual study patients with ich consistently experienced urinary crcl greater than estimated crcl predicted based on -gault equation. as renally eliminated medications are routinely dosed based on mathematical estimates of renal function, further study is needed to optimize medication regimens in this patient population to prevent underexposure. the cognitive reserve hypothesis suggests that variations in patient pre-morbid status such as education, occupation and brain morphology influence outcome. this has been extensively validated in patients with alzheimer's disease. an important component of cognitive reserve is brain morphology, which can be quantified with measures such as whole brain-or gray matter volume. this study examines use of novel measures of brain morphology to measure cognitive reserve in patients with sdh. patients with ct-documented sdh were screened. we identified patients who had a clinically indicated post-morbid mri, telephone interview for cognitive status (tics) and barthel index (bi) at discharge and follow-up. mri was used to measure several volumes such as whole brain-, gray matter-, left vs right caudate-, hippocampal and intraventricular csf volume using a freesurfer pipeline. primary outcome measures were tics at and bi at months results: -up. regional - ) (sd), ---- at discharge and - . at follow-up ( -- . ) at mo. we found a positive correlation between intraventricular csf volume and bi at mo (r = . , p= . ). there was also a significant correlation between left caudate volume and bi at months. brain morphology did not correlate with tics outcome at months. quantitative imaging can be used to predict functional outcomes in patients with intracranial hemorrhages. as we continue enrollment we hope to generate meaningful no and brain tumors. christian hernandez, vivien v. lee, bichun b. ouyang, torrey t. birch. rush university medical center/department of neurological sciences, chicago, il, usa. it remains unclear which patients with intracerebral hemorrhage (ich) benefit from surgical hematoma evacuation, and the patient factors associated with the decision to pursue surgical intervention are largely early surgical intervention for ich and to investigate if an age bias exists at our institution. one hundred and twenty consecutive patients who were admitted to the neurosciences intensive care unit with primary ich between april and january were retrospectively reviewed. multivariate regression analysis was used to analyze if select patient factors were associated with the decision to pursue early surgical intervention. in total patients were analyzed; patients ( %) were female (mean age . ± . ), patients ( %) had supratentorial ich, and patients ( %) underwent hematoma evacuation. in univariate analysis age, race, and gender were not significantly a intervention. the only factors associated with hematoma evacuation were gcs score and ich volume. after controlling for significant variables, multivariate analysis showed that the only factor associated with surgical intervention was ich volume (or . , p= . ) . surgical intervention did not affect discharge disposition (p= . ), but was associated with a longer length of stay ( vs days, p= . ). in this analysis, ich volume was the only predictor of hematoma evacuation in patients with primary ich. age and sex did not influence patient selection for surgical intervention. surgical treatment did not affect patient disposition at discharge, but was associated with longer hospitalizations. further investigation is needed to determine which patients with ich benefit most from early hematoma evacuation. studied. we investigate factors associated with admission systolic blood pressure (sbp), including hemorrhagic transformation (ht) and discharge outcome. this is a retrospective study of consecutive ais patients presenting from april to march . demographic and clinical data were collected. admission sbp was divided into three tiers: . the primary outcome measure was in-hospital mortality. seven hundred seventy six patients were included (meanwere patients with sbp> ( . %), with sbp - ( . %), and with sbp were ry of hypertension ( . %; p . premorbid use of antihypertensives did not differ among the three groups. there were no differences in proportion of ht ( . % vs. . % vs. . %; p= . ). although patients treated with iv-tpa were evenly distributed among tiers ( . % vs. . % vs. . %), more patients with sbp had mrs - (p= . ). compared to sbp was associated with lower odds of in-hospital mortality (or . , %ci= . - . , p= . ). this remained significant after adjusting for age and nihss (or . , %ci . - . , p= . ). normal presenting sbp (< ) in patients with ais was associated with worse discharge functionaloutcome and higher in-hospital mortality. these differences may be related to other associated medical conditions such as pre-existing heart failure. further research is needed to define the ideal range to maintain sbp after ais. between april and february , patients with non-traumatic, non-aneurysmal and nonmalignant parenchymal cerebral icb were identified. the associations of nihss at presentation (nihssp), nihss at hours (nihssd ), size of icb, comorbidities, and infection with los were investigated retrospectively. the mean age for the patients was . ± . years and % were male while most patients were white ( %). the most prevalent comorbidity was hypertension ( % nihssd is a useful measure of los and should be collected for patients with icb. nihssd at upper teens present most challenges to discharge and should be the aggressive focus for discharge planners. incidence of infection and ventilator need is high in this population, adding to the challenges. although oral factor xa inhibitors (fxai), used for the prevention and treatment of venous racranial hemorrhage (ich) than warfarin in clinical studies, intracranial bleeding is still associated with high morbidity and mortality. moreover, there are no specific guidelines for managing these bleeds other than empirical institution-based hemorrhage protocols. there is a need to understand the real-world management, outcomes, and resource utilization of fxai-associated major bleeding in order to potentially improve morbidity and mortality in these patients. five us medical centers participated in a retrospective study of patients admitted to the hospital with lifethreatening bleeding on or after january while on apixaban, rivaroxaban, or low molecular weight heparin (lmwh). baseline characteristics, treatment patterns, outcomes, and resource utilization were assessed. ich patients were reviewed and are reported specifically. this interim report includes major bleed patients, including ich. the majority of ich were hypertensive [ ( %)], ( %) were on concomitant anti-platelet with fxai, ( %) were diabetic and e ich was spontaneous ( %) and trauma ( %). in the management of ich bleeding, % of patients received clotting factors (e.g. pcc), whereas % received interventions (e.g. radiological embolization). within days of discharge, ( %) died, of which occurred during the admission. for the patients who did not die, length of hospitalization was . ( . - . ) days, with only discharged patient restarting on an anticoagulant. this study provides a real-world picture of patients receiving fxais or lmwh, experiencing lifethreatening intracranial bleeds. despite efforts to restore hemostasis, mortality remains high and substantial healthcare resources are expended. this highlights the need to develop specific strategies for managemen prophylactic seizure medications are not recommended by guidelines for patients with intracerebral hemorrhage, yet are prescribed to nearly % of them. there are few data on disparities in their use. we tested the hypothesis that there are differences in the administration of seizure medication, specifically we electronically retrieved information from patients who were diagnosed with intracerebral hemorrhage from healthlnk, a multi-center electronic repository in chicago, il, from - ("multicenter cohort"). from through , we prospectively identified patients with intracerebral hemorrhage at one site ("prospective cohort"). there were , patients in the multicenter cohort from four sites. the use of levetiracetam varied with -americans (or . , % ci . - . , p< . ). in the prospective cohort (n= ), hematoma location, older age, depressed consciousness, larger hematoma volume and no alcohol abuse were -americans to receive levetiracetam (or . , % ci . - . , p= . ). african-americans were more location was independently associated with levetiracetam administration (p< . ) disparities in the use of levetiracetam and they are confounded by hematoma location, a datapoint not typically available in administrative datasets. deviation from guidelines for the use of seizure medications is common and rational, and any impact on outcomes is uncertain greater gains in late recovery for intracerebral hemorrhage patients with more debilitating initial injury. multiple intracerebral hemorrhage (ich) studies have examined differences between discharge and month outcome. however, few studies have examined late recovery specifically between -and month endpoints. the aim of this study was to identify potential factors predicting late recovery in ich patients. twenty-four patients diagnosed with primary ich at yale-new haven hospital were prospectively enrolled between july , and july , . outcomes were assessed using barthel index (bi) at discharge, months, and months. repeated-measures regression analysis was conducted using age, admission glasgow coma scale (gcs), ich volume, intraventricular extension, and ich location, to compare outcomes at discharge, months, and months. there was a significant improvement across time points (p = . ), with follow-up testing showing improvement between discharge and months (p < . ), discharge and months (p = . ), and months and months (p = . ). regression testing resulted in a significant relationship of time (p = . ), time x gcs (p = . ), time x ich volume (p < . ), time x ich location (p < . ). plots show increased late recovery (i.e., between and months) for patients with lower gcs scores, larger ich volume, and deep ich location. patients with more devastating initial ichs show greater gains in late recovery between and months. these results suggest initial disability at months may not represent overall recovery and support continual follow-up out to one year. while extensive studies have examined the outcomes of intracerebral hemorrhage (ich) patients under the age of , few studies have examined outcomes in an elderly cohort (> years). the aim of this case-control study was to determine the independent effects of age on outcome after ich. nineteen ich patients prospectively identified at yale-new haven hospital above the age of were matched against patients below age , based on ich location (lobar, deep, cerebellar, brainstem), ich volume (> cc), presence of intraventricular hemorrhage (ivh), and admission gcs ( - , - , - ). the matched groups were compared via univariate analysis to examine differences in morbidity while there was no difference in pre-ich disability (mrs > ; p > . ), at months elderly patients exhibited higher morbidity (mrs > , p = . ). despite these differences, there were no differences in overall mortality between groups at discharge or at months and no differences between barthel index at months. despite greater morbidity as defined by mrs, elderly patients with ich do not significantly differ from younger patients in mortality rates or ability to perform activities of daily living at discharge and months. these results may warrant further studies to provide more accurate prognostication after ich in elderly populations. hypertension after intracerebral hemorrhage (ich) is associated with hematoma expansion, morbidity and mortality. there are currently no recommendations to standardize the critical care approach to acute blood pressure (bp) management in ich. we performed a large retrospective cohort study to examine practice variability in bp management in acute ich. care center using local get with the guidelines data. we abstracted time-stamped clinical variables including all documented bp measurements, and medications administered, as well as hematoma location from the electronic medical record. all acute ich patients are admitted to the neuroicu and comanaged by neuro-intensivists and vascular neurologists. we used descriptive statistics to summarize overall population and treatment characteristics. - ) years, and % were female. and % other. electronic medical record data were available in subjects, of which ( %) received continuous infusion for bp control within hours of admission ( % nicardipine, % clevidipine). a systolic bp goal was charted in ( %) and ranged from to mmhg. these goals were modified in % during the same admission ( % increased, % decreased). overall, unique oral antihypertensives were administered ( % received a beta-an ace inhibitor, and % a diuretic). hypertension requiring continuous antihypertensive infusion is common after ich. there is high practice variability in bp targets and choice of antihypertensive medications. a prospective study of a systematic and protocolized approach to antihypertensive medication use in ich is necessary to determine if reducing practice variability improves outcomes. intracranial hemorrhage (ich) has long been thought to be a devastating consequence in the setting of end-stage liver disease. due to its association with abnormal coagulation, the prognosis is thought to be poor, and frequently leads to withdrawal of care. our aim with this study was to assess the true overall mortality rate of ich in end-stage liver disease and compare it to mortality of ich in the general population. all patients > years of age admitted to mayo clinic from to with a subsequent diagnosis of non-traumatic ich and end-stage liver disease were identified. patients presenting with primary epidural, subdural, intraventricular, or subarachnoid hemorrhage were excluded. using actuarial methods, day, day, and year mortality rates were calculated. patients with simultaneous diagnosis of ich and end-stage liver disease were identified. of the patients were female ( %) and patients were male ( %). the mean age at diagnosis was years. the mean systolic blood pressure in the mortality cohort was mmhg, compared to mmhg in the survival cohort. the day, day, and year mortality rates were %, %, and % respectively. ich associated mortality in end-stage liver disease does not significantly differ when compared to ich mortality in the general population. the mean systolic blood pressure at presentation did not specifically correlate with an increased incidence of ich associated mortality. these findings are important in the practice of neurocritical care, confirming that poor prognostication and expedited withdrawal of care should be reconsidered. future directions will include mortality adjusted by hemorrhage location, size, and presence of intraventricular extension. kcentra® (human prothrombin complex concentrate) is the first fda-approved non-activated -factor prothrombin complex concentrate for the urgent reversal of vitamin k antagonist agents in adults with acute major bleeding. the recommended dosing is based upon the units of factor ix, which can vary within each vial (range from vial size to reduce waste and some based upon the exact factor ix content. this variation in dosing may be associated with complications in care and has never been evaluated. underdosing of the medication can lead to suboptimal response and overdosing the medication can cause thromboembolic events. the purpose of this observational trial is to assess the current prescribing practices of kcentra® in neurocritical care unit patients across the united states and evaluate the impact on patient response and safety. additionally we plan to characterize current approaches to repeat dosing. this was a retrospective observational study of adult patients across centers who received kcentra for reversal of warfarin-related bleeding between january , and december , . descriptive statistics and tests for comparison will be utilized to evaluate differences in dosing, outcome, and the occurrence of adverse events. statistical significance will be defined as p-value < . . data collection is ongoing but the full results will be presented during the meeting. result of this study will document the real-world use of kcentra® in patients with severe life threatening bleeding and assess the impact of variations in prescribing practices on patient responses. there is a paucity of data regarding this topic and combining data from multiple neurocritical care units will be timely in identify optimal dosing strategies. perihematomal edema (phe) associated with intracerebral hemorrhage (ich) has been suggested to have an impact on both mortality and functional outcomes in spontaneous, supratentorial ich. there have been no studies examining the impact of phe in infratentorial hemorrhage. the aim of this study was to evaluate the impact of absolute phe volume as well as phe expansion rate in cerebellar hemorrhages at the time of discharge and at months. patients diagnosed with primary cerebellar ich at yale new haven hospital were prospectively enrolled between july , and july , . patients were evaluated using mrs and bi at discharge and months. ich and edema volumes on ct were measured using a semi-automated threshold based approach and phe expansion rate was the difference between initial and follow-up phe volumes divided scale (gcs), ich volume, intraventricular (ivh) volume, edema (phe), and phe expansion rate from baseline to first follow up ct scan before decompression ( h window). at discharge, patients with higher morbidity (mrs > ) exhibited higher ich volume (p = . ) and phe volume (p = . ) on admission ct and a trend for greater rates of phe expansion (p = . ). these differences were not significant at months and when adjusted for ich volume. plots suggest an association between higher phe rate and lower bi scores at months. phe may have a clinically significant impact in patients with cerebellar ich at time of discharge, but these results are limited by a small sample size. these results warrant further studies and suggest therapies to ameliorate edema may be a treatment option for cerebellar ich. yahia thrombolysis and adjunctive stent retriever thrombectomy (srt) is associated with better perfusion and outcomes. despite benefit, % to % of patients had poor outcomes. thrombectomy in ais with lao within hours is performed as secondary after iv thrombolysis, which may be associated with delay. the purpose of our study is to evaluate the safety, feasibility, recanalization rate and outcome of primary str within hours without intravenous thrombolytic in ais from lao. srt as an alternative to iv rtpa. consecutive patients who underwent primary srt for lao within patients with lao; mean age . ± . years and mean nihss ± ; chose primary srt after informed consent. near complete (tici b in ) complete (tici in ) was observed in all ( %) patients. recanalization from symptoms and groin puncture was . ± . and . ± . minutes respectively. immediate post-thrombectomy, hour and day nihss score was . ± . , . ± . and . ± . respectively. asymptomatic perfusion related hemorrhage developed in patients ( %). days outcomes; mrs %, mrs . %, and mrs . %. our study demonstrates that primary srt in ais from lao occlusion is not only safe and feasible, but associated with complete recanalization and good outcome. further study is required. currently, no reliable predictive tools are available to determine which patients with a large hemispheric infarction (lhi) will progress to cerebral herniation (ch). we sought to determine whether continuous measurements of blood pressure variance (bpv), heart rate variance (hrv), and entropy within hours of admission would enhance the ability to predict future ch in lhi patients. patients presenting within hours of onset from an internal carotid artery (ica) or middle cerebral artery and november . patients with ch were matched : by age and nihss with patients who did not have ch. shannon entropy and standard deviation were used to measure the instability of hr and between groups. a model predicting ch utilizing the admission factors of age, gender, nihss, intraarterial (ia) therapy, and thrombolysis was compared to an admission model enhanced with bpv, hrv and entropy hours after admission. data from patients were analyzed (median age years old, median nihss , % women). there were no differences in the proportion of patients with a left hemisphere syndrome ( %), undergoing ia therapy ( %) or thrombolysis ( %) between groups. ch was observed a median of days after the ictus. at hours after admission, median measures of bpv, hrv and entropy were significantly higher in the ch group (p< . ). a model of admission factors enhanced with physiologic data was better able to predict ch than a model with admission factors alone (roc: . v. . , p= . ) poster early recognition of which patients with large hemispheric infarction (lhi) will develop malignant cerebral however, the early time-course of edema has not been adequately studied. we applied volumetric in the first hours, prior to development of midline shift (mls). we identified lhi patients with scans within six hours of onset and subsequent scans early ( - while all recently published endovascular stent-retriever randomized clinical trials (rcts) were positive, their designs differed considerably particularly with regard to the extent of intravenous rt-pa use prior to thrombectomy. here, we assessed whether rt- we adapted a method previously published by us to develop a pooled outcome model relating percent utilization of rt-presenting > , subjects and a range of - % utilization of rt-pa. we correlated percent rt-pa and baseline - ) and mortality. this model includes ± p<. statistical interval surfaces to assess whether a trial's outcomes surpasses the variability of the pooled sample (neurology : - , ) . stent retriever rcts were compared against the model. the mrs model showed excellent fit: r-square= . , p< . . each stent retriever trial's outcomes exceeded mrs improvement varied dramatically according to %rt-pa, with the greatest improvement in those with % rt-pa use. when we included all case series and testing their outcomes at their baseline nihss and percent rt-pa use, shortest overall treatment times also related to improved outcomes (p=. ). mortality trends were similar in that lowest mortality was seen in those trials with highest rt-pa use and the trial with higher than expected mortality had the lowest rt-pa use. an outcome model including % iv rt-pa permitted analysis of stent-retriever therapy compared to a large sample. best outcomes were related to higher rt-pa utilization and shorter treatment times, suggesting a strong treatment interaction between modalities. based on these results, until studied prospectively, iv rt-pa, if administered rapidly, should not be bypassed prior to thrombectomy. intra-arterial mechanical thrombectomy (iamt) is currently considered the standard therapy for acute thrombectomies performed under general anesthesia (ga) may adversely affect functional outcomes. we report our experiences with iamt performed routinely under ga at the montreal neurological hospital (mnh). this is a retrospective analysis of adult patients admitted to the mnh from january to april with ais from proximal intracranial occlusions of the anterior cerebral circulation. all patients were assessed both clinically and radiologically. forty-two patients underwent iamt for ais. twenty-eight patients were included for analyses ( had procedures under conscious sedation, had missing months assessment). clinical outcomes were (mrs) outcomes (mrs --good and poor outcome groups respectively. sixty-eight percent of the good outcome group received iv tpa, as compared to % in the poor outcome group. patients in the good outcome group were also more % in the poor outcome group]. intraprocedural map drops below mmhg observed in patients in the good outcome group versus non in the poor outcome group. in our small retrospective single centre study about thrombectomy for ais under ga, our -month outcomes are comparable to larger studies where thrombectomies were done under conscious sedation. pending the results of ongoing prospective trials about the use of ga during iamt for ais, our results do not support the reservations derived from recently published retrospective data on the use of ga in this context. conservative initial management of young adults with severe hemispheric stroke in a comprehensive stroke center reduces decompressive craniectomy rates pooled european trial results of early decompressive craniectomy (dc) did not require radiographic mass effect at the time of dc. early surgery for supratentorial cerebral hemorrhage does not improve recovery or survival compared to initial conservative medical management. early vs delayed dc for hemispheric a prospective inpatient neurosurgical database from october to march was queried for neurocritical care admissions for hemispheric - under irb approval. a retrospective chart review was conducted using a structured questionnaire using the electronic medical record. we identified patients who met the inclusion criteria for the pool were managed with medical treatment only (mto) with average maximal septal shift of . mm and pineal shift of . mm. twelve patients ( %) underwent dc with average maximal septal shift of . mm and group, mto, and dc were respectively: mr - % vs % vs %; mr - % vs % vs %, and death % vs % vs %. four patients in the mto group declined dc; died and one survived with mr of . no patients developed brainstem herniation prior to referral for decompressive craniectomy. surgical complications death or survival with severe disabilities. time of recanalization since symptoms is a strong predictor of outcome in patients who underwent stent retriever thrombectomy from middle cerebral artery occlusion. hours since symptoms have not been clearly investigated especially, those with large artery occlusion (lao) and underwent stent retriever thrombectomy (srt) . objective: to identify the predictors of outcome in ais patients from middle cerebral artery (mca) occlusion with large clot burden (lcb > mm) and underwent srt, who recanalize less than hours versus more than hours since symptoms. software was used to analyze the data. ais patients who underwent srt in mca; age . ± . years and mean admission nihss ± . complete (tici ) and partial (tici b) recanalization was observed in . % and . % respectively onset was ± minutes. presenting nihss of . dropped to , and at immediate, hours and days post srt respectively. good univariate analysis, recanalization time, immediate and hours post srt nihss were predictors of outcome (p-value= . , . and . respectively). in multivariate analysis, time of recanalization since symptoms (p-value= . ) and baseline mrs (p-value= . ) continued to be the predictors of good outcome. our study demonstrates that patients with lao from mca who recanalize less than hours of symptoms onset have good chance of good outcome compared to those who recanilize more than hours. therefore, all ais patients with lao should offer early srt to achieve a good functional outcome. further studies are required. jennifer a. frontera. neurological institute, cleveland clinic, cleveland, oh, usa. prospectively collected data of heartmate ii (n= ) and heartware (n= ) lvad patients from a single blood stream infection [bsi]), specific pathogens mann-whitney u, chi--wise logistic regression analyses. of patients, lvad infection occurred in ( %) including: bsi in ( %), wound infection in infect p< . ). driveline and wound infection were not a - . , associated with bsi (aor . , %ci . - . , p= . ). there was no association with any specific infectious pathogen. precautions to mitigate i demonstrate a causal relationship. the frequency of dysphagia is greater than %. the early clinical evaluation of swallowing disorders can help define approaches and avoid oral feeding, which may be detrimental to the patient. the aim of this study was to identify predictive clinical factors associated with enteral tube feeding in acute ischemic our database were reviewed. clinical early ct score (asp association. of the patients, used enteral feeding tubes ( . %). the mean age ( . years -sd . ), mean gcs ( . -sd . ), mean nihss ( . -sd . ), and aspect score ( . -sd . ) were significantly higher in the tube group. logistic regression showed that only age (odds ratio [or], . ; % confidence interval [ci], . - . . p= , ), nihss score (or, . ; % ci, . - . , p= , ) and nihss (dysarthria) subscore (or, . ; % ci, . - . , p= , ) were independent predictors of enteral tube feeding. a - in conclusion, combining information about age, nihss, nihss subscore, may be a useful predictor kyushu university, fukuoka, japan. tissue plasminogen activator (te designed and developed an information and communication ipads, pcs, and bigdepartments before the patient's arriva number of calls is reduced. we compared the number of times that emergency room (er) nurses called for computed tomography (ct) or magnetic resonance imaging (mri) between before and after the system introduction. before this system, er nurses called for ct or mri an average . and . times, respectively; after system introduction, the average number of times decreased to . and . , respectively. therefore, this system -pa. also, it automatically records the transitions between could improve treatment times for iv tclinical trial to confirm the tool's efficacy. an important and controversial issue of peri-(est) is the management of sedation and airway. according to retrospective data the widely favored intubation and general anesthesia (ga) appears associated with worse functional outcome compared to "conscious sedation" (gs) in the non-intubated state. siesta is a prospective, monocentric, outcome assessor-blinded, : randomized, parallel-group interventional study comparing non-intubated vs. intubated patients receiving est for acute ischemic endpoint is the improvement of the national institute of health s enrolment of the intended patients has been completed. sixty of the recruited patients are female these patients, % received pre-procedural rtpa. seventy-eight patients were randomized to cs, ( %) of these had to be converted to ga during the procedure. we will present preliminary results of the study, including the primary endpoint improvement in nihss after hours and selected secondary endpoints. the aim of this study is the prospective randomized investigation of potential advantages of the non- in young chung. departments of neurology , seoul national university bundang hospital, seongnam, korea, republic of. cerebral edema during therapeutic hypothermia us hypothermia. the authors retrospectively reviewed patients with large hemispheric infarction who were treated with therapeutic hypothermia and hyperosmolar therapy from to . patients who were dead or underwent hemicraniectomy was defined as failure of therapeutic hypothermia. infarction size was measured as sum of restricted area in diffusion weighted imaging which were performed on admission. b -ct was carried out regularly after onset of therapeutic hypothermia. shift of septum pellucidum, pineal gland and choroid plexus calcification were measured in b-ct. seventeen patients were enrolled after exclusion of patients whose b-ct was inadequate to evaluate. ten patients were successfully treated with therapeutic hypothermia (group success, n= ). six patients were dead and patient had hemicraniectomy (group failure, n= ). initial infarction size between two groups was not significantly different. both septum pellucidum shift (sds) and pineal gland shift (pgs) were significantly different in groups on . ± . days after onset of therapeutic hypothermia (mean sds . vs. . mm ; mean pgs . vs. . mm). specificity and positive predictive values for the failure calcification shift was not significantly different in groups during therapeutic hypothermia. degree of progression of cerebral edema on . ± . days after onset of therapeutic hypothermia helps to excellent in predicting fatal outcome. the main limitation of this study include its retrospective singlecenter nature, which may limit generalizablility of the study. aminocaproic acid for reversal of tissue plasminogen activator (tpa) related hemorrhagic transformation in acute ischemic stroke. -thrombolytic ich. aminocaproic acid (aca) inhibits binding of plasminogen to fibrin, hence inhibiting fibrinolytic property of tpa. there is limited report a case series of aca use for reversal of post-tpa ht. we reviewed the and identified patients treated with iv tpa. patients with post-tpa ht who received iv aca were identified. data on demographics, clinical characteristics, nihss, ich score, new thrombotic events during hospitalization, and hospital and intensive care unit (icu) length of stay (los) were collected. a total of patients developed post-tpa ich, of which received aca. % of patients were male, mean age of . ± . years. patients received tpa within a mean time of ± minutes from symptom onset, pre-tpa mean nihss was . ± . . mean time for ht after tpa administration was . ± . hours, with a hematoma volume of . ± . mm . in addition to aca, % received cryoprecipitate, % platelets, and % fresh frozen plasma transfusions. % of patients had no hematoma expansion and % developed a new thrombotic event. mean hospital los was ± days and mean icu los was ± days. at the time of discharge % had an mrs of , % mrs and % mrs . in this retrospective case series % of patients had hematoma expansion despite receiving aca, while % had a new thrombotic event. further research is warranted to determine the utility of aca for the treatment of post-tpa ht. large vessel occlusion (lvo). while studies have analyzed difference in blood clot constructs, limited data is available understanding the effect of prior anti-platelet use on endovascular therapy (evt) for ias patients with lvo in the middle cerebral artery (mca). we aimed to determine if prior anti-platelet use had effect on evt procedure time, recanalization rate, and functional outcome measured by the modified a retrospective chart review was conducted of consecutive ais patients who underwent evt of lvo of mca at the university of kansas medical center from - . outcomes were measured using total procedural and fluoroscopy time, procedural recanalization score using the modified thrombolysis in cerebral infarction score (tici), time to recanalization, incidence of sich, and -month mrs. univariable and multivariable analysis were performed. . for all) were similar between antiplatelet use versus those without. in separate multivariable models (adjusting for all significant variables), antiplatelet use was not associated with tandem ica occlusion, total procedure time, fluoroscopy time, good recanalization, or -month mrs. no impact was found of prior antioutcomes in ais patients undergoing evt. these findings should be further confirmed in a larger database and prospective cohort study. the study evaluated the effect of a neurology-specific heparin infusion protocol with more frequent ptt monitoring and a narrower goal ptt range ( . x normal) on rate of hemorrhagic or thromboembolic events. this is a retrospective cohort study evaluating patients before (october -september ) and after (october -september ) implementation of a neurology-specific heparin infusion protocol. all patients > years old receiving intravenous heparin with a diagnosis of acute ischemic st evaluated for inclusion. primary outcomes are time to first therapeutic ptt and time to therapeutic ptt range. secondary outcomes include rate of intracranial hemorrhage, rate of thromboembolic events, protocol compliance, number of subtherapeutic and supratherapeutic ptt values, time to initiation of oral anticoagulation, duration of heparin infusion, and number of heparin titrations. time to therapeutic ptt range was . hours in the pre-protocol group (n= ) and . hours in the post-protocol group (n= ) (p= . ). number of ptt values per patient was . in the pre-protocol group and . in the post-protocol group, of which . % and . % were therapeutic, respectively. percentage of supratherapeutic ptt values was . % and %, respectively (p= . ). time to first ptt, time to first therapeutic ptt, and percentage of subtherapeutic ptt values were not significantly different. assessment of secondary clinical outcomes is ongoing. our neurology-specific heparin protocol resulted in a faster time to therapeutic ptt range with a higher percentage of therapeutic ptt values and fewer supratherapeutic ptt values. investigation regarding change in incidence of hemorrhagic and thromboembolic complications is ongoing. hospital moyses deutsch, in the southern city of são paulo is indicated for the use of rtpa intravenously ctive to demonstrate experience the use of intravenous retrospective study, in all cases of isch to february . protocol indicates the use of alteplase patients with inclusion criteria, the period between the onset of symptoms and hospital admission up to . hours and no contraindication to the use of thrombolytics, nihss calculated on admission and hours after thrombolysis. computed tomography (ct) on admission and after hours.evaluation required by neurological telemedicine hospital israelita albert einstein shortly after the conclusion of the tc cranio. trough has been triggered in cases. time between onset of symptoms and drug administration, patients less than minutes, patients between and minutes, patients - minutes .the average nihss at admission was , with patients showed a reduction of or more the points nihss score within the first hours. patient non-symptomatic intracranial hemorrhage and symptomatic intracranial hemorrhage and deaths during the period. all patients receiving alteplase in the recommended time interval and underwent ct cranio control. some cases were not triggered by the evaluation of neurology telemedicine. there was improvement in nihss score similar percentage observed in reference studies. the protocol implementation has been adequate excellent support of telemdicina neurology team. good profitability of time and therapeutic efficacy. the mortality that correlated with the severity of patients and the nihss admission. this data ratifies the intracerebral hemorrhage (ich) is approximately % and non-ich bleeding over %. hypofibrinogenemia occurs in approximately % of tpa-treated patients and i cryoprecipitate is often used to restore fibrinogen levels, despite limited published evidence. cryoprecipitate has several limitations, including the need for abo matching, thawing, and concerns regarding potential transmission of viral pathogens. riastap, a purified fibrinogen concentrate, is a promising alternative to cryoprecipitate for the reversal of hemorrhage post-tpa. the objective of this study was to evaluate the safety and efficacy of riastap for the treatment of post-tpa hemorrhage. a single-center retrospective observational analysis was conducted to evaluate patients who received riastap for the treatment of postmeasure was reversal of hypofibrinogenemia. hypofibrinogenemia was defined as a fibrinogen level < hospital mortality. eleven patients were included in our analysis. the average dose of riastap administered was , units. five patients had hypofibrinogenemia prior to riastap administration, with a mean fibrinogen level (iqr to ). the six patients who were not hypofibrinogenemic at baseline had minimal effect on fibrinogen levels post-- . to ). one patient was diagnosed with a deep vein thrombosis days post-riastap administration and no infusion reactions were reported. in-hospital mortality occurred in . % of our patient population. riastap administration successfully and safely treated hypofibrinogenemia in patients with post-tpa hemorrhage. casey catheter-associated urinary tract infections (cauti) are the most prevalent hospital-acquired infections (hai), and account for more than , cases annually and , deaths per year. cauti is the most common hai in neuroscience intensive care units ( immobility and urinary retention. we implemented a team-driven multimodal quality improvement initiative to reduce cauti and catheter-utilization rates in the nsicu. we convened a multidisciplinary cauti prevention team including nurses, advance practice providers, physicians, and infection control specialists. we developed a cauti surveillance program that involved review cauti and catheter utilization rates. we applied root cause analysis to target improvement opportunities, and implemented interventions including best-practice catheter insertion techniques, modification of bowel regimen, and guidelines for timing of catheter removal. we also implemented a daily goals tool to prompt standardized team communication surrounding catheter removal on morning interdisciplinary rounds. we performed poisson generalized linear model analyses, controlling for linear time trends and testing with sandwich errors. we analyzed data before and after implementation of interventions, spanning a time period of months. -- . ), as did mean catheter days per -- . ). we observed a % reduction in cauti rate adjusted by catheter days ( % ci %, %), p = . . there was an % reduction in catheter utilization rate adjusted by patient days ( % ci %, %), p = . . a team-driven multimodal approach to cauti reduction resulted in significant decreases in cauti and catheter utilization rates in the nsicu. team-driven interventions enhance communication and shared -up is ongoing to evaluate sustainability. non-neurological complications involving a single or multiple organ systems during intensive care in critically ill patients of traumatic brain and spine injuries is significant cause of poor prognosis but often not well managed. the aim of this study was to assess the frequency of such complications in neuro icu and assess their impact on morbidity and mortality. a prospective observational study on patients of varied demographic profile admitted in neuro icu over a period of months for injury and associated multisystem involvement was conducted. significant predefined parameters addressing the non-neurological complications occurring during their icu stay were recorded including disturbances and bleeding complications. the study period was from admission to the icu till the discharge from the icu or demise. % of patients developed respiratory complications in the form of chest infiltrate ( %) and atelectasis ( . %). . % of patients suffered from cardiovascular complications. % of patients had dyselectrolytemia, commonest being hypernatremia due to hypovolemia ( %). sepsis was observed in . %. bleeding diathesis and acute renal injury were observed in % & . % of patients respectively. % of the patients succumbed to injury out of which . % was due to non -neurological cause. further results will be discussed in detail with inferences at the meeting. intensivists in neuro icu must consistently assess and treat the non-neurological complications in traumatic brain and spine-injured patients and deliver appropriate care to bring down the mortality and morbidity and improve outcome. neurocrit care ( ) :s -s transcranial doppler (tcd) is a useful ancillary test in neurologic critical care for monitoring patients at with elevated intracranial pressure and cerebral vascular resistance. the normal values of cerebral blood flow velocity and pis are significantly distorted by nonpulsatile blood flow, as in patients on venoarterial extracorporeal membrane oxygenation (va-ecmo) circulation. this analysis evaluates changes in pi measurements in patients on va-ecmo following cerebral vasodilation, vasoconstriction, increased intracranial pressures, or cerebral circulatory arrest. data from tcds in patients on va-ecmo in the cedars sinai medical center cardiac surgical icu were reviewed. mean pis were calculated for each patient using gosling's pi formula. the values obtained were compared with ejection fractions (ef) obtained within hours of tcd. pis were globally low or absent in all tcds. the non-demonstrable pi seen in one patient is from severely diminished cardiac function, resulting in tcds were performed at the initiation and conclusion of va-ecmo cannulation. the pi values for these tcds correlated directly with changes in efs. also, an abrupt rise in pi to normal value was seen with placement of a total artificial heart and return of pulsatile circulation. we demonstrate that patients on mechanical circulatory support demonstrate low-absent pis on tcds. ion or cerebral circulatory arrest. moreover, rising pis in patients with improving cardiac function should not be confused with elevated intracranial pressures. venous thromboembolism (vte) prophylaxis in underweight patients with neurologic injury remains unaddressed by recent guidelines and primary literature. this study aimed to describe vte prophylaxis strategies employed in this population and compare the impact of underweight and non-obese patients on thrombotic and bleeding events. underweight and non--care unit from september , to july , were retrospectively identified. underweight was defined as a body -obese as a bmi . excluded if they received > vte prophylaxis regimen, had an icu length of stay < hours, or received vte prophylaxis for < hours. patients were stratified to non-obese and underweight groups and subsequently matched : , on age and diagnosis. prophylaxis regimen, prevalence and type of the most common regimen in the underweight (n= ) and non-obese (n= ) groups was unfractionated (ufh) units subcutaneously every hrs ( . % vs. . %; p= . ). only underweight patients received ufh units subcutaneously every hrs ( . % vs. . %; p< . ). non-obese and underweight patients had no difference in the proportion of overall bleeding ( . % vs. . % p= . ) and thrombotic events ( . % vs. . % p= . ) while receiving vte prophylaxis. further analyses revealed a statistically significant difference in the proportion of underweight patients that developed intracranial hematoma expansion while receiving prophylaxis versus non-obese patients arge dispositions were seen between groups. current practice does not reflect a consistent dose reduction for neurologically-injured, underweight patients. caution should be considered when using increased doses of ufh in neurologically-injured patients. continued assessment of vte prophylaxis is needed to confirm these findings. patients in the neuro intensive care unit (nicu) commonly need vasopressor infusions for various reasons. the traditional approach is to insert central venous catheters (cvc) for this purpose. cvcs carry among others. phenylephrine is a commonly used vasopressor in the nicu. the purpose of this study was to evaluate the safety of phenylephrine infusion through peripheral intravenous catheter (iv). retrospective review of consecutive patients admitted to the neuro icu and administered phenylephrine infusion through peripheral iv line. one hundred patients, mean age years (sd ± ) were included in the analysis. fifty-four ( %) were men. eightydisease. the most common indications of phenylephrine were hemodynamic augmentation ( %), multifactorial transient post-operative hypotension ( %) and hypotension due to other causes ( %). most common location of iv line was proximal upper extremity ( % antecubital, % forearm) with gauge of the iv line between ( %) and ( %). average maximum rate of phenylephrine infusion duration of hours (sd ± , range to ). central line was eventually placed in % due to physician preference and in another % due to a change of vasopressor to norepinephrine. there were any complications. infusion of phenylephrine through peripheral iv appears safe when used in moderate doses for the short term and can be considered in lieu of placing a central line solely for this purpose. this may reduce the complications associated with central lines. osmotic therapy continues to be standard care in the medical management of cytotoxic cerebral edema. the long term use of monotherapy is often limited by side effect profile. the combination of low dose mannitol and hypertonic saline may provide synergistic effect by combining mechanisms of action, while limiting dose-related toxicities of either agent. we investigated safety and efficacy endpoints for combination therapy. a single-center retrospective cohort study from august to december . identified patients were administered combination mannitol and hypertonic saline for > hour duration. the primary outcome criteria, sodium fluctuation, and central pontine myelinolysis. patients (mean age ± , % male) were identified. underlying neurological injury included % brain injury. % had neurosurgical management. the average number of mannitol doses given was , and the average duration of hypertonic saline was hours. the range of mannitol dose was . - . percentage of osmotic therapy doses were held for pred mannitol, % held hypertonic saline). aki occurred in ( %) patients ( -stage aki, -stage central pontine myelinolysis. low dose combination osmotic therapy was tolerated with no central pontine myelinolysis and rare sodium fluctuations; however transient low grade aki was common. further study is needed to evaluate the relative efficacy of single and combination osmotic therapy in the neurocritical care population. clinical characteristics of nonconvulsive status epilepticus diagnosed by simplified continuous eeg monitoring at an emergency intensive care unit. the clinical characteristics of nonconvulsive status epilepticus (ncse) presenting in icu in japan is limited. our institute provides a noninvasive monitoring system of two-channel simplified continuous eeg (seeg) for the bedside monitoring of cerebral activities. the present study aimed to elucidate the clinical characteristics of ncse in patients with altered mental status (ams). this single-center retrospective study comprised patients who were hospitalized between march , and september , at the emergency intensive care unit (icu) of the kagawa university hospital. primary outcome was the ncse incidence. the secondary outcome was the comparison of duration of icu stay, hospital stay, and a favorable neurological outcome (fo), as assessed using the tal between the groups with and without ncse. fo and poor neurological outcomes (po) were defined as mrs scores of - and - , respectively. simplified continuous electroencephalogram (seeg) was monitored in patients (median age, years; . % males) with acute ams. ncse was observed in ( . %) of the patients with ams. rates of fo, duration of icu stay, and hospital stay were not significantly different between the ncse and non-ncse groups (p = . , p = . , and p = . , respectively). approximately % of the patients with ams admitted to emergency icus developed ncse. the outcomes of ams patients with and without ncse did not differ significantly when appropriate medical attention and antiepileptic drugs were initiated. seeg monitoring may be recommended in patients with ams in emergency icu to obtain early detection of ncse followed by appropriate intervention. approximately , people per year will need mechanical ventilation secondary to neurological injury resulting in significant mortality. delaying liberation in neurologically impaired patients otherwise ready for liberation is a source for significant hospital charges. there is no clear guideline to suggest one spontaneous breathing trial (sbt) over another in predicting the liberation success. zero pressure support and zero positive end expiratory pressure (peep) or zeep is a traditional method assessing patient's readiness for mechanical ventilation liberation. however, neurologically injured patients with was to assess mechanical ventilation liberation in patients who failed zeep and subsequently passed pressure support trial. retrospective analysis of liberation in intubated patients in a neurosciences intensive care unit. all patients were initially challenged with zeep. if passed, patients were liberated from mechanical mcnemar's exact test. p value < . was considered significant. adult (> years old) patients were included. the majority of patients were successfully liberated from mechanical ventilation using minute zeep trial alone (n= , . %). eleven ( . %) patients failed . %) required reintubation. ten ( . %) this study shows that the majority of patients can be successfully liberated from mechanical ventilation successful liberation from mechanical ventilation. neurocrit care ( ) :s -s vancomycin establishey using nonmem software by the department of pharmacy of nanjing drum tower hospital in neurosurgical intensive care unit patients. according to the patient's gender, age, body weight, serum creatinine (scr), serum albumin (alb), the actual measured value. during the period from march to march , patients including male and female, whose age is ± years old ( - years old), were grouped and copies of blood concentration of vancomycin were measured. the average concentration was . m the actual measured value (r= . , p< . ), the mean absolute percentage error (mape) was . . neurosurgical intensive care unit patients for drug value prediction and drug dosage guidance. but because of coma, the body weight estimation has errors (about %). the renal function sometimes changed by contrast agent and diuretic drug has an impact on predictive results. by adjusting methods, accurate prediction rate increased to nearly %. xi liu-deryke, sindhuri s. avula, jason j. vilar. florida hospital orlando/pharmacy department, orlando, fl, usa. little data exists concerning clevidipine in this population. large variations in bp during the first hours is an independent predictor for poor outc aneurysmal subarachnoid hemorrhage (asah) admitted to neuroscience intensive care unit from january through december were identified retrospectively. patients were included if they received clevidipine or nicardipine for initial acute bp management, and bp goal was defined by the prescribers. bp variability was measured by standard deviation (sd) of mean arterial pressure (map) over the first hour of therapy. seventy three patients were included in the analysis (clevidipine n= ; nicardipine n= ). admission and % asah. baseline map between clevidipine and nicardipine group was comparable ( vs. mmhg). the number of bp recordings was similar between groups (clevidipine vs. nicardipine ; p= . ) and the average time to goal was minutes and minutes, respectively (p= . ). the average map during the first hours was similar (clevidipine vs. nicardipine mmhg; p= . ). although not statistically significant, clevidipine group had a higher percentage of bp above goal compared to nicardipine group ( . % vs . %; p= . ). there was no significant difference in bp variability between clevidipine and nicardipine group (sd . vs. . mmhg; p= . ). our study did not find a difference in bp variability between clevidipine and nicardipine following acute long corrected qt interval (qtc) has been associated with malignant ventricular arrhythmias specifically present in neuro intensive care unit (nicu) patients. in addition to medical causes, acute neurologic insult has been shown to cause multiple neuro-cardiac manifestations including qtc prolongation. prevalence ge and surgical icu patients which have different disease processes compared to nicu. retrospective review of consecutive patients admitted to the neuro icu and having abnormal qtc interval. ninety-five patients, mean age years (sd ± ) were included in the analysis. fifty four ( %) were men. average duration of hospitali ( %), subdural hemorrhage ( %), and cerebral hemorrhage ( %). fiftycardiovascular disease, % had abnormal ejection fraction. thirty-seven patients ( %) needed abnormalities were observed throughout the hospitalization and patients frequently received qtc prolonging drugs. mean qtc was ms (sd ± , range - ). there were episodes ( %) of nonsustained ventricular tachycardia which did not lead to any immediate consequences. one patient had cardiac arrest following anesthesia for hemicraniectomy. initial rhythm was asystole followed by fine ventricular fibrillation and therefore could not be clearly attributed to prolonged qtc. there were no episodes of tdp. -sustained ventricular tachycardia was observed without leading to cardiac arrest. no episodes of tdp were observed in these patients. deep venous thrombosis (dvt) of the lower extremities is a common cause of morbidity and mortality among neurologically injured patients. the data on incidence and prevalence rates of dvt among high medical or surgical intensive care unit with very limited information on patients in neuro-intensive care units (nicu). the aim of the present study is to assess the incidence and prevalence of deep vein thrombosis among patients admitted with acute neurologic injury. our institution routinely conducts ultrasound screening within hours of admission and -month period. data was abstracted and analyzed to assess the prevalence of dvt in this period. we excluded patients presenting with superficial vein thrombosis, hematoma and chronic venous scarring. over a period of one year; the prevalence of dvt was . % (n= ). of the cases that were diagnosed with dvt; more than one-half ( . %) presented with dvt at the time of admission. patients ( . %) acquired dvt during hospitalization. majority of the patients with dvt at the time of admission are caucasian males with mean age and mean saps ii score of . , ranging between and . prevalence of dvt at the time of presentation to the neuro icu is relatively high. further research is s neurocrit care ( ) :s -s practice guidelines recommend that practitioners should not prescribe prolonged prophylactic systemic antibiotics (ppsa) after neurosurgical procedures, even if drains are left in place. we sought to evaluate ) current practice patterns related to ppsa administration to neurosurgical patients with drains and devices and ) practitioner perception about the need for ppsa in this population. we surveyed members of the neurocritical care society on use of ppsa (defined as maintenance antibiotics after the time of insertion) and personal perception about the need for ppsa in patients with intraparenchymal monitors, subdural drains, subgaleal dra -pratt spinal drains, and lumbar drains. of respondents, routine institutional use of ppsa was reported by fewest respondents reported use with subgaleal drains and the most respondents reported use with -pratt spinal drains with instrumentation. respondents had varying personal opinions on the need while the lowest ( %) was for patients with subgaleal drains. it is on the use of ppsa in patients with neurosurgical drains is necessary to optimize patient care. transition to comfort measures only (cmo) in an intensive care unit (icu) is a common but delicate process that requires a well-organized multi-disciplinary and multi-professional care model. the goal of this survey was to understand potential deficiencies and inconsistencies in the transition to cmo in order to develop a process to improve the quality of care provided to patients at their end-of-life. after obtaining irb approval, a web-based questionnaire was distributed to attending physicians, residents, fellow trainees, bedside nurses, respiratory therapists and spiritual care team members, who deliver care to patients in neurological, medical, trauma-surgical, and burn intensive care units at the university of washington's harborview medical center. overall survey response was . % ( out of ). the concept that transition to cmo is a multidisciplinary process was not universal with only . % of all bedside nursing and respiratory therapists feeling invited and actively engaged in the discussion about cmo. the majority of respondents ( %) encountered at least one 'less than ideal' transition to cmo. deficiencies identified included gaps d interprofessional conflict ( . %). most participants ( %) agreed that a formalized process might reduce round the transition to cmo. we identified several barriers towards an optimal, collaborative transition to cmo in icus at a large academic medical center, highlighting the need for a formalized process. such a process would ensure communication between various disciplines and professions, and offer healthcare providers opportunities for dialogue to address all the issues resulting in a smooth transition to cmo. dexmedetomidine's propensity to cause bradycardia is well documented in non-neurocritically ill patients. e units (icu) when defined as heart rate (hr) < bpm. neurocritically ill patients have been excluded from all randomized trials. the aim of this study is to assess the development of bradycardia in patients with neurologic injury who have received dexmedetomidine for sedation in the icu. was done via nursing driven protocol with no loading doses. primary outcome was the incidence of bradycardia (hr < bpm) during first administration. secondary outcomes were percent decrease in hr from baseline and time to event analysis using cox regression. mortality in the icu was collected. a total of patients were included ( % male, mean age years, mean saps ii ). the most bradycardia occurred in patients ( . %). the average maximum dose was higher in patients who infusion duration did not vary. baseline hr was lower in bradycardic patients ( ± bpm vs. ± bpm, p= . ) and a larger mean percent decrease in baseline hr was observed ( . % ± . vs. . % ± . ). median time to first bradycardic event was hours [ . - . ] which was significantly impacted by baseline hr (hazard ratio . ; % ci, . - . ; p= . ). mortality was significantly lower in patients who developed bradycardia, . vs. . % (p= . ). these data indicate that bradycardia associated with dexmedetomidine occurs considerably among the neurocritically ill. future assessment of clinicall development would further contribute to the limited data of dexmedetomidine use within this patient population. medical complications after subarachnoid hemorrhage. medical complications occur frequently after subarachnoid hemorrhage (sah). their impact on outcome has been previously described, but was not validated in international series of sah. we evaluated consecutive patients admitted to a tertiary hospital in brazil with sah from january - ) at discharge. we calculated the frequency of medical complications according to prespecified criteria and eva of poor outcome. thirty-six% had a poor outcome; mortality was . %. the most frequent complications were hyperglycemia ( %), fever ( %), pneumonia ( . %), hypotension (< mm hg systolic) treated with vasopressors ( . %) and venous thromboembolism ( . %). hyperglycemia (odds ratio [or], . ; % confidence interval [ci], . - . ; p= . ) significantly predicted poor outcome after adjustment for age and hunt-hess grade. hyperglycemia affected more than one third of patients with sah and was significantly associated with poor functional outcome. critical care strategies directed at maintaining normoglycemia may improve outcome after sah. s neurocrit care ( ) :s -s blood pressure (bp) can be measured in critically-ill patients using non-invasive (oscillometric) blood pressure (nibp) and intra-arterial blood pressure (iabp) monitoring. the accuracy of nibp compared to the "gold standard," aibp, has been questioned. nibp monitors generally tend to over-read at low values and under-read at high values compared to iabp. previous studies exploring nibp-iabp correlations have generally been performed on patients not receiving continuous infusions of vasoactive medications. since many critically-ill patients receive vasopressors and antihypertensive agents, we wanted to study the relationship between simultaneously-measured nibp and iabp recordings in this patient population. we prospectively identified patients (n= , target n= ) admitted to a neurosciences icu, who had simultaneous iabp and nibp monitoring while receiving intravenous infusions of manually abstracted via retrospective chart audit. covariate and demographic variables were also abstracted and entered into an electronic spreadsheet. statistical analysis performed using sas v . . initial results from subjects ( % caucasian, % male, mean age . years, mean bmi . ), observations. independent-samples t-tests showed a significant difference between nibp vs iabp readings: ([sbp: m= vs mmhg respectively; p mmhg ( . %)]. bland-altman plots demonstrated good inter-method agreement between nibp-iabp measures (when visually excluding outliers) and -aibp sbp differences at higher blood pressures. preliminary analysis indicates a statistically significant difference between nibp-iabp readings for patients on vasoactive medications. yet when visually excluding outliers, there is good inter-method agreement. data from the entire cohort will be available for presentation at the ncs annual meeting and will be helpful in choosing appropriate bp monitoring methods for patients on vasoactive infusions. new-onset refractory status epilepticus (norse) is an important syndrome often associated with a poor outcome. the aim of the present study was to review norse cases in our hospital and to determine the main factor that may improve patient outcomes. we retrospectively reviewed our hospital medical records and database of electroencephalograms (eegs) over a years period (may -may ). in our facility, we performed -h continuous eeg monitoring using the international - system. of the monitored patients, we excluded those who were meningitis, herpes encephalitis, and history of epilepsy. we discussed their causes and neurological outc (go) was defined as a mrs score of - , whereas a poor neurological outcome (po) was defined as a score of - . moreover, we attempted to determine the main factor that influenced the neurological outcomes. we identified patients who had undergone eeg, and identified six norse patients among them. the on arrival was . all patients were diagnosed with limbic encephalitis and all had nonconvulsive status treatments, such as steroids, were delayed in all po patients. on the basis of our data, the cause of all norse cases was limbic encephalitis. in po patients, definitive treatments, such as pulse steroid therapy, were delayed. this is a relatively small study. further research is needed to identify the factors which could improve outcomes. multi-drug resistant organisms (mdro) are an increasing concern in health systems. pathogens such as pseudomonas aeruginosa, acinetobacter baumanii, and carbapenamase-producing enterobacteriaceae hold highest mortality rates especially when the central nervous system is involved. when mdros are cultured treatment options are becoming limited and reliance on medications such as colistin and aminoglycosides is becoming more prevalent. however, penetration of these therapies into the central nervous system is concerning therefore local administration is a potential concomitant therapy. this study was a retrospective chart review from to for all patients with documented mdros who received intraventricular colistin. seven patients from to met inclusion criteria. the average age of the patients included was years old, were males, and the median length of intensive care unit stay was days. the dose of colistin used for each patient was mg via intraventricular route. the duration of therapy ranged from - days and all cerebrospinal fluid cultures were sterile at days after administration of colistin. each patient received concomitant systemic antibiotics while receiving intraventricular colistin. six of the seven the use of intraventricular colistin was not associated with any reported adverse events. the use of intraventricular colistin was associated with positive clinical outcomes with no reported adverse effects. myasthenic crisis: epidemiology, economics and opportunities for change -a single center retrospective analysis. avinash b. kumar, vikram v. tiwari, kevin k. scharfman, justin j. calabrace. vanderbilt university medical center, nashville, tn, usa. myasthenia gravis (mg) patients are admitted to the icu for myasthenic crises characterized by immunoglobulin (ivig) or plasmapheresis and supp and care flow maps of patients admitted to our institution this is an irb-approved, retrospective cohort study of patients admitted to a tertiary neuro icu. we included adult (age > years), with a diagnosis of mg who received plasmapheresis or ivig therapy. the demographics and clinical data were summarized for patients in the ivig and plasmapheresis cohorts. we also compared the icu and hospital los and in addition the hospital cost data for patients in both cohorts. the final cohort included hospital encounters for individual patients ( female) admitted between - . the mean age on admission was . ± . y. there was no significant difference between c ventilation; the median duration of mv was . d (range - ). the median readmission rate was . ± . . ). patients had multiple crisis readmissions (> ). this cohort was socially challenged ( divorced, analysis included patients ( in ivig cohort and in plasmapheresis cohort). the mean hospital costs (variable direct-technical) in ivig cohort was approx. $ more than the plasmapheresis cohort. there was no statistically significant difference between in the limited financial analysis. . % of patients were either medicare or medicaid patients, . % wer the disease burden on patients and hospitals of this orphan condition are significant and continues beyond the icu. evidence based care pathways need to be explored for the management of this high resource utility disease. botulism is a rare potentially fatal and treatable disorder caused by a bacterial-produced toxin that affects the presynaptic synaptic membrane resulting in a characteristic neuromuscular dysfunction. it is caused by either the ingestion of the toxin or the bacteria, inhalation, or wound infection. we present our we report consecutive cases of botulism presenting to university medical center of el paso. medical records where reviewed to obtain demographic information, clinical presentation, treatment and outcome. in popping and had abscesses in the administration areas. by history the most common %, ophthalmoplegia %, ptosis %. interestingly enough, in those patients with the documentation the pupils were reactive in %. all patients required mechanical ventilation and all were treated with the trivalent antitoxin. thirteen patients were disc derivatives (mostly -monoacetylmorphine and -monoacetylmorphine) was associated with the development of botulism. its presence in the us-mexican border is not surprising since is frequently produced in latin america. its association with the development of botulism should be recognized early to allow a prompt diagnosis and treatment with the antitoxin. a clinical feature worth noting is the presence of normal pupillary light reflex in nearly half of patients thus a normal pupillary response should not be used as a finding to exclude botulism. in clinical trials limits the discovery of effects that may be particularly relevant to underrepresented populations. clear iii, a presented an opportunity to evaluate african american (aa) enrollment. investigators across u.s. hospitals screened , patients over a -year period: % aa; . % asian; . % native american; . % pacific islander; . % white; . % mixed race; and . % not reporting. the mean age for aas was younger at . (sd: . ) vs. . (sd: . ) for whites (p= . ). the randomized-to-screened ratio for aas was . vs. . % for other racial groups (p< . ). higher . %, p= . ); northeast ( . % vs. . %, p< . ); south ( . % vs. %, p= . ); and west ( . % vs. . %, p=nonsignificant). african americans were less frequently excluded due to non-hypertensive etiology ( . % vs. %, p< . ), not having ventricular drainage ( . % vs. . %, p= . ), dnr status ( . % vs. . %, p= . ) and unstable bleeding ( . % vs. . %, p= . ); and more frequently excluded for prior disability ( % vs. . %, p= . ), larger hemorrhages ( . % vs. . %, p= . ), and by investigator decision ( . % vs. . %, p< . ). of the patients who refused consent, aas accounted for . % vs. . % of whites. in an unadjusted logistic model, the odds ratio for successful enrollment of aas was . (p< . ) vs. whites, and . (p< . ) after adjustment for age and hispanic ethnicity. the age < , - and - subgroups maintained higher adjusted odds ratios than whites at . (p< . ), . (p< . ) and . (p< . ) respectively; the above subgroup was not significantly different. others have reported difficulty enrolling aas into clinical trials. clear iii suggests this may be a misperception s neurocrit care ( ) :s -s pipeline that utilizes machine-learning algorithms to integrate clinical data and quantitative eeg (qeeg) trends, providing continuous estimation of prognosis. a collaboration involving two academic centers in the u.s. assembled a retrospective clinical and eeg database of adult subjects with cardiac arrest and return of spontaneous circulation who underwent continuous eeg monitoring. four qeeg features were included in the model: regularity, tsalis entropy, alpha-to-delta ratio, and voltage < uv. only the first hours of eeg data were evaluated in this analysis. poor outcome was defined as cerebral performance category of - at discharge. ten fold cross validation resampling method was utilized, and model performance evaluation metrics were area under roc curve (auc), sensitivity, and specificity. the algorithm provided an hourly estimation of poor clinical and eeg data was available for a total subjects. mean age was . years and overall mortality was . %. one hundred and twenty subjects ( . %) had poor outcome. our multiparametric qeeg method achieved optimal performance for mortality prediction at hours (auc . ), with a sensitivity of % and specificity of %. optimal poor outcome prediction performance was achieved at hours (auc . ), with a sensitivity of % and specificity of %. at a false-positive rate of %, the sensitivity for poor outcome was %. alpha-delta ratio and voltage < uv were independently associated with mortality and poor discharge outcome at hours (p< . ). employment of machine-learning methods in qeeg analysis allows early and robust outcome prediction in cardiac arrest. this approach has potential to facilitate real-time individualized prognostication in cardiac arrest. secondary brain injury may be a significant barrier to survival following extracorporeal membrane oxygenation (ecmo) for, otherwise reversible, cardiorespiratory failure. prevalence of brain injury phenotypes on neuroimaging were described in our prior wor neurological injury on outcomes in adult patients on ecmo. a retrospective cohort of ecmo-treated adults. clinical and outcome data was obtained from electronic chart abstraction of clinical and physi of decannulation. % (n= ) of ct scans and % (n= ) of mris had abnormal findings. intracranial hemorrhage was seen in % patients with neuroimaging. in addition, % of mris revealed diffuse significant difference in survival to hospital discharge and mean modified with or without neuroimaging during ecmo ( % vs. %, p= . ; mrs, . ± . vs. . ± . , p= . ). however, in the group undergoing neuroimaging, normal scans were associated with better survival to hospital discharge ( % vs. % p< . ) and lower mrs ( . ± . vs. . ± . , p= . ). ( . %) of survivors who did not get neuroimaging and ( %) of those who got neuroimaging achieved abilty to perform independent adl at discharge (p= . ). all patients with ability to perform independent adl in neuroimaging group had normal scans. ( %) of survivors who did not get neuroimaging and ( %) of those who got neuroimaging were discharged home (p= . ). all surviving patients in the neuroimaging group who were discharged home had normal scans. secondary brain injury in ecmosurvival and functional outcomes. a prospective study has been planned to better understand mechanisms mediating this effect. neurocrit care ( ) :s -s re-verse ad is an ongoing, phase , cohort study evaluating the extent to which idarucizumab, a humanized fab fragment specifically reverses dabigatran's anticoagulation effect in patients with serious bleeding or requiring urgent interventions. dabigatran is a direct acting oral anticoagulant approved for -valvular atrial fibrillation and venous thromboembolism treatment and prevention. in re-ly, dabigatran and mg bid were associated with significantly lower annualized rates of intracranial hemorrhage (ich) than warfarin ( . %, . % and . %, respectively). nonetheless, the mortality rate with ich in the context of any anticoagulation remains high, probably reflecting the effect of hematoma expansion. whether idarucizumab improves clinical outcome in dabigatran-treated patients this analysis of the first patients enrolled in re-verse ad focuses on patients with ich. patients presenting with ich were given intravenous idarucizumab g as two . g bolus infusions administered effect, based on central laboratory determination of dilute thrombin time (dtt) or ecarin clotting time (ect). we compared the clinical outcome of this re-verse ad interim analysis with dabigatran-treated ich patients in re-ly. in this interim analysis, patients with dabigatran-associated ich were enrolled in re-verse ad. complete reversal of anticoagulation was observed by dtt and ect within minutes of idarucizumab administration. preliminary results from this interim analysis indicate that the mortality rate of ich patients re-ly. idarucizumab reversed anticoagulation in ich patients and appears to improve mortality rates in dabigatran-treated patients with ich versus historical controls from re-ly. results from additional patients in re-verse ad will provide further information on the effects of idarucizumab reversal in patients with ich. ****permission was not granted to print this abstract**** s neurocrit care ( ) :s -s callie electroencephalography (eeg) has clinical and prognostic importance for comatose survivors of cardiac arrest. recent interest in quantitative eeg (qeeg) analysis has grown. the qualitative effects of sedation ing effects of sedatives on qeeg are poorly characterized in anoxic injury. we hypothesize that sedation would decrease amplitude-integrated eeg would predict neurological recovery. we routinely monitor comatose post-arrest patients with eeg for this prospective study, we included consecutive eeg-monitored patients who had protocolized sedation interruptions, excluding those with contraindications to interruption such as seizure or hemodynamic instability. we used persyst v to quantify sr, aeeg, and adr and calculated medians for min immediately prior to sedation interruption and the last min of interruption. we used nonparametric tests to determine if the qeeg signal changed pre-to post-and whether this differed by outcome (cerebral performance category - at hospital discharge vs - ). of screened subjects, met inclusion criteria (median age years, % male). sedation regimens varied ( propofol; fentanyl; midazolam). median duration of sedation interruption was min, and did not differ by sedative type. pre-interruption, higher adr and aeeg and lower sr predicted favorable outcome. post-interruption, sr decreased (median change - . , iqr: - . to ), aeeg increased ( . , (p= . ), but aeeg and adr changes did not differ by outcome. in acute anoxic brain injury, sedation increases sr and decreases aeeg. larger decreases in sr with sedation interruption predict worse outcomes, which may reflect a susceptibility of deafferentated cortex to suppress in response to sedation. ashley r. hedges, gary g. davis, brianne b. wolfe, erin e. lingenfelter, gregory g. hawryluk, safdar s. ansari. university of utah hospital and clinics, salt lake city, ut, usa. for patients presenting with subarachnoid hemorrhage (sah) or traumatic brain injury (tbi), levetiracetam has begun to emerge as a preferred alternative to phenytoin for seizure prophylaxis following initial presentation. however, the optimal dose of levetiracetam has not been determined. a retrospective review of electronic medical records identified patients that received levetiracetam for seizure prophylaxis for sah or tbi in a level one trauma center from may , to october , . the goal of this research was to quantify the combined seizure incidence (including both clinically observed seizures and those confirmed by electroencephalogram) in patients receiving levetiracetam mg twice daily compared to levetiracetam > mg total daily dose. among patients captured, % were male, with a mean age of years old. for patients receiving seizure incidence was observed, . % vs . %, in patients receiving levetiracetam mg twice daily this was observed despite no difference in potential confounders, includ trend towards increased levetiracetam failure rates was observed in the lower dosing scheme of mg twice daily. t electroencephalograms ordered ( vs , p= . ). no difference in adverse effects were observed our project suggests that patients may benefit from a standardized levetiracetam dosing scheme of mg twice daily. treating intraventricular hemorrhage (ivh) with a fibrinolytic (ivf) therapy such alteplase via a catheter is becoming an increasingly popular intervention. with the conclusion of the clear iii trial a larger cohort of patient data is available to update past meta analyses. mortality and good functional outcome after thrombolytic treatment was reviewed in patients with hypertensive ivh. a literature search was performed from to march to collect all literature on ivh treatment with ivf. seventeen papers meeting our inclusion and exclusion criteria were collected for further analysis. ivh patients with vascular abnormalities and traumatic injuries were excluded. mortality and functional outcome was assessed to compare ivf treated and control groups in all publications. there was a significant difference in mortality favoring the treatment group at days, days and days ( %ci, . - . ; p= . ; %ci, . - . ; p= . ; %ci, . - . ; p= . ). pooling mrs and gos good functional outcomes, there was a significant difference favoring the treatment group at , , and days ( %ci, . - . ; p= . ; %ci, . - . ; p= . ; %ci, . - . ; p= . ). there was a non-significant trend in mrs scores favoring the treatment group. a significant difference in gos score favoring the treatment group was found at , , , and days ( %ci, . - . ; p= . ; %ci, . - . ; p= . ; %ci, . - . ; p= . ; %ci, . - . ; p= . ). treatment of hypertensive ivh with thrombolytic may improve functional outcome and reduce mortality compared to control groups as early as days, a trend that continues to days for mortality and days for functional outcome. different effect sizes are generated when different functional outcome tools, such as mrs and gos, are used. an aging population and increasing use of anticoagulants and antiplatelet agents to prevent ischemic hematoma (ssdh) and sdh related to trauma (tsdh). we sought to study the association of antiplatelet agent and warfarin use in sdh patients admitted to our neurosurgical icu. warfarin were studied. neurosurgical methods of sdh evacuation and re-evacuation were studied as well as hemostatic factors such as international normalized ratio (inr) within the first hrs, blood products and hemostatic agents given to reverse coagulopathy or antithrombotic effects. demographic information such as age, gender and comorbidities were noted and indication for antithrombotic agent. we excluded major trauma (level ) associated with sdh at our center. from january to may , we admitted sdh patients, of which . % required evacuation ( -> , mean = . ), and on ( %) underwent redo evacuation (range in days -(date range - days). hour inr rates in warfarin related sdh were all < . except for . of these , only one patient required re-operation. mort in our patient population, sdh was associated with a need for evacuation in . % of all patients, of which a higher rate of reagents. mortality was also higher in the warfarin associated sdh patients. consecutive patie complications were prospectively enrolled. medical critical care attendings (micu), neurocritical care attendings (nicu), residents (res), and nurses (rn) predicted the following: ) -month functional -month quality of life (qol). patients were followed up at months and their functional status and qol were compared to the predicted values. functional outcomes were dichotomized to good (mrs - ) vs. poor (mrs - ). (of ) patients had -month mrs predicted by all provider groups. fifty-four ( %) patients had good outcome and ( %) had poor outcome. the micu, nicu, res, and rn providers had similar predictive values ( % ci) for accurately predicting good outcome ( % ( - ), % ( - ), % ( - ), and % ( - ), respectively). nicu was most accurate in identifying poor patient outcome, % ( - ), followed by micu % ( - ), rn % ( - ), and res % ( - ) (p= . , . , and < . , respectively). when patients who transitioned to comfort measures only (n= ) were excluded from the analysis, the nicu team was more accurate at predicting poor outcome. fifty-three survivors had qol predicted by all provider groups. the accuracy of qol predi neurocritical care attendings are better than healthcare providers without neurological training at predicting poor -month functional outcome in neurocritical care patients. however, the overall predictive accuracy for -month mrs and qol was similar between healthcare provider teams. there are significant limitations in providers' ability to predict long-term functional outcomes. patients with severe acute brain injury (sabi) raise important palliative care considerations associated with sudden, devastating injury and uncertain prognosis. the goal of this study was to explore how family members, nurses and physicians experience the palliative and supportive care needs of patients with sabi receiving care in the neurosciences intensive care unit (neuro-icu). design: semi-structured in-person interviews were audiotaped, transcribed, and analyzed using thematic analysis. setting: thirty-bed neuro-subjects: forty-seven interviews were completed regarding patients receiving care in the neuro-icu with family members (n= ), nurses (n= ) and physicians (n= ). hope varied depending on the par away, generally in the process of conveying prognosis, while families expressed hope as an action that supported coping with their loved one's acute illness and its prognostic uncertainty. ( ) participants described the loss of personhood through brain injury, the need to recognize and treat the brain-injured patient as a person, and the importance of relatedness and connection, including personal support of families by clinicians. in their pursuit to recognize and preserve personhood, physicians used stories from patients and families to inform them about patient identities, while nurses focused on providing supportive, empathetic care to patients and families. support for hope and preservation of personhood challenge care in the neuro-icu as identified by families and clinicians of patients with severe acute brain injury. specific practical approaches can address these challenges and improve care to meet the needs of patients and families in the neuro-icu. despite increasing evidence that early mobilization strategies are effective, we showed patients were not adequately mobilized in two argentinean hospitals. we implemented a progressive-mobility protocol and examined its feasibility, safety and applicability in our neurocritical patients. prospective observational implementation study of a progressive-mobility protocol for neurocritical patients admitted to icus of two university hospitals in argentina. all patients were evaluated twice daily for level of movement and clinical stability. patients progressed as tolerated from passive movement implementation baseline to icu patients admitted in months - after implementation began (two month start-up phase not analyzed). there were pre-implementation patients with assessments ( % post-operative, % traumatic -implementation patients with measurements ( % postpopulations: median age years ( % ci - ), nearly % were men. mobilization was . times - . ) after protocol implementation. two thirds of pre-implementation patients ( . %) were not mobilized compared with only . % post-implementation (p< . ). among mechanically ventilated patients, . % of pre-implementation assessments showed no mobilization vs. . % post. post-implementation patients with an endotracheal tube had a lower rate of mobilization ( . %) than ventilated patients with a tracheostomy ( . %). passive movement, turns and full assistance to sit up and transition out of bed to chair was achieved for . % and . % achieved higher levels ( , , ) . mobility sessions with the physical therapist were < minutes in % of the cases. no mobility-related adverse events occurred. mobilized following protocol implementation. this prospective study demonstrated that early and progressive mobility among neurocritical care patients in argentina is feasible and safe. psychiatry, geriatrics, and oncology have adopted comprehensive approaches to predict outcomes accounting for important constructs such as spirituality and resilience. critical illness often occurs as a sudden catastrophic event leaving patients with significant long-term cognitive, behavioral and neurological disturbances. impact of resilience and spirituality on recovery in this setting has not been investigated. we have designed a study to validate two important scales, connor davidson resilience scale- and brief rcope spirituality scales for surrogate responders. hours with one or two surrogate responders will be included. this prospective cohort study will collect demographic, laboratory and radiographic data in a redcap database. for every patient enrolled, the cd-risc-and a behalf, themselves, and for each other. each patient will complete two resilience and two spirituality scale cd-risc and three spirituality scales . the scales will be administered to the patient ,if possible, prior to discharge; at months and at months. if patient ing followup. cars study has screened patients in days, enrolling patients. common diagnoses include subarachnoid hemorrhage ( ), cns malignancy ( ), intracranial hemorrhage ( ), unruptured aneurysm ( ), subdural hematoma ( ). based on current enrollment, this unique methodology for surrogate validation of scales is feasible. by august , an anticipated subject will be recruited. surrogate validation of quantitative measurements of resilience, spirituality can provide new insight into prognostication and patient centered critical care. active family engagement in the intensive care unit (icu) could improve patients' and families' experience with care, interactions with the healthcare team, and outcomes. this study examined the perceptions and attitudes of family members regarding increased engagement with passive mobilization of neurocritical care patients. an educational video on passive mobilization of icu patients was developed to engage family members to participate as valued members of the healthcare team. an anthropologist and a nurse or physician (study team) invited family of neurocritical care patients in an academic medical center icu in argentina their perceptions of engagement with care. a multidisciplinary team ( mds, rns, anthropologists) completed the analysis. thirty-two family members ( % female) of icu patients participated. the study team observed and the family participants reported to be positively surprised by: the format of learning by video that was different from how they usually received daily information; the information in the video was more detailed than anything previously taught; the invitation to watch the video and engage in patient's care was new and unexpected as was the opportunity to provide opinions on how to improve the video instruction. a newly authorized them to touch the patient and participate in care. they reported increased hope about prognosis and perceived an improved relationship with the healthcare team. only one family member considered the video irrelevant. family members' attitudes and perceptions toward this low cost approach to engagement were positive. this approach to teaching and engagement may help humanize the complex icu environment. - % of americans believe in the concept of miracles. we hypothesize that a belief in miracles leads to consultation rate of palliative care. addressing a patient or family's belief in miracles and understanding what a miracle signifies early in the neuro- the critical illness resilience and spirituality (cars) study is a prospective cohort study currently -icu at mount sinai hospital with an expected length of stay of at least hours and surrogate responders. as part of the study, all recruited patients and their families primary outcome is tracheostomy and peg tube placement. secondary outcomes include length of stay, full code status, and palliative care consultation. these groups will be matched with regards to the disease specific sever regression will be used to compare rates of the primary and secondary outcomes. the cars study has screened patients screened and enrolled patients so far. of those enrolled, the most common diagnoses include subarachnoid hemorrhage ( ), cns malignancy ( ), intracranial hemorrhage ( ), unruptured aneurysm ( ), subdural hematoma ( ). this is an ongoing study, we anticipate recruiting patients by the end of august, . belief in miracles could potentially influence continuation of aggressive measures in a shared decisionparadigm in the neuro-icu. mary m. barden, teddy t. youn, carolina c. maciel, sonya s. zhou, david d. greer. department of neurology, yale-new haven hospital, yale school of medicine, new haven, ct, usa. withdrawal of life-sustaining therapy (wlst) for predicted poor neurological outcome is a common cause of death among post-cardiac arrest patients. recent guidelines recommend against wlst before hours post-arrest. early wlst perpetuates a self-fulfilling prophecy that may contribute to premature death in some patients who otherwise would have survived with good neurological recovery. a retrospective cohort of resuscitated cardiac arrest patients from january to march at a single tertiary academic medical center was reviewed. patients were evaluated for outcomes at hospital discharge and (when applicable) the timing of and reason for wlst. prognostic indicators including clinical examination, electrophysiology, and neuroimaging were analyzed and findings were compared to day of wlst. of patients, ( %) had wlst due to perceived poor neurological prognosis. median day of wlst for this reason was post-arrest day . when stratified according to treatment with targeted temperature management (ttm), the median day of wlst remained day for both ttm-treated and non ttm-treated groups. of patients with wlst, the phrase "no chance for meaningful recovery" was used in documentation for ( %), mri results were cited as indicative of poor neurological prognosis for ( %), and pupillary light reflex was present day post-arrest (or day post-complete rewarming) in ( %). in a retrospective cohort of resuscitated cardiac arrest patients, wlst for predicted poor neurological outcome was the most common cause of death. the median day of wlst was post-arrest day . many patients with wlst had present pupillary reflexes on day post-arrest (or day post-complete wlst in the setting of indeterminate prognostic indicators undermines accurate neurological prognostication of post-cardiac arrest patients and perpetuates a self-fulfilling prophecy of poor outcome. brain injury global hypoxic ischemic brain injury (hibi) is a major cause of death and disability worldwide. invasive monitoring of brain function enables goal-directed treatment strategies that optimize cerebral physiology, reduce secondary brain injury (sbi), and potentially improve outcomes. we report a series of patients with hibi where intracranial monitors were placed to guide clinical management. retrospective analysis of patients with hibi cared for at a large academic center over a year period. all patients received therapeutic hypothermia (th) to °, continuous eeg monitoring, and had a bundle of invasive monitors placed through a multi-lumen cranial bolt. the full bundle consisted of an icp monitor, brain oxygen (pbto ) monitor, cerebral blood flow (cbf) probe, and cerebral microdialysis probe. patients received the full bundle, while the others received a partial bundle. patients were treated using a tiered algorithm designed to optimize cerebral physiological parameters. precipitants of hibi included cardiac arrest ( patients), airway occlusion during anesthesia induction ( patient), and hanging ( patient). mean patient age was years. average time between initial injury and probe placement was hours. average duration of monitoring was . days. no adverse events occurred after monitor placement. episodes of deranged cerebral physiology-including intracranial hypertension, brain hypoxia, cerebral glycopenia, metabolic crisis, and reduced perfusion leading to treatment changes occurred in of patients. they occurred up to days after initial injury, and in all cases would have otherwise been clinically silent. of patients died in the hospital. the surviving patients all regained consciousness and were discharged to acute rehabilitation facilities. we did not find invasive intracranial monitoring after hibi appears safe and identifies physiological states associated with sbi. goal directed treatment utilizing multi-modality monitoring in hibi merit further study. is associated with worse patient outcomes; however, it can be difficult to reliably detect. delirium prevention is therefore a potentially beneficial strategy and is most effective in patients who are at high to evaluate whether the advanced practice providers (app's) would both use the dps and also find the dps easy to use. during a --bed neurocritical care unit at a large -stratify consecutive admissions of patients with ais a descriptive statistics. the apps completed a -item questionnaire that included the system usability scale (sus) and open-ended questions to determine the usability of the dps, as well as to assess for facilitators and barriers for the use of the dps. no individual patient data was collected. patients admitted with ais and ich (n= ) were assessed by the app's using the dps. compliance with dps use was of apps (n= ). the sus score ( . ) was mid-point between "acceptable" and "excellent." facilitators and barriers for use of the dps were identified. the dps was easy to use and was consistently used by the app's. adoption of the dps with this patient population can be a first step to identify the most atthis vulnerable population. the intensive care unit is a complex learning environment with variability in a number of external factors. prior studies of neurology residency training in the neurological intensive care unit have focused on general exposure. this study aims to evaluate resident perception of neurocritical care training. an online survey was sent to program directors and neurocritical care members for distribution to neurology residents. the survey consisted of free-text or selection style questions that focus on resident perception of neurocritical training. statical analysis for group differences was completed with t or fisher exact tests a total of responses ( . % response rate) was obtained. of those responders, completed a freetext question regarding needed improvements to neurointensive care training. % responded with needs for educational changes, and these responders did not differ from other responder in average required practitioners ( % vs % p= . ), and neurocritical care attendings ( % vs % p= . ). this is the first study to examine neurology residents' concerns with neurocritical care rotations. there is little neurocritical care educational materials focused to neurology residents, but the emergency assess the neurocritical care educational training priorities during neurology residency are warranted. our institute had several cases of conflict come to light in the evaluation of patients being evaluated for death by neurological criteria. provider understanding and awareness of clinical guidelines was found to be low across all sub-specialties. it was deemed important to follow appropriate procedures based on published guidelines and a standardized process to provide appropriate care for each patient, optimize icu resource utilization and strengthen provider and public trust. due to medical, legal and ethical issues involved , an institutional standard was called for . -specialties about discrepancies, we revised the institutional policy to reflect emphasis of educational gaps and reflect the latest published guidelines and practice updates . we created an education module , a standardized template in electronic medical to allow escalation in case of conflicts . the project led to increased participation and satisfaction amongst the clinical providers in the icus when n education source to evaluate patients with a consistent approach based on published practiced parameters. we observed a trend in decrease in length of stay and variance for brain dead patients since donation referrals as well timely initiation and effectiveness of family discussions in irreversibly confirming this is in a survey model. a standard care pathway towards evaluation of patients with death by neurological criteria can be successfully implemented at an institutional level in a tertiary care academic medical center. establishing and maintaining optimal brain perfusion is a crucial endpoint for resuscitation and postcardiac arrest care. a recently fda-approved device that employs laser and pulsed doppler now provides clinicians with the cerebral flow index (cfi), a non-invasive measure of brain perfusion. we sought to determine if cfi provided by the ornim c-flow device can be used as a simple and valid measurement of brain perfusion after resuscitation in cardiac arrest patients. we performed a single-center prospective observational inception cohort study of adult patients with cardiac arrest starting in october . comatose patients with sustained return of spontaneous circulation (rosc) within minutes of maneuvers were included. the ornim cflow was connected as soon as feasible after rosc. clinicians were blinded to cfi values. primary outcome was survival at discharge and secondary outcome was neurological assessment using the cerebral performance categories (cpc) scale at discharge. a total of patients have been enrolled as of may . half ( . %) were out-of-hospital arrests and neurological outcome (cpc or ). mean interval between arrest and start of monitoring was hours with a mean duration of hours. adequate signal was available . % of the monitoring time. mean cfi in survivors was . , compared to . in non-survivors (p value . ). patients with good neurological outcome at discharge also had a higher mean cfi, although the small sample size precludes any conclusion. our results demonstrate that cerebral perfusion monitoring using the ornim cflow after cardiac arrest is feasible. it also suggests that higher cfi might be associated with survival at discharge. as enrollment progresses and more data are collected, further insight on the potential role of cfi as a neuromonitoring tool might emerge. tuberculous meningitis (tbm) is the most devastating form of tuberculosis, yet rates of neurological complications and mortality are uncertain in high-income countries. we used administrative claims data on all admissions at nonfederal hospitals to identify adult patients with tbm in california between -- , and florida between - . our outcomes of interest were mortality and the fo seizure, hydrocephalus requiring a ventriculoperitoneal shunt, vision impairment, and hearing impairment. kaplan-meier survival statistics were used to assess the cumulative rates of neurological complications and death. we identified patients with tbm, of whom . % ( % ci, . - . %) developed at least one neurological complication or died. more than two-thirds of these complications occurred during the initial hospitalization for tbm. individual neurological complications were not uncommon: the cumulative rate of - . %), the rate of seizure was . % ( % ci, . - . %), and the rate of ventriculoperitoneal shunting was . % ( % ci, . - . %). vision impairment occurred in . % ( % ci, . - . %) of patients and hearing impairment occurred in . % ( % ci, . - . %). the mortality rate was . % ( % ci, . - . %). nd death even in high-income countries such as the united states. neuropalliative care in peru: emergence from the conspiracy of silence the development of palliative care in peru remains limited, particularly for non-oncologic services such as palliative and end-of-life care in patients, families, nurses and physicians in a specialized neurological institute in lima, peru. we used a mixed methods approach consisting of surveys and qualitative, semi-structured interviews that were recorded, transcribed and analyzed using thematic analysis. surveys identified a substantial need for palliative care in the neurological institute ( % of doctors and of do emerged from qualitative interviews evolved around communication about end-of-life choices in neurologic disease. knowledge about advance directives was limited among both clinicians and families, and prognosis, and who should tell them. however, the perception that a physician should be honest, and that suffering and pain should be avoided at all times was unanimous. barriers to transparency in patientphysician communication included ( ) expectation of cure with medical treatment; ( ) families' trust in god training in communication, symptom management and end-of-life care; and ( ) a paternalistic culture. participants identified several challenges specific to palliative care in neurologic disease. in a country without a palliative care training program and no legal basis for advance directives, families and clinicians are emerging from a culture of silence about serious diagnoses and end-of-life care choices. our findings emphasize the need for palliative care education for neurology providers and the public in peru. a trained physician must perform the brain death examination in a systematic fashion in order to recognize and prevent potential sources of error. given the infrequency at which brain death presents in a hospital setting, clinicians may not always have the opportunity to observe a brain death examination during their training. in this study, we plan to evaluate the effect of medical specialty and expertise on documentation errors. we performed a retrospective chart review of brain death examinations between jan. to july st at the university of pittsburgh medical center presbyterian. physician specialty and training level, documentation errors, and confirmatory tests such as cerebral blood flow (cbf), electroencephalography (eeg), and computed tomography angiography (cta) were collected from medical records. exams. ams carried out. the most common completion of documentation by at least one examiner. attending physicians, residents and fellows were responsible for % ( neurology and neurosurgery residents have limited exposure to the brain death examination. regardless communication with patients and their families is of central concern in healthcare. however, evidence shows that it is often poorly addressed, especially at times of rapid health status changes and periods of clinical uncertainty. acute neurological emergencies pose an inherently unique challenge in communication. while emerging studies have addressed communication gaps and strategies to improve them in various critical care settings, none have assessed this issue in acute neurological emergencies ongoing irb approved prospective observational study in a bed neurocritical care unit in tertiary care academic medical center all patients admitted to the unit and all clinical providers participating in their care screened for inclusion. direct observation of discussions between clinical providers and families by a questions addressing the satisfaction, understanding of treatment options, impact on health care decisions and ways to improve communication five patients have been enrolled in the study, so far. the results are analyzed for concordance between tween answers is considered between all participants for general satisfaction with the communication (as well as family's understanding of treatment options explained to them by the physician. some disagreement on the impact of the discussion on health care decisions. qualitative domains identified by families as areas of good ical radiographic images. domains identified as needing improvement included explanation of medical circumstances and need for private room for discussions. we observed general satisfaction with communication. further enrollment will help elucidate any definitive areas of improvement and impact of communication on health care decisions. laith maali, sheema s. khan, mahmoud m. ismail, rhys r. brooks, vishnumurthy v. shushrutha hedna. the university of new mexico, albuquerque, nm, usa. cerebral venous thrombosis (cvt) usually accounts for < in their demographics, etiology, clinical features, radiological presentation, and mortality have not been previously explored. a systematic search was performed for publications in pubmed usi thrombosis", "cerebral vein thrombosis" and "cortical vein thrombosis". a total of relevant studies were abstracted with strict selection criteria and a total of patients' data were used for the final analysis. linear correlation was used for our descriptive analysis. cases reported were europe- , asia- , north america- , africa- , australia- and south america- . overall male to female ratio was : . , among clinical characteristics headache was the most common symptom and hematological factors were the most common etiology. location of the thrombosis was described mostly in the transverse sinus. intercontinental differences in relation to demographics, etiology, clinical features, radiological presentation, and mortality were identified. cvt can have significant disparity in their demographics, etiology, clinical features, radiological presentation, and mortality when compared from one continent to another. it is important for the worldwide physicians to recognize these differences and to follow the most recent guidelines, diagnostic methods and treatment to insure the best outcome and prognosis. timely communication is critical for high quality care in the intensive care unit(icu). published literature in surgical icus quotes up to % of patient caregivers receive prognostic information with mean prognostic interval . ± . days since icu admission prognostication in acute neurological injuries is challenging and uncertainty may delay communication. we assess occurrence and timeliness of goals of care communication in a neurocritical care unit prospective observational study by surveying nurses in a bed neurocritical care unit in tertiary level eriod. data was also collected during daily morning multidisciplinary huddle and verified by verbally surveying the nurses. survey results were analyzed for patients and patient encounters. in . % encounters , the nurses felt the patient's treatment plan matched patient-centered goals of care in . % encounters, a provider family discussion had occurred in the last hours. within the st hours of icu admission, . % patients were identified to need goals of care discussion in the multidisciplinary huddle, only . % had such a discussion. for patients needing goals of care addressed, a discussion occurred on an average . ± . days since icu admission. dichotomized by age, . % patients younger than years old had a discussion , if one was needed, while only % older than years had one. when dichotomized by gender, . % of males and . % of females had a provider discussion. . % females compared to % of males received a discussion on goals of care if identified as needed within st hours of icu admission. our data shows timely communication of goals of care in the neurocritical care unit with a mean time comparable to published literature. however, there appear to be demographic disparities that warrant further research. cerebral vasomotor reactivity reflect prognosis after cardiac arrest sungeun lee. ajou university school of medicine / department of neurology, suwon, korea, republic of. neurological prognostication after cardiac arrest is a difficult problem. since several studies reported good effect of target temperature management (ttm), prognostication after cardiac arrest was delayed and became complex. recently, some reports presented that impaired cerebral autoregulation was correlated with neurologically poor outcome. the aim of this study was to determine whether vasomotor reactivity (vmr) test by transcranial doppler (tcd), reflecting cerebral hemodynamic status, affected accuracy of neurological prognostication in post cardiac arrest patients. since january , patients were enrolled after cardiac arrest. patients who performed vmr test during ttm period were included and patient with unstable vital sign or malignant findings in brain ct, such as massive subarachnoid hemorrhage or severe brain edema, or poor temporal windows. primary outcome was cerebral performance category scale (cpc) at discharge. vmr test used breath-holding method during seconds. carbon d analysis. other conventional prognostication test, such as eeg, sep, et al., was performed after hours from rewarming time. we divided patients between good (cpc - ) and poor (cpc - ) outcome group and compared results from prognostic test between two groups. potential, and electroencephalography after hours from rewarming time were presented favorable results in good outcome group. (p< . ) vmr during breath-holding technique during ttm period also was more increased in good outcome group at right ( . ± . % vs. . ± . %, p< . ) and left ( . ± . % vs. . ± . %, p< . ) middle cerebral arteries. the present study shows that vasomotor reactivity is preserved in patients with neurological good outcome. to evaluating cerebral hemodynamic status by vmr test seems to be useful tool for early prognostication after cardiac arrest. michelle l. lozano, susan s. yeager. the ohio state university wexner medical center, columbus, oh, usa. as the numbers and opportunities for advanced practice providers (apps) in neurocritical care units (nccus) has increased, the integration of these providers into the health care setting has become a greater challenge. currently no data exists to support h comfort levels before and after completion orientation. this prospective, pre and post observational study was sent to newly hired nccu apps within an academic medical center. a one hundred-item survey was created to evaluate self-reported experience cus. baseline data was collected from each app. next, apps were integrated into the nccu utilizing a three month orientation program which fused a series of didactic, simulated, and precepted experiences. after e survey tool. student's t test statistics were utilized to compare before and after experience and comfort levels with items identified as necessary to perform in the nccu app role. as utilization of apps in the nccu becomes more prevalent, integration processes need developed to practice. a structured approach enables identification of high priority areas to assist with initial and and comfort levels. results indicate that further education and exposure to items such as neurologic imaging may be helpful. limitations of this study include subjective data from a small, self-reported, single institutional sample. further research of larger, more diversified sample representation is needed to validate whether these results can be generalized to other nccus. yasuhiro kuroda, kenya k. kawakita, toru t. hifumi. department of emergency medicine, kagawa university, miki, japan. brain damage after return of spontaneous circulation (rosc) varies among studies and patients despite an established modality enabling proper evaluation. evaluation of brain injury after rosc is needed for the determination of the inclusion criteria of neurocritical care, especially of targeted temperature management. literatures are reviewed and summarized. the association between admission glasgow coma score (gcs) motor score and neurologic outcome after rosc (day ) is an independent predictor of good neurologic outcome at days in patients sustaining out-of-hospital cardiac arrest who receive therapeutic hypothermia: gcs motor score , n= ( . %); score - , n= ( . %); score - , n= ( . %), p< . (hifumi ). recently no significant differences of neurologic outcome at days after hospital admission was observed between mild therapeutic hypothermia and control in the subgroup of gcs motor score or . these data show that initial gcs motor score examination immediately after rosc can at least provide baseline objective prognostic data for decisions by healthcare professionals. neurological signs such as gcs, brain stem reflex, respiratory status, and degree of shivering are potential variables that can be incorporated into a predictive model for a more precise evaluation of brain injury in cardiac arrest survivors undergoing ttm. effect of targeted temperature management should be evaluated depending on the brain injury in pcas. cydni n. williams, jennifer j. wilson. oregon health and science university, department of pediatrics, portland, or, usa. -level estimates of et utilization in pediatric ais, and explore demographic and clinical characteristics, associated interventions, and outcomes. retrospective cohort analysis of the kids' inpatient database evaluated et utilization in children with ais and age > days, identified by diagnosis and procedure codes. analyses were weighted for national estimates and compared with chi-square and t-tests. among pediatric ais patients, ( %) received et. anterior circulation occlusions were seen in % of et patients. et patient age ranged versus %, p<. ) was more common and seizure was less common ( % et versus %, p=. ) in et patients. average age was higher with et ( versus years, p<. ). other patient demographics, hospital characteristics, and critical care procedures were similar. thrombolytic agents (tpa) were common with et ( % et versus % overall). intracranial hemorrhage was similar ( % et versus %, p= . ), and varied by tpa ( % et with tpa, % tpa only, % et only, % neither). there was a nonsignificant trend toward poor outcome (death, discharge to nursing facility, tracheostomy, or gastrostomy) was seen between poor outcome and et ( % et versus %, p=. ). et in pediatric ais is uncommon, utilized mostly in older children and those with paresis. though hemorrhage was uncommon, this data suggests caution with et and tpa combination. associations between et and poor outcome may reflect disease severity bias. more research on outcomes with et in pediatric ais is needed. luis p. lee, michael m. leoncio, balagangadhar b. totapally. nicklaus children's hospital / pediatric critical care department, miami, fl, usa. and cerebral edema is the most serious complication leading to morbidity and mortality. we queried a nationally representative database to determine epidemiologic data of cerebral edema in children with dka. an analysis of the healthcare cost and utilization project's kids inpatient database for the year was performed. the database was filtered using icd- diagnosis codes for dka ( . , . , . , . ) and cerebral edema ( . ) from the age of month to years. we examined these procedures, outcome and mortality rates. sample weighing was employed to produce national estimates. chi-square test, mann whitney u test and binary regression analysis were performed using spss to analyze the data. a total of , patients with dka were discharged during . females were %. racial distribution - ) years. cerebral edema was present in ( . %) children. the overall mortality rate was . %, but the mortality rate in children who developed cerebral edema was higher at . % (or: ; % ci: - ). mortality was higher in children who had a major operative procedure ( . % vs . %; or , % ci: - ) and in those with medicaid compared to private insurance ( . % vs . % p= . ) and lower in number of chronic conditions, and hospital charges were significantly higher among non-survivors but there was no difference in the age. the overall mortality rate in children admitted with dka is . %. cerebral edema prevalence is . % and it increases mortality significantly. mullai baalaaji, sunit s. singhi, muralidharan m. jayashree, arun a. bansal. pediatric intensive care unit, department of pediatrics, pgimer, chandigarh, india. near-infrared spectroscopy (nirs), a non-invasive modality to measure regional cerebral oxygenation (rso ), is being increasingly used to monitor cerebral tissue oxygenation. we studied relationship of rso with cerebral perfusion pressure (cpp) and intracranial pressure (icp) in children with acute cns infections to determine if rso could be used as non-invasive surrogate for cpp. in a prospective observational study we enrolled children, aged < years, with raised icp due to acute cns infections after approval by institutional ethics committee. they were monitored simultaneously for rso of both frontal-- c, covidien-iic), invasive blood pressure, and icp using intraparenchymal fibre-optic catheter (codman). linear trends and correlation coefficients were used to define relation of rso with icp and cpp. a total of paired values of rso , icp and cpp were analysed. the linear trends during the first hours revealed no significant correlation between changes in rso and changes in icp and cpp from baseline (r = . , . for icp and cpp respectively). however, the trend was not uniform - % patients had no correlation between rso and cpp, % showed a positive correlation and % showed a negative correlation. subgroup analysis revealed that strength of correlation between rso and - . ,p mmhg and normal cpp were . ( . - . ,p % respectively. rso has complex interaction with icp and cpp; the changes in icp and cpp could not predict changes in rso . however, the odds for normal cpp was significantly higher when rso > % and this cut-off could be used as a non-invasive target for age appropriate cpp. refractory status epilepticus is persistent seizure activity despite treatment with one first-line and one second-line anti-epileptic medication, while seizure activity > hours is considered super-refractory. functional outcome for children with these conditions is not well defined. this study describes functional outcome for children with refractory and super-refractory status epilepticus proposing that prognosis will be variable with high mortality. survivors will be and technology dependence. this retrospective chart review evaluated children age - years who received pentobarbital infusion at texas children's hospital pediatric intensive care unit from - for status epilepticus. outcome was defined using pediatric cerebral performance category score (pcpc) at time of discharge and at the most recent clinical evaluation per the medical record. additional measures included mortality, need for medical technology (tracheostomy or gastrostomy tube), seizure burden, and number of seizure medications at discharge. children met inclusion criteria. in-hospital mortality was %, secondary to withdrawal of support ( %), brain death ( %), or cardiac arrest ( %). highest mortality occurred in acute hypoxic ischemic injury (p= . ). of survivors, % returned to baseline pcpc at discharge while % demonstrated tracheostomy and children underwent gastrostomy tube placement. seizures persisted at discharge for most patients with no prior frequency. most children required additional home seizure medications. long-term follow-up was documented for survivors up to years after discharge. % demonstrated improved pcpc and % showed decline including additional deaths. mortality in this population was high. functional outcome in survivors was variable. some children returned to neurologic baseline by time of discharge and for those who did not, continued functional improvement was possible over time. their s -injury. in addition to standard anatomic imaging, mr sequences obtained "often or always" included: diffusion--perfusionpediatric tbi subjects received an acute mri within days post-injury. fifteen adapt sites, accounting for over % of adapt enrollment, committed to recruit adapt subjects for a non-sedated mri scan at one year post -tbi. conclusion: collection of - acute mri scans from the subjects enrolled in adapt to study associations between acute mri findings and functional outcome is potentially feasible. allowing for % mortality and % recruitment rate, recruitment of - adapt subjects from adapt sites for a follow-up mri to study relationships between advanced mri measures and neurocognitive function is potentially feasible and would represent the largest such study conducted to date. antimicrobial prescribing practices and antibiotic resistance following neurosurgical drain placement: a single-center observational study andrea j. passarelli, hasan h. alhasani. christiana care health system department of pharmacy, newark, de, usa. the use of systemic antibiotics for the duration of neurosurgical drain placement has not been associated with reduced rates of drain related infection (dri) and may contribute to the development of antimicrobial resistance and clostridium difficile infection (cdi). we sought to describe antimicrobial prescribing practices, incidence of dri, and development of antimicrobial resistance and cdi after neurosurgical drain placement at our institution. this was a single center study including adult patients status post ventriculostomy or ventriculoperitoneal shunt or ommaya reservoir, and use of an antibiotic impregnated drain. bacterial cultures and c. difficile pcr during the index admission and days post-discharge were collected. antibiotic resistance was defined as an organism resistant to the prophylactic agent. prolonged prophylaxis was defined as antibiotics continued for > hours after drain placement. eighty-one patients with drains were included. the median duration of prophylaxis was . days and cefazolin was most commonly prescribed agent ( %). three of patients with evds developed dri. prolonged vs. perioperative prophylaxis. of non-dris % were resistant to the prophylactic agent used. e. coli, k. oxytoca, and s. aureus had higher rates of resistance to cefazolin compared to our institutional antibiogram, although not statistically significant. no patients developed cdi. the use of prolonged prophylaxis was not associated with a reduced reduction in dri. most bacterial isolates were resistant to the prophylactic agent used. we suggest that antibiotic prophylaxis for neurosurgical drain placement be limited to one preoperative dose within minutes of the procedure the objectives of this study are to evaluate our institution's practice for initiating seizure prophylaxis postoperatively and establish a standard of care. adult patients who underwent cerebrovascular surgery from august to july were screened for study inclusion. patients who received lev postoperatively were compared to those who did not receive lev. clinical seizures and data were obtained from retrospective review of electronic medical records. the primary outcome was seizure occurrence in the first days after surgery. secondary outcomes of the patients included in the study, there were in the no lev group and in the lev group. two seizures occurred in the no lev group while no seizures occurred in the lev group ( vs , p= . ). there were no differences between surgery type, intraoperative blood loss or proportion of asah. of the patients with asah, % were not on lev and seizure occurred. of patients with intraparenchymal or intraventricular extension, % were not on lev. average length of stay was prolonged for the lev group ( vs days, p< . ). the majority of patients did not receive lev postoperatively and there was no difference in seizure developing a standardized approach for initiating lev may decrease variability in practices and streamline postoperative care. post-operative pain control after craniotomy: a meta-narrative review craniotomy is commonly performed for the treatment of a variety of conditions including brain tumors, aneurysms, and vascular malformations. despite significant advances in the quality and efficacy of neuroanesthetic care, there are no evidence-based guidelines for the management of post-operative pain after craniotomy. uncontrolled poststay, increased hospital care costs, and poor health-dencebased clinical decision rules, clinicians often rely on institutional or expert-based opinions to guide their decisionon opioid use, there an urgent need to evaluate existing pain management protocols. hence, we conducted a meta-narrative to evaluate heterogeneity in current practices regarding management of postoperative pain after craniotomy. a meta-narrative review was performed utilizing th terms "pain" and "craniotomy". a total of articles and systematic reviews were resulted. inclusion criteria were studies from - , randomized controlled trials, retrospective studies, systematic reviews, case reports, case series published in english were included. of these, articles and systematic reviews were included in the final analysis. there is a paucity of randomized controlled trials to develop evidence based peri-operative pain management protocols in craniotomy patients. there is evidence to suggest that scalp infiltration with local anesthetic may improve post-operative pain scores immediately after surgery. the perioperative use of nonsteroidal anti-inflammatory medications may improve pain scores without a subsequent increase in management of post-operative pain after craniotomy remains a challenging problem for clinicians and patients. there is an urgent need to conduct well designed randomized controlled trials to guide perioperative pain management in craniotomy patients and to use opioid sparing techniques for improving patient outcomes. symptomatic plateau waves are characterized by paroxysmal neurological symptoms suggestive of elevated intracranial pressure such as depressed level of consciousness, pupillary dilatation, and dysautonomia in a patient with an intracranial mass lesion. cli seizures, syncope, or new brain injury. noninvasive cerebral blood flow can be measured using ultrasound-tagged infrared spectroscopy; continuous eeg is sensitive to changes in blood flow. we report two patients without invasive intracranial pressure monitoring who demonstrated changes in blood flow and eeg during symptomatic plateau waves. case series. case was a year-old man with fungal ventriculomeningitis. after a prolonged hospital course, he developed an entrapped th ventricle and began to experience periods of complete unresponsiveness with anisocoria, clonus, and tachy-or bradycardia lasting between and minutes. episodes resolved after decompression and ventricular stent placement. case was a year-old woman with intraventricular meningioma who underwent partial resection with entrapment of the right lateral ventricle. on post-operative day she developed multiple episodes of unresponsiveness, diaphoresis, clonus, tachy-or bradycardia lasting to minutes, culminating in a persistent episode requiring urgent craniotomy. in both patients, ceeg was started to assess for seizures and ornim device was used to characterize blood flow. in each, symptomatic plateau waves were accompanied by decreased blood flow, followed by attenuation of faster frequencies on the ceeg. symptomatic plateau waves may be characterized noninvasively by using surface measurements of blood flow and ceeg. this case series demonstrates that decreases in bifrontal blood flow lead to depressions in ceeg during these symptomatic plateau waves. noninvasive measurement of blood flow in conjunction with ceeg provides an adjunct to invasive icp monitoring in patients with mass lesions at an open--sseefficacy of sage- , a proprietary formulation of allopregnanolone, in patients with super-refractory status epilepti line agents (tlas) while sage-(none attributed by the safety committee to sage- ). post-hoc analyses evaluated the pharmacological effects of sage- and the effect of sage- administration in the context of multiple antiepileptic drugs (aeds), pressors, and tlas. here we examine the hemodynamic properties of sage- in the study patients, with the goal of further understanding the clinical context of sage- administration in this critically ill population. burst suppression we maintenance of the tla. key exclusion criteria were anoxic brain injury and very short life expectancy. at enrollment, patients received an average of . aeds and . tlas with an average status epilepticus duration of . days. hemodynamic measurements (heart rate, systolic and diastolic blood pressure) were collected at screening, pre-dose, during sage- treatment ( , , , minutes; , , , , , , , hours) and followwas examined. twenty-five patients received treatment with sage- . during the study, mean changes in hemodynamic parameters from baseline were limited, both for patients receiving the standard (n= patients) and high (n= patients) sage- dose. regarding hemodynamic parameters, sage- was well tolerated in the srse patients studied, suggesting for further study that sage- may not elicit immediate or sustained hemodynamic changes in srse patients. real-world studies regarding use of benzodiazepines in pre-hospital and emergency department (ed) was to analyze benzodiazepine usage patterns in se by emergency medical services (ems) and the ed of an inner-city hospital. and september to ems and hospital ed were reviewed. the associated outcomes of interest were endotracheal intubation, hospital admission, and seizure recurrence. data was analyzed via descriptive statistics. of patients analyzed, ( . %) had a history of epilepsy. benzodiazepine utilization varied; ems preferred midazolam ( . %) while the ed used lorazepam most often ( . %). benzodiazepine dosages used were lower than recommended; median dose of midazolam administered by ems was only mg and median dose of lorazepam in the ed was mg. patients received . ± . benzodiazepine doses on average. seizure activity was aborted with benzodiazepines alone in ( . %) patients and recurred in ( . %). twenty-three ( . %) patients were intubated, all post-arrival. there was no observed correlation between number of benzodiazepine doses given and baseline characteristics, decision to intubate, or incidence of seizure recurrence. all patients were admitted and ( . %) were admitted to the icu. we observed consistent underdosing of benzodiazepines used for the treatment of se by both ems and the ed. there was lower than expected achievement of seizure cessation and intubation rates were higher than reported in previous studies. further investigation is needed to identify the barriers to optimal benzodiazepine selection and dosing for se patients at our institution. super-refractory status epilepticus (srse) refers to a condition of persistent seizures that have failed treatment with first-, second-and third-line treatments. sage- , a proprietary formulation of the endogenous neuroactive steroid allopregnanolone (a potent positive allosteric modulator of synaptic and extrasynaptic gabaa receptors in animal models), is being developed for the treatment of patients with srse who have not responded to standard treatment regimens. -sse- was an open-label, phase - in patients with srse. the present analysis explores the pk properties of sage- over the course of the trial. sage- was administered as a -day continuous intravenous infusion to patients with srse and receiving third line agents (tlas) for seizure or burst suppression. patients received either a standard dosing regimen (n= ) or a high dose regimen (n= ) and were subsequently weaned off tlas and sage- . the standard dose was chosen, based on a modeling approach, to achieve a mean plasma exposure roughly equivalent to the highest endogenous concentrations measured in the third trimester of pregnancy (~ nm). since women tolerate this endogenous level without apparent adverse effects, mean (sd) steadyand for the high dose regimen wa -state concentrations were approximately dose proportional between the standard and high doses, indicating that clearance was dose-independent of infusion to allow determination of half-life or volume of distribution. in this study of patients with srse, sage- clearance was not dose-dependent and plasma concentrations were in line with target exposures. jennifer a. creed, christa c. swisher. duke university medical center / department of neurology, durham, nc, usa. ****permission was not granted to print this abstract**** seizures after resuscitation from cardiac arrest predict worse outcomes, but there is no evidence that treating seizures improves outcomes. we leveraged existing practice variation to compare the effectiveness of aggressive electroencephalography (eeg) and antiepileptic drug (aed) use to infrequent spot eeg and aed use. we performed a retrospective cohort study including comatose post-arrest patients at two academic centers from - . the same critical care group staffs both, but center uses continuous eeg (ceeg) monitoring and aggressively treats malignant eeg patterns while center uses infrequent spot eegs and rarely treats with aeds. we classified each patient's daily eegs from admission until death, malignant," or "not performed." we abstracted covariates and outcomes from our prospective registry, e rhythm, arrest location, survival to discharge and functionally favorable survival. we used multi-level mixed-effects logistic models to test for an association of center with outcomes after adjusting for eeg and clinical covariates. we included subjects (center : , center : ). center subjects were younger, arrested more often out-of-hospital and had higher illness severity (all p< . ). overall, ( %) center subjects were eeg-monitored (median days (iqr - d)), ( %) had a malignant pattern observed and median of d (iqr - d), ( %) had malignant patterns observed (less frequent myoclonic status epilepticu center comparisons). in multilevel modeling, there was no significant center effect on outcomes. after cardiac arrest, treatment at a center using aggressive ceeg monitoring and aed treatment is not associated with better outcomes at discharge. phenytoin dosing adjustment for obesity may not be necessary effective loading with weight-based dosing of phenytoin for therapeutic levels is necessary in several emergent settings. practices for dosing obese patients, those > . x ideal body weight (ibw) vary, including using total body weight (tbw), adjusted body weight (adjbw; correction factor . ), and the abernathy formula (correction factor . ). our objective was to determine whether dose adjustments were necessary for obese patients. charts were reviewed retrospectively from two tertiary medical centers from september to august . we included all admitted patients older than years of age, initiated on iv fosphenytoin for any reason, with therapeutic post-load level (total phenytoin of -in pre-mean weight-based loading doses were compared for obese and non-obese patients who achieved postload levels in the therapeutic and high therapeutic range (total level - , free . - . ), using welch's two-sample t-tests. a total of patients, non-obese and obese, met inclusion criteria, including non-obese and obese patients who achieved high therapeutic levels, desired for ongoing status epilepticus. the mean -obese and . ( % ci: . , . ) for obese patients (t = . , p = . ). dose to achieve high therapeutic levels was . ( % ci: . , . ) for non-obese and . ( % ci: . , . ) for obese patients (t = . , p = . ). our results suggest that adjustment calculations of fosphenytoin loading dose for obese patients may not be necessary, thus can all patients into high therapeutic range, especially desirable in status epilepticus, while not harmful in other patients. stephen sage- is a proprietary formulation of allopregnanolone. sage- was studied in an open-label nical study of patients with super-refractory status epilepticus (srse). the primary - . - in resolving srse in these patients. to further understand the specific patient and treatment-related parameters which may affect outcomes in this study, we performed a post-hoc analysis on the completed data set. in this open-label, single-treatment with sage- . key efficacy outcome measures were: ) successful wean off of tla(s) after hour ; and ) subsequent successful taper off sage- after hour , without recurrence in the hour period following treatment. a total of patients received open-label treatment with sage-sage- . response rate appeared consistent across varying patient demographics (gender, age, ethnicity) and baseline treatment regimens. overall, % of patients experienced at least serious adverse event (sae) and patients died during the trial. no saes and no deaths were attributed by the safety committee to sage- administration. there was little evidence of a relationship between response rate and patient demographics (gender, -trial supports further investigation of sage- in srse, and can inform inclusion criteria for future trials. the clinical efficacy and safety of sage- in the treatment of srse is being evaluated further in an ongoing phase , randomized, placebo-controlled trial. jocelyn y. cheng. drexel university college of medicine, philadelphia, pa, usa. in catastrophic neurologic injury, withdrawal of care (woc) is often considered. while woc is based on the perception of poor prognosis, the question of whether it creates a self-fulfilling prophecy has been raised. though studied in traumatic brain injury epilepticus (se) is unclear. the goal of this study was to describe the final cause of death in adults with se, and determine the impact and associated clinical characteristics of woc on mortality rates. a single-center retrospective study at an urban academic medical center was conducted between age;gender;glasgow coma scale (gcs);acute physiology and chronic health evaluation-ii (apache-ii);history of epilepsy;etiology of se;refractory se (rse);in-hospital mortality; and cause of death. -tests were used as appropriate. binary logistic regression analysis adjusted for covariates, and p < . was considered significant. of subjects, male, mean age years, there were ( . %) in-hospital deaths, ( %) due to woc. the remaining causes were cardiogenic(n= , %) and respiratory(n= , . %), with sepsis, brain death and seizures individually comprising . %(n= each). excluding woc, in-hospital mortality fell to -group without cardiac arrest (ca), inof which %(n= ) was due to woc; mortality decreased t the total cohort, there was no significant difference in baseline characteristics excepting metabolic seizure were more common in woc subjects. metabolic etiology (or: . ,p= . ) and ca (or: . ,p= . ) remained significantly associated with woc after univariate but not multivariate adjustment. withdrawal of care is a major determinant of mortality in se, and is associated with metabolic dysfunction clinical decision- an open--sse- ) evaluated the safety and efficacy of sage- , a proprietary formulation of allopregnanolone, in patients with super-refractory status epilepticus (srse). entry criteria were designed to maximize patient treatment opportunities. the objective of this post-hoc analysis was to demonstrate sage- activity despite heterogeneity of srse causes and high comorbidity burden. d-line agent (tla; with anoxic brain injury or very short life expectancy were excluded. - years) and mean status epilepticus duration was . days (range - days). probable srse causes included infection, hemorrhage, worsening cgi-s score. all patients required - tlas and - aeds at baseline. up to weans from tlas were sage- at the end of da six patients ( %) died from underlying srse cause or associated comorbid conditions. no saes were attributed by the safety committee to sage- . mean numbers of baseline wean attempts, comorbid conditions, and srse episode duration were comparable between responders and non-responders. activity despite the heterogeneity of cause of srse and comorbidity burden. delayed neurologic deterioration (dnd) from vasospasm is associated with poor outcome after subarachnoid hemorrhage. continuous eeg (ceeg) monitoring has lead to detection of eeg patterns of uncertain clinical significance -ictal-interictal continuum (iica). these have been associated with acute brain injury but variably predict outcome. we describe the types and prevalence of iica eeg patterns in patients who develop angiographic vasospasm and discharge outcomes retrospective study of adult patients with non-traumatic subarachnoid hemorrhage admitted at emory university hospital neuro-icu from january -february who underwent ceeg. ceeg were recorded using - electrode placement and interpretation of the iica eeg patterns using the american clinical neurophysiology society research terminology. in sah patients, ( %) were female and hypertensive ( %). majority had poor grade sah ( % hh grade , % grade and % grade ). moderate to severe angiographic vasospasm were detected in ( %) patients . days after admission. ceeg was initiated . days after admission. periodic discharges (pds) occurred in ( %) patients, ( . %) of which were generalized and ( . %) lateralized. rhythmic delta activity (rda) occurred in ( . %) with ( . %) generalized. stimulus induced rhythmic discharges (sirpids) were seen in ( . %) and electrographic seizures in ( . %) patients. vasospasm was common in patients with any iica patterns ( . % vs. . % p= . ), pds ( . % vs. . % p= . ) and rdas ( . % vs. . % p= . ). rdas were common in patients with discharge mrs - ( . % vs. . % p= . ) and pds were equally seen across all outcomes ( % vs. % p= . ). the observed trends were not statistically significant. iicas such as pds and rdas were common in patients who developed vasospasm but seen equally with a larger sample size is needed to support these findings. ncs and (ncse) have been reported in - % of critically ill patients. whether patients with ncse should be treated as aggressively as patients with convulsive status remains controversial. this study sing on its correlation with patients' outcome and possible predictors. in this retrospective study n= patients underwent ceeg at mount sinai neurological and neurosurgical icu (nsicu). ceeg data according to acns guidelines was collected. outcome was evaluated by mortality, glasgow outcome scale (gos), glasgow coma scale (gcs). we compared seizures were detected in % of subjects and % experienced of cg (p= . or . ci . of cg (p= . , or . , . considering clinical predictors, only gaze deviation and subtle facial movements were significant (p= . or . , p= . , . mortality and mean hospitalization length were not different. outcome was significantly different in nsicu with mean gcs being in ng and in cg (s for p= . ), but was not significantly different at discharge, as mean gos was in ng and . in cg (p= . ). our findings show that patients' history of epil rstand prognostication in these patients. raquel farias-moeller, archana a. pasupuleti, luca l. bartolini, amy a. kao, brittany b. cines, jessica j. carpenter. children's national health system, washington, dc, usa. super refractory status epilepticus (srse) ensues when there is no improvement of seizure control in response to anesthetic therapy or seizure recurrence after reduction of anesthetic agents. there is no consensus on standard of care for srse. ketogenic diet (kd) has reported success but technical challenges exist including inability to feed patients, concomitant steroid use, persistent acidotic states and ur step-by-step approach to initiation and continuation of kd in the picu. patients with srse who had kd initiation in the picu were identified from a prospective neurocritical care database with irb approval. data from the hospital course was supplemented by review of the electronic medical record. descriptive analysis was performed. neurointensivists used our step-by-step guideline to start patients on kd. nine children with srse who had kd initiated in the picu were identified. the mean age was . years (sd . ). median number of days to start kd from detection of seizures was . mean time nine children remained on the kd for months or longer. the median number of aeds trialed before kd was started was [iqr - ] and the median number of continuous infusions was [iqr - ]. after initiation of kd most patients were weaned off continuous we demonstrated the feasibility of a practical approach to initiation of kd in the picu for children with srse. these children were successfully weaned off continuous anesthetic infusions. larger studies, both in children and adults, are needed to determine the effectiveness, safety and tolerability of kd in the management of srse as well as its ease of implementation. although overall mortality of status epilepticus is high, baseline patient characteristics and co-morbidities may help to predict outcomes and shape treatment decisions. two previously published scores exist to predict outcomes: the status epilepticus severity score (stess) and the epidemiology-based mortality score in status epilepticus (emse). however, a comparison of the two scores has not previously been completed in an american population. we hypothesize that both scores will adequately predict the primary outcome of in-hospital death. we performed a retrospective analysis of all cases of status epilepticus admitted to the neuro-critical collected data on age, comorbidities, eeg findings, and seizure history. the primary outcome was inhospital death. a sensitivity and specificity analysis was completed, in addition to a student's t-test for a comparison of the two scores. forty-six patients were admitted to the nccu for management of status epilepticus during june and january , of which experienced in-hospital death. the median age of the sample was , with approximately half of the sample ( . %) having or more comorbidities. the two most common etiologies were cryptogenic (n= ) and acute cerebrovascular events (n= ). while the sensitivity of both emse and stess were very high ( % and % respectively), the specificities were very low ( . % and . % respectively). a student's t-test between those who experienced in-hospital death and those who did not was only significant for emse at the p< . level (p= . ). the specificity of emse and stess for our external validation did not correlate with previous studies; however, both tools are sensitive. the emse and stess may be useful to predict outcomes of status epilepticus in populations with few comorbid conditions, but are less helpful when patients have multiple medical problems. in , the acns published critical care eeg terminology in an effort to improve clinical research and management of patients requiring continuous eeg (ceeg) monitoring. we sought to understand the familiarity of providers in our neurocritical care (ncc) program with this terminology two years after implementation at our institution. we administered a question web-based survey to ncc fellows, advanced practice providers (apps), tanding of acns terminology, and clinical eeg application. there were attending physicians, ncc fellows, and apps. attending physicians and apps had a median of (range: , ) and years (range: . , ) experience since most recent post graduate training, respectively. all data is reported for apps and physicians respectively as percentage correct. highest rated component of the ceeg report that influenced patient management was "conversation with lected by . % of apps and % of physicians. set forth by the acns and highlight the importance of communication between ncc providers and epileptologists as well as areas of potential education for providers of all training levels. carbamazepine (cbz), an oral antiepileptic drug (aed), is a potent inducer of cytochrome p (cyp) (eg, phenytoin, fosphenytoin, phenobarbital, valproic acid, levetiracetam, or lacosamide) to reduce the -drug metabolism (reduced efficacy or toxicity). an iv cbz formulation has been developed; study ov- (nct ) evaluated bioequivalence and a (nct ) evaluated tolerability. both studies were similarly designed. eligible adult patients received a stable oral cbz regimen ( daily dosage (divided doses q h) during the confinement period (ov- : -or -min infusions q h for days, patients in the -min group were eligible to receive four -to -min infusions on day ; a: -min infusions q h for days, then one -min infusion on day ). oral cbz was resumed for days ( a: days). bioequivalence of iv to oral cbz was evaluated in ov- ; tolerability data were pooled. in ov- , -min iv cbz infusions were within the %- % bioequivalence range vs oral cbz; min infusions exceeded the upper limit for maximum plasma concentration. in both trials, patients switched to iv cbz ( -min: n= ; infusion was dizziness ( %); infusion-site reactions ( %) were the only new aes experienced by patients vs oral cbz. seizure control was maintained during the switch. to avoid potential drug toxicity reactions, it is beneficial to maintain patients on cbz. iv cbz administered as multiple -min infusions was bioequivalent to oral cbz. iv cbz was well tolerated. treatments for aneurysmal subarachnoid hemorrhage (asah) remain inadequate. eg- is a sustained release formulation of nimodipine for intraventricular delivery in order to avoid dose-limiting -label, dose escalation study of a single intraventricular dose of eg- that was designed to determine the maximum tolerated glasgow outcome scale (www.clinicaltrials.gov identifier: nct ). subjects with asah repaired by clipping or coiling were randomized within hours of asah to eg- or oral nimodipine if they were world federation of neurological surgeons grade to and had a ventricular catheter. cohorts of subjects received , , , , or mg eg- ( per cohort) or oral nimodipine ( per cohort). plasma nimodipine concentrations were sustained for days. the maximum concentration, steady state concentration and area under the curve for the first days increased with increasing dose of egbetween males and females. plasma nimodipine concentrations following eg- administration did not exceed plasma concentrations of oral nimodipine mg every hours at steady state. cerebrospinal fluid nimodipine concentrations with eg- were orders of magnitude higher than in plasma or with oral nimodipine. subjects treated with eg- (n= ) had a median intensive care stay . days less and hospital length of stay . days less than subjects treated with enteral nimodipine (n= , table) . intraventricular eg- produced sustained, dose-dependent nimodipine plasma concentrations and shortened intensive care and hospital length of stay. improved clinical outcome support conduct of a pivotal phase study of eg- . increasing exposure to ionizing radiation for medical diagnostics and treatment has raised questions about possible long term effects. this study describes the effective dose of ionizing radiation exposure in patients with aneurysmal subarachnoid hemorrhage (asah). thirty-five asah patients admitted to a university hospital between jan , and december , , greater than years old, and discharged alive were included. the primary objective was to calculate the mean total effective dose of ionizing radiation (tedir) in asah patients. secondarily, the number of asah patients with a calculated tedir greater than the annual and cumulative maximal permissible radiation dose (mprd) as described by the national council of radiation protection and measurements (ncrp) and the international commission on radiological protection (ircp) was determined. factors associated with greater than maximal exposure limits were evaluated. tedir exposure ranged from . - . millisievert (msv), with a mean (sd) of . ( . ) msv. seven , the presence of vasospasm (p< . ), external ventricular drain (evd) (p < . ), or ventriculo-peritoneal shunt (vps) (p< . ) were statistically significant factors for increased tedir in asah. demographic data, previous medical history, and location of aneurysm were not statistically significant. univariate analysis representing the degree to which tedir increases for each of these factors revealed hh class ( or ) . (p< . ), vasospasm . (p< . ), evd . (p< . ), vps . (p< . ). in multivariate analysis representing the degree in which the tedir increases, only vasospasm . (p< . ) and evd . (p< . ) were statistically significant factors. following asah, patients with severe disease requiring vasospasm treatment and shunting are at warranted. patients with aneurysmal subarachnoid hemorrhage (sah) have high morbidity and mortality related to cerebral ischemia and infarction. in this study we explored the reversibility of reduction in cerebral blood flow (cbf) after sah. we conducted a retrospective analysis using prospectively collected ct perfusion (ctp) data from sah patients. patients were grouped as good (hunt hess - ) and poor grades . ctp data were compared at baseline ( - days after aneurysm rupture) and follow-up (> days). cbf at baseline was comparable between good and poor grade patients ( . ± . vs. . ± . -up there was an improvement from baseline in both groups ( . ± . and . ± . respectively, p= . ). however, in hypoperfused areas, rcbf was significantly lower in poor grade patients compared to good grade ( . ± . vs. . ± . , p= . ) and significantly lower than global cbf in both groups (p< . ). at follow-up, only poor grade patients demonstrated an increase in rcbf ( . ± . , p= . ) while in good grade patients, rcbf remains unchanged ( . ± . , p= . ). the absolute improvement in rcbf was significantly greater in poor grade patients ow-up in both groups was not statistically different in the two groups (p= . ) but significantly lower than global cbf (p< . ). regional hypoperfusion occurs after sah. in good grade patients there is no recovery in rcbf while in poor grade patients there is partial recovery implying a biphasic response with a reversible and an irreversible reduction in rcbf. this has not been previously described in the literature and may implicate two distinct mechanisms responsible for rcbf reduction after sah. aneurysmal subarachnoid hemorrhage (asah) is an important cause of morbidity and mortality, with patients susceptible to a variety of medical complications. external ventricular drains (evds) are commonly used for intracranial pressure monitoring and csf drainage; however, this puts asah patients -associated infections (vais). many preventative strategies have been proposed and implemented over the last years. using the nationwide inpatient sample (nis) database, this study examines trends in evd usage, vai rates, and mortality over a -year period. in this retrospective analysis, data from the nis was obtained for the period of january , through december , using international classification of diseases, th revision (icd- ) codes. analysis was performed using sas . surveymeans. primary outcomes of interest were rates of evd use, vai and in-patient mortality, as well as hospital length of stay. during the study period, there were , asah admissions, with evd placement reported in . % of cases. there was no change in either evd use or rate of vai (mean vai rate of . % over the years). no change in hospital length of stay was observed. from january , to december , , despite a variety of vai-preventative strategies advocated for and implemented, the national vai rate in asah patients has not changed; however, mortality has declined by a mean arr of . % per year over the study period. this may reflect improved neurointensive care provided to this critically ill population. stable vai rates may reflect incomplete adoption of effective preventative strategies, or use of ineffective o study has previously examined these trends in asah. the purpose of this study was to determine the effect of routine use of dexamethasone on delayed cerebral ischemia and poor outcome (death and severe disability) after aneurysmal subarachnoid hemorrhage (asah). this is a single center, observational cohort study comparing patients with asah admitted to a tertiary referral center from to . a variation in practice patterns for the use of dexamethasone - mg every hours after asah exists in our institution depending on neurosurgeon preference. patients were followed prospectively for the occurrence of complications including delayed cerebral ischemia (dci), e (bad outcome defined as a mrs of - ) and months (bad outcome defined as mrs of - ). out of the patients, ( %) patients received dexamethasone during the first hours of admission. significant factors associated with steroid use were females ( % v %;p= . ) and aneurysm clipping verses coiling ( % v %;p< . ). there was no difference in hh, fisher grade, incidence of infections, or incidence of dci ( % v %;p= . ). steroid use was significantly associated with bad outcome at discharge ( % v %;p= . ), but no difference at months ( % v %;p= . ). when examined separately for coiled and clipped patients similar trends were found in both subgroups. steroid use was associated with a longer hospital length of stay (los). in multivariable regression analysis steroid use was significantly associated with worse outcome (or . ;p< . ) when controlled for age, hh grade and type of surgical intervention. the study did not detect any benefit in the use of steroids in reducing the incidence of delayed cerebral ischemia in acute aneurysmal subarachnoid hemorrhage. however, steroid use was significantly associated with longer los, and worse functional outcome at discharge. antiplatelet therapy for the prevention of peri-coiling thromboembolism in high risk patients with ruptured intracranial aneurysms thromboembolic events (tee) during or after coiling of intracranial aneurysms is the most frequent procedural complication, resulting in permanent neurologic disability in a subset of patients. in unruptured aneurysm patients, there is evidence supporting the use of periprocedural antiplatelet therapy to prevent tee. whether patients with ruptured aneurysms and subarachnoid hemorrhage should also be given peri-coiling antiplatelet therapy is less clear. we reviewed a prospective registry of endovascularly treated aneurysm patients to delineate angiographic features associated with periprocedural tee. we then performed a controlled before-andangiographic feature associated with tee) to evaluate whether selective aspirin administration would reduce the rate of periprocedural thromboembolism without increasing major hemorrhagic complications. small parent artery diameter, an incorporated branch, intraprocedural thrombus formation, and parent rate of periprocedural tee, from . % in the control group to . % in the aspirin-treated group (p = . ). tee reduction in the aspirin-treated group continued to be statistically significant even when ith tee in other large studies with an adjusted or of . ( % ci . - . ). there were no major systemic hemorrhagic -bleed, symptomatic intracranial hemorrhage, or major external ventricular drain (evd)-associated hemorrhage (p = . ). significantly reduce the rate of peri-coiling tee without increasing major systemic or intracranial hemorrhages. neurocrit care ( ) :s -s muhammad k. athar, umer u. mukhtar, umer u. shoukat, david d. boorman, fred f. rincon, matthew m. vibbert, syed s. shah, jacqueline j. urtecho, jack j. jallo. thomas jefferson university hospital, philadelphia, pa, usa. fever is frequent in patients with subarachnoid hemorrhage (sah). differentiating infectious fever from central fever can be challenging. it is important to diagnose the cause of fever in the neurological intensive care unit (nicu) because of the detrimental effects of fever on brain injured patients. we hypothesized that procalcitonin (pct) could be useful to distinguish central fever from infectious fever in patients with sah. prospective, chart review study conducted in the nicu between december and september . was clinical infection defined as positive cultures (blood, urine, sputum, mini bal, csf, and c. difficle toxin) or infiltrate on chest x-ray within days of onset of fever. sixty-twenty-- . , and had pct > . . out pct > . . using multiple logistic regression, pct between . - . had an odds ratio of . ( % ci . - . ), pct > . had an odds ratio of . , and a maximum temperature odds ratio of . (ci . - . ). using pct > . alone had an odds ratio of . ( % ci . - . ). -pv: . % with a sample prevalence of . %. roc curve area: . %. fever in sah patients. the test has high specificity and npv so it can be a valuable toll to rule out infectious fever in nicu. intraventricular hemorrhage (ivh) due to subarachnoid hemorrhage (sah) has been associated with fever, hydrocephalus, and shunt dependence. the modified graeb score (mgs) as an enhanced measure of intraventricular hemorrhage has been shown to correlate wit intracerebral hemorrhage (ich) as well as shunt dependency in sah. we evaluated the mgs's association to complications during hospital stay and impact on functional independence at discharge in sah patients. retrospective review was performed of prospectively collected data for consecutive sah patients enrolled into the university of maryland recovery after cerebral hemorrhage (reach) study. hunt and hess (hh) grade, global cerebral edema (gce), and infarct on admi team of neurointensivists. mgs was calculated from each patient's admission ct scan and dichotomized according to a cutoff value based on the median value for our sample. clinical complications during each admission were recorded, and independence of performing adl's was obtained from physical and occupational therapy notes. statistical analysis was performed using univariate and multivariate logistical regression. ninety-eight sah patients from july to november were reviewed for this study. mgs was calculated in patients and dichotomized based on a median cutoff value of . hh, gce, and admission infarcts were not found to be significantly associated with high mgs. on univariate analysis, elevated mgs was significantly associated with hospital acquired infections (uti, pneumonia, and sepsis, p< . ), fever (p= . ), hypotension (p= . ), hypernatremia (p= . ), symptomatic vasospasm (p< . ), and new i independence with adl's (p= . ). severity of ivh as measured by mgs is associated with multiple in-hospital complications. the mgs can be used as an independent predictor of loss of independence of adl's on discharge for patients with sah. ed cerebral ischemia (dci) and brain injury following subarachnoid hemorrhage (sah). while systemic corticosteroids may mitigate inflammation and promote fluid and salt retention following sah, there is limited evidence on the impact of corticosteroid administration on outcomes following sah. corticosteroids are frequently administered in clinical practice following sah for the management of post-operative cerebral edema and refractory headache. our goal was to examine the impact of corticosteroid use following sah on the occurrence of dci and poor functional outcome at discharge. retrospective analysis of data from a single center sah registry on patients admitted between - who survived > hours. a logistic regression model was created with multiple potential predictors of outcome and steroid use, and with corticosteroid use as the response variable. patients were divided into quartiles based on the propensity score. the impact of corticosteroid use on the outcome of interest (dci then poor functional outcome at discharge) was then determined while controlling for the propensity score quartile. co-variates in analysis included age, gender, ethnicity, history of diabetes or statin use, aneurysm location, aneurysmal vs non-aneurysmal bleed, treatment modality, hunt hess, modified fisher. a total of patients with aneurysmal and nonaneurysmal sah were included in this analysis. corticosteroids were administered in ( . %). dci occurred in ( . %). poor outcome (mrs> at discharge) occurred ( . %). following propensity score analysis, corticosteroid use was not associated with dci (p= . ) but was associated with a significant reduction in poor outcomes at discharge (p= . , or . , % ci . - . ). corticosteroid use following sah was not associated with a reduction in dci but was associated with an approximately % reduction in the odds of poor functional outcome at discharge. a clinical trial of corticosteroids initiated in the early period following sah may be warranted. besides the impact of the initial bleeding, cv remains the leading cause for mortality and morbidity after successful cian therapy? data of patients with cian were analyzed with regard to onset of multimodal neuromonitoring, if one or both hemispheres were monitored and for the integration of neuromonitoring values in decision months after sah using the glasgow outcome scale (gos). ct-scans were reviewed for infarctions at time of discharge. patients were in the favourable outcome group (gos - ), patients showed unfavourable outcome (gos - ). in patients of the gos - group neuromonitoring was implanted in the hemisphere with the highest transcranial doppler (tcd) values. additional monitoring was installed contralaterally if tcds increased. in of those patients, contralateral pbto values were ischemic and angiography revealed severe cv in the non cian treated hemisphere. ct scans of those patients revealed significant infarctions in the hemisphere that was not initially monitored. the patients with gos - were monitored bilaterally at early timpo small infarctions but no territorial infarct was seen at discharge. a delay in bilateral multimodal neuromonitoring might facilitate delayed cerebral ischemia (dic). this might be due to a delayed detection of a mismatch between oxygen supply and consumption. in addition severe cv is not always detectable in tcd and might thus be diagnosed too late to initiate a successful cian therapy. in contrast, new severe cv or relaspses of cv after stop of cian therapy are detected efficiently if bilateral neuromonitoring is in place and the values are acted upon accordingly. the effects of short versus longer duration prophylaxis of levetiracetam on cognitive / functional outcomes in aneurysmal subarachnoid hemorrhage and risk of development of delayed seizures tamara majic, dela d. amoussou, chrystal c. reed, asma a. moheet. cedars sinai medical center, los angeles, ca, usa. chart review performed on patients admitted from january to december with asah, who received levetiracetam seizure prophylaxis mg bid or greater for < days versus days or more. we compared the length of icu stay, delta gcs at discharge, mrs ( vs days), and incidence of delayed seizures -- . ; p < . ) lengths of icu stay for short-duration levetiracetam therapy was -- . for long-duration (p< . ). length of icu stay in low dose -- . days (p < . ). preliminary data for early and late onset seizures delayed seizures occurred with longer duration prophylaxis preliminary data suggests delayed cerebral ischemia was universally present in patients with delayed seizures. the incident rate of dci was higher in patients with early seizures ( %) vs without seizures ( %) between low dose and high dose, and between short duration and long-duration levetiracetam therapy. length of icu stay is shorter in subjects treated with low dose levetiracetam vs high dose, which may suggest that a low dose levetiracetam may have a lower adverse effect profile. the presence of delayed ischemia may warrant a longer duration prophylaxis. the longer duration prophylaxis does not seem to reduce the incidence of delayed seizures, although a longer duration of study is warranted. in spite of improvements in mortality and physical disability for aneurysmal subarachnoid hemorrhage for 'delayed brain injury' often attributable to the direct neurotoxic and neuroinflammatory influence of the initial hemorrhage burden. these processes can result in global brain atrophy and commonly manifests as new cognitive disability including deficits with memory, executive function, and language. heparin exerts a wide range of interactions postulated to antagonize multiple pathophysiological mechanisms implicated in asah. here we review low-dose iv heparin (ldivh) as a promising treatment for preventing 'delayed brain injury' in asah survivors and inform on a new multi-center randomized trial. recent studies evaluating ldivh in asah are reviewed. the astroh study is an open-label, blindedadjudication, randomized phase ii trial. the primary efficacy outcome is mean montreal cognitive assessment (moca, - , normal - ) scores at the -day follow-up and patients will be enrolled over years at academic medical centers. the primary safety outcome is any major bleeding or clinically relevant non-major bleeding. one-year outcomes are also being assessed. ldivh significantly reduced neuroinflammation, demyelination, and transsynaptic apoptosis in a rat sah model. in a retrospective study ldivh patients were compared to well-matched controls. ldivh subjects had % clinical vasospasm and % vasospasm related infarction compared to % and % respectively in controls (p= . and p= . ). in another retrospective cohort study ldivh patients (n= ) had mean moca of . compared to . in controls(n= ) (p= . ). multivariate analysis confirmed ldivh positively influenced moca scores when controlling for factors that negatively influenced cognition. the astroh study is active and enrolled its first subject in april, . ldivh is a promising treatment for asah and is currently being investigated in a multi-center randomized trial (astroh), nct . gastrointestinal bleeding (asah) patients and to determine the effect of gib on in-hospital complications and outcomes. gib in asah patients and to determine the effect of this complication on other in-hospital complications and outcomes. the incidence of gib in asah hospitalizations (n= , ) was , per , patients with . % requiring blood transfusions. multivariate independent predictors of gib included: age - gib in asah is uncommon and is influenced by patient demographics and preexisting comorbidities and significantly increases disability and mortality. twenty-six consecutive asah patients undergoing multimodal neuromonitoring including cmd were studied. interventions of full-strength enteral nutrition (en) after > hours without any feeding preceding en were identified. parameters of systemic and cerebral metabolism and insulin dose were timeand analyzed together with continuous variables to study the effect of en on brain metabolism (glucose, lactate, pyruvate and glutamate). out of interventions in total, were excluded because of simultaneous parenteral supplementation or missing values, leaving interventions in patients eligible for analysis. the mean en--glucose significantly increased from perfusion pressure (cpp), baseline serum and brain glucose levels, the baseline metabolic profile [brain metabolic di and independent of the insulin dose given during the intervention. the increase of cmd-glucose was strongly dependent on the delta increase of serum glucose (median during the intervention (p< . ). although probe location influenced absolute cmd-glucose-levels (p< . ), significant increases were even observed in perilesional brain tissue (p< . ). no change in cmd-lactate, cmd-pyruvate, cmd-lpr or cmd-glutamate levels were observed (p over . ). brain glucose levels increased during enteral feeding independent of cpp, baseline glucose levels, insulin administration, and probe location. despite this increase, no additional metabolic improvement was observed. the clinical benefit of interventions ta needs to be investigated in a prospective approach. mean platelet volume (mpv) is a common daily laboratory investigation in subarachnoid hemorrhage diseases and is postulated to signify increased systemic thrombogenicity. similarly, diabetics have elevated mpv suggestive of associated vasculopathic complications through increased thrombogenicity. with non-aneurysmal sah (nasah) as compared to aneurysmal sah (asah). hence, we investigated if vasculopathy. we reviewed charts of patients admitted with the diagnosis of sah between january and december . we compared proportions using fisher's exact tests, and constructed roc curves to find threshold values for admission mpv that had the best combination of sensitivity and specificity to predict nasah versus asah. of the patients who met the inclusion criteria were asah. diabetic patients who presented with diabetic patients, a threshold value for mpv of . fl yielded the best combination of sensitivity and specificity to predict asah vs nasah (auc= . ; % ci . , . ). using this threshold, sah is more -similar mpv association was not observed among diabetic patients presenting with sah. mean mpv at admission did not differ between diabetic patients who presented with asah ( . fl) and those who presented with nasah ( . fl, p= . ). nonng with sah. aneurysmal subarachnoid hemorrhage (asah) is associated with mortality rates up to %, and up to one half of survivors suffer from long term neurologic disability. though several clinical scores have been developed to predict in-hospital mortality and long term outcomes, there is no universally accepted score. create a new predictive model. we conducted a retrospective chart review of patients admitted with asah to a single neurocritical care unit from september to february . we excluded patients with non-aneurysmal sah (including trauma, avms, and mycotic aneurysms). demographic and clinical variables collected included age, admission gcs, admission apache ii score, hunt and hess score, presence of delayed cererbral ischemia, and hospital acquired infections. our outcome measure was glasgow outcome scale at discharge. we created a penalized logistic regression model to determine predictors of outcome. we assessed performance by estimating the area under the roc curve (auc). of patients reviewed, met inclusion criteria. the mean age of the cohort was years. . % (n= ) of patients were female. the mean apache ii score on admission was . (median . ). majority of patients (n= , . %) had a discharge gos of . a combination of predictors performed optimally: age, admission apache ii, gcs, use of mechanical ventilation and presence of hospital acquired infections. the mean auc of the model was %. at the point of maximum-accuracy on the roc curve, the sensitivity was %, and specificity was %. clinical features at admission and during hospitalization can predict outcomes in patients with asah. clinical characteristics from the first few days of the hospital admission, such as hospital acquired infections, can be added to existing models, to improve outcome prediction scores. subarachnoid hemorrhage (sah) patients may experience supply-demand mismatch of cerebral metabolism from seizures, vasospasm, cortical spreading depolarization, hydrocephalus, or cerebral edema. previous studies have focused on non-neuronal measures of cerebral autoregulation. we examine the impact of various neurocritical interventions by examining anecdotally identified intracranial eeg (ieeg) responses considered clinically impactful as well as systematic examination of repeated interventions within patients. sah patients of hunt-hess grade - underwent ) clinical multimodality neuromonitoring utilizing brain tissue oxygen cerebral oximetry, cerebral blood flow, spencer depth electrode, and fiberoptic icp through a quadconsent using time-synchronized monitoring (cns- , moberg research). we reviewed clinician anecdotes of treatment responses to vasopressors, endovascular vasodilators, anti-seizure pharmacotherapy, nimodipine, and ventriculostomy adjustments. we then assessed each patient's response to multiple grouped interventions using spectral features including alpha-to-delta ratio (adr) normalized to pre-intervention baseline (nadr). paired t-tests and scatter plots, respectively, demonstrated the impact of interventions and blood pressure on nadr. patients had available post-sah ieeg data over months. of patients with post-procedural brain responded with an increase in ieeg alpha activity power. two patients developed a decline in adr associated with asah-related vasospasm, one who had eeg improvement after endovascular spasmolysis. two patients developed scalp-negative ieeg seizures, both electroclinically improving with anti-seizure pharmacotherapy. grouped interventions showed heterogeneous responses to vasopressors and one patient with a significant, repeated response. nimodipine had no consistent discernible peri-dose impact on nadr. we display scatter plots showing the peri-intervention patient-specific correlation between mean arterial pressure and nadr. patients with aneurysmal sah may develop neuronal impairment rescuable by neurocritical care interventions. our data show these responses are patient-and statemodels of dynamic sah pathophysiology. introduction: (dci), may be an important determinant of outcome following subarachnoid hemorrhage (sah). potentially, early treatment measures such as control of intracranial pressure, blood pressure management and initiation of nimodipine may mitigate ebi. our objective was to study the impact of delayed presentation to medical care on the occurrence of dci and poor outcomes following sah. retrospective analysis from a single center sah registry. patients admitted between and for nontraumatic sah, who survived more than hours were eligible for inclusion. [vr ] the explanatory variable of interest was time from symptom onset to diagnostic ct, dichotomized at hours. covariates included age, gender, ethnicity, hunt-hess grade, modified fisher grade, hypertension, aneurysm location and treatment modality. the primary outcome of interest was poor functional outcome at discharge (defined as models were constructed with the outcomes of interest as the response variables. a total of patients were included. the median time to diagnosis was . hours (interquartile range . - . ). twenty-four patients ( . %) presented greater than hours from onset. poor functional outcome at discharge occurred in ( . %) and dci in ( . %). multivariate analysis revealed no association between delayed presentation and either dci (p = . ) or poor functional outcome at discharge (p = . ). hours from symptom onset to diagnosis as a continuous variable also did not reveal a significant association with dci or poor functional outcome. delayed presentation to medical care beyond hours is not associated with either dci or poor functional outcome at discharge following subarachnoid hemorrhage. a treatment bundle including extracorporeal cardiopulmonary resuscitation (ecpr) combined with targeted temperature management (ttm) may improve outcome of cardiac arrest (ca) patients, however, prognostication for these patients still remains challenging. we sought to examine the prognostic value of amplitude-integrated electroencephalogram (aeeg) for ca patients during ecpr and ttm. this was a single-center, retrospective analysis of adult ca patients treated with ecpr and ttm under aeeg monitoring with subhairline montage. intra-arrest cooling was immediately initiated with cold fluid infusion and extracorporeal cooling method and maintained at °c for h. patents underwent intraaortic balloon pumping (iabp) and percutaneous coronary intervention (pci) if needed. neurological outcome was assessed with the cerebral performance category (cpc) scale at hospital discharge. ecpr was conducted in patients (age . [ - ] years, % male) amongst ca or post-ca comatose patients since november . the initial cardiac rhythm was refractory ventricular fibrillation in , pulseless electrical activity in , and asystole in . the cause of ca was cardiogenic; underwent pci and needed iabp support. collapse-to-ecpr time was . min. initial aeeg patterns were; flat trace (n= ); low voltage (n= ); suppression-burst (sb) (n= ); electrographic status epilepticus (ese) recovery (cpc - ). their aeeg pattern was continuous in , low voltage in , and ese in . among rn of spontaneous circulation. patients with ese recovered after antiepileptic administration. ecpr was withdrawn in patients based on clinical and prolonged flat aeeg findings. continuous aeeg adds early prognostic information for ca patients with ecpr under ttm. the suppression ratio (sr) is a processed eeg variable estimating the percent of an eeg epoch ( - ) that is suppressed. sr has been associated with neurologic outcome after several types of brain injury and using different technologies including full montage eeg recordings and simplified processed eeg monitors. we compared sr during targeted temperature management (ttm) after cardiac arrest, using two independent blinded assessment tools. a convenience sample of adult patients treated with ttm after cardiac arrest were enrolled to compare and the full montage continuous eeg using natus equipment with persyst magicfor . seconds). machine times were recorded to synchronize, and sr results were recorded once for each subject at a time without stimulation or artifact using correlation and altman-bland analysis. adults were enrolled in this study with a median age of years, ( %) were male. during sr - ) for persyst sr . ( . - ). comparing medtronic and persyst sr, the spearman correlation was . (p< . ), and altman bland testing revealed a bias of . with % limits of agreement - . to . . bedside estimation of suppression ratio during ttm after cardiac arrest showed excellent agreement when measured with the medtronic bispectral index monitor and the full montage natus ceeg monitor though the impact of therapeutic hypothermia on neurological outcomes remains controversial, there is strong evidence that pyrexia is detrimental. posthypothermia fever experienced by cardiac arrest patients is of particular concern. this abstract examines the ability of an esophageal heat transfer device (ehtd) to maintain core temperature below °c in critical care patients, with a focus on posthypothermia fever in post cardiac arrest (pca) patients. de-identified data for subjects who received temperature management using an ehtd were collected with a condition appropriate for active temperature management. core temperature readings for each patient were recorded at least hourly; if measurements were recorded more frequently, temperature over an hour span was averaged. patient data was analyzed to determine what proportion of measurements were above °c. data from a total of patients was collected, including post-cardiac arrest patients and fever reversal cases. a total of core temperature measurement events (over an average of . h per patient) were included in the analysis. ( . %) were below °c, recorded measurements exceeded °c, and no data were recorded for time points. of the measurements recorded posthypothermia, ( . %) remained below °c. esophageal temperature modulation using an ehtd appears to be an effective method for fever prevention and reduction. visual representations of the pca subset showed an upward trend in temperature after - hours of maintaining target temperature, but before active cooling ended. this suggests that many of these patients might have become febrile in the absence of active temperature management. achieving and maintaining normothermia (nt) after subarachnoid hemorrhage (sah) or intracerebral hemorrhage (ich) often requires surface or intravascular cooling devices that are associated with a significant burden of shivering. we describe a new, closed loop esophageal cooling device (ecd: -- . c) and the shiver burden during the maintenance of nt. we enrolled mechanically-ventilated patients with sah or ich with refractory fever (> . c). temperature and bedside shivering assessment scale (bsas) were recorded every minutes for the time above c, median bsas and cumulative number of anti-shivering interventions per patient was recorded prospectively. all patients received magnesium, buspirone, and acetaminophen as baseline anti -shivering interventions. ten patients ( ich, sah) were enrolled between october and april . the median gcs at initiation was ( ---- . m , and % were women. there was a temperature reduction at minutes (mean . c to . c, p= . ) and % of patients achieved nt (median time = . hrs.; range: . - hours). nt was maintained for median -- %) time above > e time. the median number of total shiver interventions per patient was ( - ) throughout the ttm time period. no device related complications were noted. the ecd successfully achieved and maintained nt with a low shiver burden and may be a feasible option for nt in this critically-ill population. we present a case of toxic leukoencephalopathy in a young woman taking a thermogenic dietary supplement. a year old female with unremarkable pmh except being on a diet drug "remuvik" presented with a day history of severe headache, blurry vision, photophobia, phonophobia, nausea, vomiting and brief intermittent hand spasms. neurological exam was notable for mild right finger-to-nose ataxia and diffuse hyperreflexia. initial mri demonstrated extensive bilaterally symmetric t hyperintensities of the corpus callosum and periventricular white matter. csf profile was unremarkable. labs were unremarkable except for serum sodium of meq/l. approximately hours later, patient became unresponsive with bilaterally fixed-dilated pupils and decerebrate posturing. she was intubated and gms of mannitol was emergently administered with concern for cerebral edema. iv lorazepam was also given. a stat ct head showed diffuse cerebral edema. an external ventricular drain was placed emergently and % nacl was started. continuous eeg was negative for seizures. next day she started following commands and on day she was discharged home with normal neurological exam. given her presentation and mri findings, she was diagnosed with acute toxic leukoencephalopathy due to thermogenic diet pill "remuvik". patient had been taking the diet drug for months and had lost lbs. the main ingredients in remuvik are listed as resveratrol, caffeine-free green tea and l -carnitine while the remaining ingredients are unknown. similar presentation with another diet drug "thermatrim" has been previously reported. these products are not fda regulated and are easily available to the general public. the acute cerebral edema with decompensation was thought to be due to hyponatremia caused by remuvik. while the mechanism of leukoencephalopathy is not well understood and further investigation is needed, spreading awareness is the key to prevent serious adverse effects of such unregulated products. baclofen is a frequently used muscle relaxant. we report a case of, low dose baclofen causing reversible gped's (generalized periodic epileptiform discharges). on review of literature, baclofen toxicity/overdose has been associated with burst suppression patterns on eeg, with one case report of baclofen toxicity causing gped's. to the best of our knowledge there have not been reports of low dose baclofen induced significant eeg changes. case reportthe patient is an year old woman, with poor baseline functional status from advanced dementia and limb contractures, on coumadin for old dvt/pe, with sub-therapeutic inr, was admitted with new onset seizures secondary to venous infarcts over bilateral parieto-occipital areas, due to extensive venous sinus thrombosis. she was monitored on continuous video eeg and initiated on antiepileptic medications, vimpat and dilantin. eeg recording initially demonstrated occasional sharp waves, maximal in the left frontal region. however, because of excessive emg artifact caused by hypertonia, the patient was started on baclofen mg. within hours patient's mental status deteriorated and eeg recording demonstrated gped's with periods of suppression. due to concern for drug adverse reaction, baclofen was discontinued. the eeg reverted to pre-baclofen pattern, while her mental status slowly improved. she was provided supportive care and ultimately discharged to a rehabilitation facility. in this elderly dementia patient, with low seizure threshold from the acute cerebral insult, low dose of baclofen was enough to induce encephalopathy and gped's. the absence of any metabolic disturbances along with rapid resolution of clinical and electroencephalographic abnormalities after discontinuation of the drug supports the hypothesis that these findings may be the direct cerebral toxic effect of baclofen. iatrogenic encephalopathy with baclofen should be considered in the differential for elderly patients with low cognitive reserve rotational vertebrobasilar insufficiency, also called bow hunter's syndrome after the symptom-inducing head position adopted when aiming a bow, is a rare cause of posterior circulation ischemia. we present a case of an -year-old woman who presented to barnes-jewish hospital with several days of episodic vertigo and gait instability. two weeks prior to presentation she had fallen and struck her head. imaging revealed a complex c fracture as well as an odontoid fracture with posterior displacement. she began having positional spells characterized by loss of consciousness, gaze deviation, fencer posturing, and sonorous breathing. review of clinical records and literature review. the spells were initially highly concerning for seizures. the patient was monitored on continuous video eeg, however no seizures were detected during typical spells. a ct angiogram revealed an occluded right vertebral artery at the level of c with diminutive vs. absent posterior communicating arteries isolating the posterior circulation. subsequent mr angiography revealed a patent right vertebral artery with no evidence of stroke. catheter cerebral angiography demonstrated a patent left vertebral artery. turning the head degrees during the procedure, however, elicited a typical spell and completely occluded the left vertebral artery. the patient underwent occipitocervical fusion, but unfortunately suffered a multifocal posterior circulation stroke and was discharged with hospice care. we present an unusual case of rotational vertebrobasilar insufficiency that mimicked a classic sezure semiology and presented several diagnostic dilemmas in the icu. in this case, traumatic injury resulted in likely bilateral positional vertebral artery occlusion with resultantly profound brainstem ischemia. bow hunter's syndrome should be considered in all cases of positional neurological spells, particularly in the setting of neck injury. optic nerve sheath diameter (onsd) measurement using ultrasound has been proposed as a reliable method for non-invasive assessment of intracranial pressure (icp). we report a case of using onsd to monitor icp in a tbi patient with elevated icp undergoing medical treatment with acetazolamide. we hypothesize that a difference in onsd could be detected with ultrasound before and after treatment. patient is a year old man with mild tbi due to assault. his head ct reveals a long calvarial fracture extending along the superior sagittal suture line and posteriorly into the left parietal bone, as well as a large epidural hematoma overlying the frontoparietal vertex near midline, and causing inferior displacement and extrinsic compression of the superior sagittal sinus. his physical exam reveals a young man with right orbital ecchymosis who is sleepy but easily arousable with a gcs of and no motor deficits. dilated fundus exam by ophthalmology reveals grade - papilledema consistent with elevated icp. the patient complains of persistent headaches and nausea that is unremitting. acetazolamide was started to decrease icp. we measured onsd with a sonosite ultrasound device prior to start of acetazolamide and days afterwards. two measurements were taken on each eye, one in the horizontal and vertical orientation each. the average onsd was . mm on the right eye and . mm on the left eye prior to initiation of treatment. on the day after treatment onsd was . mm on the right and . mm on the left eye. the patient's headache improved and nausea resolved. the next day onsd was . mm on the right and . mm on the left eye. headache and nausea completely resolved. this case report affirms that ultrasound measurement of onsd could be used reliably to assess icp noninvasively during the course of treatment for elevated icp. manoj k. mittal. kansas university medical center/ neurology, kansas city, ks, usa. timing of brain death evaluation could be crucial in maintaining organ perfusion for donation. a new bedside cerebral blood flow monitor (cflow monitor from ornim) has not been previously studied for determining the timing of brain death examination. we present here a case illustrating the role of bedside blood flow monitoring in determining the timing of brain death evaluation. a year-old-woman presented with acute right middle cerebral artery stroke and bilateral internal carotid artery occlusions. she was not a candidate for intravenous thrombolysis or endovascular therapy due to unknown time of symptoms onset. her initial nihss was (right gaze deviation, mild aphasia, mild dysarthria, left facial droop, left hemiparesis, left sided decreased sensation and neglect). day- , she got intubated for hypoxic respiratory failure. day- , ct head showed cerebral edema with midline shift of mm. patient was not a decompressive hemicraniectomy candidate. day- , patient was comatose. day- , patient lost bilateral pupillary reflex. ct head showed worsening midline shift of mm with right uncal herniation, bilateral anterior cerebral artery and left posterior cerebral artery stroke, and brainstem compression. day- , bedside cerebral blood blood flow monitoring was started with right sided cerebral blood flow index (cfi) of and left side cfi of . patient met criteria for brain death except that she was still breathing over the ventilator. patient was extubated for comfort measures. after minutes patients stopped breathing. her cfi dropped < bilaterally. patient underwent cardiac arrest after minutes and then both cfi were < . patient was not a candidate for organ donation. bedside cerebral blood flow monitoring may assist in determining the timing of brain death evaluation in comatose patients with imminent brain death. patients with cfi < may be considered for brain death evaluation. our finding needs further confirmation. aneurysmal subarachnoid hemorrhage patient. icus are high cost in the u.s., comprising about % of the us gdp. pressure is being placed on hospitals and intensivists to reduce costs, including earlier palliative care engagement to shorten length of stay.. as the u.s. migrates to a value-based system, further pressure will be made on reducing prolonged and expensive icu interventions, similar to quality adjusted life year (qaly) cutoff values to justify costs. a young year old man presented with worst headache of his life, and was found comatose by ems and referred to our neuroicu. he had a . cm giant basilar asah with intraventricular hemorrhage. the aneurysm was coiled endovascularly with external ventricular drain placed. he required therapeutic hypothermia, osmotherapy, induced hypertension and balloon angioplasty and intraarterial verapamil for refractory basilar and bilateral middle cerebral artery vasospasm. he had refractory intracranial pressure from global cerebral edema and around post-operative day # required bifrontal craniectomy. later percutaneous tracheostomy, peg tube, and ventriculoperitoneal shunting were performed. his total costs exceeded $ , u.s. dollars. one year later, his modified rankin scale was zero, and he went to college. his qaly (quality adjusted life year) for the rest of his year was . given a utility of . his physicians felt he should live to a normal life expectancy of years of age, q is quality of life weight = (perfect health, utility = ), l is residual life expectancy = more years. his qal-expectancy , is about life-years gained which divided over his life span is about $ , /year and less than the current cms reported value of $ , per year. this case exemplifies how high cost care can be delivered to deliver cost-effective, high quality care and underscore the need for integrated high-complexity neuroicu care. early mobility in the intensive care unit setting is associated with a number of positive effects including improved quality of life. though there is a strong body of evidence supporting early mobility in medical intensive care units, the benefits of very early mobilization after acute stroke are yet unclear as early hemodynamic variability in patients with impaired cerebral auto regulation is of concern. another potential barrier to early mobilization is the presence of an external ventricular drain (evd) for cerebrospinal fluid diversion and intracranial pressure (icp) monitoring. this case demonstrates hemodynamic and icp responses to progressive, device assisted mobility interventions during the acute phase of intracerebral hemorrhage (ich) in the setting of persistent elevations of icp requiring two evds. a year-old man was admitted to the neuroscience critical care unit with an acute thalamic ich and intraventricular hemorrhage requiring placement of two evds. starting on day following ich onset, the patient underwent progressive mobilization following the johns hopkins nccu activity and mobility algorithm. range of motion exercises were performed initially, progressing to supine cycle ergometry followed by incremental verticalization using the tilt table (sara combilizer®arjo huntleigh inc.,il). blood pressure, heart rate, oxygen saturation, and icp were recorded before, during and after the mobility interventions. no adverse neurologic effects were noted during these mobility interventions. recorded hemodynamic variables and icp remained within the set goals throughout. moreover the patient was able to tolerate degrees of verticalization on the tilt table. progressive, device assisted early mobilization was feasible when titrated by skilled healthcare professionals in a critically ill hemorrhagic stroke patient with evds. studies on larger patient samples are needed to improve our understanding of the hemodynamic and neurophysiologic responses to establish safety of progressive early mobilization of critically ill patients with acute stroke. anand venkatraman, ayaz a. khawaja, angela a. shapshak. university of alabama at birmingham / department of neurology, birmingham, al, usa. we describe a case of a patient with uncontrolled hypertension (htn) and prior intracranial hemorrhage (ich) who developed an intracranial hemorrhage shortly after consuming redline, a heavily-caffeinated energy drink. a -year old caucasian male with prior history of ich and chronic untreated htn was transferred to our service for evaluation of . x . cm ich in the left thalamus. blood pressure had been elevated in the emergency room there and he had been started on a nicardipine infusion. nih stroke scale was . ich score was . admission labs were normal. urine drug screen was negative. on questioning, patient revealed that symptoms had started within hours of consumption of bottle of redline, an energy drink. he was not a regular user but did consume it whenever he needed to get a lot of work done. mri of the brain did not show any vascular malformation or other lesion. multiple remote hemorrhages were seen in the subcortical areas. we stared lisinopril and weaned off his nicardipine infusion. he was discharged with minimal deficits. the high caffeine content is the most likely component of the drink that led to the ich, given that high caffeine consumption is linked to increased risk of hemorrhagic strokes. caffeine also has effects on platelet aggregation and endothelial function that could raise stroke risk. generalizability is limited by the fact that the patient had uncontrolled htn and prior ichs. however, given that % of adults in the usa have uncontrolled htn, and given that ich account for - % of all strokes, a large population is at risk. to our knowledge this is the first report of intracranial hemorrhage following consumption of an energy drink. consumers must exercise caution, especially in the setting of uncontrolled risk factors. elena schmidt, varada v. nair, gene g. latorre. suny upstate university hospital / department of neurology, syracuse, ny, usa. often times medications given in emergency cases have unintended consequences, sometimes posing even more harm than the reason for their administration. we report a case of a young lady with history of anaphylactic reaction who received i.m. epinephrine after developing allergic reaction to antibiotic, resulting in bilateral intracerebral hemorrhage (ich). our case is of a year old female with history of anaphylactic reaction who had been recently started on cephalexin for orbital cellulitis. she was sent to ed after having a syncopal event in the doctor's office. while in ed, the patient was administered . mg of : , epinephrine i.m. because of suspected anaphylactic reaction. shortly after, she complained of nausea, vomiting and developed right sided weakness and numbness. immediate ct head revealed two areas of ich, within the left parietal and right occipital lobes. extensive work-up ensued, with cta head and neck (negative for vessel anomalies), cerebral dsa (negative for vasculitis), mri brain w/wo contrast (negative for malignancy or amyloid angiopathy), ct thorax and abdomen (negative for malignancy). serum studies for vasculitis work-up were also unrevealing. echocardiogram did not show evidence for chronic hypertension such as lv hypertrophy. although there have been reports in the literature of spontaneous intracranial hemorrhage (intraparenchymal or subarachnoid) after various ways of epinephrine administration, in our patient's case, the extensive work-up done to exclude other etiologies stands out. this strengthens the hypothesis that epinephrine, causing an acute spike in blood pressure, ultimately led to spontaneous ich. in addition, the case of our patient is unique in that she developed two areas of ich, in a location typical for posterior reversible encephalopathy syndrome (pres), a syndrome known to be caused by significant elevation in blood pressures, suggesting a common underlying pathophysiology. careful consideration of indications should occur before administering such potentially harmful treatments. "last known normal" (lkn) time remains the standard for determining the onset of acute ischemic stroke and appropriateness of providing acute therapies. as older adults become more familiar with social media platforms, these applications may become a source of recognizing when a patient was lkn. we report an year-old woman who was "found down" at home. the patient lived independently, and was able to crawl to a telephone for help. on arrival to the emergency department, she had a right middle cerebral artery syndrome with an nih stroke scale of . she had a decreased level of arousal and severe dysarthria which precluded assessment of her lkn. the patient's son reported that he had last seen her normal hours prior, placing her outside the time window for acute therapies. however, the patient's granddaughter reported that the patient had been logged into facebook < hour prior to her admission "chatting" and commenting on photos. "timestamps" of comments left on photos by the patient provided exact times of the patient's activity. the only logical means of being able to perform these relatively high-functioning tasks would have been if the she was normal at the time of posting, thereby establishing her lkn. the patient was treated with systemic t-pa followed by endovascular therapy for a proximal m occlusion. the patient had rapid improvement of her stroke symptoms. she was discharged home with an nih stroke scale of . this patient's recent use of the social media was critical in determining the patient's lkn, leading to lifesaving acute stroke therapy. providers should be aware that social media may serve as a useful source of symptom onset information. in this case, it led to good outcome and discharge home. bilateral recurrent artery of heubner (rah) infarctions have been seldomnly reported in the literature. even more so for those cases that have occurred subsequent to neurosurgical extensive resections of large invasive olfactory groove meningioma. rah, a branch of the anterio-inferior cerebral artery, supplies anterior limb of the internal capsule, anterior caudate, putamen and globus pallidus. infarction typically results in contralateral paresis of the arm and face. other symptoms can occur i.e. choreiform movements, abulia, attention disorder, impaired memory, apathy, decreased spontaneity, depression, dementia etc. we present a case of bilateral rah infarcts as a complication of a large olfactory groove meningioma resection. we did an extensive chart review of our patient during post-operative neurointensive care unit stay, rest of the hospital stay and discharge follow up at month. our patients brain mri done as a part of routine post-operative imaging showed bilateral caudate head infarcts in the territory of rah. post-operative exam was significant for a left hemianopsia and right super quadrantopsia with color desaturation. patient did not experience any new weakness or movement related problems. he did have changes in cognition (forgetfulness & irritability) along with a subjective loss of sense of smell but these were consistent with his pre-op assessment. olfactory groove meningioma's comprise % of all intracranial meningiomas, are slow growing and tend to engulf and compress neighboring structures. most common complications of olfactory groove meningioma resections are post-operative cerebral edema, csf leak, seizures, cns infections, hydrocephalus and rarely brain ischemia. bilateral rah infarction, although rare has been reported in literature in association with vascular anomalies and other stroke risk factors. cerebral infarction involving the aca territories remains a known adverse complication of large olfactory groove meningioma resections, but bilateral infarcts due to these have not been reported before. angioinvasive aspergillus associated stroke in an immunocompetent host. aspergillus vasculitis is an under-recognized cause of stroke in immunocompetent hosts, especially when other risk factors are present. we present a case of autopsy proven angioinvasive aspergillus causing strokes in an immunocompetent host, and review the characteristic imaging findings to aid diagnosis. -year-old female developed cardiogenic shock after three-vessel-coronary artery bypass grafting (cabg) using saphenous vein grafts requiring intra-aortic balloon pump placement. this was complicated by aortic dissection, and she underwent replacement of the ascending aortic arch. refractory cardiogenic shock ensued for which she underwent placement of veno-arterial extracorporeal membrane oxygenation. postoperatively, she was noted to be in coma, and a non-contrast ct of the brain showed small multiple small ischemic strokes bilaterally. with persistent multi-organ failure, she was ultimately transitioned to comfort care and passed. autopsy revealed multiple perivascular petechial hemorrhagic infarcts involving white matter, deep gray matter and cerebellum on gross specimen. histopatholgic study showed aspergillus associated acute and chronic inflammation of blood vessel, and surrounding gliosis. aspergillus was also found in coronary grafts and kidneys. aspergillus associated cerebral vasculitis was considered less likely, as cabg, extracorporeal membrane oxygenation (ecmo) device-related thrombosis and acute mi were the leading differentials for stroke here, and no obvious immunosuppression was evident. cerebral aspergillosis can occur from direct spread from sinus infections or through hematogenous mode, and seemed to have originated from coronary grafts in this case. aspergillus has a predilection for posterior circulation arteries, and lacunar-type infarcts or petechial hemorrhages within the midbrain, thalami, or corpus callosum are characteristic. these findings should raise suspicion for aspergillus, especially without objective evidence of other mechanisms of stroke. early initiation of anti-fungal therapy may improve the likelihood of survival, and confirmatory testing in the form of blood vessel imaging, csf analysis and fungal blood cultures should be performed in suspected cases. autoimmune ganglionopathy: a rare cause of cardiac arrest kelly braun. neurological institute, cleveland clinic, cleveland, oh, usa. autoimmune autonomic ganglionopathy is a rare disorder characterized by pandysautonomia that occurs as a result of autoantibodies to ganglionic nicotinic acetylcholine receptors. we describe a year old male with autoimmune ganglionopathy previously treated with ivig who suffered cardiac arrest and anoxic brain injury as a complication of this disorder. the patient had a history of multiple autoimmune diseases (dm , autoimmune hepatitis, hashimoto's thyroiditis, celiac disease, antiphospholipid syndrome and ulcerative colitis). to alleviate his pre-syncopal lightheadedness related to dysautonomia, he would typically kneel and place his head on his folded arms. the patient was found unresponsive in this position in pea arrest. he underwent cpr followed by therapeutic hypothermia ( °c x h). the initial exam off sedation showed an obtunded patient with intact pupillary and corneal reflexes, but no tracking or command following. though he moved all extremities spontaneously, the movements were not purposeful and had a choreiform quality. notable labs were an elevated achr ganglionic neuronal antibody ( . nmol/l on hospital day and . nmol/l on hospital day ; normal < . nmol/l). mri brain showed symmetric diffusion restriction and flair changes throughout the brainstem, thalami and cerebellum, however there was no cortical diffusion restriction. eeg showed generalized intermittent rhythmic slowing, which was maximal bifrontally. he was treated with methylprednisolone mg daily for days and transitioned to prednisone mg daily. at the time of discharge to an acute rehabilitation facility, the patient followed most simple commands and moved all of his extremities against resistance, though he was noted to have diffuse hypotonia. to our knowledge, this is the first reported case of cardiac arrest attributed to autoimmune autonomic ganglionopathy. while rare, this is a serious complication of this syndrome. bibhukalyani das, shantanu s. shubham. institute of neurosciences kolkata, kolkata, india. global burden of tuberculosis is still high particularly in developing world. india is the largest tb burden country accounting for / th of the global incidence.cns tuberculosis is the most severe form of infection with microbacterium tuberculosis.emergence of mdr(multi drug resistant) tuberculosis has compounded the risk and adverse outcome. fatality rate of mdr tb meningitis is % with significant functional impairment in most of the survivors. mortality > % if patient is hiv positive. we report a case of yrs old girl from eastern india case of mdr -cns tuberculosis with a protracted clinical course of years. she developed a whole range of complications including hydrocephalus, optochiasmatic arachnoiditis with secondary optic atrophy, multiple tuberculomas, cerebellar and brainstem tubercular abscesses and siadh with hyponatraemia. our case is notable for few rare complications in the form of transverse sinus thrombosis secondary to chronic meningitis necessitating oral anticoagulation . the patient also developed various side effects of long term att such as -(i) att induced hepatitis. (ii) moxifloxacin induced seizures and re-adjustment of antiepileptics due to interaction with antitubercular drugs. she was managed with antitubercular drugs ( first line drugs) along with second line drugs (amikacin, levofloxacin, cycloserine, ethionamide) her clinical course was complicated by obstructive hydrocephalus requiring evd, vp shunt and shunt revision . developed acute sdh possibly secondary to shunt and required surgical drainage . later she developed posterior fossa tubercular abscess and needed craniectomy. pus from tubercular abscess grew mtb resistant to rifampicin and isoniazid. so the patient was maintained on second line drugs, ultimately succumbed to hospital acquired pneumonia. cns tuberculosis if associated with multiple medical, surgical complications, impose real critical care challenges compounded by mdr which often encountered in a developing country like india. megan lange, rebecca r. horrell. university of maryland medical center, neurocritical care unit, baltimore, md, usa. super-refractory status epilepticus, defined as seizures persisting despite anesthetics, is associated with high morbidity and mortality. here we present two cases of super-refractory status epilepticus intractable to aggressive therapies, including but not limited to anesthetics, electroconvulsive therapy, and immunotherapy. in both cases, the patients developed sepsis and cardiac arrest following prolonged hospitalizations with subsequent termination of seizure activity and improvement in electroencephalogram findings and neurologic exams. a review of the literature revealed a variety of publications describing super-refractory status epilepticus as a result of sepsis or cardiac arrest, but there is limited data describing either complication as therapeutic for status epilepticus. we propose that the systemic effects associated with profound sepsis, or the brief electrographic silence occurring in the setting of cardiac arrest could have played a role in halting seizures in these patients. we describe two theories regarding the potential mechanism by which cardiac arrest or sepsis could play a role in termination of seizures. exploration into specific mediators involved in these conditions and their relationship to status epilepticus could uncover therapeutic targets. targeted therapies could demonstrate promise in effectively treating super-refractory status epilepticus, thereby improving morbidity and mortality rates. ticagrelor is approved for prevention of cardiovascular events in adults with acute coronary syndrome (acs) . we present a patient with sah who developed thrombus during coiling procedure that was treated with abciximab followed by ticagrelor and aspirin, with potentially devastating consequences. a -year-old male presented after sudden onset severe headache. imaging revealed sah from a ruptured basilar tip aneurysm. the patient was neurologically intact with mild confusion, but declined during transfer and required intubation. an external ventricular drain was placed for hydrocephalus. during cerebral angiogram with coil embolization, a thrombus formed on the coil. intra-arterial abciximab was used with resolution of thrombus. he was extubated post procedure. aspirin and ticagrelor ( mg twice daily) were prescribed. the following day, the patient became increasingly lethargic with an increased respiratory rate ( s). he reported no perception of increased work of breathing. portable chest radiograph demonstrated only mild pulmonary edema. he did not have an oxygen requirement. venous blood gas demonstrated a ph . with a pco of , suggesting a respiratory alkalosis. transcranial dopplers demonstrated normal velocities, but the patient was considered for cerebral angiogram given a high concern for vasospasm with his neurologic exam. ticagrelor was stopped the following day. the patient's tachypnea and mental status rapidly improved. ticagrelor reversibly inhibits the platelet p y adenosine phosphate receptor and is indicated for prevention of cardiovascular events in adults with acs. in patients with both cerebral hemorrhage and a need for antithrombotic therapy, this reversible agent may become more widely used. dyspnea is a known side effect of ticagrelor, occurring in . % of patients (p< . ). dyspnea causes respiratory alkalosis and the resulting hypocapnea results in vasoconstriction. in this case, mental status change after administration of ticagrelor suggests that patients at risk for vasospasm may be particularly vulnerable to its side effects. over the past years, the americas have experienced waves of emerging and re-emerging arboviruses that cause neuroinvasive disease, including west nile virus, chikungunya virus, zika virus, and dengue virus. these viruses pose great challenges for traditional candidate-based infectious disease diagnostics that already fail to identify a causative pathogen in approximately % of encephalitis cases. we present the case of a year-old girl with a history of renal transplant managed with mycophenolic acid, tacrolimus and prednisone who presented to an emergency department with two days of high fevers, chills, upper back, neck pain and rash followed by encephalopathy. one month prior to presentation she attended summer camp by a lake in the angeles national forest, california. her hospital course was complicated by status epilepticus. cerebrospinal fluid (csf) analysis demonstrated a mixed neutrophilic and lympocytic pleocytosis. mri of the brain demonstrated symmetric t hyperintensities and edema in the bilateral thalami and leptomeningeal enhancement in the thalamus, cerebellum, brainstem, cervical spine and caudal equine. an extensive diagnostic work-up for infectious causes of encephalitis was performed and only identified epstein-barr virus. research protocol. unbiased mds of rna extracted from her csf and processed through a custom bioinformatics pipeline identified west nile virus. subsequently, convalescent serum serologies confirmed west nile virus infection. this case provides a first proof-of-principle that mds can detect even low level arbovirus burden in the csf of a patient with acute meningoencephalitis. given the rapidly changing landscape of viral causes of encephalitis in the americas, the ability of mds to comprehensively detect a huge array of microbes with a single assay may make it an optimal method for early identification of emerging causes of viral encephalitis, including in the transplant patient population. cladophialophora bantiana is a dematiaceous mold with a predilection for causing central nervous system infection, particularly in normal hosts. there is no standard therapy and mortality rates from this disease remain extremely high approaching %. here we describe a case involving a year-old immunocompetent man who presented with new onset seizures. brain imaging revealed bifrontal ring enhancing lesions concerning for abscess.the patient underwent surgical debridement of the lesions and bilateral intracavitary treatment with amphotericin b using ommaya reservoirs for several months. after approximately months of treatment which included surgical debridement , oral voriconazole and intracavitary amphotericin b, our patient is off all antifungals and no longer receiving intracavitary treatment. he remains fully functional with a nonfocal neurologic exam, being monitored with serial brain mris. due to rare incidence of cerebral phaeohyphomycosis, there are no clinical trials to help formulate standardized treatment guidelines despite its high mortality . this case places emphasis on an early aggressive multimodal approach for treatment of cerebral phaeohyphomycosis using a combination of surgical debridement, intracavitary antifungal injection, and oral antifungal therapy. does neurocritical care need to improve outreach to non-neuro specialties? firas abdulmajeed, mb. chb, bart b. nathan, md, fcns. university of virginia/ department of neurology, charlottesville, va, usa. the number of neuro-critical care(ncc) fellowship positions has been increasing yearly. the number of applicants has plateaued over the last years, leaving many programs with unfilled fellowship positions. the demand for neurointensivists is on the rise. trainees have come from neurology traditionally, with a limited number from internal medicine (im). we hypothesize that the relative paucity of im fellows was in part due to insufficient knowledge of ncc. we surveyed im residency programs in the united states, asking program directors to forward our survey to their residents. on another survey, ncc fellowship directors were asked: ) how many trainees and how many faculty hires from im and/ or em have they had within the last five years internal medicine residencies survey results: we obtained individual responses, responses were complete. how long is the ncc fellowship? n= % year % years % years residents of what specialty can apply to a ncc fellowship? n= . % (neurology, neurosurgery, anesthesiology, im and em) % neurology only % neurology, neurosurgery and anesthesia knowledge of san francisco matching system? n= % yes. % no do you know about the application cycle for the ncc match? n= % yes. % no knowledge of emergency neurological life support? n= % yes % no ncc fellowships' directors survey results: of the programs responded fellows with im/em background that were trained within the last years: / neuro-intensivists with im/em background hired: / im residents appear to have little knowledge of ncc fellowship. a lack of awareness of enls could affect the quality of care provided for neurological emergencies. additionally, for the specialty to grow and fill unmatched fellowship positions,current training and outreach strategies to non-neurology trainees may need to be improved somatosensory evoked potentials (sseps) are a sensitive, minimally invasive technique used to identify injury from the posterior columns of the spinal cord to the somatosensory cortex. the role of sseps as a neuromonitoring tool, in the neuroicu has not been well established. we present a case using sseps as a neuromonitoring tool illustrating electrical improvement along with clinical and radiographical improvement in a symptomatic chiari i malformation. year old female who was months postpartum after vaginal delivery with epidural analgesia presented with headaches, diplopia and nausea/vomiting. after arrival to er, she acutely developed flaccid quadriparesis with ophthalmoplegia and loss of airway while awake and following commands. given the concern for intracranial hypotension, we administered mannitol, hyperventilated and placed in trendelenburg position. head ct showed cisternal effacement in the setting of a likely pre-existing chiari malformation with cerebellar tonsillar. decompressive surgery was not an option initially given her dysautonomia and neurologic instability whenever the patient was not in trendelenburg. during her prolonged course, she had two mris of her brain and spinal cord which showed chiari i malformation with syrinx at c and presyrinx down to t . there was cervical spine venous engorgement and csf block at the level of the foramen-magnum. she was evaluated with serial sseps which initially showed low amplitude n response that improved with her clinical improvement. ssep is a minimally invasive method to electrically assess the somatosensory pathway integrity from the spinal cord, brainstem and cortex. given its sensitivity to the function of the dorsal columns of the spinal cord and medial lemniscus of the brainstem, sseps may be a useful monitoring adjunct to follow the evolution of posterior fossa lesions in patients that may not tolerate other means of monitoring and/or transportation, such as mri. review of prospectively maintained patient database identified one case of status epilepticus in a patient with cns-ptld. we present a case report with literature review. a -year old hispanic woman with a history of renal transplant years prior, presented with episodic confusion and gait ataxia progressing over two weeks. she was on immunomodulation with mycophenolate. patient had witnessed periods of behavioral arrest. continuous electroencephalography (ceeg) demonstrated right temporal sharps and - second epochs of bi-frontal - hz activity, some of which were associated with non-stereotyped movements of her left shoulder and trunk, suggestive of se. she received benzodiazepines followed by levetiracetam (renal dose) and phenytoin load for seizure control. mri brain without contrast demonstrated multifocal infiltrative t -hyperintense white matter lesions, most prominent in right temporal lobe. csf analysis demonstrated rbc, (l %) wbc, protein, glucose, culture and gram stain were negative. there were unmatched csf bands with an unremarkable cytology. csf pcr was positive for ebv and viral load was detected at copies/nl. other csf microbial assays including jcv were negative. stereotactic right temporal brain biopsy demonstrated areas of necrosis, axonal disruption, loss of myelin with polytypic plasma cells, cd and cd positive b cells and cd positive t cells on immunohistochemistry consistent with a diagnosis of polymorphic ptld. despite treatment with dexamethasone and rituximab, patient continued to remain critically ill and eventually received palliative measures. among transplant recipients, pcns-ptld is rare but debilitating with varied neurological presentation. high degree of suspicion, early diagnosis and treatment are paramount for survival. cortical myoclonus caused by activation of cortical areas subjacent to multiple subdural hematomas is an unusual mechanism of epilepsy. we report the case of a patient with an extra axial bleeding and myoclonic seizures evaluated with ictal fdg-pet. case report a year old male was admitted to our hospital because of worsening symptoms of cardiac failure of chagasic etiology. due to hemodynamic instability he was treated with the placement of an intraortic balloon pump. sixteen days after hospital admission, he presented intermittent generalized myoclonic jerks. on initial examination he was alert and oriented to time and place, had preserved strength in all limbs, although presenting with very frequent clusters of myoclonus. initial investigation with a head ct showed multiple foci of extra axial bleeding, distributed over the frontal and parietal areas. the electroencephalogram (eeg) confirmed the suspected diagnosis of myoclonic seizures, exhibiting generalized polispike-slow wave complex. due to the multiplicity of bleeding sites, with no obvious reason for spontaneous bleeding other than regular anticoagulation, the patient was submitted to a whole-body fdg-pet in order to exclude the possibility of dural metastatic implants. fdg-pet showed areas of cortical hypermetabolism adjacent to the bleeding foci, probably reflecting an epileptogenic mechanism of cortical activation. there was no evidence of hypermetabolism directly over the extra-axial areas of bleeding, what ruled out the hypothesis of dural metastasis. a diagnosis of spontaneous subdural hematomas associated to anticoagulation was given after all other causes were excluded. the patient was treated with sodium valproate and had sustained improvement of the myoclonic seizures. the bleeding areas were eventually reabsorbed, but the patient died from complications of cardiac failure. our report is the first to illustrate the mechanism of cortical activation leading to epileptic status in a patient with multiple subdural hematomas detected by ictal fdg-pet. to present a case of early onset myoclonic status epilepticus (mse) after cardiopulmonary arrest with incomplete resolution of myoclonus and good cognitive outcome. a year-old man presented status post cardiopulmonary arrest and cpr in the field with return of spontaneous circulation (rosc) after arrival to the hospital and cardioversion. the patient was intubated and treated with therapeutic hypothermia, but developed clinical mse with normal eeg within hours. he was aggressively managed with propofol, levetiracetam, and fentanyl. initial mri demonstrated diffuse hypoxic ischemic injury. mri on the th day of admission demonstrated improvement but a new white matter lesion in the splenium of the corpus callosum. after multiple unsuccessful attempts to discontinue fentanyl and days of treatment, the patient was given a poor prognosis based on the aan mse practice parameters and was placed on do not escalate care orders. propofol was slowly decreased; however the patient improved significantly throughout hospitalization with improved language and cognitive examination and only mild residual reflex myoclonus at the time of discharge. mri imaging had completely resolved by the th day of hospitalization. the patient's final diagnosis is lance-adams syndrome of action myoclonus incompletely controlled with levetiracetam. aggressive and prolonged treatment including therapeutic hypothermia in young patients with early onset mse was effective despite aan practice parameters. this patient survived with good cognitive outcome and with relatively modest deficits. further research is needed to assess whether improvements in intensive care unit capabilities over the past decade may contribute to improved outcome in young patients with cardiac arrest and whether practice parameters should be revised. at the start of this protocol, the serum sodium was and one-hour urine output was liter. this protocol was continued for hours. endocrinology was consulted and recommended changing to ddavp. serum sodium was [np ] and one-hour urine output cc prior to first dose of ddavp university of washington, department of surgery, seattle, wa, usa. earlier feeding results in improved outcomes in adults with severe traumatic brain injury (tbi) and in the overall pediatric intensive care unit (picu) population. current practices of nutrition initiation in children with tbi are not well described. this multicenter study evaluated timing and factors associated with nutrition initiation in children admitted to picus with tbi. we hypothesize that severely brain injured patients would have a delay in initiation of enteral nutrition. we retrospectively analyzed the multicenter pediatric trauma assessment and management database (ptam) from . patients with severe tbi were defined as glasgow coma scale (gcs) < with n in this group was compared injury, abdominal procedures were compared between the two groups. chi square and fisher exact tests were used for dichotomous variables; non-parametric tests were used for continuous variables. multivariable regression analysis with a stepwise procedure was performed to ascertain the best set of variables associated with delayed initiation of enteral nutrition. of patients admitted to the five ptam picus with severe tbi, ( %) were fed < hours from admission. patients with gcs < were fed a median . hours from admission (iqr . - . ) compared to . hours (iqr . regimen, higher injury and illness severity scores and lower minimum gcs were significantly associated with feeding initiation > hours. on multivariable analysis, scheduled bowel regimen, higher prism score and lower minimum gcs were significantly associated with nutrition initiation > hrs. lower gcs is independently associated with delayed initiation of enteral nutrition in children with tbi, independent of severity of injury or abdominal injury. all patients that suffered ca within hours of sah onset were identified from a prospectively collected characteristics, and outcomes of those with and without ca in the setting of sah using binary logistic regression. only % (n= ) of sah patients had ca within hours of the bleed. % (n= ) of those with ca had f these patients died while in the hospital. three patients had a ventricular fibrillation (vfib) arrest, and one of these patients (n= ), and half of these patients survived. % of patients were comatose after the arrest, most of which underwent cooling (goal temperatures - ). % of deaths in our cohort were from withdrawal of life support (n= ). increased aneurysm size (or . for each mm, % ci . - . ), amount of sah (or . , , and global cerebral edema (or . , ci . - . ) were associated with noncomatose patients and those with vfib arrests may have a better prognosis. acute herniation at the time of bleeding as indicated by large volume sah and global cerebral edema may be the underlying mechanism of most early cardiac arrest in sah patients. early identification of delayed cerebral ischemia (dci) following aneurysmal subarachnoid hemorrhage (sah) could allow more effective intervention. statistical methods that predict dci using variables collected routinely during icu care such as trends in vital signs and laboratory values have shown promise in recent studies. however, these studies have not all employed methods to guard against model overfitting. in this study we use cross validation to obtain minimally-biased estimates of the value of passively collected icu variables for predicting dci. early identification of delayed cerebral ischemia (dci) following aneurysmal subarachnoid hemorrhage (sah) could allow more effective intervention. statistical methods that predict dci using variables collected routinely during icu care such as trends in vital signs and laboratory values have shown promise in recent studies. however, these studies have not all employed methods to guard against model overfitting. in this study we use cross validation to obtain minimally-biased estimates of the value of passively collected icu variables for predicting dci. dci occurred in % of patients. penalized logistic regression selected features for inclusion in the final predictive model, derived from gcs, heart rate, mean aterial blood pressure, respiratory rate, spo , ventricular drainage, and sodium data. the mean auc of the model was %. potentially clinically relevant (sensitivity, specificity) points on the roc curve included ( , )% and ( , )%. dci occurred in % of patients. penalized logistic regression selected features for inclusion in the final predictive model, derived from gcs, heart rate, mean aterial blood pressure, respiratory rate, spo , ventricular drainage, and sodium data. the mean auc of the model was %. potentially clinically relevant (sensitivity, specificity) points on the roc curve included ( , )% and ( , )%. subarachnoid hemorrhage (sah) remains a highly morbid disease leading to > -related year of life lost before age . mechanisms of sah-related early brain injury and vasospasm remain microrna (mir)- a is released in response to hypoxia and promotes angiogenesis. we hypothesize that higher levels of mir- a is associated with outcome in human sah. functiona -up every months. good functional outcome is defined as mrs % reduction in caliber of any vessel on post-sah day cerebral angiogram. in sah subjects we compared csf and plasma mir- a by quantitative pcr on post-sah days , and between outcome groups. data are normalized using log-transformation and then compared using student's t- study population has mean age of . % has hunt and hess (hh) grade > . good outcome at months is associated with higher plasma mir- a levels on post-sah day (p= . ) and day (p= . ). after adjusting for important predictors of outcome (hh grade; age), plasma mir- a on post-sah day remains strongly associated with outcome (p< . ). plasma mir- a levels were not associated with vasospasm. mir- a is present in csf and is elevated in sah compared to controls (p< . ), but csf mir- a showed no association with functional outcome or vasospasm status. higher plasma mir- a level at post-sah day is independently associated with -month sah outcome. mechanistic experiments are necessary to determine whether mir- a expression is neuro-protective in sah. validation studies in larger, independent cohorts are necessary to validate mirna- a as a accurate assessment of renal function remains a unique challenge in patients with aneurysmal subarachnoid hemorrhage (asah). mathematical estimates of creatinine clearance (crcl) routinely used are often inaccurate in this setting. patients with asah have been shown to exhibit a hyperdynamic response leading to an enhanced renal clearance. no studies exist evaluating the directly measured creatinine clearance of patients with asah over time. this was a single-center prospective observational study of adult patients with asah admitted to the nsicu between january and july . eight-hour urinary creatinine clearances were performed daily to directly measure crcl until the patient no longer had a foley catheter or the patient left the nsicu.-gault equation. statistical significance was defined as p-value < . . fifty patients with asah were enrolled in the study. the study sample was % female with a mean age of . ± . years. the median hunt and hess grade was (iqr - ) and the median modified fisher grade was (iqr - ). additionally, the median admission gcs was . (iqr - ) and median admission sofa score was (iqr - ). the mean urinary crcl over the study period was . ± . patients with asah consistently experienced urinary crcl greater than estimated crcl predicted based on -gault equation. as renally eliminated medications are routinely dosed based on mathematical estimates of renal function, further study is needed to optimize medication regimens in this patient population to prevent underexposure. agitated delirium is frequently encountered after acute brain injury, but data is limited in patients with nces of agitation in these patients. via records of antipsychotic or dexmedetomidine administration, and agitation was confirmed via chart study team. outcome was assessed at months using interview for cognitive status (tics), and lawton-iadl score. agitation developed in of patients ( . %) and was most common in the first hours after admission, and in patients with hunt and hess grades and . agitated patients were significantly more in half of these patients a complication appeared to occur within hours of the onset of agitation. patients with agitation had increased icu and hospital lengths of stay, but this was not significant after controlling for other predictors of length of stay. for patients with hunt and hess grades - , agitation was not independently associated with functional impaired at months compared to those without agitation after controlling for other predictors (lawton > ; p = . , or . , % ci . - . ). patients with sah frequently experience agitation requiring medical treatment, especially early in their clinical course, and especially in non-comatose patients with higher clinical grades. agitation is also associated with the development of multiple hospital complications, and may have an independent impact on long-term outcomes. seizures after subarachnoid hemorrhage (sah) are a frequent complication. sah patients are typically prescribed prophylactic anti-epileptic drugs (aed) for three to seven days. phenytoin has fallen out of favor as aed prophylaxis due to its association with worsened outcome as well as drug interactions. newer aeds including levetiracetam are more commonly used despite an incomplete understanding of their effect on outcome. retrospective analysis was performed of prospectively collected data for consecutive sah patients enrolled into the university of maryland recovery after cerebral hemorrhage (reach) study between -hess (hh) and modified fisher score (mfs) was adjudi a team of neurointensivists. retrospective analysis of cumulative dose of levetiracetam was divided into groups of low-dose (= , mg) using the median as a cutoff. concordance and discordance was noted. pearson chi-square was used. association of levetiracetam dose and quetiapine use as a surrogate of in-hospital delirium was also investigated. multi-variate logistic regression was used to determine predictors of ability to perform activities of daily living (adls) in survivors. asah patients from july to november were reviewed for this study. cumulative levetiracetam dose was calculated in patients and dichotomized into high-dose (>= , mg) or lowdose groups. hunt-hess was found to be significantly associated with high-dose levetiracetam. on multivariate analysis, high-there is a trend towards increased use of quetiapine in the high-dose levetiracetam group. full analysis will be provided at time of presentation. an extended course of levetiracetam is an independent predictor of loss of independence in activities of daily living after sah. there is also a trend toward increased delirium. larger, prospective studies are necessary for a more complete understanding of the impact of seizure prophylaxis on functional outcome after subarachnoid hemorrhage. myocardium: a case series and review of the literature. intra-aortic balloon pump (iabp) counterpulsation has been used to maximize cerebral blood flow in patients with subarachnoid hemorrhage (sah), refractory vasospasm and evidence of cardiac dysfunction. neurogenic stunned myocardium (nsm) pr lv dysfunction. we present cases with sah, vasospasm and iabp placement, including cases with nsm. we also reviewed the literature with the goal of examining the safety of iabp for cardiac dysfunction after sah, outcomes and selection criteria for its use. we searched for cases of sah and iabp placement at the university of kansas medical center (kumc) from to . patients met criteria and all had a secured aneurysm, refractory vasospasm and echocardiograms prior to iabp placement. we collected demographics, vitals, ekg, troponin, medications, iabp and icu complications, discharge and follow-up mrs. however, at follow-r outcome. literature review identified patients -up. our results indicate that patients that have iabp placement in the setting of sah, vasospasm and cardiac dysfunction may have a good outcome if they are younger, have evidence of reversible nsm and avoid icu complications including pe, uti and sepsis. the patients level of mobility and independence at discharge may not be indicative of overall functional improvement. a significant complication of non-traumatic sub-arachnoid hemorrhage (nt-sah) is the development of delayed cerebral ischemia associated with cerebral vasospasm. milrinone, an inotrope and a phosphodiesterase inhibitor, has been used intravenously, intra-thecally and intra-arterially as a delayed cerebral ischemia treatment and prophylaxis. the purpose of the current study is to systematically review the available evidence on its efficacy for that indication. articles from medline, embase, cochrane library, clinicaltrials.gov, reference lists of relevant articles, and gray literature were searched. study selection criteria were used and strength of evidence was graded. neurological outcomes and side effects were assessed. of articles identified, studies met the selection criteria and analyzed. the level of evidence varied and was generally low. this systematic review helped determine the current state of evidence for the efficacy and safety of milrinone in the management of delayed cerebral ischemia in the context of nt-sah. the available evidence is promising but of generally low quality suggesting the need for a randomized controlled trial. blood lactate variability: a strong independent predictor of neurological outcomes in patients with aneurysmal subarachnoid hemorrhage blood lactate levels during intensive care unit (icu) management of patients with aneurysmal subarachnoid hemorrhage (sah) can be used as an indicator of not only volume status but also aerobic glycolysis caused by excessive catecholamine levels and impaired lactate clearance. to determine whether blood lactate variability (lv) can predict neurological outcomes in patients with sah, we assessed the standard deviation (sd) of blood lactate level of each patient during icu stay. we retrospectively reviewed all patients at the age of years or older who were consecutively hospitalized in kagawa university hospital with sah and at least five arterial lactate measurements between january , and may , . patients were divided into two groups with a mean lactate to identify independent predictors of unfavorable neurological outcome. unfavorable neurological outcomes occurred in . % of a total of patients. in both groups, there were increases in unfavorable neurological outcomes with increasing sd of lactate (quartile , %; that sd of la correlated with unfavorable neurological outcomes (p < . ). multiple logistic regression analysis showed that sd of lactate (odds ratio, . ; % confidence interval, . - . , p < . ), age, and h&k grade were independent predictors. this study demonstrated that increased lv was an independent predictor of unfavorable neurological outcomes in patients with sah. the main causes of mortality and morbidity after aneurysmal subarachnoid hemorrhage (saha) are rebleeding and delayed cerebral ischemia secondary to cerebral vasospasm. the use of milrinone, an inotropic and vasodilator agent, is described in as one option to treat vasospasm in patients with refractory symptoms. our objective was to describe the experience of our neurocritical care service with the use of milrinone in accordance with the montreal protocol for patients with refractory vasospasm. a retrospective study based on data obtained from medical records of patients suffering from saha and refractory vasospasm treated with milrinone from february to february . from saha patients admitted to our hospital during the study period, were identified with refractory were female and % of patients were pre-hypertensive. a total of % of the patients had hunt-hess scores between - and % scored or in the modified fisher scale. vasosespam was identified after -- . days. in % of the patients hypertension was induced with norepinephrine as an initial treatment. the mean duration of the treatment - . days. two cases were treated with intra-arterial milrinone and angioplasty. the most common adverse event during the use of milrinone was hypotension ( %). death occurred in patients. favorable functional outcome at the discharge was observed in % of the cases. in conclusion, the use of milrinone seems to be a safe option in the treatment of delayed cerebral ischemia secondary to vasospasm, especially in services where the availability of endovascular treatment is not a routine. (sah). however, pathomechanism and etiology of this elevation leading to poor outcomes remains uncertain. this study investigated the effect of troponin elevation on multi-organ dysfunction and outcomes in patients with sah. admitted to the neuroscience intensive care unit from july to january . among patients, patients were eligible for inclusion with investigation of serum troponin level at admission. troponin elevation (> elevation were older ( . ± . vs . ± . years; p < . ) and more often had a loss of consciousness ( . % vs . %; p < . ), symptomatic hydrocephalus ( . % vs . %; p = . ), and a higher hunt-hess score ( . ± . vs . ± . ; p < . ) and modified fisher score ( . ± . vs . ± . ; p < . ) at ictal period. during hospitalization, patients with troponin elevation more often had a respiratory failure ( . % vs . dysfunction ( . % vs . %; p = . ) and more often treated with vasopressure ( . % vs . %; p = . ) and longer duration of mechanical ventilation ( . ± . vs . ± . day; p = . ) than those without troponin elevation. troponin elevation in the acute stage of sah is associated with multi-organ dysfunction. thus troponin to mitigate early brain damage in subarachnoid hemorrhage (sah), we have been treating world federation of neurological surgeons grade (wfns) grade patients with therapeutic hypothermia (th) for days immediately after onset. management after rewarming was problematic since fever in sah is associated with vasospasm and poor outcome. we studied the feasibility and safety of endovascular cooling to maintain prophylactic normothermia following initial th in patients with severe sah. th (core body temperature . °c) was initiated, using surface cooling, immediately after the diagnosis of wfns grade sah was made. the ruptured aneurysm was surgically clipped as soon as feasible. around postoperative day , after rewarming to °c, an endovascular catheter with cooling balloons jugular vein and connected to xp® temperature management system (asahi kasei zoll medical corp.) for days. prospectively collected data were analyzed. . days. nine patients developed shivering with increased temperature and were given acetaminophen and dexmedetomidine. there was no evidence of vasospasm or additional cerebral infarction during endovascular cooling, and no catheter-related sepsis or thromboembolic event. after removal of the cooling catheter, vasospasm-related cerebral infarction and fatal bacterial meningitis related to spinal drainage occurred. three-month outcomes were good recovery (n= ), moderate disability (n= ), severe disability (n= ); vegetative state (n= ), and death (n= ). elimination of fever burden in the first days after onset was safe and feasible with combined surface and endovascular cooling in patients with wfns grade sah. disease processes. this study examines: ) the relationship between admission lactate and the clinical and radiographic severity of asah, and ) whether levels predict outcomes including vasospasm, delayed cerebral ischemia (dci), and inpatient mortality. this is a retrospective analysis of consecutive asah patients with lactate drawn on admission.compared to those with normal levels. differences between groups were compared using chi-square tests for categorical variables, and independent t-tests for continuous variables. spearman correlations were calculated between lactate levels and mean values for continuous variables. elevations in lactate were associated with admission gcs, hunt & hess (hh) grade, fisher score, serum white blood cell count (wbc), troponin i (tn), glucose, and ventilator-free days (vfd). positive correlation was found between lactate and hh, fisher score, wbc, tn, and glucose. an inverse correlation existed between lactate and gcs, and vfd. compared to survivors, non-survivors had significantly higher lactate levels. all results were considered significant with a p-value < . . no association between lactate and the development of vasospasm or dci was found. higher admission serum lactate is positively correlated with hh grade, fisher score, serum wbc, tn and glucose, but negatively correlated with admission gcs and vfd. presence of an elevated lactate was also predictive of inpatient mortality. this is the first report of correlation between early lactate and asah severity, and conflicts with prior results suggesting an association between lactic acid and the development of dci. further studies are needed to determine whether lactate elevations relate to hypovolemia, acute inflammatory response, elevated sympathetic outflow, or other cause. with malignant cerebral infarction with high osmotic pressure therapy. some patients need decompressive hemicraniectomy or expire due to cerebral herniation after ttm. hence this study was performed to determine associated factors in case of failure of ttm in patients with malignant cerebral infarction. from january to december , a study was performed in patients with malignant cerebral infarction occurred within hours at neurological intensive care unit. all patients were diagnosed hyperosmotic fluid therapy and ttm. we defined failure of ttm to cases treated by decompressive hemicraniectomy or death due to brain herniation. a total of patients, ttm were failed in patients. failures of ttm were common in patients without recanalization after thro ( fever occurs in - % of critically ill neurological patients, and small temperature elevations are correlated to increased morbidity. it is therefore crucial to acutely control the temperature of such patients. systems currently available are resource intensive and not always readily available in units, resulting in delays in treatment. emcools pads and are composed of multiple cooling units filled with graphite and water, with an adhesive underside that allows for efficient heat transfer. pads are stored at - c, and are available for immediate use. the retrospective analysis of the emcool device included all subjects that had the device applied in the neuroscience intensive care unit (nsicu), with consistent temperature data recorded. preliminary subarachnoid hemorrhage ( %), intracerebral hemorrhage ( %), subdural hemorrhage ( %), and pituitary tumor ( %). all subjects were febrile ( treatment period. the bedside shivering assessment scale was recorded at each application. c, t avg = . c) drop in temperature at mins c) achieved at mins. unconscious patients displayed a much higher rate of cooling at t as c). of the total subjects, % had shivering events upon application (bsas ), device. preliminary results show the emcools pads are an effective and safe method to control temperature elevations in neurologically critically ill patients. all even numbered posters will present on friday all odd numbered posters will present on saturday all poster sessions are in prince george exhibit hall a from : pm superior sagittal sinus thrombosis (ssst) accounts for only . - % of all strokes, with a traumatic etiology representing an uncommon occurrence. current guidelines advocate treating ssst with anticoagulation regardless of etiology, though efficacy is controversial and not yet studied in the traumatic brain injury (tbi) patient population. we recognize the importance of alternate treatment modalities of post-traumatic ssst, particularly surgical alternatives, and the dilemmas faced with anticoagulation therapy in the trauma population. we report a case of a -year-old male admitted with ssst who suffered severe tbi secondary to a pedestrian versus automobile collision. imaging demonstrated bifrontal and right temporal lobe hemorrhagic contusions, scattered subarachnoid hemorrhage, diffuse cerebral edema, multiple nondepressed skull fractures, and ssst. on post trauma day two, the patient clinically deteriorated; an external ventricular device (evd) was placed, and therapeutic heparin drip was started, despite the presence of intracranial hemorrhage and risk of evd-related hemorrhage. the patient developed refractory elevated intracranial pressure (icp) mandating initiation of pentobarbital to achieve burst suppression on continuous electroencephalography (ceeg) and serial administration of . % hypertonic bolus and mannitol for two weeks. hemicraniectomy and endovascular treatment were entertained though not pursued due to anticipated complications associated with concomitant anticoagulation therapy. anticoagulation was briefly interrupted for evd removal on post trauma day . he was extubated on post trauma day and transitioned to warfarin. repeat imaging showed complete recanalization of the superior sagittal sinus. the patient was discharged to inpatient rehabilitation after a -day hospital course. management of ssst secondary to tbi remains controversial as these patients present with multiple confounding factors, further complicated by the lack of treatment guidelines. further studies are needed to determine which independent or combined medical and surgical treatment modalities will decrease morbidity and mortality in this patient population. takotsubo cardiomyopathy (tc) is known to occur in patients with subarachnoid haemorrhage (sah) but is rarely reported in patients with traumatic brain injury (tbi). here we present a tbi patient with complicated clinical course developing severe tc and compared to previously published reports. case report and literature review. a years-old-woman was admitted to our tertiary care hospital because of tbi with admission glasgow coma scale score of . computed tomography (ct) scanning of the brain revealed an acute subdural hematoma and traumatic sah over left hemisphere and a small left frontal hemorrhagic contusion. six hours later she deteriorated and head-ct showed significant progression of right frontal hemorrhage with intraventricular expansion and a midline shift. hematoma evacuation was immediately performed. postoperatively the patient developed cardiogenic shock necessitating an increasing dose of noradrenaline, neosynephrine and dobutamine to achieve a cerebral perfusion pressure of > mmhg. echocardiography demonstrated severe left ventricular myocardial dysfunction suggestive for tc, supported by raised troponin-t and nt-probnp levels and abnormalities in ecg. continuous infusion of levosimendan was added and maintained for hours which led to stabilization allowing noradrenalin to be decreased the following days. repeated echocardiography days later showed normalized cardiac function. the patient's condition gradually improved and was extubated after days fully awake with mild left facial-brachial weakness. here we present a complicated case of tc with tbi developing cardiogenic shock within hours of admission. we will compare the patient's tc characteristics and clinical course with published cases (n = ) of tc with tbi. further studies of tc in patients with tbi and the utility of levosimendan is warranted. management of post-operative central diabetes insipidus (di) is focused on replacing urine output with free water. this may not always be sufficient, and desmopressin (ddavp) is needed. the use of ddavp, however, is known to cause profound changes in sodium particularly if the triphasic response postpituitary surgery is occurring. herein, we report a case using a dilute vasopressin bolus protocol in managing hypovolemia in acute, post-operative, central di. case report comparing two protocols for di management. statistical analysis was performed on serum sodium, urine specific gravity, and urine output using student t-test. p< . was considered significant. anti-programmed cell death (pd- ) antibodies are an effective treatment option for nsclc and other cancer entities. anti pd- antibodies including nivolumab can induce immune-related adverse events (iraes) in a number of organ systems. neurological iraes can be life-threatening and necessitate appropriate investigation and management by a neurologist. myasthenic syndromes have rarely been described. here we present a case of a man who developed a lambert eaton myasthenic syndrome thought to be a nivolumab-related immune adverse event. a -year-old man on nivolumab for metastatic nsclc developed asymmetrical ptosis followed by facial diplegia, dysarthria and dysphagia and fatigable limb weakness. he had clinical features of lambert eaton myasthenic syndrome with striking truncal, shoulder and pelvic girdle fatigable weakness that demonstrated a temporary increase in strength during the first few contractions. he developed neuromuscular respiratory failure requiring noninvasive positive pressure ventilation. his muscle reflexes were initially absent and after repeated attempts could be elicited. his mri brain was normal, csf was within normal limits and his serum and csf antibodies against ach receptors, musk and voltage gated calcium channels were negative. he weakened after an initial mg/kg dose of prednisone. plasma exchange resulted in a significant improvement of his weakness and the ability to wean the patient off noninvasive positive pressure ventilation. it is important to recognize that neurologic immune-related adverse events associated with nivolumab can cause lambert eaton myasthenic syndrome. early recognition and aggressive treatment with plasma exchange can be life-saving. neuroendocrine tumor (net) of middle ear is extremely rare. many names have been ascribed to these seemingly benign neuroendocrine lesions including middle ear adenoma (mea), adenomatous tumor and carcinoid tumor (ct). 'neuroendocrine adenoma' has also been used to better describe the histologic nature of these tumors. here we present the first case of carcinoid tumor of middle ear (ctme) complicated by dural sinus thrombosis and bony metastasis. a year old man presented with right sided facial palsy for hours and progressive hearing loss for months. physical examination revealed perforated right tympanic membrane with visible purulent material. ct scan of the head showed a small right cerebellar infarct. the mri demonstrated right cerebellar hemorrhagic venous infarct and a heterogeneous middle ear mass extending into the internal auditory canal. mrv revealed thrombus in the right sigmoid and transverse sinus.cervical spine mri revealed diffuse osseous metastases .the histology and immunohistochemistry (ihc) after surgical resection was consistent with ctme. proliferation rate of> % was seen by ki staining. he suffered massive intracranial bleed on heparin therapy and passed away. the nets of head neck region are divided in categories based on histology and ihc. ) well differentiated ct, / hpfs and ki- > %. although regional metastasis is not uncommon, only cases of distant metastasis have been reported in the past. our patient was diagnosed to have atypical carcinoid but the ki- was > % which is consistent with small cell cancer. the new classification system that takes the ihc and presence of metastasis into consideration to classify these tumors is much more clinically relevant. more research is necessary to find out the biological markers for better prognostication of this rare cancer. sung m. cho.neurological institute, cleveland clinic, cleveland, oh, usa. acute transverse myelitis is an acquired inflammatory spinal cord disorder, which can be due to infection, autoimmune disorders, or malignancy, however, the cause is often unknown despite an extensive workup. we describe a rare case of acute transverse myelitis caused by coxsackie b /b virus. a -year-old male with no past medical history presented with a viral prodrome of flu-like symptoms followed by severe headache, neck stiffness, photophobia, encephalopathy and paraplegia. mri of the brain with contrast was unremarkable, but mri of the spine showed an extensive longitudinal, nonenhancing t cord signal change from c -t without hemorrhagic components. lumbar puncture revealed rbc, wbc, protein, and glucose ( mg/dl serum glucose). extensive serum and csf work-up was negative for hiv, wnv, ebv, cmv, lyme, vzv, hsv, nmo antibody, ace, paraneoplastic panel, cytology, cryptococcus, and csf bacterial and fungal cultures. ct chest and blind transbronchial needle lymph node biopsy were negative for sarcoidosis. serum coxsackie b ( : ) and b (> : ) antibody titers were significantly elevated. the patient was treated with intravenous methylprednisolone mg for days along with plasmapheresis for sessions. the patient had improvement in lower extremity strength during his hospital stay and was discharged to a rehab facility on a steroid taper. at one-month follow up, the patient had complete recovery of lower extremity strength as well as bowel and bladder function and was ambulatory. at -month follow-up, mri and csf studies were markedly improved. transverse myelitis due to coxsackie has been reported in serotypes b , b , a , a , however only three cases of b or b related transverse myelitis have been reported and this is the first case, to our knowledge, with both b and b related transverse myelitis. external ventricular drains (evds) are necessary for select patients admitted to the neurointensive care unit (nicu). evds are critical to the management of diseases such as subarachnoid hemorrhage, traumatic brain injury, and acute hydrocephalus. we report a case of a woman with poor-grade aneurysmal subarachnoid hemorrhage who experienced inadvertent intraventricular non-iodinated contrast injection during vasospasm evaluation with ct angiography. we provide a review and analyses of adverse evd related injections reported in the literature and summarize management recommendations. a pubmed search was performed for unintended evd injections from to . unique cases were selected and classified by the type of inadvertent injection and location of the event. acute management was categorized by the use of evd manipulation, lumbar drain placement, and supportive medical therapies. cases involving ventriculoperitoneal shunts, ommaya reservoirs, or other intrathecal device systems were excluded. a total of seven unique cases were identified, four involving contrast administration and three involving medication administration. the sentinel event in five cases occurred outside of the nicu. acute management with evd manipulation was employed in six cases; three of these cases also used lumbar drains. three cases necessitated intubation. our patient received prophylactic dexamethasone and levetiracetam, underwent immediate evd manipulation, and placement of a lumbar drain. continuous eeg monitoring and daily head cts were performed until intraventricular clearance was noted at hours. acute management of inadvertent intraventricular injections entails immediate evd manipulation and possible lumbar drain placement to facilitate rapid csf clearance of injected substances. intubation may be required immediately depending on exposure. inadequate distinction between compatible drain tubing and relative inexperience of providers managing the evds likely contributed to the errors in these cases. the increased incidence of these events outside of the nicu suggests additional safety measures may be warranted when patients with evds travel off-unit. an unusual presentation of isolated brain abscess in non-traumatic convexal subarachnoid hemorrhage: a case report to present a unique case of isolated brain abscess presenting as non-traumatic convexal subarachnoid hemorrhage (csah) six days before radiologic signs could be seen. to our knowledge only one other case of csah due to brain abscess has been reported thus far. a -year old man with no past medical history or prior trauma presented with acute onset of transient left hemianesthesia lasting ten minutes. computed tomography (ct) of the head revealed csah. we were presented with a diagnostic dilemma when magnetic resonance imaging (mri) of the brain, magnetic resonance angiography (mra) of the head and neck, magnetic resonance venography (mrv) and conventional angiography failed to show the cause of csah. the patient was discharged in a stable condition, but returned six days later with worsening symptoms, including left hemiparesis. repeat mri with contrast revealed a cerebral abscess in the same location as the prior csah. csah without clear evidence of trauma due to abscess is a rare occurrence. we suggest in cases of csah where imaging techniques present no abnormalities, follow-up imaging within seven days should be considered. jonathan marehbian, diane d. chan, david d. greer.yale new haven hospital, department of neurology, new haven, ct, usa. spinally-mediated reflex movements can be present in brain dead patients. however, abnormal movements have long been a challenge in the clinical determination of brain death. in this report, we describe delayed plantar extension with noxious nail bed stimulation that has not been previously described in brain death. a -year-old male suffered severe anoxic brain injury following respiratory failure due to heroin overdose. his clinical exam and apnea testing were consistent with brain death with the exception of a reproducible delayed plantar extension with noxious nail bed stimulation. ancillary testing with technetium m nuclear scan (spect) demonstrated no cerebral blood flow, confirming that the finding was spinally-mediated. novel movements are important to document in order to aid in the timely determination of brain death, and to avoid unnecessary and potentially confounding ancillary testing. the mechanism underlying delayed plantar extension is likely spinally mediated. vascular perforation during a neuroendovascular procedure is an unexpected and feared complication, which can lead to fatal outcomes. a prompt recognition and initiation of treatment are paramount. endovascular strategies to address this complication have been widely described. however, the goals of therapy in the neurointensive care unit (neuroicu) remain unclear. we report two cases in which endovascular strategies associated with aggressive intensive care resulted in a good clinical outcome at discharge. case report. vessel perforation occurred in patients during neuroendovascular interventions: a left-carotid stenting and an ica-aneurysm embolization with balloon-assisted coiling. once contrast extravasation was demonstrated, heparin was immediately reversed and endovascular strategies were performed to minimize the complications. sah was present in the initial head ct in both cases. in the neuroicu, targets of therapy were a) systolic blood pressure (sbp) < mmhg, b) mechanical ventilatory support, and c) seizures and vasospasm prophylaxis with phenytoin and nimodipine respectively. one of the patients developed mild hydrocephalus and left upper extremity weakness, with mri showing tiny right hemispheric strokes, while the other one, did not show any focal deficit. both patients were discharged home few days later with mrs of and , respectively. iatrogenic vascular perforation is an uncommon complication that occurs secondary to inadequate manipulation of the catheter, guide wire, devices, or forceful contrast injection. clinical care strategies aim to prevent fatal outcomes. we recommend reversing heparin; provide an adequate ventilatory support, maintain a strict control over the sbp, and seizure and vasospasm prophylaxis. but, larger studies are required to determine the standard of care since endovascular therapy is rapidly becoming first-line of treatment for neurovascular conditions. cerebral hyperperfusion syndrome (chs) symptoms range from severe unilateral headache to seizures, focal symptoms and intracerebral hemorrhage, usually occurring follow carotid endarterectomy (cea)/ carotid stenting (cas). we describe a case of a patient who developed chs after spontaneous recanalization of carotid intra-stent thrombosis. case report. years old african american male who had recently placed left cervical stent was transferred to baptist medical center with new evidence of intra-stent thrombosis. he was started on heparin drip and sbp was augmented with levophed for sbp> . two days later, the patient developed excruciating headache followed hours later by acute onset of right upper extremity and face twitching associated with severe hypertension. the bp was controlled, protamine was given to reverse heparin and keppra was loaded to treating seizures. cta at this time showed recanalization of carotid in-stent stenosis and ctp confirmed hyperperfusion of frontal and parietal lobe with neither evidence of new ischemic area nor bleeding. fortunately, inspite a delay in diagnosis by hours, patient did not suffer intracranial hemorrhage. most patients who develop chs will have complete recovery if it is discovered and treated early.aggressive prophylactic blood pressure control is the main treatment. for those who are diagnosed late and those progressing to ich, the prognosis can be devastating with mortality rates up to %. considering the importance of blood pressure control in the cerebral hemodynamic, studies have been done, trying to find a better tool to predict the best bp target in order to prevent chs. near infrared spectroscopy (nirs) is a non-invasive and reliable technique that monitor the cerebral hemodynamic. had nirs been deployed during anticoagulation, the diagnosis of cerebral hyperperfusion syndrome would have been made at the onset of headaches and would have avoided the development of seizures and potentially a life threatening hemorrhage. the triphasic response: water imbalance after neurosurgery : a case reportbibhukalyani das, indranil i. ghosh.institute of neurosciences kolkata, kolkata, india. water balance disorders after neurosurgery are well recognized, but detailed reports of the triphasic response are scarce. we describe a -year-old woman, who developed the triphasic response with hyper and hyponatraemia after resection of craniopharyngeoma. a -year-old female (no previous medical history, no medication, normal electrolytes and endocrine parameters) with mri showing s/o craniopharyngeoma underwent neurosurgery using a subfrontal approach to resect the craniopharyngeoma while leaving the pituitary stalk intact (according to the surgical notes). within a few hours of an uneventful postoperative recovery she started having polyuria and hypoosmolar urine with hypernatremia. being normoglycaemic and not on any diuretics a diagnosis of central diabetes insipidus was made treated with desmopressin nasal spray and drinking water ad libitum. improvement occurred over the next postoperative day when desmopressin was discontinued. on the third day she developed with hypoosmolar hyponatremia along with seizure treated with % saline and fuid restriction. two days later polyuria returned and was ultimately discharged with desmopressin tablets and advice to take fluids ad libitum. na this case illustrates the dramatic and sudden changes in water balance that may occur after neurosurgery. the pathophysiology of the triphasic response appears to be early hypothalamic dysfunction, subsequent release of vasopressin from the degenerating pituitary and, finally,depletion of vasopressin stores. it has been difficult to identify patients at risk, but predisposing factors appear to relate both to the disease (macroadenoma, microadenoma, craniopharyngioma) and to the surgery (degree of manipulation). successful prevention probably involves a psychological switch by not waiting until frank dysnatraemia has developed, but to act as soon as urine output and tonicity change. this requires an index of suspicion for treating and consulting physicians and specific instructions to nursing staff, especially in nonintensive care settings. refractory status epilepticus (rse) has high mortality and is difficult to treat. when traditional therapies fail ketamine may be considered. ketamine is associated with limited reports of adverse cardiac events during anesthesia, but not during treatment for rse. we evaluated occurrences of cardiac arrhythmias associated with ketamine. retrospective chart review of neurocritical care patients in a tertiary academic medical center who received ketamine infusion for rse between october and april . ten patients were admitted to a neurologic intensive care unit and received ketamine infusion for rse. etiology of rse included autoimmune/infectious process ( ), ischemic stroke ( ) and subarachnoid hemorrhage ( ). of the ten patients who received ketamine, three had documented cardiac events without prior cardiac history. one patient remained clinically stable and did not require intervention. another patient required escalating doses of ketamine infusion (maximum mg/kg/hr) for rse secondary to presumed leptomeningeal disease, had an asystolic event and expired. the third patient was on low dose ketamine ( . mg/kg/hr) for rse secondary to subarachnoid hemorrhage, and developed multiple arrhythmias including recurrent episodes of asystole. once ketamine was discontinued the patient stabilized. arrhythmias are not uncommon in critically ill patients, but this is the first report of cardiac arrest associated with the use of ketamine for rse. although sympathomimetic properties of ketamine may provide vasopressor sparing effects, which reduce the need for vasopressors to counteract the hypotension commonly seen with other anesthetics used in rse, it may put patients at risk for cardiac arrhythmias. in addition, ketamine has direct negative ionotropic effects and may raise pulmonary artery pressures. caution should be employed when ketamine is used in rse in patients with other independent risk factors for cardiac events. a year-old veterinary technician with headache and fever for days presented with altered mental status and myoclonic jerking. initial lp showed white cells and elevated protein ( mg/dl). recurrent clinical seizures occurred for days prior to transfer to our institution. his exam demonstrated diffuse hyperreflexia and coma; eeg demonstrated up to . hz frontally-predominant rhythmic delta but no unequivocal seizures. extensive workup revealed no evidence of infectious, toxic, or immune-mediated encephalitis. mri demonstrated bithalamic injury and a region of questionable periventricular nodular heterotopia in the right parietal region. subsequently, he developed recurrent clinical and unequivocal electrographic seizures from the right parieto-occipital region. five periods each lasting > hours of anesthesia-induced eeg burst suppression failed to stop seizures, qualifying him as super-refractory status epilepticus. after weeks of failure to wean from anesthetia, invasive monitoring for seizure localization was carried out using strips and depth electrodes. multiple seizures were recorded, localizing to the medial occipital lobe, which was subsequently resected along with the region of pathologyconfirmed heterotopia. seizures gradually improved, requiring anti-seizure drugs and a ketogenic diet. he regained consciousness with preserved higher cognitive functions (language, memory) and personality months later as his antiseizure drugs were successfully decreased. his motor recovery was limited by critical illness myoneuropathy. new-onset focal super-refractory status epilepticus may respond to surgical resection in extreme cases. close collaboration with a multidisciplinary team of epileptologists and neurosurgeons can lead to resolution of seizures and eventually recovery. in patients with leptomeningeal metastases (lm) and elevated intracranial pressure (icp), transient neurologic events secondary to plateau waves -temporary elevations in icp -may occur. there is a paucity of clinical reports correlating video-eeg with definite or presumed plateau waves in patients with lm. case report and literature review. pubmed was queried for 'leptomeningeal metastases and eeg', 'leptomeningeal metastases and plateau waves' and ' leptomeningeal metastases and intracranial pressure'. a -year-old woman was transferred to our hospital for further care of a pituitary microadenoma noted on outside imaging. she had a history of hodgkin lymphoma treated with radio-chemotherapy. during her admission, she developed episodes of confusion and video-eeg monitoring was initiated. while there were no electrographic seizures, several events, between to minutes in duration, of delayed or absent verbal responses, eye rolling, staring and alternating gaze preferences to both sides were noted. all these coincided with abrupt onset of marked background slowing, evident through generalized - hz delta, mixed with some theta frequencies. review of outside and repeat imaging with mri of the brain with contrast revealed brain and leptomeningeal metastases. cerebrospinal fluid examination showed raised opening pressures and malignant cells, leading to a subsequent diagnosis of primary signet ring cell cancer. we found one additional report describing video-eeg correlates of presumed plateau waves in patients with lm. our clinical description of transient neurologic events in this patient adds to the current literature of paroxysmal manifestations owing to raised icp in patients with lm. awareness of this clinical phenomenon may serve as a surrogate of raised icp before clinical signs of the same develop in patients with lm. it may also help delineate the cause of raised icp due to cns metastases in a patient with a corresponding history of cancer. background: terson's syndrome is the development of intraocular hemorrhage (ioh) in association with subarachnoid hemorrhage (sah). we report a case of terson's syndrome and review the literature. case report: a yr woman presented with severe neck pain and somnolence. ct imaging showed fisher grade sah with aneurysms in the right internal carotid and posterior communicating arteries. she developed low pressure hydrocephalus treated with ventriculostomy. on hospital day she developed vision loss. ophthalmologic examination demonstrated bilateral vitreous hemorrhages with near complete fundoscopic resolution by day . over the next months she underwent pars plana vitrectomy (ppv) of the left eye two times. current vision od / , os / . discussion: the incidence of terson's syndrome among patients with sah is documented to be between - %. in prospective studies, ioh was found in up to % of patients with sah compared to only % in retrospective studies suggesting under-reporting. this is likely because ioh is found more often in higher severity bleeds where patients cannot self-report visual loss due to decreased loc. patients with ioh are more likely to have worse neurologic outcomes and die more often than those with lower grade bleeds without the development of ioh. along with fundoscopy, hand held ultrasound may be used for bedside diagnosis. erm development is the most common intraocular complication from terson's syndrome and occurs in - % of patients. complete or near complete return of visual acuity is less likely without surgical intervention. visual acuity has been show to recover better and faster if ppv is performed within days. there is no literature on incidence of visual loss after acute phase of sah. conclusions: routine evaluation with imaging and fundoscopy may help in detecting ioh sooner in the clinical course and has the potential to decrease long-term morbidity. iatrogenic underfeeding in critically ill patients is often unrecognized and underestimated. an international prospective study of critical care units showed patients received only . % and . % of prescribed calorie and protein needs. the inability to initiate enteral nutrition within - hours of icu admission or frequent interruptions of the enteral regimen lead to insufficient nutrient delivery and a compounding energy deficit. an increase in infectious complications is associated with negative energy balance in patients with subarachnoid hemorrhage (sah). a quality initiative project was developed at mayo clinic florida to measure time to reach enteral nutrition target and common interruptions of enteral nutrition. the target subjects were mechanically ventilated patients in medical and transplant icu; however the quality measure has recently extended to the neurocritical care unit. data collected included clinical diagnosis, sofa and apache ii score, subjective global assessment (sga) score, nutric score, enteral tube type and regimen, and reason and duration for interruption of nutrition. a year old subject with sah and posterior fossa avm resection was deemed low nutrition risk with sga score a and nutric score . enteral nutrition was initiated via nasoenteric tube within hours of intubation. target enteral goal rate was reached within hours. the patient received % of calorie/protein needs of the days. the most common enteral interruption was for procedure; primarily head ct, for longest duration of minutes. the interruption of enteral nutrition in neurocritical care patients is likely unavoidable due to procedures. these disruptions, however, need not result in iatrogenic underfeeding. neurocritical care units may utilize volume-based enteral protocols to allow nurses to compensate for lost nutrition with increased enteral rate. neurogenic pulmonary edema is challenging to manage in the context of aneurysmal subarachnoid hemorrhage (asah) due competing priorities between organ systems. we present a case of refractory neurogenic pulmonary edema due to asah necessitating extracorporeal membrane oxygenation (ecmo). case report. a year-old female with a history of hypertension and diabetes presented neurologically intact with hh f asah due to a left posterior communicating artery aneurysm. she underwent coil embolization on sah day and remained intubated after the procedure due to development of flash pulmonary edema. transthoracic echo demonstrated normal left ventricular function. on sah day after unplanned extubation, she was temporized on noninvasive ventilation until reintubation the following day. she progressed to severe ards requiring high-dose sedatives and paralytics which obscured her neurologic exam. on sah day , a day course of intrathecal nicardipine was initiated for elevated left mca transcranial doppler velocities. on sah day , her respiratory status further declined and veno-venous ecmo was initiated as rescue therapy after head ct did not demonstrate new hemorrhage or infarct. throughout the day ecmo course, a low-dose heparin infusion was utilized along with vasopressors to optimize cerebral perfusion pressure (cpp). she was decannulated on sah day . surveillance ct head demonstrated left-sided ischemic infarcts in multiple vascular territories. on sah day , she was discharged to an outside facility for ventilator weaning. upon discharge, she was alert and followed commands with her left arm, however she was aphasic without movement of her other extremities. veno-venous ecmo was performed in an asah patient after coil embolization. although the patient did not develop intracranial hemorrhage, her course was complicated by severe vasospasm and delayed cerebral ischemia (dci). while ecmo is a rescue therapy for severe hypoxemia, its effect on cpp remains uncertain and may potentiate dci. key: cord- - ihuqvei authors: thomas, william b. title: nonneoplastic disorders of the brain date: - - journal: clin tech small anim pract doi: . /s - ( ) - sha: doc_id: cord_uid: ihuqvei computed tomography (ct) and magnetic resonance imaging (mri) are helpful in the diagnosis of many nonneoplastic brain disorders in the dog and cat. the ability of ct and mri to depict normal and abnormal anatomy facilitates the identification of developmental anomalies, including hydrocephalus, chiari malformations, arachnoid cysts, and cerebellar hypoplasia. these imaging modalities also allow the detection of hemorrhage and infarction and are therefore useful in the evaluation of spontaneous cerebrovascular disorders and head trauma. finally, many inflammatory diseases, such as encephalitis, brain abscess, and parasite migration, cause abnormalities detectable by ct and mri. although more research on the imaging features of specific nonneoplastic brain disorders is needed, current information indicates that ct and mri are useful in the management of these disorders. imaging strategies for ct and mri are similar to those described for intracranial neoplasia. (refer to the article entitled "intracranial neoplasia" by kraft and gavin in the may issue.) throughout this chapter, the mri features of the various disorders are those depicted with spin echo imaging. readers should refer to the article entitled "advanced imaging concepts: a pictorial glossary of ct and mri technology" by tidwell and jones in the may issue for a description of other pertinent mri techniques such as gradient echo and inversion recovery pulse sequences, magnetic resonance angiography, and diffusion/perfusion imaging. disorders of brain development ecent advances in imaging techniques have greatly improved the ability to detect pathologic processes in the brain, localize lesions precisely, and predict the type of disease more accurately than ever before. although most reports of computed tomography (ct) and magnetic resonance imaging (mri) of brain disease in veterinary medicine have focused on the diagnosis of brain tumors, these imaging methods are also valuable in the evaluation of various nonneoplastic brain diseases. the purpose of this article is to provide an overview for imaging some of the more frequently encountered nonneoplastic diseases of the brain. clinical features of each disease are included because imaging can supplement but never replace a careful history and thorough physical and neurological examination. typical pathological changes are also mentioned, because ct and mri reflect gross and microscopic pathology and an understanding of the expected pathological changes can be very helpful in predicting imaging findings. ideally, a review article such as this would be based on systematic research and clinical data. unfortunately, the current literature on imaging of nonneoplastic brain disease in veterinary patients is fairly sparse. therefore, the information presented in this article is based on the limited data regarding veterinary patients supplemented by the much more complete information on comparable diseases in human patients, as well as my own experience. as more information becomes available, the conclusions in this article may have to be modified. hydrocephalus is a pathological condition in which there is accumulation of cerebrospinal fluid (csf) within the cranium. this usually occurs within the ventricular system (internal hydrocephalus) but can involve the subarachnoid space (external hydrocephalus)) hydrocephalus is not a specific disease, but rather a multifactorial disorder with a variety of pathophysiological mechanisms. csf is produced at a constant rate by the choroid plexuses of the lateral, third, and fourth ventricles; the ependymal lining of the ventricular system; and blood vessels in the subarachnoid space. the csf circulates through the ventricular system into the subarachnoid space, where it is absorbed by arachnoid villi. hydrocephalus can be caused by a blockage of the flow of cse called obstructive hydrocephalus, or secondary to decreased volume of brain parenchyma, termed hydrocephalus ex vacuo. (increased formation of csf is virtually never a cause of hydrocephalus.) a number of conditions, such as infarction and necrosis, can result in decreased volume of brain parenchyma and hydrocephalus ex vacuo. obstruction to csf flow can occur anywhere along the pathway from its formation to the site of absorption in the cranial and spinal arachnoid villi. obstruction within the ventricular system or at its outflow through the lateral apertures is called noncommunicating hydrocephalus because the ventricular system does not communicate with the subarachnoid space. obstruction within the subarachnoid space or at the level of absorption in the arachnoid villi is called communicating hydrocephalus. ~ hydrocephalus can be classified further as congenital or acquired. congenital hydrocephalus is most common in toybreed dogs. the causes are diverse and include genetic factors, developmental anomalies, and intrauterine or perinatal infection or bleeding in the brain. congenital hydrocephalus may be associated with a wide range of other nervous system anomalies, including meningomyelocele, chiari malformation, dandy-walker syndrome, and cerebellar hypoplasia. clinical signs of congenital hydrocephalus include an enlarged, domeshaped head with persistent fontanelles and open cranial sutures. neurological deficits include abnormal behavior, disturbed consciousness, ataxia, circhng, blindness, seizures, and vestibular dysfunction. in mature dogs, diseases such as tumors and inflammatory diseases can cause acquired hydrocephalus. neurological deficits are similar to those m puppms, but if hydrocephalus develops after the cranial sutures have closed, malformation of the skull does not develop. , ct and mri allow accurate assessment of ventricular size, extent of cortical atrophy, and the presence of any focal lesions that may account for the hydrocephalus. imaging is also useful in monitoring patients after surgical placement of ventriculoperitoneal shunts used for treatment. changes in ventricular size can be monitored, and the presence of complications such as subdural hematoma or hygroma can be evaluated. ventricular size is usually assessed subjectively, noting the progressively greater proportion of the intracranial volume occupied by the lateral, third, and/or fourth ventricles , ( fig ) . several investigators have provided quantitative measurements. when measured at the level of or caudal to the lnterthalamlc adhesion, hudson et al state that lateral ventricles are considered enlarged ff lateral ventncular height exceeds . cm or the ratio between the height of the lateral ventricle and the width of the cerebral hemisphere (ventriclehemisphere ratio) exceeds . . spaulding and sharp consider the lateral ventricles enlarged if the ratio between lateral ventricular height and the dorsoventral height of the cerebral hemisphere exceeds . . however, there is a poor correlation between clinical signs and ventricular size, and symmetric or asymmetric enlargement of the lateral ventricles is relatively common in normal adult dogs and puppies. q° therefore, diagnosis of hydrocephalus must be based on clinical features, not just ventricular size. hydrocephalus ex vacuo can be distinguished from obstructive hydrocephalus based on enlarged cortical sulci and subarachnoid space secondary to atrophy of brain parenchyma (fig ) . in obstructive hydrocephalus, the site of obstruction may be identified by dilatation of csf spaces proximal to the obstruction, and normal or collapsed spaces distally. for example, obstruction at the level of the third venmcle would be expected to result in enlarged lateral ventricles but no enlargement of the mesencephalic aqueduct and fourth ventricle (fig ) . dilatation of all the ventricles and the subarachnmd space implies an obstruction at or near the arachnoid vilh. unfortunately, this simplisuc approach has limited accuracy. for example, % to % of human patients with communicating hydrocephalus have little or no &latation of the fourth ventricle. obstructing masses, such as tumors, granulomas, and cysts, may be identified, especially on postcontrast images (fig ) . mri is more sensitive than ct in showing small focal lesions, especially those in the caudal fossa) periventricular edema may be identified in some patients with hydrocephalus. experimentally, acute obstructive hydrocephalus in dogs causes edema starting at the dorsolateral angles of the lateral ventricles and spreading into the adjacent white matter, n on ct, this is evident as blurring or loss of the normally sharp ventricular margins. the edema is best appreciated on t -welghted mri as increased intensity compared with normal white matter. ~ periventrlcular edema is most frequently associated with acute hydrocephalus and increased intraventricular pressure, rather than chronic, relatively compensated hydrocephalus with normal intraventricular pressure. imaging techniques make it possible to readily identify ventriculomegaly but may give little clue as to its clinical significance. it is therefore necessary to interpret the finding of ventriculomegaly in context with clinical features. chiarl described four unrelated types of malformations of the brainstem and cerebellum in human patients. the most common is chiari i malformation, which consists of caudal displacement of a portion of the cerebellum through the foramen magnum into the cervical portion of the vertebral canal. the cause is an underdeveloped occipital bone that induces overcrowding of the caudal fossa, which is accommodated by caudal displacement of the cerebellum. many human patients with this malformation develop hydromyelia (a dilatation of the central canal of the spinal cord that is lined by ependyma) and/or syringomyelia (an accumulation of fluid within the spinal cord that is not lined by ependyma). the term syringohydromyefia is often used because it can be &fficult or impossible to tell whether the cavity is lined with ependyma except at necropsy. syringohydromyelia in chiarl i malformation is caused by obstruction of csf flow at the foramen magnum. the brain expands as it fills with blood during systole, inducing a pressure wave in the csf that is accommodated in normal subjects by rapid movement of csf from within the skull to the vertebral canal. with obstruction to rapid movement of csf through the foramen magnum, the caudal portion of the cerebellum moves down- ward with each systolic pulse, acting as a piston on the surface of the spinal cord. this relentless compression of the spinal cord propels csf into and within the syrinx. some pauents also have hydrocephalus attributed to obstruction of csf flow in the crowded caudal fossa. clinical signs of chiari i malformation in human beings can develop in childhood or adulthood and include head and neck pain, myelopathy, or encephalopathy. , a similar malformation has been reported m adult dogs with neck pain and tetraparesls. ~a diagnosis is best made on sagittal mri of the craniocervmal junction (fig ) . the caudal portion of the cerebellum is displaced into the vertebral canal to a variable degree , the cerebellomedullary cistern is small or absent and the caudal fossa may appear subjectively overcrowded. hydrocephalus and syringohydromyelia may be evident. - syringohydromyelia often involves the caudal cervical or cranial thoracic segments, so this entire region should be imaged. all patients with syrmgohydromyelia should have imaging of the craniocervical region to rule out a chiari i malformation or other obstruction of csf flow. chiarl ii malformation, also known as arnold-chiari or cleland-chari malformation, involves caudal displacement of the brainstem and cerebellum through an enlarged foramen magnum. the fourth ventricle is elongated and extends caudal to the foramen magnum, and the brainstem may be kinked. chiari iii malformation is displacement of the cerebellum through a cervical spina bifida resulting m a cervmal encephalocele. chiari ii and iii malformations are not well described in small animals. chiari iv malformation is severe cerebellar hypoplasia and is discussed separately. in human patients, the dandy-walker complex is a group of malformations consisting of an enlarged caudal fossa, hypoplasia of the cerebellar vermis, and cystic dilatation of the fourth ventricle that nearly fills the caudal fossa. the cerebellar hemispheres are usually hypoplastic as well. other anomalies are also common, including hydrocephalus, hypoplasia of the corpus callosum, and syringohydromyelia. dandy-walker malformation is caused by outflow obstruction of the fourth ventricle in the developing embryo. this causes dilatation of the fourth ventricle, which enlarges upward between the developing cerebellar hemispheres, preventing their fusion. when the cerebellar hemispheres do not fuse, the vermis does not form. analogous malformations have been described in the dog and cat. ~< - in contrast to human patients, most dogs and cats with this syndrome do not have obvious enlargement of the caudal fossa, ls- neurological deficits typically occur at a young age and primarily reflect cerebellar dysfunction, including ataxia, hypermetria, intention tremor, and vestibular dysfunction, ls- on ct and mri, dandy-walker malformation is characterized by an enlarged caudal fossa filled by an enormous fourth ventricle and a small cerebellum. , , °, the cerebellar vermis may be absent, producing a cleft in the middle of the cerebellum. hydrocephalus may also be evident. . a variety of in utero msults and heritable defects may cause failure of normal development of the cerebellum, resulting in a hypoplastic or absent cerebellum. the most common cause in cats is in utero or permatal infection with the feline panleukopenia virus. cerebellar hypoplasia has also been reported in dogs, in which a heritable basis has been suspected in some cases, but in utero infections cannot be excludedy , single or multiple animals within a litter may be affected. there is nonprogressive ataxia, hypermetria, and intention tremor, first apparent at about the time the animal begins to walk. ct or mri shows a small or absent cerebellum. the remainder of the caudal fossa is filled with cse other anomahes, such as hydrocephalus, may also be apparent. = arachnoid cysts (also called intra-arachnold cysts) are accumulations of fluid surrounded by a membrane resembhng the arachnmd mater. they carl develop in the subarachnold space anywhere along the neuraxis. congenital arachnoid cysts are developmental anomalies originating from a splitting or duplication of the arachnoid mater. the cyst wall is formed by several layers of arachnoid cells. acquired arachnoid cysts may result from postinflammatory loculauon of csf caused by trauma, infection, or hemorrhage. in human beings, congenital intracranial arachnoid cysts may be asymptomatic or cause neurological deficits as the cyst progressively enlarges and compresses adjacent neural structures or interferes with csf circulation. enlargement of arachnoid cysts occurs because of fired production by the cyst wall or an anatomical communication functioning as a oneway valve between the cyst and the subarachnoid space. ~ intracranial arachnoid cysts have been reported in the dog and cat. z , the most common locatmn is the subarachnoid space between the cerebellum and the tentorium cerebelli. clinical signs may occur in immature or mature animals and include smzures, paresis, abnormal behavior, and cranial nerve deficits. in some patients, the cyst is an incidental finding on imaging. on ct, the cyst has well-defined margins and contains fired that is isodense wath csf (fig ) . there is mal, or intraventricular. epidural, subdural, and subarachnoid hemorrhages are often associated with trauma and are discussed later. intraparenchymal hemorrhage can be primary or secondary and can extend into the ventricular system. the cause of primary intraparenchymal hemorrhage is incompletely understood. people with this disorder often have systemic hypertension and fibrinoid degeneration of arteries in the b r a i n y although intracranial hemorrhage caused by hypertension is poorly documented in dogs and cats, primary hypertension and hypertension secondary to other disorders, such as renal disease, hyperadrenocorticism, and hyperthyroidism, are well recognized. these animals may be predisposed to cerebrovascular disease and intracranial hemorrhage. secondary causes of intracranial hemorrhage include trauma, infarction, congenital vascular malformations, intracranial tumor, vasculitis, and coagulopathies. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] the clinical signs of intraparenchymal hemorrhage consist of a sudden onset of neurological deficits referable to a focal brain lesion. signs may progressively worsen as the hematoma expands, compressing adjacent neural structures and increasing intracranial pressure. - - computed tomography ct is exqmsitely sensitive to acute hemorrhage. because the attenuation of x-rays is primarily attributable to the globin portion of blood, there is a linear relationship between ct attenuation and hematocrit. ° the attenuation of whole blood with a hematocrit of % is approximately hounsfield units (hu). in comparison, normal gray matter has an attenuation of to hu, and normal white matter, to hu. ° acute hemorrhage in a patient with a normal hematocrit is therefore immediately evident as increased attenuation on ct ( fig ) . , hemorrhage in patients with severe anemia may be less obvious. an acute hematoma may he surrounded by a hypodense region corresponding to edema, and there is often an associated m a s s effect. ' the attenuation of extravasated blood increases for the first hours with clot formation and extrusion of low-density serum and subsequent increase in hemoglobin concentration. ° after that, the attenuation gradually decreases as the result of lysis and phagocytosls of erythrocytes, which starts at the periphery and progresses centrally. °~ the hematoma eventually becomes isodense at about month after onset. °- use of contrast agent is unnecessary in most acute hematomas and may obscure the inherent hyperdensity, confusing the diagnosis. however, use of contrast agent may be helpful if there is a small hemorrhage with mass effect out of proportion to the size of the hematoma. in this instance, the differential diagnosis includes bleeding into a tumor, and contrast may be necessary to visualize the tumor. ° in hematomas not associated with underlying neoplasia, enhancement first appears at the periphery of the hematoma at approximately to days because of neovascularization. . - a ring pattern of enhancement may persist for to weeks. ° although variations can occur, the mri features of most intracranial hematomas follow a predictable course over time. factors intrinsic to the lesion that affect images include the age of the hemorrhage, whether the bleeding is arterial or venous, the location of the bleeding, and the presence of any underlying lesions. operator-dependent factors that affect the images include the mare magnetic field strength, the exact pulse sequence parameters used, and the method of echo formation. hemorrhage can be thought of as an iron salvage pathway, in which iron from the extravasated erythrocytes is mobilized from hemoglobin and converted to short-term iron-containing proteins for transfer to the reticuloendothelial system, or to long-term storage proteins for local deposition. during this process, oxyhemoglobin is converted in a stepwise fashion to deoxyhemoglobin, methemoglobin, and finally ferritin and hemosiderin. these various forms of hemoglobin affect the appearance of hemorrhage in three ways: ( ) protein effects that are present with all forms of hemoglobin; ( ) paramagnetm relaxation caused by paramagnetic molecules, which is significant only with methemoglobin; and ( ) inhomogeneous susceptibility effects induced by paramagnetlc forms of hemoglobin (deoxyhemoglobin and methemoglobm) within erythrocytes. , protein effects. relaxation times are shortened in the presence of proteins in water solutions. this is caused by the changing magnetic fields of nearby nuclei as the molecules undergo brownian motion. protein effects are generally proportional to protein concentrations and result in shortening of t and t ; that is, increased intensity on tl-weighted images and decreased intensity on t -weighted images, compared with pure water. paramagnetic effects. biological substances containing unpaired electrons have magnetic properties dominated by the magnetic effects of these unpaired electrons. the magnetic fields of the unpaired electrons are normally oriented randomly such that there is no net magnetization. however, when an external magnetic field is applied, the unpaired electrons tend to align parallel to that field, resulting in enhancement (increased magmtude) of that applied field. substances that have no intrinsic magnetic field m the absence of an applied magnetic field, but align with and thus enhance that applied field, are termed paramagnetic. some forms of hemoglobin contain iron with paramagnetic properties, which greatly affects the mri appearance. if water molecules approach a paramagnetic center, there is an interaction between the nuclear magnetic dipoles of the water (protons) and the magnetic dipoles of the paramagnetic center (unpaired electrons). this proton-electron dipoledipole interaction shortens relaxation ume of the water protons. for proton relaxation enhancement to occur, however, the water proton must come within about . nm of the paramagnetic ions' unpaired electrons, because the magnitude of this interaction is inversely proportional to the sixth power of the distance between the dipoles. these paramagnetic effects are more prominent on tl-weighted images than on t -weighted images. they will therefore result in an increased signal on tl-weighted images, similar to the effects of gadolinium-based contrast agents. (paramagnetism of mri contrast medium is also discussed in the tidwell & jones article in the may issue.) inhomogeneous susceptibility effects. when paramagnetlsm is confined to a small region (such as within erythrocytes), there is an inhomogeneous distribution of paramagnetic susceptibility that creates microscopic field gradients. water molecules diffusing across the erythrocyte membrane experience a fluctuating magnetic field that results in dephasing and shortened t relaxation, a process called inhomogeneous susceptiblhty effect. in spin-echo sequences, inhomogeneous susceptibihty effects result in signal loss because of shortened t relaxation. this leads to decreased intensity on t -weighted images. hematoma evolution. these three relaxation mechanisms along with proton density contribute to image contrast during the various stages of hematoma formation (table ) . because numerous factors can effect the appearance of intracranial hemorrhage on mri, the following summary is necessarily oversimplified but generally applicable to spin-echo sequences at . to . t. (refer to the tidwell &jones article in the may issue for a discussion on gradient echo imaging of hemorrhage.) furthermore, the timing of various stages may vary significantly, and different stages often overlap. , the precise dating of specific hematomas is notoriously inaccurate, so the nomenclature of the temporal stages of hematomas is somewhat arbitrary. oxyhemoglobm. freshly extravasated blood from arterial bleeding is composed of intact erythrocytes containing primarily oxyhemoglobin. the iron in oxyhemoglobin is in the ferrous form (fe+ ). because there are no unpaired electrons in the iron (or other atoms), oxygenated blood is not paramagnetic. in the absence of paramagnetism, peracute hematomas appear as a high-proton-density region, with slightly shortened relaxation times, compared with water, mainly because of the protein content of blood. this peracute stage of a hematoma usually persists for fewer than hours. because of their transient nature, peracute hematomas are rarely seen in clinical practice. they are isointense to slightly hypointense on t weighted images and hyperintense on t -weighted images, and therefore appear similar to many other brain lesions. ,. thus, ct is the preferred imaging modality if peracute hemorrhage is suspected. deoxyhemoglobin. after a few hours, the oxygen tension within the hematoma is reduced, resulting in the formation of deoxyhemoglobin (acute hematoma). deoxygenation is usually complete by hours. removal of molecular oxygen changes the distribution of electrons in the ferrous ion, leaving four unpaired electrons in the outer shell. these unpaired electrons confer deoxyhemoglobin with paramagnetic properties. the paramagnetic iron of deoxyhemoglobm is contained within a hydrophobic crevice in the hemoglobin mdlecule. this prevents water from coming close enough to the paramagnetic ion to induce paramagnetic (dipole-dipole) interaction, thus, the hematoma is still isointense to slightly hypointense on t -weighted images. as long as the erythrocyte membrane is intact, the paramagneuc deoxyhemoglobln is localized within the cell. this results in inhomogeneous suscepub]lity effects# acute hematomas that contain intracellular deoxyhemoglobin consequently appear very hypointense on t -we]ghted images. at this stage, any surrounding edema appears as a hyperintense perimeter on t -weighted images) intracellular methemoglobin. as oxygen tension within the hematoma falls further, deoxyhemoglobin is oxidized to methemoglobin (subacute hematoma). in whole blood, methemoglobin begins to accumulate at the rate of about % per day, after the first days. s conversion to methemoglobin is maximal when the p is approximately mm hg. if the oxygen tension is higher or lower, conversion to methemoglobin is slowed, affecting mri contrast. the iron in methemoglobin is in the ferric (fe + ) state, which has five unpaired electrons in its outer shell and is highly paramagnetic. also, one of the coordination sites of the methemoglobln molecule is occupied by a water molecule that is rapidly exchanged with other water molecules in solution. as a result, water is positioned within . nm of the paramagnetic iron. this allows paramagnetic (dipole-dipole) interaction to shorten t relaxation, causing methemoglobin to be hyperintense on tl-weighted images. this hyperintensity begins at the periphery of an intraparenchyreal hematoma and progresses inward, probably because the outer rim of the hematoma has the optimal oxygen tension for the oxidation of hemoglobin. , at this stage the hematoma is still hypointense on t -welghted images other causes of t hyperintensity or t hypointenslty include fat, calcification, mucinous material, intratumoral melanin, flow effects, and enhancement with paramagnetic contrast agents extracellular methemoglobin. soon after methemoglobin formation begins, glucose reserves in the erythrocytes are depleted and hemolysis ensues. this eliminates the inhomogeneous susceptibility effect as the methemoglobin becomes uniformly distributed. this prolongs t , and the hematoma is once again hyperintense on t -weighted images (rebound hyperintensity). on the other hand, tl-weighted images are not affected and therefore continue to show hyperintensity. this paradoxical state of t and t hyperintensity may persist for month or more (fig ) . ferritin and hemosiderin. after to weeks, modified macrophages (gitter cells) infiltrate from surrounding brain and remove iron from the hematoma (chronic hematoma). this eventually eliminates the remaining protein and inhomogeneous susceptibility effects. the center of the hematoma eventually either collapses or is replaced by cse the iron is deposited at the periphery of the hematoma as hemosiderin and ferritin, which behave paramagnetically. the iron in these storage forms is not accessible to water, so paramagnetic (dipole-dipole) interaction does not occur, but the inhomogeneous susceptibility effect shortens t . a chronic hematoma has a rim that is hypointense on tl-weighted images and very hypointense on t -weighted images. the rim becomes thicker as the hematoma resolves. whenever intracramal hemorrhage is identified, it is important to determine if it is associated with an underlying tumor or is caused by a nonneoplastic lesion. the use of a contrast agent often allows identification of an underlying tumor. ° an important finding in a hemorrhagic tumor is persistent surrounding edema (decreased attenuanon on ct, hyperintensity on t -weighted images), whereas edema has usually resolved by the chronic stage of a nonneoplastic hematoma. in neoplastic hemorrhage, mri signal intensity patterns are more heterogeneous and the temporal evolution of intensity patterns is often delayed compared with nonneoplastic hematomas, probably because hypoxia within the tumor delays methemoglobin formation. °, neoplastic hemorrhage often lacks the well-defined hypointense rim characteristic of nonneoplastic hematomas in their subacute and chronic stage. °,~ this is because the persistently altered blood-brain barrier of tumors may allow more efficient removal of ferritm and hemosiderin. in situations in which the diagnosis is still uncertain, repeat scanning is often useful because this allows evaluation of the expected temporal changes. ° the most common is the arteriovenous malformation (avm). clinical signs are caused by spontaneous hemorrhage and are usually suggestive of a focal cerebral lesion. the onset of signs is usually acute and occurs in middle-aged to older animals. > the relatively late onset of signs associated with a congenital lesion can be explained by contmued hemodynamic stress and consequent attenuation of the abnormal vessels, which eventually leads to hemorrhage, z° when a cerebrovascular malformation has bled, early ct or mri usually shows intraparenchymal hemorrhage (fig ) . ct of capillary malformations is often normal, but may show an isodense to slightly hyperdense mass. contrast enhancement is usually minimal. mri is more sensitive, and shows a lace-like region of stippled contrast enhancement with no or subtle abnormality on unenhanced images. a a cavernous malformation appears on ct as a focal hyperdense region with variable calcification with mild contrast enhancement. on mri, a cavernous malformation is seen as a central region of mixed intensity, corresponding to methemoglobin, surrounded by circumferential rings of hypomtense hemosiderin and ferritin) whenever a spontaneous intraparenchymal hematoma is identified, it is important to look for any associated large vessels to suggest a vascular malformation. however, the failure to identify large vessels does not entirely exclude a vascular malformation, because compression or obliteration of vessels by adjacent hematoma, extremely slow flow, and thrombosis may obscure the abnormal vessels. , although ct and mri are useful in detecting hemorrhage associated with vascular malformations and depicting the vascular anatomy of some of these lesions, catheter angiography or magnetic resonance angiography (mra) is often necessary for complete assessment of cerebrovascular malformations m human patients. , ,~ (refer to the tidwell & jones article in the may issue for a discussion of mra.) obstruction of flow in the vessels of the brain can result in a sudden onset of neurological signs caused by infarction. arterial obstruction can be caused by thrombosis or embolism. a thrombus is a blood clot developing within a vessel that causes obstruction at the site of formation. embolism is occlusion of a vessel by a fragment of blood clot or other substance that has flowed to the site of obstruction from a distant location. because of abundant venous anastomoses, venous infarction is less common than arterial thromboembolism. in human patients, cerebrovascular thrombosis or embolism is often secondary to atherosclerosis. atherosclerosis also occurs in dogs, especially older dogs, dogs with hypothyroidism, and miniature schnauzers with idiopathic hyperlipoproteinemia. , , s atherosclerosis associated with these conditions can lead to cerebral thromboembohsm and neurological dysfunction. - other diseases associated with cerebral thromboembolism in dogs include sepsis, coagulopathy, neoplasia, and heartworm infection. > ° the hallmark of brain infarction is an acute onset of focal bram dysfunction. neurological deficits depend on the site of the lesion and are typically asymmetric. involvement of the forebrain, such as with thromboembolism of the middle cerebral artery, usually results in contralateral hemiparesis with decreased postural reactions. seizures are very common in dogs and cats with infarction affecting the forebrain. there may be contralateral bhndness with normal pupillary light reflexes, and the patient may circle or turn toward the side of the lesion. lesions in the cerebellum may cause ataxia, hypermetria, vestibular dysfunction, or opisthotonos. brainstem involvement is characterized by gait deficits ranging from ipsilateral hemlparesis to tetraplegia, cranial nerve deficits, and abnormal levels of consciousness, including coma. , , , , , , nonhemorrhagic infarction computed tomography. changes may be detected on ct as early as to hours after onset of signs and consist of a slight decrease in attenuation and subtle mass effect. these changes are related to edema and reach a maximum at to days (fig ) and resolve by to weeks after infarction. the location and shape of the lesion correspond with the distribunon of the involved vessel(s), most commonly the middle cerebral artery. abnormal contrast enhancement may be seen as early as hours but often does not become evident until about week after infarction. , enhancement is most apparent at the periphery of the lesion and reflects growth of new capillaries without a normal blood-brain barrier. enhancement of hypodense infarcts can result in isodense lesions, thereby masking their presence. for this reason, unenhanced as well as enhanced ct should be performed. in the chronic phase ( to weeks), the hypodense region becomes more sharply marginated as necrotic tissue is resorbed. ultimately there is a loss of parenchymal volume with attendant dilatation of adjacent sulci and ventricles. contrast enhancement does not usually occur in the chronic stage because the integrity of the blood-brain barrier is restored. magnetic resonance imaging. early changes on mri consist of a subtle increase in intensity on t -weighted and proton density-weighted images. these changes reflect edema and can be detected as early as hour after vascular occlusion. mri is thus more sensitive than ct in early infarction. also, mri is more sensitive in detecting small infarcts and those involving the brainstem. in acute infarction, tl-weighted mri is less sensitive than t -weighed and proton density-weighted images and may be normal. ~ parenchymal enhancement with gadolinium is uncommon within the first hours. , the use of functional mri techniques such as diffusion and perfusion studies for the detection of acute infarction is currently being investigated and is discussed in the arucle by tidwell &jones in the may issue. after the first hours, the hyperintensity on t -welghted and proton density-weighted images becomes more obvious (fig ) . ' ' during this time, tl-weighted images may show decreased signal. , gyral swelling and mass effect are more prominent, becoming maximal to days after onset of occlusion. parenchymal enhancement becomes evident within to days and may persist for to weeks. after several weeks, the signal changes seen on earlier scans become smaller and better defined. there is focal atrophy with dilatanon of nearby sulci and ventricles. there may be a collection of fluid with the s~gnal characteristics of cerebrospinal fluid. contrast enhancement does not usually occur. the above description applies to nonhemorrhagic or "bland" infarcts. however, many infarcts will have attendant bleeding caused by reperfusion of damaged blood vessels. this results in a hemorrhagic infarct. petechial hemorrhage into an infarct may result in an isodense lesion on unenhanced ct because of the combined effects of the brain edema, which decreases attenuation, and acute hemorrhage, which increases attenuation. mass effect caused by the edema usually provides a clue to the presence of a lesion. if hemorrhage is a large component of an acute infarct, unenhanced ct shows a hyperdense hematoma surrounded by hypodense edema. these changes are often confined to a vascular territory, a feature that is helpful in differentiating hemorrhagic infarctions from other causes of hemorrhage. ° in the subacute phase, the region around the infarct may enhance, increasing the possibility of hemorrhage within a tumor. mass effect from a hemorrhagic infarct is usually minimal or decreasing at the time of maximal contrast enhancement ( to weeks), which is useful in differentiating between hemorrhagic infarct and tumor. ~ the mri features of hemorrhagic infarction are similar to those of lntraparenchymal hemorrhage. ° compared with other causes of lntraparenchymal hemorrhage, hemorrhagic infarcts tend to have a higher p because of earlier revascularization and collateral perfusion. the higher p decreases the amount of deoxyhemoglobin, and therefore minimizes the acute t relaxation effect. uncontrolled seizures or status epileptmus may result in neuronal degeneration progressing to necrosis. the distribution of lesions varies somewhat among individual patients, but the hippocampus, basal nuclei, and frontal and pyriform lobes of the cerebrum are most severely affected. f° lesions are usually bilateral, but may affect one side more severely. f° these changes are thought to be the consequence of ischemia secondary to accumulation of cytotoxic agents and a mismatch between brain metabolism and blood flow during prolonged seizures. persistent or reversible mr lesions have been described in human patients after seizures, and similar abnormalities have there is also a smaller wedge-shaped region of hyperintensity in the vascular territory of the right middle cerebral artery. se, / , . t. been described in dogs, [ ] [ ] [ ] the most consistent finding is unilateral or bilateral lesions of the hippocampus, pyriform lobe, and frontal lobe. the lesions are hypointense on t weighted images and hyperintense on proton densityweighted and t -weighted images. there is minimal mass effect and no or moderate contrast enhancement tm (fig ) . these lesions may persist or disappear on subsequent scans. head trauma results from a variety of causes, including motor vehicle accidents, bites, kicks, and gunshot wounds. previously, imaging of head trauma was limited to skull radiography for the detection of fractures. plain radiography, however, cannot identify many traumatic brain lesions, such as hemorrhage, and therefore provides only limited diagnostic information. the development of ct provided a sensitive means for detecting and localizing intracranial hemorrhage, permitting expeditious surgical treatment, and improving outcome. mri has been shown to be similar in sensitivity for detection of hemorrhagic lesions, but is much more sensitive than ct for detecting nonhemorrhagic lesions, such as shearing injuries of white matter. neuroimaging should be considered early in the management of animals with head injury and marked impairment of consciousness or neurological deficits that progressively worsen despite initial medmal therapy. the most critical issue is to detect potential hematomas that may be treatable with sur-gery. in general, ct is the diagnostic study of choice for initial evaluation, because it can be completed quickly and is sensitive to acute hemorrhage, r ct also provides fine anatomic detail of bone when viewed at a wide window width allowing accurate characterization of any skull fractures (fig ) . although mri is slightly more sensitive than ct for detection of hematomas, those that are not seen on ct are usually small and typically managed conservatively. a disadvantage of mri is the longer examination ume and the difficulty in monitoring unstable patients in the mri environment. therefore, if ct is available, mr examination is usually delayed until the patient is stabilized. in patients with severe head trauma, mri should be considered in the first weeks after injury, because most parenchymal lesions are more easily detectable during this period. epidural hematomas accumulate in the potential space between the inner surface of the skull and the dura mater. they are usually found in the temporoparleteal region, and have been caused by laceration or tearing of the middle meningeal artery by skull fracture. the arterial force of the bleeding dissects the dura away from the bone, often resulting in a rapidly expanding mass. clinical signs may consist of rapidly progressing focal neurological deficits and deterioration in consciousness. however, patients with associated parenchymal brain injury may have severely impaired consciousness at the time of trauma. on ct, an acute epidural hematoma is typically a well-defined, biconvex lesion between the inner table of the skull and the underlying depressed dura and brain. tm the attenuation of the hematoma is initially greater than brain parenchyma and increases further during the first few hours with coagulation and clot retraction. with time, the attenuation decreases with clot retraction, erythrocyte lysis, and hemoglobin degradation. the hematoma becomes smaller and fades to isodense and then hypodense within or weeks. the inner surface of an epidural hematoma is dura mater, which normally enhances with intravenous contrast material, but this enhancing margin becomes even more prominent as a neovascular membrane develops over time. on mri, the intensity varies depending on the age of the hematoma, as described in the section on intracranlal hemorrhage and summarized in table . occasionally, an epidural hematoma may not have the classic lenticular shape or associated skull fracture, making it difficult to differentiate it from a subdural hematoma. mri can be helpful in this regard, because the medially &splaced dura mater is usually directly visualized as a thin line of low signal separating the hematoma from the underlying compressed brain parenchyma. mri is also superior in the detection of subacute and chronic hematomas, which may be isodense on ct subdural hematomas accumulate within the potential space between the pia-arachnmd and dura mater. they are usually caused by tearing of veins that traverse the subdural space. subdural hematomas appear to be less common m dogs and cats with head injury, compared with human patients. clinical signs may consist of progressive asymmetrical neurological deficits and decreased levels of consciousness. an acute subdural hematoma appears on ct as a hyperdense, crescentshaped collection conforming to the inner surface of the skull. tm mass effect is evident and may be compounded by contusion and edema of the underlying brain parenchyma. acute hyperdense hematomas may not be vislble on a narrow window width (soft tissue window), appearing only as an apparent thickening of the skull, since the bone and hematoma may have the same pixel brightness, r mass effect is usually present, however, providing a clue in their detectlon. widening the window width may be necessary to distinguish an acute subdural hematoma from the dense skull, rs as with other intracranial hematomas, the density of a subdural hematoma decreases over time, becoming isodense to gray matter by to weeks. accordingly, subacute subdural hematomas may be difficult to detect on ct but are readily detectable on mri. a chronic subdural hematoma ( to weeks old or older) is hypodense compared with normal brain on ct and is surrounded by a well-defined capsule (fig ) . this results in a more focal collection of blood with a straighter medial edge compared with crescent-shaped acute subdural hematomas. the capsule of a chronic subdural hematoma enhances with intravenous contrast material and may calcify. tm subarachnoid hemorrhage is bleeding into the csf-filled subarachnoid space. posttraumatic subarachnoid hemorrhage is relatively common and often associated with cortical contusions. acute subarachnoid hemorrhage is evident on ct as increased attenuation of the sulcl, fissures, or basal cisterns, with the degree of increased attenuation being related to the amount of blood in the subarachnoid space. with time the attenuation decreases and subarachnoid hemorrhage may not be detectable after the first week, unless rebleeding has occurred. acute subarachnoid hemorrhage is usually not detectable on mri, probably because the po of the subarachnoid csf is too high for the conversion of oxyhemoglobin to deoxyhemoglobin and methemoglobin. however, mri is excellent at detecting subarachnoid hemorrhage in the subacute or chronic stage. i brain contusions are common after head trauma and consist of heterogeneous regions of hemorrhage, edema, and necrosis, often located in the superficial gray matter. in human patients contusions tend to be multiple and bilateral and are much less likely to be associated with severe initial impairment of consciousness compared with diffuse axonal injur~ initial ct findings are often limited to faint, ill-defined hypodense areas mixed with tiny regions of hyperdense hemorrhage. contusions in which edema and necrosis predominate may not be visible imtially on ct but often become apparent several days later as regions of decreased attenuation and mass effect caused by edema. s mri, because of its greater sensitivity in detecting edema, is better at detecting early contusions, which appear hypointense on tl-weighted images and hyperintense on t -weighted images. head trauma that involves rapid angular acceleration may result in diffuse axonal injury. these shearing injuries result from differences in elastic and inertial properties between different but adjacent brain tissues/s, in human patients, these injuries are characterized pathologically by disruption of axons, especially at the junction of gray and white matter of the cerebrum, and at the corpus callosum, basal nuclei, and cranial aspect of the brainstem. there is subsequent axonal swelling and infiltration with macrophages. these patients present with severe impairment of consciousness starting from the moment of injury. " ,s mri is much more sensitive than ct in detecting diffuse axonal injury in human patients, although even mri findings usually underestimate the true extent of these injuries. ct is often normal, but may show scattered hemorrhages. the mri appearance reflects the prolonged t and t values of increased tissue fluid (edema). there are multiple, small elliptical lesions in the white matter. these lesions are hypomtense on tl-weighted images and hyperintense on t -welghted images. , infectious and inflammatory diseases inflammatory diseases are important diagnostic considerations for patients with brain disease. infectious agents, such as viruses, protozoa, and fungi, cause many inflammatory diseases, but for others the etiology is unknown. despite the numerous causes of mflammatory brain disease, the affected tissue can respond only in a limited number of ways. thus, many of these diseases appear similar on imaging studies and differentiating the potential etiologies based on imaging features alone may be impossible. furthermore, it may be difficult to &scriminate between inflammatory diseases and other categories of disease, such as neoplasia and vascular disorders. accordingly, results of imaging studies must be interpreted in context with clinical features and results of other laboratory tests, especially analysis of cse i all inflammatory brain diseases share a common pathological feature--an influx of leukocytes into the brain (cerebritis or encephalitis) or meninges (meningitis). because of the close anatomical association of these structures, more than one area of the nervous system can be involved in the inflammatory process. for example, inflammation of the meninges and brain is called meningoencephalitis, s the most common cause of meningitis in dogs is steroidresponsive meningitis-arteritis, a nonseptic suppurative meningitis of unknown etiology that responds to immunosuppressive dosages of corticosteroids, s infectious causes of memngitis are less common in small animals and include bacteria, viruses, fungi, and protozoa s pathologically. acute leptomeningitls results in congestion and hyperemia of the pia-arachnoid and distension of the subarachnoid space by an exudate containing leukocytes. clinically, affected patients show fever, spinal pain, cervmal rigidity, and stiff gait. several complications can occur m the ensuing days to weeks. there may be extension of the infection to the neural parenchyma, resulting in focal or diffuse encephalitis, myelitis, or abscess. inflammatory exudate may obstruct csf pathways, producing hydrocephalus. endogenous host inflammatory mediators can result in disruption of the blood-brain barrier, cerebral edema, and increased intracranial pressure. definitive &agnosis of meningitis is based on analysis of cse neuroimaging is useful in detectmg some of the complications associated with meningitis and when the differential diagnosis includes other diseases. neuroimaging features of experimental bacterial menmgitls in dogs is comparable with naturally occurring bacterial meningitis in human patients. r in human patients with uncomplicated early bacterial or viral meningitis, unenhanced ct and mri are often unremarkable or show mild dilatation of the ventricles or subarachnoid space (fig ) . with more severe involvement, there may be diffuse or patchy brain edema. postcontrast ct or mri may show abnormal enhancement of the leptomeninges. in experimental studies in dogs, tl-weighted mr images with gadolinium showed abnormal leptomeningeal enhancement better than ct. r mri also identifies complications such as encephahtis more effectively than ct. encephalitis generally refers to nonpurulent inflammation of the brain and is distinguished pathologically from suppurauve inflammation of the brain (cerebritis) assooated with bacterial infection. viral encephalitides of small animals include canine distemper and feline infectious peritonitis. other causes of encephalitis include rocky mountain fever, canine ehrlichiosis, toxoplasmosis, and neosporosls. finally, there are encephahtides of unknown etiology, such as pug dog encephalitis and granulomatous meningoencephalitis. distemper encephalitis. the two most common clinical forms of distemper encephalitis are acute encephalitis in young dogs and chronic encephalitis in mature dogs. immature dogs with distemper encephalitis typmafly suffer a rapid onset of systemic illness characterized by conjunctivitis, nasal discharge, cough, vomiting, and diarrhea. neurological dysfunction can occur during or after the systemic illness and includes seizures, abnormal behavior, blindness, and paresis. mature dogs are more likely to develop chromc, multifocal encephalitis with a predilection for the white matter of the brainstem. many of these dogs have an adequate vaccination history, and signs of systemm illness are often absent or transient. °- these patients often have slowly progressive gait deficits or vestibular dysfunction. °, ct of dogs with chromc distemper encephalitis may be normal or show focal or multifocal hypoattenuating lesions with a predilection for the white matter. these lesions may have uniform or ring-like enhancement (fig ) . some lesions may be associated wlth hypoattenuating edema and mass effect. lesions are typically hypointense or poorly defined on tl-weighted mri, hyperintense on t -weighted images, and enhance with contrast agent. feline infectious peritonitis. feline infectious peritonitis (fip) is a systemic disease of cats caused by an immune response to a corona virus. neurological signs are generally associated with the parenchymatous (dry) form of fie neurological deficits referable to brainstem involvement predominate and include ataxia, paresis, and vestibular dysfunction. [ ] [ ] [ ] imaging features of fip reflect the pathological changes, which consist of pyogranulomatous inflammation of the leptomeninges, choroid plexus, ependyma, and brain parenchyma. hydrocephalus is common and is probably secondary to obstruction by ependymltis. - the brainstem and fourth ventricle are consistently involved, but other regions of the central nervous system can be affected. the inflammatory process primarily affects the inner and outer surfaces of the brain with only secondary extension into the parenchyma. recognition of this surface-related pattern can be helpful in differentiating fip from other bram diseases in the cat. ct may be normal or show hydrocephalus. mri may show ependymitis, choroiditis, and memngitis. this is evident as hyperintensity of the ventricular lining, choroid plexus, and meninges, respectively, on t -weighted mri and abnormal enhancement with gadolinium-based contrast agent , (fig ) . fungal infections. many fungal agents can sporadically infect the nervous system, causing meningitis or granulomas. cryptococcus neoformans is the most common fungal infectmn to involve the nervous system of dogs and cats. in cats, this organism generally induces a mild, nonsuppurative meningitis or encephalitis, whereas affected dogs typically develop a granulomatous reaction in the brain and meninges. neurological deficits can be acute or chronic and include seizures, lethargy, ataxia, and vestibular dysfunction. °° on ct, mass lesions (cryptococcomas) appear as single or multiple isodense or hypodense masses with ring or solid enhancement and surrounding edema. , , i° leptomeningeal enhancement may also be apparent if the meninges are involved. ,i° hydrocephalus may occur secondary to meningitis or obstruction of csf pathways by the mass. , in human patients, mri is more sensitive than ct and may show clustered foci of signal abnormahties that are lsointense to csf on all sequences. these lesions represent small granulomas or dilated virchow-robin spaces filled with fungal organisms and mucoid. these are often bilaterally symmetrical, and are located in the basal nuclei and midbraln. these lesions do not enhance with gadolinium and are not associated with mass effect or edema. similar changes have been reported on mri of canine cryptococcosis.i° cryptococcomas appear as masses that are hypointense on tl-weighted images, hyperintense on t -welghted images, and enhance with gadolinium. < ° other fungal organisms sporadically infect the central nervous system, including blastomyces dermatldis, histoplasmosis capsulatum, aspergfllus spp, coccidiodes immitis, and phaeohyphomycosis (fig ) . l° qn necrotizing encephalitis (pug dog encephalitis). a necrotizing form of encephalitis has been recognized in pug dogs, maltese terriers, and yorkshire terriers between months and years of age. n -n signs include progressive seizures, abnormal behavior, blindness, ataxia, and walking in circles. pathological changes consist of multifocal necrosis and nonsuppuratlve inflammation, with a striking predilection for the white matter of the cerebrum. lesions are often bilateral but asymmetrical, n - ,n enlargement of the lateral ventricles secondary to shrinkage and cavitation of the cerebral hemispheres (hydrocephalus ex vacuo) is common n ,i n (fig ) . in yorkshire terriers, the brainstem may be preferentially revolved. the etiology is unknown. in acute forms of the disease, ct may show one or more focal hypodense lesions, most commonly affecting the cerebral hemisphere. the lesions may or may not enhance with contrast agent. mri shows the early edematous changes as increased signal intensity on proton density-weighted and t -weighted images and decreased signal intensity on tl-weighted images. in acute cases, there is often substantial mass effect and minimal if any abnormal enhancement with contrast medium (fig ) . differentials include neoplasia, other inflammatory lesions, and acute infarction. in more chronic cases, necrosis and cystic changes usually predominate. the centers of the lesions appears similar to csf; that is, hypodense on ct, very hypointense on tl-weighted images, and very hyperintense on proton density-weighted and t -weighted images - (fig ) . lesions are usually located in the white matter of the cerebral hemisphere, often in the area lateral to the ventricles. ii typically there is no mass effect or even a reverse mass effect (shift of surrounding tissue toward the lesion). lesions usually do not enhance, but may have a ring pattern of enhancement. , asymmetric enlargement of the lateral ventricles is common. the primary differential is chronic infarction. however, in necrotizing encephalitis the lesions are not confined to a specific vascular territory as is typical of infarction caused by thromboembolism. the onset of signs (sudden in infarction versus slow onset in chronic necrotizing encephalitis) ts also helpful. granulomatous meningoencephalomyelitis. granulomatous meningoencephalomyelitis (gme) is an inflammatory disease of the canine central nervous system characterized pathologically by an accumulation of mononuclear cells in the parenchyma and meninges of the brain and spinal cord. lesions may be disseminated or focal. in the disseminated form, lesions are distributed throughout the central nervous system, with a predilection for the white matter of the cerebrum, cerebellum, caudal aspect of the brainstem, and cervical spinal segments. the focal form is manifested as a single granulomatous mass, most commonly located in the cerebrum, with smaller disseminated lesions, ns-ln the cause is not known. adult dogs of any breed can be affected, although females and toy and terrier breeds are at increased risk. dogs with disseminated gme usually have rapidly progressive signs including neck pain, vestibular dysfunction, paralysis, and seizures. the focal form is manifested as chronic, gradually progressive signs, with seizures being the most common. iis- the clinical presentation of focal gme often mimics that of a tumor. on ct, disseminated gme is seen as multiple foci of ill-defined contrast enhancement involving the parenchyma and meninges. some lesions may be associated with hypoattenuating edema and mass effect. other inflammatory diseases are the primary differentials. focal gme appears on noncontrast ct as an isodense or hyperdense mass, most commonly located within the cerebrum or at the cerebellomedullary junction (fig ) . ' on mri, focal gme is usually isointense or slightly hypointense on tl-weighted images and hyperintense on proton density-weighted and t -weighted images (fig ) . enhancement is variable, including no enhancement, ring-pattern enhancement, or moderate homogenous enhancement. ,t ,i there may be edema in the white matter surrounding the mass. , , asymmetric enlargement of the lateral ventricles has also been reported. the primary differentials are neoplasia and other inflammatory lesions. biopsy is often necessary for definitive diagnosis. focal infection of the brain with pyogenic organisms is uncommon in small animals. bacteria may gain access to the brain through penetrating wounds; secondary to direct extension from infections in the eye, ear, nasal passages, or meninges; or via hematogenous spread from extracranial sources, i with hematogenous spread, lesions often arise at the graywhite matter junction of the cerebrum, s clinical signs reflect a progressively worsening focal brain lesion. i several reports detail the pathological and ct features of experimental cerebritis/abscess in dogs. , ° these imaging features are similar to those reported in human patients with spontaneous brain abscess. tm pathologically, serial changes occur over to weeks, starting as cerebritis and culminating in abscess. focal but poorly localized areas of scattered necrosis, edema, vascular congestion, and perivascular inflam- matory infiltrates characterize cerebritis. at this stage, unenhanced ct shows only an irregular, poorly circumscribed region of low attenuation, t - scans obtained immediately after contrast administration show ring-like enhancement. on delayed scans, contrast diffuses into the center of the lesion, starting peripherally, until the center of the lesion may be completely filled with contrast by minutes after admmistra-tlonj - t the inherent sensitivity of proton density-weighted and t -welghted mri to aheradons in tissue water enables earlier detection of cerebritis compared with ct. , these images show increased signal intensity indistinguishable from or slightly hypointense to surrounding edema, sg,j on t weighted images, cerebritis is isointense to slightly hypomtense to adjacent brain parenchyma, with associated mass effect. , over a period of to weeks, untreated cerebritis may progress to abscess formation when the central zone of necrosis becomes liquefied, better defined, and encircled by a collagen capsule, which is formed by fibroblast migration from the surrounding vessels. because of relatively poor vascularization of white matter, the medial aspect of the capsule may be somewhat thinner. this predisposes to expansion of the abscess into white matter, the formation of daughter abscesses medially, or rupture into the lateral ventricles, lz , °, the capsule is visible on unenhanced ct as an isodense rim that is visible because it is bordered medially by a hypodense liquid center and surrounded by hypodense edema (fig ) . the edema may be greater in volume than the abscess itself, causing much of the mass effect. on contrast-enhanced ct, the rim is usually smooth and brightly enhancing. there is no diffusion of contrast into the necrotic center on delayed scans as there is with cerebritis, n - on tl-weighted mri there is mild peripheral hypointensity representing edema and a more markedly hypointense liquid center. the capsule is a discrete rim that is isointense to slightly hyperintense. on t -weighted images the abscess center is isointense to mildly hyperintense to gray matter. the capsule is seen as a dramatic hypointense rim, possibly caused by paramagnetic free radicals within phagocytic macrophages. the ring pattern of enhancement parallels the enhancement seen on contrast-enhanced ct. the differential diagnosis for a ring-enhancing lesion includes primary brain tumor, metastasis, infarction, granuloma, and resolving hematoma. . helpful clues that may identify abscesses include the time course, location, temporal pattern of enhancement, and predisposition for the abscess rim to be thinner medially, s cuterebra. dogs and more commonly cats can suffer brain disease caused by aberrant migration of cuterebra larvae. [ ] [ ] [ ] fly larvae attach to the host and burrow into the subcutaneous tissue. the developing larva ( to mm long) may migrate under the skin and enter the brain, most likely through the nasal passages and cribiform plate. , pathological changes in the brain consist of multifocal meningoencephalitis with malacia and hemorrhage • - affected animals typically have access to outdoors and develop signs from june to october, coinciding with the larval migration portion of the cuterebra life cycle. a recent history of upper respiratory disease is common, likely reflecting migration of the larvae through nasal passages. there is an acute onset of neurological dysfunction, most commonly referable to a focal forebrain lesion. seizures, abnormal mentation, circhng, hemlparesis, and unilateral blindness are common. , clinical and pathological features in cats are similar to what has been previously reported as feline ischemic encephalopathy.i a mottled appearance to the brain has been reported on ct of an affected cat} based on my observations, ct may show focal or muhifocal regions of decreased attenuation with minimal mass effect. the may be one or more tract-like regions of contrast enhancement (fig ) . lesions may be hypointense on tl-weighted mri and hypermtense on t -weighted mri. edema is fairly minimal, and there may be small regions of hemorrhage. contrast enhancement is s~milar to that described for ct. an enhancing tract (arrows) extends from the cribiform plate through the right cerebral hemisphere. this cat, which lived outside, presented in october, days after suffering a sudden onset of sneezing followed by seizures, left hemiparesis, depression, and circling to the right. clinical signs gradually resolved over the next weeks, so the diagnosis was not confirmed by necropsy, but the clinical features are consistent with intracranial migration of a cuterebra larva. and does not enhance. i the intraparenchymal location is helpful in differentiating these lesions from arachnoid cysts, which are associated with the subarachnoid space. ,~- ct and mri are helpful in identifying and characterizing many nonneoplastic brain disorders in dogs and cats. the imaging features of some of these disorders are unique, permitting definitive diagnosis based on imaging results and clinical features. however, the imaging findings for other brain disorders are nonspecific. in these instances, ct and mri often allow detection and localization of abnormalities, but definitive diagnosis may require other laboratory tests or surgical biopsy. as the use of ct and mr] becomes more widespread in veterinary medicine, further research in the imaging findings associated with various nonneoplastic disorders will improve our ability to diagnose and manage these conditions. imaging the brain (first of two parts) canine hydrocephalus. comp contln ed pract vet computed tomography in evaluation of hydrocephalus diagnosis and management of an atypical case of hydrocephalus, using 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domestic cat magnetic resonance imaging cerebrovascular disease key: cord- -feqqx n authors: carminati, marco; fiorini, carlo title: challenges for microelectronics in non-invasive medical diagnostics date: - - journal: sensors (basel) doi: . /s sha: doc_id: cord_uid: feqqx n microelectronics is emerging, sometimes with changing fortunes, as a key enabling technology in diagnostics. this paper reviews some recent results and technical challenges which still need to be addressed in terms of the design of cmos analog application specific integrated circuits (asics) and their integration in the surrounding systems, in order to consolidate this technological paradigm. open issues are discussed from two, apparently distant but complementary, points of view: micro-analytical devices, combining microfluidics with affinity bio-sensing, and gamma cameras for simultaneous multi-modal imaging, namely scintigraphy and magnetic resonance imaging (mri). the role of integrated circuits is central in both application domains. in portable analytical platforms, asics offer miniaturization and tackle the noise/power dissipation trade-off. the integration of cmos chips with microfluidics poses multiple open technological issues. in multi-modal imaging, now that the compatibility of the acquisition chains (thousands of silicon photo-multipliers channels) of gamma detectors with tesla-level magnetic fields has been demonstrated, other development directions, enabled by microelectronics, can be envisioned in particular for single-photon emission tomography (spect): a faster and simplified operation, for instance, to allow transportable applications (bed-side) and hardware pre-processing that reduces the number of output signals and the image reconstruction time. the impact of application specific integrated circuits (asics), in particular, of cmos analog front-end interfaces for solid-state sensors and detectors, differs significantly among various application areas. for example, the field of high-energy and particle physics has been heavily reliant on integrated circuits for the readout of the detectors and parallel processing of signals for decades [ ] . instead, different from experimental physics, whose advancements are often constrained by the performance of electronics and instrumentation, in the field of bio-medicine, the role of microelectronics appears less consolidated nor univocal. in fact, despite a large penetration of micro-fabrication techniques in this field, and a considerable volume of publications, asics are rarely pivotal in the success of micro-analytical devices, especially from a commercial point of view. in this brief tutorial review, we focus on non-invasive medical diagnostics and discuss some challenges for the future development of integrated electronics, with reference to diagnostics in particular. non-invasive medical diagnostics comprise two complementary approaches: (i) imaging internal organs by means of energy penetrating through the skin and tissues, and (ii) taking out of the body a liquid sample for bio-chemical analysis ( figure ). non-invasive imaging can be performed by the main advantage offered by the deployment of cmos asics in micro-analytical devices is miniaturization. massively parallel readout systems (with thousands of channels, such as [ ] or [ ] ) can be squeezed into a chip footprint of a few millimeters inside. the miniaturization of electronics matches the concurrent miniaturization of fluidics (locs handle volumes of samples in the microliter range) and of micro-machined transducers and electrodes. the main challenges which still need to be addressed in this area can be grouped into two classes: (i) at the circuit level (ii) at the level of packaging and interfaces. at the circuit level, one consolidating trend is the reduction in power dissipation, both for thermal issues, critical in high-density chips, as well as the increase in the battery lifetime in the case of portable (and implantable) applications. in order to reduce the power dissipation in analog front-ends, different approaches can be adopted. amplifiers can be shared among different circuit blocks [ ] or stacked to re-use the same bias current [ ] . individual ac-coupled transistors can be stacked [ ] and self-biased [ ] . analog processing (signal shaping, feature extraction) can be tailored to the type of signal and the first approach is mostly based on sophisticated and expensive scanners, which require special facilities, the handling of radioactive material and skilled personnel, thus, are almost exclusively located in hospitals. the second approach, instead, is nowadays mostly pursued within the lab-on-a-chip (loc) paradigm, aiming at the realization of portable and automatic micro-analytical platforms. the main advantage offered by the deployment of cmos asics in micro-analytical devices is miniaturization. massively parallel readout systems (with thousands of channels, such as [ ] or [ ] ) can be squeezed into a chip footprint of a few millimeters inside. the miniaturization of electronics matches the concurrent miniaturization of fluidics (locs handle volumes of samples in the microliter range) and of micro-machined transducers and electrodes. the main challenges which still need to be addressed in this area can be grouped into two classes: (i) at the circuit level (ii) at the level of packaging and interfaces. at the circuit level, one consolidating trend is the reduction in power dissipation, both for thermal issues, critical in high-density chips, as well as the increase in the battery lifetime in the case of portable (and implantable) applications. in order to reduce the power dissipation in analog front-ends, different approaches can be adopted. amplifiers can be shared among different circuit sensors , , of blocks [ ] or stacked to re-use the same bias current [ ] . individual ac-coupled transistors can be stacked [ ] and self-biased [ ] . analog processing (signal shaping, feature extraction) can be tailored to the type of signal and communication channel [ ] and it is generally preferred to fpga-based digital elaboration [ ] . in order to reduce the energy consumption in data transmission, analog compression [ ] and pulse-coded communication can be adopted [ ] . a low-power design is typically opposite to a low-noise design, for instance, in terms of the flicker noise of mosfets, but is clearly fundamental in pushing down the limit of detection (lod) of target molecules. in order to analyze the strategies and compromises in noise minimization, we consider the case of current amplifiers. their application in bio-sensing is ubiquitous, spanning from electrochemical detection (where the charge is exchanged between the electrodes and redox molecules in the solution, figure a ) to optical detection (where the current is photo-generated in the photo-detector). as shown in figure e , the input-referred current noise of a classical transimpedance amplifier (tia) is given by the sum of three contributions: the thermal noise of the feedback resistor (r f ), the input-equivalent current noise of the amplifier (i n ) and its voltage noise (v n ). the latter becomes the dominant term in the total noise spectral density at high frequencies [ ] . the voltage noise produces an input noise current proportional to the value of the total capacitance (c tot ) connected at the input. c tot includes the feedback capacitance, the amplifier input capacitance, the sensor capacitance and the parasitic capacitance of the connection between the sensor/detector and the amplifier input. evolutions of the basic tia scheme, such as integrator-differentiator configurations, enable the combination of low-noise with extended detection bandwidth [ ] . additionally, for integrators (i.e., charge amplifiers) the minimization of the c tot is crucial. sensors , , of communication channel [ ] and it is generally preferred to fpga-based digital elaboration [ ] . in order to reduce the energy consumption in data transmission, analog compression [ ] and pulsecoded communication can be adopted [ ] . a low-power design is typically opposite to a low-noise design, for instance, in terms of the flicker noise of mosfets, but is clearly fundamental in pushing down the limit of detection (lod) of target molecules. in order to analyze the strategies and compromises in noise minimization, we consider the case of current amplifiers. their application in bio-sensing is ubiquitous, spanning from electrochemical detection (where the charge is exchanged between the electrodes and redox molecules in the solution, figure a ) to optical detection (where the current is photo-generated in the photo-detector). as shown in figure e , the input-referred current noise of a classical transimpedance amplifier (tia) is given by the sum of three contributions: the thermal noise of the feedback resistor (rf), the input-equivalent current noise of the amplifier (in) and its voltage noise (vn). the latter becomes the dominant term in the total noise spectral density at high frequencies [ ] . the voltage noise produces an input noise current proportional to the value of the total capacitance (ctot) connected at the input. ctot includes the feedback capacitance, the amplifier input capacitance, the sensor capacitance and the parasitic capacitance of the connection between the sensor/detector and the amplifier input. evolutions of the basic tia scheme, such as integrator-differentiator configurations, enable the combination of lownoise with extended detection bandwidth [ ] . additionally, for integrators (i.e., charge amplifiers) the minimization of the ctot is crucial. in order to minimize this noise contribution, three strategies can be adopted: (i) canceling the ctot with an inductor, (ii) reducing the sensor capacitance, and (iii) reducing the parasitic capacitance. it has been shown that by placing an inductor parallel to the ctot it is possible to improve the noise performance (of about one order of magnitude) thanks to the resonance [ ] . this approach has two main limitations: (i) the enhancements are limited by the quality factor of the inductor, and (ii) the noise reduction takes place only in a narrow bandwidth around the resonance frequency (tens of mhz), thus being suitable only for impedance sensing at a fixed frequency. a very relevant design guideline is the reduction in the capacitance associated with the sensor geometry, typically an electrode collecting the signal charge, whose area should be minimized. of course, very often, the amount of collected charge is also proportional to the sensor areas, thus, in order to maximize the signal-to-noise ratio (snr), noise should be minimized while preserving the signal amplitude. in the case of electrochemical sensors, despite a decrease in the working electrode area, the capture of molecules by means of this electrode should be simultaneously enhanced, with respect to passive diffusion, by means of active solutions, such as magnetic, electrophoretic, dielectrophoretic, thermal and fluid-dynamic ones. this approach proved to be very successful in the in order to minimize this noise contribution, three strategies can be adopted: (i) canceling the c tot with an inductor, (ii) reducing the sensor capacitance, and (iii) reducing the parasitic capacitance. it has been shown that by placing an inductor parallel to the c tot it is possible to improve the noise performance (of about one order of magnitude) thanks to the resonance [ ] . this approach has two main limitations: (i) the enhancements are limited by the quality factor of the inductor, and (ii) the noise reduction takes place only in a narrow bandwidth around the resonance frequency (tens of mhz), thus being suitable only for impedance sensing at a fixed frequency. a very relevant design guideline is the reduction in the capacitance associated with the sensor geometry, typically an electrode collecting the signal charge, whose area should be minimized. of course, very often, the amount of collected charge is also proportional to the sensor areas, thus, in order to maximize the signal-to-noise ratio (snr), noise should be minimized while preserving the signal amplitude. in the case of electrochemical sensors, despite a decrease in the working electrode area, the capture of molecules by means of this electrode should be simultaneously enhanced, with respect to passive diffusion, by means of active solutions, such as magnetic, electrophoretic, dielectrophoretic, thermal and fluid-dynamic ones. this approach proved to be very successful in the field of radiation detection, where the silicon drift detector (sdd) outperformed other solid-state detectors in terms of noise thanks to properly-shaped electric fields, which force the collection of the generated charge (across a wide depleted detection area) to drift towards a miniaturized anode [ ] . another drawback of shrinking the electrode area is the increase in the access impedance in the case of ac-coupled sensing, both in solid-state [ ] and biological applications, such as impedance flow cytometry [ ] . another approach to reduce the sensor capacitance is the repartition of a large sensor area into n smaller ones, each one connected to an independent readout chain. in this way, the individual capacitance of each sensor is reduced by a factor of n. if the output signals of all n parallel chains are then summed, the signal will increase by a factor of n (i.e., it will recover a value equivalent to the case of a large area), while the noise (summed in power, since it is uncorrelated among chains) will only increase by √ n, thus leading to an improvement of the snr of √ n. for example, this has been used in the readout of silicon photo-multiplers (sipm) [ ] . this interesting solution implies a growth in power and area occupation due to the multiplication of the readout chains. furthermore, it is important to control the layout of connection between the sensor and the front-end: while the sensors capacitance decreases by a factor of n, the parasitic capacitance of the interconnection typically does not scale down and can become the dominant term. finally, in order to fully profit from miniaturization and to preserve the detection performance by minimizing the length (and parasitics) of the interconnection, the transducers and the readout chip should be closely coupled and, when possible, monolithically integrated. from the noise point of view, the micro-sized sensor-on-chip solution is optimal [ ] . figure shows a broad range of bio-sensing technologies that have been integrated on cmos platforms: electrical and electrochemical, photonic, magnetic, micromechanical and nano-fabricated. their position along the bottom horizontal axis qualitatively highlights the increasing technological complexity of integration on a cmos substrate. rf electronics and on-chip coils even enable single-chip nmr and electron spin resonance detectors [ ] , targeting, in particular, point-of-care diagnostics [ ] . several efforts have been undertaken to improve the compatibility of bio-sensing with cmos platforms: one example is the reduction in the temperature of fabrication of silicon nano wires (down to • c), thus making them compatible with the standard cmos process [ ] . field of radiation detection, where the silicon drift detector (sdd) outperformed other solid-state detectors in terms of noise thanks to properly-shaped electric fields, which force the collection of the generated charge (across a wide depleted detection area) to drift towards a miniaturized anode [ ] . another drawback of shrinking the electrode area is the increase in the access impedance in the case of ac-coupled sensing, both in solid-state [ ] and biological applications, such as impedance flow cytometry [ ] . another approach to reduce the sensor capacitance is the repartition of a large sensor area into n smaller ones, each one connected to an independent readout chain. in this way, the individual capacitance of each sensor is reduced by a factor of n. if the output signals of all n parallel chains are then summed, the signal will increase by a factor of n (i.e., it will recover a value equivalent to the case of a large area), while the noise (summed in power, since it is uncorrelated among chains) will only increase by √n, thus leading to an improvement of the snr of √n. for example, this has been used in the readout of silicon photo-multiplers (sipm) [ ] . this interesting solution implies a growth in power and area occupation due to the multiplication of the readout chains. furthermore, it is important to control the layout of connection between the sensor and the front-end: while the sensors capacitance decreases by a factor of n, the parasitic capacitance of the interconnection typically does not scale down and can become the dominant term. finally, in order to fully profit from miniaturization and to preserve the detection performance by minimizing the length (and parasitics) of the interconnection, the transducers and the readout chip should be closely coupled and, when possible, monolithically integrated. from the noise point of view, the micro-sized sensor-on-chip solution is optimal [ ] . figure shows a broad range of biosensing technologies that have been integrated on cmos platforms: electrical and electrochemical, photonic, magnetic, micromechanical and nano-fabricated. their position along the bottom horizontal axis qualitatively highlights the increasing technological complexity of integration on a cmos substrate. rf electronics and on-chip coils even enable single-chip nmr and electron spin resonance detectors [ ] , targeting, in particular, point-of-care diagnostics [ ] . several efforts have been undertaken to improve the compatibility of bio-sensing with cmos platforms: one example is the reduction in the temperature of fabrication of silicon nano wires (down to °c), thus making them compatible with the standard cmos process [ ] . in the case of electrochemical sensing, the "electrode-on-chip" solution is apparently straightforward. the highest metal layer, commonly exposed to realize the bonding pads, can be used for patterning sensing electrodes. while this is simple in dry applications [ ] , it is more complicated in the case of bio-chemical sensing in liquid for two reasons: (i) materials and (ii) morphology. in fact, the metals commonly adopted to realize this metallization (aluminum and copper) are not suitable for electrochemical sensing, where noble metals (such as gold, silver and platinum) are preferred in the case of electrochemical sensing, the "electrode-on-chip" solution is apparently straightforward. the highest metal layer, commonly exposed to realize the bonding pads, can be used for patterning sensing electrodes. while this is simple in dry applications [ ] , it is more complicated in the case of bio-chemical sensing in liquid for two reasons: (i) materials and (ii) morphology. in fact, the metals commonly adopted to realize this metallization (aluminum and copper) are not suitable for electrochemical sensing, where noble metals (such as gold, silver and platinum) are preferred thanks to a stable (i.e., minimally reactive) behavior. consequently, post-cmos metallization is performed to electrochemically grow the proper metal on top of the working electrode. the morphology of the pad presents two additional issues: the roughness of the inner surface (even when avoiding the diamond of vias, visible in figure a , typically realized to strengthen the stack of metal layer for wire bonding) is not negligible (~ nm) and this inner area is surrounded by a µm-tall shoulder due to the lifting of the top passivation layer (sin) on the metal. both issues can be solved, for instance, by evaporating a sensing area that extends on the side of the pad (on the flat nitride capping) as recently proposed [ ] . sensors , , of thanks to a stable (i.e., minimally reactive) behavior. consequently, post-cmos metallization is performed to electrochemically grow the proper metal on top of the working electrode. the morphology of the pad presents two additional issues: the roughness of the inner surface (even when avoiding the diamond of vias, visible in figure a , typically realized to strengthen the stack of metal layer for wire bonding) is not negligible (~ nm) and this inner area is surrounded by a µm-tall shoulder due to the lifting of the top passivation layer (sin) on the metal. both issues can be solved, for instance, by evaporating a sensing area that extends on the side of the pad (on the flat nitride capping) as recently proposed [ ] . to quantify the improvement in noise performance enabled by on-chip sensing, different figures of merit (fom) can be adopted. for instance, in capacitive resolution, a Δc-fom can be defined at the input-referred noise spectral density in zf/√hz, normalized on the amplitude of the forcing ac voltage signal. for dry sensing (detection of micro-particles in the air), the Δc-fom improved from zf·v/√hz of a discrete-component implementation to zf·v/√hz of a monolithic integration [ ] . other figures of merit can include the power dissipation (tens to hundreds of mw for this application), area occupation, maximum operating frequency and detection bandwidth [ ] . for measurements in liquid, we can consider the current resolution: in nano-pore current sensing, the current resolution (for a khz bandwidth) improves from . parms of the state-of-the-art discrete amplifier (with a miniaturized and cooled head-stage and integrator front-end with periodic reset) down to . parms with an integrated amplifier and on-chip electrode [ ] . taking as an example cmos capacitive sensors, a steady improvement of the Δc-fom down to zf·v/√hz has been observed in the last decade [ , ] , where the capacitance resolution has moved from the attofarad to the zeptofarad domains, achieved by miniaturization (parasitics reductions) and differential sensing [ ] in the mhz range and leveraging resonance in the ghz range [ ] . beyond the circuital and morphological challenges illustrated above, a pervasive diffusion of asics for biochemical detection is still hampered by additional technological challenges which include packaging, patternable passivation and the fluidic interface with the off-chip world. different from all other application areas of microelectronics, here packaging has to protect the chip and its electrical interconnection (such as bonding wires) from environmental agents such as dust and humidity, while allowing the liquid sample to contact only specific areas of the chip with a spatial accuracy down to fractions of the pad size, i.e., to tens of micrometers ( figure ). packaging has to be reliable (to avoid leakage and aging during the device lifetime), bio-compatible (to avoid contamination of the biological sample) and cost-effective (since a very sophisticated packaging easily becomes the most expensive step of fabrication, as witnessed, for instance, in mems [ ] and silicon photonics [ ] ). coupling a cmos asic to a microfluidic device is often complicated by the difference of materials (silicon vs. plastics, different metals) and disparity of sizes (mm-sized cmos to quantify the improvement in noise performance enabled by on-chip sensing, different figures of merit (fom) can be adopted. for instance, in capacitive resolution, a ∆c-fom can be defined at the input-referred noise spectral density in zf/ hz, normalized on the amplitude of the forcing ac voltage signal. for dry sensing (detection of micro-particles in the air), the ∆c-fom improved from zf·v/ hz of a discrete-component implementation to zf·v/ √ hz of a monolithic integration [ ] . other figures of merit can include the power dissipation (tens to hundreds of mw for this application), area occupation, maximum operating frequency and detection bandwidth [ ] . for measurements in liquid, we can consider the current resolution: in nano-pore current sensing, the current resolution (for a khz bandwidth) improves from . pa rms of the state-of-the-art discrete amplifier (with a miniaturized and cooled head-stage and integrator front-end with periodic reset) down to . pa rms with an integrated amplifier and on-chip electrode [ ] . taking as an example cmos capacitive sensors, a steady improvement of the ∆c-fom down to zf·v/ hz has been observed in the last decade [ , ] , where the capacitance resolution has moved from the attofarad to the zeptofarad domains, achieved by miniaturization (parasitics reductions) and differential sensing [ ] in the mhz range and leveraging resonance in the ghz range [ ] . beyond the circuital and morphological challenges illustrated above, a pervasive diffusion of asics for biochemical detection is still hampered by additional technological challenges which include packaging, patternable passivation and the fluidic interface with the off-chip world. different from all other application areas of microelectronics, here packaging has to protect the chip and its electrical interconnection (such as bonding wires) from environmental agents such as dust and humidity, while allowing the liquid sample to contact only specific areas of the chip with a spatial accuracy down to fractions of the pad size, i.e., to tens of micrometers ( figure ). packaging has to be reliable (to avoid leakage and aging during the device lifetime), bio-compatible (to avoid contamination of the biological sample) and cost-effective (since a very sophisticated packaging easily becomes the most expensive step of fabrication, as witnessed, for instance, in mems [ ] and silicon photonics [ ] ). coupling a cmos asic to a microfluidic device is often complicated by the difference of materials (silicon vs. plastics, different metals) and disparity of sizes (mm-sized cmos chips vs. cm-sized fluidics) [ ] . a high-density placement of electrical and fluidic interconnect is typically achieved with a photo-patternable material deposited from the liquid phase, conformally covering bonding wires, which is cured and selectively removed to expose only the sensing electrode. the main challenge of this powerful approach lies in the preservation of the electrode surface cleanness (at the atomic level since the electrical double layer interfacial capacitance depends on the first ionic layer) after dry or wet etching of the passivation. a systematic review of the possible coupling strategies is reported here [ ] . sophisticated examples include both clean-room based post-cmos approaches, achieving, for instance, planarization, gap filling of the cmos chip embedded in a die carrier and coupled to taper joints [ ] , as well as lab-based solutions such as direct writing of a sacrificial channel [ ] . sensors , , of chips vs. cm-sized fluidics) [ ] . a high-density placement of electrical and fluidic interconnect is typically achieved with a photo-patternable material deposited from the liquid phase, conformally covering bonding wires, which is cured and selectively removed to expose only the sensing electrode. the main challenge of this powerful approach lies in the preservation of the electrode surface cleanness (at the atomic level since the electrical double layer interfacial capacitance depends on the first ionic layer) after dry or wet etching of the passivation. a systematic review of the possible coupling strategies is reported here [ ] . sophisticated examples include both clean-room based post-cmos approaches, achieving, for instance, planarization, gap filling of the cmos chip embedded in a die carrier and coupled to taper joints [ ] , as well as lab-based solutions such as direct writing of a sacrificial channel [ ] . in order to achieve cost-effectiveness, all these challenges should be addressed in a way compatible (in terms of production time and scalability) with large-volume industrial manufacturing. for this reason, polydimethylsiloxane (pdms), which is the workhorse elastomer solution for laboratory-grade microfluidics, fabricated by means of replica molding and which offers excellent bio-compatibility, can hardly become a well-established industrial solution due to the cost and delicate steps in the fabrication process such as degassing and peel-off. other polymers offering similar rapid prototyping versatility but a better resistance to chemicals and operation at high pressures have been identified [ ] . additive manufacturing ( d printing of plastic filaments or resins) [ ] , the micro-milling of rigid plastics (such as polycarbonate and pmma) and laser ablation are all promising techniques for the fabrication of microchannels that, unfortunately, are all characterized by the sequential operation of a single machining head, not easily scalable to mass production. an emerging solution that can better suit the industrial manufacturability of biochips is represented by photo-patternable dry resists, such as sinr [ ] . finally, the standardization of the design flow and of fluidic components and interconnects (similar to that of an electronic design) is still a chimera in this field and should be pursued in order to achieve market success in genomics and real-time, as well as point-of-care diagnostics, with the same effort that was devoted to the integration of the sample preparation on-chip. in order to achieve cost-effectiveness, all these challenges should be addressed in a way compatible (in terms of production time and scalability) with large-volume industrial manufacturing. for this reason, polydimethylsiloxane (pdms), which is the workhorse elastomer solution for laboratory-grade microfluidics, fabricated by means of replica molding and which offers excellent bio-compatibility, can hardly become a well-established industrial solution due to the cost and delicate steps in the fabrication process such as degassing and peel-off. other polymers offering similar rapid prototyping versatility but a better resistance to chemicals and operation at high pressures have been identified [ ] . additive manufacturing ( d printing of plastic filaments or resins) [ ] , the micro-milling of rigid plastics (such as polycarbonate and pmma) and laser ablation are all promising techniques for the fabrication of microchannels that, unfortunately, are all characterized by the sequential operation of a single machining head, not easily scalable to mass production. an emerging solution that can better suit the industrial manufacturability of biochips is represented by photo-patternable dry resists, such as sinr [ ] . finally, the standardization of the design flow and of fluidic components and interconnects (similar to that of an electronic design) is still a chimera in this field and should be pursued in order to achieve market success in genomics and real-time, as well as point-of-care diagnostics, with the same effort that was devoted to the integration of the sample preparation on-chip. when the target molecule in the patient is not accessible from a fluid sample, nuclear imaging techniques with molecular selectivity are needed. the combination of different imaging techniques, offering complementary information, is becoming a consolidated trend in radiography. typically, molecule-specific techniques (pet and spect) are combined with those providing anatomic information (such as ct and mri) in order to register (i.e., align/overlay) both images (simultaneously acquired) and correctly locate the pathology in the body, as illustrated in figure . when the target molecule in the patient is not accessible from a fluid sample, nuclear imaging techniques with molecular selectivity are needed. the combination of different imaging techniques, offering complementary information, is becoming a consolidated trend in radiography. typically, molecule-specific techniques (pet and spect) are combined with those providing anatomic information (such as ct and mri) in order to register (i.e., align/overlay) both images (simultaneously acquired) and correctly locate the pathology in the body, as illustrated in figure . the main challenge posed by simultaneous imaging is clearly the mutual compatibility between the two scanning systems. secondary challenges are the complexity and cost, to be compared with the clinical advantages (i.e., benefits for patients and clinicians, especially in terms of improved diagnostics and insight). today, the adoption of integrated circuits is limited to the front-end of the acquisition chain in the gamma cameras pixels. we foresee that future breakthroughs in this field can be enabled by augmenting the range of functions implemented in silicon. pet is a nuclear imaging technique that relies on the emission of a pair of counter-propagating gamma photons (at an energy of kev), generated by the annihilation of a positron with an electron [ ] . the positron is produced by the decay of a radiotracer and this recombination takes places in the body within a short distance (~ mm) from the radioligand. the major trade-off governing the performance of pet is between measurement time, sensitivity and injected activity [ ] . there are two main development avenues. one is the extension of the axial field of view in order to improve the solid angle capturing gamma photons. recently, the first results of a total-body pet have been reported [ ] . the explorer systems feature an axial field of view of cm, extending along the whole body, and it is fully covered by , detection channels producing ~ tb of data per scan. thanks to a -fold increase in the signal with respect to traditional clinical scanners (capturing only a few percent of the emitted photons), the same snr can be achieved by reducing the activity injected into the patient or by reducing the measurement time down to seconds. the latter result would lead to an unprecedented capability of tracking fast dynamics. clearly, asics are pivotal in handling tens of thousands of channels and reducing the burden of data processing by implementing data preprocessing on-chip. the main challenge posed by simultaneous imaging is clearly the mutual compatibility between the two scanning systems. secondary challenges are the complexity and cost, to be compared with the clinical advantages (i.e., benefits for patients and clinicians, especially in terms of improved diagnostics and insight). today, the adoption of integrated circuits is limited to the front-end of the acquisition chain in the gamma cameras pixels. we foresee that future breakthroughs in this field can be enabled by augmenting the range of functions implemented in silicon. pet is a nuclear imaging technique that relies on the emission of a pair of counter-propagating gamma photons (at an energy of kev), generated by the annihilation of a positron with an electron [ ] . the positron is produced by the decay of a radiotracer and this recombination takes places in the body within a short distance (~ mm) from the radioligand. the major trade-off governing the performance of pet is between measurement time, sensitivity and injected activity [ ] . there are two main development avenues. one is the extension of the axial field of view in order to improve the solid angle capturing gamma photons. recently, the first results of a total-body pet have been reported [ ] . the explorer systems feature an axial field of view of cm, extending along the whole body, and it is fully covered by , detection channels producing~ tb of data per scan. thanks to a -fold increase in the signal with respect to traditional clinical scanners (capturing only a few percent of the emitted photons), the same snr can be achieved by reducing the activity injected into the patient or by reducing the measurement time down to seconds. the latter result would lead to an unprecedented capability of tracking fast dynamics. clearly, asics are pivotal in handling tens of thousands of channels and reducing the burden of data processing by implementing data pre-processing on-chip. the second development direction is the use of the time-of-flight (tof) information to improve the spatial resolution, sustained by the push to improve the timing resolution of photodetectors and readout electronics. a " ps challenge" has been launched [ ] in order to stimulate step-changes in scintillator materials and detection approaches (looking, for instance, to prompt emissions), as well as in electronics [ ] . both perspectives clearly impact on the design of asics for pet: the first in terms of the number of channels and scalability and the second in terms of the intrinsic timing performance (currently in the~ ps range). if we take the coincidence time resolution (ctr fwhm ) of a full detection system as a figure of merit to compare asics in terms of the timing performance (to be compared with similar scintillator and photodetector conditions), we can observe a continuous improvement trend. considering lyso crystals and × mm pixels, the triroc asic ( [ ] ) achieved ps, tofpet ( ) ps and stic ( [ ] ) ps. for smaller pixels ( × mm ) flextot v reached ps and nino ( ) ps [ ] . spect differs from pet in that it does not rely on proton annihilation: the radiotracer decays, directly emitting gamma-rays. in this case, a collimator is needed to select the trajectories of the photons impinging of the gamma camera. tomographic images are then reconstructed from the planar projections imaged by the gamma cameras surrounding the patient. different radiotracers can be employed, even simultaneously to map different molecules, if the energy resolution of the detector allows the discrimination of the photopeaks. the most commonly adopted is a metastable isotope of technetium ( m tc) which has a line at kev. photons at such an energy are not absorbed within the thin silicon wafers and, thus, direct detection cannot take place. instead, an indirect detection approach is adopted. figure illustrates the typical architecture of a solid-state gamma camera. in particular, this scheme refers to the insert system which will be considered as a reference design. each individual gamma photon is absorbed in the scintillator (here a csi:tl crystal of mm thickness) producing a handful of visible photons, collected by the photodetectors placed at the bottom of the crystal. given the limited number of photons, photodetectors with internal multiplication are commonly used. previously, photo-multiplier tubes (pmt) were employed, but they are being systematically replaced by their solid-state equivalent: silicon photo-multiplers (sipm). they offer a much higher compactness and, of utmost importance for mri compatibility, much better compliance with magnetic fields. sipms are typically organized into tiles (here × pixels of mm side in rgb-hd technology by fondazione bruno kessler, italy). the second development direction is the use of the time-of-flight (tof) information to improve the spatial resolution, sustained by the push to improve the timing resolution of photodetectors and readout electronics. a " ps challenge" has been launched [ ] in order to stimulate step-changes in scintillator materials and detection approaches (looking, for instance, to prompt emissions), as well as in electronics [ ] . both perspectives clearly impact on the design of asics for pet: the first in terms of the number of channels and scalability and the second in terms of the intrinsic timing performance (currently in the ~ ps range). if we take the coincidence time resolution (ctrfwhm) of a full detection system as a figure of merit to compare asics in terms of the timing performance (to be compared with similar scintillator and photodetector conditions), we can observe a continuous improvement trend. considering lyso crystals and × mm pixels, the triroc asic ( [ ] ) achieved ps, tofpet ( ) ps and stic ( [ ] ) ps. for smaller pixels ( × mm ) flextot v reached ps and nino ( ) ps [ ] . spect differs from pet in that it does not rely on proton annihilation: the radiotracer decays, directly emitting gamma-rays. in this case, a collimator is needed to select the trajectories of the photons impinging of the gamma camera. tomographic images are then reconstructed from the planar projections imaged by the gamma cameras surrounding the patient. different radiotracers can be employed, even simultaneously to map different molecules, if the energy resolution of the detector allows the discrimination of the photopeaks. the most commonly adopted is a metastable isotope of technetium ( m tc) which has a line at kev. photons at such an energy are not absorbed within the thin silicon wafers and, thus, direct detection cannot take place. instead, an indirect detection approach is adopted. figure illustrates the typical architecture of a solid-state gamma camera. in particular, this scheme refers to the insert system which will be considered as a reference design. each individual gamma photon is absorbed in the scintillator (here a csi:tl crystal of mm thickness) producing a handful of visible photons, collected by the photodetectors placed at the bottom of the crystal. given the limited number of photons, photodetectors with internal multiplication are commonly used. previously, photo-multiplier tubes (pmt) were employed, but they are being systematically replaced by their solid-state equivalent: silicon photo-multiplers (sipm). they offer a much higher compactness and, of utmost importance for mri compatibility, much better compliance with magnetic fields. sipms are typically organized into tiles (here × pixels of mm side in rgb-hd technology by fondazione bruno kessler, italy). figure . architecture of the gamma camera of the insert spect system: the current signals of silicon photo-multiplier (sipm) pixels are read by two asics [ ] , featuring a low-impedance input stage, programmable shaper, peak stretcher and fast comparator to trigger the acquisition of events by the fpga-based daq unit [ ] . the current signal produced from a single sipm can span from the µa to the ma range, with a typical duration in the tens of ns range. given the large capacitance of the photodetector (~ nf), differing from biosensors (typically in the pf range) and sdds (in the sub-pf range), the additional [ ] , featuring a low-impedance input stage, programmable shaper, peak stretcher and fast comparator to trigger the acquisition of events by the fpga-based daq unit [ ] . the current signal produced from a single sipm can span from the µa to the ma range, with a typical duration in the tens of ns range. given the large capacitance of the photodetector (~ nf), differing from biosensors (typically in the pf range) and sdds (in the sub-pf range), the additional parasitic capacitance of the interconnection (in the pf range) is not too critical, and the readout asic can be placed at a reasonable distance on the pcb. in order to grant a low input impedance, bandwidth and stability in these conditions, different topologies can be adopted. in the angus asic [ ] , the weak positive feedback of a themes current conveyor is successfully implemented. sipms are biased at v. the possibility to individually adjust the input potential with a dac allows for the correction of gain mismatch across the channels (typically~ %) and, more importantly, to selectively kill hot pixels affected by fault or large noise (dark counts). the tiles of sipms are typically cooled (here between • c and − • c by refrigerant fluid) to reduce such a noise. the attenuated current pulses are then shaped by a programmable rc filter (~µs time constant), setting also the baseline. a fast discriminator triggers the acquisition of all channels and a peak stretcher allows the external -bit adc to sequentially sample all outputs through a multiplexer. an fpga acquires all the signals (at a rate of~ k frames per second) and transmits them to a laptop through an optical digital bus [ ] . the operation of the insert system is shown in figure a . the spect scanner is placed inside a standard mri scanner, connected to a custom-designed and shielded transceiver coil placed inside the bore of the spect static ring, which contains gamma cameras and the collimator. figure b shows the preclinical version of the scanner [ ] , while figure c shows the clinical prototype [ ] , the only existing mri-compatible sipm-based spect insert for human brain imaging. the main features of the two instruments are summarized in table . sensors , , of parasitic capacitance of the interconnection (in the pf range) is not too critical, and the readout asic can be placed at a reasonable distance on the pcb. in order to grant a low input impedance, bandwidth and stability in these conditions, different topologies can be adopted. in the angus asic [ ] , the weak positive feedback of a themes current conveyor is successfully implemented. sipms are biased at ~ v. the possibility to individually adjust the input potential with a dac allows for the correction of gain mismatch across the channels (typically ~ %) and, more importantly, to selectively kill hot pixels affected by fault or large noise (dark counts). the tiles of sipms are typically cooled (here between °c and − °c by refrigerant fluid) to reduce such a noise. the attenuated current pulses are then shaped by a programmable rc filter (~µs time constant), setting also the baseline. a fast discriminator triggers the acquisition of all channels and a peak stretcher allows the external -bit adc to sequentially sample all outputs through a multiplexer. an fpga acquires all the signals (at a rate of ~ k frames per second) and transmits them to a laptop through an optical digital bus [ ] . the operation of the insert system is shown in figure a . the spect scanner is placed inside a standard mri scanner, connected to a custom-designed and shielded transceiver coil placed inside the bore of the spect static ring, which contains gamma cameras and the collimator. figure b shows the preclinical version of the scanner [ ] , while figure c shows the clinical prototype [ ] , the only existing mri-compatible sipm-based spect insert for human brain imaging. the main features of the two instruments are summarized in table . mutual compatibility between spect and mri electronics entails several critical aspects. in order to reduce the distortion of the magnetic field due to the spect insert, electronic components (free of ferromagnetic metals such as nickel, present in connectors, plating pins and iron cores of inductors) and materials should be carefully selected. in particular, the introduction of metals in the mr bore should be minimized. for instance, collimators are fabricated by laminated layers or powder-epoxy mixtures to avoid solid regions and, thus, reduce the paths for eddy currents. at an electronic level, it is crucial to reduce the irradiation of disturbances from the spect in the regions of the rf spectrum (~ mhz). to minimize the impact of mri on spect electronics, it is important to design special circuit geometries and layouts (avoiding loops and solid ground planes), add filtering on tracks that could pick-up rf interference and apply mri-compatible shielding. the fundamental design guidelines and the results of compatibility tests are reported here [ ] . another direction of development at the system-level is to lighten and simplify the instrument and make it movable, in particular to make it a bed-side scanner. this would avoid the need to bring the patient to the room and might be relevant either during surgery (where intra-operative gamma probes are already used) or to promptly study sudden events such as epileptic seizures and strokes. since the first movable mri has been recently cleared by the fda in the usa (model lucy by hyperfine, targeting stroke), a transportable spect/mri system for the bed-side is foreseeable. the key to make a movable mri system is in the use of low-field (and thus lighter) magnets [ ] . the key to realizing a movable clinical spect is the reduction in the weight/size of the collimator, the detector refrigeration system (in the case of multiplication devices) and the electronics (again an opportunity for microelectronics to reduce the bulkiness and power dissipation in data processing). additionally, the increase in speed by reducing the image-reconstruction time (currently in the hour time-frame, compared to acquisition times of about min) is clearly related to new paradigms in the operation of spect, aiming to achieve quasi "real-time" imaging. one of the major challenges hindering the scaling up of static preclinical spect systems to larger ones (i.e., with a larger field of view) is related to the growth in complexity in terms of the number of channels and signals travelling in the system (especially from a reliability point of view), and in terms of the processing time. one promising way to address both aspects is to shift the processing from the digital domain back to the analog domain, i.e., closer to the front-end. the reduction in the number of output channels can be achieved by using smart algorithms for machine learning (particularly for the estimation of the spatial coordinates of absorption of each gamma-ray photon) based on a partial readout of the crystal and by, for instance, principal component analysis and multiplexing strategies [ ] . so far, they have been demonstrated in software post-processing and in discrete-hardware implementations (such as the decision-tree classification of gamma events embedded in a microcontroller [ ] ), but it is evident that an integrated implementation of such strategies in asics would offer significant benefits in terms of: (i) compactness, (ii) the robustness of signals and reliability, and (iii) processing time, as demonstrated by several emerging examples of hardware acceleration in image processing and machine learning based on neural networks on-chip [ ] [ ] [ ] . in order to increase the robustness of the signals through the long connection from the scanner to the base station placed in the control room, outside of the mri room, and decouple them from electrical interferences, optical fibers are typically employed. in the case of the insert system, a m digital optical daisy chain composed of two rings with nodes each has been implemented. since the operation of powerful digital processing platforms, such as fpgas, inside the bore there can be severe issues of heat dissipation and mutual compatibility, it is possible to envision a tighter combination of readout asics with silicon-photonics transceivers, potentially on the same monolithic silicon platform as the robust analog transmission and direct modulation of thousands of optical signals injected in optical fibers, as recently proposed for high-energy physics [ ] . we have summarized some recent results, development strategies and directions for integrated circuits and electronics for biomedical applications. two apparently distant, but complementary, application areas in non-invasive diagnostics can both significantly profit from the advancements of cmos technology. targeted, yet cross-disciplinary, development of microelectronic designs and integration solutions can consolidate the pivotal role of integrated circuits in bio-sensing. clearly, each application domain poses specific challenges and offers a very different performance of molecular detection: for example, the dynamic range of a micro-impedance sensing chip is - db, while mri can reach db at the expense of size, cost and measurement times that are several orders of magnitude larger. some of the most relevant challenges have been discussed: packaging and the noise/power compromise in micro-analytical devices; scaling to a large number of channels; migration of processing from digital to analog, at least for the reconstruction of the position of the scintillation event; and transition towards transportable systems for medical imaging scanners. the impact of the fabrication cost significantly changes between the two application domains: when considering disposable diagnostic kits (with a production cost in the order of~ $), the fabrication of silicon chips in cmos foundries is economically sustainable only for mass production. instead, when considering medical imaging scanners (with prices in the~m$ range), small-volume and, thus more expensive, asic productions are still acceptable. in conclusion, the current covid- pandemic has raised urgent concerns about diagnostic tools. the possible combination of ct scans of the chest with antibody-based assays for early, accessible and systematic diagnostics of the sars-cov- [ ] is a vivid example of a possible effective combination of complementary diagnostic tools. integrated circuits for particle physics experiments liquid biopsy: a perspective for probing blood for cancer single-cell recording of vesicle release from human neuroblastoma cells using -ch monolithic cmos bioelectronics impedance spectroscopy and electrophysiological imaging of cells with a high-density cmos microelectrode array system low-power and low-noise capacitive sensing ic using opamp sharing technique a low-power current-reuse analog front-end for high-density neural recording implants a . -na ecg amplifier achieving . / . nef/pef using ac-coupled ota-stacking comparative analysis of information rates of simple amplifier topologies an aquatic wireless biosensor for electric organ discharge with an integrated analog front end assessment of analog pulse processor performance for ultra high-rate x-ray spectroscopy toward wireless health monitoring via an analog signal compression-based biosensing platform a low-power high-speed ultra-wideband pulse radio transmission system noise limits of cmos current interfaces for biosensors: a review resonant noise-canceling current front-end for high-resolution impedance sensing design and test at room temperature of the first silicon drift detector with on-chip electronics design guidelines for contactless integrated photonic probes in dense photonic circuits miniaturized impedance flow cytometer: design rules and integrated readout music: an channel readout asic for sipm arrays advances in high-resolution microscale impedance sensors towards low-cost, high-sensitivity point-of-care diagnostics using vco-based esr-on-a-chip detectors integrated circuit technology for next generation point-of-care spectroscopy applications biocompatibility of silicon nanowires: a step towards ic detectors multichannel zf rms resolution cmos monolithic capacitive sensor for counting single micrometer-sized airborne particles on chip integrated nanopore sensing platform with sub-microsecond temporal resolution cmos based capacitive sensors for life science applications: a review note: differential configurations for the mitigation of slow fluctuations limiting the resolution of digital lock-in amplifiers oscillator-based reactance sensors with injection locking for high-throughput flow cytometry using microwave dielectric spectroscopy wafer-level fan-out for high-performance, low-cost packaging of monolithic rf mems/cmos roadmap on silicon photonics lab-on-cmos integration of microfluidics and electrochemical sensors system-on-chip considerations for heterogeneous integration of cmos and fluidic bio-interfaces rapid prototyping polymers for microfluidic devices and high pressure injections d printed microfluidic devices: enablers and barriers microfluidic structures for large-scale manufacture combining photo-patternable materials sensors for positron emission tomography applications total-body pet: maximizing sensitivity to create new opportunities for clinical research and patient care first human imaging studies with the explorer total-body pet scanner* the -ps challenge high-frequency sipm readout advances measured coincidence time resolution limits in tof-pet triroc, a versatile -channel sipm readout asic for time-of-flight pet a silicon photomultiplier readout asic for time-of-flight applications using a new time-of-recovery method a comparative study of the time performance between nino and flextot asics characterization of the detection module of the insert spect/mri clinical system validation and performance assessment of a preclinical sipm-based spect/mri insert clinical sipm-based mri-compatible spect: preliminary characterization spect/mri insert compatibility: assessment, solutions, and design guidelines low-field mri: an mr physics perspective characterization of highly multiplexed monolithic pet / gamma camera detector modules a sipm-based directional gamma-ray spectrometer with embedded machine learning machine learning on-a-chip: a high-performance low-power reusable neuron architecture for artificial neural networks in ecg classifications on-chip sparse learning acceleration with cmos and resistive synaptic devices adaptive neuromorphic systems: recent progress and future directions use of silicon photonics wavelength multiplexing techniques for fast parallel readout in high energy physics covid- diagnostics, tools, and prevention. diagnostics acknowledgments: all the students and technical partners of the insert project (mediso, fondazione bruno kessler, nuclear fields, san raffaele hospital and university college london in particular) are warmly acknowledged for contributing to this -year-long effort. the authors declare no conflict of interest. key: cord- -kck e ry authors: nan title: th annual meeting, neurocritical care society, october – , , vancouver, canada date: - - journal: neurocrit care doi: . /s - - - sha: doc_id: cord_uid: kck e ry nan aging is associated with greater stroke risk and diminished stroke recovery. while the effect of aging on stroke recovery is well defined, the influence of aging on neuronal network activity and its correlation with stroke recovery is poorly understood. to study this, we performed serial whole-cortex imaging of spontaneous and evoked neuronal activity before and after stroke in young and aged mice and correlated those findings to behavioral outcomes. young ( - m, n= ) and aged ( m, n= ) thy -gcamp mice, underwent behavioral assessment and imaging before and , , , and weeks after infarct. infarcts were induced via exposure of somatosensory cortex to a laser ( mw, m) after injection of the photosensitive dye rose bengal. imaging followed placement of plexiglas windows and consisted of awake ( m) and anesthetized sessions ( m) with gcamp excitation via flashing of a nm led and acquisition via an emccd camera ( . hz framerate). somatosensory activation was via forepaw shock ( ma at hz for s x blocks). behavioral response was assessed by quantifying forepaw use during cylinder exploration ( m). aged and young mice exhibited similar baseline contralateral forepaw use (aged . ± . %; young: . ± . %) and evoked somatosensory cort . ± . x - ). whole-brain gcamp flourescence power in delta ( - hz) and infraslow ( . - . hz) ranges was significantly (p< . ) lower at baseline in aged mice. after stroke, aged mice developed greater long-term dependence on the unaffected limb (wk : aged . ± . %; young: . ± . %) - ). -stroke decrement in whole-brain gcamp fluorescence power was observed in aged animals. stroke in aged mice is associated with a greater decrement in local network activation, global mechanisms underlying age-related differences. hypernatremia and hyperchloremia is common after moderate-severe traumatic brain injury (mstbi) from saline resuscitation, osmotherapy administration, fever with insensible losses, limited free water administration, and diabetes insipidus. in isolation, hypernatremia and hyperchloremia are independent predictors of mortality in critically-ill patients; but this association has not been studied in mstbi, or in combination as physiologically occurring in patients. we examined whether hypernatremia and hyperchloremia in combination are independent predictors of in-hospital mortality in mstbi patients. we retrospectively analyzed prospectively collected data of consecutive mstbi patients enrolled in the optimism-study over a -year period. a semi-automated process provided all sodium and chloride values from the index hospitalization. time-weighted-average(twa)-sodium and chloride representing their "burden" over the entire hospitalization were calculated using a published formula. univariate and multivariable logistic regression were applied adjusting for impact-model-variables as validated predictors of mstbi mortality, osmotherapy, icu length-of-stay and ventilatory days. of patients analyzed, ( %) died. unadjusted mortality rates had a dose-response relationship with increasing sodium and chloride ( % for twa-sodium - mmol/l and % for twa-sodium > mmol/l; % for twa-chloride - mmol/l and % for twa-chloride > mmol/l; all p< . ). separately, twa-sodium (per mmol/l increase adjusted-or . ; %ci . - . ) and twachloride (per mmol/l increase adjusted-or . ; % ci . - . ) independently predicted mortality. in combination, however, twa-chloride remained an independent predictor of in-hospital mortality (per mmol/l increase or . , % ci . - . ), while twa-sodium did not (c-statistic . ; hosmer-lemeshow p< . ). to our knowledge, this is the first study to show that when concomitantly adjusting for hyperchloremia and hypernatremia burden, only hyperchloremia is independently associated with early mortality in mstbi. while not proving cause-and-effect, this suggests that hyperchloremia, and not hypernatremia as previously reported, deserves further attention in mstbi. if validated, this may have treatment implications for mstbi patients in the acute care phase. hyperosmolar therapy, with hypertonic sodium chloride (nacl) solution is often used in the treatment of cerebral edema and elevated intracranial pressure. recent reports have demonstrated that in patients with subarachnoid hemorrhage (sah) treated with hypertonic nacl, hyperchloremia is associated with the development of acute kidney injury (aki). we report a trial which compared two hypertonic solutions with different chloride content on the resultant serum chloride concentrations in sah patients. a low chloride hypertonic solution for brain edema (acetate), is a single center, double-blinded, double-dummy, pilot clinical trial comparing bolus dosing of . % nacl versus . % nacl/na-acetate for the treatment of cerebral edema in patients with sah. randomization occurred once patients who received hypertonic treatment for cerebral edema and/or elevated intracranial pressure (icp) developed hyperchloremia (serum cl- group, and to the hypertonic nacl/na-acetate one. the groups were well balanced in terms of severity of the sah, age, gender and risk factors. differerences between the serum chloride and sodium measurements, assessed from randomization to maximum during the icu course, were comparable between the nacl and nacl/acetate groups (cl: . ± . vs. . ± . , p= . ; na: . ± . vs. . ± . , p= . , respectively). nacl/acetate had a more prominent effect on immediate post dose sodium (increase of . ± . vs. . ± . ,p< . ). the rate of aki was lower in the na-acetate group ( . % in the nacl group vs. . % in the na-acetate group, p= . ). hyperchloremia preceded aki in . % of the cases; however, the time interval between hyperchloremia and aki was only a median of . days ). intention to treatment analysis demonstrated that treatment with hypertonic nacl/na-acetate hypertonic versus standard hypertonic nacl solution for patients with mild hyperchloremia, resulted in less events of a -center trials are needed to corroborate these results. up to . million people in the united states are living with physical, cognitive, and psychological sequelae after tbi. patients that sustain a moderate to severe tbi (mstbi) are heavily reliant on caregivers during their inpatient stay and for post-discharge care. there are limited data on how best to support caregivers in their role. the purpose of this study was to develop a checklist based on qualitative data that can be utilized by caregivers and clinicians to re-examine the particular needs of the caregiver at different periods in the acute, subacute, and chronic timeframe. patients with mstbi and their caregivers were recruited from two intensive care units (icus) in one institution to participate in semi-structured interviews at hours, one month, three months, and six months post-injury. transcripts of each interview were analyzed by two investigators who independently coded responses using a predetermined code list adapted from previously identified needs and concerns of other similar populations. based on the particular coded segments, a checklist and a list of strategies were derived to address the needs and concerns of caregivers. a total of patient-caregiver dyads were enrolled from x-y, with interviews completed; interviews with caregivers and with patients. caregiver interviews resulted in unique codes that corresponded to varying caregivers' needs and concerns which were developed into a checklist and list of strategies. the needs and concerns of mstbi caregivers should be assessed over time to provide the support necessary to assist in the care of mstbi survivors. implementation of a checklist, as well as a list of strategies, can allow for tailored interventions that improve the transitions of mstbi survivors from the icu to subacute/chronic care environments. malignant cerebral edema (mce) develops in a subset of those with hemispheric strokes, precipitating neurological deterioration and death if decompressive hemicraniectomy (dhc) is not performed in a timely manner. however, prediction of which patients will develop mce is imprecise based on baseline clinical and radiographic features imaging quantifies development of cerebral edema. we employ a recurrent neural network that learns from serial clinical and imaging data to enhance early prediction of mce. we identified patients with hemispheric stroke who had nihss and ct scans performed at baseline automated algorithm; midline shift (mls) was measured at the level of the septum pellucidum. we trained a recurrent neural network that incorporates sequential data and compared its performance to those of traditional models. we tried to maximize sensitivity for predicting mce (dhc or death) while optimizing prediction of those not requiring dhc (negative predictive value, npv). nine patients required dhc or died from mce. a linear classifier incorporating age, baseline nihss, and serum glucose had high npv ( %) but only % sensitivity for mce. a probabilistic gaussian mixed model (gmm) improved sensitivity to %. incorporating -hour nihss into gmm improved prediction (sensitivity %, npv %). the neural network was able to predict all cases of surgery and all of those not requiring surgery with % accuracy prediction. recurrent neural networks incorporating sequential clinical and imaging data from the first -hours after stroke may enhance our ability to predict which patients will need dhc. our promising pilot evaluation of this approach study requires validation in larger external stroke cohorts. aneurysmal subarachnoid hemorrhage(sah) survivors live with long term residual physical and cognitive disability. we studied whether neuromuscular electrical stimulation(nmes) and high protein supplementation(hpro) in the first two weeks after sah could preserve neuromotor and cognitive function as compared to standard of care(soc) for nutrition and mobilization. sah subjects with a hunt hess(hh) grade> , assigned to soc or nmes+hpro. nmes was delivered to bilateral quadriceps and gastrocnemius muscles daily during two minute sessions along with hpro(goal: . g/kg/day) between post bleed day(pbd) and . primary endpoint was atrophy in the quadriceps muscle as measured by the percentage difference in the cross sectional area from baseline to pbd on ct scan. all subjects underwent serial assessments of physical(short performance physical battery,sppb) cognitive(montreal cognitive assessment scale,moca) and global functional recovery(modified rankin scale,mrs) at pbd , , and . twenty-five subjects(soc= ,nmes+hpro= ) were enrolled between december and january with no between group differences in baseline characteristics( years old, % women, % hh> ). median duration of interventions was days(range - ) completing % of nmes sessions and % of goal protein intake. no difference in caloric intake between groups, but hpro+nmes group received more protein( . +/- . g/kg/d v . +/- . g/kg/d,p< . ). muscle atrophy at pbd was less in nmes+hpro group( . +/- . % vs . +/- . % ,p= . ). on univariate analysis, higher atrophy was correlated with lower daily protein intake (r=- . ,p= . ); and worse month moca (r=- . , p= . ),sppb(r=- . ,p= . ) and mrs(r= . ,p= . ). nmes+hpro subjects performed better on sppb(p= . ), were observed to have a lower mrs(p= . ) and obtained a higher moca(p= . ) than soc at pbd . nmes+hpro may reduce acute muscle wasting in lower extremities with a lasting benefit on recovery after sah. to better understand whether nmes and/or hpro are responsible for observed benefits, a larger, multicenter study is underway. increasing authorization rates for organ donation is the best way to grow the number of organs available for life-saving transplants. in order to improve our authorization rates and thereby provide more organs for life-saving transplants, our organ procurement organization (opo) partnered with donor hospitals to -led donation conversations and intensified the focus on a collaborative donation process. ned in the the opo during the authorization process by providing a timely notification of a potential donor and by work together on the timing of the donation discussion. the overall authorization rate has improved from % in to % currently. during this time frame, --led conversations has been compelling and a significant factor in improving authorization rates. equally impactful to improved authorization rates has been a % increase in cases involving a collaborative donation process (measured by timely referral and collaborative mention of donation). developing a strong partnership between an opo and a donor hospital is paramount to a successful donation process. critical factors such as timely referral notification and collaboration regarding the timing of the donation discussion can positively influence authorization outcomes. moreover, we -led donation conversations will lead to further increases in authorization which results in more lives saved through donation. quantitative eeg analysis is one part of multimodal monitoring in the intensive care unit due to high temporal resolution and ease of deployment. previously we have shown that dynamical properties of eeg signals can be used to differentiate focal vs. diffuse causes of coma (kafashan et al., ) , and that the intrinsic reactivity of eeg signals -a measure of responsiveness of the eeg to endogenously rare events -correlates with gcs score (inri, khanmohammadi et al., ) . here, we explore the possibility of localizing brain lesions using these dynamical features of eeg signals. we collected retrospective data from comatose patients (gcs< ) defined to have a focal injury. the patients underwent eeg recordings and imaging for routine purposes at barnes-jewish hospital nnicu. index (inri) , which consists of identifying intrinsic events, obtaining brain-state trajectories, and quantifying brain-state trajectories. we then used a neural network-based classifier to map the inri to lesion location using supervised learning paradigms with cross-validation. we used imaging to identify anatomical location of lesions and project them to a two-dimensional headmap. we trained a neural-network classifier to predict d lesion location from the inri dynamics of each eeg channel. we then assessed the correlation between predicted location and actual location using a cross-validation protocol. predicted locations significantly correlated with injury location (r> . ) when compared to correlations with randomly selected patients (r~ ). the results point to a systematic change in underlying neuronal-dynamics induced by brain lesions, that was captured through eeg dynamics and the concept of intrinsic reactivity. here we developed and evaluated a framework to localize brain injury through novel analysis of eeg dynamics. the results here, together with our previous work, suggest brain injuries can be detected and localized using eeg recordings. to examine whether changes in intracranial pressure (icp) waveform morphologies can be used as a biomarker for early detection of ventriculitis. of consecutive patients enrolled prospectively in a hemorrhage outcomes study from to , ( %) patients required external ventricular drainage (evd). only the culture-positive ventriculitis seen in ( % of all evds) patients were included in current analysis. based on our es per week, and additionally if infection was suspected. evds were left open for drainage, with icp monitored hourly by clamping. using wavelet analysis, we extracted uninterrupted segments of icp waveforms. we extracted dominant-pulses from continuous high-resolution data using morphological clustering analysis of icp pulse (mocaip). then we applied hierarchical k-means clustering using dynamic time warping distance to obtain morphologically similar groupings. we applied a top-down approach to split the clusters further, which stops when the mean distance of the waveforms to the centroid is less than a pre-clusters and further-split clusters (when equipoise existed) were categorized for broad comparison by clinician consensus. we extracted , dominant pulses from . hours of evd data. , pulses ( . %) occurred before positive culture, , pulses ( . %) were during culture positivity, and , pulses ( . %) occurred after clinical diagnosis was made. k-means identified clusters, which were further grouped into meta-clusters: tri/biphasic (green), single-peak (yellow) and artifactual (red) waveforms. . % of dominant pulses were tri/biphasic before ventriculitis, which reduced to . % during and . % after (p< . ). one day before the first positive cultures were collected, the distribution of meta-clusters changed to include more single-peak and artifactual icp waveforms (p< . ). the distribution of icp waveform morphology changes significantly prior to the clinical diagnosis of ventriculitis, and may be a potential biomarker. inducing normothermia with temperature modulating devices (tmds) is often associated with significant shivering. we tested the ability of a novel transnasal tmd to induce and maintain normothermia with minimal shivering in endotracheally intubated (et) cerebrovascular patients. single center study utilizing coolstat transnasal cooling device to achieve core temperature reduction by inducing an evaporative cooling energy exchange in the turbinates and upper airway thru a high flow of dehumidified air into the nasal cavity and out the mouth. primary goal was the ability to induce normothermia(t<= . c) within hours in et patients with fever(t>= . c) refractory to acetaminophen. continuous temperature measurements were obtained from tympanic and core(esophageal or bladder) temperature sensors. safety assessments included continuous monitoring for hypertension, tachycardia, and raised icp(when monitored). ent evaluations monitored for any device related nasal mucosal injury. shivering was assessed every minutes using the bedside shivering assessment scale(bsas). duration of device use was limited to hours, as regulated by the e care for temperature management. ten subjects(median age: years, bmi: . kg/m , %men) were enrolled with normothermia achieved in % of subjects. one subject did not achieve normothermia and was later refractory to other tmds. median baseline temperature was . +/- . c, with a reduction noted by hours( . +/- . v. . +/- . , p< . ) and sustained at hours( . +/- . v . +/- . , p= . ). time to normothermia was . +/- . hours. the median bsas was (range: - ) with only episodes necessitating meperidine across hours of study monitoring. no treatment was discontinued due to safety concerns. ent evaluations noted no device related adverse findings. inducing normothermia with a novel transnasal tmd appears to be safe, feasible and not associated with significant shivering. a multicenter trial testing the ability to maintain normothermia for hours is currently underway. traumatic coma is thought to be caused by disruption of the subcortical ascending arousal network (aan). this hypothesis has not yet been tested because tools to map aan connectivity in living humans have only recently become available. we implemented high angular resolution diffusion imaging (hardi) on an mri scanner in the intensive care unit to determine whether patients presenting with traumatic coma have disrupted aan connectivity. we performed high angular resolution diffusion imaging (hardi) in patients with acute severe traumatic brain injury who were comatose on admission and in matched controls. we used probabilistic tractography to measure the connectivity probability (cp) of aan axonal pathways linking the brainstem tegmentum to the hypothalamus, thalamus and basal forebrain. to assess the spatial specificity of cp differences between patients and controls, we also measured cp within four subcortical pathways outside the aan. compared to controls, patients showed a reduction in aan pathways connecting the brainstem tegmentum to a region of interest encompassing the hypothalamus, thalamus, and basal forebrain (patients: median . , iqr [ . , . ] controls: . [ . , . ], p = . ). examining each pathway individually, brainstem-hypothalamus and brainstem-thalamus cps (pc < . ), but not brainstemforebrain cp (pc = . ), were significantly reduced in patients. only one subcortical pathway outside the aan showed reduced cp in patients. we provide initial evidence for the reduced integrity of axonal pathways linking the brainstem tegmentum to the hypothalamus and thalamus in patients presenting with traumatic coma. our findings support current conceptual models of coma as being caused by subcortical aan injury. aan connectivity mapping provides an opportunity to advance the study of human coma and consciousness. limited knowledge about the physiology underlying coma recovery has decreased clinicians' ability to identify patients likely to benefit from continued intensive therapy. machine learning using quantitative eeg (qeeg) has shown potential to improve outcome prediction in cardiac arrest, but the relationship between qeeg trends and coma recovery had limited evaluation in large multicenter studies. seven hospitals contributed clinical and eeg data from comatose adult subjects with cardiac arrest who underwent continuous eeg and targeted temperature management. qeeg features evaluated included background frequency, burst-suppression ratio(> %), epileptiform discharges, and entropy. we utilized random forests to predict good (cpc - ) vs. poor (cpc - ) outcome at -months. model performance was evaluated using the auc at h intervals up to h. we analyzed , hours of eeg (+ tb) for , subjects ( good outcomes). unfavorable eeg features were common in subjects with good or poor outcomes (epileptiform discharges: %, % and burst-suppression: %, %, respectively). epileptiform discharge frequency peaked after rewarming in subjects with good outcome ( spikes/min at h), but continued increasing during cooling and rewarming for those with poor outcome ( - spikes/min from h- h). shannon entropy was always higher in subjects with good outcome. burst-suppression strongly predicted outcome for all centers but during different times, while epileptiform discharges predicted outcomes in five centers, entropy in three, and alpha-background in only one. outcome prediction was best with qeeg during cooling rather than after rewarming (auc . vs. . at h and h, p< . ). maximal auc at h for individual centers ranged from . - . . early qeeg trends carry useful information for coma recovery prediction, but marked heterogeneity in qeeg trends across centers can limit performance and reproducibility of machine learning prognostication algorithms. coexistence of favorable and unfavorable qeeg features in the same patient is common, suggesting that generalizable models for coma recovery prediction must leverage temporal trends. human consciousness depends on ascending projections from the brainstem. brainstem lesion mapping studies have identified a coma-specific sub-region of the dorsolateral pontine tegmentum. however, loss of consciousness (loc) can also occur following injury to cortical regions remote from the brainstem, a phenomenon that commonly occurs after penetrating head trauma but remains poorly understood. andexanet alfa has been shown to reduce anti-factor xa activity however outcome studies are lacking. we compare the efficacy of four-facto -pcc) vs andexanet in patients with factor xa inhibitor related bleeding. retrospective study was performed january to march , including patients with factor xa inhibitor related bleeding of whom wer -pcc vs treated with andexanet. outcome was analyzed using glasgow outcome scale (gos) at discharge, presented as good (score - ) and poor ( - ); length of stay (los) and invariables, and t-test for continuous variables. -pcc or andexanet were included in the study. bleeding source --pcc; vs andexanet cases, % of total -pcc n= , andexanet n= ) and trauma ( -pcc -pcc group was . d vs . d in the andexanet group; icu stay corresponded to . vs . days, respectively. outcomes evaluated through gos did not differ -pcc group vs % in andexanet group, -pcc group vs . % on andexanet group, p= ). unexpectedly, in-hospital mortality was higher on andexanet group -pcc group ( . %); with a similar trend observed in the cns subgroup. -pcc as a factor xa inhibitor related bleeding reversal agent was as effective as andexanet based on outcome scale, constituting an essential option for hemostatic control as cost differences can limit the use of andexanet. the mechanism by which early administration of tranexamic acid (txa) reduces mortality in traumatic brain injury (tbi) is poorly understood. in-vitro models suggest the glycocalyx is preserved with early txa administration, indicating that txa may inhibit glycocalyx breakdown. we hypothesized that early txa administration would result in vascular endothelial preservation as evidenced by lower levels of thrombomodulin, syndecan- , icam, and vcam. we analyzed a subset of subjects from the prehospital txa for tbi trial, which examined the efficacy and safety of prehospital administration of txa compared to placebo in patients with moderate or severe tbi who were not in shock. blood samples were collected upon admission and at hrs. glycocalyx breakdown markers were quantified using a luminex analyte platform. clinical variables were compared using wilcoxon rank-sum tests for non-parametric continuous data and chitests for categorical data. differences in median marker levels were evaluated using t-tests performed on log-transformed variables. significance was set at . . data from patients [placebo (n= ), txa (n= )] were analyzed. groups were well-matched for age, sex, injury mechanism, admission injury severity score, head abbreviated injury score, and presence of intracranial hemorrhage (ich) on admission ct. no differences were observed in any median marker levels on admission or at hours. however, admission levels of syndecan- in patients with ich (n= ) who received txa were lower than those in the placebo group ( . pg/ml [ . - . ] v. . pg/ml [ . - . ], p= . ). no differences in thrombomodulin, icam, or vcam levels were detected at either timepoint in the ich subgroup. administration of txa early after injury may attenuate endothelial release of syndecan- in patients with moderate or severe tbi and ich, potentially suggesting a selective role for txa in endothelial gl despite a rapid increase in the use of the oral factor xa inhibitors rivaroxaban and apixaban over recent years, there remains no standard management for associated life-threatening hemorrhage. andexanet -approved reversal agent available but its place in therapy remains controversial due to its high cost and a lack of head-to-head trials comparing it to four-factor prothrombin complex -pcc). we conducted a retrospective review of adult patients admitted with ich associated with rivaroxaban or apixaban and -pcc for anticoagulation reversal between may and april . the primary outcome was hemostatic efficacy using the annexa- study rating system (excellent, good, or poor) based on initial and repeat non-contrast ct head imaging within hours. secondary outcomes included the occurrence of thromboembolic events and -day all-cause mortality. we excluded patients whose hematoma was surgically evacuated before the -hour ct or who received multiple reversal products. ich patients met the inclusion criteria: andexanet patients ( spontaneous and traumatic) and -pcc patients ( spontaneous and traumatic). ( %) andexanet patients achieved excellent -pcc patients ( -pcc patients, ( %) achieved good (p= . ) and ( %) achieved poor (p= . ) hemostasis. thromboembolic events following -pcc patients (p= . ). thirty-day all-cause mortality occurred in ( %) andexanet patient and ( %) -pcc patient (p= . ). -pcc for reversing ich associated with rivaroxaban and apixaban. limitations include our small sample size and -pcc in this population now that andexanet alfa is widely available. a quality improvement project was undertaken to understand the risks of central venous catheter associated venous thromboembolism (vte) in the neuroicu setting. all patients who were admitted to the neuroicu and required a central venous catheter from / / to / / were included in the study. all catheters were placed under ultrasound guidance using the seldenger technique. the site of catheter insertion, duration of dwell time and subtype were recorded for each catheter that was placed. catheters were categorized as cooling catheters, large bore and dialysis catheters, or standard multi-lumen infusion catheters. clinical suspicion for vte such as extremity edema or unexplained hypoxemia triggered the standard of care use of ultrasound and/or lung ct angiography for diagnosis. vtes with an appropriate chronology and in the same vascular distribution as the suspected catheter were categorized as catheter associated. catheters in patients were included in the analysis representing catheter*days. a total of catheter related vtes were observed in our cohort. in a mixed neuroicu cohort the overall vte rate was . per patient days which is in line with prior published rates. multi-lumen infusion catheters had the highest rate of vte ( . ± . ) and cooling catheters had the lowest rate ( . ± . ). surprisingly, the highest rate of vtes was observed in catheters placed in the subclavian vein across catheter types ( . ± . ). we observed that multi-lumen infusion catheters had a higher rate of vte compared with cooling and large bore catheters. this finding may be related to longer dwell times for multi-lumen catheters ( . ± . vs [cooling] . ± . and [large bore] . ± . ). the subclavian vein was the site with the highest rate of vte which may be related to more lateral approach taken with ultrasound guided subclavian catheter placement. patients on direct acting oral anticoagulants (doacs) have high mortality after intracranial hemorrhage (ich). prothrombin complex concentrate (pcc) has been used off-label to treat ich while on doacs. pccs effect on laboratory markers of anticoagulation have varied. whether or not a change in laboratory markers of anticoagulation impact outcome is unknown. retrospective, single center design assessing patients on doacs that presented with ich and received pcc. the primary outcome is to describe changes in anti-thrombelastography (teg) parameters before and after receiving pccs. hemostatic efficacy (defined by international society on thrombosis and haemostasis criteria), and thrombosis rate are also reported. thirty five patients were included. patients were . +/- . years old and % were male. . % had traumatic brain injury related hemorrhage, % had primary intracerebral hemorrhage, . % had subdural hemorrhage, and . % had subarachnoid hemorrhage. median glasgow coma score at was . units/ml +/- . units/ml. on average teg r time decreased +/- seconds and teg act time decreased +/- seconds. hemostatic efficacy was excellent or good in % of patients and poor in %. thrombosis rate was . %. overall mortality was %. there was a modest response in laboratory parameters after giving pcc to patients with doac associated ich. the mortality in this cohort was high. whether a laboratory response in coagulation dosing, laboratory response, hemostatic efficacy and patient outcomes. in critically ill patients with tbi, agitated behaviors may often be threatening for patients safety and for clinical teams. antipsychotics are commonly used for the acute management of these agitated behaviors. however, animal tbi models suggest that repeated use of antipsychotic agents reduce cognitive and functional recovery. it remains unknown if the use of these agents negatively impact the functional recovery of tbi patients. our objective was to describe the use of antipsychotic agents and agitation/delirium monitoring practices in critically ill tbi patients. we conducted a retrospective observational study of adult icus in canada that manage tbi patients. consecutive adult patients with moderate/severe tbi admitted to icu between january and december were included. data were collected using standardized forms for up to a maximum of days in icu or until transfer out of icu. the primary outcome was incidence of antipsychotic use. we included patients ( patient-days) with a moderate ( %) or severe ( %) tbi. the majority tbi included falls ( %), mva ( %) and assaults ( %). antipsychotics were used in % of patients for a total % of patient-days. quetiapine, haloperidol, olanzapine, and risperidone were used in a %, %, %, % of patient-days, mostly for agitation, an unclear reason or delirium ( %, % and % of total patient-days, respectively). a delirium monitoring tool was used % of patient-days whereas the rass and sas were used in % and % of patients-days, respectively. despite uncertainties regarding their efficacy and safety, antipsychotics are frequently used in critically ill moderate/severe tbi patients in canada, mostly for the management of agitation. sedation/agitation tools are mostly used for the monitoring whereas delirium tools are more rarely used. traumatic venous sinus thrombosis (tvst) is increasingly detected on neuroimaging in acute head trauma, and may be an important contributor to elevated icp refractory to standard medical/surgical treatment, and in turn, higher morbidity/mortality and more complex icu course. we sought to identify clinical and neuroimaging features predictive of refractory icp issues in tvst patients treated in an urban level i trauma center. retrospective query of electronic radiology database from to using the phrase "venous sinus thrombosis". cases were reviewed and scored by a fellowship-trained neuroradiologist to define degree of occlusion (partial vs complete) and cause of sinus occlusion (extrinsic compression vs intrinsic thrombus vs both). additional patient characteristics included demographics, mechanism of trauma, cerebral venous sinus involvement, laterality, skull fracture, extra-axial hemorrhage and invasive neuromonitoring. refractory icp was defined as at least one spontaneous icp elevation >= minutes during icu stay despite use of first tier therapies for icp control. odds ratios were computed and adjusted by multivariate logistic regression for patient age, gender and initial gcs to determine association with refractory icp. among patients with radiologic diagnosis of tvst, developed refractory icp ( / = . %). statistically significant variables associated with refractory icp included involvement of internal jugular vein (aor= . , % ci . - . ), involvement of transverse sinus (aor= . , % ci . - . ) and presence of temporal bone fracture (aor= . , % ci . - . ) . potentially protective factors included sinus pathology secondary to extrinsic compression (aor= . , % ci . - . ) and coexisting epidural hemorrhage (aor= . , % ci . - . ). involvement of the internal jugular vein or transverse sinus and temporal bone fracture may represent sensitive features of tvst predisposing to refractory icp issues, while extrinsic compression of a sinus alone was found to be protective. monitoring cerebral autoregulation in traumatic brain injury (tbi) patients can indicate an individual cerebral perfusion pressure (cpp) target for which autoregulation is best preserved (cppopt): this offers a precision medicine approach with hypothetical advantage over the current 'one size fits all' strategy. large retrospective data suggest that managing cpp close to cppopt has a benefit in outcome. a prospective evaluation of cppopt guided therapy is needed, but before performing an outcome study it is necessary to assess the feasibility and safety of such a protocol. the primary objective of cogitate (cppopt guided therapy assessment of target effectiveness) is to demonstrate feasibility of individualising cpp at cppopt in tbi patients, expressed as the percentage of monitoring time for which cpp is within mmhg of regularly updated cppopt targets during the first days of intensive care unit (icu) admission. secondary objectives are to investigate the safety (increases of the treatment intensity level) and physiological effects of this strategy (changes in autoregulation indexes, organ function parameters). cogitate is a phase ii non-blinded, randomised controlled trial currently ongoing in the icu of cambridge, leuven, nijmegen and maastricht. severe tbi patients requiring intracranial pressure directed therapy, are enrolled in the first hours after icu admission and allocated into two groups. in the intervention group the cpp target (cppopt) is calculated using a (modified) algorithm previously described by liu x et al. and clinically reviewed -hourly. the control group uses a fixed cpp target ( - mmhg). patient re have been recruited so far. randomising between a fixed and variable cpp is feasible. after completion of recruitment and follow up in terms of assessment of safety and physiological parameters, we will consider progressing to a phase iii study. selective reduction of non-classical monocytes has been associated with reduced neutrophil activation in murine traumatic brain injury (tbi) models. similarly, cd -/cd -t cells or double negative t-cells (dnt) may exacerbate ischemic brain injury. this study sought to assess the expression of peripherally isolated t-cells and monocytes after acute tbi. all patients admitted with primary tbi to the neurotrauma icu between november and november were eligible for study. consent was obtained and blood samples were obtained within hours of injury. samples were compared to healthy age-and sex-matched controls. conventional flow cytometry techniques gating on all patients admitted with tbi to the neurotrauma icu between november and november were eligible for study. consent and blood samples were obtained within hours of injury. samples were compared to healthy age-and sex-matched controls. conventional flow cytometry techniques, gating on cd + and cd + were employed to identify t-cell and monocyte populations, respectively. data were analyzed using cytometric fingerprint binning and t-sne embedding, which captures the set of multivariate probability distribution functions and generates maps that facilitate quantitative comparisons. patients were compared to controls. after computational analysis, distinct t-cell phenotypes were identified, of which were statistically significantly different between patients and controls expressed as a fraction of cd + cells. three of these eleven subsets had a cd -/cd -(double negative) phenotype that were depressed among patients: cd -/cd -/cd + . % versus . %, p= . ; cd -/cd -/ + . % versus . %; p= . ; cd -/cd -/ +/ + . % versus . %; p= . . there was a three-fold decrease in the fraction of type , non-classical monocytes in patients than in controls [ . (iqr . - . ) versus . (iqr . - . ); p= . ]. similar patterns in monocyte expression were observed for the patients who had repeat analysis at hours. in this preliminary study, there were notable reductions in dnt populations and non-classical monocytes in patients with acute tbi, which may suggest recruitment to the cns. prior studies suggest that dnt play a critical role in the perpetuation of cerebral ischemia after acute stroke and that type monocytes modulate neutrophilwarranted. much of the secondary injury that occurs after traumatic brain injury (tbi) results from coagulation derangements related to disseminated intravascular coagulation (dic). extracellular vesicles (evs) are small ( . transduction. evs are released from all cell types, including platelets, endothelium, and granulocytes which are responsible for dic. we hypothesized that specialized flow cytometry techniques could identify a unique ev signature of dic in acute tbi. ev fluorescence panels were created assessing for endothelial cells (cd +, cd +), platelets (cd , cd a+, cd b+), erythrocyte markers (cd +) as well as brain specific biomarkers (s b). using a modified flow cytometry instrument for detection of small particles, side scatter signal is used to estimate ev size. samples were treated with triton, which disrupts vesicular membranes, abolishing evs. samples were prepared in trucount tubes with a known number of lyophilized beads, which enabled the determination of the plasma volume. all combinations of positive/negative expression were counted. there was no significant difference in the total number of evs in the panels between the patients and controls. of combinatorial analyses in the first ev panel, the following were significantly elevated after bonferroni correction: cd +/cd + . evs/ul plasma v controls (wilcoxon rank sum p= . ); cd +/cd + . evs/ul plasma v . controls (p= . ); cd +/cd a+ . evs/ul plasma v . controls (p= . ). brain biomarkers were also elevated: s b . evs/ul plasma v. . controls (p= . ). evaluate whether this expression correlates with secondary microvascular brain injury. s b evs (membrane bound, not free soluble protein) are significantly elevated in tbi patients; if reproducible, the significance of this remains to be elucidated. diabetes insipidus (di) following transsphenoidal craniotomy may lead to significant metabolic derangements. serum sodium imbalances are frequent and important; both hypo-and hypernatremia can be devastating neurologically. a project aimed at improving di management through predictive assessments and ddavp protocols could potentially improve patient outcomes. however, few predictors for the postoperative development of di have been reported. after institutional irb exemption, the records of patients undergoing endonasal transsphenoidal craniotomy between july and december were retrospectively reviewed. demographics, preoperative medical or radiologic diagnoses, medications, and laboratory values as well as intraoperative blood loss, urine output, and ddavp administration were assessed for correlation with the incidence of postoperative development of di using logistic regression. development of postoperative di was defined as postoperative ddavp administration and/or ddavp use upon or after discharge from hospital. of the patients developed postoperative di. patients . , and . , respectively). similarly, patients with increased intraoperative blood loss, increased intraoperative volume administration, nd intraoperative ddavp or vasopressin administration were also more likely to develop postoperative di (pwith logistic regression modeling adjusted for associations between outcome and potential risk factors, patients having a documented or clinical suspicion for a preoperative endocrinopathy had seven times higher odds of developing postoperative di compared to their peers (p-value . , % ci . - . ). in administration, and ddavp were independently associated with an increased risk of postoperative di; the odds of postoperative di were seven times higher in patients with a documented or clinical suspicion findings. the seminal mechanical thrombectomy (mt) trials had a median age of years. though some of these trials included nonagenarians, there is little data on their outcomes. we aimed to compare the procedural, discharge outcomes and complications, of mt for acute ischemic stroke (ais) in patients with ais admitted to two comprehensive stroke centers were enrolled prospectively in a mt, procedural outcomes, complications, and discharge disposition were compared in propensity scorematched groups (matched for nihss, pre-stroke mrs, ivdefined as a discharge to home/acute rehabilitation. of the ais patients, / ( %) nonagenarians underwent mt compared to / ( %) ) were propensity score-matched with a median admission nihss of and , and median aspects ( % vs %, p= . ), whereas ica ( % vs %, p= . ), and m ( % vs %, p= . ) occlusions were similar between the two groups. time to groin puncture ( ± vs ± ; p= . ), revascularization time ( ± vs ± ; p= . ), complication rates ( vs . %; p= . ) and inhospital deaths ( % vs %; p= . ) were similar among the two groups. % of nonagenarians had we present one of the largest series of mt among nonagenarians with % successful recanalization rates. in propensity score analysis almost half of nonagenarians ( %) were discharged to home/rehab, which is comparable to a younger cohort ( %). aggressive management is warranted in the oldest of the old. early neurologic deterioration (end) occurs in up to one third of stroke patients and is associated with poor outcome. no consistent definition of end exists regarding degree of nihss decline and timeframe. we evaluated the definition of end, predictive factors, and day outcomes in a cohort of critically ill stroke patients. this study is a retrospective review of consecutive ischemic stroke patients with nih stroke scale (nihss) intervention factors were obtained. end was defined as a delta nihss > at hours from admission. reperfusion was defined as a thrombolysis in cerebral infarction (tici) score of > b, cerebral edema treatment as any icp-lowering therapy, and poor outcome as mrs > at days. multivariable logistic regression analyses were performed to assess factors associated with end and poor outcome. patients (median age years, % women, median nihss ) met study criteria. % experienced end. admission nihss, administration of tpa, receipt of intraarterial therapy, and successful reperfusion were not associated with end. end was independently associated with older age (p= . ), sex (p= . ), and treatment of cerebral edema (p= . ) after adjusting for cerebral herniation and tracheostomy. poor outcome was associated with older age (p= . ), higher delta nihss (p< . ), not receiving tpa (p= . ), and placement of percutaneous endoscopic gastrostomy tube (p= . ). end patients had a higher median day mrs (p< . ). end as defined by a delta nihss > at hours predicts poorer outcome, but was not associated with tpa or intraarterial therapy, which contrasts with prior literature. this variance could be attributed to the end timeframe defined as hours rather than the typical samples sizes and comparison of end timeframes could clarify observed findings. annexa- was a single-arm, prospective, open-label study of andexanet in patients presenting with major bleeding within patients with spontaneous intracranial hemorrhage (ich). brain imaging was performed at baseline, and at and hours post andexanet treatment. subdural hemorrhage (sdh) thickness and ich volumetric analysis was performed using quantomo software. co-primary efficacy outcomes were change in anti- of patients enrolled in annexa- , nontraumatic ich was present in patients, including intracerebral +/-intraventricular in patients, subarachnoid in patients and subdural in patients. in this cohort, mean age was years (sd . ) administration was . hours (iqr . - . ); median time from symptoms to ct was . hours (iqr . - . ); and median time from ct to andexanet administration was . hours ). median intraparenchymal volume was . ml (iqr . - . ). among efficacy evaluable patients (baseline anti-treatment overall. in patients treated < hours after baseline imaging, hemostatic efficacy was . %; - hours after baseline imaging, . %; > hours, . %. within days, death occurred in patients ( . %). andexanet reduced anti--or apixaban-associated nontraumatic intracranial bleeding and with a high rate of hemostatic efficacy up to hours after treatment. spontaneous intracerebral hemorrhage (ich) is associated with high rates of mortality. multiple scoring systems exist however the original ich score remains most commonly used. we hypothesize that patients undergoing scuba, compared to medically managed patients, would have lower -day mortality than predicted. we performed a retrospective observational cohort study of consecutive nontraumatic spontaneous ich patients treated at a single, tertiary care, academic center from december to june . patients for each patient based on the admission ich score. a total of ich patients were included. the median age was (q = , q = ), gcs ( , ), and nihss ( , ) . sixty-three were deep hemorrhages and had intraventricular hemorrhage. median pre-operative volume was . ml ( . , . ). the expected -day mortality was . % while the observed mortality was %. on -day follow up, a mrs of - was seen in % of patients. patients undergoing scuba have an absolute risk reduction of . % in mortality than predicted by the ich score. good outcome to moderate disability, defined as mrs - , was achievable in almost half the introduction andexanet (coagulation factor xa [recombinant] inactivated-zhzo), a specific reversal agent for factor xa % of patients with major bleeding in the annexa- trial. however, little is known about the clinical factors associated with a hemostatic response in patients with intracranial hemorrhage (ich) receiving andexanet. annexa- was a prospective, single-arm, open-label study of andexanet in patients with acute major treatment was rated by an independent adjudication committee as excellent, good, or poor/none based on pre-specified criteria. all ich patients with evaluable he were included in the analysis. univariate and indication for anticoagulation, baseline antianti-platelet use, time from last dose to andexanet (and other time intervals), neurologic function, and hematoma characteristics were performed to identify factors predictive of he. of ich patients enrolled, ( . %) had evaluable he. in patients with ich, baseline antitime from symptoms to andexanet were all significantly associated with he. in multivariate analysis, time from last dose ( . h for excellent/good; . h for poor/none), time from symptoms to andexanet ( . h for excellent/good; . h for poor/none), and time from symptoms to scan ( . h for excellent/good; . h for poor/none) were independently associated with he. in ich patients treated with andexanet in the annexa- study, various time intervals were predictive of hemostatic efficacy. these findings suggest that shorter time intervals are associated with lower he and are consistent with the known relationship between time from symptoms and the risk of hematoma expansion. alterations in functional connectivity are associated with persistent cognitive deficits in survivors of aneurysmal subarachnoid hemorrhage (sah), but causation remains unknown. therefore, we sought to and behavior could be assessed. we used functional optical intrinsic signal imaging to measure spontaneous hemodynamic fluctuations -operated (n= ) and sah (n= ) mice. we tested behavior using the morris water maze, open field test, y-maze, and rotarod. timepoints were from days to months. we used the anterior prechiasmatic injection model of sah. . ), and visual cortex ( . vs. . ) at day following sham procedure or sah, as measured by the proportion of brain surface with a correlation coefficient > . (sham vs. sah, respectively, p< . ). -independent ng sah. a global connectivity index remained decreased until month following sah ( . vs. . , p< . ). an interhemispheric connectivity index was also he hidden platform test on the morris water maze (p= . ) and open field test ( vs. m, p= . ) at approximately weeks. there were persistent deficits on the y-maze for at least months ( % vs. % alternation, p= . with repeated measures at and months). there was no significant effect of sah on rotarod performance. we studied whether high-protein supplementation (hpro) and neuromuscular electrical stimulation (nmes) after subarachnoid hemorrhage (sah) could be a safe and feasible approach to reduce muscle wasting and improve long term recovery. assigned to standard of care (soc) or nmes + hpro. nmes was delivered to bilateral quadriceps and gastrocnemius muscles during two -minute sessions daily along with hpro (goal . g/kg/day) between post bleed day (pbd) and . tolerability was measured during each nmes session by assessing for agitation or discomfort. safety measurements included increased heart rate, blood pressure, or intracranial pressure (when monitored) during nmes. stimulation sites were assessed after each nmes for muscle injury or skin trauma. hpro tolerability was assessed by monitoring for gastric retention or emesis. safety measures included aspiration and evidence of acute kidney injury. nmes and hpro were discontinued if subjects refused. the goals were to administer at least % of nmes and hpro. muscle wasting was assessed with serial ct scans of the thighs. twenty-five subjects (soc= , nmes + hpro= ) participated with no differences in baseline characteristics ( years old, % women, % hh> ). median intervention days were (range: - ), with % of nmes sessions completed. two subjects had transient muscle soreness but no other adverse events. no adverse events were associated with hpro. the hpro group received % of the goal and more protein than soc (mean difference: . +/- . g/kg/d, p< . ). muscle atrophy at pbd was greater in soc group ( . +/- . % vs . +/- . %, p= . ). nmes and hpro are safe and feasible after sah. a larger pilot study is underway to understand whether nmes and/or hpro may beneficially impact neuromotor recovery after sah. lipocalin- (ngal) is released by activated neutrophils and astrocytes and mediates neuro-inflammation and iron regulation in hemorrhagic stroke models. blood ngal is an early biomarker in human ischemic l and neurofunctional outcome in sah patients. magnetic luminex assay, r&d systems) and assessed modified rankin scale (mrs) every months. patients with renal or severe liver dysfunction, active malignancy or intracranial infections were excluded. poor outcome is defined as mrs> . vasospasm was defined as > % reduction any vessel caliber on cerebral angiogram. continuous variables were compared with student's t or wilcoxon rank sum test depending on data distribution. one-way anova was used for multi-group comparison. sah cohort has mean age of . years, % women, % with poor -month outcome and % developed vasospasm. higher plasma ngal on post--sah days - (p= . ) and (p= . ) are associated with poor -month outcome. higher plasma ngal on postand ngal on post-sah days -- . ) early elevation of plasma ngal on post-sah day is associated with vasospasm and poor -month -sah - are associated with poor -month outcome. larger population studies are needed to validate plasma ngal as a potential sah biomarker. patients with aneurysmal subarachnoid hemorrhage (asah) are at risk of rebleeding prior to aneurysm obliteration. while placebo-controlled studies have shown that administration of either -aminocaproic acid (eaca) or tranexamic acid (txa) can decrease rebleeding, there has not been a comparison of the two in this patient population. because of a national shortage of eaca in , our hospital changed to txa. the purpose of this study is to describe the outcomes of asah patients treated with either eaca or txa. this is a retrospective chart review of patients who presented with an asah between / / and / / and were treated with either eaca or txa to prevent aneurysm rerupture. descriptive statistics were used. there were patients with asah who received eaca and who received txa. the groups were eaca group and . % in the txa group. the average time from admission to drug initiation was . ± . hours in the eaca group and . ± . hours in the txa group. no patient in either group experienced aneurysm rerupture after receiving the drug. similar numbers of patients in both groups had cerebral ischemia (eaca: % vs. txa: %) and extracranial thrombosis (eaca: % vs. txa: %). although txa is known to lower the seizure threshold, we found no increased incidence of seizures (eaca: % vs. txa %). there was a modest cost difference in favor of txa vs. eaca. there does not appear to be any major differences in outcomes in patients with asah treated with either eaca or txa for the prevention of aneurysm rerupture and a slight cost savings favoring txa. a larger prospective study is required to confirm these results. outcome prediction after aneurysmal subarachnoid hemorrhage (asah) is based on scores, which are determined once at admission. however, the occurrence of delayed ischemic neurological deficits (dind) depends on multiple concomitant and continuously changing factors. the goal of the study was to establish an automated analysis pipeline to predict dind from multimodal data. multimodal data (patients' history, imaging and laboratory values among others) from patients with asah were analyzed. dind was defined as new ischemia or perfusion deficits in native or contrastenhanced ct/mri and/or cerebral vasospasm in conventional, ct-/mr-angiography. a ranking of the features was performed by univariate regression analysis. only cases with < % of missing values were included in the model. among the tested features, the top , with a false discovery rate < . , were selected. missing values were imput random forest machine learning algorithm was applied. the performance of the prediction was estimated on the fly by predicting the observations that were not used for building the tree ("out-ofbag") across all trees. the final data matrix contained events described by features from patients. in the final model, the out-of-bag estimate of error rate was %, which reflected a % accuracy. the importance plot for different features revealed the importance of some parameters known in the context of inflammatory response, which is linked to the pathophysiological cascade leading to dind. these included counts of leucocytes, monocytes, neutrophils, and lymphocytes. however, other laboratory parameters, such as zinc and selenium, appeared to be of high importance in the model, which was somewhat unexpected. machine learning algorithms may be helpful to filter out predictive features from a large number. these features might be subsequently investigated regarding their predictive value on the occurrence of dind after asah. innate inflammation is a recognized mediator of dci after sah. we have shown that neutrophils and the neutrophil-derived enzyme, myeloperoxidase (mpo), mediate memory deficits in dci. how mpo affects memory is unclear. there is evidence that mpo, and its substrate h o , may act through astrocytes or directly on neurons. here we test mpos action on astrocytes and neurons. primary neuronal and astrocyte cultures were developed from wt and c bl/ thy -gcamp mice. to test if mpo or h o are toxic to neurons or astrocytes, cells were incubated with mpo ( . u/ml), h o ( . %), and mpo/ h o and evaluated with live/dead cell viability assay (thermofisher). to test if neuronal firing is affected by mpo, the same experimental conditions were examined in c bl/ thy -gcamp using video microscopy. neuron activation was stimulated with kcl (final concentration mm). addition of h o led to death in neurons and astrocytes. mpo did not affect cell death in either group. interestingly, mpo/ h o showed less cell death than h o alone suggesting a neuroprotective benefit of mpo. in neurons, kcl administered to untreated neurons led to continuous firing as evidenced by intense calcium signal. mpo addition did not change the firing rate when compared to baseline. after . hours of mpo pretreatment, activation with kcl showed a suppressed firing rate suggesting neuronal depression. the addition of mpo/ h o showed the same firing rate suppression as mpo alone. this study suggests that mpo acts directly on neurons to decrease function. in our model of neutrophilinduced development of dci, mpo is released in the meninges, diffuses to the brain parenchyma and acts directly on neurons to affect memory. this needs to be tested more thoroughly in an in vivo model of sah. how mpo specifically affects memory in neurons is an area of interest in our laboratory. delayed cerebral ischemia (dci) is a feared complication of subarachnoid hemorrhage (sah), leading to worse outcomes. electroencephalography (eeg) provides a useful, continuous monitoring tool for dci risk (claassen ; kim ; rosenthal ) and late-onset epileptiform discharges (ed) have high predictive value for dci (kim ; rosenthal ) . however, optimal parameters to assess ed contribution to longitudinal dci risk are unknown. we hypothesize that the evolution of ed frequency after sah can provide early identification of those at high dci risk. we analyzed continuous eegs from patients with moderate to severe aneurysmal sah. ed were identified using a commercial detection algorithm (scheuer ). we calculated ed frequency (per hour) after sah and compared mean ed frequencies between dci and control patients. we also evaluation, we performed group based trajectory analysis (gbtm) and calculated hourly receiver operating curves (roc). ed rates were higher in both dci and control groups during the clinical dci "risk period" of day - . overall mean ed frequency were significantly higher in dci patients (t-test, p= . ), including only pre-dci ed assessment (t-test, p< . ). hourly mean ed rates remain higher in dci patients from days - . using gbtm, we identified three distinct trajectories associated with dci ( %, %, %, p= . ), with group number selection optimized based on bayesian information criteria. hourly area under the roc (auc) calculations of ed frequency yielded a maximum performance of . . natural history of ed frequency in all sah patients coincides with the "high risk" time-period of dci. patients with dci have higher mean frequencies that remain elevated throughout this dci risk period. gbtm and auc calculations suggest longitudinal analysis of discharge frequency can differentiate dci risk, but integration of other waveform characteristics are needed to optimize prediction. aneurysmal subarachnoid hemorrhage (sah) has high morbidity and mortality. time to aneurysm repair, whether earlier or later in the course of the disease, may impact outcomes. however, optimal timing remains controversial. our goal was to describe the association between time to aneurysm repair and mortality and functional outcome. this study was conducted in two reference centers -one in rio de janeiro and one in porto alegre july to march , every adult patient admitted to the icu with aneurysmal sah was enrolled in the study. data were collected prospectively during the hospital stay. patients were divided into four groups according to the moment of aneurysm repair after bleeding: < days, to days, > days and not repaired. the primary outcome was in-hospital mortality. dichotomous variables were analyzed using twomortality as the reference group ( to days). a total of patients were included. median age was years, mostly female ( %). in the univariate analysis hydrocephalus, rebleeding, postoperative neurological deterioration (up to hours after procedure), delayed cerebral ischemia, as well as mortality and poor outcome, were associated with the different timing of aneurysm repair. in the multivariate model for mortality, poor grade sah, hydrocephalus, post-procedure neurological worsening and dci were independently associated with higher mortality. additionally, late repair was associated with lower mortality (or . ) as compared with occlusion between to days. our study shows higher mortality in patients submitted to aneurysm occlusion procedure between days and after ictus, when compared to late repair. more studies are needed to define the best timing of aneurism repair in patients that are not submitted to early occlusion. the biological mechanisms that influence abnormal cortical neurophysiology after aneurysmal subarachnoid hemorrhage (sah) are uncertain. we hypothesized that soluble st (sst ), a plasma marker of the innate immune response, is associated with events of electroencephalography (eeg) deterioration including new epileptiform abnormalities (eas) or new eeg background deterioration. -approved biospecimen repository, we evaluated patients with at least days of eeg monitoring and an early sst measurement (collected < days following sah). eas were defined as sporadic epileptiform discharges, lateralized rhythmic delta activity (lrda), lateralized periodic discharges (lpd), or generalized periodic discharges (gpd). background deterioration was defined as decreasing alpha delta ratio (adr), relative alpha variability (rav) or worsening focal slowing. the association between sst level and eeg-identified eas or new background deterioration was compared using the wilcoxon rank sum test. patients met inclusion criteria. early sst was collected at mean . ± . days after sah; patients had a subsequent sst measurement at ± . days. ( %) patients developed new eas during eeg monitoring, ( %) developed new background deterioration, and ( %) developed neither. median sst in patients developing new eas was higher ( . ng/ml ]) than in patients who did not develop new eas ( . ng/ml ], p= . ). this association between elevated sst and new eas was not present for sst samples collected at later time points. there was no difference in sst levels between patients who developed new background deterioration ( . ng/ml ) compared with those who did not ( . ng/ml ], p= . ). among patients admitted with aneurysmal sah, elevated sst in the first days is associated with the development of new eas on eeg monitoring. this association was not present at later time points, suggesting that the early inflammatory response may be linked to abnormal cortical neurophysiology. glial-mediated inflammation occurring early after status epilepticus (se) in rodent models has been implicated in the subsequent development of spontaneous recurrent seizures (srs). while this suggests anti-inflammatory strategies may be a target for therapeutic intervention, the appropriate timing for such an intervention is unclear. the aim of this work is to define the timing of early inflammatory changes using pro-inflammatory mir- and anti-inflammatory mir- a as biomarkers in a kainic acid mouse model of se. se was induced in - week old male c bl/ j mice (n= per timepoint) using intraperitoneal injections of mg/kg kainic acid. the onset of se was defined as the first class seizure using a modified racine scale. the intensity of the se episode was estimated by the total number of discrete class v seizures observed. after hours, the se was aborted with diazepam, and hippocampal tissue was harvested at hr, hr, hr, hr and hr. rna was isolated using trizole (life technologies) followed by qrt-pcr analysis to define the steady-state expression levels of mir- and mir- a and their targets, socs we observed a > fold increase in expression levels of mir- , reaching peak levels at hours. expression levels of mir- directly associated with the intensity of se. the level of socs mrna expression decreases after the peak expression of mir- . as the levels of mir- a were only conclusions mirna- expression shows an early increase within hours of se, reaching a peak at hours. mir- a shows a non-mir- initiated after se to determine if this can prevent the development of srs. nurses routinely screen for changes in neurologic status with serial clinical assessments. the objective of this study was to employ mixed methods to determine inter-rater reliability (irr), protocol adherence, and acceptability of a new tool we developed called serial neurologic assessment in pediatrics (snap) compared to the glasgow coma scale (gcs). snap assesses mental status, cranial nerves, communication, and four-extremity motor function/strength, with scales for children < -months, -months to -ye -years-old. snap was designed for use in a diverse population, including patients who are intubated, sedated, and/or have developmental disabilities. irr of independent snap assessments by pairs of trained nurses was assessed with multilevel cohen's kappa and linear weighted kappa, calculated through clustered bootstrap method to account for multiple assessments. we assessed protocol adherence with standardized observations. we conducted semi-structured interviews to assess acceptability and feas we thematically analyzed interviews in accordance with modified grounded theory framework. critical care nurses performed paired snap assessments on patients ( < -months; months to --years). there was substantial agreement between nurses (average kappa= . < -months; . -months to --years), and irr was unchanged for children who were intubated, sedated, and/or had developmental disabilities. irr was unchanged based on degree of experience using snap and for day vs. night-shift nurses. nurses had % protocol adherence. snap was easier to use and more precise at describing neurologic status of patients who were intubated, sedated, and/or had developmental disabilities than gcs. % of nurses preferred to use snap over gcs. when utilized by nurses, snap has substantial irr, excellent protocol adherence, and is acceptable and feasible to i neurologic decline. several studies demonstrate significant gender disparities in professional societies for critical care and neurology, but data for neurocritical care is lacking. we examined gender representation trends within the neurocritical care society (ncs), the largest international professional society for this subspecialty. we hypothesized that female representation has increased with achievement of gender equality in . a multidisciplinary writing group obtained approval from the ncs executive committee and endorsement by the women in neurocritical care (wincc) section. after review by the rush university irb, access was granted for the following rosters: general membership, board of directors, officers, committees, annual meeting speakers, grant, fellowship and other award recipients. we differentiated between female, male and unidentified gender. available membership rosters from listed members, with gender unknown for > %. in , of members . % were females, . % males, and . % unidentified. as of , / presidents ( . %) and - , female committee members increased from % to %; female committee chairs increased from % to %. to date, / ( . %) christine wijman young investigator awardees were female with no female recipients of the best scientific abstract award ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . % of presidential citation awardees - % from -e representation in guidelines writing groups ranged between %- % ( - ), and - % in consensus statements writing groups ( ) ( ) ( ) ( ) ( ) ( ) . - % ( awardees were women. within the ncs, a longitudinal increase in female representation has occurred over the last years but gender equality has not been achieved. we recommend focused efforts to facilitate inclusion and gender equity within ncs. with the push toward using large data sets in critically ill patients, the use and management of registries is becoming more relevant. clinical registries provide insight about associations and patterns in diagnosis, disease, and treatment. the integrity of the data is of utmost importance. this poster describes the quality control and data management methods for maintaining the integrity of a multicenter trial registry. we employed modifications to van den broeck's method of data organization to clean and manage the end-panic registry. the data management consisted of five phases: ) screening phase, ) data organization , ) diagnostic phase, ) treatment phase, and ) missing data phase. the screening phase consisted of distinguishing missing and extraneous data elements, outliers, inconsistent patterns/distributions and unexpected analysis results. the data organization phase consisted of treating blank cells and highlighting errors with data input. the diagnostic phase was used to clarify the true nature of the data points, and make sure the data presented was biologically possible. the treatment phase consisted of correcting variables. the missing data phase consisted of determining whether the missing data was informative or noninformative. currently the multi-center registry houses ~ . million discrete data points from , patients. there was a high correlation between the texas, ohio and california locations, and npi, dvl, cvl, mcvl, and pupil size. there was a low correlation between the texas, ohio and california locations, and pupil latency and presence/absence of cataracts. missing data was informative for age, race and ethnicity, and distribution of missing data caused an inquiry into methods for collecting data and implementation plans for change. this interdisciplinary method for cleaning and managing the end panic registry was able to identify and rectify errors. we would recommend others to use the methods to build, clean and manage clinical registries. objective was to describe current state of quality improvement (qi) processes implemented in neurocritical care units (nccu). a -question-survey was sent to members (physician, nurses, and pharmacists) of the neurocritical care society. we describe factors affecting the presence of nccu qi, barriers to qi, awareness of stroke (stk, cstk), stroke get with the guidelines (gwtg), trauma quality improvement program (tqip) and american academy of neurology (aan) performance measures, and examined factors affecting satisfaction with current practices. the response rate was . %; . % of respondents were from us teaching hospitals, . % practiced in dedicated neurocritical care units, and . % in a program with a neurocritical care fellowship. . % reported a dedicated nccu qi program. comprehensive stroke center (rr . , % ci . - . , p = . ), dedicated nccu (rr . , % ci . - . , p = . ), and ncc fellowship programs (rr . , % ci . - . , p = . ) were more likely to report dedicated ncc qi staff. external ventricular drain infection was the most commonly tracked ncc qi metric ( . %). respondents indicated the highest level of awareness for cstk ( . %), stk ( . %), and gwtg ( . %), but indicated a relative lack of awareness for tqip ( . %), and aan ( . %) perform satisfaction with existing ncc qi were: presence of a hospital qi program (rr . , % ci . - . ), p = . ), presence of a formal ncc qi program (rr . , % ci . - . ), p = . , and dedicated ncc qi staff (rr . , % ci . - . ), p < . ). insufficient hospital ( . %) and departmental support ( . %) were reported common barriers to the successful implementation of an nccu qi program. a dedicated staffed nccu qi program occurs in a minority of neurocritical care units, and the lack of such programs may lead to clinician dissatisfaction. institutional and departmental support may be critical elements of a successful and satisfactory implementation of nccu qi. the development and implementation of a nurse driven rounding model was instituted in the neuro icu of an academic medical center to increase effectiveness of team communication, practice autonomy and integration of nursing input into the interprofessional care plan. clinical nurses and neuro-intensivists developed a structured rounding tool to guide the nursing presentation of clinical information on rounds. the interprofessional team underwent education on expectations and processes. the rounding tool underwent a number of revisions over a -month period based on feedback from all team members and evolving patient care priorities. all team member roles in the rounding process were clearly defined with nursing leading patient assessment and goals. nursing satisfaction surveys assessed nursing attitudes regarding autonomy, decision making and rn-md communication via a point likert scale; mean values for each question domain were compared pre-and post-implementation. in total, nursing surveys were analyzed, pre-implementation and nurses postimplementation. mean response values evidenced significant improvement across all domains in the post-implementation group: autonomy ( . vs . , p< . ), rn decision making ( . vs . , p< . ), p< . ) . survey participation was good in both groups ( % pre-and % post-implementation). nursing satisfaction across multiple important domains improved following implementation of a nurse driven structured rounding model. application of a nurse-facilitated, structured model creates a standardized reliable process that can be observed by all team members in order to deliver data driven, high quality, efficient and effective care. multiple models for program development and care delivery in pediatric neurocritical care (pncc) have been proposed with varying degrees of success. here we present a unique model for building a dedicated pediatric neuro-intensive care unit (pnicu) through creation of a community of practice (cop). cop represents a mechanism for collective learning and production of repertoire of best practices through knowledge sharing, development of social capital, and support for organizational change. we utilized a bolman and deal -frame for organizational functioning (structural, human resources, political, symbolic) to describe the development of our pncc cop. we evaluated our pnicu with the standards outlined by the neurocritical care society (ncs) for a level neuro-intensive care unit. structural factors included forming pncc leaders across specialties (neurology, critical care, neurosurgery, radiology, nursing), opening (in ) a state-of-the-art, unique pnicu which includes wired rooms for continuous eeg monitoring and multimodal neuro-monitoring, meeting / ( %) of ncs standards. human resource factors included creating core groups of physicians and nurses with a primary role in pnicu, providing ongoing education through workshops, lecture series, and certification including enls and tncc, meeting / ( %) of ncs standards. politically, a pncc fellowship-trained, board-certified physician serves as medical director coordinating conception of collaborative partnerships across multidisciplinary experts. simultaneous creation of other specialty cohorts in pediatric critical care aided in departmental acceptance for the program, meeting / ( %) of ncs standards. symbolically, we set forth our shared purpose and strong commitment to foster cop that advances knowledge and best practices for pncc. using cop principles, we have accomplished many of the ncs standards over a relatively short period of time. we plan to further develop the program with particular focus on education, certification, and expansion to include allied health professionals. our roadmap may be applicable to any institution interested in developing a pncc cop/pnicu. intravenous (iv) anti-hypertensive infusions are often used acutely in patients with intracerebral hemorrhage (ich). there is a lack of standardization of titration and variation in goal blood pressure, and therefore their use is associated with increased icu length of stay (los) and cost. we examined the use of anti-hypertensive infusions in ich patients in our institution and developed a quality improvement intervention to reduce duration of infusion, icu los, and cost. patients were included if they were admitted to our icu from september -march with an icd- diagnosis of non-traumatic ich and received iv antihypertensive infusions. interventions introduced starting in november included interdisciplinary task force formation, provider education, updated rounding checklist, and emr order with clear blood pressure target. the primary outcome measure was duration of anti-hypertensive infusions determined by retrospective chart review, and secondary outcome measures of icu los and cost data were obtained from our finance department. over months, mean antihypertensive infusion duration reduced from . hours (n= ) to . hours (n= ). icu los reduced from . to . days. proportion of cases with discordant blood pressure goal documentation reduced from . % to . %, while discordance in documented goals to actual orders reduced from . % to . %. there were no significant increases in countermeasures (infusion restarts, icu readmission, and aki due to blood pressure lowering). extrapolating from finance data, and our baseline infusion duration and icu los data, iv antihypertensive infusions cost ~$ /hour. our improvement suggested $ in estimated cost savings in months. icu accommodation cost was approximated at $ /hour, for an estimated $ additional cost savings. a quality improvement based intervention targeting management of hypertension resulted in reduced duration of anti-hypertensive infusions, icu los, and cost. the intervention was feasible and ongoing data collection is warranted to assess sustainability. mortality and long-term-disabilities secondary to stroke are high. educating high-risk population with early stroke symptoms has been outstanding. however, education of post-stroke consequences (requiring resuscitation codes and goals-of-care awareness) is lagging. this study evaluates the understanding of such concepts by the admitted stroke patients (high risk population) and visitors (general population). were asked to answer a preliminary question about their original code status then read a self-explanatory sheet followed by revealing their revised code and goals-of-care choices. we used within-group logistic-regression-analyses to determine changes of codes among original coders and types of novel codes among post-survey coders. this included proposition of new short-term resuscitation (str-strp [partial]) codes. we used between-group chi-square-analyses to determine differences in education between groups. the odds of changes in no-coders were . , . in patients and visitors, (p-value= . , < . ) respectively. the odds of changes in dnr-coders= . , . , partial-coders= . , . , full-coders= . , . times those of the no-coders respectively (p-value< . ). the odds of novel-dnr-coders= . , and . , , . , . , . times those of novel-no-coders respectively (p-value< . ). str-coders originated from other-codes> no-coders. between-group analyses showed %, % of patients versus visitors changed their code status respectively (p-value= . ). goals-ofcare choices indicated tolerance towards temporary measures (tracheostomy and feeding-tube placement) and hemiplegic disabilities without poor mentation among the majority (~ - %) as a target for continuing care. pre-event (stroke) documentation of code status was approved among the majority of participants ( %). there is a misunderstanding of the resuscitation codes among both admitted stroke patients and general population. however, the difference between both indicates reception of some education among the stroke patients. str-strp are a good alternatives for many people. pre-event documentation -stroke outcome awareness are needed. early integration of palliative care improves communication, decision-making and social support in patients with acute stroke in the neurocritical care unit. the primary objective of this study was to analyze how early palliative involvement impacts communication between the healthcare team and patients/families. in this ongoing prospective study, patients with moderate to severe ischemic and hemorrhagic strokes were randomized into control and intervention arms. the control arm received routine icu care and the intervention arm received an early palliative care consultation. study assessments with the patient or surrogate decision maker were obtained at day - , and day - of icu care. comparisons were made for total scores on the questionnaire on communication (qoc), decisional conflict scale (dcs), and hospital anxiety and depression scale (hads). we performed an interim analysis utilizing the student's t-test and chi -square test on spss , with results below as mean + standard deviation. of patients enrolled ( intervention and control), % and % were female (p = . ). the average age was + and + years (p = . ). the majority ( % and %) were ischemic strokes (p = . ). admission nihss was + and + (p = . ). there was no difference in total qoc ( + , + , p = . ), hads ( + , + , p = . ), or dcs ( + , + , p = . ) scores. when comparing responses to individual questions, a trend toward improvement in qoc responses was observed "using words you can understand" (p = . ) and "answering all questions about illness" (p = . ). early integration of palliative care may improve communication between healthcare providers and patients/families, specifically with regards to using appropriate language that is understandable. routine daily chest radiographs (cxr) in mechanically ventilated patients (mvp) are often performed in the icu for "monitoring" purposes, despite lack of specific indications. routine daily tests are of questionable value and may increase costs without clinical benefit. the society for critical care medicine and choosing wisely campaign promote indication-based test ordering. studies involving medical-surgical icus demonstrate that indication-based versus routine daily cxrs in mvps results in cost-savings without jeopardizing outcomes. we implemented a quality improvement initiative targeting reduction of routine daily cxrs in mvps in the nsicu. we convened an interprofessional team of attending physicians, fellows, medical students and nurse practitioners. we conducted educational campaigns promoting evidence-based cxr utilization practices. standardized discussion of indication for cxr was incorporated into rounds. iterative process improvements were adopted beginning june . cxr utilization rates in mvps were measured the first weeks of , and and compared pre/post-intervention. hospital length of stay (hlos) was evaluated to monitor for complications resulting in prolonged hospitalization. implementation of indication-based ordering strategies decreased cxr utilization in mvps in the nsicu without increasing hlos. value-based care quality improvement initiatives can reduce costs without compromising clinical outcomes. patients transferred from nsicu to lower acuity units are vulnerable to readmissions and hospital acquired complications. standardized handoffs may help reduce this risk within academic institutions where physician trainees possess varying levels of clinical experience. we sought to implement a standardized handoff (i-pass) within inpatient neurology, focusing on high risk patient populations. residents and attendings were surveyed about inpatient handoff practices to inform implementation of i-pass. an electronic survey was administered in to residents and inpatient attendings in neurology at university of north carolina (unc). handoff practices among inpatient services (wards, consults, nsicu, and epilepsy) were evaluated. surveys assessed perceived quality of handoffs, as well as problems with handoffs leading to adverse events. surveys were sent to physicians ( residents, inpatient attendings); responses ( residents, inpatient attendings) were obtained (response rate, . %). -six percent of residents and % of attendings reported that problematic handoffs had been the primary or contributing factor to one or more adverse events. overall quality of handoffs involving nsicu patients transferred to lower acuity units was reported as a concern, with % of residents indicating the quality of these handoffs to be poor. in ranking inpatient services for prioritization of handoff interventions, % of residents identified nsicu handoffs as either their first or second highest priority. we also found residents exhibited a self-performance bias, with % reporting that they provided all pertinent information during handoffs most of the time, and only % reporting that they received all pertinent information during handoffs most of the time. inpatient handoffs are perceived as problematic by residents and attendings, with handoffs involving transfer of nsicu patients identified as high priority for targeted intervention. unc neurology has since implemented i-pass protocols to improve the safety of handoffs involving nsicu patients. targeted temperature management (ttm) to - c is the standard of care for post-cardiac arrest patients. recent literature has demonstrated a new trend of worsening morbidity and mortality postarrest due to under-utilization of ttm. management of post-arrest patients is a multidisciplinary health care effort, and knowledge of ttm rationale and protocol varies. normothermia ( - . c) also could have neuroprotective benefit in other clinical scenarios and is another indication for ttm. we hypothesized that a focused educational intervention would improve ttm protocol compliance. a multidisciplinary team developed a standard educational presentation and a question exam given as a pre-and post-test to residents, fellows, and critical care nurses. baseline data on ttm use was established followed by month prospective data collection post-intervention. data was extracted from arctic sun® machines on all ttm cases (post cardiac arrest and normothermia). the primary outcome was compliance with the ttm protocol measured by correct temperature target goals and appropriate duration, assessed by chi-square analysis. the secondary outcome measure was individual score improvement, evaluated by -variable students t test. there was a total of ttm cases pre-intervention, and ttm cases post intervention. there was a trend toward increased ttm protocol compliance ( % to %), however this was not statistically from pre-test (n= ) to post-test (n= ) after the education presentation (p< . , ci . to . ) among all health care participants. the resident, fellow, and nursing scores increased from % to %, % to %, and % to %, respectively. educational interventions for physicians and nurses caring for post-cardiac arrest and neurocritical care patients improved knowledge gaps and helped improve compliance with ttm protocol. additional education and process improvement activities are warranted to further improve protocol compliance, which may improve patient outcome. identifying the appropriate level of care needed for a patient presenting with acute intracerebral hemorrhage (ich) is often imprecise. the utility of prior work in triaging patients is limited by exclusion of non-primary ich patients, which is often difficult to determine prior to admission. this study aims to identify which admission factors are associated with icu level of care on presentation. this is a single-center retrospective review of patients admitted to our institution with ich in , regardless of etiology. all patients were admitted to the neurocritical care unit (nccu). icu level of care was defined as the need for mechanical ventilation, administration of vasoactive or insulin infusions, continuous renal replacement therapy, ventriculostomy, treatment of cerebral edema, temperature management, management of status epilepticus, or neurosurgical intervention. logistic regression was used to identify characteristics associated with icu level of care. patients (median age , % female, median admission gcs , median ich volume ml, % with ivh, % lobar, % infratentorial) were admitted with ich. ( . %) required intensive care. the most common interventions required were mechanical ventilation ( patients, . %), antihypertensi with need for intensive care included age ( vs. ), admission gcs ( vs. ), deep location of ich ( . % vs. . %), ich volume ( ml vs. ml), and presence of ivh ( . % vs. . %). on multivariate analysis, age (p = . ), admission gcs (p < . ), and deep location (p = . ) were independently associated with the need for intensive care. among all patients presenting with ich, age, admission gcs, and location of hemorrhage may help identify ich patients who need icu level of care. the impact of emergency neurological life support (enls) course on provider knowledge and selfreported comfort in management of neurocritically ill patients in a low-middle income country such as cambodia is unknown and explored in this study. in-person enls courses with english to khmer translated slides were conducted in hospitals in phnom penh, cambodia in may, . wilcoxon signed rank test and matched paired t-test were used to examine pre and post-course scores on translated knowledge-based multiple choice tests. a descriptive analysis was performed to evaluate provider comfort in management of neurocritically ill patients pre and post-course and amongst individual enls modules. overall, / healthcare providers participated; ( . %) physicians and ( . %) nurses. thirtythree ( . %) had acquired base specialty training in cambodia, ( . %) had completed subspecialty training in critical care medicine and ( . %) previously cared for neurocritically ill patients. pre-test sores were % [iqr ]; post-test scores were . % [iqr ]. though not statistically significant, posttest scores were higher for providers who had base specialty training in cambodia ( . % vs. . %, p = . ), subspecialty training in critical care medicine ( . % vs. . %, p = . ) and previous experience caring for neurocritically ill patients ( . % vs. %, p = . ). most ( %, n = ) reported that enls training had prepared them for management of neurocritically ill patients. enls courses may enhance the knowledge and comfort of healthcare providers in managing neurocritically ill patients in low-middle income countries, however this may depend on prior experience and minimizing language barriers. the impact of enls courses on outcomes in neurocritically ill patients in low-middle income countries warrants further study. neurocritical care has become increasingly subspecialized.yet, due to limited availability of dedicated neurocritical care units (nccus), often patients may need to be admitted to icus other than nccus. this survey based study was conducted to explore self-reported knowledge in recognizing and managing some common neurological emergencies such as stroke, status epilepticus, raised intracranial pressure etc among critical care nurses at a comprehensive stroke center. in january , we engaged nurses from icu units in this qi project-which included medical, surgical, neurocritical care, cardiac and cardiothoracic units as well as post-anesthesia care unit (pacu) and interventional radiology units. using institutional redcap anonymized surveys were sent to the nurses.information on demographic and critical care work experience was recorded. all participants answered questions with a likert type scale on their knowledge of several common neurological emergencies. nurses ( females, males) participated in the survey. ( %) had been working in an icu for years or longer. their self-reported level of knowledge in managing neurological emergencies revealed that more than half the participants did not feel comfortable managing patients with evds, ich, sah, raised intracranial pressure, tbi and traumatic spine injury patients. more than % of nurses were not satisfied with their current level of training to deal with neuroemergency and supported the need for dedicated training/ study time. icu nurses report gaps in fundamental knowledge in recognizing and managing common neuroemergencies. this highlights the need for providing ongoing training and education about neuroemergencies to critical care nurses to help maintain competencies. simulation training has been increasingly adopted in critical care specialties to promote active learning and create a reproducible platform for feedback. the role of advanced simulation as a core component of training in neurocritical care remains unclear, which may be due to uncertainty about the degree of fidelity needed. our objective was to determine if trainee knowledge and/or confidence differs when using standardized patients as compared to a multi-media simulation platform in a neurocritical care concepts training course. methods junior neurology residents engaged in simulated neurologic emergencies: a right mca stroke case, status epilepticus case, and a pontine hemorrhage/coma case. the mca stroke and status epilepticus cases were portrayed by trained standardized patients for half of the residents (group sp), while the other half interacted with the manikin supplemented with video clips of pertinent neurologic exam findings (group mv). both groups interacted with the manikin for the pontine hemorrhage/coma case. before and after the course, residents completed a -question multiple-choice test on management of neurologic emergencies and a survey about their confidence in managing neurologic emergencies. a detailed task checklist was used to assess decision making during the simulations. both resident groups had statistically significant higher knowledge and confidence scores after their training sessions (knowledge: pre: % vs post: %, p< . ; confidence: average pre: . to post: . , p< . ). however, there was no statistically significant difference between the two groups in either knowledge or confidence. the task checklist demonstrated significant variations in treatment practices and provided individualized areas for teaching. this pilot study suggests that trainees' knowledge and confidence in the management of neurocritical care concepts increases following simulated encounters, regardless of whether an actor-patient or multi-media simulation platforms is used. use of a task checklist uncovered important variations in protocol adherence among novice physicians. the accurate evaluation and determination of brain death has broad consequences on life-saving organ donation, closure for families, and length-of-hospital-stay. we have observed a concerning variability of brain death testing knowledge and comfort amongst neurology attendings and trainees at our institution. we aimed to create and apply a combined didactic and simulation training program to increase the knowledge and comfort in brain death evaluation, using our approved institutional brain death policy as reference. we hypothesized that participants who attended the training would show a measurable increase in their knowledge and comfort in the clinical evaluation of brain death. an experienced neurointensivist (> years of clinical practice) presented a -hour didactic session on brain death criteria, evaluation, and pitfalls to neurology residents and attendings. a high-fidelity simulation was implemented to allow practicing the brain death examination. knowledge and comfort levels were measured before and after learners had attended both sessions using electronic -exact-tests were applied to examine changes in knowledge and comfort in brain death testing pre-and post-exposure to the educational sessions. participants ( residents, attendings) completed pre-exposure, and ( residents, attendings) have completed post-exposure questionnaires thus far. knowledge significantly improved from pre-to post-exposure ( % correct, range - % improved to % correct, range - %; p= . ). comfort levels in performing the brain death examination pre-exposure also increased from pre-to postexposure (pre: "very comfortable- %","somewhat comfortable- %","neutral- %","somewhat or very uncomfortable- %" to post: "very comfortable- %", "somewhat comfortable- %","very uncomfortable- %" [p= . ]). exposure to a single combined didactic and simulation session improved the knowledge and comfort levels immediately post--exposure questionnaire response rates, as well as measurements of knowledge retention over a -and -month period and accurate application in practice. the safety and benefit of early mobilization in general intensive care units (icu) has been found to improve outcome and decrease length of stay. however, there is a lack of literature on early mobilization in the neuro icu (nicu) specifically, due to the complexity of the patients in the nicu and their disease processes. traditionally, patients were kept on bedrest after subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, and neurotrama, due to neurologic limitations such as fluctuation in mental status, requirement for sedation and paresis. additional challenges associated with mobility in this population include the potential for positional changes to impact intracranial pressure physician comfort level and concern for adverse neurological outcomes such as vasospasm or increased bleeding also decrease mobilization. while it is imperative to be cautious with nicu patients, prolonged bedrest and restricted mobility come with its own set of complications including muscle atrophy, decreased activity tolerance, delirium, pressure sores, nosocomial infections and deep vein thromboses. we sought to develop an early mobilization guideline that would help multidisciplinary staff identify which patients in the nicu should be mobilized early. a nicu physical therapist and the director of the nicu identified criteria for patients who were appropriate/inappropriate for early mobilization. all patients in the nicu should be mobilized early with the exception of the following exclusion criteria: unstable respiratory status, status epilepticus, contraindication to holding sedation, rass - , changing/worsening neuro exam, icp > mm hg, mean arterial pressure < or > mm hg, oxygen saturation < %, acute myocardial infarction, > vasopressors, clinical vasospasm, perfusional state, guidelines on early mobilization in the nicu can optimize patient mobility while minimizing complications associated with mobilization. introduction delivery, nurses must develop leadership skills and serve as full, collaborative partners with physicians and health professionals ( ). registered nurse (rn) inclusion into rounds has been shown to: improve interdisciplinary collaboration, incorporate learning in the workplace, increase leadership skills and improve team members' perception of unit flow and culture. attending physicians, rns, neurocritical care fellows, nurse practitioners, pharmacists and respiratory therapists were surveyed via surveymonkey to examine opinions regarding current rounding processes and potential opportunities in the neurocritical care unit (nccu). responses were aggregated to create scores for each topic, with the priority areas being the lowest relative scores based on a -point likert scale. survey responses were collected from nccu staff members ( % response rate). based on survey results, priority areas to enhance rounding satisfaction included: increasing collaborative decision making, creating entire team efficiency, completing rounds in a timely manner, increasing engagement and minimizing extraneous conversations and activities. other targeted areas for improvement included reserving time for prolonged family meetings for post-rounds, as well as focusing educational time and consistently utilizing the rounding checklist. based on areas of opportunity, a multidisciplinary committee was developed. one item created to enhance processes was the development and implementation of an rn facilitated presentation tool. to support this, a standardized presentation script and handoff tool were created and executed. six-month follow up survey results are pending at the time of submission. strategies to improve communication in multidisciplinary rounds are key to decreasing errors and improving care delivery. it is likely that a systematic data presentation by bedside rns will improve: staff perceptions of rounds, collaboration among all multidisciplinary staff members and rounding efficiency. the department of neurosurgery has a readmission rate goal of less than . for the fiscal year and less than . for the fiscal year of . over the past four fiscal quarters there has been an increase in the department's readmission rate, always exceeding the institutional goal. all readmissions in the institution's dashboard for q and q for and q and q of were reviewed by way of chart review. these were divided into spine vs cranial, planned vs unplanned readmission, reason for readmission and consistency vs inconsistency with the institution's dashboard. in q the dashboard reported a readmission rate of . . the final calculated actual readmission rate was . . in q the dashboard reported a readmission rate of . . the final calculated actual readmission rate was . . in q the dashboard reported a readmission rate of . . the final calculated actual readmission rate was . . in q the dashboard reported a readmission rate of . . the final calculated actual readmission rate was . . the most common reason for unplanned n reason for planned readmissions were shunt placements after lumbar drain trials. the dashboard was correct in predicting planned vs unplanned readmissions . % of the time. the coding on the backend of the institution's dashboard is missing many staged and planned readmissions and is only accurate in coding planned vs unplanned readmissions half of the time. this is resulting in falsely elevated readmission rates. despite the initial uptrend in readmissions, the actual readmission rates of the department are down trending and always below the institutional goal. this likely translates to other departments within the hospital. there needs to be a more efficient way to improve the coding and accuracy of the institution dashboards. the critically-ill neurological patients managed by specialized neurocritical care team is associated with improved outcome. in korea, limited data are available on improved outcomes after initiation of neurointensivist co-management in neurocritical care units (ncu). we evaluated the impact of a newly appointed neurointensivist on the mortality of patients admitted to the ncu. the study was conducted in intensive care unit (icu) beds of a large academic tertiary care hospital. neurointensivist co-management was initiated in march . the retrospective observational study compared the outcomes of patients before and after neurointensivist co-management. a total of patients were included, prior to and after the initiation of neurointensivist comanagement. patients admitted after neurointensivist co-management were older and had higher apache ii scores. icu mortality was significantly decreased in patients managed by neurointensivist ( . % vs . %, p= . ). the length of icu stay and duration of ventilator days were shorted in patients without co-management. neurocritically ill patients managed by specialized neurointensivist showed better clinical outcomes despite increased severity. social media has changed the way individuals communicate with each other and has altered the way society obtains information. in the past ten years, multiple articles have been published highlighting the ability to utilize social media for education of medical, nursing and pharmacy students. to our knowledge, cross discipline education utilizing these platforms has yet to be evaluated. with over . to implement a pharmacist led, social media based nursing education program and evaluate the perceived value of this education. a curriculum consisting of basic pharmacy related issues was developed and topics were posted to the ok users weekly. a pre-and post-education survey was sent out evaluating the program's effectiveness. email. of those nurses who received the pre-and post-education survey, a total of % and % completed the survey respectively. of those who completed the survey % received education via -education survey, there were no statistically significant differences in nursing performance on fact based questions after receiving education (p-value > . on all assessment questions). overall, % of the respondents reported a positive learning experience and wanted to continue this method of education delivery. the educational content. this project demonstrates the potential of utilizing social media as a means of cross discipline education; however, the solitary utilization of this platform should be used cautiously as this did not improve performance on assessment questions. consequently, targeted temperature management (ttm), either to maintain normothermia or induce hypothermia, is often advocated as a therapy to improve outcomes in brain injured patients. the physiological pathways that promote fever associated brain injury, and how these pathways might be modulated by ttm, remain unclear. this study examined the effect of fever and hypothermia on cerebrovascular pressure reactivity, a validated proxy of cerebral autoregulation. we included patients treated for brain injury from a single academic center. all patients had intracranial pressure (icp), invasive brain temperature, and arterial blood pressure (abp) recorded patient, mean prx over all periods of fever (> °c), normothermia ( - °c), and hypothermia (< °c) were calculated. differences in mean prx during normothermia, fever, and hypothermia epochs were then analyzed using paired student's t-test. the relationship between prx differences and total time spent normothermic was analyzed using linear regression. spent at a normal brain temperature (p = . , r = . ). in contrast, hypothermia was not associated with impaired cerebral autoregulation (p = . ). this study supports the hypothesis that impaired cerebral autoregulation may be one mechanism through which fever worsens outcome in brain-injured patients. the effect of fever on cerebral autoregulation appears to be more pronounced in patients that spend a longer amount of time in a normothermic state. interestingly, hypothermia was not associated with reduced prx, suggesting that the possible benefits of therapeutic hypothermia do not occur by improving the autoregulatory state. veno-arterial extra corporeal membrane oxygenation (va-ecmo) provides hemodynamic support in patients with refractory cardiogenic shock. these patients have a % incidence risk of cerebrovascular complications according to the extracorporeal life support organization database. reliable neuroassessments and neuroimaging are often limited by heavy sedation and risks of transporting these patients. transcranial doppler (tcd) can be a useful tool for cerebral hemodynamic assessment in these patients. we present four va-ecmo patients where tcd spectral waveforms provided key information on cerebral blood flow despite non-pulsatile flow. interpretable spectral waveforms were obtained in three of four patients. extensive embolization obscured flow patterns in one patient but clear cerebral perfusion with non-pulsatile waveforms was seen in the rest. two of the three remaining patients had high intensity transient signals (hits), suggesting cerebral microembolization. one patient showed pulsatility in cerebral waveforms despite no gross change in cardiac output on echo that helped guide decision to initiate ecmo wean. ecmo settings included flow at - l/min, map - mmhg, and paco between - mmhg. mca mean flow velocities were comparable to the systemic bp, and ranged from - cm/s in three patients and - cm/s in one patient. one patient suffered cerebral edema and two expired from withdrawal of care on sedation after multisystem organ failure without a chance neurological or neuroimaging assessment. the fourth patient retained consciousness and the ability to follow commands, but died from a massive gi bleed. tcd spectral waveforms can be useful bedside tools for patients on va-ecmo to assess for cerebral perfusion patterns. presence of hits reflecting microembolization can guide perfusionists to check for pulsatile flow, their relationship with systemic hemodynamics and va-ecmo settings is needed. cranial ultrasonography has a long history of use in neonates, but inadequate windows have limited its use in adults. a hemicraniectomy provides an obvious window for point-of-care intracranial imaging, providing similar views traditionally seen on ct and mri. we describe a standard approach and settings, presenting sample imaging demonstrating key anatomic landmarks. the hemicraniectomy ultrasonography preset was created and optimized using a phased array transducer with a - mhz frequency range. imaging parameters were tested and saved for d grayscale mode, with an emphasis on tissue harmonic imaging, adaptive image processing, and dynamic range. axial views are obtained from the ipsilateral temporal window, approximating the pterion, adjusting the probe to display a well-aligned view using the lateral ventricles as a landmark. by convention, the probe marker is placed anteriorly. the depth and focus are set to visualize the brain he probe craniocaudally permits visualization of the entire cranial vault. parasagittal and coronal views are obtained by placing the probe at the vertex, off midline, ipsilateral to the hemicraniectomy. several structures are clearly visualized and are available as landmarks for orientation. the ventricular system can be easily identified as hypoechoic spaces similar in appearance to ct or mr imaging. the brainstem and cerebellum, with its associated folia and peduncles are also easily seen. the thalami are identified as strongly hypoechoic paramedian structures. pathologic findings that can be easily seen include hydrocephalus, hemorrhage, and edema. aneurysm clips are hyperechoic with streak artifact, and ventriculostomy catheters can be seen as subtle hypoechoic areas within the cortex. hemicraniectomy pocus can be used to visualize the intracranial vault to facilitate evaluation of structural lesions and pathology at the bedside. the authors advocate adding hemicraniectomy pocus to the neurocritical care imaging arsenal in patients where this view is available. pain assessment is a challenge in critically ill patients with impaired consciousness, either because of sedation or concomitant severe brain injury. automated pupillometry has been used to assess the response to noxious stimulation in such patients. skin conductance, which has been used in the operative setting, has not been tested in this setting yet. the purpose of the study was to compare the pupillary response and skin conductance to pain stimulation in critically ill unconscious patients. prospective ongoing study including adult (> years) patients admitted to the intensive care unit of a university hospital and who were unconscious (glasgow coma scale < with a motor response < ) for several reasons. automated pupillometry (algiscan, idpupillary reflex dilation during tetanic stimulation. the tetanic stimulation ( hz) was applied to the skin area innervated by the ulnar nerve and was stepwise increased from to ma until pupil size had increased by % compared to baseline. the maximum intensity value allowed the determination of a pupillary pain index score ranging from (no nociception) to (high nociception): a pupillary pain peak per second ( concomitantly to tetanic stimulation. twelve patients (median age [ranges= - ] years; male gender / ) were included so far; eight patients had a primary brain injury ( / anoxic injury) and others were sedated because of shock with concomitant respiratory failure. all patients were under continuous intravenous sedation and analgesia; / were on vasopressors and / on continuous neuromuscular blockade. median gcs at the moment of pain assessment was [ - ] and median ppi was [ - ]; patients ( %) had adequate pain control. no changes of skin conductance variables were reported during pain stimulation. skin conductance was unable to detect insufficient nociception in critically ill unconscious patients. the cerebral arterial time constant (tau) reflects the time it takes to fill the cerebral arterial bed with blood during one cardiac cycle, and is derived from arterial blood pressure (abp) and middle cerebral artery flow-s with/without vasospasm (vsp) and delayed cerebral ischemia (dci) after aneurysmal subarachnoid hemorrhage (asah). ( ) ( ) . angiographic vsp and dci were adjudicated by neurointensivists. artifact-free cerebral arterial compliance and resistance. statistical comparisons were made using a two-tailed mann-whitney u-test. of asah patients, ( %) developed vsp and ( % of vsp) developed dci. patients had unilateral and bilateral vsp ( & % of vsp). one patient with unilateral vsp was available for monitoring prior to diagnosis. this patient had increased asymmetry in tau over time prior to diagnosis (slope: . s/day, r¬ : . ). tcd measures in patients were available prior to angiographic diagnosis of bilateral vsp, showing initial marginal asymmetry similar to the unilateral vsp case, then slightly decreasing asymmetry over time (mean slope: - cm/s higher in dci (p< . ). tau was . s greater for dci patients, however this did not reach significance (p= . ). explore the relationship of tau asymmetries with vsp and dci after asah. these may provide further insights into the pathomechanisms of vsp and dci while also having potential as a tool for earlier diagnosis of these important complications. pupillometry is more accurate and has higher inter-rater agreement than subjective pupil size and reactivity estimation. limitations include using a single high-intensity flash to evaluate the direct pupillary response only. we present preliminary data on using virtual reality-based pupillometry (vrp) with graded-intensity flashes and bilateral pupillary recording to monitor patients with large hemispheric infarction (lhi). we utilized a virtual reality headset-based system, i-pas (neurokinetics, pittsburgh, usa) to perform pupillometry. a total of homogeneous illumination flashes ( . to . cd/m², . sec on, . - . sec off) were presented to each eye while infrared cameras recorded pupillary area (mm ) continuously at samples/sec. this permits measurement of latency, magnitude and velocity of direct and consensual pupil constriction and dilation at each light intensity. : we performed pupillometry as described above in patients admitted with lhi from middle cerebral artery strokes. patients required decompressive craniectomy (dc) during the hospital course while the other patients did not require dc. bilateral graded-intensity pupillometry detected subtle changes in pupillary reactivity (peak constriction velocity in mm /s) prior to clinical deterioration, which were very pronounced when compared to normal control performance. singleneuropupillary index (npi) did not detect a change in pupillary reactivity in all but the most severe deterioration. virtual reality-based, graded intensity pupillometry is feasible in the intensive care unit and appears ed to set cutoff values that may aid in clinical decision making. limited access to conventional eeg results in significant delays to important diagnostic information, especially in patients with suspected non-convulsive seizures (ncs). recently, the rapid response eeg technology has proven to be clinically valuable. however, the economic aspect of this new technology has not been studied in detail. we retrospectively reviewed the use of the rapid response eeg device in our small community hospital over months since its launch in december . we performed limited chart review and collected information regarding eeg diagnosis, length of stay, and transfer to mothership hospital. we evaluated the clinical and economic impact of the device by considering the patients' clinical outcome and the estimated cost of hospitalization (~$ - /day) and transfer ($ - , ). metrics are not precise and are only estimates. the device was used in a total of patients. the treating physician or the nurse applied the device with and one with post-anoxic burst suppression. in patients with status epilepticus, seizures were aborted successfully, and median length of stay was . (national average of days). all patients were treated locally without requiring transfer to the main university hospital. considering the cost of rapid response eeg infrastructure and disposables (<$ , ) compared to conventional eeg systems (~$ , - , ) and eeg technologists (estimated to cost ~$ , - , ), and estimated range of $ , to $ , in annual savings because of shorter los and lesser transfers, this new technology seems economically advantageous. rapid response eeg system enabled significantly faster and easier access to eeg and helped detect a relatively high number of patients with gross eeg abnormalities. adopting the rapid response eeg improved emergent ncs detection and treatment in a cost-effective manner. patients requiring neurocritical care frequently have neurologic fluctuations of uncertain significance. we hypothesized that severe and prolonged events of neurologic deterioration (nd) have the greatest impact on discharge neurologic status and serve as intermediate indicators of poor outcome. we extracted nurse-documented gcs scores from electronic health record (ehr) data of consecutive patients admitted to a neurosciences intensive care unit (icu) or undergoing intracranial pressure monitoring (april - ) best initial -hour gcs (bestgcs- h), ) maximum magnitude of gcs decline (maxgcsdecline), ) duration of the episode of maximum gcs decline (dur-max), and ) the maximum duration of any gcs decline >= points (max pt-dur). we fit a -fold cross-validated logistic regression model predicting the final gcs - (vs. - ) and tested it in a % hold-out sample. we then evaluated the rates of poor outcome for combinations of these parameters. , consecutive admissions ( , unique patients) met inclusion criteria ( % with severe bestgcs- h ( - ), % with moderate bestgcs- h ( - ), and % with mild bestgcs- h ( - )). bestgcs- h, maxgcsdecline, dur-max, and max pt-dur, respectively, were independently associated with poor discharge gcs (or per standard deviation were . [ %ci . - . ], . [ . - . ], . [ . - . ], and . [ . -with a -point maxgcsdecline, the rate of poor outcome was % for patients with a severe bestgcs- h and >= -hour max-dur; % for patients with a severe bestgcs- h and < -hour max-dur; . % for patients with a mild bestgcs- h and >= -hour max-dur; and . % for patients with a mild bestgcs- h and < -hour max-dur. both the magnitude and duration of nd events are independently associated with neurological status at discharge. these empiric, informatics-derived thresholds may serve as useful intermediate outcomes facilitating the testing of biological associations and therapeutic interventions aimed at promoting neurologic recovery. unit. deteriorati worsening. we hypothesized that nonearlier than clinical deterioration. we prospectively collected data from patients with acute brain injury who are at a high risk of perfusion disturbance (sah, mmd, and severe anterior circulation ischemic stroke) between may and may . non--ry seconds neurological worsening were assessed using perfusion imaging and were categorized as hypoperfusion group and hyperperfusion group. baseline compared. non-monitoring should be highlighted in patients with high risk of deterioration. intracranial cerebral pressure (icp) monitoring is an integral part of acute brain injury management. while invasive icp monitor is the gold standard, there are several medical conditions that preclude its placement. non-invasive icp assessment tests (e.g. optic nerve sheath diameter, optic nerve disk elevation, pulsatility index, pupillary reactivity etc) have moderate accuracy when used individually. the aim of the present study is to validate a multimodal approach for intracranial hypertension detection. in this prospective study, patients with acute brain injury who had an evd placement for both icp measurement and treatment were included since march . we measured bilateral optic nerve sheath diameter (onsd) by ultrasound, bilateral optic nerve disk elevation (onde) by ultrasound, bilateral middle cerebral artery (mca) pulsatility index (pi) by using transcranial doppler and assessed pupillary reactivity with or without pupillometer as part of multimodal assessment for measuring intracranial pressure. we assessed the correlation and agreement of these values with icp measured by the evd. we included measurements in patients with acute brain injury. the presence of two or more values of mean onsd greater than mm, unilateral or bilateral presence of onde and mean mca pi greater than . has % sensitivity ( % ci . - . ) and . % specificity ( %ci . - . ) for predicting icp greater than mmhg. non-invasive multimodal assessment can be easily done by bedside, requires minimal training and seems to correlate well with increased icp. raised icp following acute brain injury is associated with poor outcome. monitoring with early detection is important in reducing sustained icp crisis. previous studies demonstrated rheoencephalography (reg) reflects cerebrovascular reactivity and may substitute invasive monitoring techniques. we hypothesized using a correlation coefficient between slow spontaneous changes in reg and systolic arterial pressure to calculate regx. reg measurements were obtained from ten patients with acute brain injury. analog waveforms of reg and arm bioimpedance pulse waves were recorded with a bioimpedance amplifier. we used the icm+ program (prx) calcu bioimpedance pulse waves (regx) instead of icp and invasive arterial pressure. visualized by previously established waveform changes on reg. a change in mean regx greater than the previous recording's mean regx value was clinically significant as opposed to absolute mean regx . one patient with a right ica infarction clinically deteriorated from moving all extremities to extensor posturing on the right and flaccid paralysis on the left with significant delta mean regx. another with bilateral aca distribution ischemic infarctions worsened from flexor to extensor posturing with significant delta mean regx. lastly, a patient with ventriculoperitoneal shunt malfunction repair improved from gcs to with multiple significant delta mean regx values between recordings. our series demonstrated clinical significance of patient specific delta mean regx suggesting importance of presenting mean regx for detection of changes in intracranial compliance. like presenting blood pressure and relative changes in blood pressure rather than absolute changes in blood pressure or specific values, regx was shown significant in a similar manner. regx is a realistic means of future noninvasive neuromonitoring. dialysis is characterized by markedly increased rates of stroke and cerebral micro-vascular disease, though the mechanisms by which dialysis modalities impact cerebral hemodynamics have not been well studied. this case series compares intra-dialytic cerebral hemodynamics measured by transcranial doppler (tcd) in patients receiving intermittent hemodialysis (ihd) versus peritoneal dialysis (pd). ten outpatient end-stage renal disease (esrd) without stroke were identified. tcd mean flow velocity averaged. six patients administered hemodialysis were followed over minutes, with mean arterial d every minutes. there was no statistically significant difference between dialyses group and no significant change over time. to quantify volatility in patient measurements over time, we calculated the coefficient of variation -sum test. to test if there was a difference in volatility between dialyses groups, we used a wilcoxon rankgroup (p < . ). in this small case series, though cerebral hemodynamics are not significantly different among stable measures are more stable over time for patients on the peritoneal dialyses group. end-stage renal disease (esrd) patients with acute neurologic injury are at risk of altered cerebral hemodynamics during dialysis. here, we present transcranial doppler (tcd) images revealing marked intra-dialytic increased distal vascular resistance and compromised flow velocity in an esrd patient with acute traumatic brain injury. the patient underwent continuous tcd monitoring during hemodialysis to monitor intra-dialytic cerebral hemodynamics. a year-old man with esrd on chronic presented with headaches after a fall. ct head revealed mm right convexity acute subdural hematoma with - mm leftward midline shift and right parietal parenchymal contusion. on arrival to the neuro-icu, the patient was afebrile, hemodynamically stable, and fully oriented with no focal deficits. repeat ct head six hours from initial was stable. the patient was started on his outpatient prescription of dialysis (dialysate na meq/l, blood flow rate ml/min), run without heparin. within first hours of hemodialysis patient developed progressive rightsided headache, which evolved to vomiting, decreased in level of consciousness, and left-sided weakness. he intermittently opened eyes to stimulation but required persistent painful stimulation to answer orientation questions. he had no changes in mean arterial pressure during hemodialysis. his serum bun had decreased from to mg/dl, and his serum sodium remained unchanged. emergent ct head was stable from prior. intra-dialytic tcd waveforms revealed progressively increased distal resistance to flow, measured by pulsatility index (pi) at his bilateral middle cerebral arteries (mca), and compromised mca velocities. this change was dramatic on the right, the same side as his subdural hemorrhage and cerebral contusion. esrd patients with critical neurologic injury are at risk for altered cerebral hemodynamics during dialysis. tcd ultrasonography may be a practical bedside tool to screen for patients at particular risk, and guide medical decision-making regarding dialysis prescription for esrd patients in the neuro-icu. point of care ultrasound (pocus) differs from diagnostic ultrasound in being often performed by clinicians and focused to acquire only relevant images to answer a specific clinical question. most ultrasound modalities have differentiated clinical indications where pocus is appropriate: the use of echocardiography to rule out tamponade in shock is considered pocus while the assessment of diastolic dysfunction in heart failure deserves a diagnostic exam. neuroultrasound has been used in various clinical indications like vasospasm, intracranial stenosis, collateralization, and emboli monitoring. these studies are mostly performed by sonographers as diagnostic studies. with emerging interest in assessing pocus indications, we performed a systematic literature review to identify all clinical indications of neuroultrasound and used a delphi based review by three experts to differentiate clinical indications where neuroultrasound could have point-of-care uses. two authors (lmh, gb) performed a systematic review to identify all reported modalities and clinical indications of neuroultrasound (tcd, duplex, b-mode, carotid, ocular and temporal) in medline, embase, cochrane, and scopus databases. three experts (jgd, ct, as) were surveyed using the delphi method to review each clinical indication and modality on whether it was focused on diagnosis or management and whether the clinical indication was a valid pocus. differences in opinion were settled with a final face-to-face discussion to reach a consensus. the systematic review determined total clinical indications of point of care use of neuroultrasound individualized by disease and modality. in indications it was considered a diagnostic adjunct, in instances it was considered an aide in management, and in instances it was determined to aid in both diagnosis and management decisions. there are many point of care indications of neuroultrasound in neurocritical care. this consensus opinion can guide clinicians to clinical indications where point of care use can aide in bedside diagnosis and management. in a systematic review, we reported current literatures on neuromonitoring methods in left ventricular assist device(lvad) population. we searched five databases (pubmed, embase, cochrane library, web of science, scopus, clinicaltrials.gov) related to lvad and neurological monitoring methods from inception through january . of unique citations, studies ( participants) met the inclusion criteria. the median age was . (interquartile range . - . , . % male). study designs were retrospective observational studies (n= ) and prospective observational studies (n= ). neuromonitoring methods studies included transcranial dopplers(tcd) for emboli monitoring(n= ) or cerebral autoregulation monitoring (n= ), traditional neuroimaging (ct/mri) (n= ), cerebral oximetry(n= ), carotid ultrasound (n= ) and plasma vad, articles studied pulsatile- current evidence on neuromonitoring in lvad is limited and there is no consensus on the indication and effectiveness on use of any neuromonitoring methods. the publications have significant heterogeneity adequate power are warranted to develop an optimal neurological monitoring protocol and prevention strategy. midbrain compression secondary to cerebral edema or hemorrhage results in high mortality and morbidity. quantitative pupillometry holds promise as a bedside indicator of worsening anatomic tissue shifts. because pupil reactivity relies on an intact neural network through the diencephalon and brainstem, compression can lead to changes in pupil size and reactivity. we studied markers of compression and pupillometry within hours of head ct in patients with anterior ischemic stroke (ais) or supratentorial intraparenchymal hemorrhage (iph) causing mass effect. we reviewed scans from patients with unilateral injury from ais (> / of mca territory) or iph (> ml). we assessed midline (mls) and pineal gland shift (pgs), as well as novel measurements of midbrain compression including interpeduncular shift (ips) and the ipsilateral and contralateral cerebral peduncle hemi-distances to the interpeduncular cistern (icphd, ccphd). multilevel modeling was used to analyze radiographic measurements with quantitative pupil metrics including pupil reactivity (dnpi) and size (dsize) differences between eyes. pupil reactivity and size differences were significantly associated with radiographic markers of midbrain noninvasive indicators of brainstem compression. evaluation of optic nerve sheath diameter (onsd) has been widely examined as both a correlate of intracranial pressure (icp), and a potential predictor of outcome after neurological injury. recent studies have evaluated sonographic measurement of onsd, yet clinical limitations to this approach persist. evaluation of onsd measurements via routine brain computed tomography (ct) imaging has been less studied, but offers potential for detection of increased icp in the absence of invasive monitoring. previous studies have employed a cross-sectional approach to onsd measurements via ct scan, primarily among patients with traumatic brain injury (tbi). however, no studies have evaluated serial correlations between ct onsd measurements and icp to evaluate strength of correlations during hospitalization, and across diagnosis types. the purpose of this study was to investigate correlations between onsd via serial ct imaging and icp among adult patients with neurological injury. retrospective cohort study of all adult patients admitted with acute neurological injury requiring icp monitoring and critical care admission. n= . diagnosis type included tbi ( %), aneurysmal subarachnoid hemorrhage ( %), intracranial hemorrhage ( %), cranial mass ( %), and other ( %). there was a strong, positive correlation between right/left onsd across all time points (r= . - , p< . ), suggesting a consistent bilateral response. correlations were strongest between initial inpatient ct scan onsd readings and icp (r= . , p< . ), but decreased over time. patients with increased icp across all diagnosis types experienced higher onsd values upon presentation to the emergency department (ed) and on serial ct scans throughout hospitalization (range . mm- . mm, p< . ). urements as a potential indicator of increased icp in the absence of invasive monitoring. serial ct brain imaging is often performed to evaluate for intracranial changes during hospitalization, and measurement of onsd during this imaging can contribute to decisions regarding more invasive monitoring. monitoring of burst-suppression-pattern (bsp) in electroencephalography (eeg) is relevant to control barbiturate-induced coma. currently, the assessment of bsp is based on continuous observation of the eeg with manual counting of bursts per minute (bpm) by experts, which is prone to inter-rater variability. we evaluated the reliability of a new algorithm for automatic bsp-detection compared to manual assessment in two thiopental-induced burst-suppressed patients. a bipolar -channel eeg-montage was recorded. the montage was bandpass filtered into typical eeg rhythms and segmented into secs -moonen metric, a distance matrix between all epochs in the first hour of data from patient us to cluster this matrix into clusters: burst, suppression and artifact. we labelled the rest of the (test) data from patient and patient by training support vector machine classifier from the labels produced by clustering. the eeg was scored by a neurologist to get ground truth bpm ranges (min, max for intervals of minutes to hour) for both patients. the algorithm provided estimated ranges of bpm for these intervals. the pilot data shows a high correlation of automatic burst counts compared to the manual counting. we found a significant pearson correlation (patient : . , p< . , patient : . , p< . ) and linear regression coefficient (patient : . , p< . , patient : . , p< . ) between estimated and ground truth bpm ranges. the automatic detection of the bursts provides an objective and fast assessment of bsp. the algorithm showed a slightly lower sensitivity due to the missing detection of very short or low bursts. we are ation. ventilated neurocritically ill patients is unknown and explored in this study. a retrospective cohort study was performed on patients admitted to the neurocritical care service between / / and / / , hospital-wide o shut down for maintenance and a switch to olerated with lowest being % owest spo of > % and spo < % amongst the patients in the pre and post-o shutdown groups. -tolerated. with the risk of hyperoxia and its potential negative effects on neuronal injury, a subset of neurocritically whole body hypothermia has been used as a treatment for patients with severe traumatic brain injury (tbi) since many years. invasive brain temperature monitoring is the most commonly practiced for target temperature management in these patients; however, complications are common due to the invasive nature of the procedure. the objective of the current investigation was to evaluate the association between brain temperatures obtained using a non-invasive sensor (accucor) and an intracranial pressure/temperature (icp) catheter during selective brain cooling in patients with tbi. aluated during a selective brain cooling over hours using both a parenchymal icp catheter (raumedic -pt) and the accucor sensor, with a catheter positioned in the nasopharynx. mean temperature values for each participant were obtained along the cooling intervention. outlier values derived from the accucor sensor were detected and removed prior to comparison. the variation in brain temperatures was calculated by mean temperature differences obtained using both measuring devices for each participant. mean brain temperature values were very similar between devices: . °c ( . °c- . °c) for the icp catheter and . °c ( . °c- . °c) for the accucor sensor (p-value: . , % ci: - . to . ). the median temperature difference between the devices was . ºc (minimum: - . °c, maximum: . °c, p-value: . ). our results suggest that there were no differences between brain temperature measurements conducted using the icp catheter and the non-invasive accucor sensor. this conclusion highlights the precision of non-invasive temperature monitoring, a safe alternative to the current invasive practice. monitoring procedures. sepsis-associated encephalopathy (sae) is a multifactorial syndrome, characterized as diffuse brain dysfunction that occurs secondary to infection in the body without overt central nervous system infection. the prognosis for sae is associated with the degree of cerebral damage. we investigated the relationship between the wavelet coherence of cerebral oxyhemoglobin (oxyhb) among different channels and outcomes in patients with sae. consecutive patients with sae were included. moreover, we included normal controls (n= ) for comparison. the cerebral oxyhb data were collected using functional near-infrared spectroscopy (nirsit, obelab inc.). the coherence between sections of prefrontal oxyhb oscillations in five frequency intervals (i, . - hz; ii, . - . hz; iii, . - . hz; iv, . - . hz; and v, . - . hz) were analyzed using wavelet coherence. in addition, we analyzed the coherence of electroencephalography (eeg) signal in three frequency intervals (delta, - hz; theta, - hz; and alpha, - hz). we evaluated the outcomes using glasgow coma scale (gcs) cores at discharge. the patients were categorized into three groups of normal control, good outcome (gcs - ), and poor outcome among the included sae patients (mean age, . years; and male, . %), patients ( . %) had a good outcome. in the poor outcome group, phase coherence was significantly lower compared to good outcome and the normal groups, especially for the myogenic frequency interval iii ( . ± . vs. . ± . vs. . ± . , p < . , respectively). however, the phase coherence of eeg signal was similar in two groups. our results demonstrated that the lower phase coherence of oxyhb in the myogenic signal, which originated from the vascular smooth muscle cells in the brain, was related to the poor outcome in sae patients. this suggests that evaluating cerebral dysfunction using wavelet coherence of oxyhb could be a useful outcome predictor following sae. external ventricular drain (evd) placement is a common procedure in the neurointensive care unit and intracranial hemorrhage (ich) is a recognized complication. in this study we sought to determine the factors associated with ich development after evd placement. retrospective study performed at a tertiary hospital. we identified all patients in whom an evd was placed over a month period. electronic chart review was done to obtain basic demographics, past medical history, use of antiplatelets/anticoagulants, type of catheter placed and presence of intracranial hypertension (ih). computed tomographies were reviewed to identify evd-associated ich. ichs were classified into symptomatic (gcs decline > points, intubation, outcome of death, or new focal continuous variables were analyzed with a proportion of the means test. the sample was comprised of subjects, had evd-associated ich. the median age was years. there was no significant difference in race or gender between patients with ich and those without ich. age, catheter type, history or inpatient use of anti-thrombotics, recent surgery, tpa use, heparin use, history of hypertension, hospital outcome, prior stroke, symptomatic hemorrhages, and icp spikes were analyzed, but only age ( . hemorrhage and . non-hemorrhage, p = . ), history of antithrombotic use ( / hemorrhage and / non-hemorrhage, p = . ) and icp spikes ( / hemorrhage and / non-hemorrhage, p = . ) were significantly associated with ich occurrence. three significant factors were associated with tract hemorrhages; age, history of anti-thrombotic use, and icp spikes. two of these factors have been previously supported by prior studies however, no prior study has correlated icp spikes to evd hemorrhages. additional studies may further validate the association between icp spikes and evd-related tract hemorrhages. targeted temperature management(ttm) aimed at helping to improve neurological outcomes associated with ischemic stroke have been studied continuously. however, it is not well known whether the parameters in ttm initiation, induction, maintenance will affect neurologic prognosis. we restrospectively reviewed medical records of the patients with large hemispheric infarction(lhi) who underwent ttm at snubh neurological intensive care unit from . . . to . . . onset to ttm initiation, induction period, ttm maintenance duration were investigated and dichotomized. neurologic prognosis was determined by the month death and modified rankin scale(mrs). a total of patients were included in the study. longer onset to ttm initiation(> hours) was associated with less month death. shorter ttm induction period(<= hours) was associated with less death rate, more fair outcome(mrs - ). ttm maintenance duration(within days or more) was not statistically correlated with neurologic prognosis. shorter ttm induction period may reduce death in lhi through maximizing icp control effect. the high mortality rate in patients with shorter onset to ttm initiation is likely to be related to the severity of initial symptom(mean nihss vs ). non-pulsatile continuous blood flow can cause endothelial dysfunction and small vasculature injury. the impact of non-physiologic blood flow on cerebral autoregulatory function and brain injury has not been extensively studied. we report a case of posterior reversible encephalopathy syndrome (pres) in a patient supported by a continuous flow pump, venoarterial extracorporeal membrane oxygenation (ecmo) for acute cardiogenic shock secondary to iatrogenic ventricular septal defect (vsd). a year-old male with hypertrophic cardiomyopathy was admitted for elective septal myectomy with an ascending aorta and hemi-arch replacement. the surgery was complicated by an iatrogenic vsd requiring urgent va-ecmo cannulation for cardiogenic shock. on day , ct brain achieved for poor neurological examination revealed extensive bilateral parietal, occipital and cerebellar hypodense lesions consistent with the typical imaging features of pres. a repeat ct brain on day depicted further extension of brain injury to the bilateral frontal lobes. due to worsening neurologic status, the decision was made to place an intracranial pressure monitor and lower the ecmo flow to return to a pulsatile flow state. the patient was closely monitored for improvement with paco levels, serial ct scans, and neurologic examinations. repeat ct scans on pod and depicted improvement in the bilateral cytotoxic edema with paco levels improving to - mmhg at a reduced ecmo flow rate of . - . l/min. his neurologic examination also improved with spontaneous movements noted in all four extremities. although neurologically cleared for heparin loading, he remained too hemodynamically unstable for open surgical repair and his surrogate decision makers decided to withdraw life-sustaining therapy. our case report illustrates the limited knowledge on the consequences of ecmo's impact on cerebral dynamic cerebrovascular autoregulatory changes in real-time that occur with patients with continuous flow pumps. hospital-onset unresponsiveness (hou) may occur in patients hospitalized for non-neurological conditions; while hou tends to be a transient systemic event, it may also indicate underlying neurological problems. quantitative pupillometry provides npi (neurological pupillary index), a quantitative measurement of pupillary light reflexes that have been traditionally assessed via subjective visual impression. we determined the clinical usefulness of npi in predicting the outcomes of patients who have experienced hou. hou was defined as a newly developed altered mental status and cases coded as "unresponsive" in the acdu (alert, confused, drowsy, and unresponsive) scale. we analyzed the demographics, radiological findings, etiology of hou, npi, in-hospital mortality, and -month modified rankin scale (mrs) scores. a total of cases in patients were analyzed, out of which cases ( %) had been assessed with quantitative pupillometry. cerebral herniation syndrome (chs) was found in ( %) cases; higher npi was associated with decreased risk for chs (odds ratio, . ; % confidence interval [ci], . - . ; p= . ), and no other factors were associated with the risk of chs. a total of ( %) cases showed in-hospital mortality. after controlling for clinical covariates and the presence of chs, lower npi was independently associated with increased risk for in-hospital mortality (odds ratio, . ; % ci, . - . ; p= . ). at a cutoff value of . , the specificity and sensitivity of npi for predicting in-hospital mortality were % and %, respectively. multivariate analysis showed an independent association between lower npi and unfavorable clinical outcomes (common odds ratio, . ; % ci, . - . ; p= . ). npi, a quantitative index of pupillary light reflex, was significantly associated with the risk of cerebral herniation and in-hospital mortality in non-neurological patients with hou. measuring pupillary light reflexes through quantitative pupillometry may be useful when responding to hou cases. target temperature management (ttm) improves survival and neurologic outcome and is recommended for cardiac arrest (ca) survivors by international guidelines. shivering is both an anticipated consequence and a major adverse effect of ttm. the bedside shivering assessment scale (bsas) is a simple, validated four-point scale that enables repeated quantification of shivering at the bedside. in this study, we examine the association between time to return of spontaneous circulation (ttrosc) and shivering (defined as bsas > ). data on post-cardiac arrest patients treated with ttm were collected from apache outcome database and medical records. baseline characteristics included age, apache iii scores, ttrosc (minutes), time to target temperature (ttt, minutes), and bsas > (percentage of hours bsas > /total number of hours bsas was done). outcome was survival to hospital discharge with good neurologic outcome. group and group included patients with ttrosc below or above the median respectively. all patients received continuous infusions of fentanyl and sedatives (propofol, midazolam, and/or dexmedetomidine) as per our institution's protocol. compared to group (n = ), group (n = ) had similar age ( ± vs ± , p = . ), similar apache iii scores ( ± vs ± , p = . ), longer ttrosc ( ± vs ± , p = . ), similar ttt ( ± vs ± , p = . ), more shivering ( . % vs . %, p = . ), and similar survival with good neurologic outcome ( % vs %, p = . ) respectively. ttrosc was strongly positively correlated with shivering (pearson correlation coefficient, r = . ). in comatose survivors of cardiac arrest who received ttm, longer ttrosc (indirect measure of brain injury) was associated with more shivering. these findings should be further investigated in prospective studies. pupillometry assessment of the pupillary light reflex (plr) is gradually replacing manual plr assessment. this new technology has led to a recent increase in clinical research and subsequent need to validate those results. mcnett et al. recently investigated the association between intracranial pressure (icp) and serial pupillometer values and found that pupillometry readings are different significantly in the setting of increased icp. this is a replication of the mcnett study in a larger multicenter cohort to explore these findings. data from the establishing normative data for pupillometer assessments in neuroscience intensive care (end-panic) registry include over , patients with a neurological condition. subjects with documented icp readings provided , observations (daily mean icp values) which were included in this analysis. statistical analysis (sas v . ) included descriptive statistics and to examine the differences . subject mean age was years, % were female and . % were caucasian. student t-test analysis was used to explore for differences. excepting latency and right eye npi, lower plr values were associated with higher icp (compared to low or normal icp) for all mean pupillometer/plr variables for both left and right eyes (t range [- . to . ]; p-value range [< . to . ]). the findings confirm and extend those of mcnett. patients with increased icp tend to have lower pupillometer readings. automated pupillometer is a non-invasive method that provides prediction of the icp trends which can help neurocritical care professionals in assessing patients with neurological conditions. encephalopathy is a common complication in cirrhotic patients. clinical manifestations are diverse, but few data are available on pupillary abnormalities in such patients. the aim of this study was to evaluate whether automated pupillometry could detect pupillary dysfunction in this patients' population. prospective ongoing study including the assessment of the pupillary changes to light stimulation using automated pupillometry (neurooptics, irvine, usa) in adult cirrhotic patients after icu admission. the degree of encephalopathy was scored by the glasgow coma score (gcs). severity of cirrhosis was assessed by the child-pugh and meld scores. severity of liver encephalopathy was assessed according to standard criteria. different biological variables, including ammonium (nh ), was measured to pupillary assessment. the median values of pupillometry-derived variables were collected for both eyes. -pugh and nh levels were found with any of the pupillometry-derived variables. no differences in pupillometry-derived variables were observed across different degree of liver encephalopathy. automated pupillometry did not show correlations between pupillary abnormalities and the severity of critically ill patients with liver cirrhosis. prognostication in comatose survivors of cardiac arrest (ca) remains challenging. the purpose of this study was to determine if early quantitative analysis of resting eeg can improve prediction of commandfollowing by post-ca day . we prospectively enrolled patients admitted after ca. clinical care was performed according to our institutional protocol, which includes continuous eeg monitoring. -minute resting eeg epochs were clipped daily; clips were excluded if seizures or other confounders were present. epochs from post-ca days - were preprocessed for artifact reduction, then analyzed for three quantitative metrics: power spectral density, permutation entropy, and coherence. we created a predictive model using partial least squares regression analysis to distinguish eeg data as from patients who would or would not recover command-following by post-ca day . cross-validation of results was accomplished with a -times random assignment of % of data as training set and % as testing set. eeg clips were analyzed from patients ( . % female, age . +/- . years, pre-morbid mrs . +/- . and cpc . +/- . ). cardiac arrests occurred out-of-hospital in %, witnessed in . %, and had bystander cpr in . %. mean time to rosc was +/- minutes, . % had a shockable initial ekg rhythm, and . % of patients received therapeutic hypothermia. prior to day , . % regained consciousness and . % had withdrawal of care. using eeg data alone, predictive ability (expressed as average area under the receiver operating characteristics curve) yielded auc . +/comparison, the same model was constructed using clinical features (absence of pupil and corneal reflexes by day ) or laboratory testing (peak nse level). the model combining clinical, laboratory, plus eeg data yielded auc . +/- . , an improvement vs clinical features (auc . +/- . , p< . ) or nse levels (auc . +/- . , p< . ) alone. quantitative eeg analysis may provide adjunctive prognostic information regarding short-term recovery of consciousness. international guideline recommended pupillary light reflex (plr) and/or cortical response (n ) to short-latency somatosensory evoked potentials (sseps) at hours after return to spontaneous circulation as the only strong predictors of unfavorable outcome in comatose patients after cardiac arrest. the aim of this study was to compare this algorithm with a multimodal approach including other prognostic tools. post hoc analysis of an international multicenter (n= ; n= patients) prognostic study on automated pupillometry in comatose post-ca patients. the primary study endpoint was the accuracy of npi in predicting -month unfavorable neurological outcome (uo), defined as cerebral performance category (cpc) of - (severe disability, unresponsive wakefulness or death). patients with findings on plr, sseps, npi and eeg were included; the highest nse was also recorded, whenever available. an npi < on day , a discontinuous eeg background or clinical myoclonus over the first days, bilaterally absence of n calculated as: false positive / favorable outcome. we included patients; ( %) of those had uo. using the approach of guidelines, unfavorable outcome at day was observed in / patients with absent plr and / with absent n ; / ( %) patients with uo were identified. using the multimodal approach, uo was identified in / patients with npi < , in / patients with discontinuous eeg, in / patients with myoclonus and this study suggests that a multimodal approach, including npi, eeg, sseps and nse, could identify a after physicians introduced the idea to declare death based on loss of brain functionality, many countries incorporated brain death into their legal criteria for death. we sought to learn about the global legal perspective on brain death declaration (bdd). we collected legal documents about declaration of death around the world by searching national legislative databases and google. we utilized google translate to convert all documents into english then searched for references to criteria for bdd. in cases where there was conflicting information, we consulted local experts. we located legal documents on death declaration for countries, of which included a reference to brain death. legally stipulated criteria for bdd were identified for / countries. with respect to prerequisites for bdd legal stipulations existed in: / countries on confounders to exclude, / countries on an observation period before bdd, / countries on the minimum temperature for bdd and / countries on the minimum blood pressure for bdd. an assessment for coma was legally required in / countries. the fact that spinal reflexes do not preclude bdd was included in the legal criteria for bdd in / countries. a broad reference to an assessment for brainstem areflexia was legally mandated in / countries. the legal criteria included specific reflexes to test in / countries (pupillary / , corneal / , oculocephalic / , oculovestibular / , gag / , cough / , and other / ). every country legally required an assessment for the inability to breathe spontaneously, but only / described apnea testing in detail. the number of clinical exams required for legal bdd ranged from - . ancillary testing was legally required in / countries. the legally stipulated criteria for bdd differ around the world. standardizing the global legal perspective on bdd would help prevent ) variability in practice and ) false bdds. up to % of patients monitored with pupillometry during therapeutic temperature management (ttm) after cardiac arrest will have sluggish (sl) or non-reactive (nr) pupils. the neuroimaging findings and injury patterns of these patients have not been reported. adult patients treated with ttm after cardiac arrest with available pupillometry data from the neuroptics npi- were studied. discharge outcome was classified as poor (po) if the cerebral performance category score was - , and as good if - . pupil size, percent constriction, and constriction velocity were determined throughout ttm using data from the worst eye at each assessment. the neurological pupil index (npi) was scored from (nr) to (brisk), with values < considered sl. computed tomography (ct) and magnetic resonance (mr) neuroimaging was reviewed by a neuroradiologist blinded to pupillometry and outcome data. poor outcomes occurred in / ( %) patients with nr pupils during ttm, / ( %) patients with sl pupils, and / ( %) with normal (nl) pupil reactivity. pupil size did not predict outcome, but pupillometry data during ttm predicted poor outcome with auc . - . . when nonreactive pupils were first detected, / ( %) were < mm. % of patients had ct imaging, and % had mr imaging a median of (iqr - ) hours after recovery of spontaneous circulation. cerebral edema or herniation were identified in / ( %) nr vs / ( %) sl and / nl patients (p< . ). midbrain injury identified by t sequences was identified in / ( %) nr/sl patients versus / ( %) nl patients (p= . ). midbrain abnormalities were identified more often in patients with nr/sl pupils than edema/herniation ( % vs %, p= . ). a minority of patients with sluggish or non-reactive pupils after cardiac arrest have evidence of cerebral edema or herniation. midbrain injury is a more common mechanism to explain this common neurologic deficit. cardiac arrest (ca) survivors are often comatose and their arousal recovery is dependent on the extent of hypoxic-ischemic injury (hii). long-term neurologic outcomes are variable, difficult to predict, and biased by withdrawal of life-sustaining therapy. somatosensory evoked potentials (ssep) remain the gold standard for predicting arousal potential, but is not broadly available. we hypothesized that early hi-resolution mri may help assess arousal recovery potential as predicted by electrophysiologic outcome. comatose survivors of cardiac arrest admitted to an icu between june and january who underwent ssep and mri were retrospectively identified. d-hii burden in predefined regions. semi-automated region-of-interest (roi) tools in mipav were used to draw borders on dwi around the upper brainstem including the ascending reticular activating system (aras) to assess voxel intensity and derive hii volumes. our outcome of interest was ssep findings classified in two prognostic categories: indeterminate (bilaterally present n s or unilateral presence of n s) and poor prognosis (bilaterally absent n s). we used paired t-tests to compare presence of signal abnormality and rois between patients with sseps predicting poor outcome or indeterminate prognosis. consecutive ca survivors (mean age of . , % female) were included. no significant differences were noted in baseline characteristics between groups though time to rosc was noted to be vs mins for indeterminate and poor outcomes (p = . extent did not predict ssep status. no significant difference was noted in the voxel intensities on adc in the midbrain or pontine tegmentum. quantitative mri measures of hii extent may be superior in predicting arousal potential in comatose survivors of ca compared with manual rating. a quantitative image analysis pipeline is being developed for measuring aras lesion burden and predicting electrophysiologic based outcomes in ca. despite promising preclinical results, the application of intra arrest therapeutic hypothermia (iath) during cardiopulmonary resuscitation have produced controversial results in clinical trials. the aim of this review was to analyze the effects of such therapy on relevant outcomes in patients suffering from out-of-hospital cardiac arrest (ca). the following databases have been searched up to th may for human trials: pubmed (from ), embase (from ), cinahl (from ), the cochrane library (from ) and ovid/medline (from ). the search strategy will use the following terms: "arrest" or "cardiac arrest" or "heart arrest" and "intra arrest" or "during cpr" or "intra cpr" and "hypothermia" or "therapeutic hypothermia" or "cooling". references from identified studies and relevant review articles have also been searched for additional eligible citations. the search has been limited to english publications and has been conducted in accordance with the international liaison committee on resuscitation (ilcor) process of evidence evaluation. a total of six human studies (n= ; treated with iath) including four randomized controlled trial (loe ), one retrospective and one prospective controlled study (loe ) were identified. two studies used trans-nasal evaporative cooling and others intravenous cold fluids. overall rate of return of spontaneous circulation was similar between iath patients and controls ( / ) when compared to control group. no differences were found in the subgroup of shockable vs non-shockable rhythms. different effects on outcomes were observed according to the method used to induce iath when compared to controls. iath was not associated with improved outcomes when compared to standard of care. however, the method used to induce iath may potentially influence the beneficial effects of such intervention. amantadine may improve functional recovery in the subacute state following brain injury. we aimed to characterize eeg signatures in patients with acute brain injury (abi) receiving amantadine that did and those that did not recover consciousness. we studied a consecutive series of patients with acute brain injury patients who were treated with amantadine as a neurostimulant between september and december . all patients were initially comatose and underwent eeg prior to and after the initiation of amantadine. the ability to follow commands was assessed daily based on prior published methodology (claassen et al, annneurol ). eeg features that were assessed included sleep stages, posterior dominant rhythm (pdr), and power spectral density plots. we applied a multivariate regression model using generalized estimating equations (gee) to identify eeg features correlated with recovery of command following. eegs were analyzed by a board certified neurophysiologists. -free eeg clips), patients ( %) recovered consciousness during hospitalization. ich was the most common etiology in ( %) patients, followed by sah in ( %) patients. on average amantadine was given for +/- days. patients ( %) had seizures, only patients ( %) after starting amantadine. in our gee model, age (p= . ), sleep structures (p= . ), pdr (p= . ), and cumulative dose of amantadine (p= . ) were all associated with recovery of command following. spectral features corresponding to higher levels of anterior forebrain corticothalamic integrity correlated with higher levels of consciousness in % of recorded patients after days of amantadine use. the best spectral pattern per patient was seen . days on average prior to recovery of consciousness. eeg may provide a biomarker that indicates subsequent recovery of consciousness in unconscious patients with an acute brain injury that are treated with amantadine. depletion of cerebral glucose (i.e., cerebral glucopenia) occurs commonly and is associated with poor outcome in traumatic brain injury and subarachnoid hemorrhage. however, the incidence of cerebral glucopenia after diffuse hypoxic-ischemic brain injury (hibi) is unknown. we characterized the burden of cerebral glucopenia after hibi and its association with markers of physiological distress and outcome. we retrospectively analyzed cerebral microdialysis data from a cohort of patients with hibi. patients survived sudden cardiac arrest and patient had severe hypoxia after polysubstance overdose. hourly values of cerebral glucose, lactate, pyruvate, and glycerol as well as continuous intracranial pressure (icp), arterial blood pressure (abp) and interstitial brain oxygen (pbto ) were recorded. associations between average glucose/patient-day versus average lactate:pyruvate ratio, glycerol, icp, pbto , and abp were analyzed using linear regression. burden of glucopenia (defined % time with glucose < . mmol/l) was analyzed by patient-day. the relationship between glucopenia burden and discharge outcome was analyzed using the wilcoxon rank sum test. lower cerebral glucose was associated with higher cerebral glycerol (p= . ), higher lpr (p= . ), higher icp (p< . ), and lower pbto (p= . ) levels. there was no association between abp and cerebral glucose (p = . ). glucopenia burden increased progressively over time and peaked by postinjury day . / patients had good outcome (defined as return of consciousness prior to discharge). there was no association between outcome and cerebral glucopenia burden (p = . ). cerebral glucopenia is common after hibi and associates with markers of cellular distress. the burden of cerebral glucopenia progressively increases over several days and appears to peak more than week after injury. although there was no association between outcome and glucopenia burden, the number of patients in this study with good outcome was low. the utility of cerebral glucose monitoring after hibi merits further study. international guideline recommends using bilaterally absence of pupillary light reflex (plr) and/or bilaterally absence of the cortical response (n ) to short-latency somatosensory evoked potentials (sseps) at hours after return to spontaneous circulation to predict unfavorable outcome in comatose patients after cardiac arrest. the aim of this study was to compare this algorithm with a multimodal approach including other prognostic tools. retrospective study of adult (> years) cardiac arrest patients admitted from january to march and who underwent multimodal monitoring. we collected demographic characteristics and cardiac arrest data, together with sseps, the presence of burst-suppression on early eeg, a neurological pupillary index on the automated pupillometry < at after arrest and a neuron-specific enolase (nse) -month unfavorable neurological outcome (uo) with cerebral we included patients; ( %) of those had uo. using the approach of guidelines, unfavorable outcome at day was observed in / patients with absent plr, in / with absent n and / with combined absent pupillary light reflex and n ; / ( %) patients with uo were identified. using the multimodal approach, uo was identified in / patients with npi < and / patients with bs on eeg. among the others, uo was associated with absent n in / patients and with high nse values in / patients. this approach identified / ( %) patients with unfavorable outcome. the area under curve to predict uo for the approach of guidelines was . , which increased to . with the multimodal approach. this study suggests the a multimodal approach, including npi and bs on eeg, sseps and nse, has a higher predictive value for uo than recommended predictive tools. there is a high prevalence of seizures following cardiac arrest (ca), but not well studied among survivors with good neurological recovery. we describe the prevalence of clinical and electrographic seizures, anti-epileptic use, and eeg characteristics of ca survivors with good neurological outcomes. adults with return of spontaneous circulation (rosc) after in-hospital or out-of-hospital ca between / - / were eligible. a consecutive sample of survivors with included. prevalence of seizures and antiepileptic drugs (aed) use within -months after discharge were collected using a questionnaire administered via in-person or phone. a board-certified clinical neurophysiologist reviewed the eeg. of patients surviving to discharge, ( %) with -months follow-up were analyzed. average age was ± years, ( %) were women, ( %) patients had witnessed arrest, ( %) received defibrillation, with an average rosc duration of ± minutes, and a median cpc of at discharge. there were no clinical seizures reported during hospitalization. of available ( %) patients with raw eeg (median duration of days), only ( %) patients had electrographic seizures, ( . %) had continuous background as their best eeg pattern, ( %) with discontinuous background, ( %) with epileptiform discharges, and ( %) patients had burst suppression pattern that recovered later to a normal eeg pattern. none of the patients had any malignant eeg patterns, ( %) exhibited reactivity to a verbal or tactile stimulation and ( %) had the presence of sleep structures and posterior dominant rhythms. surprisingly, ( %) patients were discharged on an aed. clinical seizures and aed use were reported in / ( %) at -months follow up. both short and long-term seizure burden are very low among the cardiac arrest survivors with good neurological recovery. underlying factors related to high utilization of aed before discharge warrants further investigation. objective: early neuro-prognostication in the intensive care unit pediatric patients is essential to enable effective care planning, triaging level of care, and family support. in coma, the reliability of biomarkers such as electroencephalogram (eeg), anatomical neuroimaging to determine potential for consciousness and future functional capacity are less established in children. herein we present two case studies highlighting resting state functional mri (rs-fmri) as a clinically new means defining real-time brain function in the pediatric critically ill population. rs-fmri measures spontaneous low-frequency fluctuations in the blood oxygen dependent (bold) signal to investigate the networks of the brain. a standardized acquisition of data on a tesla mri under light tool melodic. whole brain networks determined by independent component analysis with false discovery rate at p< . to detect major brain networks. cases describe two critically ill children. one, with severe brain injury related to acute necrotic encephalopathy, and the other with diabetic ketoacidosis induced cerebral edema and uncal herniation. both had slow eeg background with sleep features approximately a week after presentation and were comatose by exam on the day of rs-fmri. rs-fmri detected normal brain function in the long-range fronto-parietal network, intact language-area networks, and default mode network. atypical networks were detected in brainstem and deep grey in both children. by hospital discharge, both children were awake and communicative with spontaneous movements. case one remain with tracheostomy with intermittent ventilation, case two had residual left hemiparesis, vision and language intact, mild cognitive deficits. in the cases reviewed, rs-mri may offer an objective measure of functional brain capacity and potential for meaningful recovery with preservation of language and long range connectivity networks in critically ill pediatric patients. provision of positive end-expiratory pressure (peep) through a conventional ventilator during apnea testing for brain death determination removes the need for additional equipment such as a peep valve, allows for use of high peep during apnea in patients with severe hypoxic respiratory failure and facilitates detection of respiratory effort on flow scalars. the advent of ventilators that permit deactivation of the apnea backup setting has made such testing possible. our goal was to examine the feasibility of peep use with conventional mechanical ventilation during apnea testing, with a focus on premature termination and inadvertent external triggering. performed without disconnection from the ventilator (dräger evita® infinity® v ), with deactivation of the apnea backup. this was a convenience sample based on availability of appropriately trained -support and peep - cmh o. apnea was confirmed by absence of chest rise and respiratory effort on the flow scalar. adequacy of respiratory stimulus was established by a co > mmhg and -point co rise from baseline. endpoints included early termination of the apnea test prior to minutes because of patient instability, any oxygen desaturation below % and inadvertent external triggering. inadvertent external triggering required repeat of apnea testing. ten patients underwent apnea testing while connected to the ventilator. apnea testing for at least minutes was successful in all patients. apnea was confirmed in all cases. no patient suffered oxygen desaturation below % or other instability. there was one instance of inadvertent external triggering caused by jostling of tubing, necessitating repeat testing. apnea testing with provision of peep through a conventional ventilator to improve tolerance is feasible. inadvertent external triggering is uncommon but may occur. despite well-defined aan guidelines on brain death declaration, there is marked variability in its practice nationally. this highlights the need for targeted brain death education initiatives. communication with surrogates or families about a brain death diagnosis and its implications is integral to brain death declaration, yet this has not been studied in a simulation setting. we developed a brain death simulation curriculum at our institution addressing knowledge and surrogate communication skill development. as part of this curriculum, multi-disciplinary critical care fellows completed a pre-curriculum multiple choice (mc) knowledge test and survey (likert - scale) evaluating comfort and confidence. a mandatory one-hour neurocritical care attending-led didactic regarding guidelines and technical aspects of brain death examination was conducted. subsequently, each fellow performed an observed brain death examination (simman g mannequin) with feedback followed by a standardized family scenario with delivery of a brain death -simulation survey, mc questions, and provided feedback. statistical analyses used -tail wilcoxon signed rank test (p<. ). thirteen critical care fellows participated (neurology[ ], anesthesia[ ], trauma[ ], pulmonary[ ]). only one fellow had previous formal brain death training with the majority [ %, (n= )] only participating in - brain death declarations. there was significant improvement across all measures: self-rated knowledge ( . to . , pre-simulation to post-simulation, p= . ), knowledge relative to peers ( % to %, p= . ), confidence ( . to . , p= . ) and comfort ( . to , p= . ) with performing a brain death exam, and comfort with family discussion ( . to . , p= . ). test scores improved from % to % after simulation (p= . ). all fellows found the curriculum beneficial (with all aspects wellreceived). critical care fellows may lack experience with brain death declaration. didactics coupled with simulation-based education can improve objective knowledge and comfort with brain death declaration and surrogate communication. there is a growing disparity between availability and demand for neurologic expertise, particularly in smaller community hospitals. telemedicine has helped to bridge this disparity with respect to cerebrovascular disease and is used increasingly to deliver other types of neurologic expertise to patients. while the nihss is widely used in telestroke, other formalized neurologic exams have not been well studied. we seek to determine whether the components of a brain death exam can be reliably performed via telepresence. patients suspected of meeting brain death criteria were enrolled from july to may . standard bedside neurologic exam (bne) performed by the attending neurointensivist in accordance with our institutional protocol was compared with the telepresence neurologic exam (tne) performed by a study neurointensivist blinded to the findings of the bne and a trained bedside assistant. we analyzed the agreement between examiners regarding findings of coma, corneal reflex, pupillary light reflex, oculovestibular reflex, oculocephalic reflex, cough, gag, motor response, and apnea. we enrolled patients over months. proximate causes were intracerebral hemorrhage ( / ), anoxic brain injury, ( / ), and cerebral infarction ( / ). all examination components performed in the bne could be completed by tne. in cases, neither examiner could assess all exam components. in cases spinal cord injury precluded oculocephalic testing. in case refractory hypoxia precluded apnea testing. bne and tne agreed in % of testable components. in cases testing pupillary light reflex was reported as difficult in the tne but not the bne. all telepresence examiners reported high confidence that the exam findings were consistent with brain death. preliminary findings from our pilot study suggest that the use telepresence for brain death examination introduction traumatic brain injury (tbi) is often followed by the loss of con increases each day following the injury, but the contents of consciousness, also known as qualia, do not uniformly return. while there is some information about brain regions supporting arousal, less is known about circuits encoding contents of consciousness. some evidence supports a role for the thalamus in consciousness, but it is controversial whether it supports arousal, or has a more nuanced role in consciousness. to address this question, we combined intracranial recordings in patients recovering consciousness with neuroimaging of thalamocortical circuits. electrophysiology we recorded electrocorticography (ecog) from prefrontal cortex and anterior cingulate cortex, as well as scalp electroencephalography (eeg) from a standard - montage, during singleand parietal cortex based on coherence between the evoked responses in these regions when acc was stimulated. radiology. regions of structural damage were extracted from the post-tbi mri and diffusion tensor imaging (dti) radiographs. tractography using dsi studio™ was performed with seed regions placed in the bilateral mediodorsal nucleus of the thalamus. we found that in patients with injury isolated to the cortex and/or white matter, the cortico-cortical functional connectivity across frontoparietal networks was preserved, and these patients recovered consciousness. however, a patient with thalamic injury failed to recover consciousness, despite an increased level of arousal following injury. the functional connectivity across cortical regions was drastically lower following thalamic injury, even when the cortical damage was minimal. we propose that integration and communication of information across frontoparietal networks, which is required for contents of consciousness, is dependent on thalamic input. thus future efforts have to be focused on restoring this input. brain herniation is a deadly event that requires rapid administration of hyperosmotic agents (hoas) such as . % nacl. a recent retrospective study showed that intraosseous (io) cannulation provides a safe route for rapid administration of hoas compared to central venous catheters (cvc) and peripheral intravenous catheters (piv). prospective study to measure the time-to-treatment for . % nacl or mannitol via io, cvc, or piv. a data collection form ("brain code narrator") was created by nurses and providers to prospectively collect clinical data, hemodynamic measures, and time-to-treatment and administration route for hoas during brain codes. in addition, demographics, diagnosis, serum sodium (na+) and complete blood cell count, as well as immediate and delayed complications, and outcomes were collected. brain code narrator was used to collect data for patients: males with median (iqr) age ( - ) years. diagnosis included intracerebral hemorrhage (n= ), subarachnoid hemorrhage (n= ), and other (n= ). all patients were intubated. most patients were co-treated with induced hyperventilation. . %nacl ( cc) via cvc and io route and mannitol ( gm) via piv were administered during , , and events with median time-to-treatments of ( , ), ( , ) and ( , ) minutes, respectively (p value < . for all comparisons). no adverse events, such as hypotension or tissue injury were noted. preliminary data suggest that during brain herniation, administration of . % nacl via io or cvc is more rapid than iv mannitol. io cannulation for . % nacl may be an alternate route of administration of hoas during brian code. additional data will be provided regarding herniation reversal and long-term hematologic abnormalities. stress hyperglycemia is common in the critically ill and is associated with poor neurological outcomes in cardiac arrest patients. it is unknown whether glycemic dysregulation have different prevalence according to cardiac arrest etiology. we hypothesized that overdose-related cardiac arrest (odca) patients are more vulnerable to hypoglycemic events given the circumstances of arrest. we retrospectively studied cardiac arrest patients treated at two urban hospitals from the multimodal outcome characterization in comatose cardiac arrest (mocha) registry from - . we examined glucose dysregulation (hypoglycemia blood glucose [bg]< mg/dl, hyperglycemia bg> mg/dl) within first h from arrest in odca and non-odca cohorts. statistical analyses included paired/unpaired t-tests, chi-al dysfunction was defined by scores of gos- of the patients, ( . %) were odca. there were no differences in bmi, gender, ethnicity, or therapeutic hypothermia (th) treatment across cohorts, but odca patients were younger ( ± vs ± year-old; p< . ), had lower prevalence of diabetes ( . vs . %; p= . ) and lower hemoglobin a c ( . vs . %; p= . ). mean bg reduction from - h to - h in odca patients was significantly smaller ( . ± . vs . ± . mg/dl; p= . ) despite no difference in mean peak bg. bg nadirs were lower in odca patients ( . ± . vs . ± . mg/dl; p= . ). patients developed glycemic dysregulation: ( %) odca vs ( %) non-odca; odca patients were nearly two times more likely to develop hypoglycemia (rr . [ . - . ]; p= . ) but had no increased risk of hyperglycemia (rr . [ . - . ]). among patients with glycemic dysregulation, odca was associated with higher risk of in-hospital death or neurological dysfunction (or . [ . - . ]; p= . ). despite exhibiting blunted bg reductions to hyperglycemic treatment, odca patients were more susceptible to hypoglycemia in the first h postmanagement strategies should account for cardiac arrest etiology. sedation and neuromuscular blockade (nmb) in patients undergoing targeted temperature management (ttm) after cardiac arrest (ca) are recommended for patient discomfort and management of shivering. this study assessed the association between nmb use and neurological outcome in comatose survivors of ca who received ttm. data on post-cardiac arrest patients treated with ttm were collected from apache outcome database and medical records. ttm of °c or °c is chosen based on critical care physician's discretion. baseline characteristics included age, apache iii scores, time to return of spontaneous circulation (ttrosc, minutes), time to target temperature (ttt, minutes), and shockable rhythm (sr, %). outcome was survival with good neurologic outcome. compared to the no nmb group (n = ), the prn nmb group (n = ) and continuous nmb group (n = ) had similar age ( ± and ± vs ± , p = . , . ),similar apache iii scores ( ± and ± vs ± , p = . , . ), comparable ttrosc ( ± and ± vs ± , p = . , . ), longer ttt ( ± and ± vs ± , p = . , . ), comparable percentage of sr ( % and % vs %, p = . , . ), and similar proportion of patients with tt of vs ( % and vs %, p = . , . ) respectively. survival with good neurologic outcome was achieved in % in no nmb group vs % in prn nmb group (p = . ) and % in continuous nmb group (p = . ) in the present study, in comatose survivors of cardiac arrest who received ttm, use of nmb had no effect on neurologic outcome. the apnea test is an essential examination for the determination of brain death. however, hypotension, hypoxemia, and other complications during the apnea test can affect the stability of brain-dead patients, as well as organ function for recipients. therefore, it is necessary to establish standard guidelines for apnea testing. the modified apnea test (mat) comprises delivery of % oxygen through the endotracheal tube connected to manual resuscitator (ambu® bag) with the positive end-expiratory pressure (peep) valve after disconnection of -nine instances of the conventional apnea test (cat) were performed in brain-dead patients; instances of the mat were performed in brain-dead patients. the mean duration of the apnea test was . ± . minutes in the cat group and . ± . minutes in the mat group. there were no significant changes in paco , pao , or ph between the cat and mat groups (p = . , . , and . , respectively). in overweight patients (body mass index prevented dramatic reductions in pao and sao (p < . for both). in the patients who had hypoxic brain injury due to hanging, differences in pao and sao in the mat group were significantly smaller than in the cat group (p < . ). although mat, which was invented to maintain peep, was not efficient for all brain-dead patients, it could be helpful in selected patient groups, such as overweight patients or those who had hypoxic injury due to hanging. clinicians should consider this reliable short-term apnea test. coma is a serious complication that currently has no good biological markers. the hypothalamus plays an important function in consciousness circuity. orexin a/b, a neuropeptide produced in the hypothalamus has an excitatory effect on multiple target areas in the brain. previous orexin studies ry (tbi), stroke and comatose states. the goals of our study: ( ) the utility of orexin as a marker of coma recovery, ( ) the correlation between orexin and recovery at and days, ( ) correlation of orexin and glasgow coma score/score (gcs) over time, a prospective, irb approved study with a target n= with a diagnosis of coma due to stroke, including hemorrhagic, and tbi, treated in the neuro critical care unit at stony brook university ho collected from an external ventricular drain (evd) and corresponding blood serum samples on days , , and . there was no modification to the clinical treatment of individual patients. dictive of whether patients recovered consciousness vs deteriorated. logistic regression showed the relative risk of recovery vs. deterioration: , ( %ci - . ± . , . ± . , respective p-values= . e- , . epredictive of initial coma severity (gcs), with a correlation coefficient, r = . . correlation between - . , - . ). dictive of poor overall not appear as significant as the baseline level in predicting recovery. there has been limited research over the past decade on how race impacts survival from cardiac arrest. it has been suggested that black patients are more likely to have unsuccessful resuscitation and lower rates of survival to discharge, however, it is unclear if this difference is secondary to hospital factors or patient specific factors. more research is needed on racial disparities in post-arrest outcomes at urban medical centers. multimodal outcome characterization in comatose cardiac arrest (mocha) is an irb-approved multicenter observational study. this study sample consists of consecutive cardiac arrest patients treated at two urban hospitals from - . the sample includes both patients who experienced in-hospital and out-of-hospital cardiac arrest. the outcome of interest was in-hospital mortality. associations between race and mortality were evaluated by chi-square and relative risk (rr) with % confidence interval. we included white ( %) and black patients ( % were all found to be at no increased risk for in-hospital mortality relative to other gender and race combinations. there was no difference in location of cardiac arrest (i.e., inhospital vs. out-of- the lack of racial differences in mortality could possibly be explained by the similar rate of out-ofhospital arrests, similar initial non-perfusing rhythms, lower socioeconomic status of all patients, and strong focus of the participating hospitals on addressing racial disparities in the healthcare system. hyperglycemia is associated with poor clinical outcomes in critically ill patients, such as post-cardiac arrest (ca) patients. post-ca prognostication studies have studied clinical examinations, electrophysiology, biochemical changes, and/or neuroimaging, but studies regarding patient blood glucose levels are mostly limited to mortality outcomes. new analysis of glucose trends is needed to guide ca prognostication in order to determine favorable outcomes regarding neurologic functioning. this study was conducted using the irb-approved multimodal outcome characterization in comatose cardiac arrest (mocha) registry. the sample included ca patients admitted to a university-affiliated urban hospital from - . case selection was determined by availability of serial glucose measurements over the first hours post-ca and outcome scores at hospital discharge. poor functional outcome was defined as modified rankin scale (mrs) - or glasgow outcome scale extended (gose) - . statistical analysis included chi-square tests, and prognostic value was calculated by sensitivity. there was no significant difference in outcome regarding age, sex, race, or ethnicity. the study sample consisted of % diabetic patients, with no significant difference in outcome. patients with glucose levels > mg/dl at least once during the first hours post-ca were associated with poor functional outc there appears to be a correlation between glucose > mg/dl within the first hours and poor functional outcome. however, it is still difficult to reliably predict poor vs. good functional outcome due glucose management are needed to better understand this relationship. post-cardiac arrest organ injury is associated with high mortality rate after icu admission. despite improvement in the post-cardiac arrest care, temporal changes in patients' severity, intensity of care and neurological outcome remain poorly defined. the aim of this study is to describe how epidemiology of cardiac arrest characteristics, therapies and outcome have changes over years. retrospective study including adult (> years) cardiac arrest patients admitted from january to march after ca to a university hospital. we collected demographic characteristics and cardiac arrest data, together with main therapies and monitoring during icu and hospital mortality. a total of patients (median age [ - ] years; male gender %) were included over the study period. time to rosc was significantly longer in period i and iv when compared to others (p< . ). icu length of stay and lactate levels on admission were also significantly higher in the period iv than others. there was a progressive and significant increase of out-of-hospital ca, non-cardiac origin of arrest and non-shockable initial rhythm from period i to period iv. also, there was a significant increase in the number of patients developing acute kidney injury and hypoxic hepatitis over time, from period i to period iv. despite a more frequent use of coronary angiography and multimodal neurological monitoring, hospital mortality increased (from period i, % to period iv, % -p< decreased (period i, % to period iv, % -p= . ) over time. in this study, severity of anoxic injury and the incidence of post-cardiac arrest organ dysfunction increased over time. this was associated with a higher proportion of patients with poor outcome. pressure reactivity index (prx) based optimal cerebral perfusion pressure(cppopt) is associated with outcome after traumatic brain injury, but is not explored after cardiac arrest. we examined post-arrest patients who underwent invasive intracranial monitoring to explore characteristics of prx and cpp, and whether these were useful predictors of survival. we included all comatose cardiac arrest patients without primary neurological pathology that underwent invasive intracranial monitoring between - at our institution. cpp, mean arterial pressure(map), prx, cppopt, and deltacpp (cpp-cppopt) were calculated. systemic and brain physiologic measures were compared across the primary outcome of survival. in this pilot study we demonstrated the feasibility of acquiring cpp, prx, and cppopt for post-cardiac arrest patients. in this sample, none of the systemic and brain physiologic measures were associated with survival but the approach is limited by the bias towards poor outcomes in patients receiving monitors. interestingly, cppopt obtained from invasive intracranial monitoring generally ranged within physiologic norms. deltacpp for the single patient with good outcome was positive and small, consistent optimizing cerebral perfusion after cardiac arrest improves outcome are warranted. prognostication after cardiac arrest is challenge because of many confounding factors during hypothermia, severity of the brain injury is a key determinant of whether maximal resources, such as the use of extracorporeal membrane oxygenation (ecmo), mechanical circulatory support, or even coronary artery bypass grafting, are advisable or appropriate. therefore, early and accurate prognostication is essential for decision of therapeutic plan including maxima intensive modalities. in this study, we focused not only the prognosis estimation using mri but also initial ct-based prognosis estimation where features captured by modern deep learning (dl) technique were commonly used. we selected total cardiac arrest patients having initial ct at er, and brain mri after hours from cardiac arrest. diffusion weighted image (dwi, b = ), and apparent diffusion coefficient (adc) images calculated. cerebral performance category (cpc) scores were used as the main outcomes of survivors after cardiac arrest. both experienced neurologist and emergency medicine tried to predict the devised two cascaded deep convolutional neural networks (deep cnns). even fully experienced neurologist and emergency physician could not predict the cpc score exactly with the initial ct scan only and even additional diffusion mri (accuracy : %- % with initial ct only - % with additional diffusion mri). by using dl technique, among subjects of train set, subjects had the correct prognosis score ( . % accuracy) and among subjects of test set, subjects had the correct prognosis score ( . % accuracy) with initial ct scans only. with additional diffusion mri, . % accuracy and % accuracy. in visually equivocal initial ct scans, dl was more related to quantification than visual assessment. dl is superior and very useful for accurate prognostication especially with visually equivocal initial ct scan. cardiac arrest (ca) is associated with a high risk of dying and of neurologic impairment in survivors. target temperature management (ttm) improves survival and neurologic outcome and is recommended by international guidelines. this study assessed the association between the initial acute physiology and chronic health evaluation (apache) iii score and neurological outcome in comatose survivors of cardiac arrest who received targeted temperature management (ttm). data on post-cardiac arrest patients treated with ttm were collected from apache outcome database and medical records. ttm of °c or °c is chosen based on critical care physician's discretion. baseline characteristics included age, gender, apache iii scores, time to return of spontaneous circulation (ttrosc, minutes), time to target temperature (ttt, minutes), and shockable rhythm (sr, %). outcome included hospital mortality, and good neurologic outcome (defined as discharge to home or rehab). compared to the bad outcome group (n = ), the good outcome group (n = ) had similar age ( in comatose survivors of cardiac arrest who received targeted temperature management, the apache iii score calculated in the immediate post-cardiac arrest period was a poor predictor of neurological outcome. brain dead patients are victims of trauma, entering the health care system through emergency department (ed).in the ed, these patients are received with injuries and de-arranged physiological conditions that depends on time sensitive treatment and have the potential for improvement with proper management. our study tries to find out the predictors at admission that contributes to brain death (bd) so that their timely intervention can prevent bd a retrospective analysis of the data related to severity of injuries, physiological parameters and laboratory investigation including ct scan of the head at the time of ed admission of each patients were assessed once they were diagnosed brain death. logistic regression analysis was employed to determine the independent factor. p value of < . was considered significant. results brain dead patients records at the time of admission were analysed. on univariate analysis we found glasgow coma scale (gcs) < , blunt trauma chest (btc),skeletal injury, intraventricular hemorrhage (ivh),skull fracture,subarachnoid hemorrhage (sah),midline shift (mls),mean blood pressure (mbp)< mmhg,use of ionotropes, hemoglobin (hb)< mg/dl,international normalization ratio(inr)> . ,albumin< mg/dl,sodium level (na)> meq/dl,urea > mg/dl significantly related to bd.on further multivariate analysis ,we found gcs< (or- . ), btc (or- . ), ivh (or- . ), mls (or- . ), mbp < mmhg (or- . ), inr> . (or- . ), albumin < mg/dl (or- . ) and na level > meq/dl(or- . ) at the time of admission are strongly associated with bd. our study tried to find the predictors at the time of admission which may contribute to bd. addressing them may prevent patient from becoming brain dead. biomedical technology in critical care is advancing at a rapid rate, offering the potential to substantially improve performance through improved efficiency and productivity. recent evidence suggests that visual assessment of pupillary size and reactivity has limited interrater reliability and accuracy, hence, we examined the introduction and implementation of an automated pupillometer in an academic neurological icu. we evaluated clinicians' perceptions about the added utility of the pupillometer to the standard visual pupillary exam. -minute bedside education and demonstration of the pupillometer by a 'superuser', we conducted usability testing at the bedside. participants completed the end-user testing methodology, where they completed specified tasks designed to test the pupillometer's features and later completed a questionnaire regarding their ease of use and interpretation of results, comfort and confidence using the pupillometer, and their behavioral intention to use the pupillometer if adopted into the clinical environment to date, participants have completed questionnaires. participants were allowed repeat enrollment in the study. the participant's professional designations include registered nurses, residents and fellows and the majority have practised in the icu for to years. most of the participants are somewhat comfortable ( / ) performing the traditional visual pupillary exam and somewhat confident ( / ) with the results obtained from this exam. twenty-one, out of responses, were very comfortable in using the pupillometer, / were somewhat comfortable, and / were neutral. if this technology is introduced into icu, the majority ( / ) will use this device to conduct pupillary exams, and / would consider changing management based on the pupillometer results. this study outlines a strategy to evaluate usability and implementation of a newly adopted technology into the critical care environment. improved implementation methods and evaluation of implementation processes are necessary for successful adoption of new technology in acute care settings. propofol infusion syndrome (pris) is a rare complication of propofol infusion. it is characterized by metabolic acidosis, rhabdomyolysis, acute renal failure, hyperlipidemia, and rapid cardiac failure. risk factors for developing pris are: propofol infusion > hours, dosing > mg/kg/hr, critical illness, malnutrition, and use of vasopressors. we present a case of pris that developed after propofol infusion was turned off. a year old woman with medically intractable epilepsy and developmental delay, presented with generalized tonic clonic status epilepticus. she was refractory to benzodiazepines, so she was intubated and started on a propofol infusion. at mcg/kg/min of propofol, she was still having generalized clonic tonic seizures. she was transferred to our neurological icu for continuous eeg monitoring. propofol infusion was increased to mcg/kg/min ( mg/kg/hr) to control her seizures. she remained seizure free for hours. propofol was weaned over hours because she became hypotensive and required norepinephrine. when the propofol was turned off, cpk was , lactate was . , and creatinine was . . she received propofol for hours. twelve hours after propofol was stopped, she developed a metabolic acidosis, lactate increased to . , creatinine increased to . , urine output decreased, and cpk increased to > , . she then developed bradycardia with wide complex qrs, which progressed to asystole. she could not be resuscitated and died. our patient developed pris after propofol infusion was off for hours. she had many risk factors for developing pris, including high dose of propofol, critical illness, malnutrition, and use of vasopressors. pris can occur after propofol infusion has been stopped, and should be monitored for after the infusion has been discontinued in patients that are at increased risk. subdural hemorrhage (sdh) is a common cause of morbidity. we sought to study the impact of antithrombotic drugs on nontraumatic sdh. we retrospectively reviewed medical records of , patients admitted at massachusetts general hospital for sdh during to based on a research patient data registry. there were patients without history of head trauma included in the analysis. baseline demographic and clinical characteristic data were collected. the outcomes including gcs, modified rankin scale (mrs), sdh size, sdh expansion, surgical evacuation, mortality rates, length of stay (los), bleeding and thromboembolic complications were compared between two groups. multivariate logistic regression was performed to analyze association between poor outcome (mrs - ) and all potential predictors (age, diabetes, conditional variable regression method was used because of relatively small sample size to avoid overfitting the model. among patients included, ( . %) were on antithrombotic agents, either antiplatelets or anticoagulants, at presentation and ( . %) were not. anticoagulant and antiplatelet agents constitute . % and . % of nontraumatic sdh, respectively. all antithrombotic agents were discontinued on admission. nontraumatic sdh patients who were on antithrombotic agents had longer los ( . ± . , p= . ), higher rate of sdh expansion (or . ; %ci . - . ; p= . ), higher rate of disability at discharge (mrs - ) compared to no antithrombotic group (or . ; %ci . - . ; p< . ). on multivariate logistic regression analysis, antithombotic group had higher rate of poor outcome than no antithrombotic group (or . ; %ci . - . %; p= . ). use of antithrombotic agents prior to admission in nontraumatic sdh patients correlates with longer los, higher sdh expansion and increased disability at discharge. maintaining goal sodium levels in the neurocritical care population can be challenging. historically, at our institution, the supplementation of enteral sodium occurred by addition of table salt to tube feeding formulas by our dietary team. to make this therapy easier to standardize, monitor, and titrate, a new process was developed. continuous % hypertonic sodium chloride solutions are now administered enterally via feeding tubes. this also allows for the charting of the medication and immediate dose titrations. this pre-post analysis includes patients admitted six months prior to the implementation of the new enteral sodium process compared to patients admitted within one year after the new process change. demographic variables, as well as the indication for sodium goals, initial sodium levels, sodium level for -hours post-addition of enteral sodium supplementations, concomitant use of intravenous hypertonic saline, and achievability of goal sodium levels were collected. descriptive analytics were performed to compare groups. a total of patients were included in the analysis: in the pre-implementation group and in the post-implementation group. the most common indication for goal sodium levels in both groups was traumatic brain injury with head bleed; patients ( %) in the pre-implementation group and ( %) in the post-implementation group. ability to maintain serum sodium concentrations (defined as the ability to maintain goal sodium without the need for intravenous hypertonic saline for > h) within goal in the pre-implementation group was successful in % of patients (n= ) compared with % (n= ) in the post-implementation group. the use of continuous enteral % hypertonic sodium chloride solutions to target and maintain goal sodium levels provided similar efficacy compared to the addition of table salt to tube feeding formulas and is safer and easier to monitor and titrate. coagulation factor xa (recombinant), inactivated-xa inhibitor associated life--factor prothrombin complex concentrate (pcc) was utilized off- retrospective, single center, cohort study including adult intracranial hemorrhage patients who received discharge between efficacy (defined by international society on thrombosis and haemostasis criteria), thrombotic events, icu and hospital length of stay, and mortality. andexxa, coagulation factor xa (recombinant), inactivated-zhzo is indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or indication. there is no available literature supporting the use of this drug in acute neurosurgical emergencies. we present our experience of patients treated with andexxa who required acute neurosurgical interventions as a life saving measure. patients were identified from may , to may , using an electronic database report identifying those who received andexxa and subsequent chart review at a single center quaternary care academic medical facility. factor xa inhibitor and time of dosing. patient and both had an external ventricular drain placed while in the emergency room. patient suffered from a cerebral hemorrhage with hydrocephalus while patient was found to have a primary ventricular hemorrhage with hydrocephalus. both were treated with four factor prothrombin complex concentrate (pcc) at an outside hospital. there were no bleeding complications during the procedures. two patients had a craniotomy performed. patient was diagnosed with an acute subdural hemorrhage with worsening midline shift despite receiving pcc at the outside hospital. patient four had an acute-chronic subdural hemorrhage with midline shift but did not receive pcc. in both craniotomy cases, there were no bleeding complications. andexxa was used in four patients taking apixaban or rivaroxaban undergoing lifesaving neurosurgical procedures despite no the utilization of acute extracranial and intracranial stents for the treatment of cerebrovascular pathology is increasing. the optimal antiplatelet agent and dose in this population and the utility of platelet function testing is unclear. all patients from january to april who were hospitalized and received ticagrelor to maintain intracranial or carotid stent patency in which platelet function testing (verifynow) was utilized to guide dosing were collected. relevant demographic, clinical, platelet reactivity unit (pru), and ticagrelor administration data was collected and qualitative assessment of pru results was performed. data was collected on patients and the maintenance doses utilized were , , (most frequent) or mg bid and loading doses of mg or mg. a total of patients' doses were titrated in order to achieve the goal pru range ( - ). among patients given a dose of mg % had a pru in the optimal range ( - ) as compared to % among patients given a dose of mg. twice as many patients given a dose of mg as compared to mg ( % vs %) had a pru between - . among the patients whose dose was titrated the average pru prior to dose escalation was , the average pru subsequent to dose escalation was , and the average pru prior to dose decrease was and the range in % of cases and was between - in % of cases. the utilization of platelet function testing to guide dose titration of ticagrelor to a desired pru range is feasible. a major limitation of this study is the lack of patient outcomes related to thrombosis or bleeding. rivaroxaban. the efficacy and safety of andexanet alfa have been evaluated in the annexa- study, which excluded patients receiving prothrombin complex concentrate (pcc) within the days preceding enrollment. however, there have been limited reports of patients receiving both pcc and andexanet alfa for oral factor xa inhibitor-associated major bleeding, without adverse effect. while thrombotic events were observed in % of annexa- patients, potential for additive risk when combining andexanet alfa and pcc is undefined. we describe a patient who received pcc followed by andexanet alfa for an apixaban-associated intracerebral hemorrhage, who subsequently suffered devastating embolic strokes. de-identified patient data were retrospectively collected from the electronic medical record a -year-old male presented with acute left-sided hemiplegia caused by a large right-sided temporal lobe intracerebral hemorrhage. the patient had a history of atrial fibrillation, for which he was anticoagulated on apixaban. the patient initially received intravenous (iv) pcc units/kg for prevention of hematoma expansion. the following day, minimally expanded hemorrhage was observed on repeat imaging concurrent with a measured apixaban level of ng/ml (reference range - ng/ml). as a result, high dose andexanet alfa was administered as an mg iv bolus, followed by an iv infusion of mg/minute for minutes. over the next several days, the patient's neurologic exam supratentorial strokes, likely embolic in origin. unfortunately, the patient did not survive hospitalization. the combination of pcc and andexanet alfa may carry with it substantial thrombotic risk, and cannot be routinely recommended. targeted temperature management (ttm) is used for neurological protection in patients with neurological injury but shivering during ttm can reduce therapeutic effect by increasing oxygen consumption and metabolic rate. cisatracurium used to prevent shivering has a shorter half-life than vecuronium and is not affected by liver and renal function. the objective of this study was to compare the efficacy and safety between two neuromuscular blockers in order to determine the benefit of cisatracurium. we reviewed medical records of adult neurological intensive care unit (ncu) patients who received st, to may st, . the efficacy between the two groups was confirmed by the presence of shivering and the recovery time of motor function. safety was determined by the incidence of bradycardia and hypotension, the duration of antibiotic use and the mortality rate after discontinuation of the neuromuscular blocker in ncu. recovery time of motor function was assessed using 'motor power' and 'glasgow coma scale (gcs)'. a total of patients were included in the study: patients in cisatracurium group and patients in vecuronium group. the incidence of shivering was . % and . % (p = . ) in vecuronium and cisatracurium, respectively. the median recovery time of motor function was . [ . - . ], . [ . - . ] hours (p < . ) based on the motor power score, . [ . - . ] hours and . [ . - . ] hours (p < . ) based on the motor response score of gcs, respectively. the safety was not significantly different between the two groups. recovery time of motor function was significantly shorter in the cisatracurium group than in the vecuronium group and there was no significant difference in the others. this study identified the benefits of cisatracurium in ncu under ttm. amantadine and modafinil are neurostimulants that may improve or accelerate cognitive and functional recovery after a stroke. this systematic review describes amantadine and modafinil administration patterns post-stroke, evaluates their impact on cognitive and functional outcomes, and identifies the incidence of adverse drug effects. an investigator-initiated medline search identified all full-text english-language publications describing the administration of amantadine or modafinil post-stroke from inception through october , . -stroke); intervention (amantadine or modafinil treatment); comparison (not required); outcomes (cognitive or functional recovery). amantadine and modafinil administration practices, cognitive and functional outcomes, and incidence of adverse drug effects were collected according to the preferred reporting items for systematic reviews and meta-analysis protocols (prisma-p) approach. quantitative analysis was not performed due to heterogeneity in the measures of clinical effectiveness. initially, , publications were identified. eight amantadine ( patients) and modafinil ( patients) publications were included. only ( %) amantadine patients and ( %) modafinil patients received treatment during an acute hospitalization. time from stroke to amantadine initiation was ( , . ) days and the initial dose was ( - ) mg/day. time from stroke to modafinil initiation was ( , ) days and the initial dose was ( - ) mg/day. under-responsiveness was the most common indication for neurostimulants (n= / publications; %). thirty-eight unique measures of clinical effectiveness were reported. a positive response in at least one measure of clinical effectiveness was reported in % and % of amantadine and modafinil publications, respectively. visual hallucinations (amantadine) and excitability/agitation (modafinil) were the most common adverse effects. amantadine and modafinil may improve or accelerate cognitive and functional recovery post-stroke, but higher quality data are needed to confirm this conclusion, especially in the acute care setting. levetiracetam is an antiseizure medication that is used in neurocritical care (ncc) patients to prevent or treat seizures. behavioral adverse events (ade) are reported to occur in approximately % of patients taking levetiracetam; however, the incidence of these ades in ncc patients are unknown and may be exacerbated due to their unique cns pathology. the purpose of this study is to identify the incidence of levetiracetam-associated behavioral (lab) ades in ncc patients. adult ncc patients receiving levetiracetam, admitted between november , and october , , and diagnosed with tbi, sah or ich, or cerebral infarction were included in this study. criteria for determination of lab ades included the following: ) diagnosis codes for delirium, agitation, irritability, hostility, violent behavior, insomnia, anxiety, or depression during this hospital admit; ) administration of an antipsychotic; ) positive cam-icu; and/or ) physical restraints. day of lab ade onset was determined by the start date of the antipsychotic or a positive cam-icu. there were patients included in this study; % males, median admit gcs was . the most common neurological injuries were ich ( %) and tbi ( %). lab ades were identified in ( %) patients. these were identified by diagnosis codes in % of patients, with delirium, depression, and agitation being most common; % received an antipsychotic, % had a positive cam-icu, % had restraints ordered, and % had more than one determining factor. lab ades were reported a median of (range - ) days after levetiracetam initiation. patients with tbi had the highest reported incidence of lab ades ( %). almost half ( %) of ncc patients that received levetiracetam experienced a behavioral ade, which was of levetiracetam use in ncc patients. the recommend the use of units/kg of four--pcc) or rting lower dosing strategies of apcc. in , a fixed, lowimplemented at our institution. the objective of this study was to evaluate the efficacy and safety of fixed, low-dose apcc this single-center, retrospective chart review included adult ich patients who received apcc for oral tcome was achievement of ich hemostasis. hemostasis was defined as no progression of hematoma on head ct within hours post-apcc. safety outcomes included in-hospital mortality and incidence of thromboembolic event (vte) within days post-apcc administration or up to the time of discharge, whichever came first. -four patients receiving apcc for reversal of factor xa inhibitor associated ich ( traumatic and spontaneous) were included for analysis. median age was years; % of patients had a past medical history of atrial fibrillation and % were anticoagulated with apixaban. median apcc dose was units ( - units), with a median weight-based dose of units/kg ( - units/kg). hemostasis was achieved in % of all patients with ich ( % in patients with traumatic ich, and % of patients with spontaneous ich). mortality rate was % and vte incidence was %. of hemostasis in the majority of patients and a low incidence of vte. ally ill patients, yet the optimal monitoring method is unknown. the purpose of this study was to describe the correlation between aptt and anti-xa levels in patients receiving prophylactic sq- a retrospective chart review of patients admitted years were included if they received sq--xa level drawn within hours of each other. aptt and anti-xa levels were then compared to determine correlation and descriptive analyses were performed. correlation was defined as normal aptt levels ( . - . seconds) paired with undetectable anti-xa levels (< . iu/ml), sub-therapeutic aptt ( . - . seconds) with sub-therapeutic anti-xa ( . - . seconds), therapeutic aptt ( - seconds) with therapeutic anti-xa ( . - . iu/ml), and supra-therapeutic aptt (> seconds) with supra-therapeutic anti-xa (> . iu/ml) levels. a total of patients and paired levels were analyzed. the median time between paired aptt and anti-xa levels drawn was . hours, and . % ( / ) of levels were drawn within hour of each other. anti-xa levels were drawn at a median of . hours after the sqpaired levels correlated, while . % ( / ) of levels drawn within hour of each other correlated. a spearman's correlation coefficient of . (p= . ) was found between aptt and anti-xa levels drawn within hour of each other. a sub-therapeutic aptt with undetectable anti-xa was demonstrated in . % of levels drawn within hour of each other. the sqanti-xa levels. there was no significant correlation between aptt and anti-xa levels in patients who received sq--sqh monitoring method in the neurocritically ill population. the utilization of acute extracranial and intracranial stents for the treatment of cerebrovascular pathology is increasing. the optimal intravenous antiplatelet agent for short-term bridging of patients who are unable to tolerate or do not respond adequately to oral antiplatelet agents is unclear. cangrelor offers potential advantages over glycoprotein iib/iiia inhibitors because response can be readily measured using platelet function testing (verifynow) and it has superior pharmacokinetics including a rapid on-set of effect and rapid clearance. patients with intracranial or carotid artery stents who were administered cangrelor for bridging purposes when oral antiplatelet agents were not feasible were assessed. relevant demographic, clinical and procedural data as well as cangrelor dosing and platelet function testing data were collected. patients had carotid artery stents. the indications for bridging were acute gi bleeding, inability to tolerate oral medications due to severe nausea/vomiting and two patients had an inadequate response to initial oral ticagrelor dosing based on platelet function testing. the dose of cangrelor utilized for all patients was . mcg/kg/min and all patients were on a cangrelor infusion for less than hours. platelet function testing (verifynow) was utilized to ensure adequate platelet inhibition and all patients demonstrated adequate inhibition on the prescribed dose. no stent thrombosis or bleeding was observed. cangrelor is a reasonable option when patients with intracranial or carotid stents necessitate an intravenous antiplatelet for bridging when oral antiplatelet medications are not feasible. current guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult intensive care unit (icu) patients recommend a multimodal analgesia-first strategy to minimize opioid and sedative requirements and encourage early mobilization. the purpose of this study was to evaluate the success of a stepwise multidisciplinary implementation of an analgesiafirst sedation pathway followed by introduction of an early mobility protocol in a neuroscience icu (nsicu). we retrospectively evaluated mechanically ventilated adult nsicu patients admitted to a single-center academic medical center. three-month time periods were evaluated at baseline (phase i), after implementation of the sedation pathway (phase ii), and after implementation of the early mobility protocol (phase iii). total of patients were evaluated: phase i (n= ), phase ii (n= ), and phase iii (n= ). we observed a progressive decrease in propofol use during each phase (i, ii and iii) (median . mg/day versus . mg/day versus . mg/day, respectively; p= . between phase i and iii) and increased dexmedetomidine utilization ( % versus % versus . % of patients, respectively; p< . ). opioidanalgesia requirements during mechanical ventilation were similar between groups. we observed a quicker time from admission to pt evaluation between phase ii and phase iii (median [iqr] of days [ ] [ ] [ ] [ ] [ ] [ ] versus days [ - ], respectively; p< . ). rehabilitation therapy was provided in . %, %, and . % of patients while admitted to the icu in phase i, ii, and iii, respectively (p= . ) and increased number of pt sessions provided per patient (median of [ - ], [ - ], and [ - ] sessions/patient during each phase, respectively). no adverse events related to early mobility were observed. interdisciplinary coordination and communication is necessary for effective unit-based practice changes as education alone is insufficient. a multidisciplinary approach to goal-directed therapy targeting pain management and light sedation increased opportunity for early mobility. the use of opioids in the neuroscience intensive care unit offset the balance of analgesia and reliability in performing neurological exam. in lieu of the current opioid crisis, we describe our center experience about the use of ketamine as an alternative medication with opioid sparing/lowering effect. retrospective chart review of patients admitted to nsicu with severe brain injury between november to april were performed. patients were separated into two groups of twenty by randomization and matching, each receiving either ketamine or propofol infusion. data collected includes age, gender, diagnosis, comorbidities, duration of ketamine, propofol and morphine equivalent (me) opioid dose. statistical descriptive analysis and independent samples t-test analytical analysis were performed to determine the difference of opioid use between two groups using spss software. the range of ketamine used over the mean period of . (range - ) days was - mcg/kg/min, while that of propofol over the mean period of . (range - ) days was - mcg/kg/min. / ( %) and / ( %) patients in the ketamine and propofol group required opioids respectively. the cumulative and mean morphine equivalent (me) dose for the ketamine group was . mg and . mg respectively, while on propofol, it was . mg and . mg. results of independent t-test analysis showed a significant p-value of . , indicating significant opioid dose reduction with ketamine. it is essential to recognize the effectiveness of ketamine as an opioid sparing/lowering agent with potential analgesic-sedative medication without significant side effects. introduction different indications. however, serious complications such as i -current pulmonary embolism in patients with a contraindication to unknown. this information would be needed to determine if opportunities for improvement exists. with approval from the local investigational review board (irb), during the period of - were identified from the interventional radiology department. only identified patient data was manually extracted via chart review to determine patient characteristics and a total of patients met inclusion criteria. . % were male. the most common neurocritical care diagnosis were intracranial hemorrhage( %), ischemic stroke ( %), central nervous system (cns) neoplasm ( %) and cns trauma ( %). . % of patients had at least venous thromboembolism (vte) was the most common indication ( %) followed by vte with contraindication for ac ( %), primary adjunctive treatment ( %) adjunctive prophylaxis ( %) and secondary adjunctive treatment ( %). in this single center study, to anticoagulation. andexanet alfa was approved in may for reversal of life-threatening hemorrhages for patients on anticoagulation with apixaban and rivaroxaban. since its approval the reversal of direct oral anticoagulant (doac) associated intracranial hemorrhages (ich) has been controversial. the objective of this study was to describe real world utilization of andexanet alfa at a large academic health system. we retrospectively reviewed patients who received andexanet alfa for an ich. patients were included if they received andexanet alfa from its time of approval to formulary through april , . baseline demographics, anticoagulation and reversal information was collected. a neurointensivist reviewed all imaging. intracerebral hematoma expansion was defined as > % increase in hematoma volume. subdural (sd) and subarachnoid hemorrhage (sah) expansion was defined as > % increase in maximal hematoma diameter. thirteen patients received andexanet alfa for ich. nine patients had an intracerebral hematoma, patient had an isolated intraventricular hemorrhage, patients had sd, and patient had a sah. the median age was (iqr - ) and % of patients were male. six patients were receiving a doac for stroke prevention, and a majority of patients ( %) were taking apixaban. the median glasgow coma scale was (iqr - ), and for patients with intracerebral hematomas the median ich score was (iqr - ). there was follow-up imaging available for patients, and patient had hematoma expansion. one patient died and another had interval surgery prior to repeat imaging. no patients had in hospital thromboembolic events up to days. of the patients, % of patients would have met exclusion criteria from the anexxa- trial. in this small sample of patients who received andexanet alfa for ich it appears hemostatic efficacy was achieved in a majority of patients with no thromboembolic events; however, larger trials are needed. lacosamide is a monotherapy or adjunctive therapy used for treatment of partial onset seizure that enhances slow inactivation of sodium channels. uncommonly reported adverse effects include pr interval prolongation, bradycardia, atrioventricular block, and ventricular tachyarrhythmias. an year-old male with history of atrial fibrillation, hypertension and aortic valve replacement on warfarin presented with an acute subdural hematoma after feeling lightheaded and falling. the patient reported having multiple recent syncopal episodes. he received prothrombin complex concentrate and vitamin k for warfarin reversal with an initial inr of . . he was started on levetiracetam and home medications of metoprolol and diltiazem were continued. the next evening, he had focal seizures, was given lorazepam and transferred back to the icu. he received lacosamide mg iv loading dose, and within minutes had a second episode of asystole. his blood pressure remained stable and he did not lose a pulse. he was given atropine x doses with no response therefore transcutaneous pacing was initiated. several minutes later, he became hypotensive and was started on isoproterenol and epinephrine infusions. ekg showed complete heart block. cardiology was consulted and placed a transvenous pacer. vasopressors were eventually weaned off however neuro exam remained poor. about a week later, family made the decision to transition to comfort measures and the patient passed away. lacosamide is an anticonvulsant primarily used for partial complex seizures. only a few cases of third degree atrioventricular block have been reported in the literature. this case of extreme atrioventricular bock with a lacosamide loading dose is not common, but a drug-drug interaction with metoprolol and diltiazem was suspected. prescribing lacosamide with beta-blockers or concomitant medications that prolong the pr interval should be done cautiously due to increased risk of atrioventricular block. tissue plasminogen activator (tpa) is currently the preferred agent for treatment of acute ischemic stroke. in about % of cases, patients will develop life threatening intracranial hemorrhage. currently the aha/asa guidelines and ncs guidelines recommend reversal of intravenous tpa with cryoprecipitate and platelet infusion. both society recommendations are based off low quality evidence and are given weak recommendations.theoretically, the mechanism of action of tranexamic acid (txa) makes it an appealing agent for reversal of tpa ; txa competitively inhibits activation of plasmin countering the mechanism of action of tpa. the purpose of this case report is to report and support usage of txa for reversal of thrombolysis with tpa. this is a patient case report in which an extensive review of the patient chart was conducted to provide an accurate history of events. extensive literature review was compiled to reflect current therapy guidelines and the off-label use of txa for reversal of tpa. year-old male presented to a tertiary care medical center with signs and symptoms of ischemic stroke symptomatic cerebellar hemorrhage. the delay in obtaining cryoprecipitate and platelet transfusion led the medical team to discuss alternative agents for the reversal of tpa. reversal with txa was discussed based on the medication's mechanism of action. txa mg/kg ( mg) was prepared at bedside and administered over minutes. repeat head ct showed no further progression of hemorrhage and there was an improvement in the patient's neurologic condition was noted hemorrhagic transformation following thrombolysis for ischemic stroke is a life threatening emergency. txa is an appealing option for reversal of tpa as it directly counters the mechanism of tpa and can be easily and quickly accessed. this case reports further strengthens and supports its usage. drug level monitoring is essential to optimize valproic acid (vpa) efficacy and minimize toxicity. total serum vpa levels of - mcg/ml are recommended, though free drug is more precisely responsible for vpa's pharmacologic effect. the interpretation of total vpa levels is complicated by the drug's complex protein binding characteristics. the use of free serum vpa levels has garnered interest, though the therapeutic range is not well defined. little is known about the relationship between free vpa levels and toxicity. we present a novel and unambiguous case of hepatotoxicity associated with elevated free vpa levels. de-identified patient data were retrospectively collected from the electronic medical record a -year-old male with a past medical history of refractory epilepsy was hospitalized for generalized tonic-clonic seizures. his prior home antiepileptic drugs (aeds) included carbamazepine and the vpa precursor divalproex. the patient's total and free vpa levels upon admission were . mcg/ml and . mcg/ml (laboratory reference range normal. the patient's home divalproex er dose was increased from mg twice daily to vpa suspension mg twice daily for his low total vpa level. on hospital day (hd) , the patient had a therapeutic total vpa level of . mcg/ml, but an elevated free vpa level of . mcg/ml in the setting concurrent with a free vpa level of . mcg/ml. the patient's vpa was then transitioned to alternative aeds due to hepatotoxicity concerns. the patient's clinical status later improved, and he was discharged probability scale implicated vpa as the probable cause of hepatotoxicity in this patient. measurement of free vpa levels helps guide dosing decisions and may reduce drug-related toxicity. limited case reports of osmotic demyelination syndrome (ods) treated with intravenous immunoglobulin (ivig) with or without plasma exchange (pe) are published, demonstrating variable neurologic recovery. the combination of ivig and pe led to complete neurologic recovery of our ods patient. electronic chart review to collect data for this case report. -year-old male presented with asymptomatic serum sodium of meq/l in the setting of intractable vomiting and decreased oral intake secondary to small bowel obstruction. his sodium was overcorrected by meq/l within first hours. he subsequently developed altered mental status with lethargy and became unresponsive on day with flaccid quadriparesis and minimal motor response to noxious stimuli. mri of brain revealed osmotic demyelination of central pons and bilateral basal ganglia. ivig was initiated on the day when ods was confirmed on mri. his serum sodium normalized. after day course of ivig g/kg, he could intermittently track with eyes but did not recover motor function. plasma exchange was initiated days after ivig. after sessions of pe, he started to move his right upper extremity antigravity and was attempting to verbalize. after sessions of pe, he moved all extremities antigravity, could talk although he had staccato speech and was able to ambulate with assistance. after sessions of pe, he was ambulating independently; his motor strength was +/ throughout. he was cognitively intact. at one month follow up in the clinic, he was neurologically completely intact, except for minimal upper extremity intention tremor. ivig with plasma exchange led to the remarkable neurologic recovery of a patient with ods. a randomized control trial comparing ivig monotherapy versus pe monotherapy versus the combination of ivig and pe is warranted to better clarify the appropriate treatment protocol in ods patients. digoxin is a commonly used drug in the treatment of heart failure patients but with no intrathecal indication. we describe a rare case of accidental intrathecal administration of digoxin during an elective caesarian section that lead to severe neurological deficits. a -year-old hispanic female underwent elective caesarian section with separate attempts at regional spinal anesthesia with bupivacaine due to failure of achieving adequate anesthesia with the first injection. risk management discovered that patient had erroneously received digoxin as the initial injection, confirmed by therapeutic serum levels of digoxin. two hours after delivering a healthy child, the patient's mental status deteriorated and she became unresponsive. she had three witnessed generalized tonic-clonic seizures and was emergently intubated for airway protection and received keppra. twenty-four hours in, patient remained comatose, continuous electroencephalogram revealed no seizures, magnetic resonance imaging (mri) brain showed diffuse, patchy hyperintensities involving bilateral frontotemporal lobes and basal ganglia. mri spine showed extensive cervical and thoracic cord edema. cerebrospinal fluid analysis showed white blood cells and protein count of . she received solumedrol milligram intravenous for doses followed by -day course of intravenous immunoglobulin (ivig). eleven days in, she was extubated. at discharge, she had intact upper extremity strength, intact speech, with no sensation or motor response below t level. mri showed mild thoracic cord edema. at day follow up, she had intact mental status and minimal improvement in motor strength and sensation below t . this is an extremely sad case of severe neurological deficits resulting from a grave medical error. there are only previously reported cases of intrathecal administration of digoxin in literature but the mri findings, duration of symptoms and neurological deficits were far more severe in our patient. neither cases reported use of high dose steroids or ivig either. neurological complications following organ transplantation can be a result of a myriad of infectious, toxic-metabolic, vascular and iatrogenic causes. given the wide range of possibilities, accurate diagnosis can be challenging. we present a case of acute hyperammonemia complicating renal transplantation. a -year-old female with a remote left mca stroke was evaluated for progressively worsening lethargy that started approximately a week after she had undergone deceased donor renal transplantation. her immunosuppression comprised induction with alemtuzumab plus methylprednisolone with long-term mycophenolate mofetil plus tacrolimus, and antibiotic coverage included valganciclovir, trimethoprimsulfamethoxazole and fluconazole. progressive deterioration in the level of consciousness progressing to coma with absent cough, gag reflex, sluggish pupils and no motor response resulted in the patient being intubated. neurological examination did not reveal any focal deficits besides her pre-existing right hemiparesis. pertinent investigations included an mri brain that showed no acute changes, eeg suggestive of triphasic waves and serial lumbar punctures showing elevated pressures in the - cm h o range. level of umol/l. in addition to appropriate pharmacotherapy and dietary protein restriction, the patient underwent continuous venoher mentation to baseline. additional investigations done to determine the etiology of the hyperammonemia showed the patient to be infected with ureaplasma urealyticum which was treated successfully with doxycycline and moxifloxacin. to our knowledge, this is the first report of ureaplasma urealyticum infection resulting in hyperammonemia fo management of hyperammonemia. in the absence of hepatic impairment, alternate etiologies of hyperammonemia should be sought. acute hyperammonemia requires prompt evaluation and treatment to reduce the mortality and morbidity associated with it. prevalence, characteristics, and outcomes related to ventilator associated events (vae) in neurocritically ill patients is unknown, and explored in this study. a retrospective study was conducted to examine prevalence, factors, and outcomes of patients with vae admitted to the neurocritical care service at harborview medical center between january , and december , . chi-square test, analysis of variance was used to compare patients by vae status. amongst neurocritically ill patients, vaes occurred in ( . %) patients. most common vae was ventilator associated condition, vac, ( . %), followed by infection related vac (ivac), ( . %), and possible ventilator associated pneumonia (pvap), ( . %). most common trigger for vae was an increase in positive end-expiratory pressure (peep). age (median [iqr ], male sex ( %), and bmi ( . %) were comparable across groups with and without vaes. patients with vae experienced higher intracranial pressures than those without vae( . mmhg vs. mmhg, p < . ). compared to patients without any vae, patients with any vae spent longer time on mechanical ventilation ( . vs. . days, p < . ), and in the intensive care unit ( . vs. days, p < . ). mortality ( . % vs. . %), median hospital length of stay ( . vs days) and discharge to home ( . % vs. . %) were similar across both groups. ventilator associated events are prevalent amongst the neurocritically ill. they are commonly triggered by changes in peep, and are associated with intracranial hypertension, increase length of mechanical ventilation and intensive care unit stay but may not affect mor associated with vae in subgroups of neurocritically ill patients and their impact on clinical outcomes warrants further examination. synthetic cannabinoids (sc) are a heterogeneous group of compounds initially developed to study the endogenous cannabinoid system. most sc interact with cb and cb receptors with much higher affinity -tetrahydrocannabinol. the popularity of sc is increasing in adolescents and young adults because of the ability to produce a marijuana-like high without being detected on routine drug screens. we hereby present a case of sc related status epilepticus, hypoxic respiratory failure, severe acute kidney injury (aki) and cerebral edema with fatal outcome. -year-old man with suspected sc adulteration of cbd oil presented with headache and status epilepticus. labs showed leukocytosis, triple acidosis, and tetrahydrocannabinol in urine. ct head showed diffuse cerebral edema with sulcal subarachnoid hemorrhage. intracranial pressure was elevated to - mmhg. hospital course was complicated by severe and refractory metabolic acidosis into hospitalization patient suffered cardiac arrest from pulseless ventricular tachycardia secondary to severe acidosis and metabolic derangements. after multiple attempts of resuscitation, care was withdrawn, and patient passed away. in this case, severe refractory metabolic acidosis proved to be fatal. this case highlights the many challenges in managing a critically ill patient with cerebral edema and renal failure with medically refractory metabolic acidosis. sc are undetectable on routine drug screens and exposure is difficult to establish. sc can lead to multi-organ failure and death that may result from cardiovascular events, respiratory depression, pulmonary complications, and aki. a high clinical suspicion is warranted in atrisk patients. exposure to sc may lead to cardiovascular, cerebral and renal complications that respond poorly to devise appropriate therapeutic strategies in managing such patients. benzodiazepines are the standard medication class for treating alcohol withdrawal symptoms (aws). in acute brain injury benzodiazepines may worsen delirium and its central nervous system (cns) depressant effects may decrease level of consciousness and make the neurological-exam unreliable. barbiturates have similar actions to benzodiazepines on gaba receptors and cause less cns depression. we present our center's experience with the use of phenobarbital in patients with aws and acute brain injury. retrospective chart review of twenty patients admitted in neuroscience intensive care unit(nsicu)with acute brain injury and aws was done. treatment protocol consisted of mg/kg ideal body weight(ibw) of phenobarbital loading dose divided into three intramuscular doses three hours apart, followed by a tapering daily oral maintenance dose for total of seven days. alcohol withdrawal symptoms were assessed using the ciwa score for severity. serum phenobarbital levels were drawn five hours after the third intramuscular dose. liver function tests were performed before loading dose and daily for -times the upper limit of normal triggered protocol discontinuation. none of the patients developed alcohol withdrawal seizures, one patient developed severe transaminitis. loading doses of phenobarbital did not cause hypotension. systemic toxicity was absent and phenobarbital serum levels drawn after the loading doses ranged between . - . mcg/ml (normal range - mcg/ml). patients decreased their ciwa score after the loading doses of phenobarbital suggesting improvement of withdrawal symptoms and there was decreased use of adjunctive medications (benzodiazepines) for management of aws. nine patients required adjunctive benzodiazepines and received mg or less of lorazepam. phenobarbital for management of aws was associated with minimal adverse effects and did not lead to systemic toxicity. phenobarbital can be used in patients with acute brain injury without exacerbating delirium and can decrease the need for adjunctive benzodiazepines. aneurysmal subarachnoid hemorrhage (asah) has a case fatality rate of up to % in patient that rebleed. cerebral arterial vasospasm (vsp) after asah is a leading reason for death and disability. nicardipine is used to treat hypertension and angina, and has been investigate for a potential use in the treatment of vsp after asah. intraventricular nicardine was used for treatment of severe asah after traditional methods failed (ie. ir, hypervolemia, permissive hypertension and intravenous inotropes). mg of nicardipine was mixed with preservative free saline by pharmacy to total ml in volume. ml of cerebral spinal flu drawn from the patient external ventricular device (evd). then the nicardipine solution was instilled and the evd was clamped for minutes. patient had transcranial dopplers (tcds) prior to injection and hours after injection and reopening of the evd. patient's vasospam temporized and neuro exam returned to pre spasm baseline. patient survived vasospam window and was transferred to long term care facility. in neuroscience icu (nsicu) maintaining balance between performing reliable neurological exam with adequate analgesia without causing significant sedation is challenging. ketamine has significant neuroprotective and anti-seizure properties. in spite of these unique neuro-friendly pharmacological profile, it's role in nsicu unit is not well defined. we describe our experience about the use of ketamine in neuro-critical care unit. retrospective chart review of patients admitted to nsicu in whom ketamine was used as first line agent for sedation and analgesia in intubated patients with varied brain injury from january to april was performed. safety parameters collected includes blood pressure changes, intracranial pressure changes, heart rate, arrhythmias, excess secretions and apneic spells. pco was monitored and hypercarbia was avoided. effectiveness was measured by requirement of additional sedation-analgesic medications while receiving ketamine. twenty patients with varied brain injury who were on ketamine infusion as first line agent were selected. mean age was . years (range - years) and patients were male. admitting diagnosis was hemorrhagic stroke ( %), ischemic stroke ( %), seizures ( %), carotid stenosis ( %) and tumor mass ( %). mean duration of ketamine infusion was . days (range - days) and dose range was - mcg/kg/min. no icp elevation was noted among the patients where the icp was monitored. none of the patients had uncontrollable elevated blood pressures nor major fluctuation in heart rate or respiratory rate requiring discontinuation of ketamine. ( %) patients had increased secretions without respiratory compromise. opioid use decreased significantly moreover additional sedation was not required while on ketamine infusion. ketamine is a safe and effective sedative-analgesic in neuro-critical care patients while at the same time allow for a reliable neurological examination to perform while on sedation. more research is warranted before it could be considered as the standard of care. oromandibular dystonia (omd) is a movement disorder characterized by involuntary, sustained muscle contractions of varying severity resulting in sustained spasms of craniopharyngeal muscles affecting the jaws, tongue, face, and pharynx that can lead to abnormal jaw opening or closing or tongue protrusion. these disorders are often treated with botulinum for improvement of symptoms. there is minimal literature related to omd treated for botulinum in the neurocritically ill patient population. we conducted a retrospective electronic medical record review from - of all brain-injured patients admitted to our neurocritical care unit who were diagnosed with omd and received botulinum toxin injections. etiology and location of brain injury along with clinical characteristics including resolution of symptoms were recorded. over a -year period, we injected patients with botulinum type a injection ( mouse units or m.u.) into bilateral masseter muscles for severe omd causing tongue biting/maceration and difficulty with oral care, and refractory to antispasmodics and muscle relaxant medications. among the patients, patients were sah, patient with ich/ivh, patient with bilateral brain injury after post pituitary neurosurgical procedure and patient with diffuse bilateral ischemic stroke related to sickle cell disease. all patients tolerated the procedure with no immediate complications. all patients had gradual improvement of omd albeit variable and only out of patients required a nd treatment. in this small series, injection of botulinum toxin for severe omd from brain injury causing tongue injury appears to be safe, tolerable, and efficacious in reducing enteral antispasmodics/muscle relaxants. no short-term or long-term adverse effects were noted and it helped nursing with oral care over time. larger randomized controlled trials should be performed to evaluate the effectiveness and safety of treatment with botulinum in the critically ill neurologic population. the neurosurgical intensive care unit (nsicu), a level trauma center in san antonio, cares for neuro critical patients. the use of central access catheters is essential for hypertonic fluid administration, vasoactive medications, and general critical care. in this unique population the risk of developing deep vein thrombosis (dvt) is higher compared to other patients due to reasons related to neurological injuries. the objective of this research was to determine the incidence and prevalence of dvt between the use of peripherally-inserted central catheters (picc) versus central venous catheters (cvc) in the nsicu. we prospectively evaluated consecutive patients with a cvc or picc in the nsicu from to . data was collected, by a team of apps on: surveillance vs non-surveillance ultrasounds, blood stream infections (clabsi), indwelling time, complications, and icu length of stay. a total of piccs were placed for catheter days, patients were diagnosed with a dvt related to the catheter, rate of . per catheter days. a total of cvcs were placed for catheter days, patients were diagnosed with a dvt related to the cvc, rate of . per catheter days. a total of dvts were diagnosed, one symptomatic patient and remaining dvts were identified during surveillance ultrasound. two complications were encountered during insertion of a cvc and picc which included development of hematoma on insertion of each catheter. the average length of stay for patients with a picc line was . days. the average length of stay for patients with cvc was days. the nsicu surveillance ultrasounds identified more dvts with the use of picc lines versus cvc warranted if surveillance ultrasounds should be routinely performed for nsicu patients. mortality with acute respiratory distress syndrome (ards) is as high as % in patients with subarachnoid hemorrhage (sah). many of the therapeutic modalities of ards carry potential deleterious effects on icp. we are presenting a challenging case of severe ards and sah. single case report. -year-old male who developed a sudden severe headache. emergent workup revealed a large cerebellar hemorrhage, sah with ivh and hydrocephalus secondary to a ruptured arteriovenous malformation (avm). emergent suboccipital decompressive craniectomy followed by external ventricular drain (evd) placement were performed and transferred to our facility for further aggressive care. hospital course was complicated by severe pseudomonas pneumonia with progression to severe ventilation strategies, sedation, paralysis and inhaled nitric oxide (ino) failed to correct hypoxia. on hospital day (hd) he continued to show refractory hypoxia and was placed on roto-prone® bed. continuous intracranial pressure (icp) monitoring was utilized with evd open at cmh o. prone positioning was attempted for hours daily. hypercarbia during prone positioning lead to elevated icp patient showed improvement of hypoxia, with termination of prone positioning and subsequent weaning of paralytics and sedation. he started following commands and was discharged to a long term care facility after avm embolization, placement of a tracheostomy, feeding tube and ventriculoperitoneal shunt. our patient made remarkable recovery from ards in the settings of obstructive hydrocephalus and sah. strict icp monitoring, ongoing ventilator adjustment and careful utilization of kinetic maneuvers for ards, including prone positioning, contributed. proning may be a consideration in patients with sah, obstructive hydrocephalus and ards with ongoing icp monitoring and ventilator adjustment, but larger scale studies are needed to explore its potential. paroxysmal sympathetic hyperactivity (psh) has been associated with worse outcomes following traumatic brain injury, possibly representing both a marker of injury severity and a source of secondary injury. prior studies suggest that psh is under-recognized and its treatment often delayed. the identification of admission risk factors for psh may facilitate earlier recognition, treatment, and targeted prevention. adults with severe tbi admitted to a neurotrauma icu for at least hours and hospitalized for at least days between january and december were retrospectively identified. consecutive psh-tbi patients (n= ) were identified via review of medication administration records as having been treated with propranolol and/or bromocriptine for at least hours. control-tbi patients (n= ) were matched to the psh-tbi cohort for age ( +/- years) and gcs (median ( , ) ). admission head cts were scored using marshall and rotterdam criteria. independent-samples t-tests, chi-squared, and multivariate analyses of variance were performed. age-matched cohorts did not differ by sex, race, bmi, trauma type, trauma mechanism, iss, or triss. icu admission vital signs differed between groups with psh-tbi demonstrating a higher hr (p= . ) and a trend towards higher sbp (p= . ), but no difference in core body temperature. neuroradiographic features associated with psh included significantly higher rotterdam ct score (p= . ), presence of ivh/sah (p= . ), basal cistern compression (p= . ), and trends toward higher marshall ct score (p= . ), presence of epidural hematoma (p= . ), and ct dai (p= . ). a multivariate analysis adjusting for admission gcs and sbp identified rotterdam score (p= . ), presence of ct dai (p= . ), and icu admission hr (p= . ) as independent predictors of psh. admission ct findings along with hr may help predict subsequent development of psh requiring treatment. early identification, treatment, and prevention of psh may mitigate its negative impact on tbi outcomes. hyperchloremia in patients receiving chloride-containing solutions can contribute to metabolic acidosis and acute kidney injury (aki), and has been associated with increased inpatient mortality, length of stay and aki in patients with spontaneous intracranial hemorrhage. whether hyperchloremia is a risk factor for mortality in patients with traumatic brain injury (tbi) is unknown. the purpose of this study is to determine if patients that develop moderate hyperchloremia while receiving continuous hypertonic saline (hts) have a higher risk of inpatient mortality. this was a retrospective chart review of patients admitted between january and september . included patients were over years old, admitted to the trauma service with a diagnosis of tbi, and received continuous % hts for at least hours for the management of cerebral edema. exclusion criteria were baseline end stage renal disease or hemodialysis, transition to comfort measures within hours or inconsistent documentation. the primary objective was inpatient mortality. secondary objectives were aki, hospital and intensive care unit (icu) length of stay. after tbi, mortality was higher in patients who experienced hyperchloremia, while aki and length of stay were similar. although randomized controlled trials (rcts) did not prove benefits of hypothermia for severe traumatic brain injury (tbi), brain ct images have not been evaluated in detail in these studies. we aimed to explore the prognostic value of brain ct findings in bhypo study. bhypo study was a multicenter rct to investigate the effect of therapeutic hypothermia in patients with severe tbi. the protocol included collection of brain ct data on admission and around day . using the ct database, we evaluated following findings: presence of intracranial lesion (acute subdural hematoma: asdh, acute epidural hematoma, cerebral contusion, subarachnoid hemorrhage: sah, or intraventricular hemorrhage: ivh), basal cistern compression, lesion laterality, marshall ct classification, and rotterdam ct score. hematoma thickness and midline shift were also measured. unfavorable outcomes were defined gos of to by glasgow outcome scale (gos) assessed at months. ct data were obtained from patients on admission and patients around day . there were no differences in ct findings between hypothermia group and fever control group. in the initial ct, univariate analysis showed that odds ratio (or) and % confidence interval (ci) for unfavorable outcomes were: shift > hematoma thickness ( . , . - . : p= . ), sah ( . , . - . , p= . ), sah or ivh ( . , . - . , p= . ), absent cistern ( . , . - . ; p= . ), and midline shift > mm ( . , . - . , p= . ). rotterdam score was significantly higher in patients with unfavorable outcome ( . vs. . , p< . ). regarding the day ct, bilateral lesion ( . , . - . , p< . ) and sah or ivh ( . , . - . , p= . ) were significant. no patients with absent cistern survived. patients were appropriately assigned in bhypo study in terms of ct findings. shift > thickness, sah, absent cistern, and rotterdam score were powerful prognosticator in severe tbi patients undergoing targeted temperature management. cerebral edema (ce) following traumatic brain injury (tbi) causes secondary injury and increased mortality. yet, conventional measurements of ce on head computed tomography (ct) inadequately accounts for ce. serial volumetrics may facilitate estimation of total brain volume. the objective of this study was to measure the reliability of this technique and identify a threshold for brain volume (bv) change which could be indicative of ce. a subset of patients (n = ) with intracranial hemorrhage on admission ct were identified from a prospectively enrolled cohort of subjects with trauma sufficient to warrant icu admission. using medical image processing, analysis, and visualization (mipav), two independent raters calculated bv on admission and follow-up head ct scans by measuring the volume of the intracranial vault and the absolute difference (ml^ ) and percent difference between the bv values of the two scans were calculated. intraclass correlation (icc) and pearson's correlations were calculated, and significance set at . . the overall reliability of bv measurements between raters was excellent (initial scan icc . volumetric analysis to estimate bv appears to be a reliable technique across serial head ct scans. bv changes of more than . % may represent a clinically significant threshold and should be further investigated. beneficial effects of therapeutic hypothermia in adults with traumatic brain injuries are controversial. we wanted to study the effect of therapeutic hypothermia (th) on outcomes after severe traumatic brain injury (tbi) in real practice using the nationwide inpatient sample in the united states. the nationwide inpatient sample was used to obtain data on all adults who had been discharged from to with a primary diagnosis of tbi who required mechanical ventilation, intracranial pressure monitoring, or craniotomy/craniectomy. the patients with th were assigned to the th group, and the rest were assigned to the control group. the primary outcome was in-hospital mortality, and the secondary outcomes included mean the length of stay, non-routine hospital discharge, mean hospital charges. only patients ( . %) out of a total of , underwent th. th group was younger ( . versus . years, p <. ),had a lower proportion of females ( . % versus . %, p= . ) and a higher rate of in-hopsital complication of deep venous thrombosis ( . % versus . % p = . ). when controlling for age, gender, comorbidities, in-hospital complications, hospital characteristics and disease severity, th was associated with an increased rate of in-hospital mortality (odds ratio, . ; % confidence interval, . - . ), longer mean length of stay ( . vs. . days; p< . ), and greater mean total hospital cost ($ , vs. $ , ; p< . ). there was no difference between the two groups in terms of non-routine discharge (odds ratio, . ; % confidence interval, . - . ), therapeutic hypothermia was associated with poorer outcomes in patients with severe tbi. our findings disfavor therapeutic hypothermia in severe tbi in routine clinical practice. it warrants further investigation in a prospective, randomized study. a rising incidence of subdural hematomas (sdh) has been attributed in part to increased use of anticoagulants and antiplatelets. anticoagulants also worsen the severity and prognosis of sdhs, but the impact of antiplatelets on prognosis is unclear. we hypothesized that antiplatelets would not affect sdh severity or outcome, while anticoagulants would be associated with more severe features and a worse functional outcome. we systematically identified and collected data on patients presenting with a new diagnosis of sdh in at a level i trauma center. we examined common markers of sdh severity in three cohorts of patients: those not on any antithrombotics, those on antiplatelets alone, and those on anticoagulants. categorical data was compared with chi-squared tests, and continuous data was compared with mann-whitney u tests. multivariable logistic regression was used to assess the impact of antiplatelet use on functional outcome at discharge, with a poor functional outcome defined as a score of - on the modified rankin scale. we identified patients with a new sdh during : ( . %) did not take antithrombotics, ( %) took antiplatelets, and ( . %) took anticoagulants. antiplatelets were not associated with increased sdh volume, thickness, or midline shift; anticoagulants were associated with increased volume (p< . ), thickness (p< . ), and a trend towards increased midline shift (p= . ). antiplatelets were associated with a better admission score on the glasgow coma scale (p< . ). when adjusted for age and gender, antiplatelets did not affect functional outcome (or . , p . , % ci . - . ), while anticoagulants were associated with poorer functional outcome (or . , p . , % ci . - . ). despite its known association with overall sdh incidence, premorbid antiplatelet use was not associated with sdh severity or a worse functional outcome at a level trauma center. the common data elements therapeutic intensity level (cde-til) score, quantifies the intensity of nursing and medical care aimed at preventing intracranial hypertension for patients with severe traumatic brain injury. we validated the cde til in our neurotrauma intensive care unit (nticu) and found the cde-til to be highly reflective of perceived and measured therapeutic burden but noted that the scale had a ceiling effect. specifically when icp was - mmhg and higher, the cde-til did not capture the escalating burden. in an attempt to eliminate that ceiling effect and to incorporate current h til (p-til). under a quality assurance approved protocol, retrospective chart review was performed on adult patients with severe tbi. the til score was derived using both the cde-til and the p-til for each hour nursing shift for the first full days of admission. the relationship between the cde-til and p-til and the icp were investigated. reliability testing of the p-til, including interrater reliability, and validation of the p-til are ongoing. the p-til and the cde-til are highly correlated (r= . ) and the relationship between the scores and the maximum icp are similar at icp less than mmhg. at higher icps however, the slope of p-til increases to . compared to the cde-til slope of . and illustrates a . times stronger correlation between the intensity of care level as measured by p-til and icp. the p-til has greater sensitivity for quantifying the intensity of therapy aimed at controlling icps, most significantly for patients with the highest icps, icps - mmhg and above, making it an ideal scoring system for communicating current nursing and medical needs of individual tbi patients as well as potentially predicting post-intensive care or post-discharge needs. patients are frequently brought into neurologic intensive care units in cervical spine immobilization after sustaining ground level falls or after being "found down." currently there is no consensus regarding cervical spine clearance in these patients as they are unable to participate in neurologic examination. after normal ct scans, mri scans are frequently employed to evaluate for ligamentous injury and radiographic signs of cervical instability. we conducted a retrospective chart review of patients who were admitted to the neurologic intensive care unit between and in cervical collars after ground level falls or after being found down (presumed ground level falls). patients were included in the study if they were obtunded on admission (gcs< ) with neurologic exams consistent with their cranial pathology. all patients underwent a high definition ct cervical spine or cta of the neck and were cleared if there was no radiographic evidence of fracture or instability. between - , eight patients were admitted to the neurologic intensive care unit that met inclusion criteria. average age at presentation was . years. cranial pathology on presentation included intraparenchymal hemorrhage, ischemic stroke, and subdural hemorrhage. all patients underwent a high definition ct cervical spine or cta neck which showed degenerative changes without fractures, subluxations or other evidence of instability such as increased atlantodental interval, or prevertebral soft tissue swelling. average follow up was . days range ( - ). there were no cases of cleared patients that suffered secondary neurologic injury or symptoms of cervical instability during the follow up period. our study illustrates that obtunded patients after ground level falls can safely be cleared of cervical spine precautions after a high definition ct cervical spine fails to demonstrate fractures, subluxations, or other evidence of cervical instability. this protocol limits the costs associated with mri scans and the risks associated with cervical immobilization. the elderly comprise the highest incidence of traumatic brain injury (tbi) hospitalizations and death, yet most tbi studies neglect the geriatric population. previous studies suggest women have better outcomes after tbi but are inconclusive. we examined differences in outcomes between sexes after tbi in the geriatric population. this is an observational study of patients and older admitted with tbi to a level trauma center. clinical variables including medical history, severity of injury (gcs> , gcs - , and gcs< ), mechanism of injury, and ct findings were collected. good clinical outcomes were defined as a gose > and measured at discharge and months. the chianalysis were used where appropriate. subjects were included in the analysis. ( %) women and ( %) men. average age was . (sd . ) with no significant differences between sexes. ( %) were mild, ( %) moderate, and ( %) severe. the most common etiologies were mechanical fall ( %), motor vehicle accident ( %), and syncopal fall ( . %). no differences in severity of injury or mechanism of injury were found. on admission ct, men had more contusions ( %v %;p= . ) and skull fractures( %v %;p, . ) compared to women. older age, and history of atrial fibrillation or congestive heart failure were associated with increased incidence of death. men were more likely to have in-hospital mortality ( %v %; p< . ). in multivariable logistic regression analysis controlling for other factors associated with mortality, men were significantly more likely to have in-hospital death (or- ;p= . ). at months, men were still found to have higher mortality (or- . ;p< . ). however, there were no significant differences in good outcomes between sexes at discharge ( %v %; p= . ) or months ( %v %;p= ). men have significantly higher mortality rates compared to women in the geriatric tbi population. differences are needed. partial brain tissue oxygen tension (pbto ) can be regulated by the fraction of inspired oxygen and the level of oxygen carrying capacity. we performed a systematic review of the literature using pbto directed treatment with red blood cell transfusion (rbct) to analyze clinical and physiological outcomes as well as adverse events following rbct. we performed a systematic review following the prisma guidelines and pre-registered with the prospero database. the following terms were used: [(brain tissue oxygen or brain tissue hypoxia or pbo ) and treatment] or [(brain tissue oxygen) or red blood cell transfusion) or pbo ) or traumatic brain injury) and red blood cell transfusion]. inclusion criteria were studies in which pbto was measured before and after rbct. the tool used for qualitative scoring was the grade score. risk of bias was assessed via rti and robins-i. a total of articles were screened of which four articles were included in the final analysis. the intervention performed was to administer to units of rbc depending on the hemoglobin level and the threshold set in each study. the clinical outcome was not described in any of the studies. there was an increase in pbto in all the studies, but it was primarily significant when pretransfusion pbto was less than mmhg. the grade certainty rating for the included articles was low to moderate. our review shows that a significant increase in pbto is primarily seen when pre-transfusion pbto is less than mmhg. clinical outcome and adverse events were not described in any of the included studies. in view of the known adverse effects of rbct in critically ill patients and the limited available literature we found, transfusion should only be reserved as a later tier measure for pbto correction, and possibly only when pbto is less than mmhg. withdrawal of life-sustaining therapy (wlst) is associated with % of deaths after severe traumatic brain injury (tbi). wlst frequently occurs within the first days of hospitalization, when prognosis is most uncertain. while patient factors play a role in the decision, institutional practice patterns and physician perception of prognosis also contribute, as demonstrated in canadian studies. we hypothesized that the rate and timing of wlst among patients with severe tbi vary across the united states. we conducted a retrospective cohort study of patients with severe tbi admitted in to us trauma centers included in the trauma quality improvement program. severe, isolated tbi was defined by diagnosis code and glasgow coma scale (gcs) score < . patients under , with severe non-head injuries, or with advanced directives were excluded. centers were grouped by us census region (northeast, midwest, west, south). multiple logistic regression for wlst was performed with region, patient demographics, gcs motor score, pupillary reactivity, and midline shift as covariates. regression -hospital mortality. variability may reflect inconsistent institutional practice patterns, regional cultural differences, and the difficulty of prognostication. more reliable and standardized prognostic assessments are needed in this population. introduction: pre-injury use of antiplatelet agents may increase hemorrhage size and hematoma expansion after traumatic brain injury (tbi). however, empiric platelet transfusions may result in significant morbidity and unnecessary expense and may not be justified. we sought to determine whether a thromboelastography (teg) platelet-mapping (pm) algorithm could safely reduce platelet transfusion without clinically relevant hematoma expansion. methods: a prospective standardized teg pm-based treatment algorithm was instituted to guide reversal of antiplatelet medications in tbi patients. the algorithm established reversal thresholds for arachadonic acid inhibition (aa-inhibition > %) and adenosine diphosphate inhibition (adp-inhibition > %). consecutive tbi patients were enrolled and compared to a historical cohort. hematoma volume was calculated by itk-snap. conclusions: a teg-guided antiplatelet reversal algorithm may significantly reduce platelet transfusions without clinically significant hemorrhage expansion. increasing partial oxygen arterial tension is one method to increase the partial brain tissue oxygen (pbto ). however the effects of hyperoxia on clinical outcomes and adverse effects remain elusive. to investigate the effects of normobaric and hyperbaric hyperoxia on pbto in patients with tbi, we performed a literature review following the prisma guidelines and pre-registered with the prospero database. the following search terms were applied: [(brain tissue oxygen or brain tissue hypoxia or pbo ) and treatment] or [(brain tissue oxygen) or brain tissue hypoxia) or pbo ) or traumatic brain injury) and hyperoxia]. prospective trials and observational cohort studies were included in this review. two reviewers assessed the risk of bias of each study using the rti item bank. a total of articles were screened, of which articles were included. only one study investigated the effects of combined hyperbaric/normobaric hyperoxia and another used hyperbaric as a separate intervention; the majority of studies were of normobaric hyperoxia. overall, an increase in pbto was observed with both normobaric and hyperbaric. clinical outcome was mostly missing; one study showed an absolute reduction in mortality and improvement in favorable outcome using glasgow outcome score at months. adverse events were also only scarcely reported; studies showed that hyperoxia did not induce cerebral toxicity by using markers of oxidative stress, and one study showed no evidence of pulmonary oxygen toxicity in either the hyperbaric or normobaric hyperoxia groups. normobaric and hyperbaric hyperoxia consistently induced an increase in pbto . improvement in clinical outcome was reported in some studies but did not reach statistical significance except in one. adverse events were not adequately investigated. larger prospective studies are required to investigate the clinical outcome effects of hyperoxia, its adverse consequences, and its role in the tiered approach towards brain tissue dysoxia. early prognostication, either from clinical and/or radiological information, is an important aspect in the settings of neurocritical care with limited resources. we sought to determine the values of two radiological scoring systems in predicting the outcome of traumatic brain injury (tbi) patients, which are marshall and rotterdam ct scores in indonesia. therefore, a physician can make a better priority to provide high-yield care to all tbi patients. a retrospective cohort was conducted in a national referral hospital from july to december . all tbi patients admitted to the emergency department (ed) and had an initial ct scan were included in this study. their classification of tbi and initial ct scan were reviewed and all patients were followed to see whether the patient died or alive until discharge from the hospital (in-hospital mortality). statistical analyses were conducted to find the predictive values (sensitivity, specificity, cut-off point, relative risk) of both scoring systems. of tbi patients admitted to ed, there were patients had an initial ct scan. most of them were categorized as mild tbi ( . %), then moderate ( . %) and severe tbi ( . %). in-hospital mortality was . %. with cut-off point in marshall and rotterdam ct scores, their sensitivity ( . % vs. . %, respectively) and specificity ( . % vs. . %, respectively) were similar. same things also found in their relative risks, which are . ( % ci . - . ) and . ( % ci . - . ). both marshall and rotterdam ct scores have significant values in predicting the outcome of tbi patients, thus it should be implemented in daily emergency practice to assist a physician in making further clinical decisions. midline shift (mls) in brain is a critical condition. if not diagnosed timely, it could lead to a devastating outcome. computed tomography (ct) scan is the gold standard technique to diagnose mls in neurosurgical patients. the aim of our study was to find out association between transcranial sonography [tcs] and ct scan in assessing midline shift in patients with tbi. in this prospective ongoing study, adult patients ages - years, of either gender, with tbi were included. demographic details were noted. all patients underwent ct scan, followed by tcs. mls on tcs was determined using standard technique. we noted the mls on ct scan and time window between ct scan and tcs was also measured. consciousness was assessed using glasgow coma scale (gcs) and gcs -pupil [gcs-p] scales. descriptive data are given as mean (sd) or number. spearman's correlation test was used to detect relationship between gcs and mls assessed by ct scan and tcs, and also gcs-p. the value of p< . was considered significant. a total of neurosurgical patients were studied. male to female ratio was : . the age was [ . ] years with weight of . [ . ] kg. ten patients had gcs< . the mean value of mls measured by tcs - . , p = . ). the correlation between tcs and ct scan with gcs was in significan respectively. however the value of gcs- in patients with tbi, mls can be successfully assessed using bedside, non-invasive and non-radioactive monitor tcs when compared to a ct scan. there is a good correlation between gcs and gcs -p. early post-tbi seizures are reported to occur within hours and between days - following tbi in . % and . % patients, respectively. early seizure prophylaxis with phenytoin in severe tbi patients is drugs with better safety profile have emerged as potential alternatives. the objective was to describe seizure prophylaxis practices in critically ill tbi patients. we conducted a retrospective observational study of adult trauma icus. we included consecutive adult icu patients with moderate and severe tbi admitted between jan and dec . data were collected using standardized forms. our primary outcome was the incidence of seizure prophylaxis use. we included patients with a moderate ( %) or severe ( %) tbi. the majority were men ( . %) with mean age of . (sd . ) an ( %) and mva ( %). a total of % required invasive icp monitoring. a total of patients ( %) received early seizure prophylaxis, % for moderate and % for severe tbi. phenytoin, levetiracetam or their combination were used in ( %), ( %) and ( %) of cases, respectively. twelve patients ( %) were previously treated for pre-existing epilepsy. a total of ( %) patients experienced a seizure ( at the trauma scene, in er, in icu and on the ward). among the severe tbi patients in icu for days or more, anticonvulsants were continued for the recommended days in % of cases. early seizure prophylaxis is inconsistently used in severe tbi patients in canada. phenytoin still remains the agent most used. despite the current recommendations, % with severe tbi did not receive prophylaxis and % for a shorter period than days. raised icp persistently in severe tbi patients may be detrimental. however, chest physical therapy (cpt) is equally necessary for preventing secondary factors influencing the risk in these patients. this study was intended to observe the impact of short-term rise in icp with manual cpt in severe tbi patients on outcome along with hemodynamics. this was a prospective, observational trial on adult patients, of either sex, aged - years, with severe tbi, on mechanical ventilatory support with continuous icp monitoring, and receiving cpt on regular basis, included in this study. the cpt was applied for minutes' duration and repeated after an interval of hours in between for a total sessions in a day. the measurement measured intracranial pressure, cerebral perfusion pressure, heart rate, mean arterial pressure (from start of the intervention until min after the intervention at min interval each), and gcs after each session of cpt along with final outcome/gos at the time of discharge and months. the rise in median intracranial pressure of . (- . , . ) and median cerebral perfusion pressure of . (- , . ) was significantly higher during intervention and after intervention phase. in contrast, a median heart rate rise of . ( . , . ) and mean arterial pressure rise of . ( . , . ) were comparable. however, in patients with high baseline icp (> mmhg), poor outcome was noted in terms of low gose ( , ), and higher mortality ( . %) at hospital discharge or months after injury. significant increase in icp in severe tbi patients post cpt for minutes at a time (total minutes each day) was not tolerable in this cohort. moreover, we observed significantly low gose in patients with sustained intracranial hypertension. the effect of manual technique of cpt on final (long-term) neurological outcomes remain inconclusive but with favorable respiratory outcome. survivors of moderate and severe traumatic brain injury (mstbi) require substantial care, much of which is provided by friends and family. we sought to describe the experience and unmet needs of survivors and their informal caregivers follow mstbi, particularly related to care transitions. this study was conducted in two intensive care units (icus) at a level trauma center. we conducted qualitative, semi-structured interviews with both patients and informal caregivers of mstbi survivors at hours, one month, three months, and six months post injury. informal caregivers were defined as friends or family who planned to provide care for the patient. patients were years or older with an mstbi, and not expected to imminently die of their injuries. eighteen patient-caregiver dyads were enrolled. one patient died within hours. at hours, caregivers were interviewed; at one-month caregivers were interviewed; at three months caregivers and one survivor were interviewed; and, at six months caregivers and seven survivors were interviewed. three themes were identified in the qualitative analysis of caregiver interviews: caregiver burden, caregiver health related quality of life, and caregiver need for information and support. experiences varied depending on time since injury, discharge disposition, functional neurologic outcome, caregiver access to resources, and likely multiple other additional factors. interviews with survivors were not insightful secondary to post-traumatic amnesia. this study provides new information about the experience of informal caregivers during the six months after their friend or family member survived an mstbi. caregivers reported that needs evolved over time. at three to months, few moderate to severe tbi patients were well enough to be interviewed, and information obtained by survivors was not insightful. interventions to promote caregiving may be a substantial opportunity to improve patient and caregiver-centered outcomes following tbi. vasospasm following traumatic brain injury (tbi) has a high incidence and a detrimental effect on the neurological prognosis. yet, it remains a neglected, poorly understood phenomenon and there are no guidelines for its management. herein we present a case of severe vasospasm following tbi that caused secondary delayed cerebral ischemia (dci). we further appraised the current literature aiming at identifying predictors of vasospasm in tbi. a y/o white woman presented to the hospital after a mechanical fall resulting in mild tbi with associated subarachnoid hemorrhage (sah). glasgow coma scale (gcs) at presentation was , with no neurological deficits. a non-contrast ct head revealed diffuse bilateral fronto, parietal and temporal sah without evidence of aneurysm or vascular malformations on ct angiogram (cta). toxicology screens were negative. at hours from tbi patient developed acute severe headache. a repeated cta showed right internal carotid artery (ica) and middle cerebral artery (mca) vasospasm with no ischemia identified on mri brain. patient was started on nimodipine. on day- patient developed acute left side hemiparesis and neglect with neuroimaging evidence of a complete right mca infarct. hemodynamic augmentation therapy was initiated with partial improvement of deficits. patient subsequently developed hemorrhagic conversion of the right mca infarct. on day- neuroimaging revealed resolution of vasospasm. patient had residual left side neglect and anosognosia. in line with prior literature our patient developed vasospasm in the large intracranial vessels, at hours from the tbi and earlier than in aneurysmal sah. however, differently from previous reports, gcs at presentation was > , age was > and despite vasospasm developing later than hours it was not associated with good outcome. eded to identify accurate predictors of vasospasm following tbi with secondary dci that could improve detection and management of this detrimental phenomenon. therapeutic hypothermia and/or cooling therapy has been hypothesized to have benefits in patients with traumatic brain injury (tbi). several systematic reviews (sr) are being performed to address this question, but their results are inconsistent. the objective of this study was to assess the methodological quality of sr that included randomized clinical trials (rcts) that assessed the effects of therapeutic hypothermia and/or cooling therapy in patients with tbi. a critical appraisal study was performed in order to assess any sr that fulfilled the inclusion criteria. an unrestricted search of the literature was carried out in march at four major electronic databases (medline, embase, lilacs and cochrane library). two independent reviewers selected the studies, extracted the data and appraised the methodological quality of the included sr using the amstar- (a measurement tool to assess systematic reviews) tool. an overall assessment of the confidence in the results was performed using the checklist available in amstar- website (https://amstar.ca/amstar_checklist.php). the confidence of the results may be graded as high, moderate, low or critically low. this grading is based on the adequacy of the sr to the domains of the amstar- . the search strategy retrieved references. after the selection process, sr were included. the sr were published between - and included to rcts. the overall confidence in the results from included sr was graded as critically low in . %, low in . %, moderate in %, high in . %. a high number of sr addressing similar clinical questions were published in a short period of time. the methodological quality was adequate in only few sr. clinical practice guidelines should considered this result when choosing the evidence synthesis to recommend for practice. neurogenic pulmonary edema (npe) is a clinical syndrome characterized by acute onset after central nervous system injury. the aim of this study was to investigate the clinical features of npe in patients with subarachnoid hemorrhage (sah). the authors retrospectively analyzed a total of patients with sah who were treated at our hospital from april to september . of these patients, were included in this study after the application of predefined exclusion criteria. patient demographics, aneurysm size and location, clinical characteristics, and patient outcomes were reviewed and compared between an npe and a non-npe group. sixteen patients ( . %) presented with npe at admission. among them, patients ( . %) recovered from npe immediately, and ventilatory support was withdrawn within days from onset. a univariate analysis showed that patients with npe were of younger age (p= . ), had a higher rate of vertebral (p= . ), and lower systolic blood pressure on admission (p= . revealed significant differences in the frequency of vertebral artery dissection (odds ratio (or) . , % ci . -- . , p= . ) between the groups with and without npe. no significant group differences were found in other factors, including heart rate, neurologic outcomes at discharge. vertebral art factors for npe. however, neurologic outcomes at discharge did not differ between groups, suggesting that poor outcome due to npe could be reduced by appropriate diagnosis and treatment. antibiotic-impregnated catheters (aic) are recommended for the prevention of ventriculostomy-related infections (vri). other antibiotic prophylaxis strategies following external ventricular drain (evd) placement vary widely by institution. the role of systemic antibiotics for this indication remains controversial. we retrospectively reviewed the charts of all patients having an evd placed between january , and december , . after excluding patients who died or were discharged within hours of evd placement or had an evd placed due to suspected meningitis, patients were categorized into the periprocedural (p) or no periprocedural (np) antibiotics group. patients were determined to have a vri if catheter and up to days after catheter removal. mann-whitney u test was used to analyze descriptive data and baseline demographics. chi-squared models were used to analyze the incidence of infection. included in the no periprocedural antibiotics group (age [ - ] years; % male) and were included in the periprocedural antibiotics group (age [ - ] years; % male). the most frequent indications for evd were subarachnoid hemorrhage (sah) [np: n= ( %), p: n= ( ), p< . ], intracranial hemorrhage (ich) [np: n= ( %), p: n= ( %), p= . ), and other, which included colloid cysts and tumors [np: n= ( . %), p: n= ( %), p< . ]. there were infections in the no periprocedural antibiotics group compared to in the periprocedural antibiotics group (p= . ). the most common pathogen was coagulase-negative staphylococci (n= , %). the use of periprocedural systemic antibiotic prophylaxis did not significantly reduce the incidence of vri. periprocedural systemic antibiotics may not be necessary in the setting of antibiotic impregnated catheters to reduce the incidence of infection. cerebral artery vasospasm is a rare complication of craniopharyngioma resection but can have life altering consequences including delayed cerebral ischemia if not quickly recognized and managed appropriately. we present a case of craniopharyngioma resection in a year old male complicated by refractory vasospasm and its management with intraventricular nicardipine. data regarding the operative management, time course, vasospasm and management was accessed retrospectively after patient discharge. a year old male with recurrence of a craniopharyngioma presented with left eye vision loss and was admitted to the neurosciences intensive care unit after transsphenoidal resection. intraoperatively, the tumor was noted to be adhered to the posterior communicating artery and the left anterior cerebral artery. dense invasion into the hypothalamus was noted. this portion was carefully resected to avoid progressive lethargy. computed tomography angiography revealed new mild narrowing of the left anterior and middle cerebral arteries and bilateral posterior cerebral arteries consistent with vasospasm. the patient was treated with a vasospasm bundle including nimodipine, euvolemia, and blood pressure augmentation. over the next twenty days, the patient continued to have a variable amount of vasospasm despite aggressive medical and intra-arterial management. on post-operative day . nicardipine was then infused into the evd once a day for days, resulting in rapid and sustained improvement in vasospasm. the mechanism of vasospasm following skull base tumor resection is unknown. presence of blood in the operative bed, direct surgical injury to the blood vessels, hypothalamic dysfunction and the release of inflammatory chemicals have all been proposed. treatment remains similar to treatment used in sah, utilizing nimodipine, euvolemia, blood pressure augmentation and intra-arterial verapamil. this case demonstrates the effectiveness of intraventricular infusion of nicardipine on refractory vasospasm. to present a rare case of bilateral internal carotid artery (ica) aneurysms presenting as trigeminal neuralgia (tn), with good outcome post surgical treatment. a -year-old woman presented with disabling tn for year, exclusively affecting the right maxillary and mandibular divisions. symptoms did not abate with trial of adequate doses of gabapentin, duloxetine, oxcarbazepine and indomethacin. thin-cut magnetic resonance imaging (mri) brain with and without contrast showed rare contact with wide-necked aneurysms of bilateral petrous-cavernous icas producing prominent mass effect on bilateral adjacent trigeminal nerves. carotid arteriogram redemonstrated ica aneurysms with left measuring . mm x . mm and right measuring . mm x hours post procedure, tn had completely resolved. patient was started on aspirin mg and clopidogrel mg daily and is being tentatively planned for intervention on left aneurysm. on her month follow-up appointment with neurology, she reports no recurrence of tn. in cases of aneurysmal causes of tn, presence of bilateral aneurysms causing mass effect on the trigeminal nerve at its root is a rare occurrence and needs high clinical suspicion. due to the high risk of rupture associated with giant and symptomatic aneurysms, treatment should be expedited and aggressive in order to not only address symptomatic tn but also to avoid the risk of aneurysm rupture in the future. surgical clipping and endovascular coiling with or without stenting has demonstrated remarkable symptom relief in reviewed literature for other types of intracranial aneurysm. moyamoya disease is a chronic cerebrovascular disease characterized by spontaneous and progressive stenosis or occlusion of the internal carotid artery and its branches. revascularization procedures have been shown to improve cerebral hemodynamics and decrease the risk of strokes, but several postoperative complications are known to occur. we present a case with a fairly rare complication with characteristic radiological findings after surgery. a -year-old girl with moyamoya disease underwent left superficial temporal artery (sta)-to-middle cerebral artery (mca) anastomosis with encephalo-duro-myo-synangiosis (edms), and did right sta-mca anastomosis and edms one year after the initial surgery. the procedures were uneventful and the occlusion time was minutes. she recovered from the anesthesia without neurological deficit, and mri on postoperative day (pod) demonstrated no ischemic lesions and patent bypass, although swelling of the temporal muscle attached to the brain surface was noted. on postoperative day , she experienced a transient neurological event (left hemiparesis). magnetic resonance imaging revealed large cortical and subcortical hyperintense lesions in the middle cerebral artery territory on diffusion-weighted imaging and apparent diffusion coefficient imaging. subsequently, the radiographic findings improved within several days with resolution of the symptoms. revascularization surgery for improving a patient's hemodynamics can prevent the development of strokes, but is known to be associated with perioperative cerebral infarction and cerebral hyperperfusion causing transient neurological deterioration, delayed intracerebral hemorrhage, and vasogenic edema.this case is a reminder that hemodynamic complications can develop subacutely in patients who have undergone successful revascularization for moyamoya disease. the radiological features and mechanisms of this rare condition associated with revascularization surgery for moyamoya disease are discussed. vasospasm with delayed cerebral ischemia is a rare but known complication of endoscopic transsphenoidal resection of pituitary adenoma. this complication has rarely been reported in cases of -arterial treatment have been favorable in some cases. electronic medical record review. the patient is a year old male who underwent subtotal resection of pituitary adenoma via an open right fronto-temporal approach. eight days post-resection he developed progressive headache and leftsided weakness which acutely worsened the following day. his nihss on presentation was , consistent with right mca syndrome. ct brain showed mass effect in the right frontal lobe with . mm midline shift. cta showed sluggish flow through right m branch suggestive of vasospasm. he was taken to cerebral angiogram post-op day and received right ica intra-arterial verapamil and right ica and mca angioplasty. he was started on nimodipine following the procedure. his exam improved significantly over the course of - days. he was discharged home on verapamil mg q hours. at three month follow-up his nihss was and his modified rankin scale was . in the case we present, the patient received intra-arterial treatment with verapamil and angioplasty - days after onset of symptoms. despite delayed presentation the patient ultimately achieved a favorable functional status. vasospasm and stroke post-pituitary tumor resection are complications of which patients should be adequately informed, especially when considering the possibility of good functional outcome with intraof this potentially debilitating and life-threatening complication and attention should be paid to utilizing techniques for early detection of vasospasm. neuromonitoring is an essential part of the management of neurocritical patients. many icus in developing countries manage their patients without monitoring icp. intensivists play a vital role in clinical judgments to manage their patients. raised icp are handled either by medical management or surgical procedures like decompressive craniotomy. the study aimed to see the outcome of patients with raised icp and compare medical vs surgical management in these patients without monitoring icp. a retrospective observational study was conducted among patients admitted from january to december in the icu of dhaka medical college hospital, bangladesh. patients who had etiologies of brain code, clinical presentations and or radiological findings consistent with raised icp were included. patents were grouped into neurosurgical and medical management groups. length of icu stays and mortality were observed. student's t-test and chi-square tests were used to see the statistical significance. total of patients was selected. mean age was . ± . years, and . % were male. traumatic brain injury was the most common cause of raised icp ( . %) among selected patients. . % of patients were managed medically, and neurosurgical procedures managed . % of patients. length of icu stay was higher in neurosurgical patients compared to medical management group ( . ± . vs . ± . ; p= . , non-significant). mortality was higher in neurosurgical patients compared to medical management group ( . % vs . %; p= . , non-significant). mortality was also higher in traumatic brain injury patients who underwent neurosurgery compared to medical management ( . % vs %; p= . , non-significant). neurosurgical management didn't show a better outcome in patients with raised icp when monitoring was unavailable in a resource-limited icu. chronic kidney disease (ckd) independently increases the risk of stroke and burden of ischemic small vessel disease (svd). effects of ckd on intracranial hemodynamics remain poorly defined. this study compared svd and a transcranial doppler (tcd)-based marker of intracranial vascular resistance (pulsatility index, pi) in post-stroke patients with and without ckd. within three months of a stroke. anterior and posterior circulation pi (aca, mca, and pca) significantly correlated with mri lesion volume in all patients. ckd strongly correlated with higher distal resistance (median ckd aca pi . in patients with recent stroke, mri svd volume is significantly associated with anterior and posterior circulation pi. significantly higher svd lesion burdens and anterior circulation pis were observed in patients with ckd. ckd is an independent determinant of increased intracranial vascular resistance in both anterior and posterior cerebral circulations. atrial fibrillation is associated with an increased risk of stroke and systemic embolism. we investigated the prevalence of coexisting subdiaphragmatic visceral infarction (sdvi) in patients with acute ischemic stroke due to atrial fibrillation and also evaluated independent factors of acute sdvi. we enrolled a consecutive series of acute ischemic stroke subjects with atrial fibrillation between mra or cta were excluded. all subjects were prospectively examined using abdominal mr imaging at . t and transthoracic echocardiography (tte) within days of onset. a multivariable logistic regression analysis with predefined variable (age and sex) and the potential confounders that were associated with sdvi i the mean age was . ± . years ( % males). onset-to-abdominal image time was . ± . days. among patients, acute coexisting sdvi ( renal and splenic infarctions and superior mesenteric artery occlusion) were found in patients with acute ischemic stroke and atrial fibrillation. twelve patients had a chronic sdvi; renal and splenic infarctions. no hepatic and bladder infarction was shown. severe significantly associated with the coexistence of acute sdvi and acute ischemic stroke attributed to atrial fibrillation in the logistic regression model. (adjusted or, . ; % ci, . - . ; p = . ). there was a significant relationship between the presence of acute sdvi and severe left atrial remodeling in acute ischemic stroke patients attributed to atrial fibrillation. based on these results, we suggest that abdominal mr imaging for evaluating coexisting acute sdvi should be considered in patients with acute ischemic stroke due to atrial fibrillation, especially with left atrial enlargement on tte. patients with large hemispheric infarction are likely to accumulate chloride due to commonly used hypertonic saline for lowering elevated intracranial pressure. however, the effect of chloride burden on clinical outcomes in these patients is not well studied. this study aims to investigate the impact of maximum serum chloride concentration during admission on in-hospital mortality in critically ill patients with large hemispheric infarction. we conducted a retrospective observational study of patients with large hemispheric infarction who were admitted to the neurocritical care unit, between march and june . patients were excluded if they had baseline creatinine clearance less than ml/min, required neurocritical care for less than hours. multivariable logistic regression models were used to evaluate the association of maximum serum chloride concentration during admission with in-hospital mortality. of eligible patients, ( . %) were died in hospital. compared to patients who survive to hospital discharge, those who died in hospital had higher maximum serum chloride level during admission ( . ± . vs . ± . , p< . ). each mmol/l increase in maximum serum chloride concentration was associated with increased risk of in-hospital mortality with an odds ratio of . ( % ci, . - . , p< . ). after adjusting for confounders including acute physiology, age, chronic health evaluation ii (apache ii) score, baseline serum glucose, base deficit, use of mannitol, hypertonic saline, therapeutic hypothermia, and incidence of acute kidney injury, maximum serum chloride level remained an independent risk factor associated with in-hospital mortality (adjusted odds ratio for every mmol/l increment, . ; % ci, . - . , p= . ). higher maximum serum chloride concentration was associated with higher in-hospital mortality in critically ill patients with large hemispheric infarction. these results suggest serum chloride level should be monitored as high chloride burden may cause poor outcomes on those populations. patients with acute ischemic stroke caused by large vessel occlusion may receive both ct-angiogram (cta) and digital subtraction angiogram in the process of evaluation and management of restoring perfusion. neither aha/asa stroke/imaging guidelines address indications for transcranial doppler (tcd) and/or carotid duplex ultrasonography (cus) in early stroke evaluation and most patients do not receive additional cerebrovascular imaging after reperfusion. we investigated the clinical utility of performing tcd/cus after reperfusion in guiding post-acute care stroke management. we reviewed inpatient ischemic strokes admitted to a comprehensive stroke center in . of these had tcd/cus done and had cta done prior to tcd. of these underwent either tissue plasminogen activator or thrombectomy for reperfusion. these cases were reviewed by two experts (kh, qv), who were blinded to each other, to determine if tcd/cus provided any added value after cta affecting patient management. a nominal group process was performed, using a third blinded expert (as) in case of disagreements to reach consensus. the reviewers reported cases where tcd/cus provided incremental value for management. value added by tcd/cus, as noted by experts, included detection of residual/recurrent mobile thrombus requiring anticoagulation, confirmation of reperfusion in a symptomatic patient, distinguishing between carotid stenosis and occlusion by showing string sign on carotid ultrasound, confirming hemodynamic significance of angiographic stenosis helping triage the need for stenting/endarterectomy, and new information on chronicity of carotid stenosis based on collateral flow patterns hence deferring further intervention. our experience shows a significant added value of performing tcd/cus in more than % of stroke cases in our review. the incremental information provided by ultrasound-guided further evaluation and management decisions in most of these patients. axons of the wallerian degeneration slow (wlds) mutant mice survive weeks after traumatic and ischemic nerve injuries. prior characterization of the mutant wlds protein showed that it is a fusion gene product between the non-functional, truncated n amino acids of ube b and full functional sequence of nuclear nmnat , a rate-limiting enzyme in nad+ synthesis. however, the molecular mechanisms by which the mutant wlds protein protects axons from stroke injuries remain unclear. we sought to understand how wlds is able to robustly protect axons from ischemic injuries, and in doing so possibly identify novel therapeutic targets to attenuate axonal loss in stroke. we first sought to understand the temporal and spatial requirements of wlds activity in protecting axons from ischemic injuries. to achieve this, we developed a novel tool to conditionally regulate the expression of wlds protein by modulating its post-translational protein stability. using this powerful technique, we asked how conditionally "turning on" or "turning off" wlds activity affects axonal survival following ischemic insults. moreover, as the only known function of wlds is in catalyzing nad+ synthesis, we designed a high-throughput pharmacological screen for nad+ analogs to evaluate whether the nad+ synthetic pathway mediates wlds axon protection. we found that conditional expression of wlds protein within - hrs after stroke injuries was necessary and sufficient to confer axonal survival, whereas turning off wlds activity post-injury abolished axon protection. this indicates that wlds activity is a local event in the axon, and exerts axonal protection within a critical time window even after the injury has occured. we further observed that exogenous addition of nad+, but not its precursors or immediate metabolites, was sufficient to confer axonal protection, while attenuating nad+ levels abolished wlds axon protection. this suggests that nad+ is a molecular mediator of wlds axon protection in stroke. we showed that wlds activity is a local axonal event, and uncovered a critical window of - hrs poststroke injury in which the course of axon degeneration can be halted or even reversed in mammalian neurons. moreover, we showed that this process is mediated by rising nad+ levels in axonal compartments through a novel nad+ dependent cell signaling cascade. these findings provide powerful insight into the molecular bases of wlds activity, and uncover new therapeutic targets to delay and potentially even reverse axon degeneration in stroke. unruptured intracranial aneurysm (uia) are incidentally found on the computed tomography (ct) or magnetic resonance angiography in about % of patients. because of the risk of intracranial hemorrhage (ich), the presence of uia is contraindication to intravenous thrombolysis for acute stroke. as noncontrast ct (ncct) is mostly used for thrombolytic therapy and uia is difficult to diagnose using a ncct, uia may be found after thrombolysis. among the patients with acute ischemic stroke treated with intravenous thrombolysis for consecutive years in one stroke center, patients diagnosed with uia by ct angiography immediately after thrombolysis, were enrolled. characteristics of uia and clinical outcomes such as ich and modified rankin scale (mrs) score at discharge were analyzed. among patients treated with intravenous thrombolysis, ( . %) patients were diagnosed with uia. ally relevant artery and patients an aneurysm less than mm in diameter. the median value of the initial national institutes of health stroke scale score was (range - ). the median mrs score at discharge was (range - ). there was no patient who had ich or aneurysm rupture during admission. intravenous thrombolysis could be safe and necessary to the patients with hyperacute ischemic stroke and incidental uia. recent studies suggest that variations in the constitution of the gut microbiome contribute to atherosclerotic burden and cardiovascular disease. while many gastrointestinal (gi) diseases are known to cause disruption of the normal gut microbiome in humans, the clinical impact of gi diseases on subsequent vascular disease remains unknown. we conducted an exploratory analysis evaluating the relationship between gi disease and ischemic stroke or acute myocardial infarction (mi). we performed a retrospective cohort study using claims between - from a nationally composite of ischemic stroke or acute mi. stroke and mi were assessed separately as secondary outcomes. in an exploratory manner, we evaluated the association of each gi disorder in the icd- -cm classification with our outcomes. we then categorized individual gi disorders by anatomic location, disease chronicity, and disease mechanism. we used cox proportional hazards models to examine associations with adjustment for demographics and established vascular risk factors. since this was an exploratory, hypothesis-generating study, we report only notable positive associations. among approximately , , beneficiaries, the following gi disorders were associated with an increased risk of subsequent ischemic stroke: gastric ulcer (hr, . , % ci, . - . ), duodenal ulcer ( . , . - . ), gastritis and duodenitis ( . ; . - . ), disorders of function of stomach ( . , . - . ), other disorders of stomach and duodenum ( . ; . - . ), gastrointestinal mucositis ( . ; . - . ), unspecified noninfectious gastroenteritis and colitis ( . ; . - . ) and gastrointestinal hemorrhage ( . ; . - . ). the following categories of gi disorders were associated with an increased risk of ischemic stroke: stomach disorders ( . ; . - . ), stomach and small intestine disorders ( . ; . - . ), ulcerative disorders ( . ; . - . ) and chronic gi disorders ( . ; . - . ). gi disorders were not associated with an increased risk of mi, and some demonstrated a reduced risk. several gi disorders were associated with an increased risk of ischemic stroke, but none were associated with an increased risk of mi to evaluate the relationship between serum neutrophil-to-lymphocyte ratio (nlr) levels and early neurological deterioration (end) in ischemic stroke patients with large-artery atherosclerosis (laa). we evaluated consecutive ischemic stroke patients due to laa between january and december within the first hours of admission. the nlr was calculated by dividing the absolute neutrophil counts by the absolute lymphocyte counts. among the included patients (n = ; male, . %; mean age, years), . % (n = ) had end events. in multivariate analysis, serum nlr level was independently associated with end (adjusted odds ratio, . ; % confidence interval [ . to . ], p = . ). visit time from symptoms onset, and insitu thrombosis and artery-to-artery embolization mechanisms were also found to be significant factors for end events. in the analyses regarding the relationship between serum nlr values and burden of vascular lesions, nlr levels were positively correlated with both the degree of stenotic lesions (p for trend = . ) and numbers of vessel stenosis (p for trend = . ) in a dose-response manner. we also compared the difference of serum nlr levels according to the stroke mechanisms from underlying vascular lesions. then, hypoperfusion and in-situ thrombosis mechanisms showed higher levels of nlr. however, only in-situ thrombosis mechanism had higher nlr values among the end groups compared to non-end groups (p = . ). serum nlr levels were associated with end events in ischemic stroke patients with laa mechanism. since nlr was also closely correlated with the relevant vascular lesions, our results indicated clues for underlying mechanisms of end events. transcranial doppler (tcd) can detect emboli in numerous cerebrovascular settings. although previous studies have suggested that microembolic signals (mes) may predict recurrent stroke, the practical significance of such findings remains unclear. this uncertainty has deterred the widespread use of embolic monitoring among clinicians. in a retrospective fashion, we investigated the real-world applicability of tcd by examining whether the presence of mes portends worsened clinical outcomes. we reviewed the charts of all ischemic stroke patients (n = ) who underwent mes monitoring from january to december . of the stroke subtypes reviewed, % were atheroembolic, % were cardioembolic, % were lacunar, % were dissection, % were hypercoagulable, % were cryptogenic, and % were due to other causes. +/- mes were detected in % of patients. mes were detected at an average of . +/- . db (with a detection threshold > . db). recurrent stroke was seen in % of patients (monitored over . +/- . days). patients with mes were more likely to have recurrent stroke ( % vs. %, p < . ), undergo a revascularization procedure ( % vs. %, p = . ), have a longer length of stay ( vs. days, p = . ), and have a discharge mrs - ( % vs. %, p < . ) compared to those without mes. multivariable logistic regression analysis showed that mes was an independent predictor of recurrent stroke (or . , % ci . - . ) and of poor discharge mrs - (or . , % ci . - . ) despite controlling for antithrombotic treatments and stroke subtypes. in the largest series of patients who underwent embolic monitoring with tcd, mes predicted ischemic stroke recurrence leading to worsened disability and prolonged hospital stays. given that mes can provide important prognostic information, tcd with embolic monitoring may be clinically useful in the workup of ischemic stroke. expanded patient eligibility for mechanical thrombectomy (mer) of acute ischemic stroke (ais) has resulted in a proportional increase of patients who require emergency angioplasty and/or stenting (eas) to achieve recanalization. post-stenting antiplatelet medication management continues to remain a challenge due to lack of immediate effect and rapid reversibility ideal for patients at high risk of stent thrombosis and hemorrhagic complications, especially after intravenous alteplase (tpa). cangrelor is an immediate-acting intravenous p y receptor inhibitor with rapid clearance and restoration of normal platelet within one hour of infusion termination. we describe our preliminary experience with administration of cangrelor in ais patients undergoing mer and requiring eas as rescue therapy. ten patients with ais who received cangrelor after mer were identified. median admission national tpa prior to mer. cangrelor drip was started immediately prior to eas. median duration of cangrelor drip was hours. dual antiplatelet was given a median time of hours before discontinuation of cangrelor. seven patients had repeat imaging at months confirming durable vessel patency and no restenosis. none of the patients experienced clinical deterioration, symptomatic intracranial hemorrhage, or recurrent strokes during the hospital stay. one patient underwent surgical decompression but did not develop any hemorrhagic complications. median mrs at discharge was , and median nihss at discharge was . in our case series, cangrelor was observed to be a safe alternative to oral antiplatelet drugs in the immediate perioperative period among ais patients who underwent mer and required eas, , including patients who received tpa and at high risk for malignant cerebral edema or hemorrhagic transformation who may require emergency surgical decompression. the response of the neonatal brain to hypoxic ischemic injury (hi) is developmentally specific therefore therapies for brain hi cannot be standardized across the ages. while arginases (arg; isoforms arg- /arg- ) are enzymes actively studied for their neuroprotective/neuroregenerative effects in various neurological conditions, in neonatal hi the arg effect remains unknown. to test the hypothesis that arg changes with neurodevelopment and after hi we exposed mice c bl/ (wild-type) to hypoxia-ischemia on postnatal day , as follows: permanent coagulation of left common carotid artery to induce ischemia, a h recovery period and exposure to % oxygen/balance nitrogen at °c for min to induce hypoxia. animals were perfused at h, h, h, h and day with % paraformaldehyde, brains were post-fixed, sectioned on a cryostat ( um) and examined histologically with cresyl violet stain to assess the degree of damage and arg spatiotemporal localization via immunohistochemistry. arg expression was measured by western blot and arg activity spectrophotometrically. arg expression and activity increase during development, however this increase is suppressed by hi. arg- expression increases on day after hi which corresponds to our findings of arg- accumulation at the penumbra site. cortical arg activity remains suppressed after hi, compared to that in the hippocampus, where it increases. spatiotemporally, arg- localizes into myeloid cells in cns. arg- expression increases in microglia as early as h after injury and remains elevated for a prolonged time. arg- is localized in pyramidal neurons of the indusium griseum, fasciola cinerea, neocortex and hippocampus (ca , ca ). arg- -expressing cells are damaged by hi, however they do not undergo spatial changes. microglial arg- strongly responds to hi and may play role in neuroinflammation and neuroprotection, while argand therapeutic potential of the arg-pathway in neonatal hi. sisco: helping stroke patients with thermasuit cooling trial is a phase study in ischemic stroke with rapid induction of hypothermia to within one hour. this patient had induction followed by early malignant edema requiring decompressive hemicraniectomy while c. this is the first report of hemicraniectomy in a therapeutically hypothermic patient. results y/o woman presenting with a left mca syndrome. initial imaging demonstrated left m occlusion. she received iv tissue plasminogen activator (tpa) followed by thrombectomy with tici recanalization within practice guidelines. she was enrolled in sisco trial. she was sedated with propofol, fentanyl, and versed for induction, reaching target temperature of degrees within minutes. she remained on sedation for shivering and temperature was maintained at degrees with the artic sun. imaging hours after stroke demonstrated completed infarct with edema, midline shift, and lateral ventricle effacement. hypertonic saline was initiated, and she underwent emergent decompressive hemicraniectomy. balancing the risk of worsening edema and coagulopathy caused by mild hypothermia, rewarming was initiated at . degrees c per hour. at the time of procedure patient was at . . a successful hemicraniectomy was performed without complications. six months demonstrated improvement with the patient returning home with modified rankin , and cranioplasty performed without complications. during sisco, an emergency decompressive hemicraniectomy for malignant mca syndrome was performed for a cooled patient without complication or increased bleeding. while therapeutic hypothermia has not shown an outcome benefit in previous clinical trials, these trials have had limitations rapidly reaching targeted temperature. this may have blunted the therapeutic effect. using thermasuit, patients are able to reach target temperature significantly faster. additional clinical trials are needed to determine if the therapeutic window for targeted temperature management in ischemic stroke patients improves outcome. iv rt-pa guidelines exclude therapeutically anticoagulated or thrombocytopenic patients. these exclusion criteria may limit thrombolytic therapy to patients who might benefit. the objective of this study is to determine if iv rt-pa is safe and whether it increases neurocritical care resource utilization in this patient population. retrospective analysis of iv rt-pa treated patients receiving oral anticoagulation (warfarin (inr > . )), novel oral anticoagulant (noac), therapeutic heparin, low-molecular weight heparin (lmwh), or with thrombocytopenia (platelets < k). patients were treated using smart criteria (consent obtained for off label rtafter treatment. increased neurocritical care resource utilization was defined as transfer from a primary to comprehensive stroke center solely for additional monitoring after off-label iv rt-pa use. patients were identified. patients received therapeutic warfarin and one had coagulopathy (unclear etiology); mean inr= . (range . - ). received therapeutic iv heparin, full dose ( mg/kg bid) lmwh, and therapeutic noacs. had thrombocytopenia (mean platelet count k). received intra-arterial (ia) rt-pa, and thrombectomy. there were sich ( . %); for all sichs there were mitigating factors that contributed (undiagnosed malignancy, adjunctive ia rt-pa, incorrect time of onset). two developed hematoma at the catheter site with no clinical effect. patient was transferred for the sole purpose of monitoring post off-label iv rt-pa. these data suggest that iv rt-pa can be safely administered in therapeutically anticoagulated and thrombocytopenic patients, and sich rates were similar to the ninds cohort. the use of iv rt-pa in these patients may increase eligibility for acute stroke therapy, particularly where ia therapy is unavailable. -pa in such patients does not appear to increase neurocritical care resource utilization though further study with a larger population is warranted. although proteinuria has been reported as a predictor of neurological deterioration, poor functional outcome and in-hospital mortality after ischemic stroke, scarce study investigated the relationship between proteinuria and the malignant middle cerebral artery infarction (mmcai). this study aimed to determine whether proteinuria is associated with the development of mmcai. patients with infarction in middle cerebral artery territory were reviewed. on admission, all patients underwent brain computed tomography (ct), the assessment of national institutes of health stroke scale (nihss) and alberta stroke program early ct score (aspects), and laboratory surveys, including urine analysis by using urine dipstick. patients with known intracranial lesions or possible urinary tract infection were excluded. patients with proteinuria were defined if urine dipstick demonstrates reading of + to +, while others were defined as patients without proteinuria. chronic kidney disease (ckd) was defined if either proteinuria or estimated glome identified. mmcai was determined if a progressive conscious disturbance or signs of uncal herniation were recorded with a midline shift > mm on a follow-up brain ct. we screened patients, and -five ( . %) patients developed mmcai, and ( . %) patients had proteinuria. patients with mmcai had a significant higher score of nihss, lower aspects, less likely being dyslipidemia, and more likely having ckd and proteinuria than patients without mmcai did. after adjustment for age, sex, dyslipidemia and aspects, patients with proteinuria (or= . , %ci= . - . , p= . ) and ckd (or = . , %ci = . - . , p= . ) had a signifi ml/min/ . m did not. in conclusion, proteinuria is associated with the development of mmcai. we suggest that proteinuria may be considered as a clinical predictor for the development of mmcai. although tpa has been shown to improve outcome in ischemic stroke across various etiologies, tpa is contraindicated in stroke secondary to septic emboli due to a significantly higher risk of bleeding. the goal of this study is to determine the safety and short-term outcomes of acute ischemic stroke patients who underwent mechanical thrombectomy due to septic emboli from infective endocarditis (ie). in this multi-center retrospective case series, we reached out to thrombectomy centers known to our principal investigator. we have so far collected data from hospitals across the us to look at outcomes after thrombectomy in patients who had an ischemic stroke from infective endocarditis. centers reviewed their database and did not have eligible cases. to date, we have collected a total of cases ( % male; average age ; % had a known history of ivdu). in % the valve implicated was bioprosthetic. % of the occlusions were m , with the remaining being the carotid terminus ( %) and m ( %). microbiology revealed that % were caused by streptococcus, % staphylococcus, % enterococcus, and % were polymicrobial. the average nihss on presentation was . . % had received tpa prior to the thrombectomy (of those, / were known to have ie). the average best nihss after thrombectomy was . (averaged across cases, the other case expired from new cardiomyopathy and multi-organ failure). % had hemorrhagic transformation (of those, / were tpa recipients). thrombectomy may be a safer and promising option in patients with ischemic stroke secondary to infective endocarditis. more data is required to compare the outcome of patients who received thrombectomy alone versus tpa followed by thrombectomy, and data collection is ongoing. therapeutic hypothermia may be an effective therapeutic measure for malignant cerebral infarction alternative to or in combination with decompressive craniectomy. the neuroimaging marker that suggests the favorable clinical course during therapeutic hypothermia is needed to predict the outcome and/or determine best and earliest timing to rewarm the patients. we included cases who received therapeutic hypothermia for malignant middle cerebral infarction in seoul national university bundang hospital between july and may . we measured hounsfield unit of ischemic core in serial computed tomography scans in each patient. the nadir of hounsfield unit of each patient was calculated. the difference of the nadir by the early clinical outcome (the survival at discharge) was analyzed. the mean age was . ± . and the male comprised . % (n= ). three patients underwent early decompressive craniectomy plus therapeutic hypothermia and patients received only therapeutic hypothermia. the mean target temperature was . ± . . a total of patients ( . %) survived at discharge. a total of computed tomography scans were analyzed (about scans per patient). the mean of the nadir hounsfield unit of each patient was . ± . in the deceased patients and . ± . in the survived patients, and the difference was statistically significant (p-value = . ) the nadir of hounsfield unit in the ischemic core was lower in the survived group than the deceased group in malignant ischemic stroke patients who received therapeutic hypothermia. the change in hounsfield unit in serial computed tomography scan may be used to estimate clinical course and optimal timing of rewarming or rescue craniectomy after therapeutic hypothermia. the volumetric analysis using semi-automated planimetry is currently being performed to elucidate this association further. mhz pulsed-wave transcranial doppler (tcd) increases the exposure of an intracranial thrombus to tenecteplase (tnk-tpa) and facilitates early reperfusion. the aim of the present study is to ascertain if tcd along with tnk-tpa could improve functional outcome in patients treated with tnk-tpa after acute ischemic stroke (ais). this is a single center, prospective, interventional study. patients with ais with national institutes of -tpa bolus) within hours of symptom onset, were randomly allocated ( : ) to either mhz pulsed-wave ultrasound for min. (sonothrombolysis)-intervention group or only tnk-tpa group. ultrasound was delivered using a mark head frame, immediately after the bolus of tnk-tpa. the primary outcome was improvement in the modified rankin scale score at days and . the secondary end points were the occurrence of symptomatic intracerebral haemorrhages and death. between january and march , patients were randomly allocated to the sonothrombolysis group and patients received only tnk-tpa. at the end of days, the sonothrombolysis group achieved mrs - in / ( . %) compared to / ( . %) in the tnk-tpa group. the p-value is . . the result is significant at p < . . the rate of sich and mortality were . % in each group. sonothrombolysis of patients treated with tnk-tpa for ais was feasible and safe, with some clinical benefits at days. the recanalization rates and outcome are better than studies done with alteplase. there was no increase in sich or mortality. tnk-tpa should be the preferred drug for thrombolysis in ais. the study should be carried out in multiple centers to see if the results of the present study can be validated. acute ischemic stroke is the second leading cause of death, especially if the patient did not receive the appropriate treatment geared towards a timely recanalization of the occluded vessels, including intravenous tissue plasminogen activator (iv t-pa) or endovascular thrombectomy. little emphasis is given to the augmentation of collateral flow to offset the deleterious effect of ischemia or lessen the progression of the penumbral tissue into infarction. we present our initial experience with such vasoaugmentation strategy in patients with acute ischemic strokes. we present o university. our series included patients with acute ischemic strokes. we excluded patients with a large vessel occlusion. all other patients were included regardless of whether they received iv-tpa or not. all patients had a ct angiogram including collateral imaging and ct perfusion study at baseline. after explaining to the patients or their next-of-kin, we started the patients on a standardized protocol of milrinone ( mcg/kg bolus followed by . mcg/kg/minute). outcome assessment was comparing the initial mrs and that of the mrs at discharge. chi square contingency analysis was used with a set level of significance of p < . . out of the patients, had good collaterals and had poor collaterals. one of those poor collaterals patient had good cross flow from pcom to the affected hemisphere, but still demonstrated poor collateral score. in our cohort, ( %) achieved good neurological outcome of mrs of or below with patients ( %) achieving a discharge mrs of . conclusions collaterals and small infarction core. the presence of cross flow wasn't helpful. the symptomatology of delayed cerebral ischemia (dci) after aneurysmal subarachnoid hemorrhage (asah) is variable and often challenging to detect, particularly in patients with poor-grade asah. we report severe symmetric quadriparesis as a previously unreported symptom of dci. a -yearwas significant for intact brainstem reflexes and withdrawal in extremities. initial treatments included aminocaproic acid and external ventricular drain insertion, followed by intra-aortic balloon pump placement for stress-induced cardiomyopathy. she subsequently underwent coiling of a ruptured left anterior choroidal artery aneurysm. on post-bleed day , she was noted to have new onset of decreased tone and minimal complex posturing to noxious stimulation in all extremities and severe inattention. transcranial doppler and digital subtraction angiography revealed moderate left greater than right middle cerebral artery and bilateral anterior cerebral artery vasospasm and she received balloon angioplasty and intra-arterial nicardipine twice. post intervention, her quadriparesis moderately improved but she continued to have decreased tone and delayed movement initiation. on post-bleed day , brain mri demonstrated infarcts in bilateral medial frontal lobes, bilateral basal ganglia & subinsular cortices. on day of discharge, she was able to spontaneously raise her left arm and legs, but only minimally moved her right arm to noxious stimulation. this case report adds severe symmetric quadriparesis to the myriad of possible clinical symptoms of dci after asah. awareness of this uncommon clinical presentation could lead to timely detection and management of delayed cerebral ischemia after asah and improved clinical outcomes. brain mri to determine infarct size is common in acute stroke management. many patients cannot undergo mri imaging due to instability, or imaging contraindications. a common ct head finding postthrombectomy is contrast extravasation, thought to be secondary to "leakage" of the blood brain barrier due to ischemia. we hypothesized that extravasation volume on post-thrombectomy ct scan correlates with final infarct size. using ct head as a proxy for final infarct size may help guide clinical decision making when mri scan is not possible. we retrospectively examined a prospectively collected, irb approved stroke code database from / / to / / . inclusion criteria included: anterior strokes that underwent thrombectomy, ct scan within hours of thrombectomy with contrast extravasation, a mri within days of the thrombectomy. demographics, diagnosis, imaging findings were extracted via chart review. we used the alberta stroke program early ct score (aspect) score, to approximate the area of contrast extravasation (ct) and area of dwi hyper intensity (mri). each region of extravasation on ct head was deducted from a score of , resulting in the "estimated infarct size (eis)". each region of mri dwi was was calculated. we demonstrated usefulness of aspect scoring for comparing infarct volume between ct extravasation and final dwi infarct size. post-thrombectomy contrast extravasation consistently underestimated final mri infarct volume by %. this relationship, if validated, may be useful to approximate mri stroke volume. dizziness is a vaguely-defined complaint involving the subjective experience of lightheadedness, disequilibrium, and room-spinning sensation. it is a frequently encountered problem in office visits and in the acute care setting, with approximately . million presentations to the emergency department annually. the differential diagnosis is broad, ranging from benign and of peripheral origin, to timesensitive and potentially fatal of central origin, including ischemic or hemorrhagic stroke and ms. it is estimated - % of patients with dizziness receive stroke diagnoses . despite the low percentage, diagnosis of posterior stroke is the one most feared to be missed by clinicians. we hope to establish a clinical scoring system for timely triage of presentation with dizziness. we retrospectively reviewed charts of patients admitted at hahnemann university hospital between and , following irb approved protocol. charts were chosen with primary inpatient admitting diagnosis: cerebral infarction due to thrombosis of basilar artery, dizziness and giddiness, and cerebral infarction due to embolism of post cerebral artery for a total of charts. patient charts were reviewed to identify predisposing factors, data points for each patient. of patients reviewed, were found to have infarctions involving the posterior circulation, . % diagnostic yield for stroke. we collected a total of data points to understand the disease process. predisposing factors identified were chronic kidney disease, diabetes, hypertension, and hyperlipidemia. surprisingly, previous stroke was not found to predispose to posterior fossa strokes. common exam findings on presentation were hemiparesis and hemisensory loss. statistical analysis is currently in process we discuss our results in the context of previous efforts aimed at developing clinical predictors for posterior fossa stroke in patients presenting with dizziness. high hir (hypoperfusion intensity ratio) is known to correlate with core size, infarct growth and worse clinical outcomes. traditionally larger infarcts have been associated with higher rates of malignant cerebral edema and need for decompressive hemicraniectomy. patients with high hir and malignant profile (tmax > s greater than % of penumbra) are associated with increased risk of malignant cerebral edema. as part of an ongoing study, we retrospectively identified all ais patients with lvo who underwent ctp imaging between january to june in our healthcare system within hours from symptom imaging studies (ct or mri) were analyzed. hir was dichotomized based on proportion of greater and less than . into malignant vs favorable profile and correlation for development of malignant cerebral edema and need for hemicraniectomy was analyzed using chi-square test of proportion for nominal variables and wilcoxon ranked sum tests for the (skewed) continuous and ordinal variables. a total of patients with lvo were identified with a median age of (iqr - ), nihss of . patients with high hir suggestive of a malignant profile (n= ), regardless of reperfusion, were associated with increased risk of malignant cerebral edema compared to those with a favorable profile (n= ) (p< . ). patients with malignant hir developed malignant cerebral edema compared to patients with favorable hir (rr= . , or= . ). patient with malignant hir underwent decompressive hemicraniectomy compared to none with favorable hir. higher hir and malignant profile, regardless of reperfusion, is associated with times increased relative risk of development of malignant cerebral edema. these patients benefit from close monitoring and aggressive care for malignant cerebral edema including osmolar therapy and potential surgical intervention. we present the case of a patient with basilar artery dissection with thrombus, who underwent successful mechanical thrombectomy with stenting and was ambulatory at discharge. patient is an -year-old female with past medical history of ehler's danlos disease who presented with left sided weakness after being found down by her family. nihss on arrival was (left sided weakness / ), bp / , glucose . her cta showed a basilar angiography was notable for a basilar dissection with reocclusion, which was treated with enterprise stent placement with tici reperfusion. mri post intervention revealed right pontine infarct, punctate infarcts in cerebellum. her exam at discharge was notable for improvement in her left sided strength, at / . she was subsequently discharged to inpatient rehabilitation. mechanical thrombectomy and stenting of the basilar artery remains a largely experimental procedure, with few guidelines and little data on outcomes. we present a case of a patient with a basilar dissection who at discharge was ambulatory and near baseline. blood viscosity (bv) is the intrinsic resistance of blood to flow and characterizes blood stickiness. several clinical and epidemiologic studies demonstrated an association between bv and the occurrence of major thromboembolic events. though bv appears significantly higher in cases of lacunar or cardioembolic strokes, relationships with demographic and laboratory findings during the acute stage of ischemic stroke are unknown. we investigated the relationship between baseline characteristics and bv within hours of symptom onset in patients with acute ischemic stroke. we enrolled patients aged years or older with documented histories of ischemic stroke or transient ischemic attack within hours of symptom onset. a scanning capillary-tube viscometer (sctv) (hemovister, pharmode inc., seoul, korea) was used to assess the whole blood viscosity (wbv). the mean age was . ± . years and . % were female. of patients, . % had a history of hypertension; %, diabetes; . %, hypercholesterolemia; . %, coronary artery disease; and %, stroke. additionally, . % were current smokers. sixty-one ( . %) patients were taking antithrombotics regularly. multiple linear regression analysis revealed that hematocrit was positively related with increased bv and prior antithrombotic use was related with decreased bv. hematocritadjusted partial correlation demonstrated that prior antithrombotic use was significantly associated with decreased bv. prior antithrombotic use is significantly associated with decreased blood viscosity within hours of symptom onset in patients with acute ischemic stroke. our findings indicate that antithrombotic medications prevent stroke by inhibiting platelet function and by changing the hemorheological profile. ischemic stroke accounts for % of stroke and is the second cause of death in brazil. the decision regarding thrombolytic treatment depends on clinical history, physical examination, and imaging. one challenge is the exclusion of situations called stroke mimics (sm). a total of patients admitted to the stroke unit were prospectively analyzed. they received a full clinical and laboratory evaluation for the diagnosis of stroke and aiming to rule out the sm possibility. the study looked up for stroke etiology, demographical and epidemiological data, stroke-specific scales, sis, the occurrence of seizures and blood pressure lower than mmhg at admission as variables of interest. the prevalence of sm and the use of thrombolytic therapy in this situation was concordant with medical literature. the risk associated with anticoagulation in acute ischemic stroke (ais) is uncertain. anticoagulation is generally not indicated for early secondary stroke prevention, but may be considered in certain conditions. we assessed the use of a weight-based institution-specific heparin nomogram in ais patients. -new haven hospital who received anticoagulation with a continuous heparin infusion in the setting of ais over a -month period. anticoagulation was initiated with an initial infusion rate of units/kg/hr without bolus, with subsequent increases in the infusion rate by unit/kg/hr, based on aptts obtained every six hours until two subsequent aptts were within goal range. we collected indication for anticoagulation, dose at therapeutic aptt, time to target aptt duration of anticoagulation, transition to oral anticoagulant therapy, cerebrovascular/cardiovascular events and major and minor bleeding complications. patients were included in analysis, % of which were male, with a mean age of ± years and an average weight of . ± . kg. indications for ac were: intracardiac thrombus ( %), (sub)occlusive intra-arterial thrombus ( %), arterial dissection ( %), thromboembolic events and hypercoagulability ( %). the median time between diagnosis of stroke and initiation of anticoagulation was hrs mins. the time to goal aptt was ± . hours with a mean infusion rate of units/kg/hr at time of goal aptt. % of patients were transitioned to an oral anticoagulant and % of patients experienced a cerebrovascular event while on heparin infusion. our institution-specific heparin nomogram provides a safe anticoagulation strategy in ais, but with a longer time to reach therapeutic goal aptt range compared to previously published data. a more aggressive titration strategy with consideration of a higher infusion start rate may facilitate reaching the target aptt within a shorter time frame. vertebral artery dissection (vad) is one of the most common identifiable causes of ischemic stroke in young age patients forming intramural hematoma. vad may occur spontaneously or secondarily to trauma, infection, or underlying arteriopathy. we report cases of spontaneous bilateral vad presenting with lateral medullary infarction a -year-old woman transferred to the emergency room with vertigo. days ago, she felt severe headache on the left temporal area. on neurologic examination, ptosis, facial hypesthesia, dysmetria on the left side were noted, and dysarthria, dysphagia, right beating nystagmus were noted also. she had no past medical history and no familial history of stroke or cephalo-cervical trauma. brain mri depicted acute infarction in left lateral medulla and dissecting aneurysm of right va and near occlusion of left va on carotid enhanced mra. disease was normal. she was treated with warfarin. a -year-old man visited to the emergency room with headache on the right occiput. on neurologic examination, ptosis, miosis, facial hypesthesia, dysmetria on the left side and hemibody hypesthesia on the right side were noted. he had no trauma history or risk factors for stroke except hypertension. brain mri depicted acute infarction in right lateral medulla and dissecting aneurysm in the bilateral vertebral arteries on carotid enhanced mra. laboratory tests showed no abnormal findings. all results were normal for young age stroke evaluation. he was treated with warfarin. although unilateral or bilateral vad due to trauma or underlying medical conditions has been reported, spontaneous bilateral vad is rare. it can present with lateral medullary syndrome or nonspecific symptoms such as headache only. physicians should include vad in the differential diagnosis for patients presenting with brainstem neurologic abnormality or headache, especially young patients. cerebrovascular complications (cvcs) occur in - % of patients with infective endocarditis (ie) and manifest as ischemic stroke, meningitis or cerebritis with % occurring during first weeks of treatment. ct or mri brain can diagnose cvcs but are insensitive early on, precluded in critically ill patients and only demonstrate the sequelae. transcranial doppler (tcd) can identify high-intensity transient signals (hits) associated with cerebral microembolization and may have a role in detecting emboli and preventing cvcs in ie. retrospective chart review and literature review. we found patients with strokes caused by ie at our institution from / to / . tcds were obtained on patients, abnormal for cerebrovascular abnormalities. only patients had minute emboli monitoring performed of which one revealed hits. though mri studies have shown microemboli in % of ie patients (duval ann intern med ), we only found studies using hits on tcds as indicators of stroke risk in ie. in a prospective study of patients with left-sided ie, cvcs occurred in % of patients with hits on tcds versus % of patients who did not (p= . ) ( lepur scand j infect dis ). two studies investigated and patients with cardiac sources of embolism and documented occurrence of hits in % and % of subjects, respectively, with highest prevalence of hits in patients with ie (sliwka stroke , georgiadis stroke . detection of hits using tcd emboli monitoring has a potential to be an important tool for identifying cases of ie at highest risk for cvcs, especially in the early stages of antimicrobial therapy. this can aid further research into preventative interventions beyond antibiotics like earlier valvular surgery or vacuum assisted vegetation extraction. therapeutic hypothermia is considered as an effective therapy to reduce cerebral edema and intracranial pressure for malignant middle cerebral artery infarction, which can be used as a life-saving treatment alternative to or combined with decompressive craniectomy. however, malignant hemispheric infarction involving whole anterior, middle and posterior cerebral artery territory has been regarded as untreatable by any measures. a -year-old man who had had right ventriculoperitoneal shunt for hydrocephalus since several years ago presented with global aphasia and right hemiplegia in may . the brain magnetic resonance imaging showed large acute infarction involving whole left hemisphere including anterior, middle and posterior cerebral arterial territory by occlusion of distal internal carotid artery. as his family refused decompressive hemicraniectomy, therapeutic hypothermia using surface-cooling method (arctic sun® ) was initiated with a target temperature of . . the maximal midline shift on brain ct was approximately mm, five days after stroke onset, which led to foramen of monro obstruction and hydrocephalus in the lateral ventricle of the opposite side. since the hydrocephalus was controlled by draining of the cerebrospinal fluid into the ventriculoperitoneal shunt, the right hemisphere was saved and brain edema combined with midline shift gradually improved. the patient finally survived and was discharged. this case may be the first that therapeutic hypothermia successfully treated large hemispheric infarction involving cerebral arteries without decompressive craniectomy. since the mass effect in our case was much larger than that of malignant middle cerebral infarction, we extended the duration of therapeutic hypothermia ( . ) to days, which prevented herniation syndrome. another interesting point is that we could manage contralateral hydrocephalus caused by extensive midline shift, heralding a fatal clinical course in malignant ischemic stroke, using the preexisting ventriculoperitoneal shunt. current aha / asa stroke guidelines list arteriovenous malformation (avm) as a contraindication for intravenous alteplase (iv tpa) in ischemic stroke. while the associated risk of spontaneous intracerebral hemorrhage varies across the differing types of intracranial vasculature malformations, very little data or case reports exist regarding the risk of hemorrhage with intravenous thrombolytics for ischemic stroke in patients with vascular malformations. a -year-old male with history of cirrhosis and known atrial fibrillation (not on anticoagulation) presented with acute onset left facial droop and left hemiplegia, nihss . onset of symptoms were within the . hour window for iv tpa. a ct head demonstrated an aspects score of . iv tpa was thus initiated. cta of the head and neck revealed a right middle cerebral artery occlusion. additionally, there was a subtle tortuosity of blood vessels within the dural surface of the right temporal lobe, suggestive of possible avm. given the stroke severity, tpa was continued and successful recanalization was completed by thrombectomy of the right m occlusion by aspiration, with confirmation of a dural based avm. the patient did well, with no complications from tpa or thrombectomy and was discharged home with an nihss . the decision to administer iv tpa in patients with symptoms of acute ischemic stroke is determined by last known well time and a non-contrasted ct. vessel imaging should not delay administration of iv tpa as incidental findings may arise which may cloud the use of iv tpa in patients who otherwise may benefit from therapy. this case provides further insight that iv tpa in those with intracranial vascular malformations may be given safely with minimally increased risk. the prevalence of stroke mimics (sm) can reach % of presumable stroke, according to some authors. its presentation can predict the diagnosis of sm with a sensitivity and specificity of % and %, respectively. this study aimed to comparatively evaluate these data in a population hospitalized in a stroke unit. the study prospectively analyzed a total of patients admitted according to the suspicion of sm, the definitive diagnosis, etiology, demographic and epidemiological data, specific scales for stroke including features and its sensitivity and specificity in a specific population. a cross-sectional analysis comprised ( . % female) patients, median age . years ( - ). the median nihss was ( -- in . % of patients. twenty-four patients ( . %) presented with initial suspicion of sm, which was confirmed in ( . %). after univariate analysis on were statistically significant (p = . and p = . , respectively). the multivariate logistic regression showed that the absence of facial paralysis (or= . , p= . , % ci= . - . ), seizure convulsion on admission (or= . , p= . , % ci= . - . ) and blood pressure at admission lower than mmhg (or= . , p= . , % ci= . specificity of . % and . % respectively, with an area under the curve of . (se= . , % ci= . -conclusions sensitivity and specificity, probably secondary to selection bias. these data are inferior to the literature but better adapted to this study population. information collected from chart review and direct patient care. a year-presented with pre-syncope, abdominal pain, and malaise. he was febrile and tachycardic, and subsequently admitted for sepsis. shortly thereafter, he experienced transient diaphoresis, expressive aphasia and right-sided weakness. mri brain showed punctate ischemic cerebellar infarcts. there was high suspicion for embolic phenomena from sepsis or he acutely decompensated to complete non-responsiveness during the echocardiogram. ct brain showed diffuse air emboli in cerebral vasculature and subarachnoid air. he was placed in the left lateral decubitus position and managed with high concentration oxygen. additionally, his antimicrobials were broadened to include fungal coverage. thoracic ct revealed free air in the mediastinum between the candidate for surgical repair of his left atrium due to hemodynamic instability. instead, he underwent urgent endoscopic esophageal stent placement. he then developed a stemi, also thought to be due to air embolus, and went into cardiac arrest with return of spontaneous circulation achieved. the following day, he developed renal failure and coded again. autopsy, in addition to massive cerebral edema and cardiac ischemia, demonstrated strep oralis bacteremia, bilateral adrenal infarcts and acute tubular necrosis. is crucial for the ability to coordinate aggressive care. open surgical repair of the left atrium and esophagus offers the best chance of survival, but its use may be limited by severe sepsis and hemodynamic instability. the efficacy of mechanical thrombectomy (mt) for acute ischemic stroke (ais) due to large vessel occlusion (lvo) is well established in the anterior circulation (ac). ais from lvo in the posterior circulation (pc) differs from the ac in myriad ways, including presentation and resistance to hypoxia. we aim to characterize the differences in risk factors and outcomes of mt for ac vs pc stroke. demographic data was collected for cases of ais undergoing mt from january to january with follow-up imaging and documented functional status at discharge. operative reports were reviewed for procedural data including stroke onset to groin puncture time, number of passes of the stent retriever, and onset to recanalization time. radiology reports of postprocedural non-contrast ct images of the head were assessed. during the study period there were eligible patients ( ac and pc). atrial fibrillation ( . % and . %, p= . ) and hyperlipidemia ( . % and . %, p= . ) were more common in ac strokes while family history of stroke was more common in pc strokes ( . % and . %, p= . ). mortality erence in procedural factors or hemorrhagic complications. ac stroke but not pc stroke. our data shows that pc stroke has a higher mortality rate than ac stroke after mt with no difference in procedural factors or hemorrhagic complications. the higher mortality rate in patients with pc stroke is likely inherent to severe disability from basilar artery occlusion rather than recanalization therapy. the data also support worse functional outcome in ac strokes with increasing age and number of passes. calcinosis is a dysregulation of vascular calcium deposition characterized by small vessel calcification and secondary fibrosis. the effect of systemic calcinosis on mineralization within the central nervous system is underreported and poorly understood. a -year old man presented to icu for possible hemorrhagic transformation of a recent left mca stroke. his medical history was notable for atrial fibrillation, end-stage renal disease, calciphylaxis on warfarin, and parathyroidectomy. his post-stroke hospital course was notable for mildly elevated serum phosphorus. the patient started apixaban two weeks post-stroke as anticoagulation for atrial fibrillation, and underwent a routine ct head one day later. the scan showed extensive high-density signal along the cortex of the recently infarcted left mca territory, initially misinterpreted as hemorrhagic transformation. the signal measured at - hounsfield units, higher than expected for acute blood. a dual-energy calcium overlap map post-processing revealed the high-density material was consistent with acute mineralization, possibly potentiated by the patient's previous calciphylaxis. this case illustrates accelerated mineralization as a mimic of acute hemorrhagic transformation. dual-energy ct is useful for differentiating hemorrhagic transformation from mineralization, and may play a special role in patients with renal disease or history of calciphylaxis. this case illustrates accelerated mineralization as a mimic of acute hemorrhagic transformation of stroke in a patient with esrd and history of calciphylaxis. dual-energy ct can differentiate between intraparenchymal hemorrhage and calcification with high accuracy using material decomposition. this imaging technique may have an especial benefit in patients with renal disease or disordered mineralization. accelerated mineralization post-stroke may worsen cerebral vessel compliance and risk of future stroke, and merits further investigation. systemic inflammatory response syndrome (sirs) without infection is a surrogate of a systemic immune response and has been related with poor outcome in several vascular diseases. we investigated associations of sirs with long-term functional outcome and contributing factors after intracerebral hemorrhage (ich). we analyzed consecutive spontaneous ich-patients from our prospective cohort-study ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . sirs was defined according to standard criteria: i.e. two or more of the following parameters during hospitalization: body-temperature < °c or > °c, respiratory-rate > per minute, heart-rate > per consisted of the modified rankin-scale(mrs) at three and twelve months investigated by adjusted ordinal shift-analyses. bias and confounding were addressed by propensity score matching and multivariable regression models. of patients with ich . % (n= ) developed sirs during hospitalization. sirs-patients showed more severe ich compared to without; i.e. larger ich-volumes ( . cm³, iqr( . - . ) versus . cm³, iqr( . - . );p< . ), increased intraventricular hemorrhage ( . %,n= / versus . %,n= / ;p< . ), and poorer neurological admission status (nihss , iqr( - ) versus , iqr( - );p< . ). ich severity-adjusted analyses revealed an independent association of sirs with poorer functional outcome after three (or . , % ci( . - . );p= . ) and twelve months (or . , %ci( . - . );p= . ). increased ich-volumes on follow-up-imaging (or . , %ci( . - . );p= . ) and prior liver dysfunction (or . , %ci( . - . );p= . ) were associated with sirs. in ich patients we identified sirs to be predictive of poorer long-term functional outcome over the entire range of mrs-estimates. clinically relevant associations with sirs were documented for prior liver dysfunction and hematoma enlargement. acute major bleeding secondary to trauma is a significant complication of anticoagulated patients. in -threatening in the absence of a specific reversal agent. annexa- was a prospective, single-arm, open-label study evaluating the efficacy and safety of -primary efficacy endpoints were percent change from baseline in antiefficacy over the first hours after treatment, as determined by an independent adjudication committee. safety outcomes (including thrombotic events and death) were evaluated over days. among patients enrolled in the study, ( . %) had a bleed associated with trauma ( intracranial [ich] , non-ich). mean age was . years. eighty-three patients took apixaban, rivaroxaban, enoxaparin, and edoxaban. of the ich patients, ( . %) had bleeding in multiple compartments. the mean hematoma volume in the trauma patients with single-compartment intraparenchymal bleeding was . cc. among efficacy-evaluable ich patients, of ( . %) had excellent or good hemostatic efficacy. the percent reduction in anti-ich patients taking apixaban and rivaroxaban, respectively. the -day rates of thrombotic events and mortality were of ( . %) and of ( . %), respectively. conclusions high rate of excellent or good hemostatic efficacy, with a relatively low occurrence of thrombotic events. these results are comparable to what was observed for annexa- patients with spontaneous bleeding events, and suggest that andexanet alfa could be a safe and effective treatment in the traumatic population. -factor prothrombin complex concentrates -related ich. adult patients ( years or older) admitted to yale--related ich who evaluated at approximately hours after the baseline ct scan. secondary outcomes included mortality and modified rankin score (mrs) at hospital discharge. chi-square test and multivariable logistic regression analysis were used for unadjusted and adjusted analyses, respectively. twenty--related ich were included in the s patients received aa). majority of the patients were anticoagulated for atrial fibrillation (n= , %). group (unadju patients ( %) in aa group (unadjusted p= . ). there was no difference in mrs at discharge, patients - compared to patients ( %) in aa group (unadjusted p= . ). multivariable analyses adjusted for age, sex, race, and baseline mrs confirmed the absence of these associations (all p> . ). in our limited sample size, there was no significant difference in the degree of hemostasis achieved, allvalidate these results are warranted. symptomatic intracranial hemorrhage (sich) following mechanical thrombectomy (mt) for acute ischemic stroke (ais) due to large vessel occlusion (lvo) is a rare but devastating complication. however, it is difficult to differentiate sich from contrast extravasation on early post-procedural computed tomography (ct). we aim to evaluate the rate of sich and whether the presence of hyperdensities (hd) on post-procedural ct predicts functional outcome after mt. demographic data was collected for cases of ais undergoing mt from january to january with available follow-up imaging and documented functional status at discharge. operative reports were reviewed for procedural data and radiology reports of ct head performed immediately, and - hours post-mt were assessed. of the patients studied, ( . %, / ) had hd on immediate postoperative ct and ( . %, / ) were contrast extravasation (ce) due to resolution of hd on ct at patients developed new hd on follow-up ct, resulting in a total of patients ( . %) having ich and ( . %) having sich. in subgroup analysis, cardiac comorbidities were more common in ce patients than ich patients ( . % and . %, p= . ) with no mortality or outcome differences. diabetes mellitus (dm) was more common in sich patients than those with ce and asymptomatic ich ( . % and . %, p= . ). the mortality rate of sich patients was higher ( % vs . %) and the survivors had worse discharge nihss than pat difference in procedural factors or preference for circulation between any groups. our data show that presence of hd on immediate postoperative head ct does not predict mortality and is not related to circulation or procedural factors. sich is more common in patients with dm and associated with higher mortality rate and poor functional outcome. consecutive patients admitted to the health system with tsd -pcc between may and april were analyzed. baseline demographics and outcomes were abstracted through -up ct. tsdh volume was calculated using the abc/ method. descriptive statistics were used to analyze the -pcc and its association with outcomes. -pcc for tsdh were analyzed. the median age was [ to ], -pcc was . units/kg. patients with he had a median dose of . units/kg ( . to . ) versus . units/kg ( . to . ) for patients without he. he was seen in % of patients (rivaroxaban in , apixaban in ). among patients with he, % of patients died or went to a skilled nursing facility vs % in those without he. discharge to home or acute rehab was lower in those with he ( %) versus those without he ( %) doac use was associated with higher rates of hematoma expansion and worse outcomes in patients -pcc. treatments for the reversal of doac related tsdh should be investigated intracerebral hemorrhage (ich) is associated with peripheral immune dysfunction and infection. we aim to evaluate peripheral immune responses to ich and associations with infection and ich outcome. consecutive spontaneous ich patients admitted to a tertiary center ( / - / ) were included. patients with secondary ich and transition to comfort measures within hours were excluded. ich score, discharge modified rankin score (mrs), antibiotics use, acute clinical infections including pneumonia, bacteremia, and urinary tract infection were systematically adjudicated using modified pantheris criteria. peripheral immune dysfunction was characterized by lymphopenia and lower lymphocyte to neutrophil ratio (lnr). continuous variables were compared using student's t or wilcoxon test; univariate associations assessed using pearson's or spearman's correlation depending on distribution. ordinal logistic regression used to evaluate independent effect of lnr on discharge mrs. (jmp pro . ). cohort had mean age years, % female, median ich score [iqr - ] and median discharge mrs of . thirty-nine patients had suspected clinical infection treated with antibiotics, where only met modified pantheris criteria for infection. lower %lymphocyte (p< . ) and lnr (p< . ) on post-ich days - were associated with worse discharge mrs and higher ich scores (p's < . ). lower mean lnr on post-ich days higher mean lnr on post-ich days - (p< . ). lnr on post-ich day is independently associated with mrs (p= . ) after adjusting for ich score and sex. acute post-ich lymphopenia and reduced lnr are associated with ich score, infection and worse discharge outcome. lnr emerged as independent predictor of ich outcomes in preliminary analysis. determine how acute lymphopenia mediates ich infection risk and outcome. prolonged length of stay (los) in the intensive care unit (icu) is associated with significant medical complications and higher costs in patients with spontaneous intracerebral hemorrhage (ich). aim of this study is to assess predictors of prolonged icu los in ich. we conducted a retrospective analysis of ich patients admitted to our institution over a seven-year period. demographics, clinical data, and laboratory studies at presentation were recorded. initial ct scans were reviewed to determine location, hematoma volume, and presence of intraventricular extension. surgical interventions, insertion of an external ventricular drain (evd), and medical complications, including infections and deep vein thrombosis/pulmonary embolism (dvt/pe) were reviewed. los was calculated based on the number of midnights spent in the icu. patients spending less than -hours in the icu were excluded. ichs were analyzed. the mean age was . ± . years and . % were females. prolonged los, defined by using the point of change and cumulative sum methodology analysis after normalization of the sample, was found to be > days. intubation at presentation (p< . ), presence of ivh (p< . ), insertion of evd (p< . ), surgical evacuation (p< . ), chest infections (p< . . ) and dvt/pe (p< . ) were associated with prolonged los, while location of the hemorrhage, hematoma volume, and ich score at presentation were found not to be significant. this is a preliminary analysis to identify predictors of prolonged icu-los in intracranial hemorrhage. chest infections and dvt/pe were associated with prolonged los. surgical intervention, intubation at presentation, and insertion of evd were also independent predictors. these findings suggest that early evd weaning or shunt placement, and potentially early tracheostomy could help in decreasing the icu-los in patients with ich. diffusion weighted imaging (dwi) lesions are found in nearly % of patients with acute spontaneous intracerebral hemorrhage (sich). however, the timing of dwi lesions after sich ictus remains unknown. the purpose of this study is to estimate the timing of new dwi lesions after acute primary sich. by establishing a time frame, potential pathophysiologic mechanisms for dwi lesions can be elucidated. between september , and january , , patients were enrolled in a prospective study examining dwi lesions in acute primary sich. enrolled subjects received a research brain mri after admission blinded to the clinical teams. during the same admission, select patients received a separate brain mri as part of clinical care. subjects with scans were identified from the study cohort, and their imaging evaluated for dwi lesions. when compared to the first mri scan, the presence of a new dwi lesion on the second mri scan was defined as a new dwi event. a kaplan-meier analysis was performed to estimate the time to a new dwi event from the first mri scan. among enrolled subjects, ( . %) had two brain mris. mean age was . years, % were male, and . % were african american. the median ich score was (iqr ). median time from sich onset to first mri was . days (iqr . ). median time from first mri to a new dwi event was . days ( % ci, . to . ). median time between the first and second mri was . days (iqr . ). our data suggest that new dwi lesions occur days after sich ictus. therefore, acute interventions during the first hours after sich admission may not be associated with dwi is needed to elucidate potential mechanisms associated with dwi lesions in sich. intracranial hemorrhage (ich) is a common complication in children on ventricular assist device (vad) support, though bleed severity is highly variable. this study examined factors associated with ich requiring neurosurgical intervention in this at-risk population. children aged month- years old admitted between - with a diagnosis of intraparenchymal hemorrhage (iph) or subdural hemorrhage (sdh) while on vad support were identified retrospectively from an institutional database using icd- and icd- codes, after obtaining irb approval. patients requiring neurosurgical intervention (ns+) were compared with those who did not (ns-) using manniables). in total, children met inclusion criteria. of those, / ( . %) required neurosurgical intervention bleeds occurred in patients ( / ns+, / ns-). ns+ patients were older at bleed (mean . ± . years vs . ± . years, p = . ). all ns+ patients were taking warfarin, versus / ns-patients (p= . ); none of the ns+ patients had supratherapeutic inr. number of antiplatelet agents did not differ between groups ( . ± . ns-vs . ± . ns+, p = . ). patients received a median of ct scans (iqr - ) with no significant difference between surgical and nonsurgical groups (p = . ). among our cohort, older children and those on warfarin were more likely to require neurosurgical neurosurgical treatment, though results should be interpreted cautiously given small numbers. patients received multiple ct scans, though only a minority ultimately required neurosurgical intervention. unnecessary ct scans in this population. elevated intracranial pressure (icp), usually monitored by invasive icp-measurements, is associated with mortality in intracerebral hemorrhage (ich). the non-invasive evaluation of pupillary function using automated pupillometry is increasingly used in critical-care settings. the association of various pupillary parameters assessed by automated pupillometry with icp is unestablished, specifically the sensitivity and specificity during icp-elevation and the performance of sympathetic versus parasympathetic parameters. we enrolled ich patients admitted to our neurocritical-care unit who received invasive icpmeasurement by an external-ventricular-drain (evd). we monitored parameters of pupillary reactivity [i.e. light-reflex latency (lat; s), constriction and re-dilation velocities (cv, dv; mm/s), and percentage change of apertures (per-change; %)] using a portable pupilometer (neuroptics®) as well as corresponding icp values up to every minutes for the duration of hospital stay. receiver operating characteristic (roc) analysis was performed to investigate associations between changes in pupillary reactivity and elevated icp. sensitivity and specificity of sympathetic and parasympathetic pupillary parameters were analyzed to evaluate associations between pupillary reactivity and icp-elevation in patients ( women, mean age . ± . years), without icp-elevation and no midline shift upon neuroimaging, assessments were compared to assessments in patients ( women, . ± . years) during icp-levels > mmhg and corresponding midline shift. roc-analyses revealed a significant negative association of all assessed pupillary parameters with icp-elevation. best discriminative thresholds for icp-elevation were: cv< . mm/s, per-change< %, lat< . s, and dv< . mm/s. the highest sensitivity and specificity (i.e. . % and . %; p< . ) for an association with concomitant icp-levels > mmhg were found for a combination of the parasympathetic parameters cv< . mm/s and per-change< %. our data suggest an association between non-invasively detected changes in pupillary reactivity and elevated icp. parameters of parasympathetic pupillary modulation seem most reliable to indicate icpelevation. spontaneous ich (sich) remains a deadly complication from the use of direct oral anticoagulants -pcc for the reversal of doac -pcc in the prevention of hematoma expansion (he) in doac associated sich across a large health system. consecutive patients who were admit -pcc between may and april were analyzed. baseline demographics and outcomes were abstracted through retrospective chart review. he was defined as volume> % or > . ml between baseline and follow-up ct. sich volume was calculated using the abc/ method and ivh score. descriptive statistics were used -pcc and its association with outcomes. -pcc for sich. the median age was ( - ), % were caucasian and --pcc dose of . units/kg ( . - . ) compared to . units/kg ( . to . ) with he. he was seen in % of patients (rivaroxaban in , apixaban in ). among patients with he, % of patients died or went to a skilled nursing facility vs % in those without he. discharge to home or acute rehab was similar in both groups while rates of mortality and discharge disposition were similar between those with and without he, -pcc. treatments for the reversal of doac related sich should be investigated further. elderly patients with mild traumatic brain injury (mtbi) are frequently admitted to an intensive care unit (icu), which is potentially both harmful and unnecessary. however, little exists to inform early decision making to determine appropriate utilization of icu care. here we sought to elucidate factors available upon admission to identify geriatric patients who could safely be monitored in a non-icu setting. adults + years admitted with isolated mtbi, defined as positive radiologic study and glasgow coma scale (gcs) - , between january -december were identified. primary outcomes were ernight stay, no surgery, no intubation, and discharged home) and glasgow outcome scale (gos). positive outcome was defined as gos - and a total of patients met criteria. of these, underwent emergent neurosurgical intervention., leaving for analysis. most presented with gcs ( . %) and were admitted to icu ( . %). nearly point decrease in gcs during hospital stay. upon discharge, . % were classified gos - . predictors . ), and no home use of anticoagulant/antiplatelet medication (p = . ). presence/type of a single intracranial hemorrhage (ich) was not significantly associated with outcome, but presence of bilateral or multiple lesions independently predicted poor outcome (p = . ). overtriage of patients to an icu is costly, resource intensive, and avoidable. here, we suggest a conservative framework to assist the determination of which patients can be safely observed in non-icu population who present with mtbi. perihematomal edema (phe) is a known predictor of outcome after intraparenchymal hemorrhage (iph), but factors contributing to edema formation are incompletely understood. tissue water uptake measured using hounsfield unit density on ct scan has emerged as a predictor of edema in ischemic stroke. the aim of this study was to examine this association in iph, where the theoretical driver for edema volume is not anoxic cellular injury, but rather exposure of tissue to blood. women's hospital were prospectively enrolled between september and march . phe and hematoma were identified on ct scans performed at admission and an average of . +/- . hours later. hematoma volume, hematoma surface area and phe volume were measured. net water uptake (nwu) was calculated as the percent change in phe hounsfield unit density compared to normal contralateral hemisphere. associations between variables were examined with pearson correlations and regression analyses. hematoma volume and surface area at admission were significantly associated with phe volume on the admission scan (r = . , p < . and r = . , p < . respectively) and at the follow-up time-point (r = . , p < . and r = . , p < . respectively). there was no association between nwu and phe volume at either time-point (r = . , p = . and r = - . , p = . respectively). in multivariable analysis, hematoma volume at admission remained an independent predictor of phe volume on the follow- these results suggest that, unlike in ischemic stroke, phe volume is not related to water content. rather, hematom may suggests new avenues to predict edema formation. the risk of hematoma expansion (he) in patients with recent intracranial hemorrhage (ich) receiving therapeutic anticoagulation (ac) is not known. we aim to characterize complication rates and factors associated with he in these patients. we performed a retrospective cohort study of adult patients at harborview medical center between - , who presented with ich and were therapeutically anticoagulated within weeks after the ich for a venous thromboembolic event (vte). we excluded patients with ich due to hemorrhagic conversion of ischemic stroke, venous sinus thrombosis, or an aneurysm consequently secured. we assessed the rate of he, defined as either radiographically proven expansion requiring cessation of ac, or death due to he. t-tests and chi-squared tests were used to analyze factors associated with he. - ), % were female. we identified % sdh, % iph, and % multicompartment ichs, % due to trauma, % hypertensive, and % other etiologies. anticoagulation was initiated an average of . +/- . days after ich. overall, % developed he, one third of whom died. most patients ( %) experienced no complications, % developed minor extracranial bleeding events with ac subsequently resumed. patients with he were older ( vs. ), had higher gcs ( vs. . ), lower hematoma volume ( % vs. % > cc), larger maximal sdh diameter ( . vs . mm), anticoagulated earlier ( vs. days), and lower maximal ptt ( vs. ), although trends were not statistically significant. there was a marginally significant association between he and the presence of hydrocephalus (p< . ). while ac in patients with acute ich can be safely tolerated, there is a substantial proportion demonstrating he. our analysis was limited by the sample size. larger studies are needed to identify clinical and radiographic features associated with complications. intracerebral hemorrhage (ich) is a disease that is associated with high morbidity and mortality. we examined our center's experience with surgery for ich and clinical outcomes. we prospectively enrolled patients with spontaneous ich from to . patients were divided into two groups based on whether they received surgical or conservative management. surgical interventions included hemicraniectomy and/or hematoma evacuation. multivariable regression analysis was conducted to compare the clinical outcomes after adjusting for potential confounders. adjusted odds ratio (aor) or adjusted mean difference (amd) were reported. we included patients, ( %) had surgery and ( %) did not. of the surgical group, ( %) had hematoma evacuation, ( %) had hemicraniectomy, and ( %) had both. clinical characteristics were comparable in both groups. in the surgical group, nihss and glucose were higher and creatinine was lower compared with the nonoperative group. through multivariable analysis, we identified independent predictors of surgery in ich patients including baseline hematoma volume (aor . , % ci . - . ; p= . ) and enlargement with (aor . , % ci . increase in hematoma volume, there was a % increase in the odds of having surgical intervention. was less likely to have a favorable discharge disposition to home or inpatient rehabilitation ( % vs. %; p= . ). surgery was independently associated with longer icu length of stay (amd . , % ci . ,- . ; p= . ) and hospital length of stay (amd . , % ci . - . ; p= . ) after controlling for potential confounders. in our patient population, baseline hematoma volume and expansion were independent predictors for surgery in ich patients. after controlling for other variables, surgery did not impact ich outcomes and was associated with prolonged icu and hospital length of stay. moyamoya disease (mmd), an intracranial vasculopathy characterized by internal carotid artery hypoplasia, often presents with intracerebral hemorrhage (ich) presumably due to rupture of fragile collateral vessels. although mmd-related ich is generally managed similarly to spontaneous ich, we present a case in which standard management strategies may have led to an unprecedented catastrophic outcome. case report. a previously healthy -year-old female presented to the emergency department with right-sided weakness, dysarthria, and headache. she was intubated for airway protection. a head computed tomography (ct) demonstrated a large left basal ganglia ich. ct angiogram revealed diffuse narrowing of the entire anterior circulation with robust posterior communicating arteries. brain magnetic resonance imaging (mri) revealed prominent collateral vessels and sulcal hyperintensities ("ivy sign") consistent with mmd. given these findings, systolic blood pressure was kept under mmhg for the first hours. the following day, the patient's mental status gradually worsened. workup including repeat head ct, infectious and metabolic panels, as well as electroencephalogram (eeg) were unrevealing except for a decreased end-tidal carbon dioxide (co ). two days after presentation, the patient acutely developed fixed and dilated pupils. eeg concomitantly revealed slowing and attenuation of the background. repeat ct head showed new diffuse cerebral edema with tonsillar herniation. despite hyperosmolar therapy, paralytics, pentobarbital, and cerebrospinal fluid diversion, no improvement was noted. unfortunately, brain mri revealed multifocal brainstem infarcts with superimposed duret hemorrhages. herein, we report diffuse cerebral edema as a complication of mmd-related ich. we hypothesize that disruptions of delicate cerebral autoregulatory mechanisms led to extensive hypoxic-ischemic injury. in the setting of ich, aggressive blood pressure management coupled with relative hypocapnia may have likely caused vasoconstriction of poorly compliant arteries leading to worsened cerebral blood flow and ischemia. therefore, because of its complex pathophysiology, traditional blood pressure and co targets should be revisited in mmd-related ich. it is unknown whether admission systolic blood pressure (sbp) differs among etiologies of intracerebral hemorrhage (ich). such differences may have implications for blood pressure -lowering strategies after ich. we compared admission sbp across ich etiologies among patients in the cornell acute stroke academic registry (caesar), which has enrolled all adults with non-traumatic ich at cornell from through . trained analysts prospectively collected demographics, comorbidities, and admission sbp, defined as the first recorded value in the emergency department or upon transfer from another hospital. ich etiology was adjudicated by a panel of board-certified neurologists using the smash-u criteria. we used anova to compare mean admission sbp among ich etiologies. after verification of model assumptions, multiple linear regression was used to adjust for age, sex, race, and glasgow coma scale (gcs) score. among ich patients in caesar, admission sbp varied significantly across ich etiologies, ranging from mm hg in those with structural vascular lesions to mm hg in those with hypertensive ich (p < . ). the overall difference in admission sbp across etiologies remained significant after adjustment for age, sex, race, and gcs score (p < . by the wald test). the mean admission sbp in hypertensive ich cases was mm hg ( % ci, - mm hg) higher than in ich cases of all other etiologies combined. among patients with a history of hypertension, the mean admission sbp was mm hg ( % ci, - mm hg) higher in hypertensive ich than in ich cases of all other etiologies combined. in a single-center ich registry, admission sbp varied significantly among different ich etiologies. our results suggest that admission sbp is associated with ich etiology rather than simply representing a physiological reaction to the ich itself. incidence of clinical seizures after intracerebral hemorrhage (ich) has been reported to range from . % to %, with the majority occurring at or near onset. in the present study, we investigate incidence of clinical seizures in ich subjects during hospitalization and evaluate whether clinical seizures are associated with poor clinical outcomes at discharge. a retrospective review of consecutive patients with ich admitted to the baylor st. luke's medical center between january and december was conducted. demographics, admission gcs, admission nihss, admission mrs, incidence of clinical seizures and clinical outcome at discharge were recorded. associations between the presence or absence of seizures and clinical outcome, measured by the glasgow outcome scale (gos), were investigated using a multivariate logistic regression model. patients with ich were included. clinical seizures were identified in subjects ( . %), presenting in a median time of . days post-admission (iqr ). outcome was significantly worse for subjects who experienced a seizure compared to subjects who remained seizure-free, poor outcome (gos< ) was found on . % and . % respectively (or . , ]; p= . ). this increased risk was significant after controlling for gender, ethnicity, admission gcs, admission nihss, admission mrs higher in the seizure group compared to the seizure-free group, . % vs . % respectively (or . , % ci [ . - . ]; p= . ) after adjusting for mortality and severe vegetative state (gos , ) there was no statistical significant difference between both groups (p= . ). our study shows a significant association between clinical seizures and poor clinical outcome at hospital discharge after controlling for admission status and other type of complications; however, the presence of clinical seizures did not influence in-hospital rates of mortality. despite the well-established use of the national institutes of health stroke scale (nihss) score as a severity scale for ischemic stroke patients, it is still unclear which score is best for intracerebral hemorrhage (ich) patients. while some studies have looked at nihss and glasgow coma scale (gcs) as a predictor of mortality and -month mrs, there is a dearth in the literature looking at how they affect longer functional outcomes. in this study, we look at and compare how initial nihss and gcs predict month functional outcomes in ich patients. one-hundred patients who underwent minimally invasive ich evacuation, a standardized patient population, from december to october were retrospectively reviewed. we looked at nihss and gcs as a predictor of functional outcome at -months, defined as modified rankin scale (mrs) - . multivariate regression models were constructed using clinical and statistical inferences to predict mrs. these variables were also correlated with -month mrs in multivariate analyses. of patients, . % (n= ) were female and the average age was . (sd= . ). on admission, the median nihss was . (iqr . - . ) and the median gcs was . (iqr . - . ). multivariate logistical analyses showed that higher nihss predicts worse -month mrs, however gcs does not (p= . and . , respectively). correlation analysis with mrs at -months reveals that for every . point increase in nihss, mrs increased by . in this cohort, the admission nihss predicts -month mrs in ich patients while controlling for significant covariates, while gcs does not appear to. despite its simplicity and generalizability, the gcs lacks critical ich elements that the nihss includes. the usefulness of the nihss as a predictor of ich outcomes has been questioned, since ich patients often have depressed consciousness on presentation, however we demonstrate its utility as a predictor of -month functional outcomes. among patients with intracerebral hemorrhage (ich), it is unclear whether red blood cell (rbc) transfusions impact outcomes. we investigated the association between rbc transfusions and inhospital mortality in patients with ich. we performed a retrospective analysis using the national inpatient sample (nis) database. we used standard diagnosis codes to identify non-traumatic ich hospitalizations from through . our exposure was rbc transfusions during the ich hospitalization and the outcome was hospital mortality. we performed multivariable logistic regression to estimate the association between rbc transfusion and outcomes after adjusting for demographics, charlson comorbidity index (cci), and hospital characteristics. however, given the absence of ich severity and physiologic variable data within nis, we performed additional analyses in a separate, single-center ich cohort, adjusting for admission ich and apache-ii scores. of , non-traumatic ich hospitalizations in the nis, , ( %) patients received rbc transfusions. patients receiving rbc transfusions had more comorbidities than those not receiving rbc transfusions (cci > : % vs %). rbc transfusion was associated with increased odds of hospital mortality (adjusted or . ; % ci . - . ). in a separate cohort of primary ich patients, ( %) patients received rbc transfusions during their hospitalization. rbc transfusion was not associated with hospital mortality after adjusting for ich and apache-ii scores (adjusted or . ; % ci: . - . ). rbc transfusion was associated with increased odds of hospital mortality after ich. however, underlying medical comorbidities, acute physiologic derangements, and ich severity may account for some of these ns on outcomes after ich. deep venous thrombosis (dvt) is a common cause of morbidity and mortality in patients admitted to the neuro-intensive care unit (nicu). the aim of this work is to assess the incidence of dvt in patients diagnosed with intracerebral hemorrhage (ich) and study its demographic characteristics. a retrospective chart review of consecutive patients with ich admitted to the baylor st. luke's medical center between january and december was conducted. subject demographics, admission status, incidence of dvt, hospital length of stay (hlos), intensive care unit length of stay (icu-los) and clinical outcome at discharge were recorded. data was analyzed to assess the prevalence dvt in this period. patients with ich were included. dvt was identified in subjects ( . %). median time to dvt from diagnosis was h (iqr ) after the initial symptoms of ich. the mean age of patients with dvt was . (sd . ) and subjects ( . %) were female. . % subjects were of caucasian ethnicity, . % african-american, . % hispanic, . %asian and . % were from other ethnicities. median hlos was days (iqr . ) and icu-los was days (iqr . ). moreover, . % of patients who presented a hospital-acquired dvt had a poor clinical outcome at discharge (gos< ). ich patients admitted to the nic large prospective trials are needed to understand the baseline characteristics of patients at risk of dvt as well as the utility of surveillance and different prophylaxis methods. studies have demonstrated an association between high average systolic blood pressure (sbp), and increased sbp variability with worse clinical outcomes in non-traumatic intracerebral hemorrhage (ich). nevertheless, the optimal blood pressure target remains elusive. we aim at introducing an alternative approach to assess blood pressure in the acute phase of ich, by using the metric of sbp dose, and showing that it provides a more robust association with clinical outcome. we retrospectively evaluated ichs admitted to our institution over a seven-year period. initial ct scans were analyzed to confirm the presence of intraparenchymal blood. blood pressure was recorded at presentation and hourly for the first -hours. mean sbp (msbp) in the first -hours was calculated; sbp dose (dsbp) was calculated via the trapezoidal method from area under the curve (auc), and divided in three groups: no dsbp (no time spent above mmhg), moderate dsbp (auc spent above mmhg), and high dsbp (auc above mmhg). discharge dispositions were used as surrogates of clinical outcome. poor outcome included death, hospice, and long term acute care hospital. -one patients ( . %) had poor outcome. of the patients in the no dsbp group none suffered poor outcome; % of the patients in the moderate dsbp group, and % of patients in the high dsbp group suffered poor mean sbp in predicting patient outcomes (p< . ). high dsbp in the first -hours was associated with worse clinical outcomes, and was a better predictor compared to msbp. blood pressure dose is a promising novel metric that deserves further study in the management of ich. despite lack of ich-specific therapies that improve outcome, current guidelines recommend treatment of ich at tertiary care centers. as such, ich comprises a large proportion of inter-hospital transfers (ihts) to comprehensive stroke centers (cscs) despite studies suggesting lack of mortality benefit and low csc resource utilization. the subset of patients who derive the most benefit from a csc is unclear. here, we create a triage model to identify ich patients who can safely avoid transfer to a csc. a retrospective cohort of patients with spontaneous ich transferred to our csc was used to develop our triage model. patients with early discharge from the neuro-icu without use of any csc resource during hospitalization were identified as low risk, non-utilizers (lr--nu were identified and used to develop a triage model which minimized the likelihood of release of patients requiring csc resource. this model was tested in a replication cohort for accuracy. the development and replication cohorts comprised and patients respectively of whom ( %) and ( %) were lr-nu. initial gcs and baseline ich volume were associated with lr-nu in multivariate analysis. presence of ivh and infra-tentorial location of ich were also included. initial gcs > , ich volume < ml, absence of ivh, and supratentorial location had an auc, specificity, sensitivity, ppv, and npv of . , . %, . %, . %, and . % respectively for identifying lr-nu. in the development cohort and patient in the replication cohort had a neurosurgical intervention. however mostly these were for non-emergent avm interventions. spontaneous ich patients with initial gcs > , ich volume < ml, no ivh, and supratentorial location might safely avoid iht to a csc. validation in a prospective, multicenter cohort is warranted. metastatic cardiac myxomas have many neurologic complications, including intracerebral hemorrhage. cardiac myxomas are rare intracardiac tumors. though most myxomas are benign, the risk of malignant spread to the central nervous system (cns) is well known. we describe a case of multiple recurrent intracerebral hemorrhages (ich) occurring in the setting of a recently treated cardiac myxoma. a -year old woman with a history of resected left atrial myxoma presented with a one-day history of left ear paresthesias. computed tomography (ct) of the head was performed and demonstrated ichs within the right frontal and parietal lobes and left cerebellar hemisphere. she had presented to an outside hospital several weeks earlier with similar symptoms with imaging demonstrating similar definitive evidence of malignancy or infection. conventional angiography was negative for vasculitis. brain biopsy showed no evidence of amyloidosis or glioma. at our institution, magnetic resonance imaging (mri) of the brain with double inversion recovery also revealed no evidence of vasculitis; however, the study was concerning for multiple cavernous malformations. underwent genetic testing. no mutations associated with familial cerebral cavernous malformations syndromes were identified. several months later, she returned to the hospital with recurrent symptoms. head ct and mri re-demonstrated multiple cavernous malformations with surrounding vasogenic edema, which were mildly increased compared with prior studies. given progression of her mri findings, concern for metastatic cardiac myxoma was raised. considering that - % of patients with cardiac myxoma will have some form of neurologic complication, all should receive a comprehensive neurologic evaluation. diagnosis is made with neuroimaging and brain biopsy. primary treatment of cardiac myxoma includes surgical resection. when cns lesions are present, chemotherapy or stereotactic radiosurgery should be considered. an association between spontaneous hyperventilation, severity of disease at presentation, and poor clinical outcomes has been reported in patients with subarachnoid hemorrhage (sah). we evaluated the relationship between early breathing changes and outcomes in patients with intracerebral hemorrhage (ich). consecutive patients with spontaneous ich were enrolled in an observational cohort study conducted between and at a comprehensive stroke center. patient characteristics and functional outcome at discharge were prospectively recorded. arterial blood gas (abg) measurements and mechanical ventilation settings in the first hours of admission were retrospectively collected, when available. hyperventilation was defined as pco < mmhg concurrent with ph > . in spontaneously breathing patients, excluding mechanically ventilated patients not overbreathing the set rate of a control mode. we assessed for an association between early breathing changes, hemorrhage severity and hospital outcomes by univariate and adjusted analyses. early abg data were available for of patients. patients with abg data had more severe hemorrhages than those without (median ich score versus , p< . ). hyperventilation occurred in ( %) of cases. there was no univariate association between hyperventilation and ich score, admission gcs score or initial hematoma volume. lower initial pco was associated with greater risk of in-hospital death (or . per mmhg, %ci [ . , . ], p= . ) after adjustment for ich score, pneumonia and mechanical ventilation requirements. spontaneous hyperventilation is less common after ich than sah ( % vs %, respectively) and not associated with initial disease severity. the association between lower pco and in-hospital mortality after ich, independent of neurologic severity and comorbid respiratory complications, is consistent with findings of greater delayed ischemia and worse outcomes in spontaneously hyperventilating sah patients. these associations may be mediated by a potentially modifiable underlying mechanism such as acute shifts in cerebral hemodynamics due to pco changes. ich or sah patients often undergo interhospital transfers to tertiary centers. acute clinical deterioration diversion is often implemented via external ventricular drains (evd's). the safety and efficacy of leaving the evds clamped or open during inter-hospital transfer is not known. we aimed to implement a pilot during inter-hospital transport for hemorrhagic stroke patient. under the neuroemergencies management and transfers (nemat) program, department of neurosurgery at mount sinai health system, we implemented this protocol in october, . patients with ich or sah requiring evd placement prior to inter-transfer to a specialized center for ich or sah within our health system were enrolled. recommendations for icp management, for post-evd drainage h and cm or lower for ich were included. evd was clamped for transportation and a dose g/kg of mannitol was given just prior to transportation. icp precautions were maintained throughout transportation. ( male, female_ patients who underwent inter-hospital transfers for ich (n= ) and sah (n= ) after placement of evds for raised icp at the transferring hospital were included. all patients required endotracheal intubation for transfer. / patients had an icp less than mmhg on arrival at the receiving hospital. conclusion: protocolized care for ich and sah patients with evds and icp management during interhospital transfers for patients is safe and feasible. such a protocol could an help facilitate potentially rapid and safe life saving inter-hospital transfers for hemorrhagic stroke patients with evds in large urban health system to to hospitals with specialized definitive neurosurgical and neurocritical care. intracerebral hemorrhage (ich) during pregnancy is abound with diagnostic and therapeutic dilemmas and contributes to pregnancy-related mortality. we present a pregnant patient with ich due to moyamoya disease to highlight these issues. case report. a -year-old -week pregnant asian woman presented after developing an acute onset headache followed by loss of consciousness. in the emergency department, she was comatose with bilateral pinpoint pupils and required intubation for airway protection. initial ct head showed predominantly intraventricular hemorrhage (ivh) that emanated from the left thalamus. ct angiogram revealed highgrade stenosis of the left m segment with moyamoya collateralizations. due to hydrocephalus, an external ventricular drain (evd) was placed. the patient required admission to the neurocritical care unit for further monitoring of exam and vitals. continuous fetal monitoring, and ultimately, successful csection on day of hospitalization was performed through collaboration with the obstetrics and gynecology (ob/gyn) team. cerebral angiogram confirmed the diagnosis of unilateral moyamoya disease as the cause of the patient's ivh. the patient was discharged initially to acute rehab and then home with minor cognitive deficits. the work-up and management of ich in pregnant patients can be challenging. moyamoya disease is a non-atherosclerotic cerebral vasculopathy that can be included in the differential diagnosis for ich in pregnant woman. the most common presentation of moyamoya disease in adults is ich, and it's mainly due to the rupture of dilated and fragile vessels in the basal ganglia, and rupture of saccular aneurysms within the moyamoya collaterals. pregnancy might increase the risk of ischemic or hemorrhagic stroke in women with moyamoya, but available data is controversial. cooperation between the neurocritical care and ob/gyn teams can assist in determining the risks and benefits of medications, imaging, and the need and timing for delivery, thus assuring optimal outcomes for the patient and infant. spontaneous intracerebral hemorrhage (ich) is severely disabling, and survivors often require extensive rehabilitation to maximize recovery. recovery for survivors discharged from index hospitalization is variable and incompletely explained by discharge functional capacity. we assessed whether discharge disposition was independently associated with long term recovery potential. patients with acute ich hospitalized at a tertiary care comprehensive stroke center between and were enrolled in a prospective, observational study that recorded demographics, standard severity s was measured by the modified rankin scale (mrs) at discharge and three months. discharge disposition were ordinalized by activity engagement level from highest to lowest as follows: home, ; acute inpatient rehabilitation (air), ; skilled nursing facili ; and long-term acute care hospital (ltach), . ordinal regression was used to assess the prognostic association between discharge disposition and three month functional status by mrs, adjusting for the ich score and mrs at discharge. among patients enrolled, survived and had complete in-hospital data for analysis, and three outcomes at three months (mrs - ; . % and . % respectively), with most either bedbound or dead ( . % and . % respectively). poor outcomes were less common among patients discharged to air ( . %) or home ( . %). the adjusted model found that a better discharge disposition was associated with more favorable three month mrs (odds ratio . , % ci [ . , . ], p= . ). discharge disposition captures prognostically important characteristics in patients with intracerebral hemorrhage beyond traditional case severity and functional status measures. outcomes are poor for a large majority of patients unable to return home or qualify for acute rehabilitation. whether the prognostic characteristics requiring nursing facility care are modifiable by increasing rehabilitation services in those care environments is not known. as a reversal agent for uncontrolled or life-threatening bleeding for patients taking apixaban and rivaroxaban. approval was based on the results of interim analysis of the ongoing annexa- multicenter, prospective, open-label clinical trial. our institution began using the drug in august . we report our clinical experience. we conducted a retrospective observational study of patients admitted to stanford medical center from -associated intracranial hemorrhage. -associated ich. the mean age was (+/- ). patients were male. the mean glasgow coma scale score was . hemorrhage types included intraparenchymal hemorrhage ( patients), subarachnoid hemorrhage ( patients), and subdural hemorrhage ( patients). hemorrhage was associated with head trauma in patients ( %). ten patients ( %) had "excellent" or "good" hemostasis defined by the annexa- criteria. three patients ( %) developed deep venous thrombosis. no patients developed pulmonary embolism or myocardial infarction. -day mortality was % ( patients). we describe a case series of patients who received andexanet alfa for intracerebral hemorrhage at a large medical center. the incidence of intracerebral hemorrhage (ich) is . per , person years. nontraumatic spontaneous ich is usually seen in setting of uncontrolled hypertension or cerebral amyloid angiopathy and commonly occurs in basal ganglia, cerebral cortex, brainstem or cerebellum. spontaneous ich in corpus callosum with intraventricular hemorrhage (ivh) is very rarely seen and reported. we present an unusual case of corpus callosum hemorrhage with ivh associated with a reversible cerebral vasoconstriction pattern (rcvs) on cerebral angiography. the demographic information and clinical reports were obtained from electronic medical records retrospectively. select neuroimaging was obtained from neuroradiology department. year old caucasian male with a past medical history of chronic obstructive pulmonary disease, essential hypertension, and prior ischemic stroke with residual right hemiparesis presented in unresponsive state when he was discovered on bathroom floor. neurological examination on admission showed no verbal response, eyes open, with reactive pupils, and withdrawal to pain in left arm and leg. blood pressure on admission was / mmhg. computer tomography (ct) of head showed large ich in rostrum, genu and trunk of corpus callosum with intraventricular extension and hydrocephalus. he was intubated for respiratory distress and external ventricular drain (evd) was placed. he was also treated with intraventricular alteplase mg injection for total of doses, hours apart. blood pressure was controlled with nicardipine infusion initially, a up ct head showed resolution of ivh over the next several days, however, no significant clinical improvement was seen. patient remained abulic and akinetic. cerebral angiography performed showed right pericallosal artery beading pattern consistent with rcvs. after transition to comfort care, the patient expired on the th day of hospitalization. spontaneous non-traumatic corpus callosum ichs are rare, and while other causes have been reported, this particular etiology is likely due to rcvs. intracerebral hemorrhage (ich) is a leading cause of disability and mortality. infections are a common complication observed in ich and might be associated with worse outcomes. we aim to evaluate the association between infections and clinical outcomes at hospital discharge. a retrospective chart review of consecutive patients with ich admitted to the baylor st. luke's medical center between january and december was conducted. subject demographics, admission status, rates of infections including; pneumonia, urinary tract infection (uti), bacteremia and clinical outcome at discharge were recorded. associations between the presence or absence of infections and clinical outcome, measured by the glasgow outcome scale (gos), were investigated using a multivariate logistic regression model. patients with ich were included. infections occurred in subjects ( . %). uti was the most common infection ( . %) followed by pneumonia ( . %) and bacteremia ( . %). clinical outcome was significantly worse for subjects who experienced any type of infection during hospitalization, compared to non-infected subjects, poor outcome (gos < ) was found on . % and . % respectively (p= . ). this increased risk was significant after controlling for gender, ethnicity, ermore, an unfavorable discharge disposition -infected group, . % and . % respectively (p= . ). our study shows a significant association between infections and poor clinical outcomes at hospital intracerebral hemorrhage (ich) is a subtype of stroke associated with a high morbidity and mortality. low serum calcium levels have been previously associated with larger hematoma volumes, hematoma expansion and worse outcomes; however, the pathophysiological mechanisms are still not well understood. a confounding effect among serum calcium and magnesium levels has been previously considered. in the present study, we investigate whether hypocalcemia is associated with poor clinical outcomes controlling for serum magnesium levels. a retrospective chart review of consecutive patients with ich admitted to the baylor st. luke's medical center between january and december was conducted. serum calcium and magnesium levels were measured during hospitalization, hypocalcemia and hypomagnesemia were defined as serum levels below . mg/dl and . m/dl respectively. associations between serum calcium level and clinical outcome, measured by the glasgow outcome scale (gos), were investigated using a multivariate logistic regression model. patients with ich were included. hypocalcemia was identified in subjects ( . %). clinical outcome was significantly worse in the hypocalcemic group compared to the normocalcemic group, poor outcome (gos < ) was found in . % and . % respectively (p= . ). this increased risk was significant after controlling for gender, ethnicity, serum magnesium levels, admission gcs, admission death) was also higher in the hypocalcemic group compared to the normocalcemic group, . % and . % respectively (p= . ). our study shows a significant association between hypocalcemia and a poor clinical outcome after association. treatment of patients with intracerebral hemorrhage (ich) typically requires advanced care at a tertiary medical center. many patients present initially to regional or local emergency departments and require interfacility transportation to a referral center. mission hospital (mh) is a community-based nonacademic -bed tertiary care facility with comprehensive stroke center certification. we serve as the referral center for affiliated mission health hospitals and regional non-affiliated hospitals across counties. these hospitals are distributed throughout a mountainous and rural area with challenging terrain for transportation and limited resources for critical care transport. here, we aim to describe the current transfer paradigm and consistency of care provided during interfacility transport of ich patients prior to implementation of a dedicated ich regional interfacility transfer protocol. retrospective review of the electronic medical record was performed to identify all patients in calendar year admitted to mh with a principal diagnosis of nontraumatic ich who initially presented to another facility prior to transfer to mh. data, including demographics, transport service type, and transport sequential blood pressures, were collected. blood pressures during transport were analyzed to determine whether blood pressure exceeded our guidelines. patients with ich transferred to our referral center were identified. / ( . %) were transported via critical care transport, and / ( . %) were transported by local ems using general adult transport protocols. / ( . %) had uncontrolled hypertension as defined by or more bp readings above our guidelines. of these, / ( . %) were transported via critical care transport and / were transported via local ems. transport records were incomplete in / ( . %). elevated blood pressures during transport of ich patients are common. rural health systems are challenged by lack of critical care transport capabilities. we are currently implementing a dedicated protocol for interfacility transport care of ich patients. infratentorial intracerebral hemorrhage (ich) is associated with worse prognosis than supratentorial ich; however, infratentorial ich is often excluded or underrepresented in major studies of ich. we sought to evaluate the natural history of infratentorial ich stratified by brainstem or cerebellar location using a prospective observational study inclusive of all spontaneous ich presenting to our institution. using a prospective, single center cohort of patients with spontaneous ich between - , we conducted a descriptive analysis of baseline demographics, severity of injury scores, and long-term functional outcomes of infratentorial ich stratified by cerebellar or brainstem location. infratentorial ich occurred in ( %) of patients in our ich cohort. cerebellar ich occurred in ( %) and brainstem ich occurred in ( %). compared to cerebellar ich, brainstem ich had significantly worse severity of injury scores, including: admission glasgow coma scale (p < . ), ich score (p = . ), and national institute of health stroke scale (nihss) (p = . ). modified rankin scale (mrs) scores at months were significantly better in patients with cerebellar ich compared to brainstem ich (median [ . - . ] versus median [ . - . ], p = . ). patients with cerebellar ich were more likely to be discharged home or to acute rehabilitation (or . , % ci . - . ) but there was no difference in in-hospital mortality (or . , % ci . - . ) or cause of death (p = . ). patients with cerebellar ich who were alive at months had smaller hemorrhages and lower severity of injury on admission. patients with cerebellar ich have less severe symptoms at presentation and more favorable functional outcomes compared to patients with brainstem ich. it has been known that patients with intracerebral hemorrhage (ich) have a higher rate of acute renal tality. the factors such as medications for blood pressure control, blood pressure (bp) variations and use of contrast for imaging without history of previous kidney disease. we analyzed the records from hospitalized patients in the icu from to in a single academic center with primary diagnosis of ich and renal failure. a total of were analyzed, patients ( . %) were reported to ( . %) patients did not meet the criteria for renal risk, injury or failure and ( . %) did not have enough data for the study. antihypertensive therapy used within the first hours of admission was a combination of acei, arbs and b-blockers. patients showed a wide variability in blood pressure (max-min within a day) which could not be and use of iodinated contrast, since ct without contrast was the imaging study of choice in all patients. our observations did not show an association in between bp variability, type of antihypertensive therapy or use of iodinated contrast within the first hrs of admission to acute renal failure in ich patients either with or without history of renal disease. a larger study may be required to support this statement. milrinone, a phosphodiesterase inhibitor, has limited data as salvage therapy for cerebral vasospasm (cvs) secondary to aneurysmal subarachnoid hemorrhage (asah). to date, no study has compared patients treated with intravenous milrinone to a control group receiving standard treatment, primarily hemodynamic augmentation. we compared cvs duration in milrinone-treated patients to a control group, and evaluated additional safety and efficacy outcomes. this was a retrospective, single center, case control study. adult patients admitted to spectrum health or inclusion. the primary outcome was duration of cvs recorded on daily transcranial doppler exams. secondary outcomes assessed efficacy and safety. efficacy endpoints included, but were not limited to: incidence of ischemic stroke, interventions to treat cvs, icu/hospital length of stay (los), and in-hospital mortality. safety endpoints included vasopressor/inotrope requirements and incidence of arrhythmias. -treated and control patients. milrinone use was associated with a longer duration of cvs (p = . ), increased use of intraventricular medications for cvs (p= . ), greater vasopressor requirements (p = . ), and longer vasopressor duration (p= . ). there was no difference in arrhythmias or in-hospital mortality. icu los in milrinone versus control groups was . vs. . days (p= . ) and hospital los was . vs. days, respectively (p = . ). there were ischemic strokes in the milrinone group versus in the control group (p= . ). intravenous milrinone was associated with a longer duration of cvs in asah patients, greater vasopressor requirements, and trended towards a higher incidence of ischemic stroke, though not statistically significant. prospective, randomized, controlled trials are needed to further define the risks and benefits of milrinone therapy in asah patients. aneurysmal subarachnoid hemorrhage (asah) patients sustain several physiologic changes, including a rupture. mri is potentially useful for prognostication in asah but has not been well-studied in this patient population. we present our preliminary experience with multimodal mri in the acute period after asah. we hypothesized that changes in nodes of network critical to consciousness differ between patients with good and poor outcomes. thirty-four asah patients and healthy volunteers underwent multimodal mri at t. mri t images were segmented, and aslconsciousness (i.e., salience network, central executive network, default mode network). wilcoxon rankto test odds of modified rankin scale (mrs) - at months. asah patients had a mean age (±sd) of . ± . years, and controls were . ± . years (p< . ). prefrontal cortex - and - ). r age-matched studies with more subjects and additional mri sequences are needed to better determine mri's potential utility in asah prognostication. aneurysmal subarachnoid hemorrhage (sah) classically presents with the "worst headache of the patient's life" which can be very debilitating and persist for weeks. headache is often refractory to standard treatment, including opiates. pain is thought to be derived from meningeal irritation in the subarachnoid space. the sensory fibers in the anterior meninges are innervated by branches from the ophthalmic division of the trigeminal nerve, which is closely associated with the sphenopalatine ganglion (spg). spg blockade with local anesthetic, first described in , has used as a treatment for various types of headache disorder but has not been described in sah-associated headache. treatment approach is either transnasal or transcutaneous injection. this case series describes five patients who received spg blockade for intractable sah-associated headache. patients with acute aneurysmal sah in the neurocritical care unit were offered adjunct spg blockade for headache refractory to standard treatment. patients rated pain on a - numerical scale, both before and minutes after the procedure, which included either transnasal administration of ropivacaine using the tx device (tian medical) or transcutaneous administration of ropivacaine with decadron. ess score on admission (range - )); two ( %) received transnasal blockade and three ( %) received transcutaneous blockade. median pre-treatment pain score was (range their pain within minutes; the fifth reported % reduction of pain. transcutanous spg blockade resulted in complete pain relief in all patients. the effects were transient, and pain typically returned within hours. there were no complications associated with the procedure. repetitive spg blockade is a safe and effective adjunct treatment for sah-associated headache. a larger clinical trial is planned. tranexamic acid is recommended in the first hours after subarachnoid haemorrhage (sah) and before aneurysm treatment to reduce rebleeding. in brazil, patients are frequently submitted to delayed aneurysm occlusion after sah (> hours from ictus). the objective of this study was to evaluate the effects of tranexamic acid on hospital complications and outcome of patients with sah. all consecutive patients admitted with sah between and at a reference center were included. data were collected prospectively during the hospital stay. all sah patients within hours of ictus were considered eligible for tranexamic acid (ta) up to aneurysm occlusion. we analysed groups: no ta, low dose ta and high dose ta. the primary endpoint was mortality at hospital discharge. other outcomes included hospital complications such as rebleeding, delayed cerebral ischemia and adverse events such as deep venous thrombosis dvt) and pulmonary embolism (pe). one hundred forty five patients were included in the study. approximately half ( , %) received ta, with ( %) receiving low dose and ( %) high dose. at baseline, the high-dose ta group had more -dose group ( % vs %). patients in the low-dose group had lower rebleeding rates ( . %; p= . ) than the no-ta and high-dose ta groups. mortality was lower for the no-ta and low-dose ta groups as compared to the high-dose ta patients. moreover, patients that did not receive ta had longer icu and hospital lengths of stay. dvt/pe rates were very low in our cohort and not different between groups. our study showed that patients that received low dose of tranexamic acid had lower rates of rebleeding as compared to those that received no ta and high-dose ta. mortality was also lower in this group when compared to patients that received high-dose ta. aneurysmal subarachnoid hemorrhage (asah) carries high mortality and morbidity. symptomatic vasospasm is an important complication of asah. about thirty percent of patients with severe vasospasm do not respond to conventional management and will go on to develop delayed ischemic strokes. medical management in these patients are limited and require endovascular therapy with intraarterial vasodilators and angioplasty. milrinone has vasodilator properties and inotropic activity which has been used by intravenous and intraarterial routes for symptomatic vasospasm. in this study, we tested the safety and feasibility of intraventricular milrinone (ivm) in patients with severe vasospasm administered through the external ventricular drain (evd). a retrospective review of medical records of patients with subarachnoid hemorrhage who received ivm between - . ivm was given at a dose of . mg in ml sterile saline every hours through an evd that was subsequently clamped for h. patients received ivm for refractory vasospasm. among those, patients had ruptured asah and one patient had ruptured internal carotid artery pseudoaneurysm secondary to pituitary macroadenoma resection. the mean ivm doses were (range - doses). only one patient ( . %) developed ventriculitis days after ivm. there were no elevations of intracranial pressures with intraventricular administration of ivm. in patients with refractory vasospasm from aneurysmal subarachnoid hemorrhage, intraventricular milrinone administration seemed to be relatively safe. prospective trials are needed to further determine the safety and efficacy. rupture of cerebral aneurysm is the most common cause of subarachnoid hemorrhage (sah). hypertension is a particularly important risk factor for growing and rupture of cerebral aneurysm. in clinical practice, the non-adherence to anti-hypertensive medications is the most important cause of uncontrolled blood pressure. the aim of this study is to evaluate the effect of non-adherence to antihypertensive medications on the long-term prognosis of patients with hypertension and ruptured cerebral aneurysm based on the nationwide health claims database in korea. this study is retrospective cohort study using the national health insurance service-national sample cohort (nhis-nsc) in korea. we included non-traumatic sah patients (icd- ; i ) with hypertension who underwent endovascular coil embolization or surgical clipping for ruptured aneurysm. the primary outcome is defined as composites of recurrent stroke, myocardial infarction, all-cause death. adherence to anti-hypertensive medications is measured by calculating the proportion of days covered (pdc) based on the prescription records, which is treated as a time-dependent variable. we performed multivariate time-dependent cox regression analysis with adjustments for sex, age, diabetes mellitus, treatment morality (coil embolization or surgical clipping), and household income. -nsc, we found patients who received coil embolization or surgical clipping for aneurysmal sah. among them, patients with hypertension were included for analysis. during the . years of mean follow-up period, there were patients who had primary outcome. in the multivariate cox regression, poor adherence to antiindependently associated with increased risk of primary outcome (adjusted hr . , % ci . - . , p-value= . ). in this cohort study with real-world data, poor adherence to anti-hypertensive medications is a strong risk factor for worse prognosis in the hypertensive patients who underwent treatments for ruptured aneurysm. there is need for greater attention to adherence to anti-hypertensive medications in the high-risk patients. tcd is routinely used in aneurysmal subarachnoid hemorrhage (sah) for vasospasm surveillance. the value of tcd monitoring in non-aneurysmal sah (nasah) is unclear. in this study we sought to determine the clinical utility of performing tcd monitoring in a cohort of patients with nasah. retrospective case series study performed at a comprehensive stroke center in a university hospital. patients with sah in whom an aneurysm or other vascular lesion was not identified were extracted from a prospective database covering a year period. patients with nasah were categorized into perimesencephalic and diffuse sah based on the ct appearance. baseline demographics and clinical variables were obtained from the database. tcd results were obtained from a tcd database and conventional criteria were used to diagnose sonographic spasm. categorical variables were compared a total of nasah patients were identified; perimesencephalic and diffuse. spasm was identified in / ( %) perimesencephalic nasah patients and / ( %) diffuse nasah patients (p= . ). no differences were observed between groups in age (p= . ), discharge disposition (p= . ), median her score (p= . ) when comparing patients with spasm to those without spasm. similarly the median number of tcds (p= . ) did not differ among patients with and without spasm. the location of nasah did not influence the diagnosis of spasm (p= . ). sonographic spasm occurs in % of nasah patients but no specific clinical variable appears to influence its occurrence. the clinical significance of such finding needs further validation. complications following aneurysmal subarachnoid hemorrhage (asah) may be associated with early fluid status. this study aims to assess the relation of fluid balance and intravascular volume to outcomes including acute kidney injury (aki), delayed cerebral ischemia (dci), and vasospasm (vsp) in asah. consecutive asah patients were retrospectively collected including patient demographics and admission characteristics. intravascular volume on admission was measured by ivc ultrasound. daily fluid balance in the first days of admission were recorded along with changes in bun and cr. outcomes including dci and vsp were collected. spaghetti plots were used to illustrate trajectory patterns. a linear mixed effect model was used the test the trajectory of slopes. an interaction term between time and patient condition was used to test the slope difference between patient conditions. of patients underwent ivc ultrasound assessment of intravascular volume. patients were hypovolemic on admission with ivc collapsibility index > % or distensibility index > %. ivc slopes were found to be different by patient m balance decreased by - . ± ml/hr (p= . ) while it increased . ± . ml/hr (p= . ) in those - . ± . /hr (p= . ) while it increased . ± . /hr (p= . ) in those without dci (interaction p= . ). - . ± . /hr (p< . ) in those without vsp (interaction p< . ). patient hemodynamics on admission as determined by ivc ultrasound does not correlate with development of aki. however, fluid balance in the first days of admission may be associated with outcomes in asah. early prediction of delayed cerebral ischemia (dci) will improve management of subarachnoid hemorrhage (sah) patients. we used mass spectroscopy (ms) to undertake an unbiased interrogation of plasma proteins associated with dci. this is an observational prospective single-center study of patients admitted to a tertiary care center. serum samples from patients were obtained within hours post-admission. we performed analysis in cohorts separately at different times. the first cohort was a retrospective cohort of matched subjects ( no-dci vs dci). the second cohort consisted of matched subjects ( no-dci and dci). in both cohorts subjects were matched across dci status for age, sex and modified fisher scale. we performed t-tests across dci groups in both cohorts to identify proteins with a difference in concentrations between dci groups. we selected proteins with a p-value of < . for difference across dci in both cohorts as potential candidates. and proteins were identified in cohort- and cohort- respectively. we identified potential candidates in cohort- , and potential candidates in cohort- . six proteins were identified in both cohort- and cohort- (p-value cohort- and p-value cohort- ): complement factor h (p= . and p= . ); complement factor i (p= . and p= . ), antithrombin-iii (p= . and p= . ), histidinerich glycoprotein (hrg) (p= . and p= . ), fetuin-b (p= . and p= . ), and hemopexin (p= . and p= . ). all plasma protein levels were lower in the dci group. in our unbiased approach to identifying biomarkers of dci we identified potential candidates. the compliment cascade and antithrombin-iii has previously been identified as important in the pathophysiology of sah. of interest, we also identified hemopexin (part of the cd -heme-hemopexin scavenging system) and hrg which is associated with cerebral vessel contraction as potential -b has not been previously reported in sah. confirmatory testing needs to be performed to validate our findings. glycemic gap (gg), determined by the difference between glucose and the hba c-derived average glucose (adag), predicts poor outcomes in various clinical settings. our main objective was to evaluate various admission factors and outcomes in relation to gg. we retrospectively reviewed prospectively collected data on adult patients with aneurysmal subarachnoid hemorrhage. admission glycemic gap (agg) was defined as adag ( . ×hba c- . ) subtracted from admission glucose (ag). poor composite outcome was defined as death, tracheostomy, gastrostomy, and/or discharge to a nursing facility. spearman method was used for correlation. generalized linear model was used to test the difference in gg between patient categories. mixed effects model was used to test the difference in trajectory slopes in gg. area under the curve (auc) for roc curve was used to estimate prediction accuracy. sas . was used for all data analyses. the overall mean agg was . ± . mg/dl. agg was significantly correlated with ag (r= . , p< . ), gcs (r= - . , p< . ), lactic acid (r= . , p< . ), and procalcitonin (r= . , p< . ) on admission, but not with hba c (r= . , p= . ). there was a nonsignificant trend of higher agg in those with delayed cerebral ischemia ( . ± . vs. . ± . , p= . ). patients with poor composite outcome had both higher ag ( . ± . vs. . ± . , p= . ) and agg ( . ± . vs. . ± . , p< . ), but the difference in agg was more profound. trajectory slope in the first hours for gg did not differ in patients with poor vs. good composite outcome (- . ± . / hr vs. - . ± . / hr, p= . ), nor did it differ for pointof-care glucose testing (- . ± . / hr vs. - . ± . / hr, p= . ). agg had significantly better prediction accuracy than ag in predicting poor composite outcome (auc: . ± . vs. . ± . , p= . ). admission glycemic gap served as a better predictor of poor outcome than admission glucose. additionally, agg was correlated with ag, lactic acid, and procalcitonin, and inversely correlated with gcs. the use of standardized management protocols (smps) has been shown to improve patient outcomes for multiple neurocritical diseases. however, whether smps improve outcomes after subarachnoid hemorrhage (sah) is currently unknown. we aimed to study the effect of smps on -month mortality and neurologic outcomes following sah. a systematic review of randomized control trials (rcts) and observational studies was performed by searching multiple indexing databases from their inception through january . studies were limited -traumatic sah reporting mortality, neurologic outcomes, and delayed cerebral ischemia (dci). data on patient and smp characteristics, outcomes, and methodologic quality was extracted into a data collection form. methodologic quality of observational studies was assessed using the newcastle ottawa scale (nos). a total of , studies were identified; were assessed in full and met the criteria for inclusion. two studies were rcts and were observational. smps were divided into four broad domains: management of acute sah, early brain injury, dci, and general neurocritical care. the most common smp design was control of dci, with studies targeting this domain. overall, studies were of low quality; most described single-centre case series with small patient sizes. observational studies scored between and on the -point nos. dci and neurologic outcomes were defined inconsistently in the literature, leading to significant challenges in their interpretation. given the substantial hetereogeneity in reporting practices between studies, a meta-analysis could not be performed. the effect of smps on sah remains unknown due to major limitations in study design and quality. notable deficiencies relate to heterogeneous definitions of dci and inconsistent application of standardized neurologic assessment scales. our study highlights the need for rigorous rcts to determine whether the use of a protocol impacts outcomes in critically ill patients with sah. elevated serum chloride has been associated with increased inflammatory markers, worsened systemic hypotension, and renal injury. little is known regarding the effects of hyperchloremia on neurological outcomes after subarachnoid hemorrhage (sah). we reviewed prospectively collected data on adult patients who were admitted for spontaneous sah from to . chloride values were examined on days - . hyperchloremia was defined as serum chloride of meq/l or greater. the primary outcome was delayed cerebral ischemia (dci). secondary outcomes included hospital mortality and month modified rankin scores (mrs). chi-square test and two sample t-test were employed to assess dci and month mr analyze hospital mortality. sah patients were included in the analysis, ( %) developed dci and ( %) did not. patients with dci had higher rates of hyperchloremia on day ( % vs. %, p= . ), day ( % vs. %, p= . ), and day ( % vs. %, p< . ) than patients without dci. after controlling for age, hunt and . , p= . ) and day (or . , p= . ) were associated with higher likelihood of experiencing dci. good functional outcome (mrs - ) was seen in of patients ( %) at months. rates of hyperchloremia were significantly lower in the good outcome group at all time points. after multivariate analysis, hyperchloremia on day (or . , p= . ), day (or . , p< . ), day (or . , p= . , and day (or . , p< . ) were independently associated with decreased odds of good functional outcome at months. early hyperchloremia was associated with dci and worse functional outcomes from sah. the impact of chloride load and fluid management strategy on sah outcomes warrants further investigation. headache is the most common complaint of patients presenting with aneurysmal subarachnoid an efficacious adjuvant therapy in the management of sah-induced headache. we performed a retrospective chart review of patients treated for sah in the neurocritical care unit at a eceived steroids. dexamethasone ( mg every hours) is typically administered for - days in patients with headache refractory to acetaminophen and oxycodone. nursing documented numeric ( - ) pain scores were collected every two hours. we used paired t-tests to compare mean, maximum, and minimum daily pain scores on the day before and during steroid administration. we used multivariate analysis to assess for factors associated with steroid responsiveness, defined as an improvement of or more points in mean daily pain score. there were steroid treatment periods among patients ( % female, mean age ± . , median hunt--two ( %) were classified as steroid responsive. mean daily pain scores decreased by . points (p = . ) during steroid administration. responders reported higher pre-treatment pain scores ( . vs . , p = . ) and demonstrated greater decrease in mean pain scores ( . vs -. points, p < . ). there was no decrease in mean pain scores during the two days following therapy. in multivariate analysis, there was a weak signal that patients who underwent surgical clipping were more likely to have steroid responsive headaches (or . , . no other demographic or clinical characteristics were associated with steroid responsiveness. a subset of patients with sah induced headache may have a favorable, transient response to steroids. tterns and influence on opioid requirements. cerebral vessel vasospasm (cvv) is a feared complication following aneurysmal subarachnoid hemorrhage (asah). there has been an association between cvv and delayed cerebral ischemia which accounts for a great deal of morbidity and mortality following asah. though the majority of patients with cvv respond to blood pressure augmentation, many patients go on to develop delayed ischemic neurologic deficits despite aggressive therapy. there is some suggestion in the literature that intraventricular milrinone (ivm) may be useful in the treatment of cvv. retrospective case series of patients with asah that were treated with one or more doses of . mg index (pi) and frequency of intraventricular milrinone dosing was collected. all patients were treated at cleveland clinic in the neurologic intensive care unit between and . paired t-test analysis was patients in our cohort were dosed with ivm between and times. there were no significant differences territory. there was also no effect of ivm on cvv over time. there were no direct complications secondary to ivm in these patients. based on our results, ivm was non-therapeutic for the treatment of cvv in patients with asah. our data be conducted to evaluate the safety and efficacy of this treatment. our retrospective analysis suggests that the use of intraventricular milrinone may be non-therapeutic for the treatment of cvv. clinical and research tool for riskelement by the national institute of neurological disorders and stroke sah working group. there are few data assessing the we distributed a survey to a convenience sample of attending physicians that care for patients with questions regarding the definitions of the scale components (thin vs. thick, intraventricular blood vs no to determine the overall inter-ing. thirty-three respondents ( % neurocritical care fellowship trained, % ucns certified in neurocritical care, . % neurologists, median years (iqr - ) in practice, treating median of patients (iqr - ) with sah annually from institutions) completed the survey. twenty-three ( . %) reported r measurement of thin vs. thick blood, and . % correctly identified that blood in any ventricle is scored - . ) for the ct scans, which is considered poor agreement. agr regarding the definitions of the score components. the national institute of neurological disorders and stroke sah common data elements may require further clarification in order to standardize research in cerebral vasospasm leading to delayed cerebral ischemia (dci) is one of the most significant factors impacting functional outcome following subarachnoid hemorrhage (sah). although vasospasm is prevalent in this population, treatment options are limited. in recent years, several published case series have reported a positive effect of intrathecal (it) nicardipine for the treatment of vasospasm. we now report a single center one year retrospective cohort experience with intrathecal (it) nicardipine for the treatment of cerebral vasospasm following sah. all patients discharged in with a diagnosis of non-traumatic sah, either aneurysmal or idiopathic, were included in the analysis. demographics, risk factors, clinical course, radiological dci and functional outcome were analyzed. during , patients were admitted with aneurysmal (n= ) or idiopathic (n= ) sah. the mean age was . ± . and . % were women. low grade hemorrhage (h&h - ) was found in . %, medium (h&h ) in . % and high grade (h&h - ) in . %. cerebral vasospasm was diagnosed in . % of the patients, and it nicardipine was used in % of these patients (n= ). only . % of the patients required angiography to treat vasospasm. tcd data was available for patients who received it nicardipine. treatment reduced mean velocities in all arteries within one day (reduction of . - . %, p< . ). this effect remained through the treatment, until the vasospasm resolved. one patient suffered from bacterial ventriculitis. the overall rate of radiological dci, as found in a blinded post treatment assessment of patients' imaging, was . %. in this cohort, . % had a favorable functional it nicardipine is a safe and potentially effective treatment for cerebral vasospasm and prevention of the subsequent ischemic changes. we are currently expanding the analysis to prior years, however, future prospective controlled trials are still needed to evaluate the safety and efficacy of this treatment. patients remain at high-risk for vasospasm, delayed cerebral ischemia (dci), and hydrocephalus after diversion is often necessary in ma additional benefit over standard management by facilitating intracranial blood clearance and decreasing rate of vasospasm and dci, albeit with a possible increased risk of shunt dependency in historical studies. in this study, we assessed safety outcomes among patients who underwent this procedure. retrospective review of outcomes in pa cisternal drain placement at a single institution. between drain placement. the median hunt-hess score was , but the study population skewed towards large drain dwell duration was . days. radiographic vasospasm occurred in all but one patient ( . %) and developed meningitis/ventriculitis, none fatal. the mean length of stay in the icu was . days. sixteen patients ( . %) were discharged home, twenty-one to acute rehab ( . %), one to subacute rehab ( . %), and two died ( %). among survivors, shunt-dependency occurred in / ( . %), compared to the . %- . % range reported in prior literature. in the study population, cisternal drains appear to be safe as measured against historical cohorts, with comparable or lower shunt-dependency rates. this suggests the viability of further prospective studies to determine the appropriate population for and role of cisternal drainage in the management of asah. estimates of seizure onset after aneurysmal subarachnoid hemorrhage (asah) vary widely, reported rates range from % to %. moreover, seizures increase mortality and disability in patients with asah regardless of common asah complications such as: rebleeding, delayed cerebral injury and vasospasm. we sought to establish the frequency of seizures in asah patients, along with their impact over prognosis, during hospitalization and upon discharge. a retrospective review of consecutive patients with asah admitted to the baylor st. luke's medical center between january and december was conducted. subject demographics, admission gcs, admission mrs, incidence of clinical seizures and clinical outcome at discharge were recorded. associations between the presence or absence of clinical seizures and outcome, measured by the glasgow outcome scale (gos), were investigated using a multivariate logistic regression model. patients with asah were included. clinical seizures were identified in subjects ( . %). outcome was significantly worse for subjects who experienced a clinical seizure compared to subjects who remained seizure-free during hospitalization, poor outcome (gos< ) was found on . % and % respectively (or . , ]; p= . ) this increased risk was significant after controlling hospice, death) was more common for the seizure group compared to the seizure-free group, . % vs . % respectively, however this difference did not reach significance (or . , ]; p= . ) our results showed a low frequency of clinical seizures ( . %) after asah, when compared to other series that have identified an increased incidence of seizures through multimodal approaches. as indexed by gos, along with a non-significant trend towards an unfavorable discharge disposition, among patients with seizures. vasospasm and delayed cerebral ischemia (dci) account for % of the morbidity and mortality after aneurysmal subarachnoid hemorrhage (asah). perfusion ct has been shown to be useful in identifying vasospasm, but this technique is less sensitive to microvascular perfusion changes. mr perfusion (mrp) has been increasingly used in the acute ischemic stroke population and avoids ionizing radiation. we hypothesized mrp may predict the presence of vasospasm by providing measures of impaired cerebral perfusion. we performed a retrospective cohort study with consecutive asah patients between december and august . patients who underwent mrp for concern of dci followed by digital subtraction angiography (dsa) within hours were included. quantitative volumetric analysis was performed at several thresholds of cerebral for the presence of a tmax> lesion. exact wilcoxon rank sums test was used to compare perfusion volumes between patients treated endovascularly versus not treated for vasospasm. we identified patients with a total of mri studies meeting inclusion criteria ( patients treated, patients not treated). no tmax> s hypoperfusion lesion was identified in the untreated group, while / ( %) of the treated patients had at least some delay of tmax> s (p= . ). performance of mrp to detect vasospasm was sensitivity . ( %ci . - . ), specificity . ( %ci . - . ), ppv . ( . - . ), npv . ( %ci . requiring treatment for vasospasm. significant perfusion delay by tmax > s is present in patients requiring endovascular vasospasm treatment after asah. these results suggest that mrp may be a useful tool for patient triage for vasospasm therapy, and further studies are indicated for comparison to other screening methods for vasospasm. recent studies have suggested inflammation and immune dysregulation are important pathophysiology in aneurysmal subarachnoid hemorrhage (asah), and neutrophil to lymphocyte ratio (nlr) was considered as significant clinical predictor of unfavorable outcome including delayed cerebral ischemia (dci). we analyzed nlr of asah patients during ttm, and proposed that the changes in nlr may reflect therapeutic effect of ttm in asah. this retrospective single-center study included asah patients from november , to may , , among which patients underwent ttm after surgical procedures, and other patients didn't undergo ttm. target temperatures were . °c to °c and the durations of ttm were to days. we reviewed the changes of nrl of each patient during ttm and identified whether they had dci, and analyzed in-hospital outcome and -month outcome as measured by the modified rankin scale (mrs). there was no statistically significant difference of overall outcome between ttm group and non-ttm group, but ttm group showed slightly lower rate of dci and better functional outcomes. among the patients, patient who developed dci had higher nlr, and the decreasing rate of nlr was higher in ttm group than non-ttm group. higher decreasing rate of nlr in asah patients while undergo ttm may show the therapeutic effect of ttm. monitoring the trend of nlr value may be helpful in predicting the prognosis of asah patient and estimate the efficacy of ttm for individual patient. eventually, nlr may play important role in deciding practice strategy while treating ttm in asah patients. hydrocephalus is generally regarded as a progressive or static process, but there are few reported cases of transient obstruction of the ventricular system. here, the authors present a rare case of spontaneous symptomatic obstructive hydrocephalus that self-resolved. additionally, a brief review of the literature is performed. records of the patient presented were reviewed in a retrospective manner for all relevant information. pubmed was then searched for all relevant articles. here, we discuss the case of a gentleman in his late 's who presented with worsening confusion and lethargy in the setting of spontaneous subarachnoid and intraventricular hemorrhage. pre-hospital medication includes a daily fish oil supplement; he takes no anticoagulation or antiplatelet agents. approximately one year prior to admission, he experienced an episode of spontaneous left temporal intracerebral hemorrhage. this was attributed to amyloid angiopathy, as evidenced by multiple microbleeds observed on susceptibility weighted imaging at that time. the patient's neurocognitive status steadily declined admission, and he eventually became obtunded. in the process of transferring the patient to the intensive care unit for intubation and external ventricular drain placement, he suddenly became more awake and interactive. the patient's clinical symptoms completely resolved within - hours. no surgical intervention was undertaken. repeat head ct demonstrated that blood products seen in the third ventricle on previous imaging had now migrated into the fourth ventricle. lateral ventricular size had decreased from the prior scan. the following morning, his family members commented that the patient was back to his baseline. transient episodes of obstructive hydrocephalus have rarely been reported in the literature, and are generally associated with an inciting event such as trauma or hemorrhagic stroke. it is possible that there is a higher incidence of transient hydrocephalus, but medical/surgical interventions are performed before the condition is permitted to resolve on its own. raised intracranial pressure (icp) can be a dire consequence of extensive neurologic injury. medical management of elevated icp using intermittent doses of . % hypertonic saline (hts) and/or mannitol is relatively safe and effective for treating refractory intracranial hypertension. at our institution, prior to escalating to sedation and paralysis, hts and mannitol are scheduled. in this study, we aim to describe our experience with scheduled . % hts. methods doses of . % hts during acute admission were included in our retrospective evaluation. only patients who received scheduled . % for anticipated or acute elevated icp in the setting of high-grade subarachnoid hemorrhage (sah) were included. the primary outcome was to characterize efficacy of sustained icp control, by measuring frequency of icp > mmhg and need for escalation of icp management. safety outcomes included incidence of hypernatremia (sodium > meq) and metabolic acidosis. seven out of ( %) patients who received intermittent scheduled doses of . % hts were in the setting of highwere greater than mmhg and no patients required escalation of icp management for the duration of therapy. the median number of doses and duration of . % hts therapy were doses and days (iqr . than meq and patients ( %) developed metabolic acidosis in the setting of hyperchloremia. administration of scheduled intermittent . % hts in the setting of high-grade sah is relatively safe and achieves sustained icp control without need for escalation of icp management. comparative studies of scheduled intermittent . % hts vs alternative medical therapies for icp management are warranted. use of contrast-enhanced computed tomography (ct) studies to evaluate neurological disorders have increased due to its non-invasiveness, fast image acquisition, easy accessibility, and minimal complications. one such procedure is ct myelogram that delineates the extent of spinal stenosis and helps in neurosurgical planning. however, it can result in intracranial migration of contrast medium leading to contrast-induced-encephalopathy (cie). we report cases mimicking as subarachnoid hemorrhage after ct myelogram who subsequently developed cie. case : a -year-old man with chronic low back pain (clbp) was evaluated for confusion, headache due to "intracranial bleed". ct showed diffuse cerebral edema and hyperdensity in the subarachnoid space. external ventricular drain (evd) was placed for suspected post-sah hydrocephalus. however, ct and ct angiogram did not show any cerebrovascular malformation. the patient developed severe encephalopathy and left hemiparesis. repeat ct head showed worsening cerebral edema and hours prior to presentation. severe cerebral edema and left hemiparesis necessitated the use of dexamethasone with improvement in clinical symptoms and examination returning to near baseline. case : a -year-old man with clbp was admitted for "sah" and associated cerebral edema with hydrocephalus. the initial presentation was confusion, double vision, and headache. ct showed diffuse cerebral edema with sulcal effacement, loss of basal cisterns and dilated lateral ventricles. ct and ct angiogram did not show a days prior to presentation. evd placed for hydrocephalus was quickly weaned off the improvement of ventriculomegaly. the patient was discharged with complete resolution of symptoms. cie should be suspected in patients with encephalopathy after ct myelogram. non-contrast ct head is to be interpreted in conjunction with clinical history to avoid unnecessary procedures that might further worsen cie. seizures and ictal-interictal continuum (iic) activity may impact recovery from acute brain injury (abi). empiric antiepileptic drug (aed) intensification for electrophysiologic activity of uncertain significance is challenging to evaluate given structural neurologic deficits, variable pharmacodynamics, and potential sedative effects. we analyzed the eeg and electronic medical records to identify electrographic biomarkers predicting clinical response to aed therapy. we ascertained patients undergoing continuous electroencephalography (ceeg) during admission for abi from a prospective big data repository of clinical data including regularly sampled glasgow coma scale (gcs) scores and med -specific spectral power (alpha - hz, theta - hz, and delta . - hz) and graph theoretical metrics of eeg functional connectivity were compared at time intervals before and after aed therapy. patients met inclusion criteria. , aed doses were administered (mean . +/- . unique aeds per patient). initiating the first aed was followed by a . -point average improvement in gcs (p= . x - ); initiating a second or third aed yielded no significant change, and adding a fourth, fifth, or sixth aed was followed by a . -point worsening in gcs (p= . ). improvement in gcs hours after aed administration was heralded by decline in eeg delta power and rise in network density in the hour following treatment. decline in gcs was heralded by an early rise in delta power and decline in network density. patients with the highest tertile of eeg improvement (greatest combination of rising eeg density and declining delta power) had a consistently improving gcs trajectory in the hours following medication administration, whereas those in the lowest tertile had a consistently worsening gcs trajectory. empirically intensifying aed treatment for disorders of consciousness after abi has diminishing benefit after the initial agent. quantitative eeg biomarkers of early treatment response appears to robustly predict clinical response following aed treatment. new-onset refractory status epilepticus (norse) describes patients with no seizure history who develop refractory status epilepticus (se). the majority progress to super refractory status epilepticus (se). we present a single-center case series of super refractory norse patients to highlight unique features of this group. retrospective chart review was performed to identify adults (age> ) admitted to the columbia university neurological icu from / - / who required continuous midazolam infusions for treatment of super refractory norse. outcome was defined as modified rankin score (mrs) at hospital discharge. descriptive statistics were performed using microsoft excel. of the cases, %(n= ) had a prodrome prior to seizures (infectious, psychiatric or both). patient age was bimodally distributed with %(n= ) less than years old and %(n= ) over . the most common comorbidity was an underlying autoimmune/rheumatologic condition ( %,n= ), though most patients had no pre-existing conditions ( %,n= ). the average stess score was (standard deviation . ). the majority ( %,n= ) remained cryptogenic despite extensive testing. etiologies were identified in %(n= ) - with nmda encephalitis and two with cns infections. immunomodulatory treatment included steroids in %(n= , started on average days from seizure onset, range - ), intravenous immunoglobulin in %(n= , day , range - ) and plasmapheresis in %(n= , day , range - ). the average icu and hospital stays were (range - ) and (range - ) days, respectively. on discharge, %(n= ) had a good outcome (mrs - ), %(n= ) had fair outcome (mrs - ), %(n= ) had poor outcome (mrs - ) and %(n= ) died. compared to prior studies of all norse patients, our cohort with super refractory se were younger, had more frequent prodrome, longer icu and hospital stays and fewer identified autoimmune/paraneoplastic antibodies. the mortality rate was similar to prior studies, but among survivors, super refractory patients were less likely to have a good or fair outcome. we aimed to assess the management of refractory status epilepticus (rse) in developing (ding) and developed (dev) economies, as the management of this condition is resource intense and poorly standardized. investigators from continents collected a large cohort study of rse patients treated between / - / . case-report-forms were finalized at the annual ncs meeting. rse was defined as se that failed to respond to a benzodiazepine and at least one non-anesthetic antiepileptic agent, and was managed with midazolam (mdz) or propofol(pro). the united nations world-economic-situation-prospect was used to identify sites as being from dev or ding economies. four from dev ( patients) economies were included. patients from dev economies were slightly sicker (stess score . ± . vs. . ± . , p< . ). management of patients from dev economies more frequently involved prolonged eeg monitoring (continuous % vs. %, p< . ) but mdz ( . ± . vs. . ± . mg/kg/h) and pro ( ± vs. ± mcg/kg/min, p< . ) doses were higher in ding economies. breakthrough seizures were more common in ding ( % vs. %, or . , p= . ), but no difference in vasopressor use ( % vs. %; n.s.) or withdrawal seizures ( % vs. % n.s.) was seen. hospital ( ± vs. ± days, p< . ) and icu stays ( ± vs. ± days, p< . ) were longer for patients in ding economies. modified rankin scale at discharge was associated with higher stess scores (p= . ) but did not differ between ding and dev economies. direct comparisons between rse patients managed in ding and dev economies are challenging as the baseline level of illness differed but this dataset provides unique insights into differences in utilization of technology (i.e., eeg monitoring), medications (duration and dosage of anesthetics), and length of stay in different health care systems. larger follow-up studies need to explore matched cohorts and explore differences between private-public hospital settings. unlike most anesthetics ketamine acts as an nmda antagonist. we examine the efficacy of intravenous ketamine in the treatment of rse in a large series. retrospective case series of status epilepticus patients admitted between and who underwent treatment with ketamine, patients underwent multimodality monitoring (mmm). we compared patients with complete seizure cessation after ketamine with those without using chi-square and sample t-test. mean age was +/- years old, % of patients were female. seizure burden was decreased by % within hours of starting ketamine in patients ( %), with complete cessation in ( %). average rate of ketamine infusion was . +/- . mg/kg/h, with duration of . +/- . days. average dose of midazolam was +/- . mg/kg/h. ketamine was started on average +/- day after midazolam. patients without complete seizure control after initiation of ketamine ( / patients) were more commonly cardiac arrest patients % vs % (p=. ), and had lower stess score +/- vs +/- (p=. ). all other characteristics were not statistically significant between the two groups including; age, gender, ketamine infusion dosages and duration, apache score, and midazolam infusion dosages. patients ( %) were weaned off pressors after initiating ketamine infusion. when compared the mmm values h before and after ketamine initiation, intracranial pressure values ( +/- vs +/- ), cerebral perfusion pressures ( +/- vs +/- ), cerebral blood flow ( +/- vs +/- ), and lactate/pyruvate ratio ( +/- vs +/- ) were relatively stable. pbo values increased from +/- . to +/- . in our cohort ketamine infusion had a meaningful decreased in seizure burden in rse. our preliminary data also suggests that ketamine infusion didn't affect the intracranial pressure. continuous eeg (ceeg) is widely used to detect seizures (sz) in patients with acute brain injury. however, studies examining sz and epileptiform abnormalities (ea) using ceeg in acute ischemic stroke (ais) are limited. therefore, we aimed to describe the prevalence of electrographic patterns (sz and ea) in ais and its association with outcomes at discharge. retrospective chart review identified patients with ais who underwent ceeg between / and / . demographics, comorbidities and other relevant clinical factors including nih stroke scale (nihss) and treatment interventions were abstracted. ceeg closest to admission (median days) was reviewed for background, sz and ea (lateralized and periodic discharges (lpds and gpds) lateralized rhythmic delta activity (lrda) and sporadic epileptiform discharges (seds). computed tomography or magnetic resonance imaging of brain closest to the time of ceeg was analyzed for midline shift, hemorrhagic transformation (ht) and cortical involvement. outcomes measures were mortality and functional outcome in modified rankin scale (mrs) ( - good and > poor outcome) at discharge. of the patients, had sz and had ea ( . % lpd, . % lrda, . % gpds and . % seds). those with cortical involvement had higher rate of ea and sz compared to those with subcortical stroke ( . % vs . %, p= . ). no difference was found in sz and ea prevalence with regards to age, sex, nihss, midline shift or ht. overall mortality was . %. absence of posterior dominant rhythm (pdr) was associated with increased mortality ( . % when pdr absent vs . % when present, p= . ). sz and ea did not affect mortality or mrs at discharge. despite high frequency of ea ( %), the risk of sz in ais was low at . % and their presence did not impact functional outcome or mortality. however, eeg background with absence of pdr was associated with increased mortality. nonconvulsive seizures (ncs) are a common complication in patients admitted to neuroscience intensive care units and are associated with worse outcomes. ncs can only be diagnosed with continuous eeg (ceeg) monitoring. intermittent conventional ceeg review by neurophysiologists typically occurs - times a day, therefore patients may be seizing for extended periods of time before the seizure is detected. our study aims to evaluate the accuracy of a quantitative eeg (qeeg) trend, the automated seizure detector (asd) in detecting patients' first seizure, which could aid in rapid detection of ncs. this retrospective study includes review of ceeg and qeeg data from adult patients admitted to a single institution neuro icu who developed ncs on ceeg monitoring. independent conventional ceeg review without qeeg by two board-certified neurophysiologists determined the first seizure occurrence for each patient (gold standard). this was compared to the seizure detection sensitivity of the p asd (persyst, inc., prescott az), an algorithm with no user-adjustable settings. recordings from ncs patients were used. mean age was . years and % was female. seizures had variable durations and spatial extents. the sensitivity of p asd was . % ( % ci . - . ) and specificity was . % ( % ci . - . ). mean false alarm rate was . /hour (sd . ) in the time elapsed from the start of ceeg recording until first seizure occurrence. overall, p asd accurately detected the first seizure in % of patients, disregarding false positives. overall, median time to clinical seizure detection was . hours (iqr . hours). this analysis shows that the persyst p asd may have clinically useful sensitivity and specificity in critically ill patients admitted to a neuroscience icu. in conjunction with a low false alarm rate, incorporation of qeeg asd may lead to a reduction in time for seizure recognition. the incidence of early seizures (es) in traumatic brain injury (tbi) ranges between - %. however, the incidence of es after a non-severe tbi (nstbi) with traumatic hemorrhage (th) is unknown. moreover, the data about seizure prophylaxis (sp) in this population remains inconclusive. we aim to determine the incidence of es in nstbi and the efficacy of sp. we respectively reviewed all adult patients with nstbi with evidene of a th on presentation from to . patients with history of epilepsy or receiving antiepileptic drugs (aed) were excluded. we collected demographic data, the type, severity and mechanism of injury; the need for neurosurgical intervention (nsi); es; and sp use. a total of patients met our inclusion criteria, . % had mild tbi; mean age of . years (sd . ); . % males; and . % had subdural hematoma (sdh). same level fall was the most common ( . %) patients had an es in the sp group ( clinical) vs of ( . %) in the non-prophylaxis group (all clinical) (p = . ). levitiracetam as sp was used in . %. patients with combined sdh and traumatic subarachnoid hemorrhage or with multicompartment hemorrhage were more likely to have es than sdh alone (p = . and . , respectively). nsi was not a predictor for es in our cohort. the incidence of es in nstbi patients in our cohort falls within the previously reported ragne. however, it appears to be higher compared to reported rates for mild tbi. es were more likely in the sp group, which might indicate a clinical selection bias. prospective studies are required to further determine the predictors of es and the effect of sp on outcomes in nstbi patients. patients with psychogenic non-epileptic attacks (pnea) sometimes receive aggressive treatment leading to intubation. this study aimed to identify patient characteristics that can help differentiate pnea from true status epilepticus (se). we retrospectively identified patients with pnea and se who were intubated and underwent continuous had acute brain injury or progressive brain disease as a cause of status epilepticus were excluded. we compared clinical features, treatments and outcome between patients who were intubated for pnea and those who were intubated for se. of , patients who underwent ceeg monitoring, we identified and patients intubated for pnea and se, respectively. compared with patients intubated for se, intubated pnea patients were more likely to ( ) be < years of age ( % vs %, p< . ), ( ) be female ( % vs %, p< . ), ( ) be white ( % vs %, p< . ), ( ) have a history of a psychiatric disorder ( % vs %, p< . ), ( ) have no history of an intracranial abnormality ( % vs %, p< . ), and ( ) have a maximum systolic blood pressure < mm hg ( % vs %, p< . ). patients with - of these risk factors had a % ( / ) likelihood of having pnea, those with - had a % ( / ) chance of having pnea, and those with - had an % ( / ) chance of having pnea. sensitivity for pnea among those with - risk factors was % and specificity was %. pnea in patients presenting with emergent convulsive symptoms can be predicted with a high degree of certainty based on the presence of specific demographic, past medical, and physiologic risk factors. care should be taken to avoid over-sedation and unnecessary intubation in this at-risk patient population. a recent systematic review indicates that the mortality of status epilepticus (se) is about . % with a non significant downward trend in recent years. mortality has not changed much despite aggressive management. this study investigates trends and predictors of in-hospital mortality due to status epilepticus at national level in united states. we performed a cross-sectional analysis using the nationwide inpatient sample (nis), - , of us adult hospitalizations with status epilepticus. annual rate of in-hospital mortality was calculated using nis weighting. we identified our status epilepticus patient subset from using codes (dx = . ) from the international classification of diseases, th edition. potential factors associated with in-hospital mortality were assessed using logistic regression. of , hospitalized patients with status epilepticus, , ( . %) died during the index hospitalization. across - , . % of se patients died; with a downward but not statistically significant trend in-hospital mortality from . % ( ) to . % ( ) (p = . ). se patients with inhospital mortality were more likely to be women, older, and with a higher proportion of medical comorbidities, in-hospital complications and extreme loss of function as per all patients refined diagnosis al failure, apr drg severity, mechanical ventilation, tracheostomy, sepsis, pulmonary embolism, acute kidney injury and respiratory insufficiency. mortality due to se was lower than previously reported. mortality has had a non-significant downward trend in the years studied. age, female gender, medical complications and poor baseline functional status are important predictors. availability of aggressive treatment has not modified significantly mortality which requires further study. pregabalin (pgb) is an approved adjunctive treatment for focal epilepsy in adults. pgb lacks drug-drug interactions, has a favorable safety profile and can be rapidly titrated-attractive characteristics for its use in the neurocritically ill. however, data remain limited regarding its use in the icu setting. we are sharing our experience with pgb in neurocritically ill patients with refractory seizures. charts of eight adult patients admitted received pgb were reviewed retrospectively. demographics, antiseizure drug (asd) regimen, and h of eeg data pre-and post-pgb were analyzed descriptively. the cohort comprised eight patients ( females) with mean age of . years. mean icu stay was . days. three patients underwent a neurosurgical procedure related to their primary admission diagnosis, an asd prior to first seizure captured on eeg. prior to pgb, patients had failed on average ( - ) other asds trials. pgb was dosed - mg/day in - divided doses, following a load of - mg. pgb lead to a significant reduction on hourly median seizure burden: . to seizure/h and . to . min/h. pgb led to complete seizure cessation in patients within h and in out of within h of administration. pgb allowed for de-escalation of asd regimen in out of patients. pgb was well tolerated with the exception of mild sedation in patients, which did not warrant further intervention/neurodiagnostics. in this critically ill cohort with refractory seizures, pgb successfully aborted seizures in % of patients. include prospective pregabalin treatment protocols. to describe the first known reported case of utilization of electroconvulsive therapy (ect) to treat super refractory status epilepticus (srse) in pregnancy. we present the case of a year old caucasian female at weeks gestation with pmh focal and generalized seizures who was treated for srse successfully with ect after failed pharmacological treatment. the most likely etiology of srse was sudden cessation of medications upon pregnancy. eeg showed types of seizure activity: rhythmic theta waves over right temporal region with evolution and independent generalized seizures. treatment included use of approximately antiepileptics including , propofol, pentobarbital, magnesium, ketamine, topiramate and valproic acid over the course of days in addition to modifying epilepticus remained super refractory with appearance of mixture of sharp waves on weaning off sedation. she underwent ect with right unilateral electrode placement on day with remarkable improvement in eeg pattern and resolution of srse with single session. patient was back to baseline level of awareness at the time of discharge. on follow up in clinic, she had significant improvement in seizure control with normal fetal development and delivery. treatment of status epilepticus in pregnancy is challenging given the unknown effect of prolonged sedation or hypothermia on fetal development. alternative treatments like ect, vns, dbs, ketogenic diet and hypothermia are sporadically used. use of ect is not considered first or even second line treatment in srse, despite its safe profile, especially in pregnancy. this case adds to the available literature on the success of ect for treatment of srse and puts emphasis on the need for a clinical trial regarding use of ect in srse. the importance of neurocritical care (ncc) has been recognized. but no dedicated educational system for it exists in japan. we have established version of an educational ncc hands-on seminar. this study investigated its effects. this study was a prospective, before-after study using questionnaires and examinations. it was a full-day version . the learning concept was to identify the various methods for maintaining cerebral oxygen balance to prevent secondary brain injury. participants attended five skill sessions: intracranial pressure monitoring, trans-cranial color flow image, targeted temperature management, neuro examination, and eeg, and four scenario sessions: post-cardiac arrest syndrome, subarachnoid hemorrhage, traumatic brain injury, and non-traumatic acute weakness. they had examinations before and after the seminar. the primary outcome was the improvement on examination scores after the seminar. secondary outcomes were the degrees of satisfaction with it and confidence of participants in ncc. we evaluated the improvement of the outcome using wilcoxon signed rank test. a p-value of . or less was considered as significant. thirty-nine physicians and one nurse participated in the seminar. we excluded ( . %) participants because their answers were incomplete. we had ( . %) physicians who are in emergency or intensive care medicine, and ( . %) other professionals. their median age group was in their s (iqr: - ) with median intensive care medicine experience of years (iqr: . - . ). the percentage of correct answers, scores in the examination, improved significantly from (iqr: . - . ) to (iqr: . - . ) after the seminar (p< . ). eighteen ( . %) participants were satisfied with it, and the number of professionals who could not feel ncc-confident decreased from ( %) before the seminar to after its completion (p< . ). our seminar successfully improved the physicians' knowledge of ncc, and gave them more confidence in ncc. glutamic acid decarboxylase (gad) is the rate-limiting enzyme to convert glutamate to gammaaminobutyric acid (gaba). autoantibodies targeted against gad have been implicated in a number of syndromes with neurologic manifestations including stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and epilepsy. we highlight an atypical presentation of this rare disorder with several unique features to the neurological intensive care unit. -year-old woman with pmh of dm, remote left insular ischemic stroke, and recent right leg dystonia presented after being found down with rightward eye gaze deviation, gtc shaking, and urinary incontinence. she required midazolam, lorazepam, loading doses of levetiracetam and fosphenytoin, and propofol infusion to achieve clinical seizure control. despite these interventions, eeg showed ncse with left temporal seizures and anterior midline epileptiform discharges. propofol was titrated to burst suppression. she had several other active medical problems including kidney injury, transaminitis, and myoclonus. seizures and myoclonus were greatly improved after the addition of clonazepam; however, she remained encephalopathic. pertinent diagnostic results included ferritin , ng/ml, ldh , units/l, il- r u/ml, b -micr and serum gad ab titer nmol/l. mri brain showed prominent superior frontal lobe cortical edema. bone marrow biopsy demonstrated good cellularity without malignancy. skin biopsies on three random samples were positive for perivascular dermatitis with telangiectasia. she was started on high dose steroids with subsequent progressive mental status improvement. anti-gad ab associated vasculitis is an exceedingly rare occurrence whose diagnosis previously involved brain biopsy. this case is unique given her acute presentation with refractory status epilepticus, systemic involvement, and diagnosis on skin biopsy. while management has involved immunotherapy, specific treatment guidelines do not exist. given her marked response to clonazepam and corticosteroids, we advocate for early initiation of gabaergic medications such as benzodiazepines and use of immunotherapy. epileptic seizures are a serious complication in patients with subdural hemorrhage (sdh), resulting in increased mortality rates. the incidence of new onset seizures in these patients is unclear. we examined the incidence for new onset seizures and status epilepticus (se) in sdh patients. we examined patients diagnosed with sdh and epilepsy between september to december . we included patients with new onset seizures and extracted those who had seizures after sdh evacuation. clinical and radiographic characteristics, and outcomes of those patients were described. we screened patients diagnosed with sdh, traumatic or non-traumatic. underwent a surgical intervention and ( %) patients had a seizure during their hospital stay. among those who had a seizure, patients had prior history of epilepsy, and had a new onset seizure. although sdh patients with history of epilepsy showed higher incidences of seizures than those with no history (p= . ), sdh patients with history of epilepsy mostly did not evolve into se and those who had no history of epilepsy usually did. there was no significant difference in patients developing se when compared to those without se between the sdh thickness, midline shift, temporal lobe involvement or age of blood (acute or chronic). seizure occurrence in patients with sdh is commonly new onset; however, they are infrequent. in addition, sdh patients with no history of epilepsy have a higher tendency to develop se as opposed to patients with history of epilepsy. larger multicenter cohort studies need to be done for evaluation of these findings. sequoia hospital in redwood city, ca implemented the ceribell rapid response eeg system in to expand its access to eeg for in-patient usage. previously, the hospital had no access to after-hours eeg and the majority of their eegs happened in the icu. this quality improvement project was initiated to understand how access to rapid eeg impacted clinical care and financial metrics across at sequoia hospital. data was analyzed for all patients who received either conventional or ceribell eeg from january , including the department where eeg was conducted, time of day of eeg was ordered, time when eeg began, and clinical diagnosis based on the eeg. data was also captured on patient transfer due to lack of eeg. % of eegs were ordered after hours after the introduction of ceribell, compared to nearly no eegs done after hours before ceribell. % of patients with ceribell eegs were diagnosed with seizures. in , of ceribell eegs, eegs occurred in the in-patient unit or ed. in % of patients with a high suspicion of seizure, seizures were ruled out as a result of reading the ceribell eeg. the introduction of ceribell eegs has greatly expanded access to eegs at sequoia hospital. before ceribell was introduced, eegs mostly occurred in the icu and nearly all happened during regular hours. after ceribell was introduced, eeg was also heavily utilized in the ed and the in-patient unit and gave sequoia eeg access during after hours. as a result of this expanded access and earlier application of eegs, patients have been treated more appropriately. tranexamic acid (txa) is an intravenous antifibrinolytic agent that is used routinely for elective surgery. we report a case of inadvertent intrathecal injection of txa resulting in refractory status epilepticus. case report. a -year-old healthy female admitted for bilateral total knee replacement was inadvertently administered mg of txa intrathecally instead of bupivacaine. soon after administration, she intubated, administered levetiracetam, started on a propofol infusion, and transferred to the neurointensive care unit (nicu). she developed persistent spontaneous and stimulus induced generalized myoclonus refractory to propofol. midazolam infusion was added. nchct and cta demonstrated pneumocephalus, but no acute arterial or venous thrombosis or stroke. veeg revealed generalized nonconvulsive seizures occurring once per minute, not correlating with spinal myoclonus . propofol and midazolam infusions were increased to mcg/kg/min and . mg/kg/hr, respectively, to achieve burst suppression, and valproic acid was added. over the following week, the drips were adjusted to suppress seizure activity. by hospital day , she was weaned off all infusions without recurrence of seizures. by hospital day , she was on levetiracetam monotherapy. she was discharged to rehab after a -day hospital course, and was discharged home days after initial presentation. residual deficits at the time of discharge included mild cognitive impairment and gait instability. she remains seizure-free since hospital day on levetiracetam mg bid. we report a case of refractory status epilepticus and spinal myoclonus after accidental intrathecal txa administration. with aggressive management, the patient survived with mild residual deficits. the mechanism by which txa causes status epilepticus and spinal myoclonus is hypothesized to be related to its inhibitory effects on gaba and glycine receptors, respectively. ictal bradycardia (ib) is a serious complication of temporal lobe epilepsy. if left untreated, ib can cause serious injuries related to syncope, complete heart block and death. management of this phenomenon is controversial: should you treat the seizures or the arrhythmia? we describe the management of a patient who presented with multiple syncopal episodes and found to have symptomatic bradycardia in the setting of temporal lobe seizures. a -year-old male with a recently resected brainstem cavernoma presented with episodes of 'spacing out', face tingling and transient periods of amnesia. he was started on topamax and lamictal. several months later, he began having multiple syncopal events (upwards of a day) that eventually brought him the hospital for evaluation. he was found to be bradycardic with a heartrate in the thirties and had sinus pauses lasting up to ten seconds requiring atropine, an isoproterenol infusion and transcutaneous (tc) pacing. he was also found to have another cavernoma in the right temporal lobe. eeg revealed epileptic activity within the right anterior temporal lobe with correlation to his tc pacing and ib events. lamictal was replaced with keppra and the seizure activity was controlled. he had a pacemaker implanted, after which he did not have any further episodes of syncope and no further seizure activity. the cavernoma was resected a few months later, and he did well postoperatively. ib is an uncommon, but serious, complication of temporal lobe epilepsy. the temporal insula plays a role in the parasympathetic activity of the heart which can cause ib. it may be beneficial for patients who present with symptoms characteristic of temporal lobe seizures or repeated falls/drop attacks to have a full cardiac work up to rule out ib in order to determine if a pacemaker is warranted. the ceeg has had rapid growth within neurological monitoring within the icu, however its still disparate resource in the icus of latin america. is important to know the real situation in colombia about the accessibility to ceeg monitoring. an anonimus survey of questions was conducted from october to april . it was answered by intensivists from latin america, europe, asia and usa. (n= ) considering the accessibility to the ceeg, the ceeg clinical indications and the ceeg monitoring extends (hours) in the icu, we can conclude that colombia is aligned with other countries in the world. in the icus of colombia less than half of the intensivists make decisions in ¨real time¨ with the ceeg and have access to the qeeg modality. the most common cause for non-presciption of ceeg was scarce resources (equipment and human resorces support from a neurology service). cefepime is a fourth-generation cephalosporin with broad-spectrum coverage used to treat infections in critically ill patients. neurotoxic effects have been associated with cefepime, including myoclonus, reduced consciousness, and seizures. we report a case of a patient receiving cefepime who developed non-fluent aphasia and non-convulsive status epilepticus (ncse). two seizure drug trials (levetiracetam and fosphenytoin) failed before marked clinical and electrographic improvement with clobazam. other than cessation of the offending agent, there is little known about the management of cephalosporin associated non-convulsive status epilepticus. data was collected from our institution's health record. a -year-old female with a history of diabetes, chronic kidney disease, recent coronary artery bypass grafting, and mitral valve repair presented with pseudomonas aeruginosa cellulitis of the sternotomy site. on day six of cefepime therapy she developed non-fluent aphasia. mri brain and toxic-metabolic work-up was unrevealing. eeg was consistent with non-convulsive status epilepticus. she failed to respond to standard levetiracetam or fosphenytoin therapy. lorazepam was given with marked improvement in her eeg. clobazam was subsequently started resulting in marked improvement in the patient's language and sustained resolution of ictal pattern on eeg. epileptogenic effects of ß lactam antibiotics are thought to be due to competitive antagonism of the gabaa receptor. beside the recommendation of withholding offending agents when safe to do so, there is no guidance in the literature regarding the appropriate antiepileptic drug choices for the treatment of cephalosporin associated ncse. in this case, clobazam, a benzodiazepine, was an effective treatment. given the theorized mechanism gaba antagonism of cefepime, it is possible that benzodiazepines may ch is needed regarding the optimal seizure control for various etiologies of ncse. when treating seizures and ncse, consideration should be given to the possible mechanism of action of the suspected offending agent. hashimoto encephalopathy is a rare disease. clinical manifestations include abnormal behavior or psychosis, seizures, encephalopathy. pathophysiology is not completely known but it has been associated with autoimmune thyroiditis. we report a case of hashimoto encephalopathy with status epilepticus which responded well to steroids and relapsed following steroid taper. -year-old previously healthy woman was admitted with encephalopathy, new-onset seizures, and delusional behavior for past - weeks. mri brain was unremarkable. eeg showed status epilepticus with right fronto-central origin. she was treated with multiple antiepileptic medications including evaluation for infections, autoimmune and paraneoplastic etiologies revealed elevated thyroid peroxidase, antithyroglubulin and mildly elevated gad antibodies. whole body ct showed no malignancy. she was diagnosed with hashimoto encephopathy. she was treated with iv steroids and ivig. her clinical improvement correlated with decrease in thyroglobulin antibody levels from . to . and thyroid peroxidase antibody levels from . to . . she was discharged on oral steroids and admitted again in few weeks with a relapse of behavioral issues and seizures following steroid taper. she was treated with high dose iv steroids, this time followed by rituximab with significant improvement. she was discharged again on oral steroids with very slow taper and close follow up. our patient had hashimoto encephalopathy and had relapse following taper of steroids. hashimoto encephalopathy is rare condition and is often under-diagnosed. anti-thyroglobulin and thyroid peroxidase antibodies should be checked in patients where no other etiology of new onset status epilepticus is identified. along with seizure management, they should be treated with immunomodulators. closer follow up is needed while tapering the steroids as relapse can occur with behavioral issues and seizures and they may benefit from steroid sparing long term immunomodulatory treatment. non-convulsive seizures (ncszs) and non-convulsive status epilepticus (ncse) are common in critically ill patients. both are associated with neurophysiological disturbances, and even mortality if untreated in a timely manner. [ ]continuous electroencephalogram (ceeg) monitoring has been proven to be effective in diagnosing ncszs and ncses, and assessing the efficacy of treatment thus it is a vital investigation. [ ] we conducted a national survey on the availability of ceeg monitoring within neuro critical care units (nccu) in the uk. to ensure accuracy the consultant in charge or st - covering the nccu was contacted by telephone and asked a serious of questions regarding their use of ceeg and reporting. hospitals were identified as having either stand alone or mixed nccu. responses were obtained from of the units contacted. only % of nccus were able to perform ceeg monitoring from am- pm this dropped to % at night. in % of nccus the itu consultant did not feel confident to analayse the ceeg and make treatment decisions based upon in. the inability of % of nccu to perform ceeg is very concerning, as a single eeg may miss episodes of status, and also makes treatment to achieve burst suppression very difficult. in addition, there appears to be a training gap in ability of icu doctors ability to interpret ceeg. commissioning standards may need to be modified to encourage take of this vital monitoring technique. in addition systems such as possibly setting up a central remote analysis site for all ceeg data for england might improve time to diagnosis and treatment whilst still remaining economically. traumatic brain injury (tbi) is the leading cause of disability in children. neuroimaging is essential for the acute evaluation of moderate-severe tbi, although its prognostic utility is unclear. magnetic resonance imaging (mri) allows for detailed characterization of diffuse axonal injury (dai), the hallmark pathology described in non-penetrating tbi. higher dai grade in adults correlates with worse outcome, but this association has not been rigorously tested in children. we hypothesize that acute rotterdam score and dai grade predict short-term functional outcome in children with acute tbi. patients admitted to stanford children's hospital for acute tbi were identified via retrospective chart review based on icd and icd codes for tbi. inclusion criteria were age > mo and < yrs with blunt, closed head trauma and mri brain obtained during hospitalization. exclusion criteria included history of epilepsy, prior tbi, developmental delay, and penetrating or non-accidental trauma. the first head ct and brain mri obtained during hospitalization were used for analysis of rotterdam score and dai grade, respectively. discharge destination (home versus facility) was used as a marker of short-term functional outcome. multiple logistic regression analysis on cohort of children revealed that lower gcs and ventriculostomy were independent predictors for discharge to acute rehabilitation (or . and , respectively) versus discharge home. neuroimaging analysis revealed that more severe dai significantly correlated with discharge to a rehabilitation facility (p= . ), while rotterdam ct score did not correlate with discharge destination (p= . ). our study demonstrates that higher dai grade is associated with worse short-term outcome in pediatric patients understand the short-and long-term prognostic value of acute neuroimaging in pediatric tbi. , niteroi, brazil zika virus has been associated with several neurological complications. we aim to present three cases of zika associated subacute encephalitis, all requiring intensive care. all patients derived from the rio-zikv-gbs study cohort. all were diagnosed with mac-elisa and pcr for case : -year-old man admitted with lower extremities weakness and urinary retention, preceded by -capsular area, extending to the corona radiata and cerebellar peduncles. he was treated with a -day cycle of intravenous immunoglobulin (ivig). he was discharged one year later due to protracted weaning from mechanical ventilation. case : -year-old man admitted with lower extremities weakness, dysphagia, and dysphonia. days before he presented with and middle cerebellar peduncles, extending to pyramidal tracts. he was treated with ivig. he was discharged after acute treatment and, one year later, presented only with ataxic gait. case : year-old woman admitted with disorientation and behavioral impairment. a week before she presented with % mononuclear) with mild protein elevation. mri revealed hyperintense -t levels. she was also treated with ivig. a year later her neurological exam returned to baseline. all patients had similar clinical presentation, starting with atypical measles syndrome, later evolving to a subacute encephalitis. all showed similar radiological findings, resembling the ones observed with japanese encephalitis, another flavivirus. this new entity is likely a result of zikv-mediated autoimmune activation and it is a challenge for neurocritical care units worldwide. there are two described forms of necrotizing encephalopathy: multifocal necrotizing leukoencephalopathy (mnl) and acute necrotizing encephalopathy (ane). mnl is characterized by multiple microscopic foci of white matter necrosis and is sporadic with predilection for the pons in patients with sepsis or immunosuppression. ane is characterized by multiple foci of grey and white matter disease and is either sporadic or familial; it is typically triggered by febrile viral illness in children without evidence of cerebral infection. a case report with review of the clinical, laboratory, radiographic, and pathologic data. a -year-old woman with post-traumatic epilepsy was admitted with acute encephalopathy and respiratory failure secondary to h n and strepotococcal pneumonia. she developed refractory hypoxemia requiring proning and eventually veno-veno extra corporeal membrane oxygenation. her neurological exam declined with no response to painful stimuli and absent corneal reflexes. continuous restricted diffusion lesions of the cerebral white matter, splenium of the corpus callosum, brainstem, cerebellar peduncles, and deep cerebellum. she died after transition to comfort care and autopsy was pursued by family. neuropathologic evaluation revealed microscopic acute and subacute necrotizing lesions throughout the white matter of the cerebrum, pons, and cervical spinal cord. there were similar lesions throughout the thalamus with sparing of other gray matter structures. there was no significant lymphocytic inflammation or meningoencephalitis. this presentation is consistent with mnl, yet the thalamic involvement is more characteristic of ane. however, ane is rare in adults and typically affects both the grey and white matter. our case affected mostly white matter with microscopic lesions in the grey matter of the thalamus. this case is unique in that it has features of both known necrotizing leukoencephalopathies without clear classification. pharmacotherapy after traumatic brain injury (tbi) aims to prevent secondary insults by optimizing brain homeostasis. to better understand the relationships between medication infusions and cerebral dynamics, we investigated their associations with cerebral compliance (cc), autoregulation (ca) and heart-rate variability (hrv). a retrospective analysis of severe tbi patients admitted to the pediatric icu who underwent brain multimodal monitoring was performed. ca, cc and hrv were estimated by using different parameters: ca by using the pressure reactivity index -a pearson correlation coefficient; cc by using the rap indexa correlation between icp and pulse amplitude; hrv by heart-rate root mean square of successive differences. analysis of variance was used to investigate cerebral dynamics differences during narcotic/sedation (dexmedetomidine, fentanyl, propofol), barbiturate (pentobarbital), vasoactive (epinephrine, milrinone, nicardipine, norepinephrine, phenylephrine) and paralytic (vecuronium, rocuronium) medication infusions. children were identified ( female; ages - years). ca values were significantly higher (i.e. larger positive values) in patients who received vasoactive infusions than those who did not (epinephrine ( . ± . ), norephinephrine ( . ± . )). cc values were much larger (closer to ) in patients who received barbiturate and paralytic infusions compared to those who received narcotic/sedation infusions (pentobarbital ( . ± . ), vecuronium/rocuronium ( . ± . ), fentanyl ( . ± . ), dexmedetomidine ( . ± . ), propofol ( . ± . )). hrv displayed significantly larger values in patients who received narcotic/sedation infusions compared to those who received barbiturate infusions (propofol ( . ± . ), dexmedetomidine ( . ± . ), pentobarbital ( . ± . )). these results suggest vasoactive infusions (epinephrine and norepinephrine) are associated with impaired ca, narcotic/sedation infusions (dexmedetomidine and propofol) are associated with improved cc and greater hrv, and barbiturate infusions (pentobarbital) are associated with impaired cc and less hrv after severe tbi. prospective analysis is needed to validate these associations and investigate whether these medications may be contributors or epiphenomena of altered cerebral dynamics. sleep wake disturbances (swd) after pediatric traumatic brain injury (tbi) requiring critical care admission are poorly quantified, but may have important implications for patient recovery. we conducted a systematic review to quantify swd after pediatric tbi requiring critical care, identify interventions for swd, and determine the association between swd and other post-intensive care syndrome (pics) morbidities after tbi. injury requiring neurocritical care published after and reporting a sleep or fatigue outcome. studies focused on concussion or mild tbi without differentiation of intracranial injury requiring critical care hospitalization were excluded. risk of bias was assessed for included studies. a meta-analysis was not performed due to heterogeneity of included studies. search results yielded articles. abstract review yielded articles, and studies were included in the final analysis ( observational, case reports). we found children with tbi had significantly more swd when compared to controls. studies reported over one third of tbi patients have swd, some persisting for years after injury, but often failed to delineate phenotypes of sleep problems. most studies used subjective measures with questionnaires or interview. seven studies used a validated sleep questionnaire. three studies with total patients presented objective data on swd using actigraphy (n= ), polysomnography (n= ), and electroencephalography (n= ). outside of one case report, no studies evaluated interventions for swd following pediatric tbi. swd in children surviving tbi were associated with pics morbidities including reduced quality of life, behavioral problems, and neurocognitive impairment. heterogeneity and risk of bias among studies was high. research is needed to quantify swd, including identifying phenotypes and utilizing objective measures of sleep. evaluation of pharmacological, psychological, and behavioral interventions for swd is warranted given associations between swd and pics. current guidelines for pediatric severe traumatic brain injury (tbi) recommend maintenance of mean intracranial pressure (icp) under mmhg. increasing evidence has suggested that icp waveform characteristics may be important in understanding the impact of pressure on cerebral physiology. our study objective is to investigate strength of association of brain tissue oxygenation with icp waveform characteristics. retrospective analysis was performed on pediatric patients with tbi who underwent multimodality monitoring including measurements of pbto and icp between january , and january , . data were limited to relatively normal values of pbto between and mmhg and icp values between and mmhg. univariate linear regression was performed to assess strength of association between pbto and icp waveform characteristics including, mean icp values, icp pulse amplitude (amp), and minimum and maximum values of the icp waveforms. patients were identified ( female, ages - years [mean . ; interquartile range . - . ]). pbto was negatively associated with all icp characteristics following analysis. the correlation coefficient (r) was stronger with respect to the relationship of pbto to amp (r = - . ) as compared to mean icp (r = - . ), maximal icp (r = - . ) and minimal icp (r = - . ). p-values were < . for all measurements. these data provide preliminary evidence that icp pulse amplitude is associated with pbto . these findings suggest that icp waveform amplitude should receive greater scrutiny in understanding the impact that icp has on pbto after pediatric severe tbi though further research is necessary to confirm this finding. sarcoidosis is a systemic disease characterized by formation of noncaseating granulomas. in - % of cases, sarcoid infiltrates the central nervous system causing a myriad of clinical symptoms and imaging findings. although rare, neurosarcoidosis commonly involves the brainstem, hypothalamic-pituitary axis, leptomeninges, and spinal cord, causing symptoms such as cranial neuropathies, hypopituitarism, aseptic meningitis, and seizures. based on the review of literature, neurogenic shock as a complication of neurosarcoidosis has not been previously reported. a retrospective chart review was performed on the patient's medical records to obtain laboratory results, imaging studies, and treatment modalities. we demonstrate a case of neurosarcoidosis that initially presented with neurogenic shock, seizure-like activities, and anterograde amnesia. a -year-old african american man with neurogenic shock and seizure-like activities was transferred to our neurointensive care unit. initial workup revealed panhypopituitarism, including hypothyroidism and central diabetes insipidus. mri of neuro-axis was significant for diffuse parenchymal and leptomeningeal enhancing lesions of unclear etiology, including the hypothalamic-pituitary axis, bilateral mesial temporal lobes, and cervical spinal cord. he was intubated for airway protection and treated with dopamine infusion for hypotension and bradycardia thought to be a manifestation of neurogenic shock from his extensive cervical spinal cord lesion. despite significant cervical cord involvement, he remained with good strength throughout. he was extubated after a short course of high dose steroids and stabilization of electrolytes and endocrine function however was found to have anterograde amnesia -pet revealed hypermetabolic lymphadenopathy throughout the neck, chest, abdomen, and pelvis without cardiac involvement. he subsequently underwent lymph node biopsy which revealed noncaseating granulomas. neurosarcoidosis is an infiltrative disease process with varied clinical and imaging presentations. although neurogenic shock is classically seen as a complication from spinal cord injuries above the t segment, neurosarcoidosis affecting the cervical spinal cord can also present with neurogenic shock. the primary goal of traumatic brain injury (tbi) management is the prevention of secondary injury achieved by invasive intracranial pressure (icp) monitoring. near infrared spectroscopy (nirs) is a continuous, noninvasive surrogate measure of cerebral blood flow and oxygenation making it a potentially useful adjunct in the management of tbi. we aimed to determine the association between regional oximetry (rso ) and icp in pediatric tbi. the association between rso and icp was estimated retrospectively in pediatric patients with severe tbi. digital record using univariate dynamic structural equations modeling with a % credible interval ( % ci) for the standardized regression coefficients (src). of study patients had documented events. the association between rso and icp varied between patients and event type. no events triggered by changes in rso occurred. a significant positive (src= . , % ci= . - . ; src= . , % ci= . - . respectively). a negative r this was not significant (src=- . , % ci=- . - . ). during times without intracranial hypertension, changes in icp were positively associated with changes in rso , which may be related to changes in cerebral blood flow. our results also suggest that cerebral desaturation may be seen during periods of intracranial hypertension. our data supports the utility of nirs as an adjunct to understanding changes in icp, however further research is needed to determine if these findings are clinically relevant. rapidly progressive (< hours) primary angiitis of the central nervous system (pacns) has rarely been reported in the literature. most cases have resulted in death. here, we describe the neurocritical care course of a patient with rapidly progressive pacns who survives with a good outcome. data was collected prospectively through direct patient care and chart review. a -year-old previously healthy male presented to an emergency room in acute coma. initial head ct showed diffuse cerebral edema and a left thalamic intracerebral hemorrhage. non-contrast brain mri c perivascular enhancement suggestive of cerebral vasculitis. an external ventricular drain was placed for intracranial pressure monitoring and cerebrospinal fluid sampling, which showed a neutrophilic pleocytosis (wbc= , % pmn). brain biopsy on hospital day (hd) # was consistent with a diagnosis of necrotizing pacns. rheumatologic evaluation was negative for systemic inflammatory disease. therapy included methylprednisolone, plasma exchange, and cyclophosphamide. his hospital course was complicated by ventilator-associated pneumonia, thrombocytopenia, cerebral salt-wasting, and malignant intracranial hypertension which was treated with hypertonic therapy, barbiturate coma, and hyperintensities and resolution of perivascular enhancement. he required tracheostomy and percutaneous gastrostomy and was discharged to a ventilator facility on hd # . on discharge, he was awake and texting on his cell phone. at -month follow-up, his modified rankin score was . our case demonstrates that rapid diagnosis, early immunosuppressant therapy, and aggressive neurocritical support in collected on the optimal therapy of the patients with rapidly progressive pacns. , detroit, mi, united states cerebral amyloid angiopathy (caa)-related inflammation, or cerebral amyloid angiitis is an uncommon disease that presents with acute symptoms secondary to a solitary area of vasogenic edema. this series examines patients presenting with acute neurological symptoms and imaging out of proportion to their exam, suggesting this is a common trend in this diagnosis. cases were collected through epic review, using slicer/dicer to select patients with both snomed diagnoses of caa and cns vasculitis, and snomed diagnosis of caa concurrently treated with prednisone - . cases: ( ) year old female with prior diagnosis of caa presents with transient worsening of right arm dexterity and word-finding difficulty. ( ) year old female presented with loss of vision in the right eye lasting for hours ( ) year old female presents with two days of word-finding difficulty and confusion, using her car remote for her television ( ) year old male presenting after being unable to find words and acting out for two days ( ) year old male with prior diagnosis of caa presents with one day of confusion and nonsensical speech.( ) year old male with history of bilateral occipital hemorrhages of cryptogenic etiology presents with two days of new onset dizziness and left hemianopsia. in each case, patient was identified to have a focal area of vasogenic edema on mri that was significant and alarming in comparison to the patient's presenting symptoms. swi mri showed numerous microbleeds elsewhere to the vasogenic edema consistent with caa. considered differentials included herpes encephalitis, melas, cadasil, and cns vasculitis due to lupus, however all patients exhibited a neurological exam less severe than expected of differentials mentioned prior. all patients were administered an oral steroid regimen with taper for an average of weeks and their symptoms resolved on follow up. use of cranial ultrasound (cus) in pediatrics has been limited to neonates or infants and transcranial doppler (tcd) for stroke risk in children with sickle cell disease. we describe a clinical case showing the utility of performing cus/tcds to assess for new intracranial process in a pediatric patient where head ct was difficult to obtain due to high frequ assessment of waveforms on tcd can be a useful bedside tool in assessing progression of cerebral edema in pediatric patients unable to get a head ct. -month child with acute respiratory distress syndrome required veno-venous ecmo and therapeutic anticoagulation complicated by intracranial hemorrhage with intraventricular extension, mm leftwards midline shift, and hydrocephalus. heparin was reversed and evd was placed. since heparin sedation/paralysis. osmotic therapy was guided by elevated icp. days later, the ability to monitor icps became unreliable due to intermittent evd dra repositioning was deferred because of bleeding risk and lack of clarity whether device malfunction or unsafe because of waveforms with robust arterial diastolic flow and venous flow signifying that icp was lower than plaining unreliability of and repeat head ct showed no gross change. cus and tcd can be a useful tool to screen for high icp using midline shift and spectral waveform analysis in pediatric patients where ct may be contraindicated or challenging to obtain. the structure of intensive care has evolved as the field of medicine has created needs for specialized care. large pediatric hospitals frequently have separated cardiac icu from general pediatric icus, however further subdivision is rare, which differs from adult institutions that often have surgical and neuro icus. this subdivision capitalizes on concentration of expertise and collaboration across providers to improve patient outcomes. texas children's hospital recently opened a new pediatric icu tower and subdivided the picu into six specialty units: surgical, neurology/neurosurgery, pulmonary, hematology/oncology, medical and transitional (for patients with complex needs). we sought to retrospectively review similar patients fitting predefined neuro icu criteria both pre and post move to determine if patient outcome measures were different after cohorting patients. we conducted a retrospective review of neuro icu patients before and after our specialty icu model by comparing june-august to june-august . patients were identified using local data from virtual pediatric systems (vps, llc) and outcomes collected from the electronic medical record utilizing automated data query. primary analysis included patient demographics and outcomes including icu length of stay (los), mortality, prism- and pim- risk of mortality scores. early subgroup analysis included patients with icp monitoring devices in both cohort groups. and patients were in the pre and post cohort group respectively, of which had icp monitors in each group. median time to icp measurement was (iqr - ) and minutes (iqr - ) respectively in pre and post groups (p = . ). icu los, mortality, prism- and pim- were not statistically different. we have developed an algorithm to capture the neuro icu population for future study. preliminary investigations will hopefully confirm patients benefit from this model after programmatic maturity is achieved. west nile virus (wnv) is a mosquito transmitted arbovirus that is endemic in the united states. only % with acute infection develop fevers, and only less than % develop neuroinvasive disease. although the presentation of acute flaccid paralysis is not uncommon, it is extremely rare to visualize the destruction radiographically. here we highlight a case of aggressive neuroinvasive disease with radiographic changes. results y/o caucasian male with arthritis on methotrexate and tofacitinib presented with encephalopathy and generalized weakness. initial evaluation included mri and lumbar puncture. initial mri did not demonstrate etiology of symptoms. lumbar puncture was consistent with viral meningitis (wbc , rbc , glucose and protein ). patient was started on broad spectrum coverage. there was no growth on bacterial or fungal cultures. pcr biofire was negative for acute viruses. weakness progressed, and required intubation for neuromuscular respiratory failure. diagnostic evaluation was repeated days later. repeat mri demonstrated changes on dwi and t weighted imaging, following the motor addition to continued acyclovir, plasma exchange was initiated for an attempt at treatment. the patient's mental status improved, and he refused further treatments including tracheostomy. he was extubated and comfort care was provided given his continued neuromuscular respiratory failure. this case demonstrates severe neuroinvasive west nile encephalitis and flaccid paralysis with radiographic findings. being immunocompromised and age increase his risk for rare presentation of aggressive disease. evidence regarding adequate caloric requirements of critically ill patients with acute brain injuries is suggesting potential risk of caloric debt in neurocritically ill patients. the primary objective of this study was to determine whether guideline recommended weight-based dosing provides adequate caloric requirements compared to indirect calorimetry (ic) measurements in this population. this was a single center, retrospective, observational case-crossover study that included adults admitted within days from admission. we compared resting energy expenditure (ree) determined via ic to the lower (bmi< kg/m : kcal/kg and bmi - kg/m : kcal/kg) and higher (bmi< kg/m : kcal/kg and bmi - kg/m : kcal/kg) actual body weight-based dosing guideline recommendations. we hypothesized that guideline recommended lower-weight based nutrition will not match the caloric demand of patients with acute brain injuries. a total of metabolic studies were performed in patients ( % ich, % non-traumatic sah, % ischemic stroke, % tbi, % status epilepticus, % other etiologies). the mean age was + years, mean weighed + kg with a bmi of + kg/m , and had mean baseline gcs of + . on average ic was obtained on day of admission. lower weight-based recommended nutrition did not provide adequate caloric needs as measured by ic adjusted for obesity ( ± vs ± kcal/day, p< . ). however, higher weight-based recommendation matched the caloric demand as measured by ic ( ± vs ± , p= . ) . in this preliminary analysis, higher weight-based dosing for nutrition matched the caloric demand of critically ill patients with acute brain injury. our results need to be confirmed in future larger prospective studies. central venous catheter (cvc) insertion is common in neurocritically ill patents. standard practice is to obtain a chest radiograph (cxr) to evaluate for the presence of complications, such as pneumothorax (ptx) and catheter misplacement. point-of-care ultrasound (us) has been suggested as an alternative methodology to assess for these complications by using a flush test. patients admitted to our neuro icu between / / - / / who required cvc placement were the subject of this quality improvement analysis. cvc's were placed in the internal jugular (ij) or subclavian (sc) vein followed immediately by lung us to assess for ptx. then, apical or subcostal four-chamber view of agitated saline injected through the distal port of the cvc (ie. flush test) was performed to assess for proper placement. we observed the time delay between start of agitated saline instillation and visualization of contrast in the right atrium and ventricle. this was then interpreted as appropriate (contrast present in t (and g->a) were used to systematically mutate and explore the role of identified proteins in mediating the ags optimized adaptive stress response. we found that ags neural cells exhibit marked resistance to all metabolic stressors. this is associated with enhanced mitochondrial function and improved morphology. the functional genetic screen identified a network of evolutionarily-conserved ags transcripts imparting cytoprotection. use of dcas base editors on candidates suggested by the bio-informatics pipeline, confirmed the coordinated role of specific components of the oxidative phosphorylation (oxphos) and endoplasmic reticulum (er) stress response systems in imparting mitochondrial and neuroprotection in our in vitro model. we gained key functional insights into how specific amino acid substitutions in the machinery of the oxphos and er stress responses systems alter mitochondrial function to impart cytoprotection to metabolic insults. this detailed dissection of the ags optimized adaptive stress response pathway will serve as an template for the development of new neuroprotective treatments. acute ascending weakness with respiratory failure is a frequent syndrome encountered in the neurocritical care unit (nccu), often related to demyelinating or infectious etiology. however, here we describe a case of acute ascending weakness with encephalopathy, respiratory failure and autonomic instability that was related to confirmed endocrinological etiology. prospectively collected data was retrospectively extracted from the electronic health record in a patient known to our nccu team. a -year-old male with medical history of childhood meningitis was transferred to the nccu after initially presenting to an outside emergency department (ed) with a chief complaint of bilateral lower extremity weakness progressing to paraplegia over hours. six hours into his course in the ed, he developed bilateral upper extremity paresis and respiratory distress. physical exam in this ed was additionally notable for areflexia and a sensory level at t . he was intubated, initiated on ivig and methylprednisolone, and airlifted to our institution. upon arrival, telemetry showed frequent supraventricular tachycardias refractory to standard treatment. labs (including cerebrospinal fluid) were notable only for serum potassium < . meq/l, thyroid stimulating hormone < . uiu/ml, t . uiu/ml ( . -- . ). he was diagnosed with thyrotoxic periodic paralysis. at endocrinology's urging, the patient was given propranolol mg iv every minutes for doses, propylthiouracil and hydrocortisone. in the hours following propranolol, his potassium improved, his paralysis and encephalopathy resolved, and he was ultimately extubated without difficulty < hours after admission. review of symptoms performed after improvement revealed recent symptoms consistent with hyperthyroidism. intensivists should remain aware of the differential diagnoses that can manifest with motor weakness and respiratory failure. in this patient, severely elevated thyroid hormone led to thyrotoxicosis and subsequent profound hypokalemia. acquiring a thorough history and reviewing laboratory abnormalities remain paramount for timely diagnosis. the objective of the study is to determine the prevalence of disability among icu survivors one year after admission, and factors influencing functional outcome. we conducted a population based cohort study in the icus of the mayo clinic, rochester, mn. we enrolled consecutive patients from the mayo clinic study of aging (mcsa) and then admitted to medical or surgical adult icus at mayo clinic, rochester between january , , and december , . patients admitted to the neuroscience icu were excluded. we collected their demographic and clinical variables, length of icu stay, functional and cognitive status (before and after icu admission), comorbidities (components of charlson score), and apache were retrieved from the electronic medical records using multidisciplinary epidemiology and translational research in intensive care (metric) data mart. one-year functional outcome was categorized using the modified ranking scale (mrs) with scores to representing good functional outcome. cases were included and ( . %) patients were alive one year after icu admission. of them, patients had one-year follow-up functional assessment and ( . %) of them had good functional outcome. on multivariable analysis, poor one-year functional outcome (death or disability) was more common among women, older patients, baseline cognitive impairment (mild cognitive impairment or dementia), higher charlson scores, and longer icu stay (all p< . ). after excluding deceased patients, these associations remained unchanged. in addition, ( . %) of patients who had post-icu cognitive evaluation, experienced cognitive decline after the icu admission. approximately two-thirds of survivors maintained or regained good functional status one year after icu hospitalization. older age, female sex, greater comorbidities, abnormal baseline cognition, and longer icu stay were associated with poor functional recovery. shared decision-making using decision aids (da) is recommended by major professional critical care societies for surrogate decision-making in the icu to reduce decisions incongruent with patient values and preferences and decisional conflict. we converted a paper-based goals-of-care da in critically-ill tbi patients to a digital da. we applied eye-tracking-technology in a single-masked randomized study to understand the effects of and optimize the da navigation design to facilitate information processing. we created two digital das: ( )unmodified conversion of the paper-da with horizontal, top-justified static navigation (control) vs. ( )vertical, left-justified navigation with page subsections and page completion checkmarks (experimental), which encourages users to view pages in order. sixteen healthy participants were randomly assigned to the two groups (n= /group, masked to da assignment) and navigated through the das. using t-tests, we compared user disorientation and usability using validated scales, and eye movements (fixation and saccades) recorded with eye-tracking-technology. impact of navigation on usability was assessed with linear regression, adjusting for disorientation(system-usability-score= b + b *disorientation). disorientation was significantly less in the experimental da (mean . vs. . ;p= . ;smaller values indicating increased disorientation) with no difference in usability (mean system-usability-scale scores vs. ;p= . ;scores> indicating good usability[range - ]). regression analysis revealed a significant association between disorientation and usability (p= . ), with disorientation explaining % of the variation in system-usability-scale scores (adjusted r = . ). eye-tracking measurements revealed longer average fixation per page in the experimental da (mean . s vs. . s;p= . ) and a higher ratio of information processing to search per page (fixation-duration over total duration of both fixations and saccades on a page; mean . vs. . ;p= . ). eye-tracking-technology suggested that the experimental navigation design significantly improved the navigation experience resulting in less disorientation and participants spending less time searching and more time processing the information. while there was no difference in subjective usability, we found a significant association between improved navigability and higher usability. high-fidelity simulation has become an important mode of learning in medical education. currently, there is little data regarding the impact of simulation-based learning in neurocritical care training. in may , we presented a poster at the american academy of neurology annual meeting introducing a comprehensive simulation-based curriculum for neurocritical care training at uc san diego (ucsd). in this poster, we aim to present additional preliminary findings regarding trainee comfort levels, interest, and areas of improvement. this is a single-group pre-post study involving current residents of the ucsd department of neurology. simulation sessions consist of interactive, faculty-led, and checklist-based clinical scenarios (ischemic stroke, intracranial hemorrhage, status epilepticus, spinal cord emergencies) followed by debriefing sessions. collected data assesses for self-perceived comfort/confidence levels, future interest, and checklist item completion. between january and july , pgy - neurology residents participated in various simulation sessions on ischemic stroke, intracranial hemorrhage, and status epilepticus. prior to the session, . % of all trainees reported no more than somewhat comfortable in treating neurological emergencies despite having received some type of neurological emergency training through didactic lectures. rtable in treating the specific simulation case in observation of each simulation session pinpointed specific areas of improvement amongst trainees on an individual basis (i.e. time to intubation after benzodiazepine administration in refractory status). preliminary results suggest that simulation-based learning is valuable and applicable in the neurocritical care training process, allowing trainees to feel more comfortable in managing acute neurological deterioration and faculty to directly observe trainee skill in a controlled setting. through this project, we hope to highlight the need for simulation-based education in neurocritical care training by providing evaluative information and generalizable curricular examples. chimeric antigen receptor (car) t cell therapy for refractory/relapsed hematologic malignancy often causes severe neurologic side effects ranging from encephalopathy and aphasia to fulminant cerebral edema and death. the cause of neurotoxicity is poorly understood. we sought to develop a score based on clinical and laboratory parameters to predict which patients would develop cart-associated neurotoxicity. all patients undergoing cart therapy at brigham and women's hospital for relapsed/refractory hematologic malignancy were prospectively studied. patients were assessed daily during their admission for cytokine release syndrome (crs) and neurotoxicity. vital signs, laboratory data, and medication administration records were extracted from the medical record. logistic regression was used to determine which clinical and laboratory features were significant predictors of developing neurotoxicity. patients were included. experienced crs and experienced neurotoxicity. early (within days after cart infusion) fever and elevated serum c-reactive protein (crp), timing of crs onset, crs grade, and treatment with tocilizumab were all significant predictors of neurotoxicity. using roc curves, optimal discriminators were defined and used to derive a score to predict neurotoxicity. one point was assigned for fever, serum crp > . mg/dl, and each dose of tocilizumab administrated, zero to four points for crs grade, and zero to three points for day of crs onset. this score ranged from to for our cohort and had an auc of %; a score >= predicted neurotoxicity with a sensitivity of % and a specificity of %. bootstrap analysis was used to demonstrate robustness. we used regression analysis to develop a score that can prospectively predict which patients are most likely to suffer from neurotoxicity related to cart therapy. this score can be used for triaging and resource allocation during the care of the patients after treatment with cart therapy. when brain herniation is impending, every minute matters; so the efficient and expedient procurement of all components required for external ventricular device (evd) placement is vital to neurological preservation. the neurosurgical residents at the university of rochester medical center often struggled to assemble the appropriate supplies for an evd placement in a timely manner when patients were not yet admitted to the neuro intensive care unit (neuro icu). additionally it was difficult to track equipment use and supply costs. in response, the neuro icu's quality improvement (qi) team designed an evd "go bag" in an effort to improve delays in care, patient experience, and avoidable costs. the multidisciplinary neuro icu qi team collaborated to design a portable bag that contained all equipment necessary for evd placement. two neurosurgery residents performed time trails, in real emergency situations, by measuring the time from decision to place an evd in emergency department (ed) critical care bay, to collecting the equipment from the neuro icu and return to the bedside in the ed. times were compared with and without using the evd "go bag". the evd "go bag" decreased the time to placement of an evd by up to minutes when compared to the traditional method of retrieving all evd equipment from the neuro icu stockroom. time reduction was due to the speed of gathering supplied and the ability for the neuro icu staff to bring the evd "go bag" to the patient's bedside. the evd "go bag" allowed for better tracking of monetary costs and equipment, allowing for appropriate billing and stocking of supplies. a system was developed where the bag was checked and restocked daily by the critical care equipment technicians and the neuro icu charge nurse despite a growing number of prognostication models in neurologic emergencies, prognostic uncertainty remains inevitable and plays a central role during goals-of-care decision-making for incapacitated critically ill patients. we aimed to examine surrogate decision-makers' communication needs and physicians' strategies for communication of prognostic uncertainty during family meetings for critically ill traumatic brain injury (citbi) patients. we qualitatively analyzed semi-structured interviews of surrogates of citbi patients from two level- u.s. trauma-centers and tbi expert physicians from u.s. trauma-centers. open-ended questions about prognostic uncertainty were asked. interview transcripts were analyzed with the investigatortriangulated-inductive-framework-approach in nvivo-software. prognostic uncertainty was identified as the most difficult aspect of decision-making for surrogates by physicians and surrogates alike, although most surrogates had some pre-existing expectation or understanding of it. % of physicians observed that uncertainty is distressing for families, with % employing specific measures to limit uncertainty. over half of physicians described explaining the concept of uncertainty so surrogates understand that physicians can estimate the odds but not predict the future. physicians typically conveyed prognosis using a range of outcomes, and conveying certainty only for prognostic extremes. surrogates found uncertainty around prognosis was lessened when physicians explained all possible treatment options, with support from clinical data. roughly half noted that too much certainty in providing a prognosis, without a range of possible outcomes, led to distrust in the information provided by the physician, increasing decisional conflict. the vast majority of physicians admitted statistical uncertainty in deriving prognosis, particularly for patients with tbi, and cited mistrust of prognostic models when deriving long-term prognosis. most physicians felt that uncertainty around prognosis led to increased incidence of tracheostomy and feeding tube placement. these results provide foundational knowledge for physician-family communication, by identifying important gaps between surrogates' communication needs and physicians' practices about prognostic uncertainty. the rapid rise in social media utilization among both patients and healthcare providers has moved a considerable portion of conversation around health and disease to the digital space. today, roughly nine-in-ten american adults use the internet, with % of internet users participating in social media. the power and reach of social media platforms makes it imperative for clinicians to be aware of the trends in the public narrative around common disease processes. in this study, we analyzed the last . years of postings ("tweets") from a popular social media platform, twitter, to characterize themes and trends in the digital conversation around stroke, the leading cause of long term disability in the us. tweets under the hashtag #stroke, published from january st to april th , were extracted through symplur signals, llc. a total of , #stroke tweets were qualitatively coded and sentiment analysis was performed after selection for relevance among all homographs. accounts owned by stroke-related advocacy groups were found to be the most prolific contributors of #stroke postings, with content mostly around primary stroke prevention (risks and signs). among the most popular associated hashtags, over half of the tweets focused on comorbidities and the challenges of the stroke recovery process (top trending words included #aphasia, #lockedin, #survivor, #depression). our preliminary analysis describes trends in themes and stakeholder participation in the current #stroke online conversation. it also exposes important gaps in the public discourse beyond the setting of academic and research online communities, namely around existence of therapeutic treatments, availability of resources for patients and families navigating the recovery process, and possibility of successful recovery and long term outcomes. such knowledge around the digital stroke narrative may provide valuable context to intensivists and stroke clinicians interacting with patients and families affected by stroke. the field of autoimmune neurology, specifically the autoimmune encephalitides, has expanded since the early 's. increasingly newer antibodies to various parts of the nervous system are being identified in discovered in patients with meningoencephalomyelitis, or some spectrum of these three singular entities. data was reviewed from electronic medical records for this case report. a previously healthy year-old male initially developed a case of aseptic meningitis, progressing to encephalitis and then extensive longitudinal myelitis leading to profound paresis and respiratory failure. an extensive workup was performed, including evaluation for rare infectious and ominant leukocytosis ( /μl and /μl) and elevated protein (> mg/dl). he was treated empirically with antibiotics which were discontinued after negative results and cultures. after therapy with high dose iv steroids he had minimal improvement and pl had improvement in his symptoms. he was started high dose prednisone with plans to slowly taper after return with positive anti- in review of the literature our patient had several characteristics consistent with others who were also antipsychiatric symptoms. many reports state steroids lead to remission and improvement, however in this case our patient did not have substantial recovery until after the initiation of plex. at this time it is hether these antibodies instead represent a marker of other underlying disease from cytotoxic t cell damage to astrocytes. the united council for neurologic subspecialties (ucns) accredits neurocritical care (ncc) subspecialty fellowships and certifies neurointensivists. in , the american board of medical specialties (abms) approved the application for ncc subspecialty certification by american board of psychiatry and neurology (abpn) and the accreditation council for graduate medical education (agme) approved ncc fellowship training in . previous studies have shown significant heterogeneity in ncc fellowship training and procedural competencies and that many programs do not have the necessary resources for a transition to acgme accreditation. in , an online survey of abpn neurology diplomates was utilized to estimate the number of neurologists practicing ncc, their ncc fellowship training experiences, whether their institutions required certification in ncc, their scope of practice, and their interest in pursuing abpn certification in ncc. survey respondents indicated that they practiced ncc. based upon ucns and other data, this is estimated to be at least % of all neurologists practicing ncc. % of ucns-certified ncc respondents identified the primary scope of their practice as academic involving a fellowship program, and % of non-ucns-certified ncc responders identified themselves as private practitioners. nearly % of fellowship trained ncc respondents obtained ucns certification. % of ucns-certified ncc respondents reported that their institutions required ucns certification, whereas % of non-ucnscertified ncc respondents reported no institutional requirements for certification. over % of respondents thought ncc training was relevant to their current clinical practice. most respondents indicated that they planned to take the abpn ncc examination, and > % of respondents reported that abpn certification would most benefit them by improving their colleagues' perceptions about the quality of certification. ncc training and certification is valued by most neurologists practicing ncc, and most believe that abpn ncc certification will advance the recognition of the field of ncc. cerebral edema is a severe complication of acetaminophen-induced acute liver failure (apapprimary objective was to describe the characteristics of patients with cerebral edema in the setting of apap- this analysis is part of a large, retrospective observational study inclusive of apap-year period from a regional transplant center. we used standardized data collection tools and trained defined cerebral edema based on the interpretation of this ct by a blinded radiologist. we performed univariate analysis based on the presence of cerebral edema. of a total of patients, had data on ct brain imaging. the mean age was . ± . years, and patients ( . %) were female. of patients with neuroimaging, ( . %) had evidence of cerebral edema. patients with cerebral edema had higher average ammonia levels on day of hospital admission ( , % ci - vs. , % ci - mcg/dl). patients with cerebral edema also had significantly higher meld scores by -hours ( . , % ci . - . vs. . , % ci . - . ). this significant difference persisted for subsequent hospital days. thirteen patients ( . %) with cerebral edema received intracranial pressure monitoring. mortality within -days was . % (n= ) if cerebral edema was present vs. . % if absent (n= ). the odds of death within -days, if cerebral edema was present, was . ( % ci . - . ). one patient with cerebral edema died awaiting transplant, and received liver transplant. in this study, cerebral edema was present in % of patients hospitalized for apapwith higher mortality. elevated intracranial pressure and cerebral edema are leading predictors of poor outcomes and mortality in patients with head trauma, intracranial hemorrhages, or acute ischemic strokes. while hypertonic saline (hts) is the mainstay of treatment, recent trials in critically ill populations have demonstrated a reduction in kidney related adverse events with the use of balanced crystalloid groups when compared to . % sodium chloride (nacl). the purpose of this study is to assess adverse kidney outcomes and risk of in-hospital mortality associated with hts in a neurocritical care population. a retrospective cohort study was conducted at a large academic medical center on adult patients in the neurosciences icu who received % nacl and/or . % nacl from july , to july , . the primary endpoint was major adverse kidney events (make- ), defined as at least one component of the composite: in-hospital mortality, receipt of new renal-replacement therapy, or persistent renal ays. baseline characteristics, indication for hts, pertinent lab values including changes in serum electrolyte concentrations, total hts volume and associated sodium and chloride milliequivalents, and patient outcomes were collected. statistical analysis was performed using spss software. in the chloride increase > mmol/l group, patients ( . %) experienced the primary outcome of make- , patients ( . %) experienced in-hospital mortality and patients ( . %) experienced aki primary outcome of make- , and patients ( . %) experienced in-hospital mortality (p= . ). the primary outcome occurred more often in the chloride increase > mmol/l group and in-hospital mortality accounted for the majority of the outcome in both groups. this was not statistically significant due to the sample size and unbalanced comparator groups. social media has been shown to be a valuable tool to improve knowledge, attitudes, and skills. it has been theorized that the success of medical education through social media can be contributed to increased learner engagement, real-time feedback, and enhanced collaboration. we hypothesize that social media is underutilized in critical care medicine in comparison to other specialty fields of medicine and surgery. a list of medical specialties as hashtags were run through "hashtagify" software. this software crossreferences up to , data points on instagram and twitter and assigns a "popularity score" for certain topics. the phrase "critical care" was cross-referenced through a database of medical news run by doximity over a month in comparison to other topic tags. in total, articles concerning the topic "critical care" were posted on doximity news over days. in comparison, there were articles posted under "cardiology," under "internal medicine," and under "emergency medicine." with respect to hashtag utilization on social media, critical care was under-represented, with a popularity score of . this was in comparison to other specialties such as neurology ( ), dermatology ( ), emergency medicine ( ), and ophthalmology ( ). within the critical care hashtag, the major influencers were those representing critical care nursing. despite the large amount of news pertaining to critical care on professionally-curated forums such as doximity, there is significant under-representation in social media. within the hashtag, "critical care," the major influencers represented critical care nursing suggesting that critical care physicians are even further underrepresented. this is in line with previous research suggesting the underrepresentation of medical doctors in social media. given that social media has been shown to be a valuable tool in enhancing medical education, we believe that a greater effort should be made to engage critical care physicians on social media outlets. there is a call for increased diversity in national and international annual meeting participation in terms of attendance, committee participation, leadership, awards and speakers. the neurocritical care society annual meeting(ncs-am) speaker qualifications are not specified in the bylaws. the speakership patterns of the ncs-am have not been examined. we described the speakership patterns in ncs across a -year time span ( ) ( ) ( ) and delineated the trends of united states-neurocritical-care-fellowship- longitudinal cohort study. the ncs-am conference program, a readily available online document, for the years - , were reviewed by the study authors. speakers were identified from the conference program. our primary outcome was the trend of speaker characteristics across the -year time span. our secondary outcome was to determine speakership trends among united states-neurocritical-care-fellowshipinstitution of employment at the time of the meeting. a total of speakers were included in this study, of which % were male. majority of the speakers were us-based( %), mid-to late-career ( %) and were physicians ( %). the speakers were ± years from fellowship. in -years, there was an increased trend towards international, non-physician and early-career speakers' trained from johns hopkins university (jhu) ( , %), massachusetts general hospital (mgh) ( , %) and cornell/columbia university ( , %); while the most common sites of employment at the time of the meeting were jhu ( , %), mgh ( , %) and university of pittsburgh medical center ( , %). this is the first study to evaluate speakership trends across a -year period of the ncs-am. diversity has ble institutional bias are unclear and deserves to be studied further to better define speaker selection in the ncs annual meeting. these data may also be utilized to explore opportunities for collaboration and diversity in future ncs-ams. urinary tract infections (utis) are the fourth most common type of healthcare-associated infection, primarily caused by instrumentation of the urinary tract. there is a %- % increased risk of patients acquiring a catheter-associated urinary tract infection (cauti) for each day an indwelling urinary catheter (iuc) remains in place. in critically ill patients, iuc placement is often required for precise urine output measurement. subarachnoid hemorrhage (sah) patients often require iuc's during the cerebral vasospasm period (i.e. post-bleed day, pbd - ) to maintain euvolemia. this places sah patients at increased risk for developing a cauti. in our local neurosciences intensive care unit (nsicu), an infection control team observed higher cauti rates as compared to the hospital and national average necessitating changing our urinary catheter utilization policy. we report change in practice pattern with implementation of new unit policy the intermittent catheterization (ic) algorithm includes clinician review of the patient's total intake and output and current clinical status. retrospective chart review of cauti incidence (rate per catheter days) and device utilization ratio (no. urinary catheter days/ no. patient days) months before and after implementation of the new policy. time periods were compared using appropriate statistical tests pre-and post-intervention the ic algorithm was implemented to reduce iuc utilization rate with aim to reduce cauti rates. the time periods studied were may to april (pre-intervention period) and may to april (post-intervention period). cauti rates decreased from . ± . during the former time-period to . ± . during the latter time period (p= . ). similarly, device utilization ratio decreased from . ± . to . ± . (p< . ). in addition, use of female and male external catheter devices were encouraged leading to increased utilization systemic team based implementation of policies can result in adoption of positive practices and reduce hospital acquired infectious complications. managing neurological emergencies, particularly overnight, is very challenging for neurology trainees at the beginning of their residency. preparation is key to ensure residents have the skills, confidence, and knowledge to manage acute scenarios. we developed a one-week immersive bootcamp to educate new neurology residents about neurological emergencies prior to the start of the academic year. the bootcamp includes the fourteen emergency neurological life support (enls) modules designed by the neurocritical care society, thirteen faculty-created didactics, nine case-based discussions, and four resident-created simulations. the bootcamp teaches residents about the management of acute ischemic stroke, acute non-traumatic weakness, anoxic brain injury, coma and brain death, intracranial hemorrhage, intracranial hypertension, meningitis, neuromuscular emergencies, status epilepticus, spinal cord emergencies, subarachnoid hemorrhage and traumatic brain injury. residents are also taught about communication with families during and after neurologic emergencies in a didactic session on breaking bad news. it is important for all neurology residents to be adept at managing neurological emergencies. however, having these skills is particularly important for residents in a military program, as residents in the military may ultimately be deployed overseas or stationed at facilities with minimal support, responsible for handling all neurological emergencies, regardless of their sub-specialty. enls training and didactics teach residents about the fundamentals of neurological emergencies. case-based discussions provide residents to act out the way they would utilize this knowledge in a risk-free environment that is translatable to acute clinical situations. the combination of enls training, didactics, case-based discussions and simulations into a one-week immersive bootcamp early in residency should, therefore, provide a solid knowledge base about management of neurological emergencies for incoming neurology residents and allow them to consolidate that knowledge leading to safe and effective management of neurological emergencies. trends and predictors of in-hospital mortality for status epilepticus: national inpatient sample study head or heart: ictal bradycardia and temporal lobe epilepsy julia bevilacqua higher dai grade correlates with worse short term outcome in pediatric traumatic brain injury anna janas; scott hamilton; zachary threlkeld; max wintermark post-intensive care syndrome amongst families of icu patients, including post-traumatic stress disorder (ptsd), is highly prevalent after patient discharge but understudied. the psychological model of "attachment theory" describes how people respond when being separated from loved ones; various "attachment styles" have been associated with the development of ptsd in other settings. adults can be "secure" (comfortable depending on others and being alone) or "insecure." the hypothesis of this exploratory study was that insecure family members of neuro icu patients would be more likely to report ptsd six months after patient hospitalization compared to secure family members. eligible participants were family members of neuro icu patients at a single center who already had attachment styles (secure vs. insecure) defined via a standard survey, the relationship questionnaire, during an earlier study in . over - , these subjects were asked by mail to complete the impact of events scale-revised (ies-r) six months following discharge or patient death. participants were considered to have ptsd if ies- / returned a completed ies-r ( . %). ( . %) of these subjects reported a secure attachment style vs. out of ( . %) insecure respondents (p= . ). this small study did not show a significant difference in rates of post-discharge ptsd amongst neuro icu family members with secure vs. insecure attachment styles, however was only powered to discover a large difference between groups and the rate of ptsd in our population was markedly lower than sible association in larger cohorts with an overall higher prevalence of post-discharge ptsd would be insightful. key: cord- -hkkpw bl authors: rodríguez-sánchez, diego noé; pinto, giovana boff araujo; thomé, edval fernando; machado, vânia maria de vasconcelos; amorim, rogério martins title: lissencephaly in shih tzu dogs date: - - journal: acta vet scand doi: . /s - - - sha: doc_id: cord_uid: hkkpw bl background: lissencephaly is a brain malformation characterized by smooth and thickened cerebral surface, which may result in structural epilepsy. lissencephaly is not common in veterinary medicine. here, we characterize the first cases of lissencephaly in four shih tzu dogs, including clinical presentations and findings of magnetic resonance imaging of lissencephaly and several concomitant brain malformations. case presentation: early-onset acute signs of forebrain abnormalities were observed in all dogs, which were mainly cluster seizures and behavioral alterations. based on neurological examination, the findings were consistent with symmetrical and bilateral forebrain lesions. metabolic disorders and inflammatory diseases were excluded. magnetic resonance imaging for three dogs showed diffuse neocortical agyria and thickened gray matter while one dog had mixed agyria and pachygyria. other features, such as internal hydrocephalus, supracollicular fluid accumulation, and corpus callosum hypoplasia, were detected concomitantly. antiepileptic drugs effectively controlled cluster seizures, however, sporadic isolated seizures and signs of forebrain abnormalities, such as behavioral alterations, central blindness, and strabismus persisted. conclusions: lissencephaly should be considered an important differential diagnosis in shih tzu dogs presenting with early-onset signs of forebrain abnormalities, including cluster seizures and behavioral alterations. magnetic resonance imaging was appropriate for ante-mortem diagnosis of lissencephaly and associated cerebral anomalies. lissencephaly in mammals occurs due to the failure of neuroblasts to migrate to the cerebral cortex, during development [ , ] . it is characterized by smooth cortical appearance and by the absence of surface folds (agyria) or abnormally broad folds (pachygyria). histopathology demonstrates thickening of the cerebral cortex, altered gray-to-white matter ratio and replacement of a normal -layered cortex with a -layered disorganized cortex [ , ] . two types of lissencephaly can be distinguished in humans: classical lissencephaly (or type i), characterized by thickened brain surface with agyria or pachygyria that results from neuronal migration arrest [ , ] and cobblestone lissencephaly (or type ii), characterized by thin and nodular brain surface, resulting from glial and neuronal overmigration [ , ] . muscular dystrophy, ocular alterations, obstructive hydrocephalus, and malformation of the brainstem and cerebellum are often associated with cobblestone lissencephaly [ ] [ ] [ ] . lissencephaly has been described in lhasa apso [ , ] , pekingese [ ] , australian kelpie [ ] , wire-haired fox terrier [ ] , irish setter [ ] , and mixed-breed dogs [ ] . in humans, lissencephaly is associated with gene mutations related to brain development or cerebral metabolism [ , , ] . in addition, nongenetic causes, such as intrauterine viral infections, vascular events (hypoxia or hypoperfusion), and maternal metabolic disorders that interrupt cortical formation, have been described [ , , ] . the neurological signs in dogs commonly begin with an early-onset of seizures and behavioral alterations, leading to disability [ , , ] . clinical findings and magnetic resonance imaging (mri) features of lissencephaly in shih tzu dogs have not been reported previously, and reports of concomitant brain malformations are scarce. four apparently unrelated shih tzu dogs were presented with lissencephaly between and at the veterinary neurology service of são paulo state university (unesp), brazil. details regarding clinical features, neurolocalization, ancillary diagnostics and antiepileptic treatment are shown in table . mri was performed using a . tesla scanner (vet-mr grande, esaote, italy) in all dogs to obtain t -weighted, t -weighted, fluid-attenuated inversion recovery (flair) and postcontrast t sequences. in addition, gradient echo (gre) sequences were obtained in three dogs, and hybrid contrast enhancement ( d hyce) sequences were obtained in two dogs. all mris were evaluated and interpreted by two researchers (ra and vm). a summary of the mri findings, equipment, positioning, sequences, imaging parameters, and the contrast medium are detailed in additional file . the first case was an -month-old spayed female referred in due to seizures of suspected idiopathic origin that were poorly controlled with phenobarbital (gardenal ® , . mg/kg, orally q h; safoni, brazil). the dog was evaluated by the referring veterinarian months after the onset of tonic-clonic seizures, which had progressed over the last weeks to - seizures per week. in our service, the owner reported that the dog experienced cluster seizures that occurred over h and were treated with diazepam and thiopental. on presentation, neurological examination was performed week after cluster seizures and was unremarkable. based on a history of seizures, the lesion was localized to the forebrain. physical examination findings, biochemical profile, and complete blood count (cbc) were normal; polymerase chain reaction (pcr) for canine distemper virus in urine and indirect immunofluorescent antibody tests (ifat) for antibodies against toxoplasma gondii and neospora caninum were negative. mri showed mixed parieto-occipital agyria and pachygyria of the frontal and parietal lobes (fig. ). temporal and occipital regions lacked gyri and sulci. mri diagnosis indicated lissencephaly and supracollicular fluid accumulation (sfa) (fig. ) . treatment with phenobarbital (gardenal ® , mg/kg, orally q h; safoni, brazil) and levetiracetam as an adjunct (keppra ® , mg/kg, orally q h; ucb biopharma, brazil) effectively controlled cluster seizures after presentation. levetiracetam was discontinued after weeks. the neurological signs were nonprogressive and this dog experienced only isolated episodes (interictal period of - months) over a period of months after diagnosis of lissencephaly (> % reduction in the frequency of seizures). it was not possible to obtain information regarding survival for this dog. the second case involved a -month-old castrated male which was referred in due to the occurrence of cluster seizures. the dog was diagnosed by the referring veterinarian with presumed idiopathic epilepsy at months of age and treatment with phenobarbital was then initiated (gardenal ® , . mg/kg, orally q h; safoni, brazil). during the first months after diagnosis of presumed idiopathic epilepsy and the onset of treatment, the dog experienced both isolated seizures and cluster seizures, with an interictal period less than days. relatively low levels of phenobarbital (< µg/ ml: therapeutic window - µg/ml) were detected in serum; therefore, the dose of phenobarbital was gradually increased (gardenal ® , mg/kg, orally q h; safoni, brazil). however, despite the increase in serum phenobarbital concentration ( µg/ml), the dog continued to have repeated tonic-clonic seizures. therefore, potassium bromide (kbr) ( mg/kg orally, q h) was also prescribed month before referral to unesp. on presentation in our service, in addition to cluster seizures the owner reported behavioral changes between seizures, such as difficulties in learning basic commands, changes in sleep cycle and compulsive pacing. aggression was noted in our service during manipulation for physical examination. during anamnesis, the owner reported polyuria, polydipsia and polyphagia. biochemical profile showed increased levels of alkaline phosphatase ( : reference interval - u/l). these alterations were presumed to be associated with phenobarbital treatment. neurological examination revealed no abnormalities except for the presence of bilateral central blindness and bilateral ventromedial strabismus during cranial nerve examination. physical and ophthalmological examinations were normal. the anatomical neurolocalization was compatible with a forebrain lesion. pcr in urine for canine distemper virus and ifat in the serum for t. gondii and n. caninum were negative. mri showed absence of sulci and gyri with superficial undulations in the frontal and temporal lobes. the main gyri, including the marginal, ectomarginal, suprasylvian, and ectosylvian gyri, were absent. a rudimentary lateral rhinal sulcus was present, while the cingulate gyrus was not apparent. the internal capsule was abnormally small (fig. ) . a diagnosis of lissencephaly, internal this dog remained stable and neurological signs were nonprogressive for months after diagnosis of lissencephaly (interictal interval of - months with > % reduction in the frequency of seizures) using combined polytherapy involving both phenobarbital (gardenal ® , mg/kg, orally q h; safoni, brazil) and kbr ( mg/ kg, orally, q h). levetiracetam (keppra ® , mg/kg, orally q h for - weeks, ucb biopharma, brazil) was initially included as an adjunct treatment modality. no more cluster seizures were reported after presentation. a carbonic anhydrase inhibitor (acetazolamide, diamox ® , mg/kg, orally q h, genom, brazil) and a proton-pump inhibitor (omeprazole, gaviz ® , mg/dog, orally q h, agener, brazil) were used for supportive treatment of hydrocephalus. however, the difficulties in learning basic commands, changes in sleep cycle, compulsive pacing, strabismus and aggression were persistent despite treatment. phone conversation with the owner revealed that the dog was alive years after diagnosis. the third case involved an -month-old intact male which was referred in due to the occurrence of cluster seizures starting days prior to referral. the dog was previously treated with phenobarbital (gardenal ® , mg/kg, orally q h; safoni, brazil); however, due to poor response to treatment, adjunctive therapy with kbr ( mg/kg, orally, q h) was initiated. on presentation, anamnesis revealed that months prior to referral, the dog had experienced over isolated seizures within days and subsequent episodes monthly. at evaluation, the dog experienced two tonic-clonic seizures, and emergency treatment was provided using diazepam ( mg/kg, per rectum and repeated iv bolus x). during the -h postictal re-evaluation, neurological examination revealed central blindness, and the owner reported that the dog demonstrated abnormal vocalizations. in addition, aggressiveness during the interictal period was noted, mainly during dog handling. anatomical neurolocalization was consistent with a forebrain lesion. physical and ophthalmological examination was unremarkable. laboratory data, including pcr in urine for canine distemper virus and ifat in the serum for t. gondii and n. caninum were negative. mri of the third dog showed presence of some sulci in the temporal lobe, including the caudal sylvian gyri and lateral rhinal sulci. however, the main gyri, including the marginal, ectomarginal, suprasylvian gyri, and suprasylvian sulcus (division between the parietal and temporal lobe), were absent (fig. ) . the internal capsule was abnormally small. diagnosis was consistent with lissencephaly, asymmetrical internal hydrocephalus, and corpus callosum hypoplasia. this dog showed progressive reduction in isolated seizures throughout the year following diagnosis (> % reduction in seizure frequency) with an interictal interval of months, maintaining combined polytherapy involving phenobarbital (gardenal ® , mg/kg, orally q h; safoni, brazil) and kbr ( mg/kg, orally, q h). serum concentration of phenobarbital was not tested due to financial constraints. no more cluster seizures were observed with combined polytherapy. a carbonic anhydrase inhibitor (acetazolamide, diamox ® , mg/kg, orally q h, genom, brazil) and a proton-pump inhibitor (omeprazole, gaviz ® , mg/dog, orally q h, agener, brazil) were used for supportive treatment of hydrocephalus. behavioral changes and central blindness persisted despite treatment. overall survival was years after diagnosis, confirmed by the owners after our phone call. the fourth case was an -month-old spayed female which was referred with seizures in . the referring veterinarian suspected meningoencephalitis of unknown etiology and reported poor control of seizures with phenobarbital (gardenal ® , mg/kg, orally q h; safoni, brazil). prednisolone treatment (predsim ® , . mg/kg, orally q h; medley, brazil) was added empirically week prior to referral by the referring veterinarian. in our service, the owner reported the first isolated tonic-clonic seizure when the dog was months old. after the interictal period of months, the owner reported that these seizures began again weeks prior to examination. over the -week period before examination, during the interictal periods, subtle behavioral changes such as aggressiveness (mainly after handling), compulsive pacing, abnormal vocalizations, and licking at things were observed. the dog presented with cluster seizures in our service and was treated with diazepam. after stabilization, the postictal state in the following h was characterized by ataxia, paresis, and behavioral signs. upon neurological examination after postictal stage, consciousness, posture, gait, and postural reactions were normal. cranial nerve examination showed bilateral central blindness and bilateral ventromedial strabismus. the findings were consistent with a forebrain lesion. physical and ophthalmological examination findings, biochemical serum profile and cbc test results were unremarkable. thorax radiography and abdominal ultrasound did not show alterations. pcr in urine for canine distemper virus and , h) in the third and fourth cases. mri of the third dog showed a few sulci in the temporal lobe, including the caudal sylvian gyri and lateral rhinal sulci (arrow). the main gyri (including the marginal, ectomarginal and suprasylvian) and the suprasylvian sulcus were absent. the internal capsule was abnormally small, and internal hydrocephalus was visualized (a-d). mri of the fourth dog showed generalized agyria with an absence of sulci and thickened gray matter with smooth appearance (arrow) (e, f). rhinal sulci in the temporal lobe were not apparent and cingulate gyrus was absent (arrowhead). internal hydrocephalus and supracollicular fluid accumulation associated with dorsocaudal outpocketing of the third ventricle (type sfa-iii) were observed (g, h) ifat in the serum for t. gondii and n. caninum were negative. mri showed generalized absence of sulci and gyri and thickened gray matter. the main sulci and gyri, including the marginal, ectomarginal, suprasylvian, ectosylvian, and lateral rhinal sulci, were absent. the cingulate gyrus was not recognizable, and the subcortical internal capsule was abnormally small (fig. ) . the diagnosis was consistent with lissencephaly with sfa, internal hydrocephalus and corpus callosum hypoplasia. prednisolone was then discontinued due to lack of indication. clinical presentation and mri did not support a diagnosis of meningoencephalitis. after dose readjustment with phenobarbital (gardenal ® , . mg/kg, orally q h; safoni, brazil) and levetiracetam as an adjunct (keppra ® , mg/ kg, orally q h for weeks; ucb biopharma, brazil), seizure frequency was reduced for the first months (> % frequency reduction of seizures). adjunct treatment with levetiracetam was discontinued after approximately weeks. at the -month follow-up examination, seizure reduction with an interictal interval over - months was noted and no more cluster seizures were observed. however, the behavioral changes, blindness and strabismus observed were persistent despite treatment. a phone conversation with the owners revealed that the dog was alive at the time of writing this report years after diagnosis. malformations of cortical development have rarely been reported in dogs, but epileptic seizures seem to be a frequent clinical sign in affected dogs [ , , ] . lissencephaly represents an uncommon disorder of the cortical gyration in dogs [ , , ] . lissencephaly without concurrent intracranial malformations was described in lhasa apso dogs, in an australian kelpie dog and in a small mixed-breed dog [ , , ] . this report is the first on lissencephaly in shih tzu dogs with other concurrent intracranial malformations and the first report providing a detailed neuroanatomical description of lissencephaly identified on mri. in humans, malformations of cortical development can lead to lissencephaly type i, characterized by pachygyria or agyria with thickened and smooth brain surface [ , ] . apart from lissencephaly, cortical development disorders that may cause epilepsy as subcortical band heterotopia, polymicrogyria, and cobblestone malformations have been described [ , ] . such disorders are rarely reported in dogs [ ] . four shih tzu dogs without any known close relationship, were referred because of epileptic seizures. the dogs were not selected among breeds. the onset of seizures was at the age of , , and months. previous studies have reported the onset of seizures in dogs between the age of approximately months and years in two lhasa apso [ , ] , one pekingese [ ] , one australian kelpie [ ] , and one mixed-breed dog [ ] . in humans with lissencephaly, approximately % of patients experience earlyonset seizures earlier than -months-old [ ] . neuro-ophthalmological abnormalities have been poorly characterized in dogs with lissencephaly. central blindness was previously reported [ , ] . we detected central blindness in three out of four dogs. bilateral vision deficits were thought to derive from occipital lobe lesions. bilateral ventromedial strabismus (esotropia) was detected in two out of four dogs. only one other report has described ventromedial strabismus in a dog with lissencephaly, which was associated with an orbital anatomical abnormality or short medial rectum muscle [ ] . we assumed that maldevelopment of the primary visual cortex and visual motor control mechanism may lead to esotropia [ ] . humans with lissencephaly have visual abnormalities, including no ocular fixation or tracking, poor visual tracking, nystagmus, variable esotropia, oculomotor apraxia, optic nerve and macular hypoplasia/ atrophy, delayed visual maturation, and cortical visual impairment [ ] . approximately % of human patients with lissencephaly type i have neuro-ophthalmological abnormalities [ ] . severe mental retardation may be observed in humans with lissencephaly and is associated with neuronal migration defects in spatial learning areas [ , , ] . motor disability as early hypotonia, spastic tetraplegia and opisthotonos is observed in human cases of lissencephaly due to defects in motor areas [ , ] . humans with lissencephaly often die before adulthood [ , , ] . in our study, early onset of several behavioral changes was detected in three dogs between and months old. alterations in locomotor behavior (pacing and changes in sleep pattern), aggressiveness (irritability to manipulation) and vocalization in addition to seizures were observed. previous studies observed late-onset behavioral changes in dogs with lissencephaly over -months-old [ ] [ ] [ ] [ ] ] , aggressiveness being frequently reported [ , , ] . the different clinical pictures between human and canine lissencephaly could be explained by the fact that the cerebral cortex is less essential in dogs than in humans for motor function [ ] . in dogs, motor function may be maintained despite frontoparietal lobe (motor area) and pyramidal system lesions. however, cognitive and learning abilities may be affected [ ] . magnetic resonance imaging in dogs with lissencephaly showed thickened cortical gray matter with smooth appearance, an abnormally small internal capsule, and absence of the major gyri and sulci when compared with healthy shih tzu dogs (additional file ). previous studies did not report detailed neuroanatomical examinations of cortical gyri and sulci in dogs with lissencephaly [ , , ] . in addition, mri was informative for correct ante-mortem diagnosis of multiple congenital anomalies, determination of cerebral morphology, and the degree of lissencephaly in shih tzu dogs. lissencephaly is graded in humans using a -point grading system based on the severity and anterior-posterior brain gradient of the abnormalities. grade represents severe lissencephaly with complete agyria, while grade represents mild subcortical band heterotopia [ , ] . grades a to a are more severe posteriorly and b to b anteriorly [ , ] . using these criteria, the second (fig. e) , third (fig. a) and fourth (fig. e) cases presented here were classified as grade a with diffuse agyria and few shallow undulations in the frontal and temporal lobes. the first dog was classified as grade a due to mixed parieto-occipital agyria and frontal pachygyria (fig. a) . previous studies have reported lissencephaly grade a [ ] and b [ ] in dogs. in our study, behavioral alterations and central blindness were noted in dogs with more severe lissencephaly grade, indicating a possible correlation between mri severity and clinical signs. the grade of lissencephaly was not related to the severity of the clinical signs in previous studies [ , ] . two forms of lissencephaly have been described in humans: classic lissencephaly (or type i), characterized by abnormal thick cortical layers (four layered, with a cell-sparse zone), agyria or pachygyria without malformation of the brainstem and cerebellum [ ] . mutations in cytoskeletal genes, such as the platelet activating factor acetylhydrolase b regulatory subunit , doublecortin, and tubulin a a genes [ , , ] , can lead to lissencephaly in humans and mice [ , ] . cobblestone lissencephaly (type ii) is characterized by multiple shallow furrows, a thin cerebral mantle and malformation of the brainstem and the cerebellum [ , ] . in dogs, genetic mutations for lissencephaly have not yet been described [ , ] . in our study, muscular and ocular disorders were not observed and mri did not showed nodular brain surface and brainstem or cerebellum malformations associated to cobblestone lissencephaly [ ] [ ] [ ] . therefore, our dogs likely have lissencephaly analogous to type i human lissencephaly [ , , ] . lissencephaly is overrepresented in the lhasa apso dogs and was also reported in the genetically related pekingese breed [ , ] . considering the genetic relation among lhasa apso, pekingese and shih tzu breeds [ ] , it is possible that lissencephaly may be a genetic disease in dogs. hydrocephalus and sfa are intracranial malformations most often reported in young and toy breed dogs [ ] [ ] [ ] . enlarged ventricles (a condition known as ventriculomegaly) comprise a common finding in adult brachycephalic dogs [ , ] . dogs with only ventriculomegaly do not have increased intraventricular pressure and are considered to be asymptomatic [ , ] in our study, internal hydrocephalus was confirmed based on specific mri features that indicated increased intraventricular pressure in three dogs [ ] . hydrocephalus with concomitant lissencephaly has not been reported in dogs. in dogs, lissencephaly has been diagnosed together with ventriculomegaly rather that with hydrocephalus [ , , ] . in a human study, ventriculomegaly has been observed in . % of patients with lissencephaly type i [ ] . supracollicular fluid accumulation without concomitant lissencephaly has been reported in male brachycephalic dogs, and the shih tzu dog breed was most often reported [ ] . in dogs, most sfas are associated with dorsocaudal outpocketing of the third ventricle (sfa-iii) [ ] . an expansion of both the third ventricle and the quadrigeminal cistern is another type of sfa (sfa iii-qc) [ ] . a few cases present with enlargement of the sole quadrigeminal cistern (sfa-qc) [ ] . previously, it was hypothesized that type sfa-iii in predisposed breeds can be part of hydrocephalus rather than an anomaly itself [ ] . in our study, the first dog presented with sfa-qc and type sfa-iii was detected in the second and fourth dogs. although sfa can be related to the presence of neurological signs in dogs with lissencephaly, the clinical significance of sfa is variable and sfa may be incidental in dogs with other intracranial diseases [ ] . there is no reported genetic relationship between sfa and lissencephaly in neither dogs nor humans. in humans, supracollicular fluid accumulation is associated with a defect in leptomeninges development [ ] . corpus callosum abnormalities have been sporadically reported and are still poorly understood in dogs, typically being an isolated abnormality or associated with holoprosencephaly and inborn errors of metabolism. the most frequent clinical signs described are hypodipsia/ adipsia, tremors, and seizures [ ] . we observed concurrent corpus callosum hypoplasia in the second, third, and fourth dogs, which is not commonly reported in dogs with lissencephaly [ ] . epileptic seizures may be related to corpus callosum hypoplasia. in humans, corpus callosum abnormalities are associated with classic lissencephaly (type i), cobblestone lissencephaly (type ii) and polymicrogyria [ , ] . the antiepileptic drugs used resulted in good control of cluster seizures with mild adverse effects in the long-term follow-up ( - months). seizures were persistent, although, compared to pretreatment, a reduction in the frequency (> % or more) and severity of seizures as well as cessation of cluster seizures was observed. other signs of forebrain abnormalities, such as behavioral alterations, central blindness, and bilateral strabismus were persistent. several medications, including carbonic anhydrase inhibitor acetazolamide and proton-pump inhibitor omeprazole, with the goal of decreasing cerebrospinal fluid production, have been proposed as medical management in dogs with hydrocephalus [ , , ] . experimental studies in healthy dogs and rabbits reported that cerebrospinal fluid production was reduced after acetazolamide and omeprazole treatment, respectively [ , ] . due to hydrocephalus, the second and third dogs were medically treated with acetazolamide and omeprazole. nevertheless, aggressiveness, changes in sleep cycle, compulsive pacing, central blindness, and strabismus were persistent during the follow-up period despite treatment with acetazolamide and omeprazole. one previous report has described no significant effects on recovery of the neurological signs or ventricular volume reduction after treatment with acetazolamide in dogs with hydrocephalus [ ] . furthermore, chronic oral omeprazole therapy in healthy dogs did not affect cerebrospinal fluid production [ ] . the major limitation of this study was the lack of histopathological evaluation, which was not possible because dogs were not euthanized during the follow-up period. although transcranial ultrasonography or computed tomography may aid in diagnosis, these methods are not precise [ , ] . in our study, the use of low-field mri provided a good resolution for ante-mortem diagnosis of lissencephaly in all dogs. variations in signal intensity, identification of abnormal cortical layers and depth of cortical sulci were observed. all anatomical structures of the cerebral cortex were identified (additional file ). in agreement, previous studies performed diagnosis in dogs using mri fields between . -and . -tesla [ , , ] . mri is the modality of choice for lissencephaly diagnosis and for the differentiation of other neuronal migration disorders, showing a correlation with histopathological features in dogs and humans [ , , ] . lissencephaly should be considered an important differential diagnosis in shih tzu dogs presenting predominantly with early-onset signs of forebrain abnormalities, including tonic-clonic seizures, behavioral alterations, central blindness, and bilateral ventromedial strabismus. low-field mri may be a useful diagnostic tool to detect cases of lissencephaly. hydrocephalus, sfa, and corpus callosum hypoplasia comorbidities could also be associated with lissencephaly in shih tzu dogs. genetic malformations of cortical development a developmental and genetic classification for malformations of cortical development: update lissencephaly and other malformations of cortical development: update genetic basis of brain malformations the genetics of lissencephaly neuropathology of lissencephalies. child's nerv syst magnetic resonance imaging features of lissencephaly in lhasa apsos lissencephaly in two lhasa apso dogs lissencephaly in a pekingese lissencephaly in an adult australian kelpie veterinary neuroanatomy and clinical neurology clinical and mri findings of lissencephaly in a mixed breed dog inborn errors of metabolism leading to neuronal migration defects polymicrogyria in standard poodles lis -related isolated lissencephaly brain abnormalities in infantile esotropia as predictor for consecutive exotropia ocular findings in lissencephaly wynshaw-boris a. impaired learning and motor behavior in heterozygous pafah b (lis ) mutant mice a developmental and genetic classification for midbrain-hindbrain malformations genetic structure of the purebred domestic dog magnetic resonance imaging signs of high intraventricular pressure-comparison of findings in dogs with clinically relevant internal hydrocephalus and asymptomatic dogs with ventriculomegaly clinical and magnetic resonance imaging characteristics of quadrigeminal cysts in dogs congenital hydrocephalus multidetector computed tomographic and low-field magnetic resonance imaging anatomy of the quadrigeminal cistern and characterization of supracollicular fluid accumulations in dogs corpus callosal abnormalities in dogs inhibition of cerebrospinal fluid formation by omeprazole different effects of omeprazole and sch on canine cerebrospinal fluid production effect of certain drugs on cerebrospinal fluid production in the dog effect of acetazolamide and subsequent ventriculo-peritoneal shunting on clinical signs and ventricular volumes in dogs with internal hydrocephalus evaluation of the effect of oral omeprazole on canine cerebrospinal fluid production: a pilot study publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations the authors are grateful to heraldo andré catalan rosa for technical support with mri. data have not been published previously. supplementary information accompanies this paper at https ://doi. org/ . /s - - - .additional file : table s . doc. summary of magnetic resonance imaging (mri) findings of lissencephaly and concomitant congenital malformations in shih tzu dogs. details regarding malformation type, mri scan, positioning of the patient, sequence types, imaging parameters and contrast medium are described.additional file : figure s . doc. brain magnetic resonance imaging (mri) in a healthy shih tzu dog. transverse t -weighted (a and b) and transverse and sagittal t -weighted (c and d) imaging. the following structures were identified at the level of the interthalamic adhesion: marginal gyri (a); marginal sulci (b); middle ectomarginal gyri (c); ectomarginal sulci (d); middle suprasylvian gyri (e); middle suprasylvian sulci (f ); middle ectosylvian gyri (g); caudal ectosylvian sulci (h); caudal sylvian gyri (i); pseudosylvian fissure (j); lateral rhinal sulci (k); splenial sulci (l); cingulate gyri (m) and corpus callosum (o) (a). the following structures were identified at the level of the mesencephalic aqueduct: marginal gyri (a); marginal sulci (b); middle ectomarginal gyri (c); ectomarginal sulci (d); caudal suprasylvian gyri (e); caudal suprasylvian sulci (f ); ectosylvian gyri (g); lateral rhinal sulci (h); parahippocampal gyri (i) and caudal composite gyri (j) (b). in transverse and sagittal t -weighted images, all anatomical structures were normal, including the lateral ventricles, quadrigeminal cistern and corpus callosum (c and d). authors' contributions dnrs and rma conceived and designed the study. dnrs, gbap, eft and vmm performed the diagnostic work-up, clinical assessment, and provided professional discussion regarding the cases. rma and vmm evaluated and interpreted magnetic resonance imaging. dnrs and gbap wrote the manuscript. rma critically revised the manuscript. all authors read and approved the final manuscript. not applicable. mri equipment was acquired through funding (procedure number / - ) provided by the são paulo research foundation (fapesp). the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. this study was not submitted for ethics committee review because it is a retrospective analysis of medical records of the veterinary neurology service, school of veterinary medicine and animal science form sao paulo state university-unesp -brazil. not applicable. the authors declare that they have no competing interests. key: cord- - bllqwh authors: kalidindi, kalyan kumar varma; gupta, mayank; chhabra, harvinder singh title: a rare cause of neurological deterioration to complete paraplegia after surgery for thoracic myelopathy: a case report date: - - journal: spinal cord ser cases doi: . /s - - -z sha: doc_id: cord_uid: bllqwh introduction: progressive deterioration of neurological status post-thoracic myelopathy surgery after a clinically stable period is rare and can pose a diagnostic dilemma. we present our experience with such a case where all known etiologies were ruled out and the cause of deterioration could not be conclusively identified. the course was found to be similar to sub-acute post-traumatic ascending myelopathy (spam). however, the condition has only been described for traumatic injuries so far. case presentation: our patient presented a history of back pain and associated gait instability for one and a half months. there was no history of trauma. investigations suggested an anderson-like lesion at t –t with cord edema at the same level suggestive of instability. she underwent posterior stabilization t to l and laminectomy of t as well as t under neuromonitoring. the postoperative sequence of events included an episode of pyrexia on the fifth day of surgery, neurological deterioration from the seventh day of surgery proceeding to complete paraplegia by the fourteenth day, no response to steroid treatment and no signs of recovery till two years post surgery. mri findings were suggestive of spam, and there was no evidence of infection. discussion: ascending myelopathy is a potential but rare cause of delayed deterioration in neurological status after surgical intervention. mri findings of cord edema extending more than four levels above the involved segments is a characteristic finding of the condition. ascending myelopathy may lead to complete cord injury. the precise cause of the condition is unknown and prognosis remains poor. outcomes of surgical management of thoracic myelopathy have not been very promising. one of the main contributing factors to the poor outcome is the vulnerable spinal cord at the site of the lesion due to relative avascularity and reduced available space [ ] . the deterioration of neurological status is a known complication of surgical decompression of thoracic myelopathy detected, either intraoperatively through neuromonitoring or in the immediate postoperative period on assessment of neurological status [ ] . progressive deterioration of neurological status postoperatively is rare and can pose a diagnostic dilemma. we present our experience with one such case where all known etiologies were ruled out and the cause of progressive postoperative neurological deficit could not be conclusively identified. on thorough search of the available literature, the clinical course was found to most closely resemble an entity known as spam, which has so far been reported to occur only after significant trauma. the rarity of occurrence and lack of any published article till date warrants this case to be reported in the literature. a -year-old female was presented to our center with severe pain of weeks' duration in the mid-back. the pain was insidious in onset, continuous, of progressively increasing intensity and with a postural variation. she was unable to lie supine due to severe intercostal pain and had to sleep in a sitting posture causing severe disability. there were associated non-dermatomal paresthesias in both lower limbs. she had been bedridden for the past weeks before the presentation due to severe gait instability, resulting in an inability to walk. there were no bowel or bladder symptoms. there was no history of associated fever, significant trauma, constitutional symptoms or history suggestive of an inflammatory etiology. she had a past history suggestive of compressive cervical myelopathy two years ago when she was presented to us with difficulty in walking and weakness in both upper limbs. her neurologic status at that time of presentation was attached in fig. a according to the asia/ iscos-isncsci (american spinal injury association/ international spinal cord society-international standards for neurological classification of spinal cord injury). posterior stabilization from c to t and decompression by cervical laminectomy c to c and foramen magnum decompression was done at our center. she had a good outcome with an improvement of symptoms and regained the ability to walk without support (fig. b) . on examination, there was tenderness in the mid-back over t -t region. movements of the spine could not be tested due to severe pain. higher mental functions, cranial nerve functions and neurological status in the upper limbs were within normal limits. in both lower limbs, there was increased tone and weakness. the neurologic status was as attached in fig. c . deep tendon reflexes in knee and ankle were exaggerated and plantar reflexes were extensor bilaterally. on the basis of clinical findings, a provisional diagnosis of thoracic myelopathy was made. radiological examination revealed multiple syndesmophytes with suspected instability between t and t vertebrae on standing anteroposterior and lateral radiographs with features suggestive of diffuse idiopathic skeletal hyperostosis (dish). the patient could not lie supine in mri due to severe back as well as girdle pain and hence, an mri was done under sedation. it revealed a three-column anderson-like lesion at t -t level with cord edema behind t vertebra suggestive of dynamic cord compression (fig. ) . based on these clinical and radiological findings, the patient was advised stabilization and decompression under general anesthesia to reduce pain and prevent further deterioration in neurological status. after a thorough preoperative workup, preanesthetic checkup and written there was an incidental durotomy, which was covered with fat graft and fibrin sealant. there was no loss in the motor evoked potentials intraoperatively. there was no deterioration of neurological status on immediate postoperative assessment. postoperative antibiotics and analgesics were given according to the institute's protocol. rehabilitation was initiated. on the first postoperative day, there was a significant reduction in back pain but she still complained of severe intercostal pain around t to t region predominantly on the left side which temporarily responded to intercostal blocks, tens (transcutaneous electrical nerve stimulation) and pregabalin. the intercostal blocks had to be repeated several times postoperatively. she had hyperesthesia in both lower limbs since day two for which the dose of pregabalin was increased gradually. postoperative mri revealed an adequately decompressed cord (fig. a, b) . radiographs and ct scan demonstrated a stable fixation (fig. c, d) . the screws were well positioned. she had one spike of fever ( degrees fahrenheit) on day five of surgery for which no infective cause could be identified. the fever subsided with supportive treatment and antipyretic medication. at seven days post surgery, she started developing weakness and loss of sensations in both the lower limbs. repeat mri revealed hyper-intense signal changes extending five levels above the index level (up to t vertebra) but no static compression or instability at the index level (fig. ) . she was provisionally diagnosed as a case of subacute ascending myelopathy, a type of noncompressive myelopathy. the prognosis was discussed with the patient and attendants in detail. she was put on a high dose of intravenous methylprednisolone ( mg) for days followed by a course of oral steroids (tapering dose from to mg). there was a temporary halt in the progression of weakness. csf tap suggested no signs of infection, virological and serological workup was negative, and mri of the brain was normal. the wound was dry. there were no other signs of infection. her total and differential white blood cell counts were normal and creactive protein was normal. the weakness gradually progressed from ninth postoperative day resulting in complete paraplegia (neurological level t ) with completely absent perianal sensation and voluntary anal contraction by fourteenth postoperative day (fig. d) . mri was repeated at weeks and months post surgery, which suggested persistent edema till t vertebral level (fig. ). she underwent a comprehensive rehabilitation program and was independent in the activities of daily living at the time of discharge on the th postoperative day. there was no further recovery in her neurological status even after two years of follow up. spam has been described in the literature as an unusual cause of delayed neurological deterioration after traumatic spinal cord injury in cases where the deterioration could not be explained by mechanical instability, syrinx formation or therapeutic mis-intervention. it was originally described by frankel in [ ] . very few such cases have been reported in the literature suggesting that it is a rare entity and the condition is poorly understood [ ] [ ] [ ] [ ] [ ] [ ] . this entity has been described only in post-traumatic cases. common reported features of spam include neurological deterioration after few days to weeks of surgical spinal stabilization, an often preceding episode of pyrexia and an area of hyperintense signal extending at least four levels above the initial injury level on t mri imaging [ ] . proposed hypotheses include impairment of spinal venous drainage, arterial thrombosis, inflammatory processes or secondary injury processes. inadvertent cord handling rarely causes extension of edema more than two levels above the injured segment and should be evident in the immediate postoperative period [ ] . after an exhaustive literature search, we could not identify any case with such findings reported after atraumatic thoracic myelopathy. the case described here had clinical and radiological features closely resembling spam. the fact that there was no significant trauma and no extension of edema from the index level even weeks after onset of symptoms suggests that secondary injury processes are unlikely to be the cause for the condition. the gradual onset of symptoms, no sparing of the posterior column and no evidence of abnormal vascular markings on early and late mri suggest that arterial cause is less likely [ ] . venous congestion may involve the central gray matter more than the peripheral white matter, an axial mri finding seen in our case. however, the mri images did not demonstrate venous stasis or engorgement of surface venous structures, findings that are frequently seen in this condition when caused by a dural arteriovenous malformation [ ] . the inflammatory pathology of the disco-vertebral anderson-like lesion, radiological findings of enthesitis, the temporal progression of myelopathy and mild pyrexia suggest that inflammatory pathology may be a likely contributing factor for ascending myelopathy [ ] . cordectomy has been described as an effective treatment by meagher et al. in his case [ ] . laminectomy and pial incision as a treatment option has been proposed by okada [ ] . various other treatments proposed are anticoagulation, steroids, and mannitol. none of the treatment options proposed have been established as a standard treatment till date and the prognosis of the condition remains poor. this case report provides us with an insight into a potential cause akin to spam, which needs to be considered in a patient with progressive neurological deterioration after surgical decompression and stabilization for myelopathy. to the authors' knowledge, this is the first case report of such a condition after surgical decompression and stabilization of thoracic myelopathy. in conclusion, ascending myelopathy is a potential cause of delayed deterioration in neurological status after surgical intervention. an mri finding of cord edema extending more than four levels above the involved segments is a characteristic finding of the condition. ascending myelopathy may lead to complete paraplegia or even tetraplegia. the precise cause of the condition remains unknown and prognosis remains poor. staged spinal cord decompression through posterior approach for thoracic myelopathy caused by ossification of posterior longitudinal ligament the incidence and risk factors of postoperative neurological deterioration after posterior decompression with or without instrumented fusion for thoracic myelopathy ascending cord lesion in the early stages following spinal injury resolution of spam following cordectomy: implications for understanding pathophysiology subacute delayed ascending myelopathy after low spine injury: case report and evidence of a vascular mechanism pathological features including apoptosis in subacute posttraumatic ascending myelopathy subacute posttraumatic ascending myelopathy after spinal cord injury ascending myelopathy in the early stage of spinal cord injury sequential changes of ascending myelopathy after spinal cord injury on magnetic resonance imaging: a case report of neurologic deterioration from paraplegia to tetraplegia acute ascending myelopathy of the spine acknowledgements the authors would like to thank the concerned patient for allowing the details to be shared. conflict of interest the authors declare that they have no conflict of interest.publisher's note: springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- - dgmdtj authors: nan title: neurocritical care society th annual meeting: october - , sheraton denver downtown hotel denver, colorado date: - - journal: neurocrit care doi: . /s - - - sha: doc_id: cord_uid: dgmdtj nan ahrq guidelines for venous thromboembolism (vte) prophylaxis recommend risk stratification of patients and tailoring prophylaxis to that risk. while anticoagulation is a mainstay of optimal vte prophylaxis after trauma, little data exists to determine when tbi patients warranting neurosurgical intervention become candidates for such treatment. our group sought to determine the natural evolution of intracranial hemorrhage in these high risk patients and identify factors contributing to early radiographic stabilization. all tbi patients undergoing craniotomy and/or intracranial monitoring and surviving at least hours were followed prospectively from feb to nov . radiographic stabilization was defined as the time between injury and the final ct scan that showed no worsening during the hospital stay. kaplan meier (km) curves were used to compare time to stabilization by type of intervention. binary logistic regression was used to identify covariates contributing to stabilization within hours of injury. for the overall cohort (n= ), km curves showed no difference in time to radiographic stabilization by type of neurosurgical intervention. significant associations were found between stabilization at hours and higher presenting gcs (or: . , %ci . - . ), younger age (or: . , %ci . - . ), and male gender (or: . , %ci . - . ). subjects with a presenting gcs of > (n= ) had an % ppv for radiographic stabilization by hours after injury. the auc for the logistic regression model was . . sentinel headache refers to discrete thunderclap headache in the weeks preceding hospital admission for sah. a large proportion of these events are thought to represent aneurysmal bleeding events. repeat hemorrhages have been found to increase the extent of vasospasm in experimental models, and are often assumed to increase the risk of delayed cerebral ischemia (dci) in humans (the "double bleed effect"). cerebral performance category (cpc) is a standard outcome measure after cardiac arrest, but has limited ability to discriminate between mild and moderate brain injury. we hypothesized that many cardiac arrest survivors with good cpc scores would have significant deficits on blinded neurocognitive testing. patients initially comatose after cardiac arrest treated who awoke after therapeutic hypothermia (th) were evaluated by a neuropsychologist prior to hospital discharge with the repeatable battery for the assessment of neuropsychological status (rbans), a well-validated tool that assesses function in multiple domains compared to standardized normal values. patients admitted between nov and may awoke after th, completed the rbans evaluation after leaving the icu and ready for discharge. median age was yrs (range - ), % male, had initial rhythm vt/vf, median time to rosc was minutes (range - ). seven patients had a cpc of , patient had a cpc of , and patient had a cpc of . seven patients were discharged home and to acute rehab. attention and delayed memory were severely abnormal half of the patients (below th percentile), language and visuospatial domains were affected less often in % of the patients (below th percentile). on cumulative scores of all domains, all patients scored below the th percentile compared to age and education adjusted scores, regardless of cpc score. cardiac arrest survivors with cpc scores considered 'good' frequently had severely abnormal neurocognitive function just prior to hospital discharge. the cognitive domains most frequently affected were attention and delayed memory. more sophisticated testing with tools such as rbans may better identify components of cognitive dysfunction after cardiac arrest which may be targets for additional therapeutic intervention and be a more meaningful tool for long-term follow-up studies. introduction quantitative brain diffusion-weighted imaging (dwi) mri may help predicting the degree of functional recovery in patients ain volume with an apparent diffusion coefficient (adc) < x - mm /sec differentiated between cardiac arrest survivors who regained an independent lifestyle and those with impaired functional outcome. we aimed to validate this threshold in an external dataset. dwi mris of comatose post-cardiac arrest patients were obtained between - hours post-arrest. survivors who regained consciousness by day were assigned to one of two recovery groups: good recovery (discharged to home) and impaired recovery (discharged to a skilled nursing facility, rehabilitation facility or another hospital). the quantitative dwi data were obtained blinded to patient outcomes. the brain masks were semi-automatically created on the b images using medical image processing, analysis and visualization program (mipav). the adc values of each voxel within the brain were determined. data of patients from five us centers (columbia, mgh, mayo clinic jacksonville, northwestern, and stanford) with adequate mris were analyzed. of these, ( %) patients regained consciousness and survived to discharge: mean age ± years, % female, arrest duration ± minutes, % of patients received therapeutic hypothermia, mri obtained at ± hours post-arrest. the median (iqr) percentage of brain volume with adc< x - mm /sec was . % ( . - . ) in patients with good recovery (n= ) and . % ( . - . ) in patients with impaired recovery (p= . ). an adc< x - mm - ) sensitive and % ( %ci - ) specific for good recovery. the results of this validation study support earlier findings that quantitative dwi mri in comatose post-cardiac arrest patients is a sensitive prognostic test to predict the degree of functional recovery in post-cardiac arrest survivors. according to the universal determination of death act, death in the united states is determined in accordance with accepted medical standards, which can be national, regional, or local. as a result, significant variability in brain death (bd) determination has been reported among the best hospitals across the country. we tested the hypothesis that similar variability exists in individual states, such as michigan. michigan health and hospital association and gift of life of michigan (the local organ procurement organization) databases were reviewed for hospital bd policies. only hospitals with > beds and an intensive care unit were included. several bd determination process variables were extracted and analyzed with descriptive statistics. results / hospitals had bd policies, did not and in it was unclear. ten different combinations of physicians allowed to perform the exam were included. in . % there were no prerequisites to initiate bd and in . % no established cause mentioned. ten different temperatures to initiate bd exam were required. five different arterial blood carbon dioxide levels to establish positive apnea test were cited. a single bd exam was requested in . % of policies, a dual in . % and a single or dual in . %. confirmatory tests were optional ( %), recommended ( . %) or mandatory ( %). electroencephalogram was the most common confirmatory test ( %) and ct angiogram the least common ( %). we report significant variability in the bd hospital policies in michigan despite published guidelines from the american academy of neurology. if one accounts for additional variability in the strict implementation of these policies at the bedside level, the urgency for a uniform state-wide bd policy becomes even more obvious. intrathoracic pressure regulation (ipr) therapy is a novel therapy that non-invasively modulates pleural pressures to take advantage of the physiological benefits that occur by creating pressure differentials in the thorax. after each positive pressure breath ipr lowers intrathoracic pressure to subatmospheric levels relative to the rest of the body. this intervention enhances cardiac preload and output and decreases intracranial pressure (icp). we hypothesized that ipr therapy which has been previously shown to increase calculated cerebral perfusion pressures would also increase cerebral blood flow (cbf) in a porcine model of elevated icp. in this pilot study, four isofluorane anesthetized pigs ( . ± . kg) were subjected to a focal brain injury by epidural insertion of an french foley catheter into the left hemisphere which was slowly filled with saline to simulate a traumatic brain injury with elevated icp. in the right hemisphere, a thermal diffusion probe was used to measure cbf (hemedex, inc., cambridge, massachusetts) while a millar catheter was used to measure icp. once a stable elevated icp was confirmed, ipr therapy was applied at a level of - cmh o for minutes. end tidal co was held constant at mmhg by adjusting the respiratory rate during ipr use. tbi is a major risk factor for the development of alzheimer's disease (ad). in previous animal and human studies, an increase in the expression of amyloid precursor protein (app) after tbi was found to correlate with the disruption of neuronal activity, beta-amyloid plaque formation, cognitive decline, and even death.to date, no interventions used at decreasing amyloid plaque load after tbi have been identified. in this study, using the controlled cortical impact device we produced a severe head injury in month old xfad mice. at minutes and hours after injury, the xfad mice were treated intraperitoneally with either placebo or resveratrol (anti-oxidant; mg/kg). at month after injury, the animals were intracardially perfused with . % saline followed by % phosphate-buffered formalin. the whole brain was removed, sliced, and stained for beta-amyloid levels using immunohistochemistry. in addition, tunel+ cells were measured at the indicated time-points to determine the level of neural injury. in this study we found that treatment with resveratrol at minutes and hours post-injury resulted in a significant reduction in beta-amyloid plaque load near the injury zone (parietal cortex) (p< . ) and hippocampus (p< . ). also, the mice treated with resveratrol had reduced (p< . ) tunel+ staining. while a multitude of etiologies may lead to coma, treatments for coma remain elusive. the hypothalamic orexin pathway, critical in sleep/wake cycles, can stimulate multiple areas of the brain and provides a potential pharmacologic target towards improving arousal after coma. we used a post-cardiac arrest (ca) rodent coma model to assess whether postresuscitative orexin-a intracerebroventricular (icv) infusion after bolus injection would provide immediate and long term arousal after ca. seventeen adult wistar rats (male, - gms) were implanted with a icv cannula attached to an osmotic pump. one week later, rats underwent baseline eeg followed by -minute asphyxial ca. forty-five minutes after resuscitation, rats were randomized to either orexin-a (n= ) or saline (n= ) icv bolus and infusion. eeg was monitored continuously for hours after ca, and for minutes at hrs, hrs, hrs, and days post-ca. behavioral testing (neurologic deficit scale; nds) was also conducted at these times. eeg was quantitatively analyzed using information quantity (iq), an entropy based nonlinear previously established by us. rats receiving orexin-a almost immediately exhibited higher iq when compared to saline ( . ± . vs. . ± . ; p< . ). this acute improvement in iq appeared with slowest sub-bands (e.g.ð) improving first followed progressively by faster sub--ca. moreover, orexin--band at hrs ( . ± . -band at hrs ( . ± . vs . ± . ; p< . ). behaviorally, orexin-a allowed rats to perform significantly better on the nds at hrs ( . ± . vs. . ± . ; p< . ); hrs ( . ± . vs. . ± . ; p< . ); hrs ( . ± . vs. . ± . ; p< . ), and hrs ( . ± . vs. . ± . ; p< . ). heart rate variability (hrv) characteristics have been associated with outcome after traumatic brain injury. we sought to determine if hrv characteristics in the first hours after subarachnoid hemorrhage (sah) are associated with hospital morbidity and mortality. continuous ekgs recorded ( hz sampling) during the first hours post-sah was analyzed in of consecutively admitted patients between and . admission clinical scores, radiographic, surgical, ventilation and the pan-tompkins algorithm was applied to identify the qrs complex. fft calculations were generated for the following - . hz), low frequency (lf: . - . hz), very low frequency (vlf: . -nerated sample entropy and /f --minute (fft< . hz), or -minute individual multivariable logistic regression analyses of hospital morbidity and mortality controlling for admission hunt and hess grade, apache ii physiological sub-score, age, and mechanical ventilation status were conducted. dialysis disequilibrium syndrome (dds) is characterized by varying central nervous system manifestations secondary to cerebral edema that most often occurs after the first round of hemodialysis (hd). literature suggests that underlying brain injury may predispose patients to the development of dds. however, the pathophysiology has yet to be elucidated. herniation from hd is thought to be exceedingly rare with current dialysis methods and has not been reported in the era of modern neurointensive care. we present a case series of three patients with acute neurological injury undergoing hd in the intensive care unit that rapidly developed fatal brain edema, secondary to dds, even after several previous uneventful rounds of hd. three patients, ages , and years, with traumatic brain injury, hypertensive intracerebral hemorrhage, and ischemic stroke underwent hd in the intensive care unit. the number of dialysis sessions prior to the development of dds was , and . all three patients developed clinical signs of herniation within minutes to hours of hd. ct scans showed global cerebral edema with both transtentorial and tonsillar herniation. aggressive osmotherapy with mannitol and supersalt were ineffective in reversing the massive edema and all three patients died. two of the patients had a significant reduction of the bun ( % and %) while the third had only a modest reduction. our case series illustrates the potential dangers of hd in patients with acute neurological injury who have a high potential for worsening cerebral edema. it also reaffirms that dds with fatal cerebral edema can occur even after several rounds of hd and with current hd techniques. utilization of continuous veno-venous hemofiltration instead of hd may prevent the rapid shifts of osmoles and prove safer in neurologically injured patients. traumatic coma is believed to be caused by disruption of the ascending reticular activating system (aras), a complex network of arousal pathways projecting from the brainstem to the hypothalamus, thalamus, and basal forebrain. there is a critical lack of diagnostic tools for detecting which components of the aras network are disrupted in traumatic coma. we aimed to determine whether an advanced mri technique, high angular resolution diffusion imaging (hardi), can detect disruptions in the brainstem arousal network that are implicated in the pathogenesis of traumatic coma. we used hardi tractography to analyze neural network connectivity in two postmortem brains: one from a -year-old woman who died three days after traumatic coma, and one from a -year-old woman who died of non-neurological causes. both specimens were scanned as dissected blocks of the brainstem, hypothalamus, thalamus, and basal forebrain on a small-bore, high field ( . tesla) mri scanner. hardi tractography analyses were performed to compare the structural integrity of each component pathway of the aras network in the traumatic coma and control specimens. upon completion of imaging, both specimens were sectioned and stained for correlative histopathological analysis. hardi tractography revealed that specific components of the aras network, including known cholinergic, glutamatergic and noradrenergic projections connecting the brainstem to the thalamus and basal forebrain, were severely disrupted in the traumatic coma specimen, as compared to the normal specimen. these disruptions were consistent with histopathological tissue tears and axonal swellings. by contrast, connectivity between the brainstem and hypothalamus, and within the thalamus itself, was partially preserved in the traumatic coma specimen. hardi tractography can detect disruptions in specific components of the aras network that are implicated in the pathogenesis of traumatic coma. this advanced imaging technique may be used to elucidate the neuroanatomic basis of coma in individual patients. refractory intracranial hypertension (rich) is associated with high mortality rates and is the final pathway of many neurocritical entities, such as severe traumatic brain injury (stbi). objective: to determine modifications in intracranial pressure (icp) and cerebral perfusion pressure (cpp) following indomethacin (indo) infusion after rich secondary to stbi. indo was administered in a loading dose ( . mg/kg/ minutes), followed by continuous infusion ( . mg/kg/h) in patients with icp> mmhg for more than minutes who did not respond to first line therapies. changes in icp and cpp were observed. clinical outcome was assessed at -day according to glasgow outcome scale (gos). analysis of indo safety profile was also conducted. differences in icp and cpp values were assessed using repeated-measures anova with an a-level of p< . twenty-nine consecutive stbi patients ( men and women) with a mean age ±sd ± years wereincluded. median posresucitation gcs score at admission was (iqr: - ) with a predominance of grade iv in marshall ct classification. our findings support the effective and feasibility of indo in reducing icp and improving ccp in rich patients. future studies to evaluate different doses, lengths of infusion and longer-term effects together with effects on outcome are needed. hematoma expansion after acute intracerebral hemorrhage (ich) occurs most frequently in patients presenting within hours of symptom onset. therefore, most investigational therapies have been tested only in patients presenting ultra-early in their disease course. however, the majority of ich patients present outside this time window or with an unknown time of onset. we investigated the prevalence of hematoma expansion in these patients with delayed presentation and assessed the accuracy of the ct angiography (cta) spot sign for identifying risk of hematoma expansion. we performed a prospective cohort study. consecutive ich patients undergoing cta and follow-up head ct were enrolled over ten years. cta spot sign readings were performed by two experienced readers and hematoma expansion was assessed using semi-automated software. expansion was defined as an increase in volume of > ml or an increase of > % from baseline ich volume. hematoma expansion occurred in % of patients. when stratified by time from symptom onset to initial ct, hematoma expansion rates were: % within hours; % between - hours, % beyond hours (but with known onset), and % in patients with an unknown symptom onset time. of patients who developed hematoma expansion, only % presented within hours. the accuracy of the spot sign in predicting hematoma expansion was . for patients presenting within hours, . between to hours, . after hours and . for patients presenting with an unknown onset time. a substantial number of patients destined to suffer from hematoma expansion present either late or with an unknown time of symptom onset. the cta spot sign accurately identifies patients destined to expand regardless of time from symptom onset, and may therefore open a path to offer clinical trials and novel therapies to the many patients who do not present acutely. intraventricular fibrinolysis has been shown effective in clearing intraventricular hemorrhage (ivh) in small series of patients. we present our experience with using fibrinolytics over years. retrospective analysis of prospectively collected data of patients with ivh admitted to two neuro-icus and treated with rt-pa instillation (one patient with tenecteplase) via intraventricular catheter (ivc) until the rd and th ventricles were cleared of blood. all patients were treated by the same neurointensivist with the same instillation protocol but different doses of drug based on individual patient characteristics. the graeb and leroux semi-quantitative scales were used to measure the amount of ivh before and after the last dose. patients (mean age . years, . % male) were admitted with a median gcs . thirty-one had intracerebral and aneurysmal subarachnoid hemorrhage, brain tumors, head trauma, arteriovenous malformation.and primary ivh. t-pa was administered at a total dose of . ± . mg (individual doses ranging between . to mg), with st dose . ± . hours from admission and for a duration of . ± days. the pre-fibrinolysis graeb and leroux scores were . ± . and . ± . and decreased post fibrinolysis to . ± . and . ± . (p< . ). a significant correlation between total fibrinolytic dose and difference in pre-post amount of ivh was found for the leroux scale (pearson . , p < . ). three patients had small tract bleeds (< cc, with one bleeding profusely at the incision site requiring transfusion) and one had extension of ich in the upper midbrain. no patient developed ventriculitis. the total dose of t-pa was lower in patients who received shunt, compared to who did not ( . ± . vs . ± , p< . ). eighteen ( . %) patients had -up of . ± . days. in our large series of patients, intraventricular fibrinolysis significantly decreased ivh with minimal complications. distinguished poster ___________________________________________________________________________________ white matter lesions significantly impact on outcome after aneurysmal subarachnoid hemorrhage (asah). brain extracellular tau is indicative for axonal injury, associated with poor neurological outcome after severe traumatic brain injury, however has not been elucidated so far in patients with asah. twenty-five consecutive asah patients monitored with cerebral microdialysis (cmd) and brain tissue oxygen tension (p b to ) were included. cmd total tau, phospho-tau- and beta-amyloid -- ) levels were analyzed at a hours interval until d and -hours interval until d using an elisa-technique (innogenetics). statistical analysis was performed with non-parametric tests and a mixed effects model as appropriate. median age was y ( - y) and admission hunt&hess grade ranged from to . cmd-tau, phospho-tau-- were detectable in all patients. probe location in perilesional tissue revealed a higher overall cmd-tau level (p< . ) - and phospho-tau. cmd-tau positively correlated with cmd-lactate (r= . , p< . ). brain hypoxic (p b to were associated with increased cmd-tau levels (p< . ). no correlation was found between other variables besides a higher phospho-tau level and cmd samples categorized as brain hypoxic hyperlactatemia. patients with poor outcome -tau level during hospital-course (p< . ) but no difference in phospho-tau-- (adjusted for disease severity). cerebral tau is elevated after asah and associated with perilesional probe location and poor -months functional outcome. association with brain-morphological abnormalities and neuropsychological deficits need further investigations. neurocrit care ( ) :s -s to date only two studies have evaluated anemia status in acute intracerebral hemorrhage [ich] . on admission anemia [oaa] was associated with larger hematoma volume and lower hemoglobin levels during hospital stay were related to poorer outcome. it remains unknown whether anemia impacts outcome primarily through its effects on ich volume or itself has independent effects. this retrospective analysis included consecutive patients with spontaneous supratentorial intracerebral hemorrhage. clinical data including the pre-admission-status, neuroradiological, initial presentation, treatment, and outcome were evaluated through institutional databases, patient's medical charts and by mailed questionnaires. multivariate logistic and graphical regression analyses were calculated to evaluate associations of oaa with functional outcome and to determine independent effects of oaa. oaa was associated with larger ich volume ( . cm³ versus . cm³, p= . ), greater extent of intraventricular hemorrhage [ivh] (p= . ) and poorer neurological status on admission (p< . ). further, oaa showed a true positive and accurate association with larger hemorrhage volumes (roc: p= . ,auc> . ). multivariately, for all patients despite age, only oaa could be elucidated as independent predictor of unfavorable functional outcome (mrs > ) at days (or= . ;p= . ). comparison of separate multivariate models revealed: for oaa-patients no independent predictor could be identified, whereas in non-oaa patients ich volume demonstrated known independent effects on functional outcome (or . ;p= . ). within this study oaa was shown to be a significant predictor of an unfavorable functional outcome and has independent effects beyond its accurate association with larger hemorrhage volumes. oaa appears to be a very relevant and previously unrecognised predictor of functional outcome at days. the recognition of anemia and its treatment could possibly open up new therapeutic avenues to decrease the rate of functionally dependent patients after ich. this strongly supports the need of prospective interventional studies to evaluate the influence of anemia in patients with intracerebral hemorrhage. in patients with suspected subarachnoid hemorrhage and negative brain imaging, lumbar puncture is recommended. this test is frequently complicated by false-positive results due to a traumatic tap. we hypothesized that blood precipitating in the thecal sac following non-traumatic subarachnoid hemorrhage would be visible on mri. a prospective database for subarachnoid hemorrhage was searched for patients who received mr lumbosacral spine imaging during admission for subarachnoid hemorrhage. electronic chart review was completed. all mr studies were read and interpreted by a neuroradiologist. patients (n= ) with subarachnoid hemorrhage underwent delayed mri imaging of the lumbosacral spine an average of days (range - days) after the onset of symptoms. the median hunt-hess grade for this cohort was (range - ). the median fisher grade was . blood precipitating in the thecal sac was visible in out of patients ( %). the density of blood compared to csf was hyper-intense on t (bright) and hypo-intense on t (dark). the blood was most evident at l and s levels and layered in a dependent fashion. delayed ct head non-contrast obtained at the time of the mri ls spine demonstrated resolution of subarachnoid hemorrhage in / patients and a small amount of isodense intraventricular hemorrhage layering in the occipital horns was detected in / patients. delayed neuroimaging with ct head after subarachnoid hemorrhage has a high false negative rate. mr imaging of the lumbosacral spine detected persistent blood products settling in the thecal sac despite clearance of subarachnoid blood on ct head imaging. mr lumbosacral spine imaging could serve as a 'virtual lumbar puncture' in patients with suspected subarachnoid hemorrhage. stroke patients receiving iv tpa can be admitted to an icu or a stroke unit (su) but su admission may be more costefficient. we compared icu admission vs su admission in tpa-treated patients. during the initial years of this retrospective study, patients were admitted to the icu as we lacked a su. in the following years, patients were admitted to a new su. demographics, medical history, nihss, treatment interventions, neurologic and medical complications, and mortality were collected to determine if icu admission resulted in better outcome and less complications. categorical variables were analyzed with fishers exact test and continuous ones with proportion of the means test (t-test). we compared icu admissions and su admissions. icu admission included % males and su admission included % males (ns). median age for icu and su admission was and respectively (ns). admission nihss was for icu patients and for su patients (ns). the median length of stay in the icu was day (as per protocol) and the median su length of stay was days. intravenous anti-hypertensives (bolus) were used in % of icu patients and in % of su patients (p= . ) and continuous infusions in % of icu patients and % of su patients (p= . ). initial nihss scale of > predicted need for mechanical ventilation (p= . ). intracranial hemorrhage occurred in % of icu and % of su patients (ns). complications (pneumonia, venous thromboembolism, sepsis, or death ) did not differ. there was no difference in the proportion of patients with mrs of or less in the two groups ( % vs %). admission to the su resulted in savings of $ , per patients/day. patients receiving tpa can be safely admitted to a su resulting in significant cost savings. patients with nihss > are likely to need icu admission for mechanical ventilation. stroke patients with dysphagia have a high incidence of aspiration, which may lead to pneumonia. evidence suggests that ace inhibitor use may decrease the risk of pneumonia via their inhibitory effects on substance p degradation. the objective of this study was to investigate the association between ace inhibitor use and the development of pneumonia in hospitalized stroke patients. a retrospective case-control analysis was performed. eligible patients (n= ) were individuals admitted to saint louis university hospital with a diagnosis of acute ischemic stroke, spontaneous intracerebral hemorrhage, or non-traumatic subarachnoid hemorrhage between march st , and november th , . patients greater than years of age, who died or were discharged to hospice within days of admission, or who had a baseli excluded. cases were patients with an icd- code for pneumonia or antibiotic treatment course for at least days with a positive respiratory culture. controls were patients without pneumonia matched using primary diagnosis, baseline demographics, history of prior stroke, diabetes, hypertension, heart failure, and initial nihss scores. ace inhibitor use, length of stay, discharge disposition, and other pertinent data were collected and analyzed using descriptive statistics, chisquare, and logistic regression. there is growing evidence supporting the role of inflammation in aneurysmal subarachnoid hemorrhage (asah) pathophysiology and it is of great interest to elucidate which immune mechanisms are involved. methods asah patients (sahp) and healthy control subjects (cs) were enrolled prospectively. the protocol was authorized by the ethics committee of our hospital and all subjects (or patient next of kin) signed an informed consent. the median age of sah patients was years ( - ) and of control subject was years ( - ). we assessed leukocytes subpopulations and their activation status by multiparametric flow cytometry in cerebrospinal fluid (csf) and peripheral blood (pb) of sahp at the same time and in pb of cs. we found an increase in cd +-monocytes percentage (p= . ) in csf compared with pb in sahp and a decrease in pb of sahp compared with cs (p= . ). sahp also showed a marked increase in the expression of cd (activation antigen) in pb cd +t cells compared with cs (p= . ). additionally, csf cd +t cells showed a decreased expression of cd (p= . ) and cd (p= . ) (activation markers) compared to pb cd +t cells in sahp. similarly, pb cd +t cells in sahp showed an increased expression of cd compared with cd +t cells of cs (p= . ). csf cd +t cells showed a decreased expression of cd (p= . ) and an increased expression of cd compared with pb cd +t cells (p= . ). b and nk cells were decreased in sahp compared with cs (p= . and p= . respectively). as far as we know this is the first report that analyzes leukocytes subsets in csf and pb in patients with asah. our data suggests not only csf leukocytes recruitment (from the blood) but also an increase status of activation at this level. overall, these results indicate that asah probably stimulates both the innate and adaptive immune responses. subdural hematoma (sdh) is a common diagnosis in neurosurgical and neurocritical practice. comprehensive outcome data and management guidelines are lacking for non-traumatic sdh. thus, we aimed to determine factors associated with in-hospital mortality in a large sample of patients with non-traumatic sdh. using the nationwide inpatient sample, we included adults with a primary diagnosis of acute non-traumatic sdh (icd- code, . ) hospitalized in the united states between and . demographics, comorbidities, craniotomy treatment and discharge outcomes were identified. univariable and multivariable analyses were performed to identify predictors of in-hospital mortality. of patients with non-traumatic sdh, the mean age was . (sd . ) with % male, and . % admitted during the weekend. surgical evacuation was performed in . % of patients; . % ( . % of patients requiring surgical evacuation) required a second craniotomy. death during hospitalization occurred in . % of patients. factors significantly associated with higher in-hospital mortality included increasing age, female sex, comorbidities (congestive heart failure [chf] , coagulopathy, renal failure, liver disease), mechanical ventilation during the first days (mv), premorbid warfarin use, repeated sdh evacuation, and admission during the weekend. craniotomy was associated with decreased in-hospital mortality. in multivariable analysis, age (or . , % ci . - . ), female sex (or . , % ci . - . ), chf (or . , % ci . - . ), warfarin use (or . , % ci . - . ), mechanical ventilation (or . , ) and weekend admission (or . , % ci . - . ) were independent predictors of inhospital mortality. surgical sdh evacuation was a strong independent predictor for decreased mortality (or . , % ci . - . ). one in nine patients with non-traumatic sdh dies during hospitalization. of several predictors of mortality, the weekend effect and the decision for or against surgical evacuation are potentially modifiable factors. further investigation may lead to improvement of management practice and better outcomes. to determine the burden of structural damage of the central nervous system (cns) in patients who died in the setting of non-neurological critical illness. critically ill patients who died in the medical, surgical or cardiac icus over a year period and underwent autopsy were included. patients with known cns lesions, cardiac arrest, and those from neurological icus were excluded. brain specimens were reviewed by a neuropathologist and classified according to location and lesion type (infarct, hemorrhage, inflammation). acute brainlesions were found in of patients studied. mean gcs at admission was lower in patients with neuropathological findings ( . vs. . ; p= . ). the most common sites of injury were cortex ( . %) and hippocampus ( . %). infarcts ( . %), hemorrhages ( . %), and signs of inflammation ( . %) were the most frequent findings. patients with septic shock and ali/ards had more lesions than patients without these critical illnesses, albeit these differences were not statistically significant. ischemic brain injury is prevalent in patients dying from non-neurological critical illness and may occur secondary to cns hypoperfusion. efforts to optimize brain oxygen delivery during critical illness may be neuroprotective. after ca, microcirculatory reperfusion disorders develop despite adequate cerebral perfusion pressure. increased blood viscosity strongly hampers the microcirculation resulting in plugging of the capillary bed, arteriovenous shunting and diminished tissue perfusion. the rheologic properties of blood depend on hematocrit and plasma constituents, mainly acute phase proteins. the aim of the present study was to assess blood viscosity in relation to cerebral blood flow in patients after a cardiac arrest. we performed an observational study in comatose patients after cardiac arrest. patients were treated with mild therapeutic hypothermia for hours and passively rewarmed to normothermia. blood viscosity was measured ex-vivo at , , , , , and hours after admission using a contraves ls viscometer. mean flow velocity in the middle cerebral artery (mfv mca ) was measured by transcranial doppler (tcd) at the same time points. the median viscosity on admission was . ( . - . )mpa.s, remained stable at . ( . - . )mpa s and . ( . - . )mpa s at and hrs respectively (p= . ). from hrs after admission viscosity decreased significantly to . ( . - . )mpa s (p< . ). median mfv mca was low ( . ( . - . )cm/s) on admission, and significantly increased to . ( . - . ) cm/s at hrs (p < . ). there was a significant association between the viscosity and the mfv mca (p= . ). median hematocrite was . ( . - . )l/l on admission and subsequently significantly decreased to . ( . - . ) l/l at hrs (p < . ) in contrast, acute phase proteins such as crp and fibrinogen increased during admission (from . ( . - . )mg/l to ( - . )mg/l and ( - )mg/l to ( - )mg/l respectively (p < . ). viscosity decreases in the first days after cardiac arrest and is strongly associated (correlated) with an increase in cerebral blood flow. since viscosity is a major determinant of cerebral blood flow, repeated measurements may guide therapy to restore cerebral oxygenation after cardiac arrest. initial hemorrhage burden is an independent predictor for delayed cerebral ischemia (dci) in patients with aneurysmal subarachnoid hemorrhage (sah). among the different definitions of blood burden, cisternal plus intraventricular hemorrhage volume (cihv) has been regarded as the most sensitive blood volume definition in predicting dci. however, it is not clear whether clot clearance is associated with dci. quantitative analysis of hemorrhage volume and clot clearance was made in consecutive patients who were scanned within hours from onset. cistenal plus intraventricular hemorrhage volume (cihv) was calculated for clot burden analysis. serial cihv was measured up to days after sah onset. clot clearance was calculated up to days as a percentage of residual clots compared to the initial scan. initial clot burden and clot clearance were compared in patients with and without dci. included patients were . ± . years old with female preponderance ( . %, ( / )). dci was developed in patients ( . %). conventional risk factors were not different between patients with and without dci including age, sex, ht, dm, smoking, admission h&h scale and apache score. patients with dci had higher cihv ( . ml, ) compared with those without dci ( . ml, iqr ( . had higher odds for dci (or . , % ci ( . - . , p = . ). however, clot clearance rate was not different between patients with and without dci (day : . % vs. . %, p = . , day : . % vs. . %, p = . , day : . % vs. . %, p= . ). quantitative clot clearance rate using cihv is not associated with the development of dci while initial cihv is an independent predictor for dci. the majority of patients who die from subarachnoid hemorrhage have withdrawal or limitation of care and a focus on comfort at the end of life. ethnic disparities at the end of life has been examined in general critical care settings but not specifically in brain injured patients. patients with aneurysmal subarachnoid hemorrhage were prospectively followed in an observational database from august to january . demographic information including ethnicity was collected from medical records and self reported by patients or their family. significant in-hospital events including care withheld or withdrawn (comfort measures only, cmo) and mortality was recorded prospectively. included were patients of white, black or hispanic race. patients were included in our analysis: whites, blacks and hispanics. age was the only baseline characteristic that was different between groups. whites ( ± years) were older than blacks ( ± years) and hispanics ( ± years). no difference in morality was seen: % in whites, % in blacks, % in hispanics. cmo was more commonly ordered for whites ( %) than blacks ( %) and hispanics ( %) (p= . ). in multivariate analysis controlling for age and initially hunt-hess grade hispanics were less likely to have cmo orders than whites (or, . ; %ci, . - . ; p= . ). of the patients who died % of whites had cmo orders compared to % of blacks and % of hispanics (p< . ). in multivariable analysis controlling for age and hunt-hess, blacks (or, . ; %ci, . - . ; p< . ) and hispanics (or, . ; %ci, . - . ; p< . ) were less likely to die with cmo orders than whites. multiple assessment measures are used to evaluate post-aneurysmal subarachnoid hemorrhage (asah) outcomes / complications. the use of a common measure has not been established, thus choosing which measure to control for becomes difficult when conducting multivariable analysis in clinical research. we compared odds ratio (or) and positive predictive value (ppv) to determine measures with strongest associations with post-asah complications / outcomes. subjects (n= ) with asah were recruited from an ongoing study with measures were assessed on admission: hunt and hess (hh), fisher, claassen, glasgow coma scale (gcs), world federation of neurological surgeons (wfns), and nih stroke scale (nihss). dependent variables were measured as follows: delayed cerebral ischemia (dci) was defined as clinical deterioration due to cerebral ischemia, moderate/severe vasospasm was diagnosed using sonography/angiogram, infarction was diagnosed via head ct scan. three and month outcomes were assessed by barthel index and modified rankin scale (mrs). logistic regression and spearman correlation were used. when predicting vasospasm and dci (controlling for age, gender, clipping/coiling), fisher scale had the largest ors ( . and . ), with a ppv of . % and . % (p<. ), respectively. when predicting infarction, hh had the largest or ( . ) with a ppv of ( . %); p=. . all scales were significantly associated with poor mrs ( - ); p<. . for and -month poor mrs, fisher scale had the largest or ( . and . ) with a ppv of . % and . %, respectively. admission nihss had the largest correlation coefficient (-. ) with -month barthel index while wfns had the largest correlation coefficient (-. ) with -month barthel index (p<. ). fisher scale has the strongest association with vasospasm, dci and mrs, while hh has the strongest association with infarction. we recommend clinical studies control for fisher when investigating vasospasm, dci, and mrs and for hh when investigating infarction to determine independent risk factors. to date, there has been a shortage of evidence-based quality improvement initiatives that have shown positive outcomes in the neurosurgical patient population. a single-institution prospective intervention trial with continuous feedback was conducted to investigate the implementation of a urinary tract infection (uti) prevention bundle to decrease the catheterassociated uti rate. all patients admitted to the adult neurological intensive care unit (neuro icu) during a -month period were included. the study consisted of two -month pre-intervention observation periods (approximately catheter days) followed by a month intervention phase ( , catheter days). a comprehensive evidence-based uti bundle encompassing avoidance of catheter insertion, maintenance of sterility, product standardization, and early catheter removal was enacted. the urinary catheter utilization rate dropped from % to . % during the intervention phase (p < . ) without any increase in the rate of sacral decubitus ulcers or other skin breakdown. the rate of catheter-associated uti was also significantly reduced from . to . infections per catheter days (p < . ). there was a linear relationship between the decreased quarterly catheter utilization rate and the decreased catheter-associated uti rate (r = . , p < . ). this single-center prospective study demonstrated that a comprehensive uti prevention bundle along with a continuous quality improvement program can significantly reduce the duration of urinary catheterization and rate of catheterassociated uti in a neuro icu. continued efforts to reduce ca-uti beyond the study resulted in sustained reductions when all components of the bundle were in place and daily foley rounds were maintained as a nursing intervention. matrix metalloproteinases (mmps) are extracellular proteolyic enzymes that may modulate the neuroinflammatory response to brain injury. we sought to determine the effect of mmps on pro-inflammatory cytokine production following severe traumatic brain injury (stbi). as part of a prospective cohort study, adults with stbi underwent multimodal monitoring with high cutoff, cerebral microdialysis and arterial and jugular venous bulb catheters. the concentration of mmps and pro-inflammatory cytokines were measured in microdialysate and blood over -days. interleukin- -alpha (il- ), il- -beta, il- , il- , and tumor necrosis factor-alpha (tnf-alpha) concentrations were initially high in microdialysate and then declined to low levels. the microdialysate concentration of il- also declined after first being high, but then increased between -and -hours. with the exception of il- , il- , and tnf-alpha, the cytokine blood concentration was low to undetectable. using generalized estimating equations, we observed a positive change in the microdialysate concentration of il- [( . pg/ml)/(pg/ml); % ci, . to . ] with an increase in the mmp- microdialysate concentration. in contrast, a significant increase in the microdialysate concentration of mmp- was seen with an increase in il- -alpha [( . pg/ml)/(pg/ml); % ci, . to . ] and il- -beta [( . pg/ml)/(pg/ml); % ci, . to . ]. in blood, a significant change in mmp- occurred during an increase in the levels of il- -beta [( . pg/ml)/(pg/ml); % ci, . to . ] and il- [( . pg/ml)/(pg/ml); % ci, . to . ]. although il- levels were higher in cerebrospinal fluid (csf), no major difference in mmp or cytokine concentration was observed between arterial and jugular venous blood or, for the three patients who were also fitted with csf drainage catheters, between cerebral microdialysate and csf. stbi is associated with a substantial central cytokine or neuroinflammatory response, which may influence or be influenced by production of mmps. severity classification of traumatic brain injury (tbi) has traditionally been based on the glasgow coma scale (gcs), with mild tbi being defined as - . however, there is often a subset of "mild" tbi that requires surgical intervention. the current study examines this subgroup to decipher any symptomatology that may be helpful in identifying who these patients may be. this observational cohort study included consecutive adult patients presenting with a tbi. independent variables included vomiting, seizure, loss of consciousness (loc), alteration of consciousness (aoc), and post-traumatic amnesia (pta); these were tested for correlation with surgical intervention, the dependent variable. data were entered into redcap, a clinical data capture system housed in our center for translational science institute. the z-test for proportions was used to determine significance of symptomatology. statistical analyses were performed in jmp . for the mac. of the total mild tbi cohort (n= , ), % were male. the median age was (iqr: - , r: - ). thirty seven patients required surgical intervention. symptoms significantly associated with surgical intervention on univariate regression included vomiting (p= . ), and aoc (p . ). multiple regression analysis revealed that time (length of) loc (p= . ) and pta (p< . ) were also significantly correlated with surgical intervention. age was also a statistically significant predictor of surgical intervention (p< . ). these pilot data suggest that older patients, as well as patients who present with vomiting, loc, or pta, have a significant likelihood of requiring surgical intervention. this calls attention to proactively seeking these data and ensuring adequate neuroimaging for all patients with tbi, regardless of gcs score at presentation. the prevalence of chronic subdural hematoma (sdh) is expected to increase with an aging population and increased use of anticoagulants. we aimed to develop a tool to predict mortality after sdh. a prospective study was conducted between - of patients with chronic subdural hematoma (n= ) admitted to a tertiary neuro-icu. three-month mortality data was collected. after testing admission demographic, radiographic and - , - , ; p= . ) and herniation (p= . ) were found to be independent predictors of death in multivariate logistic regression analysis. a score was composed ( - ) with each variable weighted based on its independent strength of association with mortality (b value) as - = , gcs - = , herniation= point. overall, % of patients died and -month mortality increased with each point of the sdh score ( = %, = %, = %, = %, = %). the sdh score predicted death (or . , % ci . - . , p< . ) with an area under the curve of . , sensitivity . %, specificity . %, ppv % and npv %. the hosmer and lemeshow and nagelkercke r for this model were . and . , respectively, indicating a strong model. sdh evacuation reduced the odds of death by % when added to a multivariate model including age, gcs and herniation (adjusted or . , % ci . - . , p= . ). the sdh score allows for a reliable prediction of mortality for patients with chronic sdh. this score may help risk stratify patients for surgical treatment. we developed a novel method capable of determining the degree of conformance of observed morphological changes of intracranial pulses with their expected patterns associated with global vasodilatation and vasoconstriction, respectively. these patterns were formed as a template consisting of pulse morphological changes during co tests that were consistent for multiple subjects. we used this novel pulse morphological template matching (pmtm) algorithm to study ) the incidence of cerebral vasoconstriction/vasodilatation associated with lpr increase episodes; ) how likely cerebral vasoconstriction/vasodilatation could lead to or lag behind lpr increase. we studied microdialysis data samples collected in an average interval of . hours from severe tbi patients. the lpr increase episodes were automatically identified using a moving time-window of hours. the pmtm algorithm was applied to the continuous intracranial pressure (icp) signal time-synched to the identified lpr episodes. across all subjects, more than half of the lpr increase episodes are not associated with any detectable cerebral vasoconstriction or vasodilatation (p = e- ). comparing lpr episodes with either vasoconstriction or vasodilatation, it was more likely that vasoconstriction rather than vasodilatation occurred during an lpr increase episode (p = . ). also for out of subjects with dominant number of vasoconstrictive lpr episodes, a causality relationship between vasoconstriction and lpr increase were observed, i.e., vasoconstriction occurred in one hour before lpr increase started. across the tbi subjects studied, the incidence of either vasoconstriction or vasodilatation associated with lpr increase was low. however, about percent of subjects had a dominant number of lpr increase episodes associated with cerebral vasoconstriction. furthermore, cerebral vasoconstriction occurred within one hour preceding lpr increase. placement of an intracranial pressure (icp) monitorto guide the management of severe traumatic brain injury (tbi) patients has been historically performedby neurosurgeons. trials have suggested decreased morbidity and mortality with timely resuscitationand rigorous treatment of intracranial hypertension. we hypothesize that icp monitors can be placed by non-surgeon neurointensivists, with placement success and complication rates comparable to neurosurgeons. we retrospectively reviewed the medical records of tbi patients who required insertion of parenchymal icp monitors from may to december in a large level i trauma center. monitor placement was performed by neurointensivists (board certified by the abim in critical care medicine and by the ucns in neurocritical care). patient data recorded are age, gender, ct findings, icp monitor placement location and length of placement, complications related to the icp monitor, and patient outcomes. twenty seven ( ) these findings were comparable to published outcomes from neurosurgeon placements. we believe that insertion of parenchymal icp monitors should be considered a core skill for neurointensivists and should be included in neurocritical care fellowship training. insertion of icp monitors by neurointensivists is safe and may aid in providing prompt monitoring of patients with severe tbi. use of computers at the bedside for trending primary signals like icp or cpp brings obvious advantages in neuro-critical care unit. software can be extended to calculate secondary indices reflecting underlying pathophysiological phenomena, like disturbance of cerebral compensatory reserve and vascular reactivity. during - more than severe tbi patients were monitored using icm+ software. various modalities were used, including icp, abp, pbtio , nirs, tcd blood flow velocity, brain temperature, etc. from icp and abp waveforms secondary indices were extracted. compensatory reserve was assessed using moving correlation index between slow changes in pulse amplitude and mean icp (rap). pressure reactivity index (prx) was calculated as moving correlation between mean icp and abp. 'optimal cpp' (cppopt) was estimated as cpp corresponding to the best cerebrovascular reactivity within the period of past hours. trending compensatory reserve showed that usually it is good (rap around ) in the first few hours after admission (rap around ), with gradual deterioration triggered by aggravating brain edema. in most cases rap stayed close to + (impaired reserve). it decreased to negative values (exhausted reserve) on top of plateau waves and in refractory intracranial hypertension, indicating critical icp. prx proved to be highly variable, responding to changes in abp, icp and ventilation. it deteriorated on top of plateau waves, and at extreme values of cpp. in cases of refractory intracranial hypertension, deterioration of reactivity seemed to preceed the elevation of icp above mmhg. cppopt fluctuated during the monitoring period. absolute distance between current cpp and cppopt was strongly associated with outcome. too low cpp (below cppopt) correlated with greater mortality rate (p< . ) and too high cpp -with greater rate of severe disability (p< . ). individual observations of secondary indices calculated by icm+ software help in better interpretation of primary signals in intensive care of tbi patients. financial support: the software for brain monitoring icm+ is licensed by the university of cambridge (cambridge enterprise). authors ps and mc have a financial interest in a part of the licensing fee. to determine the differences in hospital outcomes among adult mild traumatic brain injury (tbi) patients where the severity of tbi is defined by glasgow coma scale (gcs) score. this is a retrospective chart review of consecutive adult who came to the ed department of a tertiary care hospital in north central florida. the tbi severity was classified according to gcs score, with patients with gcs score of - categorized as having mild tbi. outcome variables such as admission status, icu admission status, in-hospital death and -month death among patients with different mild gcs scores of , , and . we had a total of mild tbi patients in the specified period of time. the majority of this cohort had a gcs of ( or . %). this was followed by a gcs of ( or . %) and gcs score of ( or . %). there was a statistically significant difference between mild tbi with gcs , , (p< . , anova) with the outcomes of hospital admission ( % vs. % vs. %), icu admission ( % vs. %, vs. %), in hospital death ( % vs. % vs. . %), and month death rate ( % vs. %, vs %). there is a % increase in hospital admission rates for each point decrease in gcs score. the -month death rate nearly doubles with each incremental decrease in gcs score. there is a significant difference in outcome within "mild" head trauma across the continuum. to characterize the patterns of presentation of children with head trauma to the pediatric emergency department. this is an observational cohort study that sought to collect injury and outcome variables with the goal of characterizing the very early natural history of pediatric traumatic brain injury in children over the age of years. statistical analyses were performed using jmp. cohort (n= ) . similar multivariate model showed that as children grew older, they were more likely to be admitted in hospital because of a tbi as a result of recreational activities (p= . ) and traffic accidents (p< . ), and less likely due to sport tbis (p= . ) with adjr = %. % of the children who were admitted ended up in icu with mean icu-los of day with an iqr of - . one percent had an in hospital death. kids with amnesia were significantly more likely to be admitted to the icu (p= . , r = %). children who got admitted to icu (p= . ) and were older ( . ), were significantly more likely to be readmitted to the hospital within days. these preliminary data suggest that pediatric brain injury is not without significant morbidity. the objective of this study was to identify pre-hospital markers of in-hospital mortality in traumatic brain injury (tbi) patients due to fall. this study was an observational cohort study performed at a level- trauma center. study subjects included all adult arriving in emergency department with history of tbi due to fall over a period of months. study variables were symptoms such as vomiting, seizure, loss of consciousness (loc), alteration of consciousness (aoc) & post-traumatic amnesia (pta), glasgow coma scale (gcs) scores, vitals, pre-hospital glucose. jmp for windows & z-test of proportions were used to perform statistical analysis. the study cohort comprised of adult (median age of yrs and iqr of - ). in-hospital death (ihd) was observed in % (n= ) of the total cohort, with male ihd= ( %) greater than female ihd= ( %). pta ( %,p< . ),loc ( %, p< . ) & aoc ( %, p< . ), higher pre-hospital glucose (p= . ) were individually found to be much more significantly associated with ihds versus the whole cohort. multivariate regression analysis showed significant correlation with ihds with: ) higher age (p< . ) when adjusted for severe gcs. ) vomiting (p= . ) and longer duration of loc (p= . ), when adjusted for rest of the symptoms. % of patients presenting to ed with vomiting (p= . ) had gcs score= , and % of that sub-group suffered ihd patients presenting to emergency department with higher blood glucose and symptoms such as pta, aoc, longer duration of loc & vomiting, were more likely to have worse outcome of in-hospital deaths compared to rest of the patients. hence identifying these symptoms in fields might help to make key decisions for providing intensive care and improving the overall patient outcomes. to determine which symptoms affect severity in pediatric traumatic brain injuries (tbi). study design-this observational cohort study was performed at a level one trauma center that has a dedicated pediatric emergency department. consecutive patients age - were included. the age cutoff of years was used because it was decided that younger children may not be ale to report their symptoms, particularly to endorse aoc (alteration of consciousness) or pta(post-traumatic amnesia). the dependent variables were vomiting, seizures(sz), loc (loss of consciousness), aoc, and pta at the time of the head injury. the independent variable was ed tbi severity based of the glasgow coma score, with mild being defined as - , moderate as - , and severe as less than . the median age of the cohort was with an interquartile range of to . % were boys. in the univariate model, all symptoms except vomiting were statistically significant: seizures (p= . ); loc (p= . ); aoc (p< . ), pta (p< . ). multiple regression analysis of these factors revealed all of variables to retain statistical significance. the r coefficient of determination was %, which means that almost one-third of the variance can be explained by just these five factors (symptoms), suggesting that our multivariate model is a robust one. symptoms at time of head injury in children including seizure, loc, aoc and pta were statistically significant predictors of the severity of tbi. this data allows clinicians to judge the severity of the tbi depending on the symptoms at presentation. these pilot data may be useful in designing clinical care algorithms. icp dynamic system of an injured brain is susceptible to various acute changes disturbing the system homeostasis that should be detected by icp monitoring. such a capability is particularly useful for comatose patients. our aim was to demonstrate a novel approach to detect acute deviation from steady state of an icp dynamic system without involving significant mean icp changes. steady state of icp dynamic systems is reflected as icp pulses of similar mean icp resembling each other. therefore, a steady state indicator can be calculated by quantifying inter-pulse distances after matching their mean icp. besides euclidean distance and pearson correlation, geodesic distance was introduced as a novel metric. these different metrics were evaluated on three types of continuous icp: ) those between two consecutive imaging studies showing new acute ventricular enlargement for slit ventricle syndrome patients undergoing a trial of shunt externalization and clamping (svs+); ) those between consecutive brain imaging studies from patients under the same trial without ventricular enlargement (svs-); ) overnight recordings from patients with suspected normal pressure hydrocephalus (nph). it was expected that both svs-and nph recordings represent steady state. we observed that only geodesic distance correctly differentiated between svs+ and svs-and between svs+ and nph while avoiding discriminating between svs-and nph. it was also found that % svs+ cases, none of svs-, and . % of nph cases had a multimodal geodesic distance histogram. pulses with a large number of distant pulses at similar mean icp for the five multimodal-histogram svs+ cases fell in short time windows indicating that acute ventricular changes may have occurred in these confined time windows during which no significant changes of mean icp occurred. geodesic inter-pulse distance is a promising metric to quantify distance intrinsic to the underneath geometric structure of icp signals. patients with severe traumatic brain injury have multiple causes for acute respiratory decompensation. computed tomography pulmonary angiography (ctpa) is being used extensively to evaluate acute cardiorespiratory changes. we reviewed the use of ctpa in critically ill patients with traumatic brain injury to evaluate the results and their impact on patient care. all adult trauma patients with traumatic brain injury who were admitted to our level trauma center intensive care units for greater than hours, were identified (january -december ). those who underwent ctpa for acute respiratory decompensation were reviewed to determine the findings of these studies and the resulting interventions. we identified patients that met these criteria [ admitted to neurosurgery/neurocritical care(ncc) , admitted to trauma service(ts)]; of these patients underwent ctpa studies for acute physiologic changes (ncc- , ts- , p= . ). ts patients were significantly younger with higher severity of injury and longer length of stay. pertinent clinical finding were identified in of the ( %) studies; and included atelectasis/collapse ( %), pleural effusion ( %), pneumonia ( %) and pulmonary embolus ( %). these results prompted targeted interventions, most frequently consisting of modifications of ventilator therapy ( , %), a change or initiation of antibiotic therapy ( , %), mini-bal ( , %) bronchoscopy ( , %), vena cava filter ( , %), and anticoagulation ( , %). no change in patient management occurred after studies. agreement, for different findings, between chest x-ray and ctpa ranged from - %. patients admitted to a ts are more likely to undergo a ctpa evaluation. ctpa is a useful tool in the evaluation of critically ill patients with acute physiologic decompensation beyond the diagnosis of pe. the results of these studies provide significant insight into the underlying pathology in this patient population and offer an opportunity to direct subsequent patient care. somatosensory evoked potentials (ssep) provide valuable information of the neurophysiological state of the patient throughout a surgery and the errors in the surgical procedure are easily noticed. it is hence important to analyze and monitor the ssep during scoliosis surgery in a minimum amount of time. the study uses pca-walsh algorithm to analyze posterior tibial nerve ssep and compare with the conventional signal averaging method in twelve surgical procedures. the tibial ssep from twelve different subjects were recorded and assessed throughout the respective surgeries using a unique pca-walsh algorithm by using only trials at a time and compared the extracted ssep information with conventional method. the ssep were recorded in two bipolar channels c -c and c z -f z throughout the surgery and analyzed remotely using an automated software pca-walsh algorithm. the results are compared with the actual clinical information and presented with the merits. in all the twelve cases, the algorithm results presented consistency throughout the surgery with an average accuracy of . % when compared to the conventional method, which takes several hundred trials. the average variation in time latency was . % and in amplitude was . %, well within the limit of % following the clinical criteria. the pca-walsh algorithm is capable of automated extraction of the tibial ssep during a surgery using a minimum number of trials. the analysis using the algorithm was successful and proved conclusive to the clinical information through the different surgical procedures. the faster recording and analysis of ssep signals provides a much better perspective for neurophysiological monitoring through the surgical procedure. the authors appreciate the support provided by the national science foundation under grants cns- , hrd- , cns- , and cns- . the authors are also thankful for the clinical suppo certain admission characteristics are known predictors of adverse outcomes in moderate-severe traumatic brain injury (mstbi) patients, but explain only / of outcome variability. retrospective studies suggest that non-neurologic organ failure may contribute to / of all deaths after mstbi, but actual incidence rates of intensive care unit (icu) complications and their impact on outcome are not known. we examined the incidence rates of pre-specified medical and neurological icu complications, and their impact on in-hospital mortality and functional outcome at hospital discharge. in a prospective observational study, consecutive mstbi patients from a single level i trauma center between / - / were analyzed. poor outcome was defined as glasgow outcome scale - .multivariable logistic regression was utilized to adjust for admission characteristics and icu length-of-stay. the mean age was years, % were men, and the median glasgow coma scale and injury severity scores were and , respectively. the five most common medical icu complications were: hyperglycemia ( %), fever ( %), hypotension requiring vasopressors ( %), systemic inflammatory response syndrome ( %), anemia requiring transfusion ( %). neurological icu complications were: intracranial pressure crisis (icp; [ % of n= with icp monitor in place]), brain edema ( %), herniation ( %), intracranial rebleed ( %), clinical seizure ( %). among medical complications, hyperglycemia was associated with poor outcome (or . ; % ci - . ]) while cardiac complications (e.g. cardiac arrest, arrhythmia, acute myocardial infarction) were associated with death (or . ; % ci . - . ). when combining medical with neurological icu complications, brain edema (or . ; % ci . - ) was associated with poor outcome, while cardiac complications and brain edema were associated with death (or . ; % ci . - . and or . ; % ci - , respectively). icu complications are very common after mstbi. we identified specific potentially modifiable predictors of adverse outcomes after mstbi. confirmation of our findings in a larger cohort is warranted. too much oxygen may increase oxygen free radical production, possibly triggering cellular injury and apoptosis. although laboratory investigations support the potentially detrimental effects of hyperoxia exposure after tbi, clinical data are lacking. we retrospectively identified tbi patients admitted to our neuro-icu between july and february . we identified a total of patients with complete data including gcs, apache ii, age, gender, abg within hours of injury, and outcome (glascow outcome scale-gos at discharge from the hospital). patients were divided into groups defined a priori based on pao on the first abg values obtained after injury. hyperoxia was defined as pao of mm hg or greater, and normoxia as pao between and . poor outcome is defined as gos of - . the patients in the normoxia group (n = ) and the hyperoxia goup (n = ) were matched on baseline characteristics, age ( among a small number of patients admitted to the neuro-icu following traumatic brain injury, patients with arterial hyperoxia had a trend towards worse outcome compared with patients with normoxia. this provides scientific rationale for large prospective clinical trials of controlled oxygenation in tbi patients. elevated intracranial pressure (eicp) contributes to secondary injury in stbi, therefore its control is paramount. boluses of hypertonic solutions are usually used to reduce icp but the impact of early continuous infusions has not been widely explored. we conducted this study to compare the effect and security of hypertonic saline % (hs %) infusion vs normal saline. all stbi patients arriving to the emergency room within hours of trauma were enrolled to receive an isovolumetric infusion of hs % or normal saline (placebo) during hours. icu physicians and investigators were blinded to the sodium levels during the trial. main endpoint: number of eicp episodes (> mmhg). secondary endpoints: neurologic outcome (gos, mrankin), electrolyte and osmolality levels, and adverse events (ae). twenty non-penetrating shbi patients were included. median age was . years (iq - : . - . ). median iss was (iq - : - ). we didn´t find significant differences for the total number of episodes of eicp at h between groups ( , iq - : - vs. , iq - : - , p= . ); however, when we analyzed patients with at least one episode of eicp we found a significant low number of eicp episodes in hs % group ( , iq - : - vs. , iq - : , - , ; p= . ). we found a sodium plateau at h of infusion (hs %: . ± . vs. control: . ± . meq/l, p= . ) which lasted until the beginning of weaning from hs %. the most frequent ae was hypokalemia and no patient had renal failure. the sixmonth gos and mrankin scores had a non-significant tendency towards better outcomes in hs % group. an early infusion of hs is feasible and seems to be safe in stbi patients. serum sodium kinetics showed a plateau after h of hs % infusion with no consequences in renal function and no rebound effects after tapering. hs % continuous infusion could reduce eicp episodes and it could conduct to better neurologic outcomes at six months. traumatic brain injury causes diffuse shearing of long fiber tracts. this can be detected by quantitative dti imaging even in patients who have primarily localized contusions. in our population the cingulum, cotricospinal tracts and external sagittal striatum were preferentially affected compared to age and gender matched controls. these findings support the use of advanced mri to assess the degree of injury and inform prognosis and goals for rehabilitation. neurocrit care ( ) :s -s most deaths following severe traumatic brain injury (tbi) are associated with a decision to withdraw life-sustaining therapies (wlst)( ). however, the incidence and the impact of wlst in clinical trials is unknown. this systematic review was performed to assess if and how wlst are dealt with in clinical trials involving patients with severe tbi. we searched medline, embase, cochrane central, biosis and cinahl databases and references of included studies. all randomized controlled trials (rcts) published over a -year period (january (january - , in one of selected journals in general medicine, critical care medicine and neurology/neurosurgery were considered for eligibility if ) and reporting data on mortality. our primary outcome was the assessment of wlst. secondary outcomes were the timing of evaluation, justification for wlst, proportion of wlst among deaths, factors that may have influenced the wlst and risk of bias of rcts. two reviewers selected rcts and collected data independently using a standardized case report form. from citations retrieved, rcts were included (n= , , ranging from to patients). were single center rcts and were multicenter. the incidence of wlst was reported in studies ( . %). three studies reported crude numbers of patients, studies reported the timing of wlst and studies reported the justification for the decision to wlst. studies were considered at high risk of bias, study at low risk of bias and studies did not give enough information to conclude on the risk of bias. wlst was rarely reported in rcts involving patients with severe tbi over the last decade. considering the variation of wlst in clinical practice, we suggest that wlst should be systematically reported in rcts performed in tbi. reference : . turgeon et al. cmaj . previous pediatric brain injury studies have considered fevers as discrete events instead of as a "temperature dose." we sought to evaluate the population size difference captured at various fever thresholds in severely brain-injured pediatric patients, considering fever burden in terms of degree-hours; and to compare fever burden in pediatric traumatic brain injury (tbi) vs. cardiac arrest (ca). charts from brain- y, admitted in - within hrs of admission were included. no temperature modulation protocols existed in the pediatric icu during this period. -day core temperatures were used to generate areas-under-the-curve (auc) above fever thresholds of . , , . , and o c. these were normalized for different lengths of stay. charts met inclusion criteria, with mean patient age . y (range d - y). diagnoses distributed (non-exclusively) as ca, accidental tbi, non-subarachnoid hemorrhage (sah) intracranial bleeds, sah, strokes, non-accidental tbi, ca after tbi, and other cns pathologies. cohort mortality was %, with % suffering brain death. fever burdens were measurable in % of patients over . o c, in % over o c, and in % over o c. normalized fever burdens at these thresholds were statistically different by -way anova (p< . ), with all fever burdens being statistically less than at . o c. remarkably, a shift in threshold from . to o c resulted in a % reduction in measured fever burden. fever burdens fell from a peak of . ± . o c-h on day to . ± . o c-h on day after admission. accidental tbi (n= ) and ca (n= ) patients did not experience different fever burdens above . o c. measured fever burden is markedly affected by shifting the threshold from to . o c. tbi and ca appear to induce similar fever burdens. pediatric fever burden reference values will allow more quantitative comparisons in severely braininjured children. little is known about the natural history of function after traumatic brain injury. our objective was to track the stability of drs scores over time and to identify factors associated with worsening drs scores. we collected disability rating scale (drs) scores, which capture the cognitive ability to perform activities of daily living such as communication, motor response, feeding, toileting, overall functioning and employability, longitudinally on severely brain injured patients in neurosurgery clinic. multivariable logistic regression was used to identify patient factors that were independently associated with changes in drs score over time. patients with severe brain injury had more than one drs score collected. of these patients, had worsening scores over time. changes in scores ranged from - to (mean - . , standard deviation . ). this represented a change from partial/no disability to moderate disability for patients and from moderate to severe disability for patients. patients improved from moderate to partial/no disability while only one patient improved from severe to moderate disability. using multivariable logistic regression, there were no patient factors that were associated with worsening drs scores including gender, age, comorbidities, race, insurance status, mechanism, injury severity score, gcs or final disposition. while half of worsening drs scores were seen within the first days after discharge, were seen months or more after the hospital stay, with one seen over a year after hospital discharge. for the most part, drs scores were stable over time. a group of patients were identified who experienced significant decline in function as far out from discharge as a year. this preliminary study highlights the need to identify those at risk for decline and to set up mechanisms for long-term follow-up for those patients in need. the identification of traumatic axonal injury (tai) lesions that undergo neuronal recovery could improve prognostication in patients with traumatic brain injury (tbi) and facilitate the development of novel therapies for preventing secondary axotomy. we aimed to determine whether diffusion tensor imaging (dti) detects neuronal recovery after tai. we retrospectively identified tbi patients ( severe, moderate, mild) who underwent at least acute-to-subacute dti scans and who had at least tai lesion in the corpus callosum (cc), as defined by hyperintensity on dwi or t flair. the median number of days from tbi to image acquisition was (range - ) for the first dti scan and (range - ) for the second scan. tai lesions were manually outlined on the acute dwi datasets and then coregistered to the subacute datasets to measure longitudinal changes in lesional fractional anisotropy (fa) and apparent diffusion coefficient (adc). "neuronal recovery" within a tai lesion was defined on the final scan by mean lesional fa within standard deviations of published normal fa values for the cc. initial fa and adc values in lesions with and without neuronal recovery were compared (unpaired t-test). eleven cc tai lesions ( splenium, body, genu) were identified. fa recovered in splenium lesions ( . +/- . [mean+/-sd]) and genu lesion ( . ) on the final scan. three of these lesions were flair hyperintense, were associated with gre microbleeds, and were initially adc hypointense. splenium lesions with neuronal recovery did not differ significantly from lesions without recovery for fa ( . +/- . vs. . +/- . , p= . ) or adc ( +/- vs. +/- x ^- mm^ /s, p= . ) on the initial scan. dti may detect neuronal recovery within tai lesions, as indicated by subacute normalization of fa. acute dti biomarkers of tai reversibility were not identified in this preliminary analysis. increased intracranial pressure (icp) in patients with traumatic brain injury (tbi) is associated with higher mortality and poor outcome. mannitol and hypertonic saline (hts) have both been used to treat high icp, but it is unclear which one is more effective. we compared the effect of mannitol and hts on lowering cumulative icp burden after severe tbi. the brain trauma foundation tbi-trac® new york state database was used for this retrospective study. a total of patients with severe tbi who received only hts were identified. patients who received only mannitol were matched for age, pupillary reactivity, occurrence of hypotension on day . univariate analysis was performed to compare icp burden, cumulative hyperosmotic doses, number of icu days (wilcoxon signed rank test), and two-week mortality (mcnemar test). icp burden was defined as the total number of days with icp spikes (icp> mmhg) expressed as a percentage of total number of days of icp monitoring. cumulative hts and mannitol doses were converted to osmolar doses for comparison. the mean age and gcs were similar in the two groups ( . vs. . years; . vs. . ; hts vs. mannitol, respectively) . patients received % hts and received . % hts. all patients in the mannitol group received % mannitol. there was no difference in number of days of icp monitoring (p= . ) or number of icu days (p= . ) in the two groups. icp burden was significantly lower in hts group vs. mannitol group ( . % vs. . %. p= . ). there was no significant difference in the cumulative dose of hts and mannitol (p= . ), and two-week mortality in the two groups was similar (p= . ). hts is more effective in lowering cumulative icp burden after severe tbi compared to mannitol. this did not translate into reduction in two-week mortality, possibly due to the small sample size. spreading depressions (sds) have been consistently associated with hypoglycemia in animal studies. the frequency of these depolarization events, while influencing infarct size, also appears to be influenced by the plasma glucose concentration during experimental ischemia. low cerebral dialysate glucose have also been correlated with sd events in humans. we hypothesized that low serum glucose should be associated with an increase in the frequency of sd events in human acute brain injury. to determine the relationship between serum glucose and cortical spreading depolarizations (sds) after traumatic brain injury (tbi), subdural electrode strips were placed on peri-contusional cortex in patients from centers who underwent craniotomy following tbi. prospective electrocorticography was performed during neurointensive care with retrospective analysis of hourly serum glucose data. patients were divided into those with sds and those without and the distribution of glucose values among these two groups were compared using the -way kolmogorov-smirnov method. in patients ( %), sds (spreading depressions and peri-infarct depolarizations) were observed. the probability of a depolarization occurring increased significantly as a function of rising serum glucose (p< . ). median glucose values in patients with and without sds was . and . mmol/l, respectively. among patients with sds, glucose values recorded within minutes of the onset of an sd were higher than those occurring < minutes before an sd (p< . e- ) ( figure ). serum glucose does not appear to affect the generation of sds as it does in animals but paradoxically may be elevated. this may reflect a stress response to the initial acute brain injury and critical illness or a physiologic mechanism to increase glucose supply during sd events in which cerebral glucose utilization is increased. overall, the data suggest that plasma glucose is being managed within appropriate levels in this study group. to determine difference in tbi severity and abnormal radiologic findings in different age groups. this was an observational cohort study on all adult patients (> yrs) arriving to the emergency department, with a history of traumatic brain injury as a result of "fall" at a level trauma center in the southeastern united states. data collected included ed gcs score and head ct results. abnormal ct scans have the presence of either an intra-cranial bleed and/or cranial fracture. there were patients in the cohort with history of fall with median age of yrs (iqr of - ). we divided them into two age groups: group a: - yrs( %) & group-b: > yrs( %). group a comprised mostly of males ( %) compared to females, meanwhile group b was equivocal in gender composition ( % male). out of the whole cohort of patients, % patients had head ct performed. out of these, . % (n= ) showed an abnormal head ct. age group b ( %) had a significantly greater percentage of abnormal ct scans compared to group a ( %) (p< . ). among abnormal ct scans, group a ( %) had a significantly greater percentage of skull fractures than group b ( %) (p= . ). among patients with mild and moderate tbi (gcs> ), group b ( %) was more likely to have an abnormal ct scan than group a ( %) (p< . ), however, there is no significant difference between likelihood of abnormal head ct between group a and b for severe tbi. younger adults are at a higher risk of cranial fractures after a fall related tbi, probably due to severe mechanisms of injury. on the other hand elderly population with mild tbi mostly due to ground level falls had worse outcomes on ct scans. accumulating pre-clinical data suggests that matrix metalloproteinase (mmp) expression following cerebral trauma contributes to brain injury. we sought to characterize the temporal mmp response to severe traumatic brain injury (stbi) in humans and its relationship with outcomes. we conducted a prospective cohort study that included adults with stbi. high-cutoff, cerebral microdialysis and arterial and jugular venous bulb catheters were used to measure the concentration of mmps and other markers over -days. the concentration of mmp- was initially low in microdialysate and blood, but increased between -and -hours. mmp- blood levels were high and stable throughout the study while blood levels of mmp- were initially low and then gradually rose. in microdialysate, mmp- and - increased and then peaked between -and -hours. mmp- also increased in microdialysate following stbi while its levels were low and stable in blood. mmp- and - were initially high in microdialysate and then slowly decreased over time. while the concentration of mmp- was also initially high in blood and then progressively declined, the mmp- blood level increased with time. among the patients that also had cerebrospinal fluid (csf) drains, marked and sometimes opposite concentration trends were observed for mmp- in microdialysate versus csf. generalized estimating equations suggested that significant changes in mean microdialysate concentrations of mmp- , - , - , and - and mmp- , - , - , and - occurred with increases in microdialysate glucose and the lactate pyruvate ratio, respectively. moreover, the mean microdialysate level of mmp- increased with intracranial pressure (icp) [( . pg/ml)/mmhg; % confidence interval, . to . ] while that of mmp- decreased with cerebral perfusion pressure (cpp) [(- . pg/ml)/mmhg; % confidence interval, - . to - . ]. monitoring of mmps following stbi is feasible, and their expression may be associated with cerebral metabolism, icp, and cpp. to determine significance of laboratory markers for in-hospital death after fall related adult traumatic brain injury. this was a consecutive cohort observational study done at a level- trauma center serving surrounding counties. cohort consisted of all adult patients (> yrs) arriving to the ed with a history of fall. study variables were lab values of the following parameters on ed admission: sodium, potassium, bicarbonate, lactate, blood glucose, inr, aptt, wbc, rbc, platelets; along with pre-hospital glucose values in the field. study cohort comprised of adult subjects arriving at ed with history of fall with median age of yrs (iqr of - ). in-hospital death (ihd) was observed in % (n= ) of the total cohort, with male ihd= ( %), and female ihd= ( %). older age groups [> yr] ( %, n= ) had higher incidence of in-hospital deaths compared to younger age group - yr ( %, n= ) with p= . (ci= . - . ). in a univariate regression model higher levels of: pre-hospital glucose (p= . ), ed blood glucose (p< . ), lactate (p= . ), inr (p= . ), aptt (p< . ) and wbc (p< . ) were significant individual predictors of in-hospital death. while lower levels of bicarbonate (p< . ) and rbc (p< . ) were significant individual predictors of in-hospital death. the following multivariate regression models showed statistical significance with higher probability of in-hospital death: ) higher: ed blood glucose (p= . ), aptt value (p= . ) | lower: bicarbonate (p= . ), rbc (p= . ) with adj.r = % ) higher: aptt value (p= . ) and wbc count (p= . ) ) higher: aptt value (p= . ), older age (p= . ) | lower rbc (p= . ) and gcs scores (p< . ) with adj.r = % lab parameters such as ed blood glucose, rbc count, wbc count, bicarbonate level & aptt level are individually or simultaneously important predictors of in-hospital death in adult tbi patients with history of fall. traumatic brain injury (tbi) is an epidemic with severe consequences. brain tissue oxygen tension (pbto ) monitors detect secondary injury and direct clinical therapies to mitigate damage. blood transfusion is one therapy often used, however its effect in tbi patients is not well defined. we studied pbto data in patients who received transfusion after tbi. sixty-nine severe tbi patients were consecutively admitted to a neurocritical care unit and received pbto monitoring as part of standard clinical care for this unit. data were collected from electronic medical records as entered by the bedside nurse. patients were managed according to the brain trauma foundation guidelines. transfusions were identified through nursing comments. hourly pbto values were analyzed for up to six hours after starting transfusion. other factors were also analyzed for their potential influence on pbto readings. of patients, received a total of transfusions in the setting of pbto monitoring. two groups were identified: transfusions that led to an increase in pbto and those that did not. six transfusions resulted in increased pbto , with an average increase of . mm hg. twenty-two transfusions did not: of these were unchanged and decreased. the groups did not differ in age (mean . and . , respectively), maximum temperature (mean . and . ), minimum cerebral perfusion pressure (mean . and . ), or initial glasgow coma scale (gcs) (mean . and . ). blood transfusion is often used in the critical care setting. the effect of transfusion on brain tissue oxygen tension is variable. age, temperature, cerebral perfusion pressure, and initial gcs were not useful in distinguishing patients who benefited from transfusion. pbto only rises in a minority of patients; therefore additional prospective studies are needed to evaluate which patients are likely to benefit from transfusion. mannitol use in patients with traumatic brain injury can lead to acute renal failure and may worsen outcome. the purpose of this study is to determine the rate of acute renal failure (arf) among patients treated with mannitol and its impact on outcome in a multicenter review. we analyzed a one-year data ( ) ( ) from the premier database, a nationally representative hospital discharge database in the united states. we compared baseline and clinical characteristics of patients with traumatic brain injury (tbi) treated with mannitol in the first days of admission who developed arf to those who didn't. length of stay, cost of hospitalization and discharge status were ascertained. from a total of admissions with a diagnosis of traumatic brain injury requiring mannitol within the first days of admission, % (n= ) of patients had arf. arf is a common complication of tbi treated with mannitol. it is associated with longer length of hospital stay and increased rates of in-hospital mortality. the result highlights the importance of using alternative therapy to hyperosmotic agents such as hypertonic saline in treatment of tbi patients at risk for acute renal failure. cervical spine immobilization (csi) is a relative contraindication for percutaneous dilatational tracheostomy (pdt) because of the inability to extend the neck, making tracheal puncture at the correct level more challenging. patients with csi routinely undergo pdt at our institution, however, with both traditional bronchoscopic as well as with real-time ultrasound (rtu) guidance. our objective was to review the incidence of complications related to pdt in patients with csi versus patients without csi. we reviewed the records of consecutive patients who underwent pdt performed by a single operator at our neurocritical care unit between / - / . all patients requiring tracheostomy are screened for eligibility for pdt by the attending neurointensivist on service. we recorded the percentage of patients who successfully underwent pdt vs requiring conversion to surgical tracheostomy, the specific guidance used (bronchoscopy, rtu) and all short-and long-term complications including placement of the tube above the first tracheal ring. a total of patients underwent pdt performed by a single neurointensivist. all patients screened by the operator underwent an attempt at pdt, and all patients successfully completed the procedure without conversion to surgical tracheostomy. ninety-eight of ( %) did not require csi and ( %) required csi. in the csi group, bronchoscopy alone was used in / ( %) and bronchoscopy plus rtu in / ( %). no complications occurred in the csi group. in the no-csi group, there were ( %) complications (one tracheal granuloma and two tube dislodgments within days). no other short or long term complications were recorded. all tubes were placed below the first tracheal ring. it is feasible to safely perform pdt in patients with cervical spine immobilization using bronchoscopic and real-time ultrasound guidance. following traumatic brain injury (tbi), increased serum biochemical marker levels reflect the extent of neurological damage, prognosis and clinical outcomes. effective tbi management strategies are lacking. despite the neuroprotective effects of therapeutic hypothermia after cardiac arrest, its tbi use remains controversial. delays in achieving target temperatures in human trials taking - hours (nabish-i; nabish-ii) may have contributed to the lack of benefit. we hypothesized prompt, rapid induction of hypothermia, immediately following tbi would lower predictive serum biomarkers of brain injured swine. sixteen domestic cross-bred pigs ( - kg) were subjected to a atm ( ms) fluid percussion tbi. eight injured animals were cooled to °c within minutes of injury and maintained for hours using transpulmonary hypothermia. eight control animals were maintained at °c using similar doses of inhalational and intravenous general anesthesia. brain temperature was monitored with camino.® serum markers of tbi: s- calcium binding protein b (s- b), neuron-specific enolase (nse), glial fibrillary acidic protein (gfap) and phosphorylated axonal form of the neurofilament subunit nf-h (pnf-h) were measured prior to injury and seven times over hours. surviving animals were euthanized and necropsied five days post-injury. at , , and hours, s- b, nse and pnf-h, were lower in the hypothermia group vs. controls. gfap levels were decreased at hours. after injury, peaks and troughs of the biomarkers occurred at various intervals. s- b levels were reduced in both groups during the initial hours post-injury, with control levels increasing at hours. early initiation and rapid cooling of brain temperature to - °c for hours was associated with attenuated s- b, nse, gfap and pnf-h levels in swine. general anesthesia was associated with early mitigated s b levels. prompt therapeutic hypothermia and prolonged anesthesia may offer neuroprotection after tbi. mild traumatic brain injury (mtbi) from blast exposure represents a significant threat to military personnel. until now there has been no way of knowing what the individual service member experienced during an exposure. we report the first individual measurements recorded during combat operations and how those readings were used to assist evaluation of the injured service member. the nato role- hospital, kandahar afghanistan received the index case of a service member (sm) exposed to an improvised explosive devise (ied) blast while wearing a blast dosimetry system composed of blast gauges placed on the back of the helmet, chest, and shoulder. the gauges include status lights that allow immediate feedback for injury risk via colored lights: green = negligible (< psi peak), yellow = moderate (between and psi), and red = severe ( psi and above). in addition, time traces of the overpressure and -axis acceleration are recorded and available for download through a micro-usb port. the sm's gauges were initially checked hour minutes after the blast, demonstrating a yellow status light. the blast data downloaded from the gauges demonstrated a consistent exposure of . msec composed of a primary flow immediately followed by a secondary wave. the head gauge recorded a peak overpressure of . psi and impulse pressure of . psi-sec. there was msec of sustained pressure above psi from the primary flow. all gauges demonstrated similar blast profiles, including a secondary reflective wave. these measurements are firsts in both the recording of an individual's exposure during a blast related attack and the use of that data for patient triage and medical evaluation. blast gauges measure environmental exposure and do not diagnose mtbi, however; they do provide clinicians with important information in the evaluation of patients subjected to blast. to consider the definition of initial signs and symptoms to compare outcomes after "severe" traumatic brain injury regard to mechanism of injury. design-this study included all adult patients who presented to ed at a level- trauma center with severe (gcs score< ) traumatic brain injury. from the total cohort(n= ), % suffered tbi because of "fall" and % due to traffic accident(mvc). significant proportion of each sub-group was comprised of males ( % in-mvc with median-age= ; % in-falls with median-age= ) · for all the patients arriving to ed after a traffic accident with severe gcs: % had loc, % had aoc, % had pta, % got admitted to hospital, % had an abnormal head ct (bleed/fracture), % got admitted to icu, % had some neuro-surgical intervention and % patients died in hospital. · for all the patients arriving to ed after a history of fall with severe gcs: % had loc, % had aoc, % had pta, % got admitted to hospital, % had an abnormal head ct (bleed/fracture), % got admitted to icu, % had some neuro-surgical intervention and % patients died in hospital. · decrease in systolic blood pressure (p= . ) and increase in diastolic blood pressure (p= . ) are more likely to have a fracture after a traffic accident in severe tbi. increasing of blood pressure p= . ) and decreasing of pulse (p= . ) is significantly associated with icu admission after a fall. comparing data for two most common mechanism of injury in severe tbi suggest that some vital signs and symptoms have significant impact with outcomes depends on mechanism of injury. these observations should be studied in larger cohort to find more significant association between mechanism and outcomes. cerebral edema is the one of the most significant predictors of poor outcome after traumatic brain injury. it is still unclear what the pathophysiological and cellular mechanisms and predictors of post-traumatic edema are. the exponential growth in genetic information has opened an avenue for investigation in traumatic brain injury and implicated specific genes in the pathophysiology of post-traumatic injury edema. two examples are the aquaporin- and cacna genes, which respectively encode water and calcium channels. the aquaporin- gene on chromosome q . - . encodes the aquaporin- protein (aqp ) water channel. aqp is one of the bidirectional high capacity water channels that is primarily expressed in astrocytic foot processes in the central nervous system at the blood-brain barrier and is thought to be critical for brain water homeostasis. experimental studies showed that aqp deficient mice had significantly reduced cerebral edema and better survival in a water intoxication model. the cacna gene on chromosome p encodes the a a subunit of a neuronal calcium channel. patients with familial hemiplegic migraine and delayed fatal cerebral edema and seizures from minor trauma have been found to have mutations in cacna , which are hypothesized to enhance development of cytotoxic edema. a missense mutation is reported to enhance risk of delayed fatal cerebral edema. hypothesis: the cacna gene missense mutation s l and aqp polymorphisms will be over-represented in patients with post-traumatic cerebral edema. to perform full exon sequence analysis of these two genes in well-defined cases of excessive cerebral edema. our long term goal is to systematically investigate genetic variants as determinants of risk of excessive cerebral edema. patient recruitment is currently ongoing. it is hoped that this will further elucidate secondary mechanisms of injury specifically in the formation of post-traumatic edema and lead to targeted therapies in the future. microwave occurs when improvised explosive devices was exploded. however, the effect for brain by microwave has not been clarified. under general anesthesia, s-d rats were irradiated by head-focused microwave by microwave fixation system (model mmw- / muromachi kikai co., ltd.), which were classified in three groups ( . kw/ . sec (i), . kw/ . sec (ii), . kw/ . sec (iii), and sham group) by intensity (n= in each group). vital signs were evaluated, arterial blood gas was examined, and we checked pathologic findings by hematoxylin-eosin (he) stain immediately after microwave irradiation, post hours, hours, hours, hours, weeks, and weeks in each group. blood pressure was elevated transiently immediately after irradiation, and recovered in short period. pao was unchanged in post-irradiation phase, except in group i. in he stain, neuron was degenerated and left out especially in cerebral cortex and hippocampus, microglia cells were accumulated in these regions. these pathological changes were observed frequently and earlier, when irradiation was intense. the result was firstly reported that head-focused microwave irradiation induced brain injury in s-d rats, and this brain injury was related with intensity of microwave. pathological change was impressive because it was occurred gradually and progressive. further study will be required, whether this type of brain injury is similar with traumatic brain injury, or cerebral ischemia or not, and the study of behavioral effects of microwave irradiation is necessary, especially when the intensity of irradiation was not severe. the efficacy of decompressive craniectomy (dc) in the treatment of moderate-severe traumatic brain injury (mstbi) is a topic of debate in neurocritical care. despite the recently published randomized dc in diffuse tbi (decra) trial, it is still unclear when and for which tbi patients this procedure should be considered. in order to assess the utility of dc in evidence-based clinical practice, we present a matched case-control study that compares surgical and non-surgical outcomes among patients with mstbi. we conducted a retrospective analysis of mstbi injuries treated at a single level i trauma center from to . twenty mstbi patients aged between and years, who underwent dc, were enrolled. paired controls that underwent medical therapy only were selected according to glasgow coma scale (gcs) score and age. primary lesion type, pupil reactivity, hypotension, hypoxia and icp crisis were secondarily considered in matching cases with controls. we focused on mortality, glasgow outcome score (gos) score upon hospital discharge and gos score at months as the primary measures of outcome. in the dc group, we found that % of patients died; % had a favorable outcome at discharge ( or higher on gos); and % had favorable outcome at months. in the control standard-care group, we found that % of patients died; % had favorable outcome at discharge; and % had favorable outcome at months. pupil reactivity and gcs score on admission were the variables highly correlated with mortality. statistical analysis will be available at the meeting and presented for the first time. in this cohort, undergoing dc did not seem to confer a mortality benefit to patients with mstbi. good recovery after mstbi was observed in a larger percentage of the non-surgical group, which is consistent with the findings of the decra trial. each year in the united states, over . million patients present to emergency departments as a result of traumatic brain injury (tbi). severity classification of tbi is based on the glasgow coma score (gcs), with severe tbi being a gcs score between and . there is always a subset of "severe" tbi that requires surgical intervention. the current study examines this subgroup to decipher any symptomatology that may be helpful in identifying who these patients are. the objective is to determine which if any factors predict the need for surgical intervention in patients with severe traumatic brain injury (tbi). this study is a subgroup analysis of the larger cohort of consecutive adult tbi patients that presented to the ed. our sample included only severe tbi patients (gcs< ). besides descriptive analysis, logistic regression analysis was done to determine the significant predictors of surgical intervention in this subset of patients. lab values (sodium, potassium, bicarbonate, lactate, blood glucose, wbc, rbc, platelets, inr, aptt) and symptoms (such as-seizures, vomiting, loss of consciousness, alteration of consciousness, post-traumatic amnesia) were the dependent variables compared with surgical intervention (independent variable). of the total severe tbi cohort (n= ), % required surgical intervention. presence of abnormal head ct (bleed in % of the total cohort) is significantly associated with surgical intervention (p= . ). vomiting (p= . ), lactate (p= . ), higher wbc (p= . ) and lower platelet count (p= . ) individually showed significant association with surgical intervention on a univariate regression model. these data suggest that abnormal head cts, particularly those that result from bleeding, as well as lactate, platelet count, wbc count and vomiting are significantly associated with surgical intervention. the association of lab values with likelihood of undergoing surgical intervention is an interesting future research point. to study the potential usefulness of initial vital parameters and laboratory evaluations to predict short term prognostic this is an observational cohort study of all adult patients who came to the emergency department(ed) of a tertiary care hospital, in a month period during - . for the purpose of analysis, we considered initial vitals and lab values available for all patients. we individually compared vitals (pulse and mean arterial pressure-map) and laboratory values [sodium(na + ), potassium(k + ), bicarbonate(hco -), glucose, wbc, rbc, platelets, inr) for the following prognostic variables: abnormal head ct finding(yes/no), hospital admission (yes/no), icu admission, in-hospital death, hospital length of stay(hlos), and -month mortality using t-tests and correlations. the significant variables were then entered into a logistic regression model (for categorical variables) and a multiple regression model (for continuous variables) simultaneously to determine significant predictors of prognostic outcomes. significance level was set at p= . . increase in glucose(p= . ) and wbc(p< . ) lead to a higher likelihood of having an abnormal head ct, when controlling for map and hco -; increase in glucose (p= . ) and wbc (p= . ), and decrease in hco -(p= . ) and platelets(p= . ) increases the likelihood of getting admitted, when controlling for map, k + , and rbc; increased glucose(p< . ), decreased hco -(p= . ) and decreased platelets(p= . ) increases chances of in-hospital death, when controlling for wbc and inr; increased glucose(p= . ), increased wbc(p< . ), and decrease in rbc(p= . ) increases hlos, while controlling for pulse, k + , and hco -. the study indicates that some initial vitals and lab values can help to determine the prognostic outcomes in adult traumatic brain injury. though our study is limited by a single-site patient population, the interesting findings warrant further research efforts in this specific area. ultrasonic assessment of optic nerve sheath diameter (onsd) as a non-invasive measure of intracranial pressure (icp) has been evaluated in the literature as a potential valid technique for rapid icp estimation in the absence of invasive intracranial monitoring. the technique can be challenging to perform and little literature exists surrounding intra-operator variability. in this study we propose an examination of onsd utilizing a variety of novel ocular models, to both define the ability of the ultrasound linear array probe to capture different known onsd, and to assess intra-operator variability with the technique. here we present the model and data. we designed ocular models composed of gelatin spheres and variable three dimensional printed cylinders, which simulate the globe of the eye and variable onsd's respectively. these models will then be suspended in a gelatin background. operators will then utilize the linear array ultrasound probe on these models in order to determine onsd of sizes, with measurements each in order to assess intra-operator variability with the technique. our optic nerve sheath model offers ultrasound images comparable to in vivo, and is quick to manufacture. analyzing the data, we removed the first two measurements from the series of ten. we defined those as "practice attempts" with the technique. for the onsd models, the means were: . mm with sd of . mm ( % ci of . ), . mm with sd of . mm ( % ci of . ), . mm with sd of . mm ( % ci of . ). utilizing the standard linear array ultrasound probe for onsd measurements in our model provided reliable results with minimal intra-operator variability across variable sheath sizes. knowing this, we can further apply this novel model of onsd to us teaching and training courses with confidence in its ability and the techniques ability to produce consistent results. the objective of this study was to identify factors (signs and symptoms after injury, vital parameters, and glucose) that can be used as predictors of an intracranial bleed. this will improve identification and treatment of patients who present to the emergency department (ed) with tbis. this is an irb approved observational cohort study done at a level trauma center, and included all adult patients presenting to the ed following a tbi. data for patients presented during study variables included age, loss of consciousness (loc), seizure (sz), vomiting, alteration of consciousness (aoc), post-traumatic amnesia (pta), glucose level, pulse, and blood pressure (bp). all variables were tested for association with intracranial bleeding using chi-square tests of independence, t-tests, and then significant variables were included in a regression model. limitation of study were chart review and a single ed. the cohort consisted of , patients, of which % (n= ) had a ct scan of head. % of total patients had an abnormal head ct, and % of those had an intracranial bleed. statistical analysis indicated that loc (p= . ), aoc (p= . ), pta (p< . ) and advanced age (p= . ) were significantly correlated with having a bleed. vomiting and sz were not statistically significant. among patients who had head cts, both pulse and systolic blood pressure decreased between the first and second measurements; both pulse(p= . ) and bp(p= . ) decreased significantly less in patients with bleeds compared to those without bleeds. additionally, higher ed glucose level was associated with having a bleed (p< . ) on head ct. these data indicate that older age, loc, aoc, pta, and elevated glucose levels can be used as predictors of intracranial bleeds. sustained elevation of pulse and systolic blood pressure may also be indicative of a bleed in tbi patients. patients with moderate-severe traumatic brain injury (mstbi) commonly die from withdrawal of support, likely as a consequence of an unfavorable outcome prognosis provided to the family by the treating physician. it is unknown whether prognostication may lead to self-fulfilling prophecies, and whether the presence of intensive care unit (icu) complications may accentuate possible provider bias. in this study, we surveyed clinicians caring for patients with mstbi to examine the variability of outcome prognostication and the influence of icu complications on these predictions. we conducted an anonymous electronic survey of clinicians, including faculty members (neurology, neurosurgery, trauma, anesthesia/critical care), neurology house staff, icu affiliate practitioners and neuroicu nurses at a single level i trauma center. the survey included three tbi case vignettes and their respective icu courses. questions were designed to assess the utilization of known tbi prognostic models, relative importance of icu complications for outcome prognostication and aggressiveness of care recommended by the survey participant. a total of surveys were distributed by email or paper, and have been returned. so far, we have found that % of participants consider medical icu complications as very important in tbi prognostication. age, icu course and head ct findings are the prognostic variables considered most important to outcomes. % of non-critical care neurologists are uncomfortable providing tbi prognostication. case responses suggest that clinicians tend to recommend aggressive care (surgery), but predict unfavorable outcomes. the survey is ongoing, but complete results will be available at the meeting and presented for the first time. we have discovered great variability in outcome predictions made by clinicians with different levels of experience in treating mstbi. self-fulfilling prophecies may exist among mstbi outcomes. outcome studies should focus not only on admission variables, but also on icu complications in order to guide clinicians in providing prognostication. the objective of this study was to identify pre-hospital factors that are associated with worse severity of head injury in order to help physicians identify when tbi treatment may be necessary. this is an observational cohort study that included adult patients presenting to the(ed) following a motor vehicle collision. study variables included age, gender, seatbelt use, loss of consciousness (loc), seizure, vomiting, alteration in consciousness (aoc), and post-traumatic amnesia (pta). severity of tbi was classified according to the glasgow coma scale, with mild defined as - , moderate being - , and severe being anything less than . the gcs was obtained both in the pre-hospital and ed settings. the cohort of was % male. the median age was (iqr: - , r: - ). the breakdown of severity in the prehospital setting (n= ) was % mild, % moderate, and % severe. in the ed (n= ), the breakdown was % mild, % moderate, and % severe. pre-hospital factors significant for the z-test included seatbelt (sb) use, loc, aoc, pta, and gender. males, patients who did not wear seatbelts, and patients who had a positive loc, aoc, or pta were more likely to sustain a moderate or severe tbi. having a seizure was also significantly associated with increased tbi severity (p= . ). (see table ) additionally, the data show that the likelihood of having an abnormal head ct increases with age (p< . ). although vomiting was associated with greater tbi severity, the results were not statistically significant. early symptoms such as loc, aoc, seizures, and pta are early predictors of worse severity in patients who sustain a head injury during their motor vehicle collision. age, male gender, and lack of seatbelt use also correlate with greater tbi severity. identifying crucial symptomatic predictors of icu admissions, icu length of stay and mortality rates in traumatic brain injury (tbi) patients with history of fall. retrospective chart analysis was performed on all adult patients arriving to emergency department with history of fall at a level one trauma center for parameters like vomiting, alteration of consciousness (aoc) & loss of consciousness (loc) after tbi; post-traumatic amnesia (pta) and history of seizures before or after injury, along with outcomes such as icu admission & icu length of stay. from the total cohort (n= ), % (n= ) of patients were admitted to icu, most of them were males( %,p= . ). aoc was found to be strongly associated with icu admission ( %, p< . )[including the patients who had brief loss of consciousness of < mins( %)], and month mortality rates(p= . ) when adjusted for mild gcs scores. · icu length of stay was higher in patients admitted to icu with aoc (p= . ) and pta ( . ). icu admissions had higher day readmission (p= . ), in-hospital death (p< . ) and month mortality rate ( %, p< . ). · % of patients were found to have intra-cranial bleed when presented to ed with aoc(p= . ), and % of these patients were admitted to icu. on a multivariate regression model analysis, patients who had abnormal head ct with mild gcs on ed presentation had higher month mortality rates (p= . ) when adjusted for age. patients with symptoms such as alteration of consciousness and post-traumatic amnesia after traumatic brain injury as a result of fall are more likely to be admitted to icu with significantly longer icu length of stay. mild traumatic brain injuries in fall patients should not be overlooked in daily practices because of significant mortality rates. cardiovascular disturbances remain a leading cause of morbidity and mortality in patients with acute spinal cord injury (asci). asci patients often develop symptomatic and potentially life-threatening bradycardia. our practice has been to use albuterol elixir prophylaxis in asci patients, taking advantage of its side effect profile associated with a typical dose of mg tid or qid, to prevent further symptomatic bradycardia. evidence of efficacy with this regimen is, however, lacking. we set out to determine whether treatment with oral albuterol would decrease the frequency of bradycardic episodes in patients with asci. we retrospectively identified adult patients admitted to university of new mexico hospital between - who sustained an asci and received oral albuterol therapy. the frequency of bradycardic events (hr < bpm) before and after initiation of albuterol was collected. we compared the number of bradycardic events before and after albuterol within each subject using the wilcoxon signed rank test. bootstrap methods were used to further validate our findings. we identified asci patients who had evidence of symptomatic bradycardia before the initiation of the albuterol therapy, including hypotension and in cases bradycardic cardiac arrest. the median number of bradycardic events was ( . , iqr) before albuterol and was ( , iqr) after albuterol. we found that patient's had a significantly lower number of bradycardic events after the initiation of albuterol (p = . ). ten patients experienced less bradycardic events. the median difference was less bradycardic episodes. bootstrap estimates of the median difference were consistent with our initial analysis. albuterol appears to be an effective means of treating bradycardia in patients with acute spinal cord injury. severe traumatic brain injury (tbi) is frequently associated with eeg changes like epileptiform discharges, seizures; periodic lateralized epileptiform discharges pleds or paroxysmal delta activity. we report a case of tbi with generalized hz spike and wave pattern that did not represent seizures a y old girl without epilepsy history presented after being involved in a motor accident. initial gcs was and remained the same over the next days. ct showed contusions with small left subarachnoid hemorrhage. phenytoin was started for seizure prophylaxis. on day , she improved clinically, however, on day she had fluctuating consciousness and continuous eeg monitoring was initiated. various antiepileptic medications were tried over the next several days including lacosamide, valproate, topiramate, levetiracetam and ethosuximide (eth) without significant change clinically or on eeg. she started improving clinically on day but became extremely drowsy on day , all meds except eth were weaned. she showed improvement and was discharged to rehab on day . a prolonged eeg after months was normal and eth was weaned off. she continues to do well almost one year after and is maintaining her school grades at pre-injury level. the patient's initial eeg (day post injury) showed generalized hz spike and wave pattern occurring every - seconds which continued for days despite treatment with various anti epileptics as described. on day eeg pattern changed to generalized rhythmic delta activity( - hz) especially during arousal. mri during the stay showed micro hemorrhages in both frontal lobes and right temporal lobe reflective of diffuse axonal injury. a hz spike and wave pattern mimicking absence seizures can be seen on eeg transiently after tbi, however its clinical significance is unclear. whether it needs to be aggressively treated or not cannot be conclusively established but the longterm prognosis appears to be benign. free radical-induced lipid peroxidation (lp) has been demonstrated to lead to the formation of isoprostanes from arachidonic acid and neuroprostanes from docosahexaenoic acid. lp is common after traumatic brain injury (tbi) and constitutes one of the key mechanisms of pathology related to secondary injury after tbi. one of the consequences of lp is the compromise of neuronal calcium (ca ++ ) homeostasis, leading to ca ++ overload and activation of the proteolytic -spectrin. the purpose of this project is to characterize the concentration--spectrin degradation after tbi. this study is a prospective, single-center study of adult moderate to severe tbi patients. inclusion criteria are age > yo, closed head injury, within hours of tbi, and glasgow coma score (gcs) < . serial samples from urine, blood, and cerebrospinal fluid (csf, when available) are obtained for up to weeks after injury. demographic data and pertinent clinical information are also collected. the biomarkers ( & f t -isoprostanes, f -isofurans and f -neuroprostanes) are measured via -spectrin breakdown products (sbp) by western blot analysis. we have enrolled fifteen patients to date. preliminary results suggest that the study population is typical of tbi (mean age . years, % male, median admission gcs ). serum and csf & f t -isoprostane values are above published values for normal individuals, with csf values peaking at hours after tbi. sbp are also measured in elevated amounts in csf compared to non-tbi controls (in whom they are not measurable). preliminary data suggests that serum and csf isoprostane values are elevated after tbi. continued patient accrual, further sample analysis, and comparison to control groups is needed to more precisely define the effect of tbi on the time course of lp biomarkers. traumatic intraventricular hemorrhage (tivh) is generally considered to be associated with moderate to severe traumatic brain injury and a significant mortality rate. there exists, however, a rare subset of individuals who manifest with isolated traumatic intraventricular hemorrhage and have a good prognosis and outcome. we present a case of an -year old female who suffered polytrauma and an isolated ventricular hemorrhage following a traumatic fall while mountain climbing. her history indicated mild transient confusion and amnesia occurring around the time of the fall. her glasgow coma score was , her neurologic exam was normal and she had no neurologic complaints other than positional lightheadedness and nausea. a comprehensive exam was notable for a right hip dislocation, nasal fracture, l vertebral body fracture, right apical pneumothroax and pulmonary contusion. computed tomography of the head showed an acute hemorrhage in the left lateral ventricle prompting concerns for traumatic brain injury. no additional pathology was noted on a follow-up magnetic resonance imaging. repeat ct scan showed mild interval decreases in the size of her ventricular hematoma. the patient was discharged one week after admission and had developed no neurologic complications. she was diagnosed with concussion and isolated intraventricular hemorrhage. isolated intraventricular hemorrhage is a rare complication of traumatic head injury that can have a good prognosis and outcome. the case shows the difficulty in categorizing this particular condition within the current spectrum of traumatic brain injury and specifically highlights shortcomings with classification systems that utilize neuro-imaging abnormalities to determine severity of injury. traumatic intracranial aneurysms (tias) are distinctly uncommon, comprising fewer than % of all cerebral aneurysms. tias that develop following blunt head injuries present the clinician with both diagnostic challenges and clinical difficulties. the natural histories of giant intracranial aneurysms are generally grave owing to mass effects, severe hemorrhage, and distal thromboembolism. case report. we present the case of a -year-old male was involved in an accident in which he suffered severe head injury from a falling heavy iron hammer. the immediately unenhanced head computerized tomography showed hemorrhagic contusions, subarachnoid hemorrhage, skull fracture and basal fracture. he had been in a deep coma ever since. the computed tomographic angiography (cta) revealed a giant aneurysm of right internal carotid artery about one month after the blunt head injury. the aneurysm was measured . cm at its maximal diameter on image. of note, the patient failed to improve the following day and died on the fiftieth hospital day. giant tias are very rare but fatal complications of blunt head injury probably related to effects of vessel wall trauma and possibly a combination of neurological deterioration. in our case, the involved mechanism was suspected to be related to skull base fractures or resulted from stretching of the artery across the process during the impact. cta has a high sensitivity of about . % and a high specificity of about . % for diagnosing cerebral aneurysms (including traumatic aneurysms). apart from this, cta permits -dimensional visualization of aneurysms and assesses surrounding intracranial structures that are not visible on dsa. therefore, although -dimensional digital subtraction arteriography is currently the diagnostic gold standard in cerebral aneurysmal disease, fast and noninvasive cta may be preferred in the acute setting of tias. julio cabrera , corina puppo major burnt patients require large volumes of fluid replacement due to a generalized increase in permeability and edema caused by cytokines. fifty percent of the administered fluids produce edema in "preserved" tissues. multiple organ edema follows fluid replacement. escharotomy is frequently performed to decompress limbs and thorax, but not neck. our objective was to describe and diagnose neck-head compartment syndrome in patients with neck circumferential burns and/or neck edema by ) suspectng it and ) confirming diagnosis with the help of transcranial doppler (tcd) ultrasonography, searching for a high resistance pattern in cerebral blood flow velocity at basal cerebral arteries. tcd examination was performed before and after escharectomy in two both patients presented a neck-head compartment syndrome, evidenced by the cerebral hemodynamic repercussion of neck compression: hypoperfusion with an increased resistance pattern in dtc. p : secondary compartment syndrome due to massive fluid replacement; without circumferential burn. p : compartment syndrome in circumferential neck burn. tcd confirmed the clinical suspicion of cerebral hypoperfusion, guiding the decision to perform surgical decompression to treat it, and helped to assess the results of the decompressive surgery. introduction . % hypertonic saline is used for the treatment of increased intracranial pressure (icp) and in the prevention and reversal of brain herniation syndromes. the use of hypertonic saline in the management of combat related penetrating and severe traumatic brain injury is described. . % hypertonic saline effectively managed icp with decreased risk of hypovolemia and secondary hypotension compared with mannitol. . % hypertonic saline also preserved cerebral blood flow, decreasing the risk for secondary cerebral ischemia in acute neurotrauma patients, where hyperventilation is contraindicated. the nato hospital, kandahar afghanistan treated eleven ( ) patients with twenty-seven ( ) doses of . % saline from -march to -april . hypertonic saline was used to treat acute elevation in icp, as well as to maintain an elevated serum sodium concentration during periods of cerebral edema. all patients were treated with initial conservative icp management. external ventricular drains were placed and drainage of - cc of csf was performed in an attempt to maintain icp before using hypertonic saline. patients with life-threatening clinical signs of elevated icp secondary to brain edema or acute neurologic deterioration were potential candidates for . % hypertonic saline therapy. - ml of . % sodium chloride was administered via a central line infusion. . % hypertonic saline was successful in acutely reducing icp. a ml bolus of . % saline predictably increased the serum sodium levels allowing reliable titration and maintenance of serum sodium levels and efficient management of the patient's volume status ( cc of . % = cc of %). penetrating and severe closed head injuries have the potential to lead to neurologic emergency as a result of brain edema associated with primary tbi or following neurosurgical intervention. in a combat tbi population, . % hypertonic saline demonstrates a clinical benefit over alternative treatments by decreasing the risk of secondary cerebral injury during the management of elevated icp and was well tolerated. unintentional death was the ninth leading cause of death among elderly patients. given their comorbidity profile, many of them are also on antiplatelets or anticaogulants. we sought to characterize the burden of "pro-bleeding" medications such as antiplatelets and anticoagulants in the population aged over who sustain a head injury. this observational cohort study was conducted at a level one trauma center that has a county catchment area serving over million. the trauma acuity is high, with over % of our patients haveing iss scores over . the age cutoff of for "elderly" is based on our trauma alert activation criteria. thirty-nine percent of the cohort was on at least one type of anticoagulant or antiplatelet, as follows: warfarin %, aspirin %, clopidogrel %, asa+dipyridamole %, heparin/lmwh %.a third of the cohort required icu admission. icu length of stay ranged from - days. patient in particular, on warfarin had a significantly longer icu length of stay (p= . ) when adjusted for inr level. the median inr for the whole cohort was . with an iqr of . to . . the median inr amongst those on warfarin was . with an iqr of . to . . patients on an antiplatelet or anticoagulant agent were significantly more likely to have an abnormal head ct (p= . ). % of the patients who were on warfarin needed some sort of anti-coagulant reversal to minimize bleed. patients on warfarin were more likely to undergo neurosurgical intervention (p< . ) when compared to cohort not on warfarin. antiplatelet and anticoagulant drugs can confer additional morbidity to persons who sustain a tbi. it may be important to recognize this early, and prepare for higher level care needs. introduction therapeutic hypothermia (th) is know to cause immune suppression. determining the degree of immune suppression at the bedside is often difficult or impossible. immune cell function (icf) measures the concentration of atp from circulating cd cells following in vitro stimulation with phytohemagglutinin (pha) as an indicator of immune cell function. icf is often used in solid organ transplant programs to modulate the immunosuppressive treatment. we propose the use of ifc to determine the degree of immune depression in the patient treated with th. immune cell function, cylex inc, columbia, md was obtained in three populations of patients: group : patients treated with th, ifc obtained while at target temperate, degrees c group : patiients that were admitted to the care of the neurocritical care team, requiring icu care. group : patient from sanford renal transplant program with stable immunosuppressive therapy. the average icf of group were , of group , and of group , . patient being treated with th have a profoundly depressed icf. the level of immunosuppression is equal to if not greater that those with solid organ transplants. according to the cylex data a level of less than represents an immune suppressed state. this does not appear to be a phenomenon of the critically brain injured patient since those without th had a normal icf while further studies are in process, this data has effected out practice. we now treat patients on th as immunosuppressed patients. very early prediction of neurological outcome after cardiac arrest (ca) remains challenging. several single center studies have suggested that bispectral index (bis) can predict outcome for patients treated with therapeutic hypothermia (th). we evaluated the ability of bis to predict outcome in a multicenter study. medical centers prospectively enrolled comatose ca patients treated with th. outcome was defined as good (go) if cerebral performance category (cpc) score was - , and poor (po) if cpc - at hospital discharge (hd) and at months ( m). bis data was assessed blind to outcome for initial value after first dose of neuromuscular blockade (nmb -bisi) and at hours post-rosc (bis ). patients were enrolled with a mean age of (sd ) years, % were male, % witnessed, initial rhythm was vt/vf in %, pea in %, asystole in %, and time to rosc was . ( ) minutes. at hd, ( %) had go with similar age as po but shorter median time to rosc at (iqr - ) mins vs ( - , p= . ). go patients also had more vt/vf as initial rhythm and witnessed ca (p< . ), and more males (p= . ). on roc curve comparisons, both bisi (auc . ) and bis (auc . ) performed better than time to rosc (auc . ) or age (auc . ) -p< . for all comparisons. among ca-th treated patients, this is the first multicenter trial to confirm that bispectral index values after first dose of nmb and at hours post-rosc predicted outcome better than time to rosc, rhythm, or age. bis appears promising as a tool to predict outcome very early after ca, and may be helpful during clinical trials to stratify the severity of brain injury sustained during ca. hypotension negates the cerebral protective effect of therapeutic hypothermia (th). myocardial depression, "cold-induced diuresis," and hypokalemia can lead to refractory hypotension during the maintenance phase of th. intravascular volume replenishment and inotropic infusion are effective but cause wide swings in heart rate, blood pressure, cardiac output and acid-base status. we propose the use of vasopressin as a physiologically appropriate agent to correct hypothermiainduced hypotension. hypothesis: in swine, the investigators tested the hypothesis that an infusion of vasopressin would restore blood pressure to normal levels during th. six domestic cross-bred pigs ( - kg) were subjected to a atm fluid percussion injury to the brain followed by systemic hypothermia ( °c) for hours. the animals were turned side to side and to sternal recumbency every six hours. during phase i (first hours), the blood pressures were maintained in the normal range with intermittent doses of epinephrine and fluid boluses. during phase ii (second hours), continuous vasopressin infusion ( . ug/min) was added to maintain blood pressure. the number of episodes of hypotension (map < mm hg), the volume of fluids (liters), and the total dose of epinephrine (mg) used during both phases were compared using student's paired t-test (p> . ). in all animals, the infusion of vasopressin effectively mitigated the occurrence of hypothermia-induced hypotension. the episodes of hypotension ( . ± . v . ± . ), the total volume of fluids ( . ± . v . ± . ), and the total dose of epinephrine ( . ± . v . ± . ) administered were significantly reduced during phase ii. in order to maximize the benefits of th, hypotension must be avoided. animal studies show that despite hypothermia, hypotension causes cerebral cortical tissue depletion of atp and phosphocreatine and an increase of lactate and nadh levels. the infusion of a low dose of vasopressin reverses these anomalies and effectively mitigates hypotension. hypotension, hyperoxia, and hypoxia early after the return of spontaneous circulation (rosc) are each associated with increased mortality, while early hypertension is associated with good outcome. we assessed these variables and their relationship to outcome in cardiac arrest (ca) survivors treated with therapeutic hypothermia (th). with irb approval, we reviewed prospective and retrospectively collected data in a single-center database of patients undergoing th after ca. demographics and clinical factors were compared among patients with cpc - (good outcome) and cpc - (poor outcome) in a bivariate model. various definitions of hypotension, hypertension, hypoxia, and hyperoxia were evaluated. we constructed logistic regression models including potential confounders and the variables of interest. among patients, age, vt/vf rhythm, shorter time to rosc, witnessed arrest, bystander cpr, and stemi on initial ecg were each strongly associated with good neurological outcome, as were a lower peak neuron-specific enolase level and higher bispectral index (bis) score after neuromuscular blockade. hyperoxia (pao > mmhg) was common (present in . with good and . with poor outcomes, respectively) as were hypoxia (pao < mmhg) and hypotension. none of these factors was a predictor of outcome. logistic regression models intended to adjust for the potential confounding influences of age, time to rosc, heart rhythm, witnessed arrest, and bystander cpr, also did not identify a relationship between the variables of interest and outcome. our data did not confirm the previously described relationship between post-resuscitation factors and outcome. this may reflect an inadequate sample size, but it is also possible that post-resuscitation hemodynamic and biochemical factors are minimally important to outcome, compared to the duration and type of the arrest. further investigation in larger data sets is warranted. determining the presence of an infectious process during therapeutic hypothermia (th) can be difficult. in addition, differentiating central vs systemic fever is difficult in the brain injured patient. procalcitonin (pct) was been used to guide the use of antibiotics in sepsis and pneumonia in patients that are critically ill. we propose the use of pct to predict the presence of a systemic infection in patients during th. all patients treated with th had pct measured at the start of th. all patients were cooled with the medivance arctic sun . when the water temperature was < degree c, pct and two sets of blood cultures (bc) were drawn. sputum cultures (sc) were obtained if there was a change in sputum or during bronchoscopy. antibiotic use was determined by the neuro-intensivist results patients were evaluated; ich, tbi, cva and cardiac arrest (ca). a total of pcts were obtained. one patient ( %) had positive bc, pct of . ; patients ( %) had positive sc. remaining patients had negative bc and sc. all ca patients had increased pct > . (normal < . ) of which ( %) had positive sc and none had positive bc. of the remaining without positive bc ( %), ( %) had positive sc, all had pct < . . of the ( %) patients without positive sc, all had pct < . pct is a reliable method to exclude an infectious process in patients being treated with th that have not had a ca. while further studies are warranted, a pct < . appear to exclude both pulmonary and blood infections, while a pct < . appears to exclude a blood stream infection. from this data, pct is not a good marker for infection in the ca patient. therapeutic hypothermia (th) has become widely accepted practice for neuroprotection and improved mortality in comatose survivors of out of hospital v-fib cardiac arrest. evaluation for appropriateness of th is now part of acls algorithm. its use in non-shockable rhythms such as pea and asystolic arrest is less well established. we present our center's experience with th after cardiac arrest and review the clinical and electrophysiological parameters that may impact prognosis. this is retrospective review of medical charts including patients undergoing th after cardiac arrest at a single center from through the first quarter of . demographic and clinical data were collected. continuous eeg results were reviewed by two independent epileptologists who were blinded to the outcome of the patients. eegs were graded based on the synek scale for grading severity of eegs. patient's neurologic outcome will be assessed by grading cerebral performance category (cpc) score at the time of discharge. multivariate regression analysis will be performed on the data to identify parameters that would affect prognosis in cardiac arrest after cooling. fifty-eight patients were identified from our database. the overall rate of survival to discharge was %. the survival rate for v-fib arrest was % whereas the survival rates for asystolic arrest and pea arrest were % and %, respectively. results from the multivariate analysis will be forthcoming. our results affirm the predominant view that th indeed improves outcomes after cardiac arrest. in particular with ventricular fibrillation and pulseless ventricular tachycardia arrest, we have seen very encouraging results. patients with pea/asystolic arrest fared worse but outcomes are still improved compared to historical control. since , mild therapeutic hypothermia (mth) has been the standard of care when spontaneous circulation returns after a witnessed, out-of-hospital ventricular fibrillation arrest[ ]. at our institution, we have initiated mth for approximately fifty patients since february . a knowledge, attitude, and practices survey was conducted querying neurology residents and attendings, emergency medicine (em) residents and attendings, and internal medicine (im) residents. our aim was to identify areas of weakness so that we could strengthen the overall awareness of the utility and benefit of mth. the survey consisted of nineteen multiple choice questions, ranging from asking how many times the participant had initiated mth; to parameters for the protocol; to how it impacts survival. the surveys were completed by: ten neurology residents and five neurology attendings; twelve em residents and two em attendings; and twenty im residents. all of the neurology residents and em physicians surveyed had been the primary provider for a post-arrest patient who underwent mth. the neurology residents unanimously agreed that mth after resuscitation from a shockable rhythm is standard of care, however only % of em physicians and % of im residents agreed. % of em physicians and % of im physicians answered that mth may be initiated in cases presenting after either a shockable or a non-shockable rhythm. % of the participants acknowledged that ventricular fibrillation portends the most favorable outcome. nearly % of participants agreed that ideal rosc is less than thirty minutes. three-quarters of physicians indicated the goal temperature as - °c; however, half of the neurology residents and % of neurology attendings answered this incorrectly. in conclusion, this survey has revealed a general understanding of mth, however, each specialty has its deficiencies. we can now educate each subset of physicians in a problem-focused manner. early quantitative assessment of non-contrast brain computed tomography (ct) using specialized software correlates with outcomes of cardiac arrest survivors. the proposed algorithm compared hounsfield units (hu) in the putamen (pu) to the posterior limb of the internal capsule (plic), but the work has not been validated in patients treated with therapeutic hypothermia (th) or using standard software and equipment. we included ca survivors treated with th who underwent ct in the first h after resuscitation (rosc). hu were averaged bilaterally at two levels in the pu and plic, and the pu/plic ratio calculated by a board-certified radiologist using a ge lightspeed vct slice scanner and agfa pacs system. receiver-operator characteristic (roc) curves were constructed, evaluating pu or pu/plic to predict poor outcome (cpc - ) at hospital discharge (hd) and months ( m). patients had median age years, % male, % out-of-hospital ca, % witnessed, % vt/vf, % pea, and % asystole. median (iqr) time to rosc was ( - ) minutes. / ( %) patients had po. when stratified by outcome, ct performed . ( . - ) hrs after rosc showed similar hu measurements for plic ( . po vs . go, p= . ) but lower hu in pu ( . vs . , p= . ) and pu/plic ( . vs . , p= . ). hu values for pu and pu/plic both predicted outcome: roc area under the curve (auc) for pu = . ( %ci . - . ) and pu/plic = . ( . - . ). among patients with m outcome data, pu predicted outcome ( . po vs . go, p= . ) with auc = . ( . - . ), but pu/plic did not. early after ca, hounsfield unit measurements in the putamen, and the pu/plic ratio were lower among patients with poor outcome, but the magnitude of the differences was small, and clinical utility uncertain. additional study is warranted. global cerebral edema following aneurysmal subarachnoid hemorrhage (asah) is associated with % in-hospital mortality. therapeutic hypothermia (th) is recommended for reduction of intracranial pressure (icp) based on class i evidence; however safety in prolonged states remains poorly studied. we retrospectively reviewed all cases of refractory icp elevation at the mayo clinic florida neurointensive care unit (nicu) from - who received adjunct th for more than hours. primary safety endpoints were qtc prolongation, development of bacteremia, and coagulopathy. additional outcomes included in-hospital mortality, hospital/nicu length of stay, and functional status at months. patients with asah and/or intracerebral hemorrhage underwent adjunct th. median age was ; were male. on admission, median apache was , and wfns was higher than in , all being modified fisher - . required barbiturates in addition to sedation, paralysis and hyperosmolar therapy. th was initiated on a median of hospital day and continued for a median of days (minimum= , maximum= ). mean icp over hours prior to th was . mmhg(sd= . ; range . - . ), decreasing to . mmhg(sd= . , range . - . ) over the first hours of th. patients had external ventricular drains placed and required decompressive craniectomy on average day hospital stay (range - ). safety data showed torsades-de-pointes in , mean qtc prolongation of with mean lengthening of aptt by . . patients had bacteremia on admission with new infections (urine, sputum, blood) documented in during th. overall, ( %) survived to discharge. median nicu/hospital length of stay was / . average modified rankin score at follow up was . . hypothermia greater than hours as an adjunct to standard icp reducing therapies appears feasible in patients with refractory intracranial hypertension. however, definitive safety of prolonged th would require direct comparison with similar cohort. refractory raised intracranial pressure (ricp) secondary to intracerebral hemorrhage (ich) and severe subarachnoid hemorrhage (sah) is a life threatening condition. treatment for ricp typically induces hypothermia (th) and decompressive hemicraniectomy (hct). however, direct comparison of the efficacy of these two therapies is lacking. data from this study may help determine the sequence of therapies that might improve outcomes in this patient population. in the present study using retrospective design, we tested the hypothesis that for patients with ricp, th is as effective in reducing icp as hct, using functional outcome at discharge as defined by modified rankin scale (mrs) as the primary outcome. we retrospectively reviewed all adult patients admitted to the neurointensive care unit from to with sah and ich with resultant elevated icp, who survived the first hours after admission. exclusion criteria included: pupillary anisocoria, limitation of care within hours of admission; or hemicraniectomy or craniotomy with clot evacuation prior to icp monitoring were excluded. initial review included patients (th= and hct= ). based on univariate analysis, admitting gcs score was higher with hct ( vs , p= . ), but other baseline demographic and clinical characteristics were similar. th group had longer icu los ( vs ), los ventilation ( vs ), and higher cost. however, discharge mrs ( vs ,p= . ) was similar. our initial analysis indicates longer icu care and overall cost with th, but similar functional outcomes at discharge. subsequent analysis will include inclusion of additional patients, icp comparison and adjustment for baseline characteristics. malignant middle cerebral artery(mca) infarction is devastating ischemic stroke, which the mortality rate is up to %. therapeutic hypothermia is one of the most promising neuro-protective therapies. successful result of hypothermia for cardiac arrest renewed interest in therapeutic hypothermia for stroke. the purpose of this study was to assess whether therapeutic hypothermia can reduce the cerebral edema and can improve the functional outcome in patients with malignant mca infarction. we reviewed retrospectively patients with malignant mca infarction presented within hours of symptom onset in a single center hypothermia registry. after informed consent, patients who had refused decompressive hemicraniectomy were treated with therapeutic hypothermia and monitored in the neurocritical care unit for complications. a modified rankin scale(mrs) and national institutes of health stroke scale(nihss) were obtained at months after symptom onset. eleven patients with a mean age of ± years and an nihss score of . ± . were treated with therapeutic hypothermia( ± ). seven of eleven patients were mca infarction, and four was ica t-occlusion. the mean time from symptom onset to initiation of hypothermia was . ± . hours and the total duration of hypothermia was . ± . hours. noncritical complications included shivering(n= ), bradycardia(n= ), hypertension(n= ), pneumonia(n= ), and arrhythmia(n= ). electrolyte imbalances were common during the hypothermia (hypernatremia;n= , hypokalemia;n= , hypophosphatemia;n= ). mortality rates was %(n= ) and the mean nihss at discharge was . ± . . the mean mrs at months was . ± . in all patients and . ± . in survivals. this result shows that therapeutic hypothermia can prevent the progression of cerebral edema and improve functional outcome in acute malignant mca infarctions and ica t-occlusion. long duration hypothermia more than days appears feasible and safe in these patients. therapeutic hypothermia may be a good alternative therapeutic option to early decompressive hemicraniectomy. large clinical trials are needed whether hypothermia will be a best treatment to improve functional outcome. therapeutic hypothermia (th) is know to cause immune suppression. determining the degree of immune suppression at the bedside is often difficult or impossible. immune cell function (icf) measures the concentration of atp from circulating cd cells following in vitro stimulation with phytohemagglutinin (pha) as an indicator of immune cell function. icf is often used in solid organ transplant programs to modulate the immunosuppressive treatment. we propose the use of ifc to determine the degree of immune depression in the patient treated with th. immune cell function, cylex inc, columbia, md was obtained in three populations of patients: group : patients treated with th, ifc obtained while at target temperate, degrees c group : patiients that were admitted to the care of the neurocritical care team, requiring icu care. group : patient from sanford renal transplant program with stable immunosuppressive therapy. group , patients, average icf: group : patients, average icf: group : patients, average icf, . patient being treated with th have a profoundly depressed icf. the level of immunosuppression is equal to if not greater that those with solid organ transplants. according to the cylex data a level of less than represents an immune suppressed state. this does not appear to be a phenomenon of the critically brain injured patient since those without th had a normal icf while further studies are in process, this data has effected out practice. we now treat patients on th as immunosuppressed patients. therapeutic hypothermia (th) has become a first-line therapeutic modality in patients suffering from traumatic brain injury and cardiac arrest. shivering induced by th reduces the ability of the cooling device to achieve target temperature. this can lead to increased intracranial pressure (icp) and increased metabolic demand. the bedside shiver assessment score (bsas) has been validated in identifying and grading shivering. however, the bsas cannot identify microshivering which is visually undetectable shivering that is thought to have the same detrimental physiologic consequences as shivering. continuous channel eeg (ceeg) can detect microshivering but is labor intensive, requires specialized training to interpret results and is expensive. we propose that the philips eeg with compression spectral array lead (philips ) can be utilized to detect microshivering as effectively as ceeg but is more cost effective. the philips was placed by the bedside nurse. the lead placement varied depending on underlying injuries. patients were assessed utilizing the bsas and the philips . if high frequency activity increased on the philips , the patients were assessed using the bsas. if the bsas was then - mg of vecuronium was given to intubated, sedated patients. both patient temperature and water temperature were recorded. two patients with tbi were evaluated. the water temperature decreased and the patient's temperature increased during the periods of high frequency activity on the philips . after vecuronium, the high frequency activity ceased, water temperature increased and core temperature returned to the previously set level. the philips is a relatively low cost device when compared to ceeg that can be applied and monitored by the nursing staff to detect microshivering. additionally, we were able to validate that control of microshivering improved the th device's ability to achieve and maintain the patient's temperature goal. therapeutic hypothermia is widely accepted as a standard of practice for out of hospital cardiac arrest (ohhca). however, its implementation is still highly variable in different hospital settings. most of the current data comes from centers of excellence. we wanted to evaluate performance of implementation of "hypothermia protocol" (hp) including its complications and outcomes in our large referral community based hospital. we conducted retrospective chart review of patients who underwent hp from - . data collected included demographics, time of cardiac arrest, time of arrival to er and time to induction of hp, methods used for induction, complications and outcomes. out of the patients, patients ( %) had pulse less electrical activity (pea), ( . %) patients had ventricular tachycardia/fibrillation, and ( . %) had complete heart block as the initial rhythm. average time to arrive to er was minutes. almost % of patients had ht induction in ed, % (%) in icu and . % outside of the hospital. average time to initiate ht from the initial event was hour and minutes. average time to achieve the target temperature from the initial event was hours. inner cool was the most common modality used in . (%). lactic acidosis ( . %) was the most common complication encountered, followed by hypotension ( %), coagulopathy ( %) and seizure ( %) trend of improved outcomes with less renal failure, coagulopathy, seizure was observed with shorter induction times. time to achieve target temperature had no effect. initial rhythm, age and gender also had no impact on the outcome. shorter induction time appears to decrease complications and improve outcomes. using multiple cooling modalities also appeared to have better outcomes. however larger studies are needed to confirm this observation. earlier induction of mild therapeutic hypothermia improves survival and neurological outcome and decreases incidence of some of the complications. introduction secondary brain injury after aneurysmal subarachnoid hemorrhage (asah) is a major cause of mortality. mild hypothermia ( - c) may protect against cerebral ischemia and edema in asah patients. the aim of this study is to describe the use of ct perfusion (ctp) characteristics to initiate re-warming in patients with secondary brain injury after asah. we performed a retrospective review of all patients admitted to a large comprehensive stroke center between and with asah who were treated with hypothermia and received ctp imaging. mild hypothermia ( - c) was started because of severe vasospasm, increased intracranial pressure or cerebral edema. baseline characteristics, including clinical severity grading by hunt hess (hh) and fisher scales, were collected. clinical outcomes were measured by discharge modified rankin score (mrs) and disposition. ctp was performed with a -slice scanner. twenty patients fulfilled inclusion criteria. in / ( %) patients, re-warming was based on favorable ctp characteristics and in / ( %) based on favorable tcd findings. the mean duration of hypothermia was . days. five patients were re-warmed due to normal ctp, despite tcd findings suggesting moderate to severe vasospasm. patients, re-warming was initiated given improving tcd findings and despite less favorable ctp data (most showing "matched" abnormalities of decreased cbv, cbf and increased mtt). clinical outcomes were worse in this group; mrs better outcome was seen in all patients in whom re-warming was initiated based on normal ctp. in these patients, there was a discrepancy between ctp and tcd data. poor outcome was associated with abnormal ctp regardless of tcd findings. ctp may be a useful tool to guide treatment of asah patients receiving hypothermia. diagnosis of pediatric brain death (pbd) continues to be a significant challenge. new guidelines for pbd diagnosis were published in pediatrics in . we recently conducted a mailed survey to assess current understanding of these new guidelines and general perspectives about pbd among a convenience sample of midwest usa physicians. we developed a item survey. items included demographic questions, question about familiarity with the guidelines, and questions concerning perceived discrepancies and other attitudes toward the guidelines. we mailed our survey to physicians at university hospitals: pediatric intensivists, neonatologists, adult neurointensivists, and pediatric neurologists, three weeks after the initial mailing, we followed up with a reminder by mail and/or phone. we performed fisher's exact test to assess statistical significance of responses among different specialties. after weeks, we had a % response rate. respondents included pediatric neurologists, neurointensivists, pediatric intensivists, and neonatologists. twenty percent of respondents were unfamiliar with the new pbd guidelines (neonatologists were least familiar). twenty-three percent stated they were 'not comfortable' making a pbd diagnosis and % deemed it was either preferable or essential to obtain a neurointensivist or pediatric neurology consultation for pbd assessment. there was general agreement that the current intervals for the required exams were appropriate in children (delineated by age). interestingly, % allowed patients to remain ventilated for a significant period of time after pbd declaration. we found that a significant number of pediatric physicians are not familiar of the new pbd guidelines and there remains some variability in the assessment of these patients. pediatric neurologists or neurointensivists are still considered an important part of the process of pbd determination. the mid-position fixed pupil (mpfp) is an imperfect reference to the mid-size pupil that occurs with the complete loss of neural influence from devastating midbrain injury (primary or secondary) and death (brain and cardiopulmonary). for this reason, proper recognition and interpretation of the mpfp is critical to the neurological localization/diagnostic process and a vital element to the clinical verification of brain death. while the description of the size range of the mpfp has been dogmatically passed down from numerous classical texts ( - mm) for decades, it has not been accurately quantified. modern pupillometry offers accurate quantification of pupil size. using a portable infrared pupillometer (forsite, neurooptics inc., irvine, ca), within hours after death, we evaluated the pupil size of dead patients who did not have any previous eye surgery, known eye disease, or use of eye medications. pupils were evaluated in dead patients (mean age ) an average of hours after death. the pupil size range was . - . mm, with a median size of . mm (sd of . mm). / pupils ( %) were < mm and none were > . mm. / patients ( %) had a side-to-side difference of at least . mm. thankfully none were reactive! the mpfp is generally smaller than classically described and % fall between . and mm. % of mpfp's are less than mm. we never found any mpfp's more than . mm. subtle but frequent side-to-side asymmetry (> . mm) existed in approximately % of the dead patients. with our continued work we can finally achieve a more quantitative description of the important finding of the mpfp so that it can be incorporated into our definitive texts, enveloped into our understanding, and applied to our clinical practice. brain death diagnosis is clinical in uruguay. it is defined as the irreversible loss of brain stem functions. ancillary tests are needed as confirmatory tests in selected cases: ) impossibility or contraindication to perform clinical testing (barbiturates, facial trauma, etc.); ) non demonstrable structural lesion; ) unknown coma etiology; ) difficulties to wait for a second clinical test. the most used confirmatory test is transcranial doppler (tcd) ultrasonography. objectives: to study ) the clinical characteristics of patients in whom brain death could not be diagnosed clinically; ) tcd ultrasonographic patterns; ) number of cases in which tcd aided in management. epidemiologic and observational study. patients included: those in who brain death was suspected but the clinical examination of brain stem reflexes and/or apnea test could not be performed for different reasons. period: from to . the variables studied were demographic and clinical characteristics, tcd sonographic patterns. cerebral circulatory arrest was diagnosed when the patterns found were systolic spikes, reverberating flow, and no-flow (if a previous study had demonstrated ultrasound permeability of skull windows) in bilateral anterior sectors and posterior sector. continuous flow or systolic peaks were negative for the diagnosis of cca. patients in who the clinical diagnosis of brain death was not possible or needed to be confirmed. % adults. % were men, with an average of y.o. in adults, and y.o.in children; structural etiology %. etiology: traumatic %; vascular %; anoxic-ischemic %, infectious %, toxic-metabolic %, other %. cca was confirmed in %, systolic spikes in %. cca was discarded in %. in this group the study was repeated in %, confirming cca in %. it was not concluding in %. dtc helped in the decision to how to continue the management of the patient in % of the cases, diagnosing cca in %. there is an awkward physician and cross-institutional variability in the approach to brain death (bd) diagnosis and all of its ramifications; physiological, logistical, and psychosocial. physician variability is related, in part, to a basic knowledge deficit and inexperience. however, public confidence in the reality of bd relies on consistent and accurate diagnosis and the physician's facility with the management of its implications. our full-day ( hour) brain death simulation workshop (bdsw) was designed to enhance confidence with bd diagnosis and management. it included a didactic lecture and seven learning stations: case study analysis (recognizing brain death mimics), a high fidelity mannequin simulation (bd examination including cold water calorics and apnea testing, hemodynamic management, and diabetes insipidus management), family discussions with professional actors trained to provide feedback, and four relevant content stations. each participant was observed by a neurocritical care expert, each receiving one-on-one and group feedback. physicians participants from continents participated in the bdsw with expert faculty. all participants felt much more confident with brain death diagnosis and management. at least % were humbled by the station on "discussion of brain death with families", recognizing their need to practice communicating about brain death effectively. % felt better equipped to contemporize their local policies and advocate for enhanced uniformity of practice. our bdsw provides a model comprehensive training experience that had a favorable impact on trainee confidence and their interest and capacity to advocate for better uniformity and training of peers. . the bdsw can be part of a future tiered approach to credentialing experts in this important clinical area. . we are conducting the nd bdsw on november , with improvements based on the st workshop. neurocritical care experts must embrace the primary responsibility for preserving the integrity of bd diagnosis and educating our colleagues. the use of carbogen in apnea testing to declare brain death may facilitate achieving the prerequisite pco needed to confirm apnea testing by establishing a target end point that is typically reached faster and has been shown to limit adverse effects. as the use of extracorporeal membrane oxygenation (ecmo) in adults increases, so does the need to perform apnea testing while on ecmo. however, traditional apnea testing on critically ill patients is compounded by lung derecruitment and hemodynamic instability rendering an aborted apnea test or worse, cardiac arrest and death. the literature on apnea testing of patients on venous-arterial (va)-ecmo is minimal. per hospital protocol, a carbogen mixture ( % oxygen and % carbon dioxide) was delivered through the ventilator for an apnea test on a year old female on va-ecmo. the ventilator's mandatory rate was set at breaths/minute to adequately deliver the carbogen mixture through the artificial airway. a carbogen formula was used to calculate a target end-point of an etco of mmhg for a positive apnea test. an abg was drawn prior to the apnea test and again once the target etco was achieved. pre-apnea abg: . / / / %. the etco goal was reached within minutes and the post-apnea abg was drawn: . / / / %. the patient remained hemodynamically stable throughout the apnea test which was confirmed as a positive apnea test. the use of carbogen in apnea testing on a patient receiving va-ecmo demonstrates the possibility of performing a successful apnea test for declaration of brain death. although more investigation is needed, this case demonstrates the ability to perform apnea testing on critically ill and unstable patients while maintaining hemodynamic stability which preserves the option for organ donation. drowning victims have historically been eliminated from consideration for lung donation as aspiration may cause direct pulmonary toxicity, often confounded by significant neurogenic pulmonary edema. a significant minority of these patients ( - %), aspirate only minimal amounts of water into their lungs, protected by severe-persisting laryngospasm (dry drowning), but progress to brain death due to significant anoxic injury. historically, even with limited evidence of aspiration,transplant centers do not consider evaluating drowning victims as lung donors. however, as the division between the number of eligible recipients and available donor organs continues to grow, criteria for acceptable donor organs are expanding. once an absolute contraindication for lung donation, this practice has persisted on a per case basis but is reported infrequently with somewhat mixed results. we analyzed the unos registry of donors for lung and heart-lung transplant from january , to december , (n= ), and then examined survival outcomes from lung transplant recipients from donors who suffered drowning between to recipients (n = ) to outcomes previously reported from lung transplant recipients during that period. for recipients of lungs from donors with drowning as cause of death, unadjusted survival at one drowning victims, even when initially resuscitated, often suffer significant anoxic injury and death by neurologic criteria. while the management of drowning victims as organ donors may present additional challenges, with proper donor selection, the use of lungs recovered from carefully screened donors after drowning appears to be a safe option for the expansion of the donor pool. racial disparity in health care utilization and outcomes is an area of substantial concern. a study performed in the 's in our neuro-icu found that nonwhites were half as likely to withdraw life-sustaining therapy (wlst). this may be explained by differences in socioeconomic status (ses), cultural preference, lack of end-of-life planning, or trust in the health-care system. to better understand the basis and evolution of this disparity, we analyzed it over two more recent epochs (determining whether it has improved over time), while specifically accounting for ses. we extracted data from a prospective neuro-icu database on all ventilated patients with gcs of or less between and . we analyzed how the rate of wlst was affected by age, race, gender, insurance and socioeconomic status (quintiles based on median household income of residence zip code), marital status, receipt of surgical/icu interventions, gcs and apache ii. we then compared ses-adjusted disparity for wlst (non-whites vs. whites) in - with - . non-whites accounted for of patients ( %) and were younger, less likely to be married ( % vs. %), insured ( % vs. %), and reside in upper-income zip codes (all p< . ). rate of wlst was lower in non-whites ( % vs. %, p< . ), despite comparable overall hospital mortality. after controlling for ses and other confounders, non-white race was still associated with lower odds of wlst (aor . , % ci . - . ). this disparity was prominent in the earlier epoch (aor . , . - . ) while race was no longer a statistically significant marker in the more recent cohort (aor . , . - . ). race appears to influence the likelihood of wlst in severely brain-injured patients independent of ses. this disparity, which has been attenuated over the past decade in our icu, may be related to cultural differences or barriers relating to end-of-life planning or trust. multiple parameters have been associated with outcome in comatose post-cardiac arrest patients. anecdotal observations suggest that patients who are cooler upon ed arrival tend to have poorer outcomes; if arrival temperature correlates with outcome, it may serve as an additional tool for patient prognostication. we performed a retrospective analysis of a prospectively collected data set from comatose post-cardiac arrest patients to determine if a relationship exists between arrival temperature and outcome. of the patients, patients ( %) with out-of-hospital cardiac arrests and with arrival temperatures recorded prior to initiation of hypothermia treatment were included and divided into those with good outcomes ( subjects; mrs => ) or poor outcomes ( subjects; mrs =< or death) at months; subjects ( poor outcome survivors and who progressed to brain death) remained when patients whose poor outcome (death) was due to withdrawal of care were removed from the poor outcome group. analysis using a two-tailed unpaired t-test on subjects with good versus with poor outcomes demonstrated a significant difference in temperature on ed arrival: mean temperature of patients with good outcomes was . o c (sd= . o c), while that of patients with poor outcome was . o c (sd= . ), p= . . when patients who died due to withdrawal of care were included in the analysis, a strong trend in difference between the two groups remained, but was not statistically significant (p= . ). low body temperature upon ed arrival correlates with poor outcome in post-cardiac arrest patients and may serve as an additional prognostic variable. cooler temperatures may merely reflect longer lapsed time before return to normal circulation; alternatively, they may be a result of poor temperature regulation in more severely brain injured patients. further investigation of this issue with a larger patient pool is warranted. diencephalon injury (di) has been described in neurocritical care. consciousness alterations (ca), dysnatremia, hemodynamic instability, fever, muscle dystonia are signs of di. these symptoms are non-specific. the goal of the study was to describe structure of acute diencephalon dysfunction syndrome (adds) on the model of isolated acute di. this retrospective study evaluated all patients operated in - . inclusion criteria: adult patients in stable preoperative condition; sellar region tumors (srt); complicated postoperative period. exclusion criteria: intra-cranial complications, not related with direct di (epi-, subdural hematomas, brain ischemia). organ dysfunctions and dysnatremia were registered. patients were included, excluded. all had ca and dysnatremia. hemodynamic dysfunction developed in patients, respiratory dysfunction in patients, ileus in patients, thrombocytopenia in patients, renal dysfunction in patients, hepatic dysfunction in patient. there were groups. first (n= ) had ca, dysnatremia. icu los was . days. glasgow outcome scale (gos) had patients; gos : patient. second group (n= ) had ca, dysnatremia, one somatic organ dysfunction (sod). icu los was days. gos had patients, gos : patients. third group (n= ) had ca, dysnatremia, two sod. icu los was . days. gos , had patients; gos : patients; gos : patients. fourth group (n= ) had ca, dysnatremia, sod. icu los was days. gos , had patients; gos : patients; gos : patients. fifth group (n= ) had ca, dysnatremia, sod. icu los was . days. gos had patients; gos : patient; gos : patients. sixth group (n= ) had ca, dysnatremia, sod. icu los was . days. all died. adds consists of ca, dysnatremia, and at least one sod. severity of adds depends on number of sod. intracranial pressure (icp) monitoring is widely used in the management of patients with traumatic brain injury. icp monitoring may also be useful in other situations characterized by high icp, including cardiac arrest survivors (cas) after return of spontaneous circulation (rosc). however, no prospective study has examined the incidence of raised icp among cas. this pilot study will examine the feasibility of screening for elevated icp in cas admitted to the toronto western hospital (twh) in -using the non-invasive technique of optic nerve ultrasonography (onus) --to identify patients with elevated icp, who might benefit from invasive icp monitoring to optimize their management after they survive cardiac arrest. evidence of elevated icp will be examined by blinded ultrasonographers(usf) who will measure the optic nerve sheath diameter (onsd) in both eyes of all cas every hours from rosc. all findings will be defined in a dichotomous method (elevated/not elevated). primary outcome: incidence of major protocol violations, defined as the inability to attain of onus recordings during first hours at the specified time point (every hours) by each usf. for every major protocol violation, an audit will be done to understand the reason for the violation and tailor the protocol to improve compliance in future studies. advances in resuscitation medicine have demonstrated an improvement in patient outcomes in cas by the implementation of th. the exact mechanism of action of th is not well understood and has been postulated to partially involve a decrease in icp. no prospective data currently exists linking th with icp. using onus as a non-invasive modality, we have designed a single centre feasibility study to assess the ability of onus to measure icp in cas, as well as to aid in sample size calculations for a larger multicentre prospective cohort study. a preliminary study demonstrated that > % of whole brain volume with an apparent diffusion coefficient (adc) < x - mm /sec identified poor outcome (death/vegetative state) with % specificity and % sensitivity. we aimed to validate this threshold in an external dataset. a multicenter retrospective observational study of dwi mris of comatose post-cardiac arrest patients obtained between and hours post-arrest was performed. poor outcome was defined as death or persistent coma at day . imaging was processed in a blinded fashion using medical image processing, analysis and visualization program (mipav). the brain was semi-automatically outlined on the b images using a levelset algorithm. the adc values of each voxel within the brain were determined. outcomes were assessed blinded to quantitative dwi information. treating physicians were not blinded to the mri scans, but they were unaware of the quantitative dwi analysis. data from patients from five us centers were included: mean age was ± years, % female, arrest time ± minutes, % of patients received hypothermia, and mris were obtained at ± hours post-arrest. thirty-two percent had a good outcome. the median (iqr) percentage of brain tissue with adc< x - mm /sec was . % ( . - . ) in good and . % ( . - . ) in poor outcome patients (p< . ). an adc< x - mm /sec > % was % ( % ci - ) specific and % ( % ci - ) sensitive for poor outcome with a positive predictive value of % ( - ) and a negative predictive value of % ( - ). the odds ratio of having a poor outcome if > % of brain had an adc< x - mm /sec was ( %ci - ). quantitative dwi mri in comatose post-cardiac arrest patients holds great promise as a prognostic adjunct between and days after arrest. predicting outcome for comatose post-cardiac arrest patients is challenging and compounded by the use of therapeutic hypothermia and sedative agents. brain mri is a potential attractive prognostic adjunct not affected by drugs or metabolic derangements; however, most proposed methods require image post-processing. we assessed the prognostic value of color apparent diffusion coefficient (cadc) maps. consecutive post-cardiac arrest patients remaining comatose after resuscitation were prospectively enrolled. cadc maps were created by assigning adc values to colors ranging from red to blue. the treating teams did not see these maps. two raters independently and blinded reviewed the cadc maps and predicted month outcome as poor (glasgow outcome scale (gos) - ), or good (gos of - ). both raters were "trained" by viewing examples. the agreement between raters and the predictive performance of the cadc maps were assessed. cadc maps of patients ( % with poor, % with good outcome) were reviewed: age ± years, % females, % underwent therapeutic hypothermia, median (iqr) arrest duration min ( - ), and time between the arrest and mri hours ( - ). kappa for agreement on predicting favorable vs. unfavorable outcome was . . for the two reviewers, the sensitivity for predicting poor outcome was . ( % ci . - . ) and . ( . - . ), the specificity . ( . - . ) and . ( . - . ), and the true positive predictive rate % ( - %) and % ( - %), respectively. for mri scans acquired between - hours after the arrest (i.e. the time-interval when adc changes are most apparent), the specificity improved to . ( . - . ) and . ( . - . ), respectively. mri color adc maps are easy to interpret and may be useful for predicting outcome of comatose post-cardiac arrest patients in the first days after the arrest. color adc maps do not require post-processing and can be created in realtime. there are few reports of outcome in patients with fat embolism syndrome with diffuse mri abnormities. we report the outcome of patients with fat embolism syndrome. case a -year-old previously healthy gentleman had a right femur fracture from a motor vehicle accident. he had acute respiratory failure hours later requiring intubation. chest x ray showed bilateral lung infiltrates. neurological examination showed patient comatose with intact brainstem reflexes and extensor posturing. on day , he had fever, tachycardia, profuse sweating, and diffuse petechial rash. mri brain showed diffuse restricted diffusion lesions. he started to open his eyes in weeks and underwent tracheostomy and feeding tube placement. at month follow up he only had mild memory problems. case a -year-old previously healthy gentleman had a gun shot in the left foot. over the next hours he became stuporous. x ray showed multiple fractures including calcaneus, soft tissue swelling and subcutaneous emphysema. over the next hours he worsened and displayed extensor posturing. mri brain showed diffuse innumerable tiny infarcts. patient was noted to have episodic fever, profuse sweating, and severe tachycardia. patient had spontaneous eye opening next day and underwent tracheostomy and gastrostomy. he was transferred to a long term facility. patient improved substantially and at months follow up he was independently living at home with minor neurologic deficits. substantial improvement may occur in comatose patients with fat embolism syndrome despite paroxysmal sympathetic hyperactivity syndrome and significant mri abnormities. malignant pertussis is a rare life-threatening illness characterized by severe respiratory failure, extreme leukocytosis, and pulmonary hypertension. during , an outburst of whooping cough was experienced at montevideo, uruguay. we present the cases of two infants, and months old, suffering malignant pertussis, admitted to a university pediatric intensive care unit (picu) for severe acute respiratory failure associated with severe leukocytosis. both children showed signs of profound coma and bilateral arreactive dilated pupils while being aggressively treated. both of them showed a transcranial pattern of cerebral circulatory arrest (cca) on transcranial doppler (tcd).to our knowledge, a pattern of cca has not been previously reported like mode of death secondary to neurologic injury in this disease. both cases were very similar: a -month-old boy, incomplete vaccinatinon, malnourished. a month-old girl, vaccinated. both had suffered at one and months-old, severe bronchiolitis caused by respiratory syncytial virus, both needed days of mechanical ventilation. both were admitted to icu with cough, fever, increased work of breathing, hypoxemia and were mechanically ventilated. they presented respiratory acidosis, hipoxemia, extreme leukocytosis greater than , bilateral hyperinsuflation in chest x-ray. echocardiography: pulmonary hypertension, - mmhg spap, circulatory failure, anuric renal failure. bordetella pertussis was diagnosed with pcr of airway secretions treatment: blood exchange transfusions, milrinone, maximum dose inotropic drugs, peritoneal dialisis. after one week arreactive dilated pupils and profound coma were evident. brain death was suspected, sedation and muscle blockers were interrupted. neurologic exam confirmed brain death. tcd showed sysytolic spykes in bilateral middle cerebral arteries, basilar artery, confirming cca. necropsy performed in case showed bilateral pneumonia, small pulmonary artery branches thrombosis, neuronal necrosis, with brain edema, and renal tubular necrosis. the mode of death in these two cases was brain death, with cca. the probable pathophysiologic mechanisms were related to hyperviscosity and cardiac failure. davf's can be associated with benign or aggressive symptoms based on location and venous drainage. cerebral venous ischemia is a reversible process emphasizing the importance of early recognition and treatment of davf's. in a geographically isolated region with limited neuroscience intensive care unit (nsicu) capacity, neurointensivists are often challenged to allocate resources and triage intracerebral hemorrhage (ich) patients. we sought to assess the factors impacting the neurointensivists' triage decision for nsicu admission after ich. consecutive patients hospitalized for ich between and at a tertiary center that has the only -bed nsicu for the state, geographically isolated from the nearest nsicu (> , miles away), were studied. multivariable logistic regression models were used to test for predictors of nsicu admission, adjusted for each component of the ich score, transfer from another hospital, initial systolic blood pressure (sbp) > mmhg, and early do-not-resuscitate (dnr) order. among a total of consecutive patients hospitalized for ich, patients ( %) were admitted to the nsicu while patients ( %) were admitted to a non-nsicu unit. the ich patients were more likely to be admitted to the nsicu if they had hematoma volume > cm (or . , % ci . - . ), intraventricular hemorrhage (or . , % ci . - . ), glasgow coma scale (gcs) score of - (or . , % ci . - . ), gcs score of - (or . , % ci . - . ), infratentorial hemorrhage (or . , % ci . - . ), transfer from another hospital (or . , % ci . - . ), and sbp > mmhg (or . , % ci . - . , % ci . - . ) and early dnr order (or . , % ci . - . ). the triage decisions for nsicu admission after ich were based on clinical severity, age and early dnr status. a prospective study is needed to help establish a safe triage algorithm for ich patients in a region with limited neurocritical care capacity. using a semi-automatic threshold based volumetry algorithm. neurological status (nihss) was recorded daily and outcome was assessed at discharge using the modified rankin scale (mrs). the difference of phe volumes between day and day - , representing the edema growth (phe delta ), correlated significantly with the mrs at discharge (p= . ; f= ). this correlation was still significant, when ich volume on admission was controlled. other factors that showed a significant association with outcome at discharge were nihss (anova: p> . , f= . ) and ich volume (anova: p> . , f= . ) on admission. in a multivariate regression model only the initial nihss remained a significant predictor of functional outcome. phe growth showed a weak trend towards significance (p= . ). phe growth at the first days after symptom onset may influence early functional outcome after spontaneous ich. treatment strategies aimed at reduction of phe burden after ich may take advantage of this finding. assess the use of a -factor prothrombin complex concentrate (pcc, profilnine®), compared to fresh frozen plasma (ffp) in establishing hemostasis in warfarin associated intracranial hemorrhage (ich). dmitted to unc health-systems between / / and / / that received pcc, ffp, or both in conjunction with phytonadione for the treatment of warfarin associated ich. patients who received a factor product other than profilnine®were excluded. data collection included hematoma expansion, achievement of inr reversal (inr < . ), -day mortality and endpoints related to safety (thromboembolic events, infection, and transfusion related acute lung injury). of the patients included, patients received pcc alone, patients received pcc plus ffp and patients received ffp alone. hemorrhage expansion occurred in of patients ( %) in the pcc group, of patients ( %) in the pcc plus ffp group and of patients ( %) in the ffp group (pcc versus ffp, p= . ; pcc plus ffp versus ffp, p= . ). inr reversal occurred in % of patients in the pcc alone group, % of patients in the ffp alone group and of patients ( %) in the combination group. this study assessed the impact of profilnine®, ffp, or the combination, on achieving hemostasis based on hematoma expansion. profilnine® achieved inr reversal but appeared to be less effective than ffp in preventing hemorrhage expansion. fever after ich is common and associated with poor outcome. however, the impact of therapeutic temperature modulation (ttm) to treat fever after ich is unclear. we performed a case-control study of ttm in ich patients with fever. patients undergoing ttm with advanced temperature modulating devices were prospectively enrolled in our ttm database from - (ttm group). target temperature was c in all cases. controls were matched in severity by ich score and retrospectively obtained from a period ( ) ( ) ( ) ( ) before our routine use of ttm for ich. primary outcome was discharge modified rankin score. we enrolled patients in each group. median ich score was (range - therapeutic normothermia is associated with increased length of mechanical ventilation and nicu stays, but is not associated with improved discharge outcome. spontaneous intracerebral hemorrhage (sich) is a dynamic process with significant growth in over one-third during the first hours. catheter-based evacuation of sich plus recombinant tissue plasminogen activator (rtpa) is a novel surgical approach for which optimal timing of stereotactic catheter placement and clot aspiration are not known. we investigated factors associated with significant ich expansion (> % or . cc volume increase) on prerandomization ct scans of patients meeting criteria for the mistie trial, a multi-center phase ii clinical trial, evaluating safety and efficacy of minimally invasive surgery plus thrombolytic to treat ich. subjects randomized to surgery underwent stereotactic clot aspiration followed by injections of rtpa through the hematoma catheter every hours, up to doses, or until a clot reduction endpoint. median diagnostic ich volume was . cc (iqr . ). overall, . % of patients exhibited significant hematoma expansion at a median of . (iqr . ) hours from symptom onset. predictors of hematoma growth were smaller diagnostic ich volume (or . ; p= . ), longer interval from symptom onset to pre-randomization ct (or . ; p= . ), non-lobar location (or . , p= . ), lower initial platelet count (or . ; p= . ), and lower initial hematocrit (or . ; p= . ). age, gender, admission blood pressure, initial coagulation parameters, hematoma shape and density scores did not predict hematoma expansion. end of treatment hematoma expansion occurred in / ( . %) patients of whom had early ich expansion and underwent surgical intervention. stabilization of hematoma growth can be anticipated within hours of symptom onset in patients considered for minimally invasive surgery using the mistie protocol. smaller initial ich size, deep location and lower hematocrit and platelet counts were independent determinants of significant ich expansion before surgery. patients with early expansion may represent a group at higher risk for re-expansion with clot aspiration and thrombolytic therapy. financial support: daniel f. hanley received funding from nih grant r ns . thin-section noncontrast ct (ncct) provides a measure of thrombus composition based on hounsfield units (hu) and may predict resistance to thombolytics in acute ischemic stroke. hematoma composition may affect thrombolytic efficacy of tissue plasminogen activator (tpa) in acute intraventricular hemorrhage (ivh). we assessed the value of hematoma hu quantification as a predictive marker of ivh clearance after intraventricular tpa administration. serial ncct was performed on patients who received intraventricular tpa as part of the clear ivh trial (clot lysis: evaluating accelerated resolution of ivh) and controls with ivh treated with external ventricular drainage (evd) alone. a blinded investigator calculated hu values for ivh volumes on admission, day - and day - ncct for each patient. median ivh volume on admission for tpa-treated patients was . (iqr . )cc, and decreased to . ( . )cc at day - . mean(sd) hu for ivh was . ( . ) on presentation and decreased significantly to . ( . ) on day - , and to . ( . ) on day - . ivh hu count was significantly correlated with ivh volume at all ct timepoints: admission:p= . ; day - :p< . ; day - :p< . . there was no correlation between admission serum platelet count, fibrinogen level or hemoglobin and clot hus. only csf protein was positively correlated with ivh hu (p= . ). total ivh hus were significantly lower in tpa-treated (vs. control) patients at day - (p= . ), but not at day - . change in ivh volume from admission to day - was positively correlated with higher initial hu in tpa-treated patients (p= . ), but hu was not significant after adjustment for ivh volume and tpa treatment. hounsfield unit counts of ivh decrease significantly over the first week on ncct and the decrease is greater in tpatreated patients. unlike thrombus hus in large intracranial vessels, ivh hus are not associated with erythrocyte or platelet concentrations. higher hu is not an independent predictor of success of intraventricular thrombolysis. although neurocardiogenic myocardial injury is well described among patients with spontaneous intracerebral hemorrhage (sich), it has not been investigated systematically in patients with acute subdural hemorrhage (asdh). we sought to investigate the prevalence and characteristics of myocardial injury in patients with asdh. consecutive adult patients with a diagnosis of asdh admitted to the rush university neurosciences intensive care unit were analyzed. myocardial injury, defined as troponin i elevation (> . ng/ml) on admission or during hospital course, was identified. electrocardiograms (ecg) and echocardiograms, obtained within the first hours and read by a cardiologist blinded to the patient's history, were retrospectively reviewed. a total of patients were admitted with asdh between / and / . the mean age was years (sd years), and % were male. comorbidities included hypertension ( %), diabetes mellitus ( %), coronary artery disease or prior myocardial infarction ( %), congestive heart failure ( %), coronary artery stent or bypass procedure ( %). ecgs were normal in %. non-specific st-t morphologic changes, qrs changes or sinus arrhythmias were seen in %. st-elevations suggestive of myocardial infarction were not seen. of patients with elevated troponin, had known severe cardiac disease, and had severe medical complications (sepsis, renal failure, hepatic failure and acute lymphoma crisis). diffuse ecg changes ("cerebral t waves") and echocardiographic findings suggestive of neurogenic stunned myocardium (reversible wall motion abnormalities, apical ballooning) were not seen. although we found ecg changes to be common after asdh, myocardial injury was only observed in the context of concomitant cardiac or medical disease. classic neurogenic cardiac findings (cerebral t waves, neurogenic cardiomyopathy) were not observed. while myocardial injury in sich often is attributed to neurocardiogenic causes, these are unlikely prominent mechanisms in patients with asdh. other cardiac or medical causes are common and should be excluded. prognostication in intracerebral hemorrhage is complex and mortality remains high. while tools such as the ich score have been developed to assist with prognostication, physicians clearly use additional parameters in clinical practice. though do-not-resuscitate orders do not indicate the withholding of any treatment other than cpr, they are associated with increase risk of death in patients after ich. we sought to understand early dnr (< hours) designation in patients with hope of moving toward more precise tools for prognostication. patients admitted to the neurological intensive care unit from july to december with a diagnosis of supartentorial ich were identified. data for all patients were collected retrospectively. patients without a dnr order throughout their admission were compared to patients who received a new dnr order in the first hours of admission. patients with pre-existing dnr orders were not included. subjects were included in the study with . % made dnr within hours of admission to our nicu. factors showing a significant correlation with a new dnr order included advanced age, caucasian race, or residence in a skilled nursing facility. history of malignancy, atrial fibrillation, current use of antihypertensives or warfarin, or alcohol abuse predicted a dnr order. ich resulting in a low admission glasgow coma score, high ich score, intraventricular extension and blood volumes greater than ml correlated with a new dnr order. while individual elements of the ich score correlate with a new dnr order in this population, other characteristics were also associated with an early dnr order. early dnr orders may create a self-fulfilling prophecy if limitations of support are instituted without a clear understanding of who may benefit from aggressive care. thus, identification of factors that providers believe to be life-limiting may serve as a starting point to avoid early limitations in aggressiveness of care. intracranial hypotension is caused by low cerebrospinal fluid (csf) pressure, clinically distinguished by orthostatic headaches and neurologic signs. subdural effusions and even hemorrhage can be a secondary effect. known causes include dural punctures as well as spontaneous csf leaks. treatments are guided towards repairing the cause of the hypotension. a year-old man on coumadin for a mechanical aortic valve was transferred to our institution for evaluation of bilateral sdh. he presented twenty-four hours earlier with sudden-onset severe headache and normal neurological exam. upon transfer, he was noted to be drowsy, with a left third cranial nerve palsy. he endorsed a postural headache that worsened upon standing. mri of the brain showed small subdural effusions with subacute hemorrhage and minimal mass effect, as well as severe distortion of the midbrain with narrowing of the ventricular system, crowding of the basal cisterns and extensive pachymeningeal enhancement. mri of the spine did not demonstrate a csf leak but showed a small perineural cyst at t . the patient's headache and exam findings initially improved with lying flat. a trial of elevating his head of bed failed, with the patient further developing decreased level of arousal, frontal release signs, and recurrent left third nerve palsy. two attempts at lumbar epidural blood patch (ebp) did not lead to sustained improvement, but a thoracic-directed ebp led to durable and complete resolution of the headache and neurologic deficits. intracranial hypotension should be considered as a cause for subdural hemorrhages in the absence of trauma. clues include postural headaches and clinical evidence of brainstem dysfunction and radiographic evidence of brainstem distortion out of proportion to the size of the sdhs. ebps directed at suspected csf leaks can be effective when nondirected lumbar ebps fail. multiple guidelines recommend the reversal of oral anticoagulation when a patient experiences an intracranial hemorrhage (ich). both activated prothrombin complex (apcc) and recombinant factor vii activated (rfviia) have been utilized to reverse warfarin-associated coagulopathy. however, there have been no direct comparisons of these agents. this was an irb approved, retrospective cohort analysis of patients with ich. patients were included if they received either apcc (at least units) or rfviia (at least mg), if they had a discharge diagnosis of intracranial hemorrhage, and if they received warfarin prior to admission. patients were excluded if they were less than , or did not have documented pre-treatment and post-treatment inrs. the primary endpoint for this study was the change from pretreatment inr and post-treatment inr in the apcc group and rfviia group. secondary endpoints included change in ct measured hemorrhage volumes, icu length of stay (los), hospital los, mortality, icu discharge gcs, and thromboembolic adverse events. a total of patients were included in the analysis. of those, received apcc and received rfviia. baseline demographics were comparable; however, patients in the apcc group had a higher rate of atrial fibrillation ( % vs. %; p= . ). when compared over time, both apcc and rfviia significantly reduced the inr (p< . ); however, there was no difference in the amount of change observed between the two groups (p= . ). in addition, we saw no significant differences with regard to icu los, hospital los, mortality, icu discharge gcs, or thromboembolic adverse events. over time, an increase in ich volume was observed in both groups. in patients with intracranial hemorrhage, apcc and rfviia are associated with rapid reversal of warfarin-associated coagulopathy; however, these agents may not slow ich growth. accurate prognostication of patients with intracerebral hemorrhage (ich) is critical because it may affect aggressiveness of care and patient outcome. ich prediction models help stratify patients according to their chance of a good or poor outcome. we compared the accuracy of neurointensivists' prediction of functional outcome to outcome prediction by the ich score. adult spontaneous ich patients with an admission gcs > were prospectively enrolled. the treating neurointensivist predicted the -month modified rankin scale score (mrs) within days of hospital admission. none of the neurointensivists used the ich score routinely to help predict outcome. patient outcomes were dichotomized to good (mrs - ) and poor (mrs - ). neurointensivists' predictions were compared to the ich score using the actual -month mrs as the reference. of prospectively enrolled patients, were included: withdrew consent and were lost to follow-up. neurointensivists' overall accuracy was %, which was higher than the accuracy of the ich score at a cut-off of > ( %; p= . ) or > ( %; p= . ). at a cut-off > , the sensitivity for poor outcome prediction did not differ, but the neurointensivists' specificity for poor outcome was greater ( % vs. %; p< . ). conversely, at an ich score cut-off > the specificity for poor outcome prediction did not differ, but the neurointensivists' sensitivity for poor outcome was greater ( % vs. %; p< . ). the results were similar if, instead of the original ich score, a modified ich score was used as the comparison that had been developed on the same patient cohort. neurointensivists at our institution predict ich outcome overall with % accuracy. generally, predictions for poor outcome are more accurate than those for good outcome. outcome predictions for the individual patient by the treating neurointensivist are more accurate than those based on ich prediction models. there is continued controversy regarding glycemic control and its effect on outcomes for patients with ich as well as other icu patient populations. the relationship between ichsize and glycemic control has not been clearly defined. a retrospective review of patients with supratentorial ich and no history of diabetes between and was performed. admission blood glucose (bg) as well as bg at , and hours was measured while all patients were maintained on the same sliding scale insulin regimen. statistical analysis was performed to compare admission ich size to admission bg and subsequent bg control. bg> mg/dl (mean ± ) and mean ich size . ± . . average bg levels over average bg levels over hours were ± mg/dl. elevated admission bg was significantly correlated with admission ich size (p= . ). average bg levels over hours trended towards, but were not significantly correlated with admission ich size (r = . , p= . ). in nondiabetic patients, elevated admission glucose is significantly associated with ich size. poor outcomes associated with elevated glucose may be associated more with extent of cerebral insult than with glycemic control. the benefits of marriage on health have been known for over years. more recently, married couples have been found to have a lower risk of cancer, dementia, and heart disease. we aimed to explore the effects of marital status on outcome after intracranial hemorrhage. a prospective study was conducted between - of patients with subarachnoid hemorrhage (sah, n= ), intracerebral hemorrhage (ich, n= ) and subdural hemorrhage (sdh, n= ), admitted to the neuro-icu at a tertiarycare academic hospital. marital status was coded as married versus single, widowed, divorced or separated. modified rankin score and barthel index were compared between the two groups at -months using multiple logistic regression analysis. of patients, ( %) were married, ( %) were single and ( %) were widowed, divorced or separated. women were less likely to be married, and smoking was less common among the married (both p< . ). there was no difference in age, insurance or employment status, race, education, days to diagnosis, or history of heart disease, diabetes, hypertension, trauma or coagulopathy. after adjusting for age, admission gcs, apache physiologicalsubscore, gender, tobacco and bleed type, marriage was significantly protective against death or severe disability (mrs - ; adjusted or . , %ci . - . , p= . ) and predicted better activities of daily living (barthel index), (aor . , %ci . - . , p= . ). there was no difference in discharge disposition, length of stay or hospitalization costs. marriage is protective against death or severe disability and predicts better activities of daily living among patients with intracranial hemorrhage. warfarin associated intracranial hemorrhage leads to poor outcomes. we studied the influence of a standardized emergent warfarin reversal protocol incorporating prothrombin complex concentrates (profilnine sd®) on time to achieve the protocol was implemented in . sixty three patients ( pre and post protocol) from - with intracranial -protocol patients received recombinant factor a (rfviia); post protocol patients with inr . - and > received and - units/kg of profilnine sd® respectively. hemorrhage volumes were measured on consecutive ct scans using mipav semi-automated software. groups were similar for baseline median inr ( . vs . ), nihss ( vs ), follow-up ct time ( . vs . hours) and hemorrhage volumes ( . vs . cc) but differed in hemorrhage type: ich ( % vs %) and sdh ( % vs %), p= . . treatments also differed: vitamin k ( % vs %, p= . ), profilnine sd® ( % vs % p=< . ), rfviia ( % vs % p= . ) and number of plasma units ( vs , p= . ).time to target inr was similar ( . vs . hours) driven by pre-protocol rfviia use (rfviia used vs not, . vs . , p= . ) and this led to inr rebound in < hours. excluding rfviia, the post protocol group normalized inr faster ( . vs . hours, p= . ). the post protocol group had less absolute ( . vs cc p= . ) and relative hemorrhage growth ( % vs % p= . ) without any thrombotic events. despite comparable mortality ( vs %), post-protocol survivors more frequently achieved mrs - ( vs % p=ns). a standardized emergent warfarin reversal protocol is not only safe but leads to faster inr normalization, less hemorrhage growth, plasma conservation and possibly better neurological outcomes. perihemorrhagic edema (phe) after intracerebral hemorrhage(ich) may exceed the initial hematoma volume by to % respectively and thereby lead to increased intracranial pressure (icp), clinical detoriation or even herniation. intravenous hypertonic saline (hts) has been shown to reduce phe formation after ich. clinical data suggest that hts may be superior to mannitol in lowering icp. eusi and asa guidelines recommend the use of intravenous mannitol up to a serum osmolality (so) of mosmol/kg or hst in order to reduce elevated icp. we aimed to investigate the effect of mannitol and so on the evolution of phe after ich. nineteen patients with supratentorial spontaneous ich treated with % intravenous mannitol solution ( - ml every h) for - days and controls who did not receive mannitol or any other osmotic agents during the course of treatment were identified retrospectively from our institutional ich database. patients treated with mannitol and controls were matched for ich-volume (± ml). phe volume was calculated on ct scans using a semiautomatic threshold based volumetric algorithm. diagnostic ct scans and follow-up scans performed on days , - , - , - and - were analyzed. so, concentration of sodium and glucose were obtained from patient records. the matching resulted in similar ich-volumes in both groups (mannitol: . ± . ml, controls: . ± . ml). mean age was ( - ) years in the mannitol group and ( - )years in controls (p= . ). initial relative phe did not differ significantly in both groups (mannitol: . ± . , controls: . ± . , p= . ). there was no effect of mannitol treatment on the course of phe (f= . ,p= . ). there was no significant correlation between so and relative phe at any timepoint of follow-up. we found no effect of mannitol use and so on the evolution of phe. other underlying mechanisms may explain the shortterm effect of mannitol boluses on icp in patients with spontaneous supratentorial ich. when operating at maximum intensive care unit (icu) bed capacity where allocation of critical care resources is required, physicians may be pressured to initiate do-not-resuscitate (dnr) orders in patients with intracerebral hemorrhage (ich). we sought to assess the relationship between early (< hours from admission) dnr orders and neuroscience intensive care unit (nsicu) bed capacity in patients admitted with acute ich. we retrospectively studied consecutive patients hospitalized for ich between and at a tertiary center that has the only -bed nsicu for the state, geographically isolated from the nearest nsicu (> , miles away). multivariable logistic regression models were used to test for predictors of early dnr orders, adjusted for each component of the ich score and nsicu bed census on admission. nsicu bed census was dichotomized to full (all beds occupied) vs. not full (at least available bed). among maximum icu bed capacity on admission is not associated with the decisions to initiate early dnr orders in ich patients. this suggests that physicians were not preferentially initiating early care limitation when critical care resources were becoming scarce. dural arteriovenous fistulas (davf) are rare, acquired cerebrovascular lesions consisting of abnormal vascular connections between arteries that normally supply the dura and veins that drain the brain parenchyma -that is to say, arteries not associated with the brain parenchyma manage to drain via the dural venous sinus system. the clinical consequences of these lesions are typically hemorrhage, seizure, or venous congestion. venous congestion may present acutely with hemorrhage or subacutely with signs and symptoms such as progressive cognitive decline, seizures, or encephalopathy. parkinsonism, tinnitus, and intracranial hypertension have also been described. case report with review of literature. we describe a -year-old man with no past medical history who developed subacute onset dementia with bithalamic t hyperintensity on mri without restricted diffusion. subsequent intraventricular hemorrhage resulted in emergent transfer to our institution's neurocritical care unit for an emergent diagnostic cerebral angiogram of a borden ii/cognard iib davf with immediate angiographic embolization and obliteration. davfs are lesions with significant risk of aggressive neurologic devastation related to venous congestion and subsequent hemorrhage. the severity of davfs requires clinicians to be aware of these lesions and of their common and uncommon presentations. little is known about the ability of prognostic scores to predict outcome in patients with secondary intraparenchymatous intracranial hemorrhage (iph). our objective was to describe the clinical characteristics, ich scores at presentation and prognosis in patients with secondary iph. we performed a post-hoc analysis of prospectively collected data of consecutive patients admitted to a tertiary hospital with iph. the characteristics of patients with secondary iph were compared to those of patients with spontaneous iph. patients with secondary iph had either a positive underlying vascular lesion identified as the iph etiology or impaired coagulation at presentation (a platelet count < , per cubic mm, an inr > . , or an aptt > than seconds). a total of patients with iph were admitted to our hospital from january- to january- . of those, patients ( %) had a secondary iph ( cavernomas, arteriovenous malformations, dural fistula, reversible vasoconstriction syndrome and sacular aneurysm patients with secondary iph had lower ich scores at presentation and lower in-hospital mortality than patients with spontaneous iph. despite lower ich scores at admission, patients with secondary iph had similar functional outcomes when compared to patients with spontaneous iph. larger studies should focus on specifically developing better prognostic tools in such patients. a large number of studies in traumatic brain injury patients have shown efficacy of hypothermia for control of icp and if used for prolonged duration, has shown to improve mortality and functional outcome. for other neurologic catastrophes, due to a risk of rebound edema during re-warming, medical complications and other factors, it has either not been commonly used or been used when most of other options are exhausted. this is a retrospective analysis of patients with massive ich (blood volume of > ml), of non traumatic etiology, dominantly in brain parenchyma. all patients had intracranial pressure monitoring via external ventriculostomy catheter. hypothermia was induced and maintained at target temperature via non-invasive, surface cooling pads. modified rankling score (mrs) was recorded at months after the ictus in all survivors. patient ages ranged from to years. cause of ich was hypertension in patients and ruptured aneurysm in one patient. duration of treatment ranges from - days. target temperature required to adequately control icp ranged from - c. two patients ( %) survived with good recovery (mrs of ), one ( . %) with moderate disability (mrs of ), two ( %) with moderately severe disability and three ( . %) died. most common side effect of hypothermia was hypotension requiring pressors in five ( %), electrolyte imbalance in ( %), pneumonia in ( %), thrombocytopenia in ( %) patients. all complications were successfully treated and major complications of treatment (bleeding diathesis, septic shock syndrome, death) were not observed. controlled hypothermia for up to days is safe and feasible for the treatment of cerebral edema and intracranial hypertension in young patients with massive (> ml of blood volume) non traumatic ich. however, prolonged duration of treatment may be required for definitive control of icp. this study serves as a template for future efficacy trials. intracerebral hemorrhage (ich) accounts for % to % of strokes and is associated with substantial morbidity and mortality. it remains controversial whether surgical intervention or a conservative approach is the best option for treating ich. we assessed the hypothesis that early surgical intervention in patients with primary supratentorial ich may serve to improve -day outcome. a total of patients with primary supratentorial ich, in whom surgical intervention was indicated for hematoma removal according to the guidelines, were admitted to our hospital during a continuous -month observation period. patients with the consent to the surgical intervention (n= ) underwent surgery within hours of symptom onset and the others (n= ) were given the conservative treatment. the outcome was the proportion of patients who had an unfavorable outcome (persistent vegetative state or death), as assessed on the basis of the glasgow outcome scale (gos) at days. the -day mortality rate was . % (standard error, . %). there was no significant difference in outcome between the two treatment groups. after adjustment for other significant covariates, although a lower unfavorable outcome was found in surgical group but the difference was not significant (odds ratio = . ). among the confounding factors, presence of intraventricular hemorrhage (ivh) and low glasgow coma scale (gcs) score on admission were independently associated with poor outcome days after ich (both p < . ). we found no benefit for early surgical intervention over conservative treatment in patients with primary supratentorial ich. presence of ivh and low gcs score were strong predictors of poor outcome in these patients. given the high morbidity and mortality associated with intracerebral hemorrhage (ich), family members and healthcare providers base early supportive management decisions, at least partly, on expected prognosis. in the comatose patient with ich, this short term prognosis is most overtly characterized by regaining of consciousness. a retrospective consecutive cohort of patients, between and , with ich and admission glasgow coma scale that were associated with regaining of consciousness after coma in ich. variables associated with awakening in univariate analysis were tested in multivariable logistic regression. the group that awakened had higher initial gcs scores, smaller ich volumes, and less ivh, but was similar in other baseline characteristics. early dnr orders, in the first hours, tended to be used more frequently in patients who ultimately remained comatose, but the difference was not statistically significant. admission gcs, volume of ich, and presence of ivh identified in univariate analysis were tested along with age and gender as potential confounders of outcome in multivariable analysis. higher admission gcs score was associated with an increased likelihood of awakening from coma (or . [ %ci . - ] per category, p= . ). % of patients with initial gcs of - , % with initial gcs of - , and % with initial gcs of - regained consciousness. awakening from coma, in the cohort of patients who regained consciousness, occurred in % of patients by day , % by day , and % by day . gcs score is the single most important predictor of early awakening in patients who present in coma after ich. patients who regained consciousness typically did so within the first days of hospital admission. intracerebral hemorrhage (ich) is an infrequent but severe complication in pregnant women with hypertension, it accounts for % of all deaths related to cerebral complications in this group. a- -year-old female, g p at weeks of gestational age, with prenatal care, no relevant past medical history, presented for a follow-up visit. she was admitted with bp / mmhg, and treated with iv labetalol; the preeclampsia work-up was negative, bp range between / and / mmhg. approximately h after admission, she complained of diffuse headache, nausea, vomiting, and epigastric pain. headache symptoms increased follow by focal seizure and progression to generalized tonic-clonic seizures. magnesium sulphate and phenytoin were administered to control the seizure, immediate blood analysis revealed dic. the diagnosis of eclampsia was made, and emergency csection followed. the airway was secured with rapid sequence technique; a healthy infant was delivered under general anesthesia. the patient remained comatose hour after surgery with gcs , minutes later she demonstrated a decerebrate posture with non-reactive pupils. a non-contrast ct-scan revealed an intracerebral hematoma. dic was treated, and neurosurgeon performed a right frontotemporal craniotomy. a postoperative ct scan confirmed the resolution of the ich. the patient opened her eyes and started responding to commands by the third day, on day she was extubated and the gcs was . by the rd week, the patient was transferred to rehabilitation, where she remained for weeks. at years, she regained a full cognitive recovery. this case emphasizes that even short time hypertension should be treated aggressively to prevent ich. the prompt intervention of a multidisciplinary team (obstetric, neurosurgery, and anesthesiology) is required to ameliorate the devastating effects of eclampsia and ich. although hypertension is the commonest cause of non-traumatic intracerebral hemorrhage (ich), it is important to rule out other causes. most patients with ich have an elevated bp on presentation but many are unaware if they have longstanding hypertension. echocardiographic abnormalities may be revealing in such circumstances. we studied the incidence of echocardiographic abnormalities and their usefulness in determining the etiology of ich in these patients. we conducted a retrospective study of echocardiographic abnormalities in ich patients admitted to a tertiary university hospital between jan to oct who also had a cerebral angiogram. subjects with and without underlying vascular location (categorized as typical hypertensive location or not), history of hypertension and the presence of the following echocardiographic abnormalities: left ventricular hypertrophy (lvh), diastolic dysfunction (dd), systolic dysfunction (sd), hyperdynamic ventricular function (hvf), wall motion abnormalities, atrial enlargement (ae) and valvular abnormalities using chi-square test and fisher exact test. we then conducted a multivariate logistic regression analysis including variables with a p< . in the univariate analysis. a total of subjects were admitted with an ich. subjects had an echocardiogram and of these, also had an angiogram (conventional angiogram: , ct angiogram: , mr angiogram: ). the echocardiogram was abnormal in . % ( . % with a history of hypertension p= . ). common abnormalities were: lvh ( . %), dd ( . %), hvf( . %), sd ( . %) and ae ( . %). of these, only dd (p= . ) was significantly associated with absence of underlying vascular abnormalities on a univariate analysis. on multivariate analysis, none of the echocardiographic abnormalities showed a significant association. echocardiographic abnormalities, mainly lvh and dd are commonly seen in ich patients, however none of these abnormalities are independently associated with an absence of underlying vascular anomalies. stroke in the hiv+ population is a growing problem, though it is unclear whether hiv is an independent risk factor. we describe a series of hiv+ patients with intracerebral hemorrhage (ich). we reviewed records of all patients with diagnoses of ich and hiv/aids admitted to an academic, inner-city hospital between and . patients with traumatic hemorrhage, ischemic stroke with hemorrhagic conversion, hemorrhagic neoplasms, toxoplasmosis with hemorrhage, subarachnoid hemorrhage, and extra-axial hemorrhages were excluded. we reviewed demographics, risk factors, laboratory tests, and neuroimaging. outcomes at days were determined by modified rankin scale (mrs). six hiv+ patients ( % male, mean age ) met inclusion criteria, with patient having recurrent hemorrhages; % were black, % hispanic, and % of other racial groups. all patients met criteria for aids. risk factors included: prior stroke ( %), diabetes ( %), hypertension ( %), smoking ( %), and illicit drug use ( %). only patient was taking antithrombotic medication. the co-prevalence of hcv was %. admission blood pressure was > / in / patients. laboratory evaluation demonstrated patient with a prolonged inr (> . ) and patients with thrombocytopenia (< ). the hemorrhages were lobar in / and deep in / . only patients had vessel imaging; one had an avm and none demonstrated aneurysm or vasculitis. at days, four patients were deceased and the two survivors had mrs of and . in this cohort, hiv-associated ich occurred only in aids patients. outcomes were uniformly poor, with % of patients having a htn and unexpected predominance of lobar hemorrhages in younger patients, suggesting a distinct mechanism of ich. in gregory call and marie fleming reported four patients with what appeared to be a reversible form of cerebral vasoconstriction. since then a number of authors have reported reversible cerebral vasoconstriction syndromes (rcvs), often in association with potential etiological precipitants. the major complication of rcvs is ischemic stroke, but hemorrhagic strokes can also occur, eventually leading to permanent sequelae and even death. recent reports and case series have suggested that intracranial hemorrhages may be frequent in rcvsand its presentations may range from cortical subarachnoid hemorrhages to intracerebral hemorrhages and subdural hemorrhages. we report two cases of rcvs in middle age women, with hemorrhagic strokes caused after the prescription of dipirone, isometheptene and anhydrous caffeine, with putaminal hemorrhage, and lobar frontal hemorrhage. both cases showed complete reversion of arterial vasoconstriction weeks later by the transcranial doppler. despite the reversibility of the vascular constrictions that characterize rcvs, brain lesions are observed in up to % of the patients.most of these lesions are of ischemic nature; however hemorrhagic phenomena are not uncommon and have only been reported in %- % of the cases. isometheptene has been described as a trigger for rcvs in only a handful of patients, all of whom were women in the postpartum period. even though rcvs diagnosis demands evidence of complete reversibility of the vasospasms, differential diagnosis with sah can be made by the identification of classic rcvs triggers and assessment of the vascular patterns brain arteries. magnesium (mg) has been hypothesized to have a neurprotective effect against cerebral ischemia. several ongoing studies are examining the effect of exogenous magnesium in reducing disability and maintaining normal cerebral function. we examined initial endogenous mg levels in patients with spontaneous intraparenchymal hemorrhage (iph), in order to determine if higher mg blood serum levels would confer neuroprotective benefit. this is a retrospective study on patients admitted to a university affiliated community hospital. demographic data were obtained from a prospectively collected registry database. initial magnesium levels were gathered retrospectively from the registry database. we included all patients with iph in our analysis. for evaluating the severity and outcome of the patients with iph we used the university of california san francisco intracerebral hemorrhage (ucsf ich) score on admission / hours to quantify stroke severity and mrs on discharge to measure outcome. we employed correlation coefficients (spearman's rho) and the mann whitney test for analysis of the data. spss version was used for data processing. our review identified patients with a diagnosis of iph. the serum mg levels in patients with iph negatively correlated to ucsf ich score on admission (p= . , r= - . ) and at hours (p= . , r= - . ). there was a trend towards better outcomes at discharge in patients with higher mg levels (p= . , r= - . ). higher levels of endogenous serum mg were found to confer reduction in iph severity and progression. initial serum mg levels could serve as an early predictor of iph severity. a larger prospective study is warranted to study the effect of endogenous mg on outcomes in patients with iph. spinal dural arteriovenous fistulas (davfs) account for % of all vascular spinal malformations. the incidence is - /million/year in the general population although it is generally under-diagnosed. men are affected five times more often than women and the mean age at the time of diagnosis is - years. spinal davfs generally do not present acutely and are very rarely located in the cervical region. we present a case of atypical acute spinal cord infarct secondary to a cervical davf. case report and extensive literature search carried out to understand spinal davfs. this year old gentleman presented to our neurocritical care unit with bilateral upper extremity weakness and right lower extremity weakness proceeded by upper back and neck pain. the patient rapidly deteriorated to near quadriplegia and respiratory failure requiring prolonged artificial ventilation. initial studies included normal mri of the brain and ct angiogram of the head and neck. mri of the spine revealed abnormal signal intensity within the anterior cervical cord from c -c levels in the distribution of the anterior spinal artery. there were no flow voids to suggest dilated perimedullary vessels. however, given the clinical picture, a spinal angiogram was obtained and demonstrated a cervical davf supplied by a dural branch vessel originating from the left vertebral artery. understanding spinal vascular anatomy is important for diagnosis of spinal davfs. our case is unusual because ) acute evolution of quadriplegia and respiratory failure, ) lack of any abnormal vessels seen on mri, and ) ischemic changes restricted to the anterior spinal artery distribution. the case emphasizes the importance of proceeding with spinal angiography if the clinical suspicion of davf is high. early detection and management can lead to improved functional outcome. although coma is a syndrome commonly associated to catastrophic brain injury, this patient population remains poorly characterized. the chief goal of therapy is aimed at reversal of coma. despite this urgency, there is paucity of data regarding the factors that predict emergence. we characterize a population of patients with new onset of coma in the neuro-icu and describe clinical and structural factors that predict emergence. prospective longitudinal consecutive cohort of patients, enrolled in an intensive care setting. three hundred patients met investigation enrollment criteria between may and july . a brain lesion was identified at the onset of coma in most patients ( %). frequent etiologic factors were cerebrovascular ( %), seizures ( %), trauma ( %), cns infection ( %), or other ( %). the most frequent cerebrovascular factors were any ich ( %), ivh ( %) and sah ( %), either alone or in combination. emergence from coma was predicted by a higher initial gcs (emergence= [ - ] vs. no emergence= . [ - ] p< . ), seizures as presenting disorder (emergence= % vs. no emergence= % p= . ), and a trend to lesser frequency of ich component (emergence= % vs. no emergence= %, p= . ). the importance of mass effect as measured by midline shift reversal and cisternal compression resolution is presented in a separate poster. mortality in this cohort is %. the population of patients with acute coma is highly heterogeneous. however clinical and structural factors predict emergence. a higher initial gcs predicted recovery of coma. structural cerebrovascular lesions with less ich component had a tendency toward higher rates of recovery. non-structural treatable causes of coma such as seizures were associated with higher rates of recovery. mortality and disability remain dismal in this population. optimal blood pressure (bp) control in intracerebral hemorrhage (ich) patients remains controversial. aggressive bp reduction may limit hematoma expansion, but may also cause hypoperfusion and ischemia. we investigated the relationship bp lowering in the first hours and the presence of diffusion weighted imaging (dwi) lesions on mri. we prospectively enrolled consecutive patients presenting with an acute spontaneous ich. brain mris were reviewed for the presence of lesions with reduced diffusion attributable to tissue compression, vessel compression, or hypoperfusion ipsilateral to the hematoma. bps were recorded on hospital presentation, and at , , , and hours. of eligible patients, met inclusion criteria: age: ± years; hematoma volume: ml (iqr - ); admission nihss: (iqr - ); ich onset to maximal bp reduction hours (iqr - ); and ich onset to mri: hours (iqr - ). dwi lesions were detected in % of patients: % of patients had lesions attributed to tissue compression, % to vessel compression, and % to hypoperfusion (some patients had multiple lesion types). dwi lesions were associated with larger hematoma volumes ( vs. ml, p < . ); higher admission mean arterial pressures (map) ( vs. mmhg, p= . ); and greater average map reductions ( vs. %, p= . ). after controlling for ich volume using logistic regression: for every % of map reduction, the risk of dwi lesions increased (or . , % ci: . - . ); for each % reduction in map the risk of dwi lesions more than doubled (or . , % ci . - . ). the proportion of patients with dwi lesions increased as the maximum percent map reduction increased in a dose dependent fashion. ischemic brain lesions in patients with spontaneous ich are common and associated with hematoma volume and bp lowering. aggressive bp lowering may contribute to ich associated ischemic lesions. financial support: sources of funding: this research was supported by the nih (r ns ) to cacw, and the stanford school of medicine medical scholars program to jtk. coma is a major cause of death, disability and economic burden to the health care system. acutely comatose patients with primarily neurologic injury are at risk to develop neurologic and systemic complications. in this study, we seek to identify the timing of medical complications and their impact on mortality in acutely comatose patients admitted to neurocritical care unit. one hundred patients with acute coma for at least hours or longer were enrolled prospectively in the study from may to jan . major neurologic and systemic complications were identified prospectively and the frequency and timing of each major complication was established. of the patients studied, mean age was ± . years and % were females. a mean of . ± complications occurred. in this cohort of patients with coma, there were more non-neurological ( %) versus neurological ( %) complications. most complications ( %) were noted in the - day interval. further characterization of these complications is essential to the care of comatose patients in the nccu. pathophysiology of brain dysfunction associated with sepsis is still poorly understood. our purpose was to study the metabolic alterations and mithocondrial dysfunction in a clinically relevant model of septic shock. twelve anesthetized, invasively monitored, and mechanically ventilated pigs were allocated to a sham procedure (n = ) or sepsis (n = ), in which peritonitis was induced by intra-abdominal injection of autologous faeces. animals were studied until spontaneous death or for a maximum of hours. in addition to global hemodynamic and laboratory assessment, intracranial pressure and cerebral microdyalisis were assessed , , and hours after sepsis induction. after death, brain were removed and brain homogenates were studied to assess mithocondrial dysfunction. all septic animals developed a hyperdynamic state associated with organ dysfunction. in the septic animals, there was a progressive increase in l/p ratio and glycerol, as well as a progressive decrease in brain glucose concentration during the study period. the comparison between control and septic animals and the analysis of brain homogenates are undergoing. in this model of peritonitis, cerebral metabolism was derranged, with increasing levels of l/p ratio and decreasing levels of brain glucose during study period. these alterations may play a role in the pathogenesis of sepsis-associated encephalopathy. at sanford usd medical center, neuro critical care (ncc) patients are frequently treated with continuous infusions of % sodium chloride. it has been observed that this patient population often develops iatrogenic hyperchloremic metabolic acidosis, frequently managed with intravenous sodium bicarbonate. upon notification of a nationwide intravenous sodium bicarbonate shortage (march th , ), our ncc providers were forced to explore other potential options for managing this acidosis. it was decided that our ncc patients would be initiated on enteral sodium bicarbonate at the time continuous % sodium chloride was started. a retrospective chart review of ncc patients years and older, initiated on continuous % sodium chloride with enteral sodium bicarbonate tablets from march th , to june th , were evaluated. data collected included demographics and the following while in the intensive care unit (icu): baseline serum sodium, chloride, and bicarbonate; type of injury; acidosis defined as serum bicarbonate level < , or lower than baseline; and volume of % sodium chloride and bicarbonate administered. of the patients identified, . % developed iatrogenic metabolic acidosis during icu stay. average duration of continuous % sodium chloride infusion was days (range - days) with an average volume of % sodium chloride dispensed of , mls (range - , mls). three patients evaluated developed an acidosis during icu stay, of which were hyperchloremic at the time of acidosis. only patient required intravenous sodium bicarbonate, however the patient had been off hypertonic saline for more than day. enteral sodium bicarbonate appears to be an effective method at preventing iatrogenic hyperchloremic metabolic acidosis when initiated along with continuous infusions of hypertonic saline in ncc patients. this may be a method to conserve intravenous sodium bicarbonate during drug shortages. further studies are needed. fever is common in neurocritically ill patients. it can be from central causes, inflammatory, infectious, and other conditions. a method to differentiate infectious from non-infectious fever would allow for appropriate initiation of empirical antimicrobial therapy. apart from avoiding unnecessary antimicrobial usage, this approach can save health-care costs and limit the development of antimicrobial resistance. procalcitonin is a peptide precursor of the hormone calcitonin. procalcitonin levels rise as a proinflammatory response to bacterial infections. numerous studies have evaluated procalcitonin levels utility in the initiation and discontinuation of antibiotics in the inpatient setting; however, there is a paucity of studies regarding the use of procalcitonin levels in neurologically ill patients. this study examines the effectiveness of a procalcitonin-guided algorithm in a neurocritical care unit. a modified prorata trial procalcitonin algorithm was developed and utilized prospectively. patients that met criteria of ) admission into the neurocritical care unit ) age > years ) temperature > f in the last hrs ) no obvious source of infection were enrolled. depending on the procalcitonin level and the presence of new sirs criteria antibiotics were initiated per our algorithm. radiographical, microbiological, laboratory, and clinical outcomes were recorded to determine the accuracy of the procalcitonin algorithm in the decision to initiate or modify patient's antibiotic therapy. results from the first enrolled patients found the procalcitonin algorithm had % sensitivity and % specificity in predicting bacterial infections as the etiology of fever with a positive predictive value of %. the study population included intracranial hemorrhage ( %), ischemic stroke ( %), and others ( %). % of the study population had infectious fever while % had non-infectious fever. interim results suggest a procalcitonin-guided algorithm may be a valuable tool in differentiating infectious from noninfectious fever in the neuro-icu. further research is needed; data collection is ongoing. posterior reversible encephalopathy syndrome (pres) is defined by acute neurologic symptoms caused by vasogenic cerebral edema. recurrence of pres is thought to be rare and has not been well described. patients prospectively diagnosed with pres from - were pooled with retrospectively identified patients diagnosed with pres from - at an academic referral center. detailed clinical information and radiologic imaging results were collected. patients without clinical or radiographic resolution between episodes and patients without brain imaging available for review were excluded. of a total of patients with pres, ( %) had recurrence. one patient had four episodes, one patient had three, and ten patients had two episodes each, resulting in total pres episodes. seven patients ( %) had an autoimmune disorder. the average time between episodes was months. acute hypertension was present in of episodes. of these, mean blood pressure was / mmhg. etiologies of pres included hypertension (n= ), cytotoxic medications (n= ), sepsis (n= ), and multifactorial (n= ). renal failure was present in / episodes, and was acute in . clinical symptoms included headache (n= ), seizure (n= ), visual disturbances (n= ), encephalopathy (n= ) and focal deficits (n= ). only one patient ( %) had the exact same clinical symptoms with recurrence. ten patients had mri at each episode of pres. vasogenic edema affected the same brain areas at each episode in patients. in the rest, some affected regions were similar, but additional regions were different between pres episodes. none had entirely new areas of involvement. pres recurred in approximately % of our patients. in the majority, clinical symptoms differed at recurrence compared to the initial episode. in all patients, radiologic patterns of vasogenic edema in the repeat episode were similar to those in the initial pres episode, but also affected other brain regions in approximately %. ventilator-associated pneumonia (vap) is a common complication in comatose patients. diagnosis in this population is unreliable despite physician training and validated criteria leading to potential misdiagnosis and inappropriate antimicrobial use. we investigated clinical features associated with misdiagnosis of vap and excess antibiotic days (ead). ventilated comatose patients (glasgow coma scale motor score < ) suspected of having vap were prospectively identified in a neurocritical care unit in . vap was retrospectively diagnosed using centers for disease control (cdc) criteria by two neurointensivists and an infection control practitioner. appropriateness of the nccu team's vap diagnosis and therapy was performed using clinical, microbiologic and radiographic data. of comatose patients, cases were treated as possible vap by the nccu team. of these, patients had vap by cdc criteria. vap and non-vap groups did not differ in age, admission gcs, total ventilator days or mean total antibiotic days ( . ± . (vap) vs. . ± . (non-vap); p= . ). clinical features significantly associated with vap (vs. non-vap) were change in sputum character, tachypnea, oxygen desaturation, persistent infiltrate on chest xray and positive sputum microbiology. two-thirds ( . %) of non-vap patients received pneumonia targeted antibiotics for > days vs. . % of vap patients (p= . ), contributing eads, including vancomycin days, piperacillin-tazobactam days and cephalosporin days. median days from intubation to starting antibiotics was (non-vap) vs. (vap) days (p = . ). no pre-specified factors were associated with inappropriate continued vap treatment. inappropriate diagnosis and treatment of vap resulted in a cumulative eads in one year in the nccu. clinical differences between patients without vap who had antibiotics continued or discontinued were minimal, suggesting that clinician behaviors contribute to unnecessary prescribing. strategies to improve the diagnosis of and antibiotic use for vap in comatose patients is needed. management of hyponatremia in patients with acute brain injury can be challenging. the oral vasopressin receptor antagonist has been studied extensively in other disease process but not in acute brain injury. we report our experience regarding the efficacy and safety of tolvaptan, an oral vasopression v -receptor antagonist, for the correction of hyponatremia in acutely brain-injured patients. tolvaptan for the correction of euvolemic or hypervolemic hyponatremia. baseline serum sodium concentration was . ± . meq/l. seven patients received mg of tolvaptan once (singledose-users), and patients received another mg on the next days (double-dose-users). hours after tolvaptan administration, serum sodium concentration increased by . ± . meq/l in single-dose-users (p = . ) and . ± . meq/l in double-dose-users (p = . ). hours after administration of first dose of tolvaptan, serum sodium increased by . ± . meq/l in single-dose-users (p = . ) and . ± . meq/l in double-dose-users (p = . ). during four days of observation, the increases in the average area under the curve of the serum sodium concentration was . ± . meq/l in single-dose-users (p = . ) and . ± . in double-dose-users (p = . ). urine output increased by . ± . l during the first hr in single-dose-users (p = . ). no significant changes in fluid balance, serum creatinine and glasgow coma scale were observed. of four patients who underwent neuro-monitoring, intracranial pressures, cerebral perfusion pressures and mean arterial pressure did not change significantly compared with their baseline values. tolvaptan was effective and well-tolerated for the correction of hyponatremia in patients with acute brain injuries. validation can be done with further studies. patients with acute brain injury but normal lung function often undergo intubation and subsequent tracheostomy for the concern of airway protection. we previously described patients with primary brain injury and encephalopathy who fail extubation demonstrated signs of disrupted ventilation usually with periods of prolonged hypoventilation. we examined the clinical characteristics of patients with a tracheostomy who are readmitted to the icu with respiratory decompensation. retrospective review of patients admitted to the neurocritical care unit (nccu) of a tertiary care hospital who underwent tracheostomy from september to june . of patients who received tracheostomies during their admission to the nccu, ( %) were successfully transferred to the floor, ( %) were readmitted to the icu, and ( %) had other dispositions such as discharge to rehabilitation and withdrawal of care. there were a total of readmissions, due to respiratory decompensation and due to cardiopulmonary arrest. hypoventilation is commonly seen in neurological patients who receive a tracheostomy. potential predictors of respiratory decompensation and readmission of these patients include their brainstem reflexes and respiratory patterns as assessed by the four score as well as their duration of mechanical ventilation. twenty-two percent of neurocritically ill patients may become hypernatremic. moderate-severe traumatic brain injury (mstbi) patients may develop hypernatremia possibly from diabetes insipidus (di) or osmotherapy for brain edema treatment. retrospective studies suggest that hypernatremia (serum sodium [sna] > mmol/l) may be associated with an increased risk of death. however, these studies failed to adjust for di and the use of osmotherapy. we examined the impact of mean and peak sna on in-hospital mortality and functional outcome at hospital discharge, adjusted for these important variables. in a prospective observational study, consecutive mstbi patients from a single level i trauma center between / - / were analyzed. poor outcome was defined as glasgow outcome scale (gos) - . multivariable logistic and ordinal regression was utilized to adjust for admission characteristics, injury severity, icu length-of-stay, brain edema, osmotherapy (mannitol/hypertonic saline), and di. firth's method was used in logistic regression models to accommodate small sample sizes. the mean age was years, % were men, and the median glasglow coma scale and injury severity scores were and , respectively. higher mean and higher peak sna were significantly associated with worse outcomes, both when using the dichotomized (or . ; % ci . - . for mean and or . ; % ci - . for peak sna) and ordinal gos (or . ; % ci . - . for mean and or . ; % ci . - . for peak sna). for every mmol/l increase in mean sna and every mmol/l increase in peak sna, patients worsened by one gos category. our results suggest that higher sna values are associated with worse neurological outcome, independent of osmotherapy, brain edema and di. it will be important to determine which sna might be "too high". while autonomic instability occurs as part of anti-n-methyl d-aspartate (anti-nmda) receptor encephalitis, anti-nmda receptor encephalitis is not a recognized cause of the clinical syndrome of paroxysmal sympathetic hyperactivity (psh). we present a case of anti-nmda receptor encephalitis in which psh was a cardinal feature. a -year-old woman had a generalized tonic-clonic seizure, and then developed progressively worsening neuropsychiatric symptoms, including mania, hallucinations, echolalia, and suicidal ideation. diagnostic work-up revealed anti-nmda receptor antibodies detected in the serum and in the cerebrospinal fluid (csf). one week after symptom onset, the patient experienced intermittent episodes of sinus tachycardia, hypertension, tachypnea, diaphoresis and extensor posturing. the episodes were both spontaneous and stimulus responsive (for example, during endotracheal suctioning). the episodes, consistent with psh, were initially treated with dexmedetomidine, which was titrated to effect. gabapentin and propranolol were added later for symptom control, but eventually weaned off as her symptoms abated approximately six weeks into the illness. we believe that the autonomic instability associated with anti-nmda receptor encephalitis may often be psh. psh often goes unrecognized in patients outside of the setting of tbi, thus specific psh management strategies may be overlooked in other contexts. anti-nmda receptor encephalitis may represent the functional companion to the structural lesion encountered in tbi. recognition of psh in this setting is important to guide the management of the autonomic instability, but may also have mechanistic implications. a -year old male with history of motor vehicle accident s/p frontal sinus surgery was admitted with streptococcus pneumoniae meningitis and altered mental status. upon admission, he was febrile with leukocytosis. head ct showed left sinus opacification and csf studies were consistent with bacterial meningitis. despite broad-spectrum antibiotics and interval improvement in his head ct and csf studies, his mental status continued to decline. shortly after icu admission, he became lethargic with a new right-sided hemiparesis. cta revealed diffusely narrowed intracranial arteries most compatible with vasospasm and mri was consistent with multiple areas of infarction. his neurological exam continued to deteriorate necessitating intubation for airway protection. tcds showed bilateral mca vasospasm. initially, vasospasm was managed with nimodipine, hypertension, and euvolemia. systolic blood pressure was artificially elevated with vasopressors, inotropes, and ultimately with methylene blue. despite aggressive medical management, there was little improvement clinically. therefore, he received four sessions of angiography with intra-arterial verapamil. after the final intra-arterial verapamil treatment, he demonstrated angiographic and clinical improvement. we conclude that patient's cerebral vasospasm was a direct complication of streptococcus pneumonia meningitis. intra-arterial verapamil appears to be effective in treating pneumococcal meningitis induced symptomatic cerebral vasospasm. however, there is limited data to predict its vasodilatory sustainability and optimal treatment intervals. pneumococcal meningitis is the leading cause of bacterial meningitis beyond the neonatal period. clinical and experimental research had demonstrated that vascular alterations are common in bacterial meningitis and are associated with stroke. despite the introduction of the pneumococcal vaccine, availability of effective antibiotics, and advances in adjunctive strategies, mortality and morbidity rates associated with arterial complications secondary to pneumococcal meningitis remain high. this case is noteworthy because to our knowledge this is the first reported case of pneumococcal bacterial meningitis induced vasospasm that has been successfully treated with intra-arterial verapamil. xuemei cai , osmotic myelinolysis is a life threatening problem associated with rapid correction of chronic hyponatremia. the brain cannot readily restore organic osmolytes; thus rapid correction of serum osmolality leads to cellular shrinkage causing axonal dissociation from myelin sheaths. current guidelines state that serum sodium (sna) should be corrected at a rate not exceeding - meq/l/day but when extracellular volume depletion is the cause, vasopressin suppression after saline treatment increases risk of rapid overcorrection. there is no standard of care that directs treatment once osmotic myelinolysis occurs. we report a case of a patient who developed clinical symptoms of osmotic myelinolysis syndrome who was successfully treated with re-induction of hyponatremia which led to complete neurological recovery. a -year-old woman on thiazide treatment for hypertension developed protracted vomiting and diarrhea for several days followed by confusion and lethargy. in the emergency department, sna was meq/l. she received isotonic saline and over the next hours, sna rose meq/l. on hospital day two, her neurological condition deteriorated rapidly with development of mutism, increased tone in all extremities, hyperreflexia. osmotic myelinolysis syndrome was diagnosed on clinical grounds. she was given desmopressin with % dextrose in water (d w) to rapidly lower her lower her sna. her neurological status improved at a sna of meq/l. thereafter, sna was slowly uptitrated with desmopressin and % normal saline. she made a complete neurological recovery. mri performed at discharge and one month later showed no abnormalities. overcorrection of sna in chronic hyponatremia is a common iatrogenic problem which can lead to osmotic myelinolysis syndrome, a highly morbid and oftentimes fatal neurological condition. our case supports immediate re-induction of hyponatremia in patients with symptoms suggestive of osmotic myelinolysis at a time when imaging may be unremarkable and complete neurological recovery is achievable. posterior reversible encephalopathy syndrome (pres) is manifested by acute neurological findings with evidence of vasogenic edema on brain imaging possibly due to cerebral vascular endothelial dysfunction. the epidemiology of pres in pediatric critical care has not been well described and it may be under recognized and thus prompt treatment delayed. we performed a retrospective review of all patients with diagnosis of pres over month period (january to june ) in a pediatric critical care unit (pccu) at a tertiary care university hospital. data from hospitalization and month follow up were reviewed. there were admissions to pccu and neurology service consultations during the study. six patients were diagnosed with pres (incidence - in pccu admissions) with median age years (mean±sd; . ± . years). all patients presented at onset with generalized tonic-clonic or clonic type seizures that lasted up to hrs and returned to baseline mental status in - days. other clinical features were headache and visual impairment. risk factors preceding the onset of pres included anemia [hemoglobin . ± . g/dl], azotemia, hypertension, hypernatremia, hypocalcemia, hypomagnesemia, and recent use of chemotherapy (azathioprine, cyclophosphamide, tacrolimus and mycophenolate mofetil). brain mri demonstrated increased t /flair signal within the parieto-occipital white matter in all patients, frontal lobe changes in patients and vertebro-basilar system changes in patients. no regions of restricted diffusion were seen on diffusion weighted imaging. at month follow up, no patients had residual neurological deficits from pres and neuroimaging revealed significant resolution of white matter signal changes. pres is associated with multiple disease states including systemic lupus erythematosus, sickle cell disease, sepsis, recent use of cytotoxic medications and renal failure. knowledge of the risk factors associated with pres, its clinical presentation, and characteristic mri findings may lead to more rapid recognition and treatment. adults with neurological injury are at increased risk for tracheobronchial foreign body aspiration. this report will present a case of silent foreign body aspiration in a patient who presented to the emergency department with status epilepticus. case report and review of the literature. an year-old african american man presented to the emergency department with status epilepticus. seizures were controlled with intravenous lorazepam and fosphenytoin, and the patient was intubated for airway protection. on day four following admission to the neurosciences critical care unit, a routine magnetic resonance imaging (mri) scan demonstrated susceptibility artifact from a metallic focus which completely obscured the spine structures at c -c . upon review of the patient's previous imaging, numerous abnormalities were reported on daily chest x-rays and a foreign body was identified within the trachea on a thoracic ct from admission. a bronchoscopy was performed which revealed a watchband within the trachea and right mainstem bronchus. tracheobronchial foreign body aspiration should be considered in patients with unexplained respiratory symptoms, and a high degree of clinical suspicion should be maintained in patients with neurologic impairment. abnormalities on chest xray and computed tomography should prompt an early pursuit of the diagnosis in high-risk patients. mri, although generally considered to be a safe imaging modality, could be potentially harmful to patients with unidentified foreign bodies. hypokalemic periodic paralysis (hypopp) is a disease characterized by muscle weakness or paralysis secondary to low serum potassium levels. neurogenic diabetes insipidius (di) is a condition where patient excretes large volume of diluted urine due to low level of anti-diuretic hormone (adh). here, we report a case of hypopp in a patient with neurogenic di. a year-old right-handed hispanic male was admitted for seizures after developing a dental abscess. this patient had a history of pituitary adenoma resection at the age of with subsequent pan-hypopituitarism for which he was on hormonal supplementation. on hospital day three, he developed sudden onset of quadriparesis with motor strength in upper extremities / bilaterally and / in both lower extremities and absent deep tendon reflexes throughout. his routine laboratory studies showed severe hypokalemia of . meq/dl. nerve conduction study (ncs) revealed absent compound motor action potentials with normal sensory potentials. electromyography (emg) revealed no abnormal insertional activity or spontaneous activity. some muscles demonstrated no volitional motor units and a few others had decreased recruitment in distal small motor units. following aggressive correction of the hypokalemia he regained his full strength and repeat emg showed normal motor units, normal recruitment, but no myotonic discharges. ncs showed return of compound motor action potentials in all nerves tested. hypopp remains an important differential in an acute case of paralysis and acute management is important. we report a case of a -year-old caucasian male who presented to a community hospital with complaints of flu-like symptoms. he underwent pulmonary-vein isolation for chronic atrial fibrillation thirty days prior to admission. his history includes left frontal and right parietal ischemic infarcts, mitral valve repair, coronary artery bypass grafting, patent foramen ovale closure, and coronary artery disease. approximately hours prior to arrival, he developed nausea, vomiting, fatigue and confusion. he was febrile and appeared encephalopathic. a telemedicine stroke consultation recommended transfer to a tertiary care facility. while the initial concern was for acute cerebral ischemia, he did not meet exclusion criteria for thrombolytic therapy. the patient received aggressive initial hydration and broad spectrum intravenous antibiotics for coverage of meningitis. blood cultures, complete blood count, comprehensive metabolic panel, urinalysis, stool culture and a lumbar puncture were performed. interestingly, his blood cultures remained persistently positive for gram positive cocci in chains and clusters. occult stool was positive and his oral gastric tube demonstrated bloody drainage. the remainder of his laboratory work was unremarkable. ct scan of his head revealed old ischemic infarcts without hemorrhage or hypodensity. the patient continued to decompensate in the neurointensive care unit where he eventually required intubation. a ct scan of the chest was highly suspicious of a left atrial-esophogeal fistula. cardiothoracic surgery was notified of the atrio-esphogeal fistula and he was taken to the operating room for a right thoracotomy with repair of the fistula and intercostal muscle flap. post-operative mri brain demonstrated innumerable air emboli and diffuse areas of ischemic infarction. atrio-esophageal fistula is a very rare complication following pulmonary vein isolation, and because prognosis is dependent upon prompt surgical correction, neurointensivists should be aware of this entity financial support: none propofol infusion syndrome (pris) is a rare but devastating complication of high dose administration of diprivan in children and young adults which presents with metabolic acidosis, rhabdomyolysis and fatal cardiac dysrhythmias. we report a case of pris in a -year old, previously healthy, postpartum female who received a high dose diprivan infusion for hours at an outside institution for the treatment of presumed refractory convulsive status epilepticus. patient received diprivan mcg/kg/min for the first hours. diprivan was increased to mcg/kg/min to achieve burst suppression on the electroencephalogram. diprivan was stopped after hours due to lactic acidosis. subsequently patient developed renal failure and elevation of ck up to , .she was transferred to our institution for continuous hemofiltration and possible extracorporeal membrane oxygenation (ecmo).after transfer she developed atrial fibrillation, ventricular tachycardia and fibrillation. an ecmo catheter was placed when she was in ventricular fibrillation for minutes. after starting ecmo the patient developed asystole for hours, requiring a transvenous pacemaker. her cardiac dysfunction improved rapidly and ecmo was discontinued after days. the patient started to follow commands consistently at days after the onset of fulminant pris. mri of the brain showed a subacute right posterior cerebral artery infarct attributed to cardiac embolism. the patient left intensive care unit after weeks. close metabolic and cardiac monitoring should be applied when a patient is on high-dose of diprivan(> mcg/kg/min). diprivan should be stopped as soon as unexplained metabolic acidosis, rhabdomyolysis and cardiac dysrhythmias are noticed, and transfer the patient to a center with continuous hemofiltration and ecmo capabilities should be considered. ecmo can be a lifesaving intervention in patients with fulminant pris. postpartum cerebral angiopathy (pca) is a rare pregnancy complication. pca is often a benign condition that resolves spontaneously, but can lead to stroke or death. the purpose of this case study is to describe events that transpired in the care of a patient with severe persistent pca, for whom unconventional treatment was initiated because conventional treatment failed. retrospective and current chart reviews were conducted, including relevant medical history. objective data related to the patient's condition were reviewed. we examined the evolution of medical and nursing care as the patient's condition deteriorated despite aggressive conventional therapy, and reviewed ensuing events: multidisciplinary collaboration to search for other viable treatment options, consultation with colleagues from another major medical center regarding their experience with nicardipine and recommendations on off-label use for pca, and decision-making including the family about whether or not to administer intraventriuclar nicardipine. multiple disciplines (i.e., doctors, nurses, and pharmacists) and family members contributed to the complex decision to initiate unconventional treatment. we administered mg intraventricular nicardipine every eight hours for seven days. using transcranial dopplers, cerebral arteriograms, and clinical assessment data, we evaluated the effectiveness of this unconventional treatment. after seven days, we discontinued the nicardipine, while continuing standard treatment to maintain hypertension and hypervolemia. currently, the patient is expected to make a full recovery with few residual stroke deficits. a multidisciplinary approach, including the family in the decision-making process, enabled creative problem-solving for a challenging clinical situation. when conventional methods failed, our team collaborated to think outside the box and take a calculated risk, altering the course of our patient's condition from critical toward survival and recovery. the objective was to determine the diagnostic yield and safety of brain mri in critically ill patients with icu-acquired acute brain dysfunction. patients in the medical and surgical icus who developed acute brain dysfunction and underwent brain mri were included. patients with preexisting brain disorders and those from neurological icus were excluded. mri scans were analyzed by three specialists trained in neuroimaging. outcome variables included glasgow outcome scale at discharge ( - categorized as unfavorable and > as favorable) and death. patients underwent brain mri for evaluation of encephalopathy, seizures, focal deficit. signs of parenchymal brain abnormalities were detected in patients ( %) including white matter hyperintensities in . % and acute cerebral infarcts in . %. results from brain mri led to modification of diagnosis and treatment in % of cases. patients with mri defined lesions were more likely to have an unfavorable outcome. there were no adverse events from transportation to the radiology site or from mri performance. in icu patients with acute brain dysfunction, mri is a safe noninvasive diagnostic tool that often leads to substantial modification of diagnosis and treatment. structural brain injury contributes significantly to the pathogenesis of cerebral dysfunction during critical illness and should be taken into account even if other reasons for encephalopathy are presumed. central nervous system (cns) and intraventricular infections are a devastating complication for patient admitted to an intensive care unit. the use of intrathecal (it) antibiotics for the treatment of cns infections has been reported in small case studies. our purpose was to report patients who have received it antibiotics for intraventricular infections in our facility and discuss our findings. retrospective case series of patients who received intrathecal antibiotics in combination with systemic antibiotics for treatment of intraventricular cns infection over the past years. basic demographic and clinical measures were collected from the hospital data base. seven patients received it antibiotic therapy for cns infection. admitting diagnoses were head trauma ( ), intracranial hemorrhage ( ), and subarachnoid hemorrhage ( ). one patient had an infected ventriculoperitoneal shunt. all of the patients received an external ventricular drainage device during admission prior to developing cns infection. time from hardware placement to first positive csf culture for patient was days; patients were positive with first csf; were within days; and had his vp shunt in place for days prior to positive cultures. pathogens cultured from csf included klebsiella pneumoniae, acinetobacter baumannii and vancomycin-resistant enterococcus faecalis in patients each, and methicillin-resistant staphylococcus aureus in patient. the intrathecally instilled antibiotics were colistin, streptomycin, tobramycin and vancomycin. two of the patients cleared csf cultures in day, patient cleared in days, patients cleared in days and took days to clear csf. based on this small case series we found it antibiotic adjunct therapy as a viable option for treating cns infections as most of our patients cleared csf within days of treatment initiation. further studies are warranted to support our findings. we report a case of an esthesioneuroblastoma or olfactory neuroblastoma (onb) presenting with frontal lobe dysfunction and hence depression with rapidly declining mental status resulting from hydrocephalus and stroke meningitis. this is a year old man who presented with fever, headache and ams. he had months history of progressive headache, face pain, rhinorrhea, nasal congestion and depression. ct head showed destruction of the cribriform plate by a mass arising from the right nasal cavity with extension into the right inferior frontal cranial fossa. an evd was placed emergently for elevated icp. he was also found to have multiple strokes in the right basal ganglia and corpus callosum. an incidental mycotic aneurysm was seen at the right posterior cerebral artery. labs showed wbc of , sodium of , potassium of , bicarbonate is . a lumbar puncture was performed which showed evidence of bacterial meningitis. a diagnosis of onb was established by histopathology and confirmed by immunohistochemistry. on staging, the mass was classified as a kadish stage c tumor. he underwent coiling of the pseudo aneurysm of right pca and maxillary embolization, followed by bifrontal craniotomy and endovascular resection of tumor onb is a rare malignant tumor of neuroectodermal origin and is thought to arise from the olfactory epithelium. symptoms are related to nasal obstruction, orbital extension, invasion of thecribriform plate, paraneoplastic syndromes with hypercalcemia and hyponatremia and can cause frontal lobe dysfunction. physical examination generally reveals a vascular, polypoid mass located in the nasal cavity. mri helps to differentiate tumor from other causes of nasal obstruction. they typically stain for neuron-specific enolase (nse). there has been no standardized rct done due to rarity of the tumor but traditionally the mainstay of treatment in such locally advanced patients is combinedotolaryngologic and neurosurgical craniofacial resection followed by adjuvant radiotherapy. we describe a case of delayed ptld in a year old diabetic patient with esrd several years after multiple solid organ transplants; a successful pancreatic transplant and a rejected renal transplant. she initially presented with mild left hemiparesis and was found to have enhancing and non-enhancing both supra and infra tentorial lesions, without evidence of disease in the graft, skin or bone marrow. the histological diagnosis of ptld was made after a right frontal brain biopsy. she had intercurrent worsening of left hemiparesis post biopsy due to hemorrhagic transformation of one of the lesions. the patient initially responded to a decrease in immunosuppressive medications which included tacrolimus and cellcept however, she eventually also required rituximab and whole brain radiation to maintain remission. in this case report we highlight the manifestations of cns ptld, dilemmas in diagnosis and various strategies for management. this can be a fatal complication of solid organ transplants if not recognized and treated early. dysautonomia has been well associated with guillain barre syndrome (gbs). the dysautonomic effects of gbs may cause a variety of reversible clinical syndromes associated with sympathetic dysfunction including pres and takotsubo cardiomyopathy. pres can be a presenting feature following gbs treatment with intravenous (iv) immunoglobulins or may present later in recovery. dysautonomia resulting from gbs is the most likely explanation for this assocication while another possible mechanism can be the influence of cytokines, produced in the context of gbs, on the permeability of blood brain barrier. in this abstract we highlight a self limited case of pres presenting as an early complication of gbs. case: our patient was a year old female with hypertension who presented to an outside hospital with alteration in mental status. she had developed bilateral lower extremity weakness and difficulty ambulating for - days prior to admission. she reportedly had an upper respiratory infection about weeks prior to presentation. at the time of transfer to our hospital the patient had a generalized tonic clonic seizure and was started on keppra. she had a fluctuating mental status from being awake to stuporous. bilateral lower extremity power was / in all muscle groups. initially, deep tendon reflexes were + in lower extremities but after a few hours she became areflexic in lower extremities with + reflexes in upper extremities and downgoing plantars. mri brain t /flair images showed lesions consistent with pres. csf showed cyto-albuminologic dissociation and diagnosis of gbs was made. she was started on a day course of iv ig. she was discharged to a rehab facility with some improvement in her paraparesis and no recurrent seziures. this case report illustrates that patients can develop pres as a complication of gbs perhaps due to dysautonomia but pres may be self limited in this setting. data exists describing the outcomes of critically ill patients with specific conditions in specialty intensive care units (icu) versus general icus. severe sepsis and septic shock(ss/sh) outcomes have not been robustly evaluated in community hospitals between specialty icus. we chose to evaluate whether patients admitted to icus with ss/sh would have higher mortalities in neuroscience (ns) and cardiac (cards) icus versus general medical surgical icus (msicu). intensivists. the variables collected include age, time to antibiotics, intravenous fluids given, central line placements, code status, vasopressor requirements at hours and mortality. chi-square analysis was used to compare mortality rates. icus who were directly admitted from the ed were ns % (n = ), cards %(n= ), msicu % (n= ) p=. . the mortality rate for patients admitted with ss/sh was similar independent of the type of the icu the patients received care in. a multivariate analysis needs to be done to confirm these outcomes neurocrit care ( ) :s -s s thromboembolism is a known and feared complication of administering prothrombin complex concentrates (pcc) but the true incidence is unknown. most data is in regards to mi, dvt, pe and dic with little reported on ischemic stroke. this is the first known report in the literature of acute basilar thrombosis after reversal of anticoagulation with pcc. we present a year old women with acute basilar thrombosis after reversal of anticoagulation using pcc (profilinine sd). she was admitted with a hemodynamically stable lower gi bleed with a supratherapeutic inr of . she was taking coumadin for a recent pulmonary embolus. anticoagulation was reversed using profilnine sd units ( u/kg) and vitamin k mg intravenously. hours later she developed left facial weakness, quadraparesis and anarthria. ct brain showed no early ischemic changes. ct angiogram showed occlusion from the mid-basilar to the basilar apex with normal vertebral arteries from the origin to the site of occlusion. factor ii activity was elevated with normal activity of factor vii, ix and x. tte showed normal wall motion and ejection fraction without evidence of thrombus or shunt. pcc protocols for reversal of anticoagulation are used with increasing frequency, even in non-emergent situations. thromboembolism is a known complication of administration, even with modern formulations of pcc which include anticoagulants. risk of thromboembolism increases with doses above u/kg and with repeated dosing. the cause of thrombogenicity remains uncertain. accumulating data indicates the importance of factor ii (prothrombin) which has a linear relationship with thrombin generation. our case suggests that given potentially fatal thromboembolic complications, pcc administration should be weighed against the need for rapid correction of coagulopathy. more discussion is needed regarding complications of pcc administration, optimal dosing and uniform production of pcc products on the market. endovascular reperfusion reduces infarct volume to improve clinical outcome; however treatment effect may be diluted by subsequent care. an exploratory analysis was done to determine if discharge disposition impacted day mrs after definitive reperfusion therapy. in our study, patients discharged to snf & ar after thrombectomy have similar medical & neurological severity at admission and similar final infarct volumes at discharge. despite these similarities, patients discharged to snf had a significantly lower probability of achieving a good neurological outcome. further study is required to determine if ar should be considered in more patients to improve clinical outcomes. patients with acute ischemic stroke develop respiratory failure due to airway compromise from loss of protective reflexes or cerebral swelling. in such patients, traditional weaning parameters poorly predict successful extubation. failure of extubation increases complications, prolongs hospitalization and increase cost of care. we hypothesize that predictive factors can be identified in determining ischemic stroke patients with respiratory failure who can be successfully extubated. between january to december , consecutive patients admitted to a metropolitan academic stroke center with acute ischemic stroke and were mechanically ventilated within hours of admission were reviewed after irb approval. patients who were intubated for procedures only, extubated within hours, or placed on comfort measures were excluded, leaving patients for analysis. statistical analysis was done using sas . and univariate or multivariate logistic regression was performed when appropriate. of the included patients, the average age was . ± . years, and ( . %) were male. the median admission nihss was . and majority of patients had cardioembolic ( ) or large vessel atherosclerotic ( ) strokes. patients had posterior circulation stroke ( . %). eleven patients failed extubation ( . %). acute basilar occlusion was found to be a strong predictor of extubation failure (or= . %ci: . - p= . ) when adjusted for age, stroke severity and duration of mechanical ventilation. increasing age and higher nihss showed trend toward increased risk for extubation failure but did not reach statistical significance. hospital length of stay doubled, icu length of stay tripled, and total hospital cost doubled in patients who failed extubation. patients with respiratory failure due to acute stroke from basilar occlusion were more likely to fail extubation. patients who fail extubation had longer icu and hospital stay doubling the cost of care. further studies are needed to determine whether preemptive tracheostomy may be beneficial in this group of patients. early detection of patients likely to develop malignant middle cerebral artery (mca) infarction (mmcai) is essential to enable timely decision for promising interventions (e.g., decompressive hemicraniectomy). this study was designed to evaluate whether quantitative eeg (qeeg) could predict mmcai within hours of stroke onset. this prospective, observational cohort study enrolled patients with a mca infarct. all of them underwent eeg monitoring within hours after symptom onset. subsequently, their raw eeg data were quantitatively analyzed and the qeeg parameters including (delta+theta) / (alpha+beta) ratio (dtabr) and brain symmetry index (bsi) were computed based on the power spectral density. patients were classified in the mmcai group if they had decline of consciousness with radiological signs of space-occupying brain edema, whereas the others were allocated into the non-mmcai group. for the groups, we compared the above qeeg parameters, and clinical and imaging variables. univariate and multivariate discriminant analysis was used to determine the most accurate predictors of mmcai. of the patients included, developed mmcai. univariate analysis showed that the values of dtabr and bsi, the nihss scores on admission and a hypoattenuation on admission cerebral computed tomography (cct) scans > % mca territory were significant predictors of mmcai. the further logistic regression analysis identified bsi > . (odds ratio [or] . , % confidence interval [ci] . to . ; p = . ) and the infarct size > % mca territory on cct scan at admission (or . , % ci . to . ; p = . ) as independent predictors, and bsi > . was the better predictor, which achieves a positive likelihood ratio (lr) of . ( % ci . to . ) and a negative lr of . ( % ci . to . ). quantitative eeg allows the early prediction of mmcai, and can help in the selection of patients for decompressive hemicraniectomy. financial support: none the modified rankin scale (mrs) is a -level outcome scale used to assess level of function in neurological disease. its utility is underscored by widespread use in stroke outcomes assessment, but the basic levels of function encoded by the mrs are not specific to stroke. still, poor interobserver reliability and the requirement for expert and face-to-face interviews are problems in determining an mrs score. we have developed a question "yes/no" questionnaire, the mrs- q, and an online mrs calculator to quickly and accurately determine the mrs. we hypothesize that ( ) the mrs- q has acceptable interobserver reliability, ( ) the mrs- q can be administered equally well in person or over the telephone, ( ) the mrs- q can be administered accurately by personnel without clinical expertise, and ( ) the mrs- q allows application of the mrs to a broad range of neurological conditions. the mrs- q was administered by form or telephone. a web-based tool calculated the mrs and performed error checking. part compared the mrs- q to an mrs structured interview (n= ). part compared mrs- q administration by telephone and by paper form (n= ). part compared administration by an expert interviewer with administration by a non-expert (n= ). part examined reproducibility over weeks (n= ). agreement was very good in all study parts. in part (mrs- q vs. mrs-si), k was . and k w was . . in part (telephone vs. paper), k was . and k w was . . in part (expert vs non-expert), k was . and k w was . . in part (reproducibility), k was . and k w was . . the mrs- q can reliably determine the mrs by paper survey or over the telephone. importantly, the mrs- q survey does not require the participation of trained experts-excellent results are obtained when non-medical study personnel administer the survey. potentially inappropriate medications (pims) are medications that may increase cognitive burden and impact clinical outcomes in elderly icu patients. this study evaluates the use of pims and outcomes in elderly stroke patients. this is a retrospective study of p july . number of pims, length of stay (los), and changes in gcs and rass scores were evaluated. fisher's exact test was used to compare groups. of a significantly longer nsicu los and worse outcomes. introduction ais patients often have acutely elevated bp requiring iv antihypertensives (ivah). previous work shows aha/asa recommended antihypertensives used to reduce bp in ais commonly results in polypharmacy and its consequences: overshoot hypotension and increased mortality. this study evaluates the association between ivah polypharmacy and both clinical and economic outcomes in ais. premier, a us hospital administrative database. patients with ms-drgs to and a primary ais icd- code ( .x or .x ) were included. patients were matched in a : fashion utilizing propensity score methodology controlling icu admission, baseline characteristics, and pre-existing conditions. from january to december , study patients received at least one ivah on day one or two of hospitalization and . % of those received more than one ivah. after matching, patients remained in each group. patients in gp had a lower mortality rate than gp ( . % vs . %, p= . ), lower vasopressor use ( . % vs . %, p= . ), shorter los (median days vs days, p< . ), and lower total hospital costs (median $ , vs $ , , p< . ). t-pa use was similar between groups ( . % vs . %, p= . ). polypharmacy to treat acute hypertension is associated with worse clinical and economic outcomes in ais regardless of tpa administration. recent evidence suggests precise and reliable bp control is critical during the entire stroke pathway of care. currently recommended ivah do not reliably manage bp as single agents. in order to avoid polypharmacy and improve outcomes and costs, the ideal ivah drug needs to reliably manage and maintain precise bp control as monotherapy. financial support: authors are employees of the medicines company which markets an iv antihypertensive agent. mean corpuscular hemoglobin concentration (mchc) is a red blood cell indicie that is obtained as part of a complete blood count (cbc). mchc values reflect individual red blood cell (rbc) hemoglobin (hgb) content, and are directly affected by changes in hgb production and dna synthesis. recently another hematologic indicie: the red cell distribution width (rdw), has been shown to be an independent predictor of outcome in patients with stroke. we sought to determine if mchc on admission could be predictive of clinical outcome. this is a retrospective study on patients admitted to a university affiliated community hospital. initial mchc data were gathered retrospectively from the registry database. we included both ischemic and intraparenchymal hemorrhage (iph) stroke patients in our analysis. for evaluating the severity and outcome of the patients with ischemic strokes we used nihss on admission and mrs on discharge respectively. in iph patients, we utilized the university of california san francisco intracerebral hemorrhage (ich) score on admission / hours to quantify the severity of the stroke and mrs on discharge to measure the outcome. we used correlation coefficients (spearman's rho) and the mann whitney test for analysis of the data. spss version was used for data processing. our review identified patients with a diagnosis of iph and with a diagnosis of ischemic stroke. the mchc values in the iph group positively correlated to ucsf ich score on admission (p= . , r= . ) and at hours(p= . , r= . ), as well as to mrs at discharge (p= . , r- . ). the mchc levels for ischemic stroke patients correlated weakly and negatively to nihss on admission (p= . , r= - . ) and d-mrs (p= < . , r= - . ). mchc levels on admission correlate significantly with clinical measures of stroke severity and disability. mchc could serve as an early predictor for outcome in different stroke subtypes. in the absence of specific guidelines, there is considerable variance in pre-procedural intubation practices for endovascular treatment of acute ischemic stroke. the purpose of this study is to understand and characterize the variance in pre-procedural intubation practices and identify the reasons that influence the choice of pre-procedural intubation practices among treating physicians. we selected random cases from a prospective database of patients undergoing endovascular treatment for acute ischemic stroke and prepared a case summary providing pertinent demographic, clinical, and imaging data. twenty clinicians independently reviewed the case summaries and responded to whether they would intubate any of the patients and identified the reasons for their choices. clinicians were also asked to identify their training background (neurology, neurosurgery or radiology trained endovascular specialist, vascular neurologist or neuro-intensivist). reasons for intubation and agreement between clinicians for each case were ascertained. the decision to intubate the patient was made in of total clinical scenarios. the major reasons identified by the physicians for pre-procedural intubation were high national institute of health (nih) stroke scale scores on admission . % (n= ), labored breathing or desaturation . % (n= ), less than optimal respiratory status of patients combined with drowsiness or reduced level of consciousness . % (n= ), inability to follow command such as due to aphasia . % (n= ), seizures . % (n= ), and no reason . % (n= ). overall agreement between clinicians regarding decision of pre-procedural intubation among the case scenarios was . the decision of pre-procedural intubation varies widely among clinicians. due to recent data that suggests that decision of pre-procedural intubation may impact on patients' outcomes, better standardization of such practices is required. hyperglycemia has been shown to be associated with worse outcomes, increased hemorrhage rates, and increased mortality in patients with acute ischemic stroke (ais). we evaluated the effect of admission hyperglycemia on -day functional outcome, mortality, and hemorrhage rates in patients undergoing multimodal endovascular therapy (met) for ais. retrospective review of glucose on admission was performed in patients undergoing met between and in a tertiary care academic medical center. demographic data, diabetic status, nihss score, radiologic studies, and recanalization timi grade were analyzed, amongst other known predictors of hemorrhage and poor outcome. mean age was . + . and mean nihss . + . . hyperglycemia was present in ( admission hyperglycemia in patients undergoing met is associated with poor -day functional outcome and higher rates of in-hospital death and hi. in non-diabetic patients, hyperglycemia was only associated with increased mortality and hi. despite equivocal results for induced normoglycemia, this data justifies a prospective trial for moderate glycemic control in this patient population. previous studies suggest that low cholesterol levels are associated with higher rates of hemorrhage after acute ischemic stroke (ais). we studied the effect of serum lipoproteins and premorbid statin use on the rate of hemorrhage in ais patients treated with multimodal endovascular therapy (met). retrospective review of statin use and lipoprotein levels on admission including ldl, hdl and total cholesterol (tc) was perfomed in patients undergoing met between and in a tertiary care academic medical center. demographic data, nihss score, radiologic studies, and recanalization timi grade were analyzed, amongst other known ldl < mg/dl was associated with a higher incidence of ht (or . , % ci . - . , p= . ). hdl > was associated with higher rates of ph (or . , % ci . - . , p= . ). tc levels and premorbid statin use were not associated with higher rates of hemorrhage. statin use, ldl, hdl and tc were not independently associated with functional outcome at months. patients with hemorrhage and tc < had significantly higher rates of good functional outcome compared to those with tc > (or . , % ci . - . , p= . ). there was no significant association between statin use and rates of hemorrhage or functional outcome in patients presenting with ldl < . low ldl and high hdl levels are associated with increased rates of hemorrhage after met for ais. statin use had no effect on post-intervention hemorrhage or functional outcome regardless of admission lipid levels. despite the association between low ldl and hemorrhage, statin use in patients with a low ldl was not associated with poor outcomes. this data justifies further study of the effect of continuation and early initiation of statin therapy in this patient population. mexican americans (mas) have shown lower post-stroke mortality compared to non-hispanic whites (nhws). limited evidence suggests race/ethnic differences exist in intensive care unit (icu) admissions following stroke. our objective was to investigate the association of ethnicity with admission to the icu following stroke. cases of intracerebral hemorrhage and acute ischemic stroke were prospectively ascertained as part of the brain attack surveillance in corpus christi (basic) project for the period january, through december, . logistic regression models fitted within the generalized additive model framework were used to test associations between ethnicity and icu admission and potential confounders. an interaction term between age and ethnicity was investigated in the final model. a total , cases were included in analysis. mas were younger, more likely to have diabetes, and less likely to have atrial fibrillation, health insurance, or high school diploma than nhws. on unadjusted analysis, there was a trend toward mas being more likely to be admitted to icu than nhws ( . % versus . %; or= . ; % ci . - . ; p= . ). however, on adjusted analysis, no overall association between ma ethnicity and icu admission (or= . ; % ci . - . ) was found. when an interaction term for age and ethnicity was added to this model, there was only borderline evidence for effect modification by age of the ethnicity/icu relationship (p= . ). no overall association between ethnicity and icu admission was observed in this community. icu utilization alone does not likely explain ethnic differences in survival following stroke between mas and nhws. the medicines company, parsippany, nj, usa the relationship between blood pressure variability and inpatient outcomes and costs following ais is not well understood. using data from > us hospitals (cerner health facts®), we identified all admissions between / / and / / of - -cm diagnosis codes .x , .x ). in patients with principal diagnoses of ais, time of initial clinical presentation was designated "index time"; for those with secondary diagnoses of ais, index time was in-hospital onset of stroke symptoms. we calculated blood pressure variability (bpv) as maximum difference (md) (i.e., highest -lowest recorded bp) in the -hour period following index time. patients were igh"] vs mmhg or dys> mmhg at admission. two hundred-six patients ( male; mean age ; range - years) were evaluated. hundred and four patients ( , %) had high bp at admission. in univariate logistic regression analysis, women (p: , ), age (p: , ), tacs (p: , ), hypertension history (p: , ), ipvo (p: , ) were associated with high bp values. only tacs (or: , ; % ci: , - , ) was independently associated with high bp readings at admissions in multivariate analysis. we did not find any argument to state that high admission blood pressure is a compensatory response following brain tissue ischemia. intravenous recombinant tissue plasminogen activator (iv r-tpa) has revolutionized the management of acute ischemic stroke. however, symptomatic intracranial ( %) and severe systemic ( . %) hemorrhagic complications after thrombolysis remain a concern. we present a rare complication of r-tpa and underscore the importance of close monitoring after thrombolysis. the clinical history, laboratory, and imaging studies were reviewed. a year old man with psoriasis and morbid obesity presented with acute aphasia and right hemiplegia. he had fallen as a result, striking his right eye. his examination demonstrated right periorbital ecchymosis without ptosis, expressive aphasia, leftward gaze deviation and corresponding hemianopsia, and right facial weakness and hemiplegia. his summated nih stroke scale (nihss) was . initial cranial imaging demonstrated no blood, though did show an abnormal hyperdensity within the proximal left middle cerebral artery territory. he received iv-tpa hours from symptom onset with significant neurological improvement within minutes of thrombolysis. minutes after initiation of iv r-tpa, he rapidly developed periorbital edema with ecchymosis leading to complete ptosis of the right eye. repeat cranial imaging showed an enlarging retro-orbital hematoma. an emergent lateral canthotomy was performed of the right eye to rapidly decompress the optic nerve. within days of thrombolysis and successful orbital decompression, as visualized on repeat cranial imaging, he made near full neurologic and visual recovery. to our knowledge, this is the first reported case of a near catastrophic hemorrhagic ocular complication after iv r-tpa therapy for acute ischemic stroke. despite the suspected trivial nature of injury, thrombolytic treatment should proceed with caution in the setting of any trauma. this report highlights the importance of careful inspection and maintaining a high index of suspicion and vigilance for unanticipated complications after thrombolytic therapy. in the setting of acute or evolving stroke, outcome may be dependant on the urgent re-establishment of cerebral perfusion.options for restoring cerebral blood flow include the intra-venous or intra-arterial administration of thrombolytic agents, mechanical thrombolysis, and urgent carotid endarterectomy. there is very limited experience with emergency extracrannial-intracranial (ec-ic) bypass in this setting. we reviewed the medical records and neuroimaging studies of consecutive patients who underwent urgent ec-ic bypass in the face of acute cerebral ischemia. none were considered appropriate candidates for endovascular therapy. ages ranged from to years, average . years. average follow-up was . years. preoperative angiographic evaluation identified critical narrowing of the supraclinoid ica in , the m segment of the middle cerebral artery in , and the cervical/petrous ica in . all had progressive, refractory symptoms associated with enlarging areas of ischemic changes on diffusion-weighted mri despite maximal medical therapy including anticoagulation and antiplatelet agents, blood pressure elevation, and fluid resuscitation. all patients underwent urgent sta-mca anastomosis. in every case, bypass resulted in stabilization of the progressive ischemic symptoms; in cases, revascularization was followed by rapid, dramatic improvement of preoperative deficit. five patients awoke with transient worsening of their preoperative neurological deficit which improved over - hours. no patient demonstrated a significant new area of ischemia on mr imaging. emergency ec -ic bypass for acute ischemic injury was both safe and effective in our experience. this population was characterized by relatively young patients with severely limited collateral circulation. in this series of carefully selected patients, bypass was successful in arresting ongoing ischemic symptoms, and in some cases, resulted in rapid neurological improvement. the ability for clinicians to predict outcome is of paramount importance when treating and counseling stroke patients and families. the dragon score is used to predict outcome in patients with anterior circulation strokes that have received intravenous tpa. we sought to determine if the dragon score could be applied to patients undergoing endovascular stroke therapy. charts for patients with interventions performed by a single operator (mfs) from january to march were reviewed. presenting symptoms were used to derive the dragon score. outcome predictability was compared to the findings in the original dragon score paper. twenty-four patients underwent endovascular stroke treatment; fourteen patients presented with anterior circulation ischemic strokes. five patients had only endovascular treatment, and patients had both ivtpa and endovascular treatment. the total average time from onset to termination of the endovascular procedure was minutes. in the endovascular alone patients, patients survived with a mean dragon score of . and mean discharge mrs of . . of the patients who received both intravenous and endovascular therapy, survived with a mean dragon score of . and mean discharge mrs of . . four of the surviving patients had greater than % specificity for poor outcome (mrs - ) based on the original paper. these patients however demonstrated a good recovery with an average mrs of . . despite the extended window for treatment and recanalization, patients who receive acute endovascular stroke therapy appear to have similar outcomes to the predicted outcome using the dragon score. furthermore, our study showed that patients who were expected to have poor outcome had the potential to improve clinically. this study reinforces the benefit of endovascular stroke therapy. intracranial arterial stenosis are relatively common findings of stroke patients in asia area. we reviewed stroke database to investigate clinical risk factors related to intracranial arterial stenosis, including carotid disease, and peripheral arterial disease which reflects advanced atherosclerosis. acute stroke patients at the national health insurance corporation ilsan hospital from january to december with available transcranial doppler(tcd) examination, carotid ultrasound and ankle-brachial indexes(abi) formed the analysis cohorts. retrospective review was performed. a total of patients were included during that period, patients with incomplete tcd study due to poor insonation windows were excluded( %). according to tcd criteria, groups of intracranial arterial stenosis are defined: vessel stenosis is in patients( %), - vessels in patients( %), more than vessels in patients( %). as the arterial number of intracranial stenosis increased, abi is decreased(p= . ) and the size of carotid artery plaque is increased(p= . ). among the risk factors, diabetes, age, past stroke history are increased(p= . , p= . , p= . ) and hdl cholesterol showed tendency of decrease(p= . ). however hypertension, smoking, total cholesterol, ldl cholesterol, triglyceride and sex are not correlated with intracranial arterial stenosis. among the acute stroke patients, about a half of them have intracranial arterial stenosis and these patients tend to have higher burden of advanced atherosclerosis as evidenced by a higher prevalence of diabetes, large sized plaques of carotid artery and peripheral arterial occlusive disease. dedicated neurocritical care service in an acute-icu setting with specialized neuro nurses and physicians improves the quality of care and patient outcomes. we aimed to find out the impact of specialized focused neurocritical service as compared to a general surgical/medical icu setting in a community hospital. we retrospectively reviewed data from - , on patients who received endovascular treatment (iatpa, thrombolysis, mechanical thrombectomy, with or without intra and extra cranial stenting) in order to achieve recanalization. patients were divided into two groups: group a (n= ) general med/surg icu care in - and, group b (n= ) focused neurocritical care - . functional outcome data (mrs days) between the groups was compared through patient records. group a patients were cared for with general surgical/medical icu care nurses while group b patients were cared for by a specialized core group of - nurses specifically trained in neurocritical care. both groups were comparable in terms of age, sex, admission nihss and co-morbidities (hypertension, hyperlipidemia, diabetes, ccf, a.fib, other). group a mrs - (n= ) %, group b mrs - (n= ) %. group a mrs - (n= ) %, group b mrs - (n= ) %. group a mrs (n= ) %, group b mrs (n= ) %. mortality for both groups was comparable at % (group a n= ; group b n= ). functional outcomes of fully independent patients (mrs - ) improved from % to % when a focused neurocritical care nursing service was implemented as compared to standard medical icu nursing care. strict adherence to neurocritical care protocols and proper attention to co-morbidities is the key to improved outcomes in critically sick acute stroke patient populations. in-hospital strokes remain a significant source of morbidity for patients. paradoxical embolism has been implicated as a potential source for these strokes. to date, there is only minimal literature regarding paradoxical embolus as a cause for stroke in the hospitalized patient. over a one-year period we studied in-patient stroke alerts and their etiologies at our institution. the hypothesis of this study is that strokes in hospitalized patients are caused by paradoxical emboli. this is a retrospective analysis of prospectively collected in-hospital stroke team calls (n= ) over a one-year period. we excluded patients on the stroke service or on neurologic floors including the neurological intensive care unit. we further excluded patients that were found to have stroke-mimics by consensus. from these patients, we collected demographic information and results of transthoracic echocardiograms (tte) and lower extremity (le) duplex. the categorical data was analyzed using chi-square on jmp . . a confirmed acute ischemic stroke was found in ( %) of the in-hospital stroke alerts. the majority of stroke alerts in our institution were from the cardiology and cardiothoracic services ( . %). a tte and le duplex were available in . % and . %, respectively. two patients were identified with a patent foramen ovale (pfo) and nine with a deep venous thrombosis (dvt). one patient was found to have both a dvt and pfo which was presumed as the source of embolus. overall, there was no significant association of in-hospital stroke and presumed paradoxical embolus. the present study shows no association of in-hospital strokes and paradoxical emboli. this study is limited by the infrequent ordering of le duplexes in this at risk population but is strengthened by the available tte results. posterior circulation stroke (pcs) is associated with high mortality and poor outcome. this single centre, retrospective analysis evaluates long-term mortality and functional outcome in pcs patients treated with/without revascularization therapy (rt). between january and december , dataof consecutive pcs patients admitted to florence nightingale stroke unit within the first hours were analyzed. after evaluation with mri, eligible patients with pwi/dwi mismatch selected with eye-balling technique were treated with rt. ninety days modified rankin score (mrs) and mortality were the main outcome. eighty-two patients ( male; mean age ; range - years) were evaluated. the mean onset to door time was minutes (sd: ). seventy-eight patients were examined with mri while patients were examined with ct. twenty-one patients received rt; intravenous thrombolysis in , endovascular multimodal revascularization in and bridging therapy in patients. mean nihss score was (range: - ) [treated group (tg): ( - ); untreated group (utg): ( - ) p: , ]. arterial occlusion was present in ( %)(tg: , %;utg: , %; p: , ). mean door to treatment time was minutes (sd: ).mean onset to treatment time was minutes (sd: ).mean discharge nihss score was (range: - ) [tg: ( - ); utg: ( - ) p: , ]. discharge mrs - ratio was , % (tg: , %; utg: , %; p: , ). the inhospital mortality rate was , % (tg: , %; utg: , %; p: , ). first month (tg: , %; utg: , %) and rd month (tg: , %; utg: %). mrs - ratio (p: , vs. , respectively) also th month (tg: , %; utg: , %) and rd month (tg: , %; utg: , %) mortality (p: , vs. , , respectively) were similar between groups. in posterior circulation stroke, despite severe clinical manifestations at admission and hospital discharge, after long term follow up, the outcome in patients treated with revascularization therapy is similar to those patients with benign outcome and not necessitating any revascularization therapy from the outset. we present a case series that highlights the feasibility of decompressive hemicraniectomy (dhc) in pediatric patients with ischemic stroke. a retrospective chart review identified cases of ischemic stroke at texas children's hospital between - where dhc was performed for high intracranial pressure (icp) after standard medical therapy failed to lower icp. information was obtained about patient characteristics on admission, radiological features of the stroke, surgical procedures, complications of the dhc and cranioplasty, and clinical outcomes. we also surveyed published literature on dhc for pediatric patients with ischemic stroke. there was no mortality in this case series. case had a modified rankin score (mrs) of at a follow up visit after months. case had mrs of at a follow up visit after months. cranioplasty was complicated by epidural abscess in his case. case had mrs of at a months follow up. review of literature identified other published case series consisting of cases of dhc in pediatric patients with ischemic stroke. detailed analysis of these cases is presented in the tabular form. this case series highlights the fact that dhc can be performed safely and effectively in pediatric patients with ischemic stroke with potential lifesaving and improved functional outcome. decompressive hemicraniectomy should be considered as a therapeutic option for refractory elevated icp following large hemispheric strokes in the pediatric population. basilar artery occlusion (bao) is a devastating neurological disease that can be difficult to diagnose due to its protean manifestations, and the initial ct will often not reveal an acute infarction. we present a patient with bao who was initially diagnosed with lyme disease. a y/o female presented with neck pain, an unsteady gait, partial facial paralysis, and mild dysarthria. she was noted to have an erythematous area on her neck that contained a tick. the initial head ct was negative. lyme disease was diagnosed and ceftriaxone and doxycycline were initiated. within hours, her symptoms progressed to hemiparesis and aphasia. a stat mri demonstrated the absence of flow in the basilar and left vertebral arteries with restricted diffusion in the pontine and mid-right parietal regions. the patient was transferred to a primary stroke center, but she was outside the window for stroke rescue. acute lyme disease is characterized by lymphocytic meningitis, cranial neuropathy (particularly facial palsy) and radiculoneuritis. though these symptoms usually take weeks to occur, the initial tick bite may not be recognized thus precluding an accurate evaluation of the time course. bao may present with a similar constellation of symptoms including headache, facial paralysis, and transient paresis called the "herald hemiparesis" of bao. the fluctuating course of early bao may be confusing and a high index of suspicion is required. intra-arterial lytic therapy, mechanical thrombolysis, or a combination is recommended up to hours of symptom onset. recanalization is paramount to preserving neurologic function. unfortunately, she arrived at our institution outside the window for invasive therapy. her symptoms continued to progress to a locked-in state and she was transferred to a ltac facility. the neurological manifestations of bao may be confused with other diagnosis and a high index of suspicion is required. metabolic abnormalities negatively influence outcome in patients with traumatic brain injury, subarachnoid hemorrhage, hemorrhagic stroke and ischemic stroke with or without thrombolytic therapy. the prognostic value of many potentially correctable physiologic markers in stroke patients receiving thrombolysis is unknown. twenty-one consecutive acute ischemic stroke patients treated with tissue plasminogen activator (tpa) were retrospectively studied. multiple metabolic and physiological variables including blood urea nitrogen, creatinine, sodium, potassium, chloride, calcium, phosphorous, magnesium and body temperature were analyzed. independent t test was used to compare mean scores of these variables and determine their effect on outcome. functional status at discharge was the primary outcome measure, being fully or partially independent determined as good outcome and fully dependent or dead as poor outcome. secondary outcome was the presence of hemorrhagic conversion. seventeen patients had good outcome, mean age , while patients had poor outcome, mean age . hyperthermia and admission acute physiology and chronic health evaluation (apache) ii score were associated with poor outcome (p< . ). hemorrhagic conversion occurred in patients and was associated with hyperthermia, higher simplified acute physiology score (saps) ii score and hyponatremia (p< . for all). this single-center, retrospective study suggests that mild hyperthermia, hyponatremia and higher apache ii and saps ii scores are associated with poor functional outcome and hemorrhagic conversion in patients with acute ischemic stroke treated with tpa. further study is required to determine if correcting these variables influences outcome. alterations in electrolyte balance and other basic physiologic indicies such as glucose have been implicated in the pathophysiology of coronary heart disease. however, the relationship between the electrolyte levels and other physiologic indicies measured immediately after an acute ischemic stroke has not been clearly delineated. objective: the aim of the present study was to test whether changes in a patient's basic metabolic panel modify the severity or outcomes of acute ischemic stroke. the study is a retrospective study on ischemic stroke patients admitted to a university affiliated community hospital. demographic data were collected from the data registry. values were obtained within one hour of presentation for serum sodium (na), potassium (k), glucose (gluc), chloride (cl), magnesium (mg), bicarbonate (hco ), bun, and creatinine (cr). as well glomerular filtration rate (gfr) and temperature values were also recorded. severity and outcome were measured using the nihss on admission and the mrs on discharge respectively. correlation coefficients (spearsman's rho) and the mann whitney test were employed in the analysis of the data. spss version was utilized for data processing. results consecutive acute ischemic stroke patients met the study criteria. serum ca (p= . , r= - . ) and gluc levels (p= . , r= . ) were significantly correlated with the mrs. serum cl, ca, bicarbonate, temperature and bun were significantly correlated with nihss on admission measurements (p= . , . , . , . ; r= . , - . , ; . ; . respectively). mg showed a negative trend of correlation with the nihss on admission as well (p= . ; r=- . ), suggesting a protective effect of higher mg levels. the study shows that initial metabolic parameters, such as serum mg, ca, hco , bun, and temperature may potentially allow for early prediction of the severity and outcome in patients with ischemic stroke. hypersomnolence is not typically appreciated as a focal neurologic finding, though bilateral thalamic infarcts may present with hypersomnolence as the only neurologic manifestation. a year old man presented with acute onset confusion, somnolence and slurred speech. his neurological examination was notable for somnolence, bilateral ptosis and dysarthria. routine laboratory investigations and csf analysis were unremarkable, aside from a urine toxicology screen which was positive for opiates. initial head computed tomography (ct) with ct angiography of the head and neck were unrevealing. magnetic resonance imaging was contraindicated as the patient had an automatic internal cardiac defibrillator (aicd). a working diagnosis of opiate intoxication was made in light of the urine toxicology results. because the patient failed to improve over the ensuing hours, a repeat head ct was obtained which revealed bilateral medial thalamic infarctions. while hypersomnolence is often associated with toxic-metabolic disorders, it may rarely be the result of acute arterial stroke. in the context of stroke, hypersomnolence can be accompanied by other symptoms including weakness, paresthesias, memory impairment, sectoranopsia, and personality changes. the feature of hypersomnolence is usually the result of an infarct of perforators arising from the posterior cerebral artery, specifically the paramedian,and tuberothalamic arterial branches, which are involved in irrigation of the reticular, and intralaminar nuclei of the thalamus that are involved in arousal. concomitant neurologic signs may not be present or may be difficult to elicit in this setting as patients are often unable to participate in the neurologic exam. acute stroke should therefore be considered in the differential diagnosis of hypersomnolence. failure to consider stroke as a potential eitiology may lead to delay in acute or secondary stroke prevention. metals play key roles in epigenetic events in living organisms. zinc, cadmium, lead, selenium, calcium, magnesium, sodium, and potassium have been found to be associated with stroke risk in nhanes and other studies. the central hypothesis of this pilot study is that metals and metalloproteins may determine and distinguish stroke phenotype (ischemic vs. hemorrhagic). stroke patients at the university hospital emergency department (ed) were enrolled in a plasma banking project. after irb approval and informed consent, blood draws were performed in the ed, and demographic and clinical information recorded. we analyzed plasma samples collected within hours of symptom onset. we used the proteomic techniques of affinity chromatography (to remove the abundant proteins albumin and igg), followed by size exclusion chromatography (sec -to eliminate low molecular weight compounds and fractionate the proteins), inductively coupled plasma mass spectrometry (icpms -to identify differentially expressed metalloproteins in plasma) and electrospray mass spectrometry (to identify the tryptic peptides known to represent specific proteins in the plasma). the areas and standard deviations of the chromatograms for the metalloproteins for stroke mimics (n= ), ischemic (n= ) and hemorrhagic (n= ) stroke patients were calculated using origin software. differences between sec-icpms peak areas of the metalloproteins for the ischemic, hemorrhagic and mimic samples were examined using two-sample t-test and box chart statistics. mg, al, mn, cu, zn, se, mo and pb were studied. significantly different metals were mg, al, mn, cu and se. box chart statistics performed for the sec-icpms metalloprotein peak area data revealed significant differences in all metalloproteins except al. tryptic peptide mapping identified significant differences in metalloproteins. sec-icpms detected differences in fractions of specific metal containing proteins in the plasma of stroke patients and patients who presented with a stroke mimic. ongoing efforts are aimed at identifying potential biologically relevant stroke biomarkers from the current list of differentially expressed proteins. retrospective chart review of patients admitted to the neurocritical care unit from august to august who developed icp crises (> mm hg for > minutes) and were treated with . % hts. only data for the first ever treatment with hts were collected. patient demographics, onset and duration of action, lowest icp achieved and use of adjunctive therapies were recorded. descriptive statistics and correlation analysis were performed. complete data were available for patients. ten subjects ( %) were female, the mean age was + years. glasgow coma scale (gcs) was + and ( %) patients concomitantly received therapeutic hypothermia and pentobarbital coma. a + . % reduction in icp following administration of . % hts was observed (absolute change: + . mmhg). the mean time to icp < mmhg was + minutes and time to rebound icp > mmhg post-hts administration was minutes in % of our cohort. following treatment the mean improvement in gcs was + . a dose-response curve was generated. . % hts was associated with a % reduction in icp values in critically ill neurology/neurosurgery patients. time to clinical endpoint of icp < mmhg was minutes and in % of patients the duration of action was minutes. an improvement of points in gcs was also observed. the first description of a dose-response curve for . % hts in humans is reported. over a ten year period, we accumulated a prospective dataset of severely brain injured patients with multimodality monitoring (brain tissue oxygen monitoring and outcomes project). patients' data existed within individual excel files with heterogeneous fields. as different research subprojects arose, additional excel files were created to support new data extraction from clinical records. several issues were apparent: ( ) merging and querying data was time-consuming and rate-limiting in research productivity; ( ) users were unable to make uniform changes to all files; ( ) different users could not simultaneously enter data, ( ) auditing data entry was difficult. our goal was to convert the dataset into a relational database, to enhance clinical research efficiency. microsoft access was used to build a database with a relational backend structure and a graphical user interface (gui) frontend. a reporting tool was built for analysis, preview, printing, and customized queries. extract-transfer-load functions were programmed to create seamless data integration between the access database and the enterprise-wide clinical data warehouse (e.g. laboratory values, radiology results). it took approximately man-hours to audit existing excel data, and to load distilled data from excel files into structured database tables. it took approximately man-hours for application implementation and testing. the gui supported multiple simultaneous users' during data auditing, enforced validation rules that corrected data entry in realtime, and centralized user account management. we have provided research queries to date. excel has limitations as a tool for clinical research informatics. a relational database that is built with pre-defined rules, fields, and tables dispenses with the time-consuming step of merging and cleaning data and makes large dataset queries and analyses more efficient. it allows straightforward integration with other relational databases such as enterprise-wide clinical data warehouses, enabling expansion of queries into other clinical information systems. financial support: elsa lin is a data analyst whose salary was partially supported within the past twelve months by a grant from integra (brain tissue oxygen monitoring) for the specific purpose of creating a relational objective of this case study is to report a case of central nervous system (cns) histoplasmosis presenting as an ischemic pontine vasculitis and chronic basilar meningitis. histoplasmosis, a disease caused by fungus histoplasma capsulatum, primarily affects immune-suppressed patients and commonly involves the lung but occasionally can have variable cns presentations. a thirty-five year old caucasian immune-competent male came with worsening of aphasia and confusion after having presented four weeks prior with dysarthria, gait ataxia and bilateral upper extremity weakness. he was diagnosed with bilateral pontine ischemic strokes secondary to small vessel vasculitis and but had limited response to high dose steroids. cerebral spinal fluid (csf) examination showed elevated protein, low glucose and elevated cells suggestive of meningitis and he was started on empiric antibiotics and trials of repeat intravenous (iv) steroids. follow-up imaging revealed obstructive hydrocephalous and he underwent successful ventriculo-peritoneal (vp) shunt placement. his csf culture came back positive for h. capsulatum. csf histoplasma antigen and urine antigen were also positive. he was initially treated with ambisome but changed to voriconzaole secondary to renal insufficiency and was eventually continued on itraconazole. at one year, the patient good clinical improvement and follow-up cultures were negative. while pulmonary involvement of histoplasmosis in immune-suppressed patients is common, systemic presentation of this fungal infection in immune-competent patients is exceeding rare. clinicians should consider cns histoplasmosis on the differential diagnosis in atypical stroke cases, particularly those with chronic basilar meningitis. there is increasing incidence of dengue fever in our country and encephalopathy is the most common neurological manifestation of severe infection. however, recent studies have shown that there is increasing evidence for dengue viral neurotropism. dengue encephalitis, a distinct clinical entity have been found to be associated with the neurovirulence involving serotypes den- and den- . the objective of this study is to report the clinical course, laboratory, and radiographic findings of dengue encephalitis that did not go through the usual state of dengue fever. management of this specific viral infection will likewise be discussed. case presentation and report with literature review. a -year old filipino male, methamphetamine and marijuana user was admitted to our hospital because of seizures preceded by headache and fever. he was managed as a case of viral meningitis supported by cranial mri findings and csf studies. after nearly days, he clinically deteriorated initially from a very agitated, restless and combative state progressing to frank stupor. body temperature was uncontrollably high. repeat csf studies revealed elevated pressure, lymphocytosis, normal protein and sugar, and positive igm dengue virus. serum study for dengue virus igm capture elisa was also positive. other significant tests ruled out malaria, hiv and nmda antibody as source of encephalitis. after intravenous steroids were started, on top of antipsychotics, clinical symptoms were noted to eventually resolve. we theorize that dengue encephalitis should be considered in the differential diagnosis of acute viral meningoencephalitis though the classical manifestations of dengue may not exist. while dengue infection may be endemic in asian countries, this should be considered in other parts of the world especially when patients rapidly deteriorate in the course of the disease. immunecompetence definitely play a vital role in the recovery. steroid therapy may be life saving in very severe cases. intracranial monitors can help guide the care of patients with severe brain injury. the devices are invasive and so may be associated with complications. furthermore, accurate interpretation of the monitors' data is needed to be of potential benefit. in this study we asked whether experience influences "device failure" or interpretation. retrospective analysis was performed on a prospective database that included patients (median age ; range - ) with severe brain injury and who received intraparenchymal multimodality monitoring through a triple lumen bolt (licox imp#). a total of triple lumen bolts were placed during an -year period. device failure was defined as: ) broken or bent (n= ; . %); ) improper placement (n= , . %); and ) ineffective (no response to o challenge n= , . %). there were ( . %) devices thought to provide "incorrect" data but subsequently were found to be accurate, i.e. improper data interpretation. there was a decline in device failure over the entire study period. each calendar year was divided into quartiles. device failure incidence was %, %, % and % per quarter, i.e. was greatest during the third quarter during the time of academic and staff changeover (or . ; p = . ). in addition, improper data interpretation was greatest during the rd quarter. our data suggest that experience with multi-modality monitors is associated with a reduced incidence of device failure or improper data interpretation. educational efforts may reduce the need for device replacement. financial support: peter leroux funding from integra for research. while efforts to "go green" and promote sustainability are well-established in many sectors, there has not been an adequate push toward such practice in the healthcare and medical fields. healthcare accounts for % of all commercial energy use, bil pds of waste, and % of greenhouse gas emissions in the us. these figures requires significant for efforts to be implemented; we each subscribe to, "first, do no harm" demands that these negative environmental impacts be addressed and mitigated immediately. the intent of this report is to investigate and analyze the opportunities the healthcare industry has to embark on sustainable practices. we analyzed green architecture for new healthcare campuses and renovation of outdated facilities, submit efficiency and cost analyses of disposable versus reusable textiles, and offer observations on innovative technologies being developed to promote sustainability. this study was conducted after an extensive review of published literature, verified statistical reports presenting the cost-effectiveness and improved efficiency of pursuing an sustainable model of healthcare delivery. in cluded is a cradle-to-grave analysis of multiple facets of the healthcare/sustainability field, and addresses a number of specialist-specific avenues, including critical care and anesthesiology. energy-efficient building options -including rooftop gardens and alternative power sources -can cut energy consumption by %. healthcare providers in all fields are making efforts toward lowering the carbon footprint of hospitals by reducing greenhouse gas emissions and utilizing resourcing, second use and extensive recycling techniques and efforts. extensive life cycle assessments (lcas) prove that reusable medical textiles and tools are dramatically less expensive environmentally and financially than their disposable counterparts. while efforts are being made to promote sustainability in healthcare, more must be done. the evidence is clear: environmentally-conscious endeavors save money and help lessen the stress placed on the environment. for such a heavy-hitting culprit of consumption, the healthcare industry simply must begin implementing "green" practices based on already-present data. standard metabolic prediction equations have been validated in general critical care populations, but have not been well studied in the neurologically critically ill. we sought to determine whether: ) standard prediction equations accurately predict caloric requirements in neurocritical care patients; ) variation in resting energy expenditure (ree) exists among different subpopulations of neurocritical care patients; and whether the same factors influence ree among different neurocritical care subpopulations. indirect calorimetry measurements were retrospectively reviewed for mechanically-ventilated patients admitted to the neuro icu from january to june . the measured ree data were compared to the predicted basal energy expenditure (bee) calculated with the modified penn state university (psu-m) equation. patients were classified into neurological subtypes, stroke (n= ), status epilepticus (n= ), and other (n= ). traumatic brain injury (tbi) patients were not included. of the entire cohort, median measured ree was (iqr - ) kcal/d and median predicted bee was (iqr - ) kcal/d. the predicted bee correlated well with the measured ree (coefficient . ; p< . ) in the overall cohort. there was no significant difference in the predicted calorie requirement for stroke or status epilepticus. however, there was a suggestion that patients with status epilepticus were relatively hypometabolic (defined as ree < % of the predicted bee) compared to other subgroup populations [or= . ; % ci ( . - . ); p= . ]. factors significantly associated with ree include: maximum hour temperature, administration of intravenous sedation, body mass index (bmi) and sex. age and hospital day of ree were not predictive of energy expenditure. the psu-m predictive equation accurately estimates caloric needs for patients with non-tbi neurological injury. patients with status epilepticus may be hypometabolic relative to other neurologically injured patients, which may be due to use of multiple sedatives in this subpopulation. further research is needed to confirm these findings. the american society of anesthesiology provides guidelines for preoperative fasting for healthy patients undergoing elective procedures. these guidelines are often extrapolated to the critically ill population for procedures and extubation. we tested the hypothesis that npo practice differs between subspecialty, institution and practitioner-type. after irb approval, we conducted surveys of the memberships of the society of critical care medicine (sccm), neurocritical care society (ncs), and american burn association (aba) regarding their npo practice in critically ill patients. survey questions included frequency of use of nasogastric (ng) vs. nasoduodenal (nd) tubes, npo time prior to procedures, and npo time prior to extubation. responses were analyzed with stata . , using a one-way analysis of variance by ranks. we received a total of responses ( % response rate) encompassing practitioners from medical, surgical, neurosurgical ( responses), pediatric, cardiac, burn, trauma, and multidisciplinary icus. respondents ( . %) report % use of ng tubes, whereas ( . %) report % use of nd tubes. excluding responses from pediatric icu practitioners, the npo practice in nicus for intubated and non-intubated patients with nd tubes undergoing procedures is similar to respondents from other icus except the burn icu (p< . ). there is no difference in npo practice of patients with ng tubes undergoing procedures across all icus. nicu respondents report the most commonly used npo time prior to procedures is hours for intubated patients with nd tubes ( . %) and hours for those with ng tubes ( . %). for burn icu respondents, the most commonly reported npo time for intubated patients with nd tubes prior to procedures is hours ( . %), while hours is reported for those with ng tubes ( . %). npo practice in critically ill patients varies across the subspecialty units. further research is necessary to develop evidence-based guidelines for npo practices in the critically ill patients. patients intubated for primary neurological reasons represent a unique critically-ill population. extubation failure rates in primary brain injury (pbi) patients are - % compared to - % in the general critical care population. these populations have never been directly compared. we hypothesized that intubated pbi patients would have higher rates of extubation failure compared to non-pbi patients. retrospective cohort of intubated patients admitted to the medical intensive care unit or the neurocritical care unit in a tertiary-care university hospital between october , and september , . extubation failure was defined as requiring endotracheal intubation at hours, hours and one week. of the . failing extubation at hours did not put patients at increased risk for vap. total ventilator days were similar between pbi and non-pbi patients. pbi patients who failed at hours did not have a significant increase in ventilator days, intensive care unit days or mortality. our data indicates pbi patients are at increased risk for extubation failure compared to non-pbi patients. future prospective study is warranted to determine predictors of extubation failure at hours in pbi patients. peripherally inserted central catheters (picc) is been routinely used instead of central venous catheter (cvc) in our intensive care unit (icu) patients, that includes critical neurologic/neurosurgical patients. there are a number of studies has been done to evaluate risks of picc placement in general medical and surgical icus. a retrospective analysis to determine risk of large vein thrombosis due to picc in neurologic sub-population of patients in a general medical/surgical icu. charts and venous ultrasound studies of patients admitted to icu primarily for neurologic condition were reviewed. out of consecutive patients, underwent picc insertion. ( . %) had clinical and ultrasound evidence of large venous thrombosis attributed to picc. the presence of a picc line conferred a relative risk of . for the development of a dvt. patients with picc lines had a longer duration of stay in the icu (mean days = . +/- . ) when compared to patients without picc lines (mean days= . +/- . ) t( ) = . , p <. . routine placement of picc instead of cvc is associated with increased risk of thrombotic events in large veins in neuro critical sub population of a general icu, which may be associated with longer icu stay. more caution should be exercised before routinely using picc instead of cvc. there are many potential obstacles to guideline adoption and compliance in clinical practice. the purpose of this research was to develop a computer-readable format for clinical pathways, guidelines, and research protocols such that they could be rapidly distributed, displayed at the bedside, and driven by patient context. the goal is to increase guideline compliance and reduce errors made at the bedside. we collected institutional clinical practice guidelines from the abstract authors, guidelines from professional societies (including the neurocritical care society), and one multi-center research protocol (boost-ii). we analyzed each to look for common constructs that would form the basis of a computer-readable care path "language". we also reviewed previous attempts at computer-readable guidelines to discover what might be applicable to our system. the analysis showed considerable variation in the way guidelines are put to practice at the bedside. despite this, we found a set of generalized patterns that were used to develop a care path representation (language) that could encapsulate the content of the guidelines. structured goal-oriented steps, alarm and time couplers, and a "monitoring cycle" were designed and represented in an xml-based language. a scripting method for decision logic also was developed. software was written to read the xml script, display the care path "flow-chart", provide interaction with the health care provider, and links to related instructional content. integration with real-time multimodal monitoring data allows the care path to be driven by the context of the patient. this abstract outlines the first part of a larger project to develop an open-standard guideline format and display software that will decrease the time to adoption of neurocritical care guidelines and increase compliance in clinical practice. financial support: funding received by moberg research from nih/ninds and us army/tatrc to carry out this work. one of the authors (r moberg) is president and owner of moberg research. the objective of this study was to develop empiric treatment guidelines for patients admitted to the neurosciences intensive care unit based on unit specific antimicrobial surveillance. a prospective chart review was performed from october to april of all adult patients admitted to the neurosciences intensive care unit with positive cultures from any site. in addition to culture data and antimicrobial sensitivities, time of admission, diagnosis, placement of an external ventriculostomy device (evd), duration of cefazolin prophylaxis and risk factors for healthcare-associated infections (hai) were collected. hospitalization within days, residency in an extended care facility or hemodialysis at the time of admission were considered hai risk factors. cultures were analyzed as those occurring before or after day of nicu stay. patients residing in the unit as a result of overflow were excluded. a total of patients and positive culture results were included and analyzed by duration of icu stay < days (n= ) or > days (n= ). evd placement and cefazolin prophylaxis were present in % of patients for a mean of . days. at < days, methicillin-resistant staphyloccous aureus (mrsa) was the most common pathogen in patients with risk factors for hai. at < days without risk factors, the most common pathogens were methicillin-sensitive staphylococcus aureus (mssa) (n= ) and enterobacter (n= ) in the sputum and enterococcus (n= ) in the urine. a further analysis revealed theseisolates emerged after day of admission in patients receiving cefazolin prophylaxis. beyond days, sputum isolates predominated and consisted of gram negative pathogens (n= ), mssa (n= ) and mrsa (n= ). selective pressure from cefazolin prophylaxis was apparent in unit surveillance and emerged at or after days. based on these results, institutional empiric antibiotic treatment regimens were adjusted to cover these pathogens after day of nicu stay. the direct thrombin inhibitor dabigatran etexilate is approved for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. despite the clinical benefits of dabigatran, hemorrhage remains a feared complication due to the lack of reversal agent and limited experience with interventions to reverse dabigatran's anticoagulant effect. in addition, reliable laboratory tests to measure the degree of anticoagulation associated with dabigatran are not widely available. an interprofessional team developed institutional protocols for the management of dabigatran and dabigatran-associated hemorrhages. clinical and neuroimaging data was collected from four patients with dabigatran-related subdural hematoma, subarachnoid hemorrhage and/or intracerebral hemorrhage who were treated between november and april . data collected includes age, gender, past medical history, renal function, coagulation and hematology parameters, computed tomography findings, blood products or clotting factors administered, and hemodialysis parameters, if applicable. the patients ranged in age from - years. all patients were inappropriately prescribed dabigatran due to age over years, renal insufficiency, increased bleeding risk, and/or an unlabeled indication. serial evaluation of each patient's coagulation assays was conducted in order to quantify the degree of anticoagulation. three of the four patients received emergent hemodialysis and one patient received recombinant activated factor vii. two patients received blood products, including ffp and platelets, with no observed clinical change. all patients survived to hospital discharge. though this case series is small, it demonstrates the importance of thoroughly evaluating a patient's renal function, bleeding risk, and concomitant medications to determine the appropriateness of dabigatran therapy. it is imperative for clinicians to understand dabigatran's pharmacokinetics and recognize the major factors that increase dabigatran exposure. increased age and renal insufficiency seemed to play a significant role in the hemorrhagic cases we encountered. post-surgical cerebral venous sinus thrombosis is extremely rare. the management of this complication is challenging for neurointensivists; since anticoagulation may increase the risk of bleeding after craniotomy. a previously healthy, year-old male was found to have a right cerebellopontine angle mass on brain magnetic resonance imaging (mri) during headache evaluation. he underwent a prolonged surgery with retrosigmoid craniotomy and resection of an acoustic schwannoma in left lateral decubitus position. immediately post-operatively, the patient had a seizure. brain ct-scan showed hyperdensity in the right transverse sinus suggestive of thrombus. cerebral angiogram confirmed occlusion of the superior sagittal sinus (sss) torcula and bilateral transverse sinuses. intravenous heparin was initiated; however, due to further deterioration with brain herniation, endovascular administration of tissue plasminogen activator (rt-pa) assisted with thromboaspiration with penumbra catheter was performed, followed by continuous infusion of rt-pa ( mg/hr) via microcatheter in the sss for days. a repeat angiogram showed near complete recanalization of the sinuses. heparin was continued, but he developed heparininduced thrombocytopenia, and was switched to bilvalirudin. his hospital course was complicated with intraventricular hemorrhage, acute respiratory distress syndrome, methicillin-resistant staphylococcus aureus (mrsa) bacteremia, and takasubo's cardiomyopathy. he had residual right facial nerve palsy and hemiparesis related to pontine ischemia. his prothrombin gene mutation was positive for one copy. he was ambulating with assistance prior to discharge to acute inpatient rehabilitation. cerebral venous sinus thrombosis is a rare complication of retrosigmoid resection of cpa tumor. aggressive treatment with endovascular rt-pa administration into the venous sinuses may be life-saving, but carries significant risks in the fresh post-operative period. many lives have been lost due to the loss of the airway in critically ill patients. the introduction of the video laryngoscope has been a useful tool that has saved many lives in recent years. one of the limitations of the video laryngoscope is that despite being able to see the vocal cords and the airway beyond it may be difficult to advance the endotracheal tube into the airway. we present a novel approach using a bougie to simplify this problem. a cohort of ten patients in a community critical care unit with difficult airways were intubated using this new technique in a nonrandomized fashion over a period of six months. a video laryngoscope was used in each case with patients sedated and paralyzed with usual agents used for rapid sequence induction. historically, the bougie when used with standard laryngoscopes is introduced into the airway by line of sight and the endotracheal tube is advanced over the bougie. with a video laryngoscope a direct line of sight is not available and passing the bougie is challenging because of a degree angle from the open mouth to the airway. this new technique involves lubricating both the metal stylet with the degree turn and a french x cm bougie and advancing them to the end of the endotracheal tube. the bougie is then advanced into the airway through the endotracheal tube under direct vision through the video laryngoscope. the endotracheal tube is then advanced into the airway over the bougie. all ten patients were intubated without difficulty and without complication. this new technique should be considered as an option in securing the airway in critically ill patients. further validation testing by other investigators is warranted regarding this new technique to determine if a randomized controlled trial is justified. francis r. ventilator-associated pneumonia (vap) remains a problem in traumatic brain injury and high-risk surgery patients. we use early non-bronchoscopic broncho-alveolar lavage (screening-bal) in the surgical intensive care unit (sicu) to identify ventilated patients with bronchiolar bacteria prior to hours. we reviewed results of these screening-bals in neurotrauma patients from / to / . all ventilated patients in the sicu underwent screening-bal - hours after intubation; quantitative cultures (> cfu/ml) were used to identify positive specimens. clinical pneumonia was defined as clinical pulmonary infection score (cpis)> and subsequent positive diagnostic-bal. continuous and dichotomous data were compared from the screening-bal results and clinical diagnosis of pneumonia. screening-bals were performed in neuro-trauma patients (mean iss . ± . ) with an average head abbreviated injury score (hais) of . ± . . thirty-three of these were positive for organisms ( %). twenty-four clinical pneumonias were diagnosed and in of these patients the causative organism identified was the same organism in the screening-bal ( . % agreement; kappa . ; p = . ). one patient with a negative screening-bal developed clinical pneumonia. the median day to develop pneumonia was . ( , ). the hais was higher in patients with a positive screening-bal ( . ± . vs. . ± . ; p = . ). there were no significant differences in the age, icu length of stay, iss, or hais in patients with a positive screening bal vs. the patients that developed a clinical pneumonia. positive screening mini-bal results are associated with the development of vap by the same organism. screening bal in neuro-trauma patients may be a mechanism to identify patients who are at-risk for developing pneumonia later in their hospitalization and early identification of the causative agent. further studies are warranted to determine if intervention on these results changes clinical course. human rabies is a relatively rare disease in the united states, with approximately cases diagnosed annually. the most common exposure in the u.s. relates to bats, however canines and other animals have also been implicated. the typical incubation period from exposure to development of symptoms is - months, while periods of up to years have been described. we present an atypical case of human rabies presenting after a prolonged incubation period in the united states. we describe a case of a year old brazilian man without prior medical history who presented with progressive sensory symptoms leading to encephalopathy and ultimately death. extensive workup revealed no other causes of his symptoms, and brain tissue samples sent to the cdc at the time of his death confirmed a diagnosis of rabies by direct fluorescent antibody testing. in addition, sequencing of the virus confirmed a variant found in canines in brazil. the patient had not traveled to brazil in over years, and had no confirmed exposure other than an encounter with a wild dog in brazil without reported bites or scratches before immigrating. because the viral genotype has not been previously identified among animals in the united states, this case represents the longest confirmed human rabies incubation in the united states to date. characterization of the illness revealed loss of evoked potentials, electroencephalography amplitude attenuation, mr spectroscopy changes of the deep nuclei, and an atypical inflammatory response on pathologic testing. we speculate that either an atypical immunologic response or the patient's recent anabolic steroid use may have mediated delayed progression. this case underscores the importance of keeping human rabies in the differential diagnosis of rapidly progressive encephalomyelitis, even without an exposure history, or with a remote exposure history. the full outline of unresponsiveness (four) score has been validated as an alternative to the glasgow coma scale (gcs) in the evaluation of stuporous and comatose patients and predicts long-term outcomes. the utility of serial four score and gcs by nurses in detecting changes in neurologic exam in the neurocritical care unit (nccu) and whether high frequency monitoring after the first assessment is beneficial has not been studied. the electronic charts of consecutive patients with surgical and non-surgical brain pathology admitted to a nccu were reviewed, yielding observations of gcs, fourscore, and cranial nerve assessments. changes in neurologic exam promoting notification of a provider were abstracted from nursing notes. of patients (m:f: : , age: + yrs), had semi-elective neurosurgery, -ischemic/hemorrhagic stroke, encephalopathy/infection, -subarachnoid hemorrhage, -traumatic brain injury, -seizures, -other. admission median gcs was (iqr- ); median fourscore was ( ). comparison of q - h fourscore vs. qdaily fourscore readings showed no significant difference in fourscore by frequency of measurement (p= . ). in occurrences of change in neurologic exam resulting in provider notification, changes in mean fourscore and gcs from hours prior to the event were . (sd- . ) and . ( . ) respectively; p= . ). from hours prior to event, changes in mean fourscore and gcs were . ( . ) and . ( . ) respectively; p= . ). in one cerebral herniation event, neither scheduled fourscore nor gcs changed. use of the fourscore for serial monitoring and early detection of worsening of neurologic condition performs similarly to gcs and is less sensitive than subjective assessment of trained nccu nurses. the utility of incorporating the fourscore into the on-going nursing assessment paradigm of all nccu patients requires further evaluation. there may be subsets of patients or conditions (with lower sumscores than in our cohort) for which daily or more frequent monitoring has predictive value. a technique for real time, non-invasive blood flow monitoring would be a major asset to clinicians in neurocritical care. we studied the ability of a new hybrid technology employing ultrasound tagged near infrared spectroscopy (ut-nirs) to detect changes in cerebral blood flow (cbf) as compared to measurements by xenon single photon emission computer tomography ( xe-spect). twelve healthy volunteers were enrolled in the study. a cerox monitor (ornim medical ltd. israel) provided continuous ut-nirs monitoring of regional tissue oxygen saturation (sto ) and regional cerebral blood flow index (cfi). xe-spect (ceraspect; dsi, waltham, ma, usa) was then used to measure cbf at baseline, minutes and minutes after acetazolamide injection. ten subjects completed the study. significant increases in cbf as measured by both ut-nirs cfi and xe-spect cbf were noted minutes after acetazolamide injection. at minutes following injection, xe-spect cbf had returned to baseline while ut-nirs cfi remained elevated compared to baseline. a significant correlation between ut-nirs cfi and xe-spect cbf values was found at minutes but not minutes after acetazolamide injection. specificity and sensitivity for detecting an increase in cfi following acetazolamide injection were calculated using a receiver operating curve (roc), with an area under the curve of . (+/_ sem . ). no statistically significant changes in ut-nirs sto were noted following acetazolamide injection. ut-nirs cfi can detect increased cbf following acetazolamide injection, correlates with a gold standard, xe-spect, and the roc curve analysis demonstrates excellent discrimination. the difference in the measurements at minutes may be explained by different ratios of gray matter to white matter in the regions of interest as assessed by the two techniques. ut-nirs cfi can be more sensitive to changes in cerebral perfusion than simple regional tissue oximetry. financial support: dr gress is a member of the scientific advisory board of ornim medical ltd and holds stock options in the company. level of coma has traditionally been measured clinically (e.g. glasgow coma scale, four score, etc.), or with neurodiagnostic tests (e.g. eeg). developing more objective, longer term measures of coma could improve quantitation of arousal and modification of response to therapy. we used a post-cardiac arrest (ca) rodent coma model to test -d bodily acceleration as a wireless, continuous measure of early movement during coma arousal, and compared it to eeg based markers validated previously. five adult wistar rats (male, - gms) underwent eeg electrode implantation wk prior to asphyxia-induced min ca. four hours after resuscitation, rats were attached to a wireless eeg-accelerometer system. wideband and sub-band eeg were analyzed to yield iq, an entropy based and previously validated measure of coma arousal. we defined activity as the variability in -d acceleration as quantified by the standard deviation of acceleration. we found a significant positive linear correlation between accelerometer activity and full band eeg iq (r= . ± . , mean ± sd). when eeg sub-bands were divided into two categories ( . - hz and - hz), accelerometer activity had better correlation with higher frequency sub-bands (r= . ± . vs. r= . ± . ). during individual sub-band analysis, we were able to find a moderate correlation with the higher frequency iq - hz (r= . ± . ). these results suggest that -d acceleration based activity, measuring early subtle movements during coma arousal, correlates with eeg iq. this relationship was stronger for higher frequency sub-bands. this suggests that subtle motor activity quantitated by an accelerometer may be an acceptable indirect measure of arousal. such accelerometer-based systems also have the advantage of being more objective and affordable while also offering longer term monitoring. therefore, accelerometer-based monitoring for coma arousal may have clinical applicability in intensive care units. recent literature emphasizes the impact of vancomycin concentrations on patient outcomes, especially in serious infections such as central nervous system infections (cnsi) and pneumonia. achieving adequate concentrations is challenging in the critically ill due to changes in volume of distribution and clearance. we investigated the impact of a pvds in our neurologic units. retrospective chart review comparing outcomes of pvds (rph-group) to pre-implementation control group (md-group). adult inpatients receiving vancomycin on neurologic units (neuro icu and floor) were included in a month pre/post period. rph-group patients receiving vancomycin not consulted to pvds were excluded. outcomes evaluated number of vancomycin levels and proportion within goal range ( - mcg/ml). in md-and rph-groups, and patients were enrolled, respectively. rph-group had a higher percentage of patients with weight > kg and crcl > ml/min. icu patients accounted for % and % of the md-and rph-groups, respectively. common indications were cnsi and pneumonia in both groups. levels were drawn in md-group versus levels in rph-group. a higher percentage of levels were within goal range in rph-group ( %) versus md-group ( %, p = . ). amongst patients with cnsi, rph-group had a higher percentage of levels within goal range ( % vs. %, p = . ). icu patients in rph-group had a higher percentage of levels within goal range ( vs. %, p = . ). in icu patients, younger age (p = . ) and crcl > ml/min (p = . ) trended toward initial subtherapeutic levels despite receiving ~ mg/kg/day of vancomycin. implementation of the pvds in neurologic units resulted in higher attainment of therapeutic concentrations. in icu patients, addition of a loading dose or higher daily doses of vancomycin may need to be employed by the pvds to ensure achievement of target concentrations. intraventricular therapy (ivt) with polymyxin b (polyb), an antibiotic with similar pharmacological action to colistin (polye), by external ventricular derivation (evd) has the main goal of offering major bioavailability of the drug, since its use by intravenous and direct action are restricted by the blood-brain barrier, with penetration of only %. the patient of the present report had arterial venous malformations followed by hemorrhagic stroke, which caused elevated intracranial pressure. the objective is to show an example of the effect of ivt polyb in a patient with meningoencephalitis infection by multidrug-resistant gram-negative bacteria (a. baumannii and p. aeruginosa), that are common in the icu. a literature review was made on the subject of therapy with polyb about the pharmacological characteristics, nephrotoxicity and neurotoxicity. a comparative table of the resistance profile of the strain treated in this study was created, with the intrinsic resistance of the species. also, the development of liquor evolution (culture and routine) of the patient before the treatment was monitored, until negative liquor. the effectiveness of evd, the colonizer germ and monitoring of the serial aspects of the liquor were analyzed. the patient was treated with intravenous and intrathecal administration of polyb (ivt) from november th to november th. on / / , therapy with intravenous polyb was started: ui( . ui /kg/d) once a day, on every day of treatment; and ivt by evd: ui in solution once a day during the first three days, and on alternate days during all the treatment. as a result of the use of intrathecal polyb associated with intravenous, effectiveness was proven in the routines of liquor negative for such germs, not showing any reports of neurotoxity and nephotoxity. ivt polyb proved to be very efficient on treating meningoencephalitis quickly. no toxic effect was associated with the drug. enhancing the level of alertness in comatose patients after acute brain injury is a very challenging problem. the use of alerting agents like modafinil is reasonably established for tbi patients in the chronic phase but not in the acute settings. we retrospectively reviewed the use of these agents at our center over a five year period to determine efficacy and use patterns in the acute brain injury settings. a chart review for patients who were admitted to the nicu at dumc during ( ) ( ) ( ) ( ) ( ) and treated with an enhancing agent (modafinil, methylphenidate) for decreased level of alertness secondary to an acute brain injury. electronic records were then reviewed to confirm the intended use of the agent, and a number of clinical data elements was recorded. patients were found to meet study criteria and data elements were extracted. patients received modafinil, received methylphenidate. the average gcs was on admission and at discharge. average delay in trialing alerting agents was ( . ) days and in most cases the agents were used within a few days of withdrawal of care or discharge to hospice. outcomes varied widely with ( . %) going to nursing home, ( . %) going to rehab, . % going home and . % to hospice or death. sah was the most common injury ( . %) followed by ich ( . %), sdh ( . %) and tbi ( . %). review of documented gcs during acute hospitalization showed no significant changes during the period of alerting agent trial for any diagnosis other than tbi. in tbi a significant points improvement was seen on average. our data showed that starting methylphenidate or modafinil for the purpose of improving the level of consciousness in acute brain injury patients is not effective except for patients with traumatic brain injury. based on these observation alternative agents like l-dopa should be explored. nurses in the neurocritical care unit (nccu) are responsible for performing serial neurological exams to establish baseline and potentially detect patient deterioration. nurses spend considerable time doing frequent neurological checks but the current neurological exam is open to subjectivity. we want to quantify the agreement between nurses doing these exams. over the course of one week we tracked the neurological exams of patients admitted to the neurocritical care unit. we compared exams between the off-going and on-coming nurses. each exam consists of single elements, loc, orientation, right and left pupil size, reaction and description, characteristics of speech/communication and motor response in all four extremities. grouping right and left pupils gave element-groups. we examined change of shift (cos) opportunities. when there was more than one variation of an element-group a thorough chart review was performed to identify clinical indicators, such as medications given, to determine if there was a true clinical explanation for the variation. cos exams were the same between nurses % of the time whereas % of exams had a single variation and % contained or more single variations. of the cos opportunities with multiple variations in element-groups only exams showed a clinical reason for the change. that leaves exams with multiple unexplained variations. this accounts for % of overall total exam opportunities. nearly % of the time nurses do not agree on the neurological exam of a patient when examined before and after cos. inconsistency in terminology and methods between nurses may hinder accurate communication. a comprehensive literature search did not reveal a standard neurological exam for nccu nurses. further discussion needs to take place between neuro-nurses across the nation with the goal of defining terms and developing a national standard for the serial neurological exam performed by nurses. electrical impedance spectroscopy (eis) is novel, portable, easy-to-implement device that aims to provide rapid, affordable point-of-care detection, assessment, and monitoring of acute brain injury. an adaptation of "passive" electroencephalography (eeg), eis relies on non-invasive measurement and modeling of the conduction of minute electrical currents applied transcranially across a spectrum of frequencies. our purpose was to test of the feasibility of eis to distinguish the impedance differences between normal subjects and brain injury attributable to acute/subacute intracranial hemorrhage or subacute ischemic stroke. we performed a prospective, observational, proof-of-principle study of patients admitted to our neurosciences intensive care unit for ischemic stroke or intracranial hemorrhage, and healthy volunteers. -minute eis recordings were obtained for each patient. the eis device delivered a small "white-noise" alternating current through a pair of stimulation electrodes; voltages were recorded across three bilaterally symmetric electrode pairs in an eeg montage. log-log plots of impedance (y-axis) as a function of current frequency (x-axis, range hz- khz) were produced for each set of electrodes per patient. mean age was years (range - ); % ( / ) were female. of these brain-injured patients: (a) among all patients with subacute hemorrhage (days old), impedances dropped at higher current frequencies; (b) among all patients with subacute ischemic stroke (days old), impedances increased at higher frequencies; and (c) in one patient with acute hemorrhage (hours old), impedances were not significantly different at higher frequencies but evolved to the subacute hemorrhage pattern (a) at a day- follow-up recording. all brain-injured patients were distinguishable from normal control volunteers. eis is a noninvasive, portable diagnostic modality that has potential for clinical applications in multi-modal neuromonitoring and far-forward battlefield/ambulance arenas for diagnosing and monitoring acute and subacute brain injured patients. future development requires clinical validation, standardization, hardware and software optimization, and graphical user interface development. financial support: this work is supported by national institute of biomedical imaging and bioengineering point of care center for emerging neurotechnologies (poc-cent), subaward u eb - and by an "innovation gra hypertonic saline (hs) improves cerebral edema, blood flow, and is inexpensive. however, use of hs is complicated by reports of induced renal dysfunction and associations with increased blood-stream infection. we hypothesize hs alters renal perfusion leading to a state of relative renal insufficiency. with institutional review board approval, we retrospectively reviewed our hospital's use of hs since march of , and prospectively since october . comparisons were made between admission diagnoses, changes in creatinine (cr), and formulation of hs received ( % nacl, % nacl/sodium acetate mix, and . % nacl) to patients receiving normal saline or lactated ringers. intervariable associationswere calculated between using pearson's correlation coefficients. patients of the retrospective portion were identified. the data presented represents the first patients with data. there were significant differences in the apache ii scores and glasgow coma scale (gcs) scores between the different formulations of hs. the overall correlation of chlorine (cl -) and sodium (na + ) with creatinine (cr), and within each of the saline types, were not significant. when dichotomized by the diagnosis, significant correlations appear. traumatic brain injury (tbi) patients demonstrated moderate correlation between na + & cr of . . stroke patients demonstrated small correlations between na + & cr, and c l-& cr ( . for both). patients receiving hs outside the neurocritical care unit (nccu) demonstrated a small but significant correlation between cl and cr at . . patients receiving hs have lower gcs and higher apache ii scores. elevations of na + or cl in stroke, na + in tbi, and cl in non-nccu patients correlating with elevations in cr. as reductions in renal function predict mortality, therapies precipitating kidney injury are concerning. cl -, a potent renal vasoconstrictor, reduces renal blood flow. prospective comparisons of hs formulation and renal function are needed to further assess if formulation affects outcome and cost. first recognized after rapid initiation of nutrition in prisoners of war during world war ii, refeeding syndrome (rs) is the manifestation of fluid and electrolyte disturbances precipitation systemic dysfunction. here we report a case of rs in a patient with duchenne's muscular dystrophy (dmd). a case report and literature review. a -year-old male with past medical history of dmd, chronically ventilated and feed via a percutaneous endoscopic gastrostomytube, presented with pneumonia, sepsis, and status epilepticus. he was treated with broad spectrum antibiotics, early goal-directed therapy, and hours of electrographic seizures suppression with a midazolam infusion. admission labs demonstrated a minimally low albumin ( . g/dl), mild hypokalemia ( . mmol/l), and the presence of urinary ketones. enteral nutrition was started post-admission day (pad) one. pad found elevated serum glucose and precipitous drops in potassium, phosphate, calcium, and magnesium refractory to replacement. pad three attempts to wean the patient to his home ventilator setting failed, and he remained encephalopathic. enteral nutrition was changed to a more elemental, peptide-based formulation, and multivitamin with thiamine was added. electrolyte abnormalities persisted. pad , it was learned the family had reduced the patient's daily enteral nutrition by approximately half over six months to have him fit within his wheelchair. learning this, enteral feeds were reduced by half, advanced at a reduced rate reaching goal in days, and electrolyte abnormalities resolved commensurately. over the next three days, the patients mental status returned to baseline and ventilation improved. no cardiac or hemodynamic complications occurred, but his infections resolved slowly. a significant concern in the critically ill, the constellation of problems associated with refeeding syndrome have systemic implications. these are centered on increased cellular uptake of phosphorus following the reintroduction of carbohydrates. the role of dmd in refeeding syndrome is uncertain, and has not been previously reported. to determine hospital mortality and complication rates associated with surgical clipping and endovascular coiling of cerebral aneurysms in children, and to evaluate the trend of utilization of these procedures over the recent years in various us hospitals. from the kid's inpatient sample database for the years through , we identified a cohort of children admitted with the diagnoses of intracranial aneurysms and aneurysmal subarachnoid hemorrhage. hospital-associated complications and in-hospital mortality were compared among the clipping and coiling treatment groups. a multivariate logistic regression analysis was used to identify independent variables associated with hospital mortality. cochrane-armitage test was used to assess the trend of hospital utilization of these procedures in various hospital subtypes. after data cleansing, children were included in the analysis. two hundred ( %) children had aneurysm clipping and ( %) had endovascular coiling procedures. the coiled group was younger ( . ± . versus . ± . )and had even gender distribution. hospital mortality was higher in the clipped population, . % versus . % (adjusted odds ratio . ; % ci . , . ; p = . ). in addition, hydrocephalus, status epilepticus and pulmonary complications were higher in the clipped population (p < . ). lastly, the length of hospital stay as well as the hospital charges was higher in the clipped population (p < . ). the rate of hospitals' use of the endovascular coiling has increased in various types of hospitals over the years included in this study (p < . ). the trend in mortality rates among the clipped population remained higher ( . %- . %) compared to the coiled group ( - . %). endovascular coiling of cerebral aneurysms in children is associated with fewer deaths and complications, shorter hospital stay, and less hospital charges compared to clipping. the trend of hospitals' utilization of coiling procedures has increased during the recent years. understanding and managing complex physiologies is a critical, but difficult, problem in the neruologicial-icu. most of the information that must be assimilated in the icu exists at the level of raw data, individual test results and observations, and individual clinician notes. this mass of data obscures a holistic view of the patient, hides the development of trends, makes it difficult for clinicians to notice interactions between different variables. graphical displays and patient summaries enhanced or outperformed traditional text displays in numerous studies (elson & connelly, ; balas et al. ) , but this work hasn't yet been extended to support intracranial pressure (icp). the aim of this effort was to develop an interactive icp-specific data visualization using cognitive engineering principles. the visualization is designed to transform and consolidate complex multimodal physiological data into integrated interactive displays. we have developed a drill-down interactive visualization to enable clinicians to manage icp and identify blood pressure target goals that will ensure adequate cerebral perfusion and thereby create and maintain an optimal physiologic environment for the comatose injured brain to heal. using high-resolution physiologic monitoring data, this drill-down screen depicts the status of cerebral autoregulation using methods well described in the clinical literature (czosnyka, smielewski et al. ; jaeger, schuhmann et al. ) additionally, the drill-down provide graphical display of bloodpressure, intracranial pressure, and brain oxygen tension over time. with this interactive visualization, along with medication and lab data, the clinician can determine the target brain oxygen tension for a specific patient and whether to intervene on blood pressure, intracranial pressure or a combination of both in order to achieve a brain oxygenation goal (i.e., goal-directed therapy). the next step in this project is to conduct an experiment comparing this visualization against standard methods. nicom is a novel technique of monitoring hemodynamic status which is based on bioreactance technology. ventricular outflow causes changes in the phase of radiofrequency waves as they cross chest. measuring the phase shift enables calculation of flow. technique is entirely non-invasive. retrospective analysis of collected data. we describe the use of nicom in a tertiary care neuroscience intensive care unit. patients were monitored on the nicom from january until june for an average of days. diagnoses of patients monitored on nicom were: sah - , ischemic stroke - , ich , tbi - , sdh- , brain tumor- , spinal surgery- and others. % of patients were on mechanical ventilation, % were treated with pressors. in the first hrs of monitoring, there were plr (passive leg raising) tests and fluid challenges performed to measure fluid responsiveness. patients ( %) were fluid responsive and ( %) had an intervention. selected cases will be presented nicom system is safe and can be useful in the neuroicu setting. it can be used in intubated patients with sepsis, unexplained hypotension, hypertensive therapy in sah or during hypothermia therapy. it is also useful in non intubated, alert patients, were fluid status has to be monitored closely. although nicom is a seemingly simple-to-use technology, there were multiple clinical challenges including education of the staff, proper test performance and consistent charting. inconsistent machine calibration, use of compression stockings during a plr, and untimely sensors changes were the main problems. in the neuroicu patients with increased icp, use of fluid challenge can be safer than plr. repeated staff training resulted in more consistent data. limited information is available regarding the current state of informatics in various ncc units. we sought to assess the current state and needs for informatics infrastructure to help determine priorities and future directions of informatics research in neurocritical care. a survey instrument was developed and with the support of the neurocritical care research consortium chair, distributed to the participants/registrants of the nd neurocritical care research conference. a response rate of % ( of ) was achieved. most responders worked in an academic medical center ( . %), level trauma center ( . %) and/or mixed multi-bed (mean= . ) neuromedical/neurosurgical icu ( . %), commonly treating ich ( . %), sah ( . %), ischemic stroke ( . %), and traumatic brain injury ( . %). acquiring, integrating, storing and analyzing mm data in a comprehensive informatics architecture for clinical and research use is stated as important but is rarely achieved due to financial and technical barriers. a centralized dissemination of technical assistance and a societal statement prioritizing informatics to advance ncc research may help facilitate future adoption. access to neurocritical care units (nccus) in the mountain west is geographically limited. we evaluated practice patterns among providers in this region and hypothesized that hospital size and distance from nccus impact decisions to transfer patients with critical neurological illness. surveys were sent to hospital providers with varying degrees of access to nccus in the mountain west, to examine what factors influence decisions to transfer patients with critical neurological illness. the survey queried location, hospital size, locally represented specialties, patterns of transfer, frequency of illness presentation, influences for and against decisions to transfer such as timeframes and perceived futility, and awareness of nccus and services they provide. responses were received. responses were grouped by distance from the closest nccu and by hospital size. results showed that futility in outcome has a strong influence on decisions against transfer for smaller hospitals and hospitals that require air transport (p< . ). notably, distance required to transfer is not a strong factor in the decision to transfer patients (p= . ). for larger hospitals and hospitals within ground transport range of a nccu, patient condition, patient risk during transfer, and specialized intensivist support are less influential in transport decisions. patient transfer for critical neurological illness originates from hospitals with varying size and geographic access to nccus. while distance required to transfer does not appear to be a significant limitation, perceived futility in outcome is a strong influence against deciding to transfer. among providers in smaller hospitals at greater distance from nccus, significantly more providers have never heard of nccus or services provided. these findings suggest that therapeutic nihilism regarding critical neurological illness in smaller hospitals at greater distances from nccus influences patient outcomes. patients and providers in these locations may be significantly impacted by further education about neurocritical care and implementation of tele-neurocritical care services. neurocritical care is a multidisciplinary specialty whose participants originate from diverse medical backgrounds. review of the growing body of literature is essential for clinicians and strategies for continuing education may be expected to be unique for this field. this exploratory survey aims to define how the neurocritical care team (ncct) educates itself. a fifteen question survey was sent to all neurocritical care society members and responses were gathered over a one month period. basic statistical analyses of rates and comparisons of response rate proportions were conducted. surveys were returned ( %). % of respondents were physicians, % were non-physician team members, and % were physicians in training. regardless of background or training, individuals seek published literature through a combination of electronic-print media outlets ( %) rather than a singular approach. however, % spend the most time reading journal articles. % of ncct members review the same journals monthly and allocate individual manuscript time contingent upon interest. neurocritical care ( %), critical care medicine ( %), and new england journal of medicine ( %) are the most commonly reviewed journals. % of ncct members do not attend a journal club. academic neurointensivists ( %) and fellows ( %) are most and nurses are least ( %) likely to attend. participation in ncc subspecialty ( %) or general critical care ( %) clubs is more common than neurology ( %) or neurosurgery ( %). responders rate national meetings ( %) as their most influential educational experience. attending physicians ( %) are more likely than trainees and non-physicians ( %) to consider personal literature review most valuable (p < . ). % of all ncct members attended last year's ncs annual meeting, compared to sccm ( %) and regional conferences ( %). ncct members infrequently attended (< %) general topic neurological or neurosurgical national conferences. despite diverse backgrounds, ncct members seek continuing medical education through common subspecialty specific methods. financial support: none the contributions and perceptions of staff regarding nurse practitioners (nps) and physician assistants (pas) in neuroscience icus throughout the country are not well known. the objectives of this study were to determine the impact of neuroscience nps and pas and assess demographics of icus. all members of the neurocritical care society were asked to complete a survey to obtain their perception regarding the addition of nps and pas to the icu team. participants rated the abilities of nps and pas to promote a team environment, anticipate or prevent neurologic deterioration, address patient or staff concerns in a timely manner, safety, and communicate effectively on a - likert scale. in addition, members were asked to provide basic demographics and background information on the type and size of icu, type of providers in charge, and the role of nps and pas in their icu, including procedures performed, documents written, and number of patients per provider. both quantitative and qualitative data was collected and analyzed. a mantel-haenszel chi square and ordinal logistic regression model were used to determine the relationship between the background information and the perception of the abilities of nps and pas. the study cohort composed of % of ncs members. additional responsibility of nps and pas was associated with higher scores in safety, ability to promote a team environment, address patient or staff concerns, communication, and most importantly the ability to anticipate or prevent a neurologic deterioration (p< . for all). number of nps and pas, number of years of employment of nps and pas, number of procedures, and amount of documentation also positively affected safety. additional responsibility of nps and pas has strong potential to improve staff, patient, and family satisfaction, safety, and prevent neurologic deterioration. nps and pas should be utilized to the full extent of their role. we conducted a survey study in an academic, co-managed neuro icu to explore family satisfaction regarding the care of their surviving loved ones and compared results with concurrent data from the hospital's closed medical icu (micu). over days, we administered the family satisfaction-icu instrument to neuro icu and micu patients' families at time of icu discharge. those whose loved ones passed away during icu admission were excluded. the capture rates of families from the neuro icu and micu were . % ( surveys) and . % ( surveys in our neuro icu, patients' families could be more satisfied with several aspects of care. further study is needed to determine ( ) whether a closed neuro icu model improves family satisfaction and ( ) whether instituting a system in which the neurointensivist team regularly meets with all available families daily improves perceptions of shared decision making, even in routine situations. non-funded prospective patient registries at any given institution rely largely on volunteer clinical personnel. presupposing that an all-inclusive database would be self-defeating in this type of environment, we designed and implemented a quality improvement (qi) database with intentional iterative design. neurointensivists identified by consensus the injury/disease related events and procedures that were most important to track for qi and for judging clinical intensity of our unit. we compiled a list of syndromes that were either commonly studied by principal investigators or were common primary diagnoses in our unit. for each syndrome, we identified commonly accepted grading or intensity scores. the clinical and translational science awards electronic data entry module, redcap, facilitated data collection. consecutive patients in our icu were entered upon discharge. weekly meetings served to adjudicate disease classification, grading scores (frequently based on consensus imaging review), and discharge disposition. opportunities to enter free-text items were allowed to enhance the intentionally iterative design. in quarterly reviews, we removed items that were consistently left blank and added standardized items corresponding to consistently annotated free-text items. since its implementation in january , the neurocritical care qi patient registry has accrued separate entries. consensus-driven iterative changes to the registry have resulted in complete data entry. participation at weekly registry meetings has been consistent and enthusiastic, routinely drawing - physicians ( - fellows, - attendings). qi projects have been enabled to date. resource limitations may be a practical hindrance to achieving all-inclusive databases outside of funded clinical studies. an iterative design driven by consensus in the described approach can result in a rich database with complete data entry and continued volunteer participation. future incorporation of supplemental information sources via enterprise-wide clinical data warehouses may achieve more complete databases that comply with standardized ideals such as the common data elements. many neurology residency programs have begun implementing mandatory rotations through neurocritical care (ncc) as part of the curriculum. the added experience was thought to be beneficial for residents after graduating the program; however, we wondered how it might affect residents and patients during residency. we thought to survey residents about their programs and the amount of time they spend in ncc rotations. we also wanted to know how they felt the extra time spent in these rotations affected their consulting habits, and therefore their ability to manage cases on their own. all neurology residents in the united states were the target population for this survey. a list of neurology residency programs was obtained from the american medical academy's freida database. the names and email addresses of program directors were generated, and they were contacted by email with a link to an online survey. the respondents were neurology residents ( pgy- , pgy- and pgy- residents). of the respondents, . % stated that ncc was a mandatory rotation in their program while the remaining . % said that it was not. of those who had mandatory ncc rotations, . % said they were for - weeks duration, while . % agreed they should be - weeks long. when asked how often they ask for consultations from other specialties, residents who had mandatory rotations through ncc were more likely to say they usually do not consult other specialties, while those who did not have mandatory rotations were more likely to consult for all non-neurological issues. the survey results demonstrated that neurology residents who have mandatory rotations in ncc are more confident in their abilities to manage their own patients. this is thought to promote continuity of care and may reduce medical errors as well as healthcare cost. a botulism epidemic in a maximum-security prison cell-block posed numerous logistical dilemmas for which telemedicine served as a bridge to management. inmates in a high-security prison cell-block brewed batches of "pruno" by fermenting fruit, raw potato, and granulated sugar in reusable bags that were passed throughout the cell-block. one of the batches was contaminated with type a botulism. twenty-nine inmates were potentially exposed, but the actual exposures were initially indeterminable due to the inmates' fears of incrimination. the index case developed nausea, emesis, diplopia, and ptosis approximately six hours after exposure and presented to the emergency department (ed) two days later with generalized weakness, dysarthria, dysphagia, hypophonia, and dyspnea. he required intubation and was admitted to the neurocritical care unit (nccu). four additional inmates presented with similar symptoms within several hours of the index case. two required intubation and all were admitted to the nccu. within twenty-four hours of admitting the first five cases, nine additional inmates developed symptoms. five were evaluated in the ed; three were admitted to the nccu and two were discharged to the prison infirmary and monitored using telemedicine. two patients were initially evaluated and monitored with telemedicine at the prison. the remainder of the cell-block was evaluated by prison infirmary staff. botulinum toxin type a was confirmed with bioassay and cultures in these patients, but classic electrodiagnostic findings were absent. the eight inmates admitted were treated with hepavalent botulinum antitoxin (h-bat). obtaining the antitoxin required collaboration with the cdc for transport from several sites around the country. inmates were followed post-discharge using telemedicine and showed improvement. this botulism epidemic presented a logistical logjam. initial telemedicine evaluation and subsequent monitoring played a key role in managing nccu access and optimizing security resources for the prison, ed, and nccu. intrahospital transport of neurocritical care unit (nccu) patients is associated with accidental line removal, unplanned extubation, and hemodynamic instability. further, because patients must be accompanied by a nurse during intrahospital transport, there is an inherent reduction in home unit staffing which reduces direct patient care and monitoring for other nccu patients. the purpose of this project was to assess the impact of a neurocritical care transport nurse (ntrn) on patient safety, improved direct patient care time and improved staff satisfaction. the -month ntrn pilot program was initiated in our bed nccu. for three months, the ntrn worked five -hour shifts per week. the ntrn accompanied patients during intrahospital transports, assisted with admissions, functioned as resource nurse in the nccu, and relieved nurses for meal breaks. data was collected in real time and included time-inmotion data, adverse event records, and a pre-post work-flow surveys. the ntrn completed intrahospital transports with were zero safety events. the mean length of time for intrahospital transport prior to the pilot was significantly greater than transport by the ntrn ( vs. minutes; p<. ). the mean time it took nurses to stabilize a new admission/post-op patients was reduced from minutes to minutes. staff surveys were overwhelmingly positive with % of nurses reporting the ntrn saved them time; % reported increased opportunity for meal breaks, and % attributed reduced overtime due to the ntrn program. individual nurses reported that the ntrn program saved them an average of . minutes each shift ( . hours per shift). the ntrn pilot program was associated with fewer safety events, increased staff satisfaction, more rapid attention to patient needs and reduced overtime. the program should be implemented full time and evaluated for potential costsavings. many factors are associated with time delays to reperfusion in endovascular treatment for acute ischemic stroke (ais). we assessed if a prototypical neurointensive care unit layout where both the angio suite and ct scanner are inside the unit can reduce times to reperfusion. we compared time from ct to groin puncture (gp) in patients that were transferred from outside hospitals (osh) directly to the nicu versus those who went through our emergency department (ed). we retrospectively reviewed patients from a prospectively maintained database from october -june who underwent endovascular therapy for ais. a univariate analysis was performed to compare the patients' characteristics between the two populations and to identify differences in time intervals between ct imaging and gp. a total of patients were included in our analysis. ( %) patients were from osh. patient characteristics in both groups were similar except for osh patients had significantly less history of hypertension ( % vs %, p< . ) but had longer time intervals from last known normal to gp (median mins vs. median mins, p < . ) and lower pretreatment aspects ( % < vs. % < , p < . ). patients' transferred from osh had significantly lower times from inhouse ct to gp as compared to patients from the ed ( . +/- mins vs. +/- mins). although there was an increased number of non-contiguous multimodal imaging studies performed on ed patients compared to those from osh ( % vs %, p< . ), exclusion of these patients still resulted in a significant shorter time frame between ct to gp ( . +/- mins vs. . +/- . mins) among osh transfers. the design of an integrated biplane angio suite within the nicu reduces the times from ct imaging to gp, thereby lowering the times to reperfusion, and potentially, patient outcome. sepsis is a challenge for the intensive care unit (icu), being the main cause of death during hospitalization. it was performed a longitudinal and individualized intervention authorized by the hsja ethics committee applying the campaign 'simple actions save lives' in which educational adhesives worked as a guide for washing hands and flags for high contaminated locations. a decontamination routine of monitors, control panels, ventilators and infusion bombs was established every hours; and continued education for the health team was intensified during the intervention. two groups were created, patient enrollments in periods of days before and after the intervention, more than hours of hospitalization: group a with patients and group b with patients. the hospital infection incidence decreased by % and vap by . %. urine culture was positive in , % of those patients (n= ) in group a and in . % (n= ) in group b (a . % decrease ). the cultures of catheter tip were positive in . % (n= ) of catheters in group a, which used catheter in total, and none in group b, which used catheters. the sepsis incidence decreased by . %. septic shock was detected in . % (n= ) of patients in group a. there was a drop of the costs between groups (r , . , . %). the cost of campaign material was r$ . . this intervention was a simple form to decrease the related number of infections in the neurovascular icu, having spent irrelevant values when compared to treatment of these clinical tables. intracranial pressure (icp) management guidelines have been established; however there is no data documenting actual icp management practices in the united states, or the degree to which clinicians comply with existing guidelines. the primary aim of this study is to explore nursing and medical practice patterns associated with icp monitoring and management. a prospective multi-center non-randomized observational design was used.the study sample was composed of consented nurse/patient dyads, with dyads enrolled per study site. study patient subjects included were over age , had icp monitoring in situ, and were diagnosed with intracranial pathology. nurse subjects included were those assigned to the patient, who routinely worked in the unit, and had completed their orientation training. each dyad consented to a hour observational period, where data was collected on nurse interventions for icp management. dyads (n= ) were enrolled at hospitals between august and may . patients were primarily male %, mean age of years, and non-hispanic. nurses were primarily female %, non-hispanic, and a mean of . years of critical care experience. we observed distinct nursing/medical interventions hypothesized to reduce icp. although csf diversion and limiting stimulation were the most frequently used interventions, there was not a consistent hierarchical approach to initiating icp reduction interventions. wide variances in nursing and medical treatment patterns were observed for icp treatment threshold, first-line therapy, and the order in which interventions were initiated. despite established guidelines, variability exists throughout the u.s. in how physicians and nurses monitor and manage icp. more research is needed to compare intervention techniques to determine the impact these differences have on outcomes in patients requiring icp management. administrative data are being increasing being used to measure quality of care, for public reporting, and in pay for performance. administrative data are inexpensive, readily available, and target clinical outcomes. the aim of this study was to evaluate the use the use of administrative data in identifying potentially preventable events and iatrogenic complications in patients admitted to an academic medical center with a primary diagnosis of acute stroke. administrative data for all adults patients (> years of age) with a discharge diagnosis of stroke , . , . , . , . , . , . , . , . , . , . , . , and ) were evaluated from january -december for complications based on administrative data by looking at secondary diagnoses that were not present on admission using data from the university healthsystem consortium database. both the agency for healthcare research and quality (ahrq) quality indicators (qis) for inpatient conditions and known codes for other complications such as catheter associated urinary tract infection, pneumonia, and deep vein thrombosis or pulmonary embolus (not associated with surgery) were used to identify potential events. of the cases reviewed, many cases had at least one complication. the leading cause of potentially preventable events were related-to-infection (central line associated bloodstream infection, sepsis, catheter associated urinary tract infection, and aspiration and/or hospital-acquired pneumonia). the ahrq qi only captured a fraction of the events. patients with subarachnoid hemorrhage had the highest mortality, followed by intracranial hemorrhage. several of the deaths occurred in low risk patients and had at least one potentially preventable complication. when reviewing flagged records, a small number of events reflected opportunities to improve documentation and/or coding, with the majority of remaining events associated with opportunities for improvement. administrative data may be a useful adjunct to quality improvement efforts. financial support: co-deputy project lead for the ahrq qi project (ahrq sub-contractor). continuous video-eeg (cveeg) monitoring is often utilized in the evaluation of impaired consciousness. nonconvulsive seizures may be distinguished from metabolic disorders when triphasic waves (tw) are recorded. however, rhythmicity detected on cveeg may call into question the presence of electrographic seizures. the following case describes the transient resolution of rhythmic tws after acute administration of glucose in a patient with hypoglycemic encephalopathy. case report reviewing clinical, laboratory and electroencephalographic features of a patient with metabolic encephalopathy secondary to hypoglycemia. a -year-old woman with type- -diabetes and treated osteomyelitis of the foot presented with altered mental status. she was intubated and stuporous. cranial nerves were intact. all four extremities withdrew to noxious stimulation. plantar responses were flexor. mri brain exhibited leptomeningeal enhancement consistent with meningitis. serum bg= mg/d, and csf glucose= mg/dl. month after antibiotic treatment, she was following commands. repeat mri revealed complete resolution of leptomeningeal enhancement. during recovery, she developed sudden onset stupor with left facial movements, and underwent cveeg monitoring. eeg showed generalized, polymorphic delta/theta slowing intermixed with tws, without electrographic correlate of facial movements. during cveeg, tw activity increased in rhythmicity and frequency, coinciding with worsening hypoglycemia, with a nadir bg= mg/dl. electrographic activity was not induced or exacerbated by stimulation. administration of ml of d ( g d-glucose) resulted in transient resolution of tws within minutes, which corresponded to a bg= mg/dl. however, background slowing remained on cveeg, with gradual reemergence of infrequently occurring tws despite normoglycemia. mental status returned to baseline approximately hours after bg stabilization. rhythmic triphasic wave activity due to hypoglycemia may be distinguished from electrographic seizures after acute correction of bg, with corresponding transient resolution of triphasic waves. however, clinical response to correction of metabolic dysfunction may be delayed for up to hours. continuous-iv-midazolam (civ-mdz) is recommended for treatment of refractory status epilepticus (rse) but doses are controversial. here we compare a historical cohort (n= ) treated with low dose to a subsequent cohort of patients treated with high dose civ-mdz for rse. following the analysis of the historical cohort ( - neurology , ( ) : - ) we changed our protocol for rse allowing for higher civ-mdz doses and collected consecutive cases ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . exclusion criteria: cardiac arrest; prior treatment with a different civ-aed. we collected data on baseline characteristics, civ-mdz doses, seizure control, complications, hospital course, and outcome. high dose was compared to low dose civ-mdz on an intention to treat basis using logistic regression analysis with the significance level set at p< . . baseline characteristics were similar between groups. median maximum civ-mdz dose was . mg/kg/h (iqr . , ) for the high and . mg/kg/h (iqr . , . ) for the low dose group (p< . ), but duration of civ-mdz was the same between the two groups (median hours). "withdrawal seizures" (within hours after civ-mdz discontinuation) were less frequent in the high dose group ( % vs %, or . ; %-ci . - . ). "breakthrough seizures", "ultimate civ-mdz failure", and complications were not different. discharge mortality was lower in the high dose group ( % vs %, or . , %-ci . - . ) after controlling for age, etiology, and apache- scores. at months, mortality was similar between the two groups. lower death or vegetative state rate for those treated with high dose civ-mdz was seen at months ( % vs %; or . ; %-ci . - . ), but this finding is limited by missing -month functional outcome data in both groups. high dose civ-mdz treatment for rse can be performed safely in an icu setting and may be more efficacious in controlling seizure activity. outcome data are promising and warrant further prospective study. the clinical utility of free valproic acid (vpa) levels is unclear, and the actual free fraction (ff) of vpa in hospitalized patients is not well established. our goal was to assess and compare the total levels, free levels, and ff of vpa in inpatients and outpatients and to determine factors that may influence the ff. retrospective chart review of paired total and free vpa levels in inpatients and outpatients. demographical, laboratory, and concomitant interacting medication data were collected and analyzed. paired total and free levels were categorized based on their status in regards to the therapeutic range (i.e., subtherapeutic, therapeutic, or supratherapeutic) and whether the paired levels were concordant or discordant (e.g., both levels in therapeutic range, or mismatched). linear regression was used to assess the impact of variables on the ff. logistic regression was used to determine if variables predicted the likelihood of having discordant paired levels. inpatients had a significantly higher median ff compared to outpatients ( . % vs. . % respectively; p < . ). total levels were found to be a poor predictor of free levels (r = . ) in hospitalized patients. inpatient free levels were discordant with the therapeutic status indicated by the total level % of the time. in a linear regression model, albumin (p < . ), total protein (p < . ) and co-administration of phenytoin (p= . ) and carbapenems (p= . ) were found to significantly and independently impact the ff. multiple logistic regression indicated albumin as a significant predictor of the total and free levels being discordant in regards to therapeutic status (or . [ %ci . - . ], p< . ). inpatients had a significantly higher ff compared to outpatients. inpatient free levels were frequently discordant with the total levels in terms of the therapeutic status. decreasing albumin was a significant predictor of discordance between the free and total levels. increased continuous eeg utilization in the icu has generated an interest in faster acquisition and interpretation of eeg data. limited electrode arrays (lea) coupled with quantitative algorithms have been leveraged for this purpose. however, previous studies with lea's have suggested an inherent error rate produced by a reduced number of electrodes. the aim of the current project was to test a novel lea and determine if multiple montages could correct any error rate. with approval from our irb, short de-identified eeg segments were retrospectively collected from clinical ceeg archives. segments contained one of five primary findings: normal, diffuse slowing, periodic epileptiform discharges (peds), seizure and burst suppression. all files were reformatted into an electrode array containing a lateral chain and central electrode bilaterally. segments were distributed to four experienced neurophysiologists in two phases. in phase , segments were interpreted in a single anterior-posterior bipolar montage and compared to the original read. in phase , fifty frequently misread segments from phase were reinterpreted using four additional montages. in phase , eeg interpretations were reviewed yielding a sensitivity of % for seizure and % for peds, burst suppression, and normal. the specificity was greater than % in all cases. the sensitivity and specificity for diffuse slowing was % and %. in phase , eeg interpretations were collected with no significant improvement noted in the detection of any eeg finding. in agreement with past studies, this trial suggests that leas contain a base error rate engendered by the reduced number of electrodes. this error rate is maintained regardless of the number of available montages. the implication of these findings suggests that studies examining the use of lea's for use in seizure detection and neurophysiologic algorithms should calculate an error rate specific to the electrode array before algorithm testing. the incidence of nonconvulsive status epilepticus (ncse) and other electrographic features in comatose post-cardiac arrest syndrome patients treated with therapeutic hypothermia (th) is still under investigation. the objective of this study is to determine the incidence of ncse and other electrographic features and correlate with neurologic outcome and survival. review of consecutive subjects treated with th and receiving continuous eeg (ceeg) monitoring between may and december . demographic data, survival, and functional outcomes using cerebral performance category (cpc) scale were prospectively recorded. forty eight patients were included, with mean age of years (sd ), majority were males (n= , %) and experienced out-of-hospital cardiac arrest (n= , %). ventricular fibrillation was the initial cardiac rhythm in patients ( %). all patients received th. twenty seven patients ( %) died. seventeen patients ( . %) had good neurologic outcome (cpc or ). ncse occurred in patients ( . %), both of whom died. periodic epileptiform discharges occurred in patients ( . %), ( %) of whom had poor neurologic outcome or death (cpc - ) compared to % poor outcome in whom periodic epileptiform discharges did not occur (nonsignificant). burst suppression occurred in patients ( . %), all ( %) of whom had poor neurologic outcome or death compared to . % poor outcome in whom burst suppression did not occur (p < . ); and severe background attenuation occurred in patients ( %), ( %) of whom had poor neurologic outcome or death compared to % poor outcome in whom severe background attenuation did not occur (p< . ). ncse occurred in . % of post-cardiac arrest patients undergoing therapeutic hypothermia. outcomes are poor in postcardiac arrest patients undergoing therapeutic hypothermia with ncse, burst suppression or severe background attenuation. larger prospective studies are needed to further evaluate and characterize ceeg findings in comatose postcardiac arrest patients undergoing th. encephalopathy is a frequent occurrence in the critical care setting. previously, we have shown that patients with a primary neurologic injury and encephalopathy are at high risk for ceeg seizures. patients with a presumed metabolic etiology of encephalopathy have been poorly characterized. the purpose of this study was to identify the frequency and underlying etiology of ceeg seizures that occur in critically-ill patients with a presumed metabolic etiology. we retrospectively reviewed prospectively collected ceeg and clinical data on consecutive patients monitored from january , , to december , . we identified those patients with ceeg seizures (n= ) and included in this study only those patients with metabolic etiologies. eeg seizures were defined as evolving rhythms in frequency, distribution, and/or morphology at hz or greater for more than seconds duration. statistical analyses were performed with jmp . . sixty-six ( . %) patients were identified as having metabolic causes for ceeg seizures with the most common etiology being sepsis ( . %) which linearly increased (r = . ) in detection from in to in . other etiologies included liver failure ( . %), posterior reversible encephalopathy syndrome (pres; . %), electrolyte/glucose derangement ( . %), drug overdose/withdrawal ( . %), and renal failure ( . %). . % of the ceeg seizures were without clinical signs. a linear increase in ceeg seizures occurred with a decrease in level of consciousness (r = . ). the majority ( . %) of patients were eventually discharged for rehabilitation, but . % expired prior to discharge. this retrospective study shows an increase of ceeg detected seizures in patients with a presumed metabolic etiology from to . this increase in seizures is likely due to increased targeted monitoring. this highlights the value of using ceeg database information to target at risk populations. our results should guide the use of ceeg monitoring in the metabolic patient particularly those with septic encephalopathy. medically induced burst suppression on eeg is often seen in critically ill patients who are sedated for treatment of status epilepticus, cerebral edema, and in patients with anoxic brain injury or post cardiac arrest undergoing hypothermia treatment. previous studies have demonstrated that the majority of these patients have poor prognosis. we decided to investigate if specific eeg patterns during burst suppression in these patients would correlate with different outcomes. we retrospectively identified patients with medically induced burst suppression out of patients who had continuous eeg monitoring (ceeg) from january through december in our neuro icu. neonates and children were excluded. all eeg tracings were independently reviewed by two electroencephalographers and classified into discrete seizures, status epilepticus (se), interictal epileptiform discharges (ied), burst suppression, and epileptic bursts defined as burst suppression with ied within the burst activity. primary outcome was cerebral performance categories (cpc) at hospital discharge. of the patients, were identified to have epileptic bursts-one se, eight anoxic brain injury, two ischemic stroke, hemorrhagic stroke, five other medical conditions. the mortality rate of patients with epileptic bursts was % compared to % for those without. only % in each group had good neurologic recovery defined as cpc score of - . patients with epileptic bursts on average had longer duration of monitoring ( days versus ) due to refractory seizures and, subsequently, increased number of aeds ( . vs . ) used. similar to previous findings, the patients in our study had poor prognosis. our findings additionally show that epileptic bursts in this patient population correlated with more refractory seizures and a higher mortality rate. the presence of epileptic bursts may be used as an adjunctive indicator for prognosis in patients who are in medically induced burst suppression. larger population study is underway. epidemiologic studies in epilepsy using large administrative databases depend on accurate icd- -cm classification. we sought to determine the accuracy of icd- -cm code . (grand-mal status) for diagnosing status epilepticus (se) after hospital admission. a case-control study at an academic institution was conducted. twenty-one subjects with discharge icd- -cm code . (grand-mal status) and consecutive admissions without the code of interest were randomly selected. se was defined as neurologist documentation of continuous clinical seizure activity for five minutes or longer and/or two or more discrete clinical seizures without inter-ictal return to baseline (clinical diagnosis) and/or eeg consistent with se by board certified neurophysiologist interpretation (eeg diagnosis). all cases and none of the controls met our pre-defined criteria of se. therefore, the sensitivity, specificity, positive predictive value (ppv), negative predictive value, and accuracy of the code was %. when the diagnosis relied on clinical criteria alone, the sensitivity decreased to % with ppv of %. when the diagnosis was made by eeg criteria alone the sensitivity decreased to % and ppv of %. the icd- -cm code . is both accurate and specific for the diagnosis of se after admission at an academic institution. clinical definitions of se and the prevalence of the disease may affect the sensitivity and ppv of icd- -cm code . for the diagnosis of se. the results of our study require further validation in other cohorts. refractory status epilepticus (se) has been linked to significant morbidity and mortality. when pharmacological treatment fails, ketogenic diet has shown to suppress seizure activity in children and is gaining acceptance as an adjunctive treatment in adults. while case reports exist, there are no standard guidelines for implementing ketogenic diet in adult neurocritical care patients. the purpose of this abstract is to demonstrate a standard guideline for ketogenic diet utilization in a neurocritical care unit. a performance improvement project was undertaken to standardize ketogenic diet administration in enterally fed neurocritical care patients with medically refractory se. the guidelines include patient selection, team communication, patient monitoring, family education, patient transitions out of intensive care and measures for patient outcome from this treatment. patients admitted with se are initiated with standard pharmacologic treatment; if treatment does not result in se cessation, then ketogenic diet is reviewed. discussion with the patient's family is required to review long-term implications and potential lifestyle choices related to diet after critical illness. a standard checklist within the guidelines assures communication to all necessary organizational departments including appropriate consults. daily monitoring and discussion in patient rounds evaluates daily patient progress. team communication is focused on diet tolerance, medication carbohydrate content, concurrent pharmacologic se management and patient progression. since , after implementation of the standardized guideline, seven adult se patients have been treated with ketogenic diet. mean age was . years; range - years; two patients were male. ketosis was achieved in six of seven patients and five of six patients sustained resolution of se after ketosis was achieved. our organizational experience indicates that coordinated team care, family education, goal planning and a standardized guideline contribute to successful implementation of ketogenic diet. further research is needed to determine overall effectiveness of this therapy. status epilepticus (se) is a potentially life-threatening condition that is frequently under-recognized, may be refractory to initial treatments, and often requires admission to general intensive care units (icus) we hypothesized that admission of patients with se to the neurosciences icu (nicu) vs the medical icu (micu) might correlate with surrogates for improved patient outcome. we performed a single-center, retrospective cohort study of patients with se admitted to the nicu vs the micu in our institution between - . admission to either icu depended on bed availability and emergency medicine preference. clustering methods were used for analyses, taking into account multiple visits of the same patient. there were visits for patients with definite or probable se [ ( %) in the nicu and ( %) in the micu]. apache ii scores were significant higher in the micu group ( . vs . , p= . ). more continuous eegs were ordered in the nicu ( % vs %, p< . ). ceeg was ordered more frequently in complex partial/non-convulsive and less in convulsive clinical presentations. the nicu had a higher rate of complex partial/non-convulsive se and the micu of generalized convulsive se ( % vs % and % vs %, p< . ). admission diagnoses differed, with the nicu having a higher rate of stroke and the micu a higher rate of toxometabolic etiologies ( % vs % and % vs %, p< . ). after adjusting for covariates, no difference was found in the icu or hospital length-of-stay and modified rankin scale at discharge. management differences occurred in micu vs. nicu-managed se, possibly based on variabilities in presentation and etiology. however, no reduction in length-of-stay or different discharge outcomes between the icus was found. hongki song , taechon kang , dongjin shin although levetiracetam(lev, s-(oxo- -pyrrolidinyl)butanamide, keppra®, ucb pharma) has been reported to be well tolerated and effective in se refractory to benzodiazepine (bdz), there was little preclinical or clinical data concerning the outcomes of lev in comparison to dzp, and vpa in se-induced neuronal death. to address this relevant lack of information, we have performed the preclinical study to investigate the effect of diazepam (dzp), valproate (vpa), and lev alone, and the efficacy of lev as an add-on treatment with dzp on the se-induced neuronal death. dzp and vpa. however, it is noticeable that lev as an add-on drug with dzp could not alleviatese-induced neuronal damage as compared to effective to protect neuronal damages from se, as compared to dzp. in contrast to lev, vpa( and mg/kg) as an add-on drug with dzp significantly reduced se-induced neuronal damage as compared to dzp alone, and showed the similar effect of vpa ( mg/kg) alone. these findings indicate that, unlike vpa, lev may negatively interact with dzp, and suggest that lev may be more effective to prevent se-induced neuronal death as a first line drug than as a second line therapy after bdz treatment, and that lev as an add-on drug with bdz may not provide any additional benefit to outcome of se. temkin and colleagues found that phenytoin exerted a beneficial effect by decreasing the rate of seizures by % during the first week after a traumatic brain injury. the purpose of this study was to determine the need for monitoring and titrating to therapeutic free phenytoin levels in patients receiving phenytoin for prophylaxis within days following a traumatic brain injury. this was a retrospective study of patients for a traumatic brain injury (tbi), who met the inclusion criteria and received phenytoin for seizure prophylaxis for days following injury. eligible patients were divided to two arms: patients with phenytoin levels (n= ) and patients without levels (n= ). the primary outcome measure was the incidence of seizures in those that were monitored for free phenytoin levels and those that were not monitored for free phenytoin levels. the secondary outcome measure was the appropriateness of phenytoin dosing in regards to initial loading and maintenance dose. a total of seizures occurred in the entire study population. both seizures transpired in patients with phenytoin levels. patient was diagnosed with a seizure event on day , with free phenytoin obtained on day at a therapeutic level of . mg/l. patient had a witnessed seizure on day , with free phenytoin level obtained on day also within therapeutic range at . mg/l. there was no incidence of seizure in patients who were not monitored for phenytoin levels. inconsistent phenytoin loading and maintenance doses were identified. this study suggests that monitoring phenytoin to therapeutic levels for seizure prophylaxis did not demonstrate a decrease in the occurrence of seizures. we are unable to make recommendations given the inherent limitations of our study. a large prospective, randomized trial is needed to clarify the need for monitoring phenytoin to therapeutic levels. seizure prophylaxis for nontraumatic intracerebral hemorrhage (ich) and aneurysmal subarachnoid hemorrhage (sah) is common practice in the intensive care unit(icu). typical antiepileptics include phenytoin (ptn) and levetiracetam (lvt). previou studies have suggested worse long term outcomes with icu ptn use, but such data is lacking for lvt. in addtion, few studies have compared lvt to ptn for seizure prophylaxis in ich or sah patient in the icu setting. we hypothesize that seizure prophylaxis with lvt, as compared to ptn, for patients admitted with ich and sah will result in similar outcomes at hospital discharge as measured by the modified rankin scale (mrs). this study is a single center retrospective review from - , to ultimately include approximately adult patients with the diagnosis of sah or ich who received seizure prophylaxis with either lvt or ptn. basic demographic, past medical history, severity of illness scales; length of mechanical, icu and hosital length of stay; seizure occurrence, use of continuous electroencephalogram, data will be collected, in addition to other variables. patients with prior seizure history or seizure on presentation, do-not-resuscitate hours within hours of icu admission, will be excluded. to date, our analysis includes patients (lvt = and ptn = ). comparing ptn to ltr, univariate analysis of demographics, baseline clinical characteristics and outcomes were similar between the two groups (all p> . ). in our initial univariate analysis, functional outcome at discharge was similar between ptn and lvt when used for seizure prophylaxis in patients admitted with ich or sah. subsequent analysis will include additional patients (approximately ) with multivariate adjustment. cerebral microbleeds (cmbs) are commonly found in patients with microvascular pathology such as primary intracerebral hemorrhage, cerebral amyloid angiopathy, and ischemic stroke. however, to our knowledge, there have been no reports of cmbs or their acute appearance in patients with status epilepticus (se). here we describe two patients admitted to our neuro-intensive care unit with generalized tonic-clonic seizures. laboratory tests were unremarkable except for mild pleoc onset and did not showed abnormal findings. seizures continued despite multiple anti-epileptic drugs including phenytoin, valproic acid, topiramate, clonazepam, pregabalin, lacosamide, phenobarbital, levetiracetam, and continuous infusion of propofol, ketamine and midazolam (up to . mg/kg/hr in the first patient and . mg/kg/hr in the second patient). followup . -tesla susceptibility-weighted imaging revealed new cmbs ( lobar [ frontal, parietal, temporal, occipital, and insular], deep [ corpus callosum and deep/periventricular white matter], and infratentorial [ brainstem and cerebellum]) in the first patient (performed days after initial imaging) and new cmbs ( lobar [ frontal, parietal, temporal, and occipital], and deep [ corpus callosum and deep/periventricular white matter]) in the second patient (performed days after initial imaging). multimodal neuromonitoring was available between initial and follow-up imaging in the second patient and suggested metabolic distress (lactate-pyruvate ratio > ), cerebrovascular dysautoregulation (pressure reactivity index > . ), brain tissue hypoxia (brain tissue oxygen partial pressure < mmhg), and fluctuations of blood pressure (variance, mmhg) and cerebral perfusion pressure (variance, mmhg). cmbs may develop acutely in patients with refractory se, which may point towards microvascular disturbances in refractory seizures. further prospective studies are necessary to explore the pathophysiology and clinical implications of new cmbs in se. synthetic cannabanoids, often sold as "spice" and various other labels, are a popular product sold in incense shops and through the internet. when inhaled, consumers often report experiences similar to marijuana use, and have thus become a popular street substitute for marijuana. unfortunately, with increasing use, there has been an increase in the number of patients presenting to emergency departments due to toxic effects of these products. we describe a year old gentleman with history of bipolar disorder but no history of neurological disease who presented to the emergency department with altered mental status and tachycardia who subsequently had a witnessed tonic-clonic seizure. patient received appropriate workup for his potential toxicity. we also performed a literature search on "spice" incense found in his backpack on presentation. patient had admitted to smoking "spice" incense on questioning. patient's negative drug screen, negative workup, as well as symptomatic improvement on phenytoin supported the source of his seizure as the toxic effect of inhaled "spice". we also on literature review discovered several other cases similar to this patient's case. "spice" or synthetic cannabanoid-induced toxicity is an emerging etiology of new-onset seizure and does not appear on conventional drug screens. critical care professionals should be aware of this product to recognize and appropriately treat this toxicity. refractory status epilepticus (rse) is associated with high morbidity and mortality. etiological heterogeneity and refractoriness to treatment remain a challenge for the treating intensivist. here we present a patient with rse and folic acid (fa) deficiency. brain metabolism was hourly analyzed using cerebral microdialysis (cma -analyzer; cma -catheter). fa concentrations of brain extracellular microdialysate (famd-ec) and serum (faserum) were analyzed using elecsysfolateiii® -assay. in vitro recoveryof fa was calculated using cerebrospinal fluid (csf). a -year-old male was referred to our neurocritical care unit with se refractory to levetiracetam ( g/d) valproic-acid ( . g/d) and , mg/kg bw/h midazolam continuous infusion. the patient had a history of short bowel syndrome (sbs) after small intestine resection five months prior. admission electroencephalography showed continuous rhythmic epileptiform activity over the right hemisphere despite adding ketamine continuous infusion ( , mg/kg bw/h) and lacosamide ( mg/d). neuroimaging demonstrated diffusion-weighted-imaging (dwi)-hyperintensities over the right hemisphere. csf was normal, common causes of rse were unlikely after extensive laboratory and csf studies. fa serum was found to be lower ( . μg/l; . - . μg/l) at day two of rse. after thiopental anesthesia ( hours) and parenteral fa substitution ( mg/d), the patient was successfully weaned without electrographic or clinical seizures. repeated imaging of the brain at day showed improvement of dwi-hyperintensities. glutamate levels in md ec decreased overtime. the patient could be extubated and fully recovered to the functional level before rse. fa serum increased by % to . μg/l, post hoc analysis of fa md-ec revealed an increase by % (from . μg/l to . μg/l). in vitro recovery of fa was %, therefore calculated fa brain / fa serum ratio was initially , which is comparable to previous animal studies. brain extracellular folic acid can be measured using cerebral microdialysis. although causality cannot be proven, fadeficiency may have influenced the course of rse in our patient. the management of inter-ictal eeg patterns such as sirpids (stimulus-induced rhythmic, periodic or ictal discharges) in comatose intensive care unit (icu) patients remains poorly understood whether these are secondarily injurious to brain or simply a of marker of underlying brain injury. we describe cases of brain-injured patients with sirpids with ictal spect imaging and in regards to aggressive neuroicu management and patient outcomes. case series, n= . case # -a -year old female suffered a cardiac arrest and remained comatose after days. continuous icu eeg demonstrated nonconvulsive seizures (ncsz) and status (ncse) with up to hz maximal bilateral centroparietal head spike and wave by day # which was refractory to initial iv levetiracetam, iv lacosamide, iv phenytoin but finally responded to iv phenobarbital load ( mg/kg) and propofol infusion. sirpids were noted despite these medications with any form of tactile or auditory stimulation. we performed ictal (stimulation provoked sirpids) and interictal technetium- -spect which was negative for hyperintense focus. case # -a year old female was admitted comatose for subarachnoid hemorrhage secondary to aneurysm rupture. she received a left-sided hemicraniectomy with operative clipping of the aneurysm and drainage of a small left subdural hematoma. on postoperative day (pod) # , ceeg showed left frontotemporal sharp waves. she was placed on leviteracetam, lacosamide, benzodiazepine, propofol infusion, and phenytion. by pod # , ceeg revealed left frontal sharply countoured discharges when the patient was stimulated by nail bed pressure on examination, consistent with sirpids. by pod # an ictal spect scan showed broad areas of hypoperfusion in the left hemisphere due to infarcts but there were no findings suggestive of a seizure focus scintigraphically. spect-scan negative sirpids may be helpful in terms of deescalating aggressive brain-metabolic suppressive therapies such as propofol and barbiturates, but larger, outcome-based studies are needed. thromboelastography (teg) is point-of-care test that allows for rapid global assessment of coagulation. teg analyzes whole blood, not plasma, which better accounts for the effects of cellular components on hemostasis. we sought to determine whether there is evidence of hypercoagulability by teg and whether it correlates with discharge outcome after aneurysmal subarachnoid hemorrhage. ten patients with moderate-to-severe sah were prospectively enrolled in an irb-approved observational study of serial thromboelastography. teg analysis, using kaolin activated citrated samples, was performed on post-bleed days , , , and . thrombus velocity curves, including the maximal rate of thrombin generation (mrtg), time to maximal rate of thrombin generation (tmrtg), and total thrombin generation (ttg), were plotted for each patient. a hypercoagulable state was defined a priori as a g value of > dynes/cm or a maximum amplitude (ma) of greater than mm. secondary outcome measures included discharge disposition. mean age of patients was . +/- . years. / patients were women and / were discharged home. the mean g parameter was within the normal range ( . dynes/cm ) on day , demonstrated a hypercoagulable profile on day ( . dynes/cm ), peaked on day ( . dynes/cm ), remained hypercoagulable on days ( . dynes/cm ) and day ( . ). the day g value was significantly different from the day value (p= . thromboelastography may identify a transient hypercoagulable state that peaks around post-bleed day in patients with sah. this state reflects accelerated thrombin generation and correlates with discharge disposition. defining a hypercoagulable state in patients with sah may lead to better risk stratification and novel therapeutic interventions. financial support: this study is supported in kind by haemonetics. they supply teg machines, kits and reagents. they have neither participated in study design nor are they aware of these preliminary results. intravenous sedation has been associated with impaired cognitive recovery following critical illness but its influence on recovery following asah remains unknown. data from consecutive patients with asah admitted to columbia-presbyterian hospital and enrolled into the shop database between / - / were analyzed after exclusion of deaths and unemployment prior to hemorrhage. employment status at year was obtained through self report or through patient surrogate and trichotomized (same level, decreased level, unemployed). proportional odds models were used to test the association between the use of continuous intravenous sedation with employment and cognitive function at year after controlling for baseline demographics (age, race, occupational level, admission hunt hess grade) and hospital complications (pneumonia, infarction from vasospasm). proportional hazards model was used to examine the association of sedation with time to return to work. patients who had the primary outcome data of employment status at year were analyzed. in multivariate analysis, exposure to continuous intravenous sedation was significantly associated with worse employment status at one year (or= . , ci= . - . , p= . ). poor judgment (or= . , ci= . ,- . , p= . ) and apathy (or= . , ci= . - . , p< . ) at one year were significantly associated with worse employment status but not with sedation exposure. with multivariate proportional hazards model, sedation was a significant risk factor of unemployment (hr= . , ci= . - . , p= . ). among those who returned to work within year, patients who received intravenous sedation returned to work significantly later than those who did not (median vs. days, p= . ). patients who received continuous intravenous sedation following asah had worse one year employment status and returned to work later. although poor judgment and apathy was associated with worse employment status, they were not associated with sedation exposure. future studies should investigate the effects of intravenous sedation exposure on cognitive and functional recovery following brain injury. despite an improvement in mortality, many survivors of asah still have significant disability and impairment in quality of life. we investigated predictors of unemployment at year among survivors of asah. data from consecutive patients with asah admitted to columbia-presbyterian hospital enrolled into the shop database between / - / were analyzed after exclusion of deaths and unemployment prior to hemorrhage. employment status at year was obtained through self-report or through patient surrogate and trichotomized (same level, decreased level, unemployed).pre-morbid occupational level was trichotomized (full time, part time, housewife). proportional odds models were used to test the association between baseline demographics, pre-morbid and discharge functional status with employment status at one year. proportional hazards model was used to test the association of these factors with time to return to work. a total of patients had the primary outcome data of employment status at year. patients ( %) remained unemployed, patients ( %) worked at a decreased level, while patients ( %) were employed at the same level. after controlling for age, modified fisher scale, and discharge functional status, ethnicity (p= . ) and pre-morbid occupational level (p< . ) were significantly related to employment status. hispanics (or= . , ci= . - . ) were less likely to be employed than other minority groups with caucasian as the reference group. caucasians working full time pre-morbidly provided the greatest odds for employment (or= . , ci= . - . ) over part time employees (or= . , ci= - . ) and housewives (reference) among those who returned to work at year follow-up, patients who were employed at the same level returned to work sooner that those employed at a decreased level (median: vs. days, p= . ). unemployment among survivors of asah remains problematic, especially among certain underrepresented minorities. future studies should investigate modifiable factors which impede successful reintegration to the work force. cerebral vasospasm after aneurysmal subarachnoid hemorrhage (sah) remains a major cause of death and disability. delayed cerebral ischemia (dci) after sah is likely multi-factorial, but eventually leads to altered cerebral blood flow (cbf) and cerebral infarction. neurointerventional treatment is used for medically refractory vasospasm, but with limited data on efficacy and impact on cbf and clinical/dci outcomes. patients with sah scheduled for neurointerventional treatment of refractory vasosasm were consented for intraprocedural cbf monitoring. we measured regional cbf using two sodium iodide scintillation scalp detectors approximating the cortical vascular territory of the treated vessel. a . ml saline bolus of - mci of -xe is injected through the coaxial catheter immediately before and after endovascular treatment. tracer washout is recorded under stable physiologic conditions for . minutes. cbf is calculated using the initial slope index, the monoexponential slope of tracer washout from - seconds after isotope injection. data were analyzed including standard corrections for remaining activity and physiologic parameters (cortexplorer cbf a, ceretronix, denmark). mean arterial blood pressure, paco , serum hemoglobin, and delivery of anesthetic agents were monitored. we calculated change in cbf expressed as a mean + standard deviation using repeated measures anova before and after endovascular treatment. a total of sah patients with refractory vasospasm were enrolled in the study. moderate to severe angiographic spasm was reported in % of subjects. treatment included ia verapamil in ( %), angioplasty only in ( %), and both in ( %). mean change in cbf was + ml/ gm/min, an average of % change in regional cbf. in our prospective study of patients with endovascular treatment for refractory vasospasm, we detected a mean change of % in quantitative cbf using the intra-arterial -xe washout method. without significant radiographic evidence of large vessel change at the time of measurement, increases in cbf may be related to the microcirculatory effects of treatment. early detection of cerebral vasospasm (vs), a common complication of subarachnoid hemorrhage (sah) enables prompt initiation of treatment. screening and detection of vs is done by repeated neurological examinations and transcranial doppler (tcd) monitoring, while angiograms are used for definitive diagnosis. this study aims to test the ability of a novel nirs based cerebral-oximetry method to detect vs in the post sah period. -hess score of - were enrolled. patients underwent neurological examinations, tcds and had - minute nirs monitoring sessions daily. whenever vs was suspected, angiography was performed. clinical event was defined as the combined endpoint of angiographically proven vasospasm, flow velocity > m/s over mca or aca territories, or neurologic deficit manifested rformed using the cerox , utilizing ultrasound tagged light (utl). pathologic cerebral oximetry was defined as having cerebral saturation below % for more than % of recording time and aut > second%. patients were analyzed, of whom had angiographic vasospasm. these were correctly detected by both nirs and tcd. of combined events over the aca territory, nirs detected / events. nirs also detected desaturations in / remaining cases, when no clinical or imaging event was detected. of combined events over mca territory, had an increase in desaturation auc, and / cases with no event had increase in desaturation events. both cases of angiography proven vasospasm were detected by nirs as an increase in desaturation auc, and by tcd as increase in flow velocities. cerebral oximetry using utl based nirs is comparable to tcd in detecting cerebral vasospasm, and may be superior in early detection of clinical neurologic worsening. extracellular fluid volume (ecfv), the main determinant of total circulating blood volume, is determined by the mass balances of na+ plus k+ (mbnk). in patients with aneurysmal subarachnoid hemorrhage (asah), diminished ecfv and reduced circulating blood volume are risk factors for worsened neurologic outcomes. maintenance of a normal ecfv based on nurse entered fluid balance (fb) has been reported to be difficult. the purpose of this study was to describe the time course of fluid and electrolyte mass balances over days in a cohort of patients receiving hypervolemic or normovolemic therapy. data from a randomized trial were secondarily analyzed. the intensive management of pressure or volume expansion in subarachnoid hemorrhage trial randomized patients to receive either a normovolemic or hypervolemic fluid management protocol. the standardized fluid management protocol included maintenance iv fluids with rate adjustments or boluses based on -hourly fluid balance and cvp (when available) with a target net positive fluid balance of - l in the hypervolemia group, and < . l in the normovolemia group. mbnk was calculated using published formulae. fb and estimated mbnk were compared between groups using random-effects generalized least square regression. baseline characteristics were similar between groups. fb was higher in the hypervolemia group than in the normovolemia group (mean difference: ml/day, %ci: - , p= . ). mbnk was also higher in the hypervolemia group (mean difference: meq/day, %ci: - , p= . ). average daily fb did not reach the target in the hypervolemia group. mbnk was negative on / days in the hypervolemia group, and / days in the normovolemia group. hypervolemic therapy resulted in higher net fb and mbnk compared to normovolemic controls, but was relatively ineffective at generating a consistently positive fb or expanded ecfv. our results support the notion that hypervolemia is difficult, if not impossible, to maintain in asah patients. exposure to hyperoxia is commonly seen but it is largely unknown whether hyperoxia is beneficial or harmful in patients with subarachnoid hemorrhage (sah). we hypothesized that hyperoxia may be associated with increase in the risk of delayed cerebral ischemia (dci) and poor -month outcome after sah. we analyzed data from single center, prospective, observational cohort database between and . patient nical ventilation, and ) arterial partial pressure of oxygen (pao ) measurements. patients expired within two weeks were excluded. hyperoxia was defined as the highest quartile of an average area under the curve of pao until the development of dci (pao mmhg) or until the post-bleed day (pao three months. of patients, no baseline characteristics were clinically contributing to hyperoxia. ninety-seven ( . %) patients developed dci. outcome data were available in patients, and poor outcomes were observed in ( . %) patients. the hyperoxia group had significantly higher incidence of dci (p = . ) and poor outcome (p = . ). after adjusting for modified fisher scale, hyperoxia was independently associated with dci (adjusted or, . ; % ci, . - . ; p < . ). after adjusting for age, smoking, alcohol consumption, previous stroke, previous heart disease, hunt-hess scale, aneurysm size, acute physiology and chronic health evaluation ii score, serum glucose, hyperoxia was found to be independently associated with poor outcome measured at months (adjusted or, . ; % ci, . - . ; p = . ). our data suggest that exposure to hyperoxia after sah is associated with dci and poor -month outcome. exact mechanism and the clinical implications can be explored by further investigations. advances in management of aneurysmal sah (asah) including refinement of neurosurgical techniques, availability of endovascular options and evolution of neurocritical care have led to improved outcomes following aneurysmal sah. we evaluated outcomes in asah patients admitted to our institution(s) over the past decades. prospectively collected data of aneurysmal sah patients admitted to the johns hopkins medical institutions between - was reviewed. we compared surivavl to discharge and functional outcomes at first clinic appointment post discharge ( - days) in patients admitted between - (phase =p ) and - (phase =p ) respectively using dichotomized gos (good outcome: gos - ). consecutive asah patients were included in the analysis (p . %; p . %). there were higher rates of poor grade hunt & hess (p %, p %; p< . ), admission gcs < (p : %, p %, p< . ), known medical comorbidites (p %, p %; p= . ), associated intraventricular hemorrhage (p %, p %, p< . ) and an older population in phase (p : . , p . ; p < . ) admissions. overall in-hospital mortality was low ( . %) and there was no significant difference between the periods in survival to discharge (p> . ). good outcomes were more common in phase ( . %) compared to phase ( . %); this difference was statistically significant after correction for other confounding factors following multivariate analysis (p< . ) with -fold greater adjusted odds of good outcomes in phase . our institutional experience over decades confirms that patients with asah have shown significant outcome improvements over time. hyponatremia in hospitalized patients has been associated with increased mortality, while chronic mild hyponatremia may impair attention and gait. hyponatremia after aneurysmal subarachnoid hemorrhage (sah) is common, yet its effect on cognitive outcome remains unclear. we aim to demonstrate the domain-specific cognitive effect of hyponatremia on patients after sah. we retrospectively analysed data from consecutive patients enrolled in our columbia university sah outcomes project between april and november . subjects were excluded if withdrawal of care of death occurred in the first three days. hyponatremia was defined as a sodium level < meq/l at any time during hospitalization. univariate and multivariate analyses were performed by a poisson regression, and a preset alpha of < . was set for statistical significance. a total of were included in the study. hyponatremia developed in subjects ( %). their mean age was years (sd+/- ), and subjects were men ( %). median time to onset and nadir of hyponatremia were (iqr - ) and days . univariate analysis associated hyponatremia with worsened modified rankin scale at discharge (rr= . , ci . - . ), three-month telephone interview of cognitive status (tics) (rr= . , ci . - . ), three-month barthel index (rr= . , ci . - . ), and three-month lawton instrumental activities of daily living (rr= . , ci . - . ). after adjustment for age, gender, hunt and hess grade, rebleeding, delayed neurologic ischemic deficit, and generalized cerebral edema, hyponatremia was associated with worsened three-month tics (rr= . , ci . - . ). by one year, hyponatremia was not associated with either functional or cognitive impairment. hyponatremia-related injury after sah appears to be associated with cognitive rather than functional impairment at three months. early and aggressive reversal of hyponatremia may expedite cognitive recovery among survivors of sah. financial support: dr ortega is supported by the spotrias fellowship funded by the national institute of neurological disorders and stroke (ninds)-p ns .dr mayer consults for actelion pharmaceuticals.there are no studies have shown that decreased quality-of-life (qol) after sah is a significant problem. the factors that predict poor qol after sah remain unclear. we sought to identify predictors of a poor quality of life months after sah. we prospectively studied -month qol in a cohort of patients consecutively admitted with sah between july and may . admission clinical scores, radiographic, surgical, and acute clinical course was documented during hospitalization. twelve months after sah qol was assessed using the sickness impact profile (sip). reduced qol was defined as two standard deviations below population-based normative values on the sip. univariate statistics were used to identify candidate predictors of poor qol, and to identify significant concurrent symptoms. backwards stepwise logistic regression was used to generate multivariable models of reduced qol. at months, % of survivors who participated in the follow-up survey ( / ) reported reduced qol. univariate admission factors associated with reduced qol were non-white race/ethnicity, high school education or less, poor clinical grade, loss of consciousness, hydrocephalus, pneumonia, and cerebral infarct from any cause. multivariable analysis revealed that poor hunt-hess grade (or . ; ci % . - . ), non-white race/ethnicity (or . ; ci % . - . ), and years or less of education (or . ; ci % . - . ) were significant admission risk factors for poor qol. common significant co-morbidities associated with poor qol at months included greater unemployment, not currently driving, more financial difficulties, current symptoms (e.g., headaches), marital difficulties, fear of recurrent sah, and dissatisfaction with rehabilitation. poor qol affects as many as one-third of sah survivors, and is predicted by poor admission clinical grade, non-white race/ethnicity, and lower educational status. further research is needed to determine if improved access to support and rehabilitation services for high-risk patients groups can improve qol after sah. biochemical mediators alter cerebral perfusion potentially resulting in neurological decline and delayed cerebral ischemia (dci); a significant cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (asah). estrogens (estrone-e and estradiol-e ) are mediators that have demonstrated neuroprotective properties that could play a role in dci however few studies have evaluated the impact of estrogens on outcomes in humans following asah. this study sought to examine the association between cerebrospinal fluid (csf) e and e levels and dci following asah. csf samples were collected after hemorrhage on adult asah patients [ -males, -pre and -post-menopausal females) admitted to the nv-icu enrolled in a nih study (ro nr ). up to csf samples per patient were selected for analysis representing days - after hemorrhage. samples were analyzed for e and e using liquid chromatography-tandem mass spectrometry. dci was operationalized as radiographic/ultrasonic evidence of impaired cerebral blood flow accompanied by neurological deterioration. statistical analysis using sas(v . ) included group based trajectory and multiple logistic regression. e was detected in more csf samples than e ( % vs %). group based trajectory identified distinct populations over time for both e ( % e high) and e ( % e high) values using censored normal model. non-weighted chisquare analysis identified differences between e trajectory groups by hh (p=. ) and dci (p=. ). using log metabolite levels, higher csf e measurements were associated with higher hh (p=. ) and fisher (p=. ) scores. csf e levels were not associated with dci (p=. ). there were no differences between csf e and severity of injury or dci.there was a significant relationship between csf e and e concentrations (p<. ). these findings provide evidence that estrogen metabolites are measureable in csf and may be associated with severity of injury. future studies are warranted to further explore these findings and their association to outcomes. high-grade spontaneous subarachnoid hemorrhage (sah) patients are monitored in the icu for up to days, as they are at risk for complications. the diagnosis of treatable complications such as vasospasm of cerebral arteries, cardiac arrhythmias and neurogenic stress cardiomyopathy is often delayed by the limitations of monitoring capabilities. we hypothesized that changes in heart rate variability (hrv) would correlate with the onset of these conditions following sah. we applied computational methodology to a cohort of sah patients in a single neurointensive care unit, examining hrv profiles to identify biomarkers of vasopasm, cardiomyopathy and impending respiratory failure. hrv was quantified for individual min epochs of the electrocardiogram waveform ( hz). qrs complexes were identified and the interbeat (rr) interval time series was constructed. mean, standard deviation and coefficient of variation of rr intervals, as well as the ratio of low frequency to high frequency power spectral density and standard poincare statistics were quantified. vasospasm occurred in ( %), stress cardiomyopathy in ( %) and respiratory failure in ( %) of patients. in a sah patient with takotsubo's cardiomyopathy and respiratory failure, we found a decrease in hrv that predated the discovery of cardiomyopathy as well as the onset of respiratory distress by several hours. the early clinical detection of vasospasm, cardiomyopathy and impending respiratory failure from on-line ekg hrv analysis would be of tremendous clinical value. in the face of changing autonomic influences in the critically ill postaneurysmal subarachnoid hemorrhage patient, the finding of an early signal prior to clinical detection of respiratory failure is encouraging. a larger and more highly annotated dataset may be required to increase the signal to noise ratio to realize the clinical potential of hrv-based biomarkers. retrospective analyses have found an association between transfusion and vasospasm, medical complications and mortality in subarachnoid hemorrhage (sah) patients. yet, none of those studies assessed the timing of transfusion, whether it occurred before, or, after vasospasm or complications. we sought to clarify whether transfusion could be considered a cause or consequence of vasospasm and complications. this interim analysis indicates that transfusion is not associated with vasospasm or infection when timing of transfusion is considered; fluid overload was more common after transfusion. the most dismal sequelae of aneurysmal subarachnoid hemorrhage (asah) are the development of cerebral vasospasm and consecutive delayed infarctions. their severity is linked to the clinical grade of the initial hemorrhage and the amount of blood in the basal cisterns. together, they represent the major cause of unfavorable clinical outcome and death in asah patients. from retrospective data, a promising method to reduce the incidence of vasospasm is the use of a lumbar drain to remove the blood from the subarachnoid space. the recently completed lumas trial addressed the safety of this approach in good-grade asah patients ( ). however, so far prospective data from subjects being at high risk for vasospasm and delayed infarction is lacking. we present the protocol of the earlydrain study, a prospective randomized multicenter trial comparing an intervention group with early continuous lumbar csf drainage to a control group receiving standard neurointensive care only ( ). eligible for participation are adults suffering from asah of all clinical grades who receive aneurysm treatment within hours of ictus. primary endpoint is the modified rankin score at six months. secondary endpoints include mortality, angiographic vasospasm, cerebral infarction, transcranial doppler sonography (tcd) mean flow velocity and rate of shunt insertion at six months after hospital discharge. the earlydrain study had recently been launched and, at abstract submission, patients of planned were enrolled. interim safety analysis did not reveal any concern on the use of lumbar drains after aneurysmal sah. up to now, ten centers in germany, switzerland and canada are participating. interested centers willing to join and contribute are still much appreciated. patients with aneurysmal subarachnoid hemorrhage (asah) require management in centers with neurosurgical expertise necessitating emergent interhospital transfer (iht). our objective was to compare outcomes in asah ihts to our institution with asah admissions from our institutional emergency department (ed). data for consecutive patients with asah admitted to johns hopkins medical institutions between and were analyzed from a prospectively obtained database. we compared in-hospital mortality and functional outcomes at first clinical appointment post-asah ( - days) using dichotomized glasgow outcome scale (good outcome: glasgow outcome scale - ) in ed admissions with ihts. a total of consecutive patients with asah were included in analysis (ed . %, iht . %). direct ed admissions had a higher incidence of poor hunt and hess grade ( / ) and major medical comorbidities, with no significant differences between the groups in age, intraventricular hemorrhage, and hydrocephalus. in-hospital mortality for ed admissions ( . %) was significantly lower than that for ihts ( . %), with . times greater adjusted odds of survival after multivariate analysis (p = . ). emergency department admissions had nearly -fold greater odds of good outcomes (odds ratio, . ; p b . ) after multivariate analysis. our institutional ed sah admissions had significantly better outcomes than did ihts, suggesting that delays in optimizing care before transfer could deleteriously impact outcomes. left ventricular (lv) systolic abnormalities occur commonly after subarachnoid hemorrhage (sah). cardiomyopathy associated with sah can include either predominate apical lv systolic dysfunction (cm-apical) or predominate basal lv systolic dysfunction (cm-basal). we aimed to determine if outcomes and diastolic function were different between patients with various forms of lv dysfunction after sah. patients hospitalized for sah between and were eligible for our study. those patients with a history of heart failure, myocardial infarction, or a documented acute coronary process were excluded. echocardiograms were reviewed and a wall motion score was provided for each of lv segments. patients were classified as cm-apical if the average wall motion score for apical segments was greater than the average wall motion score for basal segments. patients were classified as cm-basal if the average wall motion score for basal segments was greater than the average wall motion score for apical segments. of patients with sah had an echocardiogram. patients had normal lv function, cm-apical and cmbasal. the in-hospital mortality was not different between those with no echocardiogram or those with an echocardiogram who had normal lv function, cm-apical or cm-basal. patients with cm-apical were more likely to have shock and pulmonary complications, whereas patients with cm-basal were more likely to have sepsis. during a median follow up of . years, patients with cm-apical had the worse survival. patients with cm-apical and cm-basal had impaired lv relaxation as compared to those with normal lv systolic function. in-hospital mortality is not different between those patients with normal lv systolic function, cm-apical, or cm-basal. cmapical is associated with shock and pulmonary complications and a worse long term survival. further work evaluating the response to medical intervention and the differences in hemodynamic profiles of patients with cm-apical and cm-basal is warranted. therapy using sodium nitroprusside (snp) intrathecal (intraventricular) aims for a more effective approach for prophylaxis and treatment of cerebral vasospasm associated to a subarachnoid hemorrhage (sah). qualitative study whose objective was to analyze clinical cases to specific approach for cerebral vasospasm related to sah. two patients, the first one is a years old female with aneurysm rupture of the left posterior communicating artery, sah fisher iii, hunt hess . the second one is years old male with artery rupture of the middle cerebral artery, sah fisher iii, hunt hess , both were submitted to embolization, leading to acute hydrocephalus, in which external ventricular drainage (evd) was established. through the evd, a prophylactic intrathecal protocol was instituted ( ml snp with , ml of normal saline , % solution applying ml nps through the evd each hours for hour by infusion pump). patients evolved well with no neurologic or motor sequel and with a modified rankin scale = . the third patient was a years old male with aneurysm rupture in anterior communicating artery, sah fisher iii, hunt hess , severe vasospasm per operative in the left middle cerebral artery (mca), treated by angioplasty with balloon. starting the treatment protocol of cerebral vasospasm by lombar catheter: dosage mg ( ml) snp, solution with ml snp at ml of normal saline , % applying ml through the lombar catheter each hours for hour by infusion pump. patient without complication with modified rankin scale = . the cost for prophylactic therapy for days was u$ , ; if the patient had developed clinical vasospasm, the cost for a day treatment would be an average of u$ . , , having a great impact on morbidity, mortality and cost of hospital stay. angiography does not reveal a source of bleeding in - % of those with subarachnoid hemorrhage. these patients usually have a benign course and favorable outcome, especially those with a perimesencephalic pattern of bleeding (pm-sah); more diffuse bleeding has been associated with higher risk of vasospasm and neurological disability. we evaluated whether amount or pattern of bleeding better predicts risk of neurological complications and outcome. methods angio-negative sah patients were prospectively studied over seven years. six were excluded when a vascular etiology was identified on repeat angiography. pattern of bleeding, amount of cisternal (hijdra score) and ventricular blood (ivh score), and ventriculomegaly (bicaudate index) were assessed. neurological outcomes included hydrocephalus, angiographic vasospasm, and delayed ischemic neurological deficits (dind, based on clinical deterioration). functional outcome was assessed at -year using the modified rankin scale (mrs). bleeding was perimesencephalic in ( %), diffuse in ( %), cortical in and ct-negative in . patients with diffuse bleeding had higher hijdra ( [iqr - ] vs. [ - ]) and ivh scores ( [ - ] vs. [ - ]), and bicaudate index ( . [ . - . ] vs. . [ . - . ]) than those with pm--v ( % vs. %, p= . ) and require ventriculostomy ( % vs. %) and shunt placement ( % vs. %, both p= . ). moderate-severe angiographic vasospasm developed in % diffuse vs. % pm-sah (p= . ), while dind only occurred in those diffuse bleeding ( %). neither hijdra nor ivh score was higher in those developing vasospasm, across or within bleeding patterns. those with diffuse sah were less likely to be discharged home ( % vs. %, p= . ) or achieve minimal disability (mrs - , % vs. %, p= . ). angio-negative sah can result in hydrocephalus, vasospasm, cerebral ischemia, and residual disability. this is more likely in those with diffuse bleeding, a disparity not explained by a greater volume of cisternal or intraventricular bleeding. independent of the cholesterol lowering effects of hydroxymethylglutaryl conenzyme a reductase inhibitors(statins), there has been much debate about their protective effect against delayed cerebral ischemia (dci). various ongoing trials are aimed at assessing their effectiveness against dci after primary subarachnoid hemorrhage (sah). there is scanty literature on dci in patients who were on statins prior to the occurrence of sah. a retrospective chart review was done after approval from the institutional review board. data was collected from july to april using the icd code for sah. patients with sah secondary to avm, trauma and surgery were excluded. demographics, baseline characteristics and occurrence of clinical dci were collected. admission home medication list was used to identify patients on statins prior to admission. all statistical analysis was done using sas. a total of patients with primary sah were included. out of patients, ( . %) were on home statin. only ( %) patients within this group developed dci while ( . %) patients in the statin naive group developed dci (p= . ). this difference persisted even after correcting for age (p= . ), sex (p= . ), race (p= . ), smoking (p= . ), history of diabetes (p= . ), stroke/tia (p= . ), peripheral vascular disease (p= . ), hypertension (p= . ), hyperlipidemia (p= . ), home calcium channel blocker use (p= . ) and fisher grade (p= . ). a multivariate logistic regression analysis with backward selection further confirmed that the only significant factor affecting vasospasm was prior statin use (p = . ). the above findings suggest that prior statin use reduces the rate of dci after sah. though the known confounders were taken into consideration, the possibility of unknown confounders cannot be completely excluded. a larger prospective study may be required to verify these effects. the potential clinical implication of this would be to put patients with unruptured and untreated aneurysms on long-term statins. patients sometimes report that surviving a near-death experience results in enhanced appreciation of the preciousness and joy of life. we sought to determine how frequent the "stroke of insight" phenomenon occurs after sah. we prospectively enrolled sah patients between and and followed up survivors with a telephone interview at and months. patients were asked "do you enjoy life more, about the same, or less than you did before your brain hemorrhage?" surrogate responses were not analyzed. global functional outcome was evaluated with the modified rankin scale (mrs) and qol with the sickness impact profile (sip). of survivors who responded to the survey, the majority ( %, n= ) reported that they enjoyed life more since the hemorrhage, whereas only % enjoyed life less. enhanced life enjoyment was associated with female gender and white (versus non--hess grade. patients with enhanced life enjoyment were more likely to report improved marital status ( % versus %, p< . ), and were less likely to have rumination on their illness (p< . ). improved life enjoyment was associated with better sip qol scores ( . ± . versus . ± . , p< . ), but had no relationship with concurrent disability on the mrs (p= . ). remarkably, % of those reporting that they enjoyed life more were unable to walk without assistance (mrs or ). the majority of sah survivors enjoy life more after their hemorrhage. increased life enjoyment has no relationship with physical disability and handicap, but is associated with improved qol. informing patients of the "stroke of insight" phenomenon may be a simple and effective way to set positive expectations and promote recovery after sah and similar life-threatening illnesses. parenteral diclofenac infusion is commonly used in neurocritical patients and has been shown to effectively decrease body temperature after aneurysmal subarachnoid haemorrhage (asah). hemodynamic side effects and in specific the effect on brain homeostasis are understudied. twenty-one asah patients with multimodal neuromonitoring of intracranial pressure (icp), brain tissue oxygen tension (p b to ), and cerebral metabolism (microdialysis, md) receiving parenteral diclofenac infusions were analyzed in a prospective observational cohort study. mg diclofenac diluted in cc normal saline was administered at the discretion of the attending neurointensivist. we analyzed core body (cbt) and brain temperature (bt) over hours and hemodynamic (cardio-, cerebrovascular) and cerebral metabolic parameters over hours after intervention. ten-minuteaverage files of cardio-and cerebrovascular parameters and hourly files of md datasets were analyzedusing a generalized estimating equation.a pre-intervention baseline was calculated for every parameter. one-hundred-twenty-three parenteral diclofenac infusions over min (iqr - min) were analyzed. cbt and bt decreased to a minimum of . ± . °c and . ± . °c, h and h after diclofenac infusion (baseline . °c± . °c and . ± . °c, respectively, p< . ). hemodynamic side effects included a % reduction of map (by ± mmhg) and cpp (by ± mmhg) resulting in increased use of vasopressors in % of interventions (p< . ). p b to significantly decreased from ± mmhg baseline by % (p< . ) resulting in brain tissue hypoxia (p b to < mmhg) in % of interventions and % (n= ) of patients. in none of the interventions with baseline p b to above mmhg, brain tissue hypoxia was observed. baseline-p b to below mmhg was independently associated with brain tissue hypoxia during intervention (p< . ). there was a trend towards higher brain tissue lactate-pyruvate ratio and lower pyruvate after parenteral diclofenac after sah is associated with hemodynamic side effects and may result in brain tissue hypoxia without significantly affecting brain metabolism. the impact on outcome needs further investigation. delayed cerebral ischemia (dci) is a complication of subarachnoid hemorrhage (sah) with significant mortality/morbidity. digital subtraction angiography (dsa) can detect cerebral vasospasm which is a surrogate marker for dci. there is emerging data that perfusion computed tomography (ctp) is useful in detecting dci. we have compared the utility of ctp and dsa in detecting dci. patients with primary sah admitted to two academic institutions between july and april were identified. patients with clinical dci who underwent dsa or ctp (image processing through vitrea®) were included. the area of perfusion abnormality was traced out to generate cerebral blood flow (cbf), mean transit time (mtt) and cross sectional area. abnormal cbf and mtt values were compared to normal symmetrical areas in the opposite hemisphere. dsa reports were reviewed to identify radiologic vasospasm. out of patients, had clinical dci( . %). in those with dci, / patients that underwent ctp had abnormalities ( . %) compared to / patients that had vasospasm on dsa ( . %; p= . ). median abnormal cbf was . ( . - . ) ml/ gm/sec compared to . ( . - . ) ml/ gm/sec in area of normal perfusion (p= . ). median abnormal mtt was . ( . - ) seconds compared to the normal area of ( . - ) seconds (p< . ). median interhemispheric cbf and mtt difference was . ( . - . ) ml/ gm/sec and . ( . - . ) seconds respectively. median area of abnormal perfusion was . ( . - . ) cm . seventeen patients underwent ctp and dsa. a normal ctp excluded vasospasm on dsa. perfusion abnormalities involving an area of less than . cm did not have vasospasm on dsa. ctp is a useful indicator of dci and is comparable to dsa. in patients with clinical dci and a normal ctp, dsa is unlikely to pick up vasospasm. as the area of perfusion abnormality increases (greater than . cm in our subset of patients), dsa is more likely to show vasospasm. aneurysmal subarachnoid hemorrhage (asah) is more common in women than in men. current knowledge on potential gender differences after an asah occurred is sparse, albeit of clinical relevance. retrospective cohort study including patients with asah admitted to a neurovascular center at a major academic center at the university hospital of bern, switzerland. patients below age and with non-aneurysmal sah were excluded. we included consecutive patients with asah between january , and february , . women were older than men (median age years [interquartile range [iqr] - ] versus [iqr - ], respectively, p= . ), and progressively overrepresented with increasing age ( . % of women for the whole cohort). of note, in the swiss population the proportion of both genders between and years is similar, with women being slightly overrepresented at older ages. global disease severity at admission, measured by the acute physiology and chronic health evaluation (apache) ii score, was higher in women than in men (median score points versus [iqr - ], p= . ) even after correction for age. the apache ii score independently predicted an unfavourable outcome and mortality as opposed to gender. we found no differences between genders in the adopted aneurysm-securing strategy, intensive care interventions (administered drugs, rates of endotracheal intubation, tracheostomy, length of mechanical ventilation and placement of an external ventricular drainage). women and men with asah confirmed to be similar in terms of medical history, clinical / radiological severity of asah, complications and outcome. in conclusion, this study confirms that women with asah outnumbered men, especially at higher age. global disease severity on admission is higher in women and predicts, independently from gender, unfavourable outcome and mortality. finally, this study finds new relevant similarities between genders. complications of aneurysmal subarachnoid hemorrhage (asah) may include hypertension and neurogenic myocardial stunning. subsequent management often involves beta blockade. high fisher grade asahs may also be complicated by cerebral vasospasm, which could have pathophysiologic influence from sympathetic nervous system stimulation or inhibition. we investigated any relationship of beta blockade to the incidence of radiographic vasospasm in asah by retrospectively examining adults admitted to the sicu at loma linda university medical center between / and / , excluding those who expired within days of admission because of inability to assess outcomes. three groups were isolated relevant to beta blockade: were never beta blocked (no/no), were started on a beta blocker after admission (no/yes), and were continued on their home beta blockers (yes/yes). records were analyzed for the development of vasospasm with or without resultant infarction, death, and discharge status. outcomes were evaluated using multivariate analysis through logistic regression and adjusted for potential confounders. odds ratios were calculated setting the or for no/no patients to . one hundred and forty five patients had vasospasm, consequently infarcted, and died or required care in a longterm facility. patients in the no/yes group had significantly increased radiographic vasospasm ]. however, despite increased incidence of vasospasm, these patients had significantly fewer deaths or need for long term care [or . ( . - . )], with decreased tendency for infarcts ]. in the yes/yes group, there was a trend toward increased vasospasm ] that led to infarction )], with decreased mortality or need for long term care in a facility [or . ( . - . )]. the use of beta blockers in asah is associated with increased incidence of radiographic cerebral vasospasm. however, despite the increased rate of vasospasm, the use of beta blockers was associated with improved discharge characteristics. patients with subarachnoid hemorrhage (sah) frequently undergo continuous electroencephalography (ceeg) monitoring in the icu. we describe commonly encountered eeg patterns in sah patients with clinical correlation. patients with primary sah admitted to two academic institutions between july and april were identified. records were reviewed to note the presence of intraventricular hemorrhagic extension (ivh), intracerebral hemorrhagic extension (ich), location of subarachnoid blood, occurrence of delayed cerebral ischemia (dci), patient outcomes and length of stay (los). eeg reports were reviewed and classified as to the presence of arrhythmic continuous slowing (acs), rhythmic and periodic slow activity of triphasic morphology (tw), epileptiform activity (ea), and coma pattern. patients with metabolic causes for tw were excluded. of patients, had a routine eeg or ceeg monitoring.thirteen ( . %) exhibited non-metabolic tw, ( . %) had ea, ( . %) had acs, patient had coma pattern and had normal eeg. the presence of subarachnoid blood around the basal cisterns did not influence eeg patterns.in patients with ivh, the presence of tw patterns was significantly more common than other patterns ( . % vs. . %;p= . ). ea was associated with dci ( . %) as compared to non-epileptiform patterns ( . %;p = . ).ea was more common in patients with ich without statistical significance( . % vs. . %;p= . ). median los in patients with tw, ea and acs were ( - ), . ( - ) and . ( - ) days respectively without significant difference. patient outcomes were similar among all groups. non-metabolic tw are scantly reported in the literature and typically associated with diencephalic and brainstem lesion. in patients with sah, the presence of ivh and not cisternal blood was associated with non-metabolic tw. dci was significantly associated with the generation of epileptiform activity and the presence of ich seemed to favor an epileptiform pattern. eeg patterns did not influence los or outcome in our subset of patients. adenosine is an endogenous purine nucleoside that causes transient heart block in the av node when administered parenterally. we describe our experience with cases of severe intraoperative aneurysm rupture in which adenosine was administered to allow for control of the intraoperative bleeding. over a year period, we have treated approximately aneurysms with open microsurgery. two-thirds were unruptured. severe intraoperative aneurysm rupture that could not be readily controlled occurred in cases. of the aneurysms had recently bled, case was an unruptured aneurysm. in all cases, the amount of bleeding precluded safe application of temporary clips. an intravenous infusion of adenosine ( mg) was given in all cases. in , there was significant bradycardia and hypotension culminating in a brief cardiac pause ( - seconds), allowing for rapid dissection and clipping of the aneurysm. in cases, there was bradycardia and hypotension, but no cardiac arrest. in cases, there was limited bradycardia and hypotension, and a second dose ( mg) was required to slow the heart enough to allow for aneurysm treatment. in such cases, the adenosine allowed us to clear the field adequately to apply temporary clips in a precise fashion, and then to clip the aneurysms properly. poor response to the initial dosing was not related to patient size or other identifiable factor. adenosine has been used safely in our experience to allow for management of severe intraoperative aneurysm rupture. in most cases, there is a meaningful cardiac pause. in some instances, patients are less sensitive, and the dose must be repeated to achieve the desire effect. no adverse cardiac or pulmonary events were associated with the use of adenosine in our series. intraventricular hemorrhage (ivh) is an established independent predictor of poorer outcome in subarachnoid-and intracerebral-hemorrhage. though, limited knowledge exists regarding the pathophysiologic mechanisms that may lead to cerebral injury and poorer outcome. this is the first report presenting in vivo data on cerebral perfusion and brain tissue metabolism during the occurrence of ivh and after intraventricular fibrinolysis (ivf). a -year-old woman with severe subarachnoid hemorrhage (sah), hunt&hess grade , modified fisher scale , was admitted to our neuro-critical care unit. within the first hours an extraventricular drainage was placed and a left-sided mca aneurysm was coiled. after obtaining informed consent from the legal attorney, the patient received invasive multimodal neuro-monitoring, consisting of a cerebral blood flow (cbf)-and microdialysis-probe placed into the ipsilateral frontal white matter. within hours after probe placement we observed a significant drop of cerebral blood flow (cbf below ml/ g/min) and an increase in l/p-ratio without significant changes in cerebral perfusion-or intracranial-pressure. imaging revealed a re-hemorrhage into the ventricular system with blockage of the foramina of monro and acute hydrocephalus. consequently, therapeutic ivf was undertaken with mg of rtpa which lead to sufficient clot resolution. after ivf we normalization of cerebral perfusion and metabolism. this is the first report on ivh and its potential mechanisms that may contribute to secondary injury in the human brain. a decrease of cerebral blood flow and disturbance of cerebral metabolism was documented during the occurrence of ivh, supporting existing hypotheses of global impairment. moreover, we could document profound treatment effects of ivf leading to a restored cbf and a stable aerobic metabolism in the investigated brain tissue. many patients with aneurismal subarachnoid hemorrhage (sah) present with acute, labile, hypertension and may be at risk for rebleeding. clevidipine, a novel, ultra-short acting dihydropyridine has been used in cardiac surgery, acute hypertensive emergencies and patients with intracerebral hemorrhage, but not in sah patients. the clash study (clevidipine in aneurismal subarachnoid hemorrhage) is a prospective evaluation of the efficacy and safety of clevidipine in controlling systolic blood pressure (sbp) before the aneurysm is secured. the primary endpoint is the number of patients achieving sbp target within minutes. post-hoc, sbps pre-infusion, during-infusion and postinfusion were compared using a generalized estimating equation. we present the first patients enrolled: men and women, mean h&h and fisher . , aneurysms coiled and clipped. mean sbp upper and lower goals were ± . and ± . mmhg. analyses included , sbp data points. all patients reached sbp target within . ± min using an infusion rate of . ± . mg/hour. the mean preinfusion, during-infusion and post-infusion sbps were . ± . , . ± . and . ± . mmhg (pre-infusion vs during-infusion p < . , pre-infusion vs post-infusion p < . , during-infusion vs post-infusion p < . ). after the st sbp control readings, sbp was above the upper target goal . ± . % and below the lower . ± . % of the time. icp did not increase during infusion (n= ). no patient rebled. in one patient the infusion was stopped temporarily times due to sbp below the target range. there were ( . %) sbp values < mmhg and none < mmhg. clevidipine controlled sbp in all patients with sah in < min and kept sbp within the selected range in . % of the time without any patient rebleeding. financial support: research grant from the medicines company to conduct this study. aneurysmal subarachnoid hemorrhage (asah) is associated with numerous adverse sequelae. patients who survive the initial hemorrhage are at high risk for delayed secondary brain injury, including cerebral infarction, neuronal cell death, white matter abnormalities, and hydrocephalus. resulting in focal neurological deficits, cortical dysfunction, and both longterm cognitive and psychosocial deficits referred to as sah-induced "delayed neurological deficits" (dnds). review of the literature revealed that heparin had previously been advocated to reduce complications of asah. here, we report on our favorable experience with the use of heparin prophylaxis in the management of patients who are at a high risk for developing sah-induced dnds. a retrospective chart review of patients that presented to the university of maryland medical center were reviewed between january and may . inclusion criteria were patients with fischer grade iii sah due to rupture of a true saccular aneurysm and were treated by surgical clipping within hours of the patient's ictal event. exclusion criteria were patients who had a localizing deficit related to an intracerebral hematoma from the ictal event. included in this study were patients that were started on an intravenous infusion of heparin and an additional patients that served as matched controls. none of the patients exhibited heparin-induced thrombocytopenia (hit). the heparin regimen used appeared to be safe. patients administered low-dose iv heparin experienced significantly fewer occurrences of ischemia-related ct hypodensities as well as symptomatic vasospasms than case controls. retrospective analysis of our clinical experience with constant iv infusion of low-dose heparin in patients at high risk for sah-induced dnds indicates early use of low-dose iv heparin infusion may be safe and perhaps beneficial in patients having undergone surgical clipping. further study with a double-blind placebo-controlled trial is warranted to establish the role of heparin in the prevention of sah-induced dnds. subarachnoid hemorrhage patients (sah) may experience cardiac biomarker elevation in serum troponin and b-type natriuretic peptide (bnp). we hypothesized that elevations in these cardiac biomarkers after sah are predictive of increased patient mortality. we retrospectively reviewed the medical records of all non-traumatic sah patients admitted from march to march including medical history, modified fisher scale on initial head ct scan, initial glasgow coma scale (gcs), serum troponin t and bnp within hrs of admission. survival data was dichotomized as either alive or dead by chart follow-up. values (> pg/ml) versus normal values against alive or dead status. we identified sah patients, with initial measured troponin, and with initial measured bnp.the mean age was (range - ) and % male. modified fisher grade was - in %, and grade - in %. the initial gcs mean was (range - ), % of patients had intracranial aneurysm, while % were 'angiogram-negative' sah. twenty sah patients died, with a mean of days post sah (range - ), six from cardiopulmonary or multiple organ failure, from sah, and unknown/other. elevated troponin was seen in % ( of ) with a mean = . (range, . - . ), and elevated bnp in % ( of patients) with a mean = (range, - ). patients with elevated levels of troponin had a greater chance of death (p= . ). patients with elevated levels of bnp also had a higher mortality (p= . ). the data demonstrate a statistically significant association with elevated cardiac biomarker elevation and risk of subsequent death after sah, which occurs not only during the immediate post sah period but after initial hospitalization. delayed cerebral ischemia (dci), length of stay and glasgow outcome scale (gos) following angiogram-negative sah (ansah) are infrequently and inconsistently described in the literature. furthermore ansah are generally considered to have a better prognosis than aneurysmal sah (asah). ansah subgroups include benign perimesencephalic sah (pmh) and aneurysmal-type or diffuse sah. we report and compare outcome data of patients presented with diffuse ansah and diffuse asah. a retrospective chart review of patients who presented to academic institutions between july- and april- who met the criteria for diffuse spontaneous sah were reviewed. the patients were further divided into ansah (n= ) and asah (n= ). delayed cerebral ischemia rates, length of stay and discharge gos were compared and analyzed between two groups using sas statistical software. discharge gos scale was dichotomized in good outcome (gos - ) out of patients, a total of ( . %) patients meet the criteria of diffuse ansah and ( . %) meet the criteria of diffuse asah. demographics and baseline characteristics including age, sex, race, hypertension, diabetes, gcs on presentation, hunt & hess score and fisher grade among two groups were comparable. overall % (n= ) of ansah and % (n= ) of asah showed dci (p= . ). mean length of stay was days in nasah and days in asah. good outcome was seen in % (n= ) in nasah and % (n= %) in asah groups (p= . ). in our patient cohort of ansah, % of patients had dci. even though it is less then asah group it is considerably higher then previously reported in the literature. furthermore length of stay and discharge gos between two groups were comparable. this study indicates that diffuse ansah is not a 'benign' condition and warrants a low index of suspicion for complications with a multidisciplinary approach to management. transcranial doppler (tcd) is a common method used to measure cerebral blood flow velocities and estimate flow resistance related to intracranial pressure (icp). we present the case of a patient with subarachnoid hemorrhage and clipped aneurysm, who, while undergoing tcds, rebled. a year old man presented with sudden-onset severe headache and neck pain. ct of the head showed a subarachnoid hemorrhage (sah) with intraventricular extension and obstructive hydrocephalus. an anterior communicating artery (acom) aneurysm was found and clipped and a ventriculostomy was placed. after surgery there was an interval decrease in the sah. eight days after the original event the patient re-bled during a tcd test because of clip failure. tcd waveforms were captured before, during the bleed and post treatment with mannitol and csf drainage from the ventriculostomy. prior to the bleed. icp was mm hg, the left mca flow velocity was cm/sec and the pulsatility index (pi) . . during the bleed the icp increased to and pi to . - . , with the waveform showing a narrow peak and decreased diastolic and mean velocity. mannitol g was given and the ventriculostomy was opened to drain. within minutes the icp decreased to mm hg, the pi improved to . , the waveform widened and the velocities returned to previous levels (video will be provided with the abstract showing the tcd changes). repeat ct of the head showed increased sa blood and extensive new intraventricular hemorrhage; catheter angiogram a malpositioned clip. the acom aneurysm was coiled successfully. we present this unique case of tcd capturing the dynamics of a real-time intracranial aneurismal bleed with significantly elevated icp. our data demonstrated the tcd pi, flow velocities and waveforms changed dramatically during the rebleeding and improved quickly with treatment. transcranial doppler (tcd) is the least invasive method to detect cerebral vasospasm but is unable to interrogate vessels beyond the circle of willis and is highly operator-dependent. we tested a novel technique whereby we record the miniscule pulsation of the skull gated with cardiac contraction and compared it to tcd in patients with subarachnoid hemorrhage. skull accelerometry was performed using a prototype device designed by jan medial, inc. (mountain view ca). the device has highly sensitive accelerometers that couple through plastic feet to the patient's scalp, arrayed with detectors over the forehead, at midline occiput, each over the temporal bones, and on the patient's vertex. they are held in place with a plastic strap. paired tcd recordings and accelerometry epochs (typically minutes of recording) were compared in patients with and without spasm. a total of accelerometry recordings were obtained in subjects with subarachnoid hemorrhage who had paired tcd recordings. this allowed distinct pairings of data sets (right, left, posterior). a unique signature was identified by a fast fourier transform waterfall technique revealing a shift in accelerometry signals to higher frequencies (representing a "bruit" of sorts) in patients with tcd identified vasospasm. an analytic model was created based on the first recordings, and validated using the remaining recordings. this revealed % sensitivity and % specificity for detection and localization of spasm. highly sensitive skull accelerometry detects a shift toward higher vibration frequency in patients with vasospasm-a cranial "bruit". this technique may be a highly sensitive tool for the detection of cerebral vasospasm following subarachnoid hemorrhage. a prospective, blinded validation study is on going to measure this novel tool's performance characteristics in a larger sample of patients. financial support: research grant from jan medical, inc. j.n. is year-old hispanic male prisoner previously healthy presented to our institution altered due to diffuse subarachnoid hemorrhage (fisher grade iv) and a bi-lobed "mickey mouse" right m middle cerebral artery (mca) ruptured aneurysm. initially, j.n.'s hunt and hess grade level of on arrival, but declined to a in the ed. j.n. was intubated and an external ventricular device was placed. the anatomy of the aneurysm was complex in nature measuring mm in maximal dimension with the superior lobe measuring . mm and the inferior lobe measuring . mm. based on the complex anatomy of the aneurysm, a -vessel angiogram was planned to treat the aneurysm with a trans-arterial coil-embolization approach. a x mm septal balloon was used with a synchro microwire, with the balloon been placed across the neck of the inferior aneurysm. the superior aneurysm was accessed with a sl- microcatheter and coiled in the usual fashion. the sl- microcatheter was then re-directed to the inferior aneurysm and coiled similarly. post-angiographic images showed complete obliteration of the aneurysm with a small neck residual to protect en passé branches. evaluation of the literature is scant with reports of bi-lobed aneurysm with the classic description of "mickey mouse" or "mirror" aneurysm. trans-arterial coil-embolization provided a safe, rapid, and effective method for coiling a complex bilobed aneurysm with no major thrombo-embolic events. trans-arterial coil-embolization is a procedure used in the treatment of gross hematoma and fistula in human and the veterinary population. to our knowledge, there is no report of trans-arterial coil embolization for the treatment of bi-lobed aneurysm posted within the usual medical research engines. our institution is presenting a novel endovascular technique in the treatment of a classic bi-lobed mickey mouse aneurysm. j.n. was able to recover fully and eventually discharge to the infirmary in federal prison. the routine practice of therapeutic hypothermia is advocated in the management of comatose survivors of out-of-hospital cardiac arrest (ohca), particularly if ventricular fibrillation is the initial rhythm. potential benefits of hypothermia were evaluated for comatose survivors after ohca due to aneurysmal subarachnoid hemorrhage (sah). following return of spontaneous circulation (rosc), therapeutic hypothermia was induced for comatose sah patients except for those with devastating brain damage on brain ct and cardiac arrest over minutes. immediately after diagnosis and evaluation of cardiac function, cooling was promptly initiated by nasogastric lavage with iced water and surface cooling under general anesthesia. the ruptured aneurysm was obliterated by surgical clipping with wide decompressive craniectomy. core temperature was maintained at -urokinase was injected via cisternal drain and nicardipine and fusdil hydrochloride were intravenously administered to prevent cerebral vasospasm. clinical outcome was assessed according to the glasgow outcome scale (gos) months later. six women, aged between and years, were eligible during the past years. their glasgow coma scale was after resuscitation. electrocardiogram on arrival was asystole in and pulseless electrical activity in patients. myocardial stunning was detected in patients by echocardiogram. surgery and hypothermia treatment were uneventfully conducted. postoperative mri revealed extensive cerebral ischemia in and vasospasm-related ischemic lesion in patient. their gos was good recovery in , severe disability in , persistent vegetative state in , and death in patients. therapeutic hypothermia was feasible for ohca patients due to sah. since neurogenic stunned myocardium could be a possible cause of cardiac arrest in sah, beneficial effects of induced hypothermia are expected just like cardiogenic cardiac arrest. appropriate prognostication methods are warranted for decision making to treat or not. autonomic shift (as), characterized by increased sympathetic nervous system activation, has been implicated in neurologically mediated cardiopulmonary dysfunction and immunodepression following stroke. however direct measurement of autonomic nervous system dysfunction is difficult to obtain routinely in critically patients. we investigated the prevalence of as defined by readily available clinical parameters and determined the association of as with subsequent infection in a cohort of patients with aneurysmal sah (asah). data were obtained from a single center cohort study of asah patients admitted from january , through april , . as was defined as at least one early routine clinical marker of neurologically mediated cardiopulmonary dysfunction (based on electrocardiogram, echocardiogram, cardiac enzyme testing or clinical diagnosis of neurogenic pulmonary edema). exclusion criteria were beta-blocker treatment a known pre-existing abnormal electrocardiogram. multivariable logistic regression models were developed to evaluate the association between as and subsequent infection after adjusting for other covariates. a total of patients were included (mean age , % male). autonomic shift was seen in / ( %), and infection was seen in / ( %). autonomic shift was associated with subsequent infection on unadjusted analysis (or= . , % ci . , . ). however, on multivariable analysis adjusting for other predictors of infection, there was no significant association between as and subsequent infection (or . , % ci . , . ). age, clinical grade, aneurysm location and presence of ich were all identified as independent predictors of infection following asah. we identified evidence suggestive of as based on readily available clinical markers in % of patients with asah. however, as defined by these clinical criteria was not an independent predictor of infection. additional studies may be warranted to determine the optimal definition of as and to determine the clinical significance of this finding. we have previously studied the effects of falling temperature on the incidence of asah at our institution over days observing , asah. we previously reported that every degree decrease in temperature was associated with . % increase in risk of asah [relative risk (rr), . , p = . ]. we looked within the same data using other metrics to identify patterns in temperature changes which might result in physiological stress that increases the incidence of asah admissions at our institution. we developed a mathematical equation based on the premise that degrees fahrenheit is the ideal external temperature for humans. our formula measured the variation above or below ° as a percentage of ° for every day of days of observation. the relationship of absolute differences between tmax and tmin was examined to see if daily temperature variation was associated with increasing incidence. the odds ratio for incident asah relative to ° was . (ci . - . ) p= . . likelihood of incident asah increased as the ratio of tmax to ° fell below zero (i.e. experienced colder temperatures). intraday variation as measured by the absolute difference between tmax and tmin was strongly associated with increasing incidence, p= . , or . , ci ( . - . ). a smaller, not larger, difference between tmax and t min was associated with increased likelihood of asah admission. colder daily maximum temperatures relative to ° f, and smaller intraday temperature fluctuations are associated with increased asah admissions at our institution. smaller daily temperature ranges correspond to seasonal periods with the least daylight in this region, and may represent sudden arrival of cold weather in warm months. both metrics support the hypothesized increased likelihood of asah with falling environmental temperatures. these new methods may assist in the development of new algorithms for asah predictions based on temperature. near-infrared spectroscopy (nirs) is a noninvasive means of measuring cerebral regional mixed arteriovenous (av) brain oxygenation. we hypothesized that frontal nirs would correlate against more established modes of vasospasm monitoring and systemic variables for severe aneurysmal subarachnoid hemorrhage (asah). case report we describe a year old male who presented with coma (gcs= , e m v t) after severe asah (modified fisher ) from a ruptured giant basilar aneurysm ( . cm x cm) who developed severe diffuse vasospasm with no change on clinical examination. frontal nirs monitoring was applied in addition to map, cpp, cbf (hemedex tm ), cardiac output (co), spo , core temperature, continuous quantitative eeg (qeeg) with alpha delta ratio (adr) monitoring, along with daily tcd. the patient developed severe diffuse vasospasm and underwent angioplasty of the mca, aca, and pca arteries and received intra-arterial verapamil. pearson's correlation coefficient was used to analyze trends in variables pre-and post intervention. values were recorded over a four-day period. calculated correlation coefficients revealed invasive cbf to right nirs r= . (p= . ) and left r= . (p= . ) but was contralateral to the cbf probe, co to right nirs r= . (p= . ) and left r= . (p= . ). coefficients with weak or negative correlation included arterial map to right nirs r=- . (p= . ) and left r=- . (p= . ), noninvasive map to right nirs r=- . (p= . ) and left r= . (p= . ), spo to right nirs r=- . (p= . ) and left r=- . (p= . ). noninvasive map to arterial map r= . (p= . ), noninvasive map to cpp r= . (p= . ), and arterial map to cpp r= . , (p= . ). nirs correlates with ipsilateral invasive cbf values (r= . , p= . ) and trends with cardiac output. nirs did not correlate with map, cpp, spo , tcd or qeeg adr data. larger prospective studies are needed to validate these preliminary results. this case report describes the use of intraventricular nicardipine in a pediatric patient for the treatment of severe cerebral vasospasm following sah from traumatic pica dissection. intraventricular nicardipine has been suggested as an adjuvant to standard therapies in adults with aneurysmal sah but its use has not been described in pediatric patients. a year-old boy was transferred from an outside hospital for treatment of severe sah following sports related head injury. he was found to have a dissecting pica psuedoaneurysm which was treated endovascularly. bilateral ventricular drains had been placed for hydrocephalus. his neurological examination declined on hospital day and ct angiogram demonstrated severe vertebrobasilar vasospasm. intraventricular nicardipine was administered in addition to treatment with transluminal balloon angioplasty, induced hypertension and nimodipine. the patient received mg intraventricular nicardipine twice daily for days and the dose was then increased to mg every hours for a total of days. both ventricular drains were clamped for min following administration. he tolerated doses without hemodynamic effects, elevations in intracranial pressure or evidence of ventriculitis. after improvement in clinical examination and mean cerebral blood flow velocities by tcd, intraventricular nicardipine was stopped. he was discharged to acute rehab and was ambulatory and preparing to restart school at age appropriate grade level at month follow up. intraventricular nicardipine was safely administered in this year-old patient with severe vasospasm following sah with a good outcome. intraventricular nicardipine should be considered as an adjuvant to standard therapies for vasospasm in pediatric patients, though further studies are needed to evaluate safety and efficacy in both pediatric and adult patients. the benefit of early tracheostomy has been well described. patients with aneurysmal subarachnoid hemorrhage (asah); however, represent a distinct population to which traditional weaning parameters may be difficult to apply. the purpose of this study is to identify admission characteristics of asah patients that predict need for tracheostomy. this was a retrospective cohort analysis of consecutive asah patients. we excluded patients with a history of symptoms longer than hours prior to transfer, expired within hours, or no ct scan available prior to cerebral angiography. we collected data including: demographics, co-morbidities, neurologic exam, labs, ejection fraction % on echocardiogram, modified fisher scale, and hijdra scale. chi-square or wilcoxon tests were performed where appropriate with subsequent multivariate analysis of statistically significant variables. the data set included tracheostomy patients and non-tracheostomy patients. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ,p=< . ). the modified fisher and all components of the hijdra scale were significantly higher in the tracheostomy group. the bicaudate index was significant ( . vs. . ,p= . ); however, presence of hydrocephalus using this index was not. in the multivariate analysis older age, lower albumin, higher pco and presence of ventricular blood by hijdra scale remained significant predictors. neurologic status on admission, advanced age, burden of systemic illness, and intraventricular hemorrhage are associated with increased risk of tracheostomy. further research in this patient population on the benefits of early tracheostomy (lower mortality, less ventilator days and less intensive care unit days) is warranted. patients with subarachnoid hemorrhage(sah) have variable outcomes, some of these leading to major disability. established guidelines advocate administration of nimodipine to patients with sah. several recent trials have investigated the utility of statins and magnesium, however there has not been much data showing clinical benefit. we present data of patients with primary sah who had therapy with magnesium, nimodipine and simvastatin for prevention of delayed cerebral ischemia (dci). patients with primary sah admitted to two academic institutions between july and april were identified. all patients received therapy with magnesium, nimodipine and simvastatin for dci prophylaxis. outcomes were categorized as good in those with glasgow outcome scales (gos) of - and poor in those with gos - . chi-square analysis was used to compare outcomes between age, sex, race, hunt-hess scores ( - vs - ), presence of vasospasm and glasgow coma scale (gcs) on presentation (below or above ). of patients identified with primary sah, . % had a good outcome. the mean age for patients with a poor outcome was . (sd . ) when compared to . (sd . ) in patients with a good outcome (p= . ). among those with a gcs - on admission, . % had a good outcome while in those with less than only . % had a good outcome (p< . ). when comparing hunt-hess scales, . % of those with grades between - had good outcomes, while . % of patients with grades - had poor outcomes (p< . ). among those who developed dci, . % had a good outcome as compared to . % had poor outcomes (p= . ). age and race failed to show any difference in patients with good and poor outcomes. we present our data on therapy with nimodipine, magnesium and statin for prophylaxis against dci. age, admission gcs, hunt-hess scale and occurrence of dci were predictors of patient outcome. intraoperative rupture during the surgical treatment of a previosuly unruptured intracranial aneurysm is a rare event. we describe our experience with intraoperative aneurysm rupture in this setting. we reviewed all cases of unruptured aneurysms treated by a single surgeon from july, to june, and identified those patients who suffered intraoperative aneurysm rupture. of unruptured aneurysms treated during this period, there were instances of intraoperative aneurysm rupture ( . %). in our experience, rupture occurred during dissection of either a perforator ( cases) or a major efferent vessel ( cases) from the aneurysm dome or of the dome from adherent overlying cortex ( case). in one instance, the aneurysm ruptured during removal of the anterior clinoid process. in cases, blunt rather than sharp dissection was being employed. in cases, bipolar electrocautery and gentle tamponade successfully sealed the rupture point. in cases, a clip placed across the bleeding site well up on the dome of the aneurysm controlled the bleeding and allowed for completion of the dissection and proper clipping. in the last case, the administration of adenosine was utilized to stop the bleeding and allow for proper clip placement. intraoperative angiography confirmed adequate aneurysm obliteration in each case. there were no clinical consequences associated with these intraoperative ruptures. intraoperative rupture during elective surgery for a previously unruptured aneurysm is uncommon. in our experience, rupture was typically associated with blunt dissection on the dome of the aneurysm. the use of bipolar electrocautery, clipping of the bleeding point, or intravenous adenosine infusion were successfully used to control bleeding in our cases. the neurovascular surgeon should be prepared to address this unlikely event, should it occur. aneurysmal subarachnoid hemorrhage (asah) is a life-threatening form of hemorrhagic stroke which is more common in women than men, typically between ages - . over the course of our nursing practice, we have observed a trend of pre-menopausal asah female patients who experience the onset of their menses during the initial week of hospitalization. we became curious as to whether there is a correlation between asah and an earlier onset menses than a normal - day cycle. retrospective, single-center review of the medical record of pre-menopausal females ages - years who were admitted to our neuroscience intensive care unit with the diagnosis of asah. chart review was specific to documentation of the onset of menses during the first week of hospitalization, medical/gynecological history with regard to last menstrual period, usual menstrual cycle characteristics, contraceptive use, past surgical history, and pertinent medications. over a month period (june -june ), we identified asah patients with being female. of the female asah charts screened, we found study patients. nine of ( %) females had documentation of starting their menses during their initial week of hospitalization for asah, much earlier than a normal range of the menstrual cycle of - days. one patient had menses documented on hospital day . this small retrospective study suggests that asah may disrupt the "normal" menstrual cycle of pre-menopausal females. to our knowledge, this is the first description of this gender and disease specific phenomenon. a prospective study is planned to better understand the role asah has on hypothalamic-pituitary-ovarian-uterine physiology. introduction - % of patients with spontaneous subarachnoid hemorrhage can have normal cerebral angiogram. vasospasm, hypoperfusion or thrombosis may hide the aneurysm. dynact is a promising new technique which may help in these cases. we present a case report that highlights the ability of dynact in identifying a thrombosed aneurysm that was undetected with routine cerebral angiogram. a year old female presented with the worst headache of her life. ct scan of the brain showed subarachnoid hemorrhage (sah) in suprasellar cistern, extending into the anterior interhemispheric fissure, bilateral perisylvian, prepontine cistern and right perimesencephalic cisterns along with extension in to the third and fourth ventricles. after the placement of an external ventricular drain, the patient was immediately taken to angio suite where a biplane cerebral angiogram showed - mm saccular aneurysm at right middle cerebral artery bifurcation and an unremarkable vasculature otherwise. repeat imaging using dynact showed the presence of a mm ruptured and thrombosed aneurysm at the right mca bifurcation. the thrombosed aneurysm was visualized and clipped surgically. this case report highlights the promising utility of dynact in identifying the culprit aneurysms. treatment of severe cerebral vasospasm in subarachnoid hemorrhage remains challenging. with failure of noninvasive therapy, endovascular modalities may be undertaken, albeit with limited efficacy; balloon angioplasty can be used only for proximal, focal spasm and intra-arterial calcium-channel blocker (ccb) bolus infusion has transient vasodilatory effects. we present a patient with severe vasospasm after subarachnoid hemorrhage, who demonstrated significant angiographic improvement with continuous infusion of intra-arterial verapamil over hours. a female in her mid- 's with sickle cell anemia presented with a hunt and hess , fisher grade iv subarachnoid hemorrhage secondary to a ruptured right posterior communicating artery. on initial assessment, the patient was localizing with only her upper extremities. the aneurysm was completely coil embolized and standard triple-h therapy maintained. on post-bleed day , the patient developed left-sided hemiplegia. angiography demonstrated critically severe, diffuse right anterior and posterior circulation vasospasm. angioplasty could not be performed due to microwire and balloon inaccessibility of stenosed anterior and posterior circulation vessels. subsequently, two microcatheters were positioned with their respective tips in the petrous right internal carotid artery (ica) and v segment of the right vertebral artery for continuous machine controlled intra-arterial verapamil infusion. dosing consisted of administering mg/hr verapamil into the right vertebral artery and mg/hr into the right ica. the patient was placed on a heparin drip and taken to the neurointensive care unit for monitoring. after hours of continuous ia verapamil infusion, angiography demonstrated significant improvement in right anterior and posterior circulation vasospasm, with only residual diffuse moderate stenosis. unfortunately, no corresponding clinical improvement was noted. prolonged infusion of intra-arterial ccb's may provide extended angiographic improvement in severe vasospasm refractory to conservative treatment and unsuitable for balloon angioplasty. with systematic study of such techniques, optimal agents and dosing for sustained vasodilation and clinical optimization may be defined. vasospasm remains a significant cause of morbidity after subarachnoid hemorrhage (sah), inducing delayed ischemic events. sah typically results in numerous complications including severe, treatment-refractory headache. fioricet® (acetaminophen mg/butalbital mg/caffeine mg) is a commonly used analgesic medication for the treatment of headache in sah. caffeine has been shown to reduce cerebral blood flow. the purpose of this study was to determine if there is an association between fioricet® administration and early vasospasm. a retrospective, medical record review was conducted, and patients were identified using the university health consortium (uhc) database. patients were included if they had an aneurysmal sah with a presenting hunt and hess grade of i-iv. data points included occurrence of clinical vasospasm, daily amount of fioricet® and other analgesics, daily pain scores, and patient demographics. a univariate analysis was performed to determine the association between extent of fioricet® exposure and early vasospasm (within the first days) after sah. a multivariate analysis was performed accounting for amount of fioricet® use, patient age, and hunt and hess grade. the population characteristics were typical of the sah population. patients who experienced clinical vasospasm received more fioricet® than those who did not have vasospasm (mean . + . tablets/day versus . + . tablets/day (p= . )). the odds ratio for vasospasm with regards to fioricet® use when controlled for age and hunt and hess grade was . ( % ci . - . ). the multivariate analysis did not yield any statistically significant associations with vasospasm. there was a significant association between fioricet® exposure and vasospasm in our univariate analysis. however, when correcting for age and sah severity, the association is not significant. thus, the data do not currently support a clear causal association. this preliminary data will be used to support a comparative study investigating headache treatment in sah. isolated complete third nerve palsy (tnp) in the setting of a subarachnoid hemorrhage (sah) is most commonly seen secondary to a posterior communicating artery (pcom) aneurysm. however, this same clinical picture with a negative angiogram and otherwise negative imaging studies becomes extremely rare. although trauma has been described as one of the most common causes of isolated tnp, concomitant post-traumatic sah and late onset isolated complete tnp has never been reported. we report a case of a delayed onset complete tnp after traumatic sah. case report. a year-old male with type- diabetes mellitus presented to the emergency department with painless diplopia and left eye ptosis three days after sustaining a fall with closed-head injury without loss of consciousness. his non-contrast head ct scan showed a fisher grade subarachnoid hemorrhage. upon arrival and throughout his hospitalization, the patient had a glasgow coma scale (gcs) of . his neurological exam revealed findings consistent with isolated complete thirdnerve palsy (tnp) involving the pupil. his neurological examination was otherwise normal. diagnostic digital subtraction angiography (dsa) was negative as it was his brain mri for aneurysm or vascular lesion. mri did however show traumatic sah pattern and small subdural hematomas consistent with trauma. laboratory findings (esr, crp, ace, c-anca and p-anca) did not raise suspicion of secondary vasculitic or ischemic causes of tnp. the patient was discharged five days after admission with no further complications but without any improvement of tnp signs and symptoms. this case illustrates an atypical presentation of traumatic sah with delayed-onset, isolated complete tnp. to our knowledge, this is the first case with these features described in the literature. his atypical presentation may represent the combination of both diabetes and traumatic injury to the cranial nerve iii in the subarachnoid space, rather than either etiology alone. diringer section of neurocritical care improved clinical outcomes after aneurysmal subarachnoid hemorrhage (asah) have been demonstrated for patients treated at high volume centers. these centers treat only % of all asah. it is common for asah patients to be transferred to high volume comprehensive stroke centers after presentation to a community hospital. this study aims to determine if the hospital of presentation has impact upon asah outcomes. a -year retrospective analysis of asah treated in a comprehensive stroke center was undertaken. the comprehensive stroke center consisted of a neurocritical care unit, dedicated vascular neurosurgeons, and endovascular and neurocritical care specialists. demographic and outcome data were collected on all asah patients who had a confirmed and secured aneurysm, survived > days from admission, and completed tcd monitoring and observation for complications of vasospasm. univariate and multivariate analyses were evaluated for differences in mortality, complications, incidence of vasospasm, discharge disposition, and length of stay. patients were included ( direct and transfer). baseline parameters known to influence outcome (age, medical complications, glasgow coma scale, fisher and hunt and hess grade) were similar between the two groups. transferred patients developed ultrasound defined vasospasm more frequently ( % versus %; p< . ) and had a greater delay in time to surgery ( . versus . days; < . ). adjusting for key predictors, direct admit patients spent . fewer days in the icu compared to transferred patients (t=- . , p= . ). multivariate analysis showed that the likelihood of vasospasm was significantly higher for transfer patients (or . , ci: . - . , p = . ). longer in-hospital stays and decreased rates of home discharge were observed in transferred patients (p< . ). mortality rates were not statistically different (transfer . %, direct . %, p= . ). asah patients admitted directly to a comprehensive stroke center have better outcomes than those transferred from lower acuity facilities. numerous advances have been made in the management of subarachnoid hemorrhage (sah) and its complications, including symptomatic vasospasm. however, the optimal management of vasospasm in patients without neurological deficit remains uncertain. we performed an electronic survey of members of the neurocritical care society (ncs) to elucidate clinical practice in this regard. an electronic survey with ten questions about different aspects of sah management was formulated. our institutional review board and ncs approved the survey. three scenarios were presented for good grade sah patients without evidence of delayed cerebral ischemia (dci): those with either normal tcd values, vasospasm on tcd, or vasospasm on angiography. members answered the survey (response rate of %). up to % of respondents utilized transcranial doppler (tcd) measurement to diagnose vasospasm, while % ( % ci, - %) used clinical examination and % ( % ci, - %) used angiography (ct or catheter). in good grade sah patients with no evidence of dci, % ( % ci, - %) of respondents indicated using nimodipine in all three scenarios. in the subset with normal tcd values, % ( % ci, - %) recommended use of hypervolemia, % ( % ci, - %) hemodilution and % ( % ci - %) induced hypertension. however, in the subset with vasospasm on angiography and no referable clinical symptoms, % ( % ci - %) recommended the use of hypervolemia, % ( % ci, - %) hemodilution, % ( % ci, - %) induced hypertension and % ( % ci, - %) endovascular therapy with intra-arterial vasodilators, angioplasty or stents. from the sample above, it appears that good grade sah patients without neurological deficit but radiological vasospasm are treated aggressively. this is not supported by current literature or guideline recommendations, which imply little benefit of aggressive therapy in such patients. further studies are needed on the optimal management of this subset of patients, in whom the effects of vasospasm remain unclear. key: cord- -slu z authors: rabbitt, angela l.; kelly, teresa g.; yan, ke; zhang, jian; bretl, deborah a.; quijano, carla v. title: characteristics associated with spine injury on magnetic resonance imaging in children evaluated for abusive head trauma date: - - journal: pediatr radiol doi: . /s - - -y sha: doc_id: cord_uid: slu z background: spine injuries are increasingly common in the evaluation for abusive head trauma (aht), but additional information is needed to explore the utility of spine mri in aht evaluations and to ensure an accurate understanding of injury mechanism. objective: to assess the incidence of spine injury on mri in children evaluated for aht, and to correlate spine mri findings with clinical characteristics. materials and methods: we identified children younger than years who were evaluated for aht with spine mri. abuse likelihood was determined a priori by expert consensus. we blindly reviewed spine mris and compared spinal injury, abuse likelihood, patient demographics, severity of brain injury, presence of retinal hemorrhages, and pattern of head injury between children with and without spine injury. results: forty-five of ( . %) children had spine injury. spine injury was associated with more severe injury (longer intensive care stays [p< . ], lower initial mental status [p= . ] and longer ventilation times [p= . ]). overall abuse likelihood and spine injury were not associated. spinal subdural hemorrhage was the only finding associated with a combination of retinal hemorrhages (p= . ), noncontact head injuries (p= . ) and a diagnosis of aht (p< . ). spinal subdural hemorrhage was associated with other spine injury (p= . ) but not with intracranial hemorrhage (p= . ). conclusion: spinal injury is seen in most children evaluated for aht and might be clinically and forensically valuable. spinal subdural hemorrhage might support a mechanism of severe acceleration/deceleration head injury and a diagnosis of aht. compared to accidental head injury, brain injuries in abusive head trauma (aht) are more severe, more often diffuse, and commonly involve hypoxic-ischemic injury [ , ] . retinal hemorrhages and noncontact injury patterns resulting in multifocal subdural hemorrhages located over the cerebral convexities or within the interhemispheric fissure are also highly associated with aht [ , ] . occult spine injuries are increasingly common in aht, likely related to increased awareness and screening for injury using improved imaging and autopsy techniques [ ] . although few spine injuries require surgical intervention [ ] , identification of occult injuries can strengthen maltreatment investigations by highlighting the severity of injury and risk of harm, and by clarifying the mechanism of abusive injuries. given the potential for detection of clinically significant injury and improved child safety, the american college of radiology (acr) recommends mri of the cervical spine in the evaluation for aht, and that whole-spine mri be considered [ ] . despite acr guidelines, the use of spine mri for aht evaluations varies among institutions [ ] , suggesting that additional research on the utility of spine mri in children evaluated for aht is needed to promote its inclusion in institutional protocols. additionally, the mechanism of some spine injuries is unclear [ ] . an accurate understanding of injury mechanism is important in the medical assessment of child maltreatment to ensure evidence-based abuse diagnoses. the purpose of this study was to assess the incidence of spine injury on mri in children evaluated for aht, and to correlate these mri findings with the clinical characteristics of this population. we hypothesized that the clinical characteristics of rotational acceleration/deceleration typical in aht (noncontact intracranial injury pattern, retinal hemorrhages, and severe diffuse brain injury) would correlate with spine injury. all procedures performed in this study were in accordance with the ethics standards of the institutional and national research committees and with the helsinki declaration and its later amendments or comparable ethics standards. our institutional review board granted a waiver of informed consent, and the study complied with the health insurance portability and accountability act of . in this retrospective case series review we identified all children younger than years who received an mri of the brain for an abuse evaluation between january and december . during this timeframe, the hospital's child protection team (cpt) used standard guidelines for abuse evaluation, including head ct in any child for whom there were concerns for aht, and in infants younger than months for whom there were concerns of physical abuse. if concerns for aht remained based on the head ct or clinical findings, the cpt recommended a noncontrast mri of the brain and spine. if a brain mri was the first-line study rather than the head ct, we included the case for analysis if the mri was part of an aht evaluation. the spine mri non-accidental trauma protocol included t sagittal, t sagittal and axial, -d t sagittal with axial and coronal reformations, axial gradient echo/susceptibility-weighted imaging, and sagittal short tau inversion recovery (stir) sequences. the upper thoracic spine was included in cervical spine mr imaging through the th thoracic vertebral body. all children who received a brain mri for an abuse evaluation were included in the study, regardless of whether an mri spine was obtained or revealed any evidence of intracranial injury. we excluded children with a medical condition that might impact the appearance of spine injuries (skeletal dysplasia, connective tissue disorder, prior spinal surgery, a history of spine injury, or bleeding disorders). two members of the hospital's cpt abstracted clinical data from the medical record. they reviewed % of charts together to establish a uniform and accurate data collection process, and the lead researcher (a.l.r.; years of experience) reviewed another % of data collection that occurred separately to ensure ongoing integrity and consistency. two board-certified radiologists (a pediatric neuroradiologist, t.g.k., with years' experience in pediatric radiology, years in pediatric neuroradiology, and subspecialty certification in pediatric radiology and neuroradiology; and a pediatric radiologist, c.v.q., with years' experience in pediatric radiology and subspecialty certification in pediatric radiology and nuclear medicine) reviewed the anonymized spine mris and recorded findings by consensus. variables included patient demographics (age, gender, race, ethnicity, insurance status); likelihood of abuse (accidental, indeterminate, abuse); whether the child received an mri of the spine and whether the imaging was of the whole spine or cervical spine only; injury severity (length of intensive care stay, ventilation time, initial mental status described by providers, initial glasgow coma scale [gcs], neurosurgical intervention, and mortality); criminal convictions; confessions; mechanism of head injury (combined, contact, undetermined, noncontact); the presence of retinal hemorrhages; and presenting symptoms of spine injury. initial mental status was recorded from the first available physical exam pertaining to the abuse concern. a presenting symptom of spine injury was any symptom documented prior to the spine mri that the treating provider or cpt consultant thought raised concern for a spine injury. the mechanism of head injury was determined using a previously described classification system based on the pattern and characteristics of the head injury [ ] . this method classified injuries as: ( ) contact: injuries from cranial impact without significant cranial acceleration or deceleration (skull fractures, craniofacial soft-tissue injuries, epidural hemorrhages); ( ) noncontact: injuries from cranial acceleration or deceleration without evidence of cranial impact (concussion, abnormal subdural collection extending from the interhemispheric region, diffuse axonal injury); ( ) combined: both contact and noncontact injuries; or ( ) undetermined: injuries from contact or noncontact mechanisms (subarachnoid hemorrhages, brain contusions or lacerations, a subdural hemorrhage not extending from the interhemispheric region). we classified children with hypoxic-ischemic injury but no intracranial hemorrhage as "undetermined" and those without intracranial injury confirmed on mri as "no head injury." abuse likelihood was determined a priori at the time of the initial cpt consultation. as standard practice, the cpt consultant assigns a physical abuse likelihood score to all cases using a previously described - scale (table ) [ ] . a diagnosis of aht is made by consensus after peer review by the cpt when a child presents with diffuse primary brain injury and extraaxial hemorrhage that cannot be reasonably explained by an accidental mechanism or a medical condition. the diagnosis is made after careful consideration of all historical and clinical data in collaboration with a multidisciplinary investigation. although information about confessions and criminal convictions was collected, this information is unreliable for an accurate medical diagnosis and was not required to classify children as abused. children < years of age were included to align with the narrow definition of aht developed by the centers for disease control and prevention [ ] . for this study, the cases were grouped into accidental ( - ), indeterminate ( ) ( ) ( ) , and abuse ( - ). cases classified as abuse were further divided into "aht" or "abuse, not aht." children with abusive extracranial injuries with no intracranial injuries, or intracranial injuries that were indeterminate for abuse were classified as "abuse, not aht." to assess the effects of selection bias, we compared variables between children evaluated for aht who did and did not receive a spine mri. outcome variables included intramedullary injury (spinal cord hemorrhage or edema); extramedullary hemorrhage (subarachnoid, subdural and extradural); spinal fracture or bone marrow edema (bony injury); ligamentous edema or disruption (ligament injury); posterior paraspinous muscle edema; prevertebral soft-tissue swelling; and vertebral and carotid artery injury. ligamentous injury was defined as ligamentous disruption or the presence of hyperintensity on stir sequences surrounding the ligaments or membranes (figs. and ). spinal hemorrhages were classified as subdural if there was epidural fatty tissue without dural displacement and epidural if the hemorrhage caused dural displacement toward the spinal cord (fig. ) . we compared clinical characteristics with the presence of spine injury seen on mri. to explore the mechanism of spinal subdural hemorrhage (sdh), we performed a post hoc analysis to compare the association between spinal sdh and the presence of other spine injuries and the presence of intracranial hemorrhage. we used the chi-square or fisher exact test to compare categorical variables. we used the kruskal-wallis or mann-whitney test to compare continuous variables. p-values < . were considered significant. we used statistical software sas . (sas institute, cary, nc) for all the analyses. the study population is described in fig. . of the children who received brain mri as part of a physical abuse evaluation, ( %) received spine mri (age range . to . months; definitely not inflicted injury accidental no concern for inflicted injury while no evaluation can completely exclude abuse, the evaluation has not raised a reasonable suspicion of abuse. the injuries or findings could be reasonably explained by accidental or benign events. mildly concerning for inflicted injury indeterminate intermediately concerning for inflicted injury the injuries or findings raise suspicion for abuse, but an accidental or benign event or preexisting medical condition cannot be excluded. very concerning for inflicted injury substantial evidence of inflicted injury abuse definite inflicted injury to a reasonable degree of medical certainty, the injuries/findings cannot plausibly be explained by accidental injury, preexisting medical illness, reasonable discipline, or benign events. of the children diagnosed with aht who had a spine mri, ( %) were abnormal. in children who had a spine mri as part of an evaluation for aht, the cpt could not ultimately confirm aht. sixteen ( %) of these children had a spinal injury (table ) . injuries in these children would have been missed if mri spine had been assessed only in children diagnosed with aht. mri spine findings often provided additional evidence of trauma when intracranial findings were otherwise nonspecific for trauma, evidence of injuries that were inconsistent with the history provided, or clinical information that influenced medical care (figs. , and ). clinical characteristics associated with spine injury among children with spine mri spine injury was suspected prior to mri in ( %) of those with spine injury, but the assessment was limited by altered mental status at initial presentation in ( %). table describes the demographics and clinical characteristics of children with and without spine injury. there was a confession of shaking in ( %) and of impact in ( %). ultimately ( %) perpetrators were convicted criminally. spinal injury was not significantly associated with an initial history of trauma (p= . ), confession of shaking (p= . ) or impact (p= . ), or criminal convictions (p= . ). when considered individually, many types of spinal injuries were associated with increased measures of injury severity; however, spinal sdh was the only injury also associated with the combination of non-contact head injury mechanism, retinal hemorrhages and an aht diagnosis (table ) . fifty-nine children ( %) who received an mri spine had an intracranial hemorrhage on mri brain. of these, ( %) had co-occurring spinal sdh. intracranial hemorrhage was not associated with spinal sdh (p= . ). none of the three children with accidental intracranial subdural hemorrhage had spinal sdh. the presence of other spinal injuries was significantly associated with spinal sdh compared to those without other spinal injuries ( % vs. %; p= . ). all but one child with spinal sdh had co-occurring subdural hemorrhage, with subdural hemorrhage in the posterior fossa. hypoxic-ischemic injury was the only intracranial finding in the one child with spinal sdh without co-occurring intracranial hemorrhage (case in table , fig. ). she did not receive a lumbar puncture for a sepsis evaluation until after completion of the spine mri. fig. abusive head trauma in a -month-old boy with multiple bruises, diffuse severe brain injury and subdural intracranial hemorrhage, liver laceration and multiple fractures. a axial t -w spine mr image shows a small epidural collection posteriorly (arrow) on the left at the base of the odontoid process with displacement of the dura; low gradient recalled echo (gre) signal was seen as well (not shown). b sagittal t -w spine mr image shows the epidural collection (thin arrow) as well as a subdural t hypointensity extending from c to t (thick arrow). c axial gre mr spine image shows corresponding low signal layering in the subdural space without epidural displacement (arrow) five of six children with epidural spinal hemorrhage were victims of aht (fig. ) ; none of the five had a lumbar puncture prior to spine mri. the one child with an epidural spinal hemorrhage not classified as having aht was a -month-old who presented with sepsis and an incidental skull fracture with a history of a short fall, and this infant did have a lumbar puncture prior to spine mri. epidural hemorrhages were not associated with bony injury. multiple extremity bruises, metaphyseal fractures, diffuse intracranial subdural hemorrhage, and severe retinal hemorrhages were also present. prolonged unilateral extremity weakness was noted after he regained consciousness. father confessed to shaking him and throwing him onto a bed and was convicted of physical abuse we found a high incidence of spinal injury ( %) in children evaluated for aht and in those ultimately diagnosed with aht ( %). the reported incidence of spinal injury in aht varies considerably ( % to %) [ , ] because of variations in the extent of imaging performed and study designs. in publications with methods like ours, which assessed for a wide range of spinal injuries regardless of whether aht was ultimately diagnosed, the incidence of spinal injury ranges from % to % [ , , ] . among these studies, jacob et al. [ ] described a similar rate of spinal subdural hemorrhage ( %) and spinal epidural hemorrhage ( %) compared to our population, but higher rates of ligament and bony injury ( % and %, respectively). in contrast, kadom et al. [ ] and oh et al. [ ] found no bony injury and spinal subdural hemorrhage in only % of cases. the addition of sagittal stir sequences improves the detection of soft-tissue injury and is useful to confirm the presence of spinal hemorrhage [ , ] , and this might have contributed to the higher percentage of injury detected in our subjects. whole-spine imaging can also result in increased injury detection compared to cervical spine imaging alone [ ] . if we had excluded thoracic and lumbar spine mri, we would have missed three children with spinal extramedullary hemorrhages and two with thoracic vertebral body fractures. additionally, -d t -w sequences used in our mri protocol might have facilitated detection of spine fractures (fig. ). research by baerg et al. [ ] , the only prospective study assessing spine injury in aht, found the lowest rate of injury ( %). the authors used strict inclusion criteria requiring loss of consciousness, and imaging findings of intracranial hemorrhage, diffuse axonal injury, hypoxic injury or cerebral edema. abuse cases without a confession or witnessed abuse were table , a -month-old girl presenting with altered mental status, lethargy and vomiting after a reported fall from standing height in a bathtub. a axial gradient recalled-echo spine mr image shows abnormal left vertebral artery flow void compatible with dissection (arrow). b t -w axial mr image of the brain shows evidence of completed infarcts in the distribution of bilateral medial branches of the posterior inferior cerebellar arteries (arrows) table , an -month-old boy found by mother unresponsive and not breathing in the crib. sagittal short tau inversion recovery spine mr image shows prevertebral soft-tissue swelling (long arrow), posterior paraspinous muscle edema (short arrow) and subtle interspinous ligament injury (arrowheads) excluded. mri stir sequences were included, but authors did not describe how ligament injury was defined or whether paraspinous muscle edema or prevertebral soft-tissue injury was recorded as injury. if we had used similar inclusion criteria, our incidence of spine findings would have remained high at %. if we had also used a more restrictive definition of injury by excluding paraspinous muscle edema, prevertebral soft-tissue injury, and ligamentous edema without disruption, the incidence of spine injury in our study would have remained comparatively higher ( %) than in baerg et al.'s ( %). useful interpretation of spine pathology in child abuse evaluations depends on clinicians' ability to interpret findings as traumatic injury and to differentiate abusive from accidental mechanisms. mri findings might overestimate the extent of disruptive ligamentous injury, limiting the utility of spine mri when the goal is to detect potentially unstable injuries requiring surgical intervention [ , ] . however, in child abuse evaluations the goal is to detect both apparent and occult injuries to outline the severity of injury to the child and support opinions regarding injury mechanism. soft-tissue pathology on spine mri does correlate with clinical impairment in adults with whiplash injuries as compared to controls [ ] . in children, choudhary et al. [ ] compared spine mri findings among aht, accidental trauma and non-traumatic cohorts. after excluding medical causes, the only spinal finding in the non-traumatic cohort was a nuchal ligament injury in a child with sepsis who sustained a -min tonic-clonic seizure. the authors concluded that bony or ligamentous spinal abnormalities in the accidental and abusive cohorts were from injury and not normal variants [ ] . although spine mri rarely resulted in additional medical treatment, it did often provide clinically and forensically valuable information including additional evidence of trauma when intracranial findings were otherwise nonspecific for trauma, and identification of injuries that were inconsistent with the history provided. consistent with other studies [ , ] , spine injuries in our subjects were often occult. none of the fractures noted on mri were identified on preceding plain radiographs. symptoms are difficult to assess in very young children and the symptoms can be masked by severe brain injury. evidence of unexplained trauma might prompt additional investigation for maltreatment and in this way affects medical decision-making. interestingly, in several children with altered mental status, respiratory distress and hypoxicischemic injury, the spine findings were the only clear table , a month-old girl with diffuse cerebral hypoxic-ischemic injury and no history of trauma and no intracranial hemorrhage. a sagittal t -w spine mr image shows linear posterior hyperintensity (arrow). b axial gradient recalled-echo spine mr image shows a corresponding hypointensity layering in the subdural space (arrow) representing hemorrhage without a posterior epidural concave displacement of the dura. c axial gradient recalled-echo spine mr image shows distal extension of subdural hemorrhage without dural displacement (arrow). prevertebral swelling, posterior paraspinous muscle edema, nuchal ligament edema, and interspinous edema were also present on short tau inversion recovery sequences (not shown) evidence of trauma (table ) . these cases suggest a need for research assessing the prevalence of spinal injury in infants who present with severe unexplained respiratory compromise. in contrast to other spinal injuries, posterior paraspinous muscle edema was interpreted with caution by the cpt because it was often thought to be the result of fluid shifts during resuscitation rather than primary injury. mri spine has only poor to moderate specificity for paraspinous muscle injury when intraoperative findings are used as a gold standard [ ] . however, in adults with whiplash injuries from motor vehicle collisions, cervical muscle strain (defined as altered structure, size and signal intensity) and muscle tears/ hematomas on cervical spine mri are significantly more common compared to non-injured controls, as are spinal fractures and bony contusions (defined as altered bone marrow signal intensity without fracture line) [ ] . similar comparative studies in children and in more severely injured patients are needed to guide the interpretation of spinal findings in children with isolated paraspinous muscle edema. although no children in the accidental trauma group had bony, hemorrhagic or ligamentous injuries, overall spinal injury and aht were not associated. spinal sdh was the only injury associated with a diagnosis of aht. the low number of accidentally injured children who received a spine mri (n= ) aht abusive head trauma, gcs glasgow coma score, icu intensive care unit data presented are median (interquartile range) for continuous variables and count (%) for categorical variables. percentages from some subgroups do not add up to be because of the rounding of numbers. bolded p-values are statistically significant a race information is missing in patients b initial gcs was not assessed in patients table clinical characteristics associated with spine injury type (n= ) . compared to those without the specific type of spine injury compared to the abuse (n= ) and indeterminate groups (n= ) might have caused a lack of power to detect differences; higherpowered comparative studies do suggest cohorts with a higher incidence of spinal injury in abused infants [ , , ] . choudhary et al. [ ] found a higher rate of both cervical ligamentous injury ( % vs. %) and spinal sdh ( % vs. %) in children with aht compared to accidental injury. when henry et al. [ ] compared spinal injury in children with aht and with accidental injury associated with non-motor vehicle crash, the authors found a higher incidence of spine injury overall in children with aht ( . % vs. . %), but the rate of ligamentous injury was similar ( . % for aht and . % for accidental head injury) [ ] . in contrast, other studies did not find a higher incidence of spinal injury in abused infants [ , ] . the lower number of children with spinal extramedullary hemorrhage in these studies might contribute to the lack of significant findings between their abusive and accidental cohorts. additionally, baerg et al. [ ] included children with severe accidental rotational acceleration/deceleration head injuries who can have spinal injury similar to that found in aht. although spinal injury and aht were not associated in baerg et al.'s study, spinal injuries were associated with other clinical findings of severe rotational acceleration/deceleration head injury typical of both aht and severe accidental head injury involving similar mechanisms [ ] . we found higher severity of brain injury in children with spinal injury and an association between spinal sdh and other injuries typical of aht. although the association between injury severity and spinal injury should be interpreted with caution because of the low number of less severely injured children who received a spine mri, it is consistent with previous literature [ , ] . like aht, spinal injury is associated with global parenchymal injury [ ] , hypoxic-ischemic injury [ ] [ ] [ ] [ ] and a rotational acceleration/deceleration mechanism of head injury in both accidental and abusive trauma [ ] . using autopsy techniques that preserve the entire spine for microscopic analysis, matshes et al. [ ] found that % of subjects with injuries involving hyperflexion/extension forces to the head had injury to the spinal nerve roots. in living children, spinal nerve root injuries are infrequently reported but might be below the current level of detection on mri [ , ] . although we did not analyze the association between hypoxic-ischemic injury and spinal injury, other research suggests that hypoxic-ischemic injury is more common in children with ligamentous spinal injury [ , , ] , and spinal sdh is rarely identified in accidentally head-injured children [ , ] . our study supports and adds to this literature by highlighting an association between spinal sdh and a combination of higher injury severity, noncontact head injury pattern, retinal hemorrhages, and an aht diagnosis. despite the association between spinal sdh and aht, the source of the bleeding in spinal sdh is debated. spinal sdh is most commonly attributed either to direct injury to spinal vasculature or tracking of intracranial blood [ ] . sequential migration of intracranial blood into the spinal subdural space has been reported in adults [ ] . case studies of children with aht report spontaneous resolution of subdural hemorrhages at the clivus, which seemed to have migrated into the spinal subdural space [ , ] . spinal subdural hemorrhage is also reported as a complication of ventriculoperitoneal shunting, where low intracranial pressure from the shunt is suspected to cause dissection between the dura and arachnoid layer of the spine, allowing migration of the intracranial subdural hemorrhage [ ] . however, in the only prospective study assessing the incidence of spinal sdh in people with intracranial subdural hemorrhage, only ( . %) of adults with intracranial hemorrhage had spinal hemorrhage; both of those people had experienced concurrent injury to the head and the back [ ] . direct vascular injury to radicular veins traveling through the spinal nerve root is also a known cause of spinal sdh in victims of aht, likely caused by traction on spinal nerve roots during hyperflexion/extension from shaking [ ] . if migration of an intracranial hemorrhage were the sole mechanism for spinal sdh, we would expect to see an association between intracranial and spinal hemorrhage, regardless of the presence of other spinal injuries. although all but one child with spinal sdh also had intracranial hemorrhage in our study, intracranial subdural hemorrhage was not predictive of spinal sdh. spinal sdh was associated with other spine injuries. the lack of association between intracranial and spinal sdh suggests that caudal migration of an intracranial hemorrhage is not the sole mechanism for spinal sdh. our findings suggest that either the spinal sdh is caused by direct spinal injury at least in some cases, or that a similar injury mechanism caused the other spinal injuries and the caudal extension of the intracranial hemorrhage into the spine. choudhary et al. [ ] also found a higher incidence of spinal sdh in children with aht compared to their accidentally injured cohort and a correlation between ligamentous spinal injury and spinal sdh. the authors proposed that traction on myodural bridges and the intradural nerve roots and dentate ligaments during flexion/extension of the spinal cord in aht could cause disruption of the dura-arachnoid interface, facilitating the migration of blood from the intracranial compartment into the spine [ ] . the association among spinal sdh, other injuries typical of rotational acceleration/deceleration of the head, and a diagnosis of aht in our subjects supports this theory. however, it is important to consider that spine mri extended past t in a minority of our subjects, so the incidence of spinal sdh might be underrepresented. additional studies using whole-spine mri are needed. there are several limitations to this study. first, there is a risk of circular reasoning if the presence of spinal sdh heightened providers' concern for aht. however, upon review of consultation reports for children with spinal injury, no children were classified as abused because of a spinal injury. to further assess for circular reasoning, aht likelihood was compared to a second classification method developed by duhaime et al. [ ] and then modified by kadom et. al [ ] that does not use spinal injury as a diagnostic consideration. because this classification system was meant for people with head injuries, people without concern for head injury were excluded. using the weighted kappa statistic, abuse classifications determined by the modified duhaime criteria and lindberg scale were significantly correlated (κ= . , % confidence interval [ci] . - . ). second, the potential for sampling bias exists. because the majority ( %) of spine mris included cervical spine only, our study might underestimate the incidence of spinal injury. the number of children with isolated lumbar and lower thoracic injuries is unknown. abused children and children with higher severity of injury were more likely to receive a spine mri, potentially causing under-detection of spinal injury in accidental, lower-severity injuries and resulting in a lack of power to detect differences between abused and non-abused children. if we assume that all children who were not imaged had a normal spine mri, the incidence of spine injury would remain relatively high at %. finally, because we did not assess inter-and intraobserver variability in radiologists' readings of the spine mris, our ability to comment on the validity of the interpretations is limited. our rates of spinal hemorrhage and ligamentous and bony spinal injury overall and within our aht population were similar or lower than reported by other studies that used methods and mri sequences comparable to those in our study [ , ] . this suggests that our interpretation of the spine mri was similar to or more conservative than those of researchers at other institutions. there is a high incidence of spinal injury in children evaluated for aht ( %) and those ultimately diagnosed with aht ( %). higher measures of injury severity were the only variables associated with spinal injury overall. however when considered separately, spinal sdh was associated with aht and with other head injuries typical of a rotational acceleration/deceleration injury mechanism. spinal sdh might support a mechanism of severe acceleration/ deceleration head injury and a diagnosis of aht when interpreted in conjunction with other intracranial and ocular findings. mri of the whole spine should be included in future studies to further examine the predictive value of spinal sdh for an aht diagnosis. while bone, ligamentous and other soft-tissue spine injuries likely result from a wider range of injury mechanisms, detection of occult injury could be clinically and forensically valuable. additional research assessing spine findings in accidentally and less severely injured children and investigating potential nontraumatic causes of posterior paraspinous muscle edema in children could further our ability to interpret spinal pathology on mri. finally, studies assessing the incidence of spinal injury in children presenting with unexplained hypoxic-ischemic injury and respiratory distress would be useful to examine the emerging link between hypoxic-ischemic injury and spinal injury in abuse evaluations. conflicts of interest none prevalence, patterns, and clinical relevance of hypoxic-ischemic injuries in children exposed to abusive head trauma clinical and radiographic characteristics associated with abusive and nonabusive head trauma: a systematic review abusive head trauma: recognition and the essential investigation spinal injuries in abusive head trauma: patterns and recommendations changes in use of cervical spine magnetic resonance imaging for pediatric patients with nonaccidental trauma acr appropriateness criteria: suspected physical abuse -child hospital variation in cervical spine imaging of young children with traumatic brain injury mechanisms, clinical presentations, injuries, and outcomes from inflicted versus noninflicted head trauma during infancy: results of a prospective, multicentered, comparative study variability in expert assessments of child physical abuse likelihood pediatric abusive head trauma: recommended definitions for public health surveillance and research cervical spine injuries in young children: pattern and outcomes in accidental versus inflicted trauma imaging of spinal injury in abusive head trauma: a retrospective study usefulness of mri detection of cervical spine and brain injuries in the evaluation of abusive head trauma mr imaging of the cervical spine in nonaccidental trauma: a tertiary institution experience cervical spine imaging for young children with inflicted trauma: expanding the injury pattern correlation of mr imaging findings with intraoperative findings after cervical spine trauma efficacy of mri for assessment of spinal trauma: correlation with intraoperative findings magnetic resonance imaging assessment of craniovertebral ligaments and membranes after whiplash trauma cervical spine imaging and injuries in young children with non-motor vehicle crashassociated traumatic brain injury are there cervical spine findings at mr imaging that are specific to acute symptomatic whiplash injury? a prospective controlled study with four experienced blinded readers spinal subdural hemorrhage in abusive head trauma: a retrospective study shaken infants die of neck trauma, not of brain trauma spinal cord injury without radiographic abnormality in children, decades later concomitant intracranial chronic subdural hematoma and spinal subdural hematoma: a case report and literature review retroclival collections associated with abusive head trauma in children acute clinical and spinal subdural hematoma with spontaneous resolution: clinical and radiographic correlation in support of a proposed pathophysiological mechanism prospective assessment of concomitant lumbar and chronic subdural hematoma: is migration from the intracranial space involved in their manifestation? thoracolumbar spine subdural hematoma as a result of nonaccidental trauma in a -month-old infant head injury in very young children: mechanisms, injury types, and ophthalmologic findings in hospitalized patients younger than years of age publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -gvc ij authors: klaunberg, brenda a.; lizak, martin j. title: considerations for setting up a small-animal imaging facility date: journal: lab anim (ny) doi: . /laban - sha: doc_id: cord_uid: gvc ij imaging techniques allow for the conduct of noninvasive, in vivo longitudinal small-animal studies, but also require access to expensive and complex equipment, and personnel who are properly trained in their use. the authors describe their planning and staffing of the nih mouse imaging facility, and highlight important issues to consider when designing a similar facility. state-of-the-art biomedical research often uses rodents and other small animals for disease modeling. a recurring issue for many investigators is the desire to obtain anatomical and physiological information from valuable research animals without sacrificing them. in vivo imaging is a noninvasive way to gain insight into the animal's anatomy and physiology ; however, the unit cost and complexity of many such methods may preclude an investigator's ability to gain access to such devices. location of the imaging equipment in a shared facility can overcome these obstacles. the vision of the nih mouse imaging facility (mif) is to offer various state-of-theart, in vivo small-animal imaging techniques in one facility. the mif is a shared resource for the nih intramural community, and currently has more than active animal protocols. at this time, the mif has three magnetic resonance imaging (mri) scanners, a micro x-ray computed tomography (ct) scanner, two ultrasound scanners, a combined luciferase/gfp imager, and a laser doppler imager. in addition to administrative personnel, the staff consists of a veterinarian, three imaging scientists, an electrical engineer, and three animal technicians. setting up this facility took planning and intellectual contributions from experts in many fields. we provide resources for a wide variety of investigators from many of the various institutes within the nih. this is not a 'how-to' manual, but we will discuss some of the issues that the principal players considered when designing and staffing the mif. a small-animal imaging facility can represent an enormous investment of capital and personnel. to obtain the maximum usefulness and ensure success, a certain amount of planning must take place before an instrument is ordered or facility construction begins. planners should recruit the advice of experts in various imaging fields and involve as many people as necessary to share in the decision-making processes, so that everyone has a voice. knowledge of the needs of the research community is one of the most important priorities in setting up any facility. a consultation with your research community will help to determine which imaging modalities are most needed. it is pointless to include an instrument that no one will use. consultation with experienced operators for each of the imaging modes chosen will elicit useful advice on special needs for each instrument. veterinarians and animal care staff should also have input because they will have a considerable impact on traffic patterns, animal care requirements, and other features. if possible, one should visit other small-animal imaging facilities. what imaging modalities do they have? what problems have they encountered, and how did they solve them? one must consider what types of animals and models could come to the facility for imaging, because these considerations will impact staffing choices, housing availability, and imaging modalities. one should also consider the health status of the animals; a facility that can accommodate immunecompromised animals has more stringent requirements. the biosafety level that the facility will maintain is also a consideration; animals carrying pathogens or treated with radiolabeled agents will require additional restrictions. the mif operates as a clean conventional facility that excludes the following specific pathogens: coronaviruses, pneumovirus of mice (pvm), sendai virus, endoparasites, and ectoparasites. to prevent cross-contamination between rodents, disposable, absorbent material covers all surfaces. all surgical instruments are steam-sterilized for survival procedures, and devices such as nose cones are either placed in cold sterilization or cleaned with a bleach-based disinfectant. planners should decide whether to design and staff the facility so that researchers can be human and animal safety should be the primary consideration when planning an imaging facility design. in addition to excluding specific rodent pathogens, the mif operates at animal biosafety level- (absl- ) [author: edit okay?]. some imaging animals may receive agents (chemotherapeutics, infectious organisms) in higher biosafety levels in other facilities. those animals cannot be imaged until they satisfy absl- requirements. planners should determine the need for a preparation room. it is possible to perform simple procedures such as anesthesia induction and tail vein catheter placement adjacent to the imaging instrument. more complicated preparations that require sterile or aseptic procedures will require a dedicated room. in the mif, there is a small preparation area adjacent to each instrument. in addition, we have a preparation room set aside for rodent procedures more complex than anesthesia induction and tail vein intravenous catheter placement. each preparation area is set up with anesthesia and physiological monitoring equipment, as well as a surgical microscope for microsurgery. we use inhalant anesthesia (isofluorane) as much as possible, and each imaging device preparation area is set up identically. all preparation areas have central gas supplies for oxygen, medical air, and nitrogen, as well as a vacuum system for scavenging anesthetic gases. anesthesia and monitoring equipment must comply with magnet safety. anything that enters the scanner room must be nonmagnetic, and any equipment within the fringe field must operate correctly. once there is an understanding of the goals of the research community, the needs of the investigators can determine the imaging techniques to be made available. some techniques, such as optical imaging, are relatively inexpensive in terms of equipment, personnel, and space. individual laboratories may have the financial capability to purchase these types of devices, but more elaborate techniques, such as mri or ct scanning, require a more substantial investment of resources. individual laboratories rarely have the funds to purchase such equipment or the means to maintain them; therefore, mri and ct are usually the core of an imaging facility. please refer to table for a summary of imaging modalities, their applications, and their estimated costs. mri is one of the most powerful noninvasive imaging methods currently available to research. this technology uses radio waves and powerful magnets to generate radiograph-like images of tissue. a strong magnetic field partially aligns the hydrogen atoms on water molecules in the tissue. a radio wave then disturbs the built-up magnetization, and radio waves are in turn emitted as the magnetization returns to its starting place. these radio waves can be detected and used to construct an image (fig. a) . unlike radiographs, the mri patient is not exposed to x-ray radiation, so repeated imaging is not a risky procedure . mri is excellent for imaging different types of soft tissue with high contrast - . researchers can use it for anatomical and functional studies. some applications include tumor growth and treatment, brain function and stroke, and cardiovascular disease. contrast agents, which are drugs that function like histological stains, increase the usefulness of this imaging method. for resource volume , no. lab trained to run the instruments independently, or whether to offer complete service, in which researchers can deliver animals to the facility and then return for images. this choice will have a profound effect on staffing requirements. the mif is designed to be a resource, not a service, so that investigators are encouraged to participate fully. even if the investigator has no desire to learn to run the equipment, it is our requirement that someone on the protocol be present and responsible for the animal during scanning. an important initial decision is whether or not the animals will be housed in the facility. the number of animals housed and the duration of housing will have an impact on space usage. animal welfare guidelines dictate space requirements that must be carefully considered. moreover, one must also consider space for traffic between housing, preparation rooms, and instruments. at the mif, we provide temporary housing (monday-friday) for mice only. we have one -ft animal room with one ventilated rack that can hold shoebox-sized cages. additionally, we have ft of animal husbandry support area for storage and cage washing. animals involved in long-term studies that must come to the mif periodically for imaging are usually returned to a quarantine facility. because of the surrounding magnetic field, an mri system requires a large area (≥ ft ). the magnet itself requires ∼ ft of surrounding clear area. the fringe field is the distance that the surrounding magnetic field extends before it drops to the level of gauss. the fringe field can occupy an area up to ft . the mri suite must have a design that prevents casual visitors from entering the fringe field. a magnetic field > gauss can adversely affect persons with pacemakers or other metallic implants. the distance to the gauss line varies widely with field strength and magnet type. there are magnets available that have a fringe field limited to a foot or less, but these cost more. mr scanners use extremely heavy magnets; therefore, most facilities locate the mr imager on the ground floor. additionally, because the magnets are cooled by cryogens, good ventilation must be present. rapid boil-off of the cryogens could lead to asphyxiation. the instrument manufacturer can provide a detailed description of space requirements and suggested architectural layouts. a facility will need to plan for additional space for the electronics and console for the scanner as well as a preparation area outside the magnetic field. this can amount to another ft . researchers currently consider a -tesla mri system an optimal field for imaging rodents. at the mif we have several bruker avance mri scanners (bruker-biospin, billerica, ma). some other manufacturers of mri consoles are varian (varian medical systems, inc., palo alto, ca), tecmag (tecmag, houston, tx), and mrrs (mr research systems, guildford, uk). a basic setup for the mri includes the superconducting magnet, the imaging console, and several probes for approximately $ , -$ , , , depending on the options. it is ideal to enclose the magnet in a room shielded from radiofrequency, but this construction would generate additional costs. the magnet itself comes with end caps that adequately shield it; however, passing anesthesia and monitoring lines becomes awkward. because of its complexity, the mri requires a scientist with not only the necessary academic qualifications, but also a technical background for operation. there are many mri measurement methods, each with many control variables, designed for specific purposes. the mr operator must be familiar with the basic physics of the mr measurement and the effect of the controls on the image outcome. if new methods are going to be developed or implemented, a postdoctoral-level scientist will be necessary. new methods require sophisticated knowledge of the hardware and computer programming. this individual will be responsible for running the scanner and maintaining the system. mri maintenance requirements include both hardware and software. hardware maintenance includes the associated magnetic field. the magnet requires liquid nitrogen and liquid helium to maintain the superconducting magnetic field. allowing for a safety margin, most magnets need liquid nitrogen once per week and liquid helium approximately twice per year. if the cryogen level is allowed to become too low, the magnetic field can spontaneously quench (i.e., lose its magnetic force). quality assurance includes regular test images of a standard sample. a small loss in performance can result in unusable images. the operating computer and software also require regular maintenance. system software requires periodic updates to install security patches, repair bugs, and add features. these updates are particularly important if the computers are on a network with outside access. despite hardware and software designed to limit external access, new security holes appear on a regular basis. a malicious attack could destroy valuable work and render the instrument useless until the base software can be reinstalled. archiving and removing old data are important parts of computer maintenance. if the number and size of the stored image files grow too large, system performance can slow or even become blocked. a policy for data management can help prevent major problems, but periodic enforcement is still necessary. this policy can range from a simple principle of moving the oldest data first to a more complicated formula based on size and age. at the mif, we encourage everyone to transfer data from the instrument as soon as possible. when data space becomes an issue, the users with the largest amount of data must export or delete files before they can resume scanning. x-ray ct is an imaging method that uses multiple radiographic views of a subject to construct an image (fig. b) . in our system, an x-ray source and detector rotate around the subject degrees while generating a number of projections or views. the mif has a microcat ii ct scanner built by imtek, inc. (knoxville, tn). other manufacturers of the manufacturer can provide exact measurements of the machine footprint. there are several micro-ct manufacturers, and the price ranges from $ , to $ , . the instrument will require one technician for operation and maintenance. this individual should have a sophisticated education in biology or a related field and be comfortable with computers. the ct scanner relies on several computers on a small network. the ct operator will be responsible for maintaining the computer system software, managing the accumulated data, and quality assurance. a good knowledge of anatomy is vital for data interpretation, and the person should be able to interpret radiographs. reporter gene technology has revolutionized the ability to track cell populations in vivo . optical imaging devices, which allow the user to monitor gene expression [author: edit okay?], are easy to operate and have no special environmental requirements. there are several different types of optical imaging. bioluminescence is an enzymatic biochemical process that produces light. the luciferase gene is first inserted into the targeted cell population. image acquisition requires live cells to process the substrate and produce light. advantages of bioluminescence include high sensitivity, and virtually no background noise; disadvantages include the need for cofactors (i.e., oxygen, magnesium, and atp) and expensive substrates (luciferin). fluorescence imaging also requires genetic manipulation; however, the technology does not require a living system to produce an image. fluorescence imaging differs from bioluminescence in that light must be applied to the tissue to generate a signal. one advantage of fluorescence imaging is the commercial availability of numerous markers (gfp, dsred, icg, and cy . ) with no need for substrate or cofactors; a disadvantage is the low signal/noise ratio due to autofluorescence. basic equipment for bioluminescence or fluorescence imaging consists of a light-tight chamber, a sensitive camera (charge-coupled device), and a computer. it is possible for the ambitious investigator to manufacture his or her own imaging device; however, commercial products are available for about $ , . the mif owns a xenogen ivis (xenogen corp., alameda, ca); other manufacturers include eastman kodak (eastman kodak co., scientific imaging systems, rochester, ny), roper scientific (trenton, nj), and advanced research technologies, inc. (saint-laurent, quebec, canada). our imaging device occupies a space measuring ft ; additional benchtop space is necessary for preparing the animal. image acquisition is simple, and it is not necessary to have a dedicated system operator. investigators can easily learn to perform their own imaging study. our system's operating software first acquires a black-and-white photographic image of the subject, then acquires the luminescent image, and finally overlays the image onto the photograph for anatomical signal mapping (fig. ) . both bioluminescence and fluorescence imaging are useful to detect tumor cells, monitor tumor growth, or track cell movement (e.g., metastasis). optical imaging can be highly specific, but it has low spatial resolution. optical data are typically two-dimensional ( d), but d methods are in development. a high throughput of animals is possible because imaging time is resource volume , no. lab micro-ct equipment include ge medical systems (london, ontario, canada), scanco medical (scanco usa, inc., southeastern, pa), and skyscan (aartselaar, belgium). each projection is the equivalent of a radiographic image. a method called 'filtered back projection' permits these projections to be reconstructed into a three-dimensional ( d) data set. a micro-ct scanner for rodents typically uses less x-ray power than a conventional clinical ct scanner, so the effective radiation exposure per scan is reduced. the highest radiation dose we have measured was rad for skin, but typical scans are much less ( rad). the radiation dose is ultimately dependent on the scan parameters (i.e., number of projections, exposure time, x-ray beam strength). ct is excellent for studying the skeletal system, certain internal organs, and fat distribution [ ] [ ] [ ] [ ] . ct can also be used for tumor studies, depending on the location of the tumor. a typical d image with -µm resolution takes about minutes to acquire; higher resolution images may take up to minutes. image reconstruction can take as little as extra minutes or up to hours depending on hardware and software options. as with mri, a contrast agent can be used to enhance the appearance of some organs. in rodents, the half-life of most clinical ct contrast agents is short, so some experimentation is required to find the optimum dose and administration regimen. a micro-ct scanner requires ∼ ft of short, usually from second to minutes. laser doppler is another type of optical imaging that uses a laser light source and the doppler effect to measure capillary blood flow (fig. ) . the equipment consists of a laser source and computer, and costs less than $ , . the footprint of the laser device is small ( ft plus computer), but its sensitivity to movement warrants placement on an antivibration table. this machine is simple to use and is highly sensitive, but it is limited to small vessels within a -mm depth. the mif owns a laser doppler imager from moor instruments, inc. (wilmington, de). another manufacturer is perimed, inc. (north royalton, oh). ultrasound imaging is a rapid, real-time in vivo technique. an ultrasound transducer broadcasts sound waves beyond the audible range into tissue. as the sound waves encounter the interfaces between various types of tissue, they are reflected. the transducer detects the reflected sound waves and uses them to construct an image (fig. ) . the depth of penetration depends on the frequency of the sound wave. the image-processing software produces an image in real time, and the various tissues within the image display different 'echogenic' properties. ultrasound machines used for rodent imaging are similar to those used clinically; however, the larger field of view offered by a clinical scanner is not optimal for imaging smaller subjects. resolution increases (and field of view decreases) as the ultrasound frequency increases; therefore, high-frequency ultrasound is ideal for rodents. ultrasound is excellent for cardiac studies and evaluation of embryonic development , . it may also be used for various organ evaluations, tumors, and guided injections. advantages of ultrasound include rapid image acquisition and ease of use; however, time is required for the operator to develop proficiency in the acquisition techniques and image interpretation. knowledge of anatomy is useful for positioning the transducers, as well as evaluating the resulting images. a well-trained operator should be able to distinguish normal and abnormal anatomy. scattering of the sound waves in the tissue often cause ultrasound images to appear 'noisy' . also, most ultrasound images are d, although some d-capable instruments are available. most ultrasound machines are built on portable carts for easy relocation. the image display is most clearly visible in low ambient light, so this should be a consideration when determining the location for ultrasound imaging. the mif owns two ultrasound machines: a siemens acuson sequoia (siemens medical solutions, malvern, pa) and a visualsonics vevo (visualsonics, inc., toronto, ontario, canada). there are many other ultrasound manufacturers, including philips (philips medical systems, andover, ma) and general electric (ge medical systems, london, ontario, canada). a commercial ultrasound imager can cost about $ , . although one can perform data analysis on the scanner, this does take time away from available scan time. an additional data-processing workstation could cost as much as $ , . the mif does not have a dedicated ultrasonographer at this time. the investigators that use our acuson ultrasound most frequently have experience in its operation and often collaborate with other investigators in need of their expertise. the mif staff is developing proficiency in ultrasonography. positron emission tomography (pet) is an excellent method to perform functional imaging in vivo [ ] [ ] [ ] . uptake of radioactive compounds can demonstrate the presence of tumor, abnormal cell function, or metabolic changes. this imaging technique can generate d data. pet imaging is highly sensitive but suffers from low spatial specificity and needs to be superimposed on an anatomical image for signal location (fig. ) . the footprint of a micro-pet system may only be ft , but it is ideal to locate the micro-pet adjacent to a micro-ct or mri because an anatomical image will be required for co-registration. this allows convenient transport of an anesthetized animal from one machine to another. micro-pet imaging presents its own set of unique considerations. the use of radioactivity dictates its own specifications. the imaging area should be in a location that allows the environment to be properly controlled and appropriate precautions taken.your institution should be able to provide you with a detailed description of the rules and regulations that govern the use of radionuclides. the imaging animals will remain radioactive for some time after imaging, so housing for these 'hot' animals must be considered. the half-lives of radionuclides in the radioactive compounds are typically short (e.g., hours), so housing vice to new users. at the mif, we train investigators to perform simple data analysis. for more complex data analysis, mif staff collaborates with the investigators. this system works well because, having trained an investigator, the technician is freed up for other duties; the investigator can often then pass that training on to new individuals in his or her group as well as other collaborators. once the user base is established, equipment needs are defined, and the facility floor plan is designed, one must consider the staffing needs. a variety of personnel are needed for a successful imaging facility. diversity of experience will enhance the resources as well as expand the knowledge base of the entire personnel staff. certain base criteria must be met for each unique position, but it is our experience that personnel experienced in imaging laboratory animals are difficult to find. many of the necessary technical procedures may be learned on site. we believe that a strong desire to learn may be more important than experience and formal education. it is important to have at least one person on the staff that is skilled in the routine technical procedures and can provide training for new staff members. as with any animal facility, husbandry staff is necessary. ideally, housing for imaging animals should be on site and accessible. the size of the animal housing facility will determine the number of necessary personnel. routine husbandry duties include daily health checks, cage changing, cage washing, room sanitation, sentinel maintenance, quality control, etc. husbandry staff is the foundation of all successful animal research programs. the qualifications of the animal care staff are dependent on how many people will be required to run the facility and in what capacity the people are expected to function. if you can have dedicated husbandry staff, their qualifications will be less stringent, and a person with aalas alat or lat experience would be sufficient. staff members who will be assisting with imaging experiments are expected to work independently, so it is ideal to have personnel with aalas latg certification or equivalent experience. if the technical staff is required to assist with (or perform) husbandry duties, they should understand that it is part of their job description so that no misunderstandings occur later. laboratory animals must be immobilized for imaging procedures. it is important for the laboratory animal technical staff to maintain a working knowledge of anesthesia and physiological monitoring for a variety of species. additionally, basic procedure skills such as venipuncture are required for the administration of imaging contrast agents and other pharmaceuticals. familiarity with aseptic techniques and rodent colony health management techniques will aid in maintaining the level of health standards for the facility. additional useful procedures include intubation of rodents, placement of rodent femoral, jugular, and carotid catheters. the computers acquiring the images and the networks they are connected to can be complicated. many of the personnel operating the imaging devices have sufficient knowledge of computer operation and software programming to repair problems as they occur; however, given the number of computers needed for imaging and personnel support, it is a good idea to have someone dedicated to their maintenance. it is important that these networks are secure and protected from any outside abuse. the mif has shared information technology personnel that maintain computer software security and upgrades. the imaging instruments require regular hardware maintenance as well as periodic repair. the best solution is to have an engineer on the staff to address these issues. it is possible to maintain a service contract with an outside company, but an internal person can aid in quicker diagnosis and repair. the mif has maintenance contract on all equipment, but the level of each maintenance plan varies from a 'parts only' plan to a full-service plan that includes yearly preventative maintenance. the mif is fortunate to have mri scientists who are knowledgable in mri mainte- resource volume , no. march animals can be a temporary situation. the availability of radioactive compounds will have the greatest impact on the success of a micro-pet program. radiolabeled glucose, oxygen, and ammonia are commercially available; however, many studies may need custom-made radioactive compounds. the ideal arrangement is an imaging suite located adjacent to the radiopharmacy that will produce the radionuclides. production of these reagents can represent the largest expense because of the need for highly specific equipment and personnel. manufacturers of micro-pet imagers include general electric and philips medical systems. micro-pet operation will also require a postdoctorate-level scientist to assemble, operate, and maintain the equipment. it is easy to generate an enormous amount of image data in a relatively short amount of time. a single image data set can range from a few kilobytes to over two gigabytes for highresolution three-dimensional data. the amount of image data generated over time can be a problem. mass storage devices must be available for data storage during analysis. if backup and archiving are required, the amount of equipment needed can be considerable. a room will need to be dedicated to computer storage and workstations for post processing images. a minimal room will have space for a rack containing data servers and network equipment. qualified information technology personnel should be able to provide additional advice. in addition to data storage, extra workstations for data processing are almost a necessity. the alternative is allowing data to be analyzed on the acquisition instruments. this reduces the need for extra computers but takes time away from the instruments. the time required for data analysis can be considerable. some consideration must be given to who will analyze data. often, users of the instrument will not have the experience or skill needed to gain the most information from the images. one solution is for image analysis to be part of the imaging service. another approach is to train the investigators to analyze their own data; this reduces the facility burden, but reduces the usefulness of the ser-nance and repair, as well as an electrical engineer who assists with mri and ct maintenance and repair. the imaging facility also needs personnel to attend to nonscientific tasks. administrators must handle daily paperwork such as budget management and supplies, as well as provide other organizational services. these people are critical, because if the facility is successful, none of the scientific personnel will have time to attend to administrative duties. the mif has shared personnel for these tasks. any facility that conducts laboratory animal research should be accessible by authorized personnel only. we cannot overemphasize this because of magnet safety, radiation safety, and animal health. traffic patterns for animals entering the facility may be necessary if the animal health level varies in different areas. the amount of personal protective equipment (ppe) needed will be defined by the types of animals in the facility, as well as the health standard. the minimum ppe for handling animals in the mif includes a disposable lab coat and gloves. because animal studies are ongoing, and we temporarily house mice, personnel must don a lab coat upon entering our facility, regardless of their animal contact. studies with nonhuman primates require a higher level of ppe that includes mucous membrane protection. standard ppe worn around the mri scanners must be nonmagnetic. an institutional animal care and use committee (iacuc) should approve every study conducted within the facility. new investigators may seek the assistance of facility personnel in writing their protocols. this gives the imaging facility personnel a chance to suggest feasible imaging modalities, preparation methods, and anesthesia regimes. the mif has a committee of experienced researchers that review experiments for feasibility, safety, and time requirement. imaging time may be scheduled on a firstcome first-served basis, or otherwise. instruments with short imaging times allow for a larger number of studies in any given period of time. when demands exceed the available scan time, one solution is to assign blocks of time for specific groups. then individuals within the group can work out their own priority for imaging. in our experience, it is easiest to have the equipment operators schedule the investigators. the operators will be most experienced with the requests of the prospective study and can schedule time accordingly. in the mif, magnet scan time during regular working hours is assigned to institutes in blocks; the remaining scan time is assigned on a first-come first-served basis. the other imaging devices require less time per scan, so it has not been necessary to assign blocks of time yet; each investigator is assigned time on a first-come first-served basis. scan time is charged back to the institute by the hour, and the dollar amount is calculated with a budget-driven formula. noninvasive imaging of rodents and other small animals is a powerful tool for biomedical research. setting up an imaging facility is a complex process that involves many decisions affecting everything from available instruments to staff composition. careful planning should help prevent operational snags. the advice of experienced people will be the most valuable asset. it is our opinion that the facility should be designed around a primary mri scanner because mr offers versatility for many applications. acquisition of other devices will be determined by the needs of the research community. growth of the facility is limited only by usage and executive decisions. staff must include a few experienced personnel, but inexperienced eager personnel can be trained to be experts. we have tried to provide an outline of some of the important considerations that went into the creation of the mif. challenges in small animal noninvasive imaging reproductive and teratologic effects of electromagnetic fields mr microscopy and high resolution small animal mri: applications in neuroscience research imaging transgenic animals in vivo imaging of gene and cell therapies electron paramagnetic resonance for small animal imaging applications molecular imaging in small animals-roles for micro-ct the use of microcomputed tomography to study microvasculature in small rodents a review of high-resolution x-ray computed tomography and other imaging modalities for small animal research high resolution x-ray computed tomography: an emerging tool for small animal cancer research advances in in vivo bioluminescence imaging of gene expression advances in ultrasound biomicroscopy noninvasive cardiovascular phenotyping in mice molecular imaging of small animals with dedicated pet tomographs high resolution spect in small animal research radio-imaging in small animals the authors would like to thank stasia anderson of laboratory of diagnostic radiology research, nih, for providing an mr image, dan schimel of the nih mouse imaging facility for providing a ct image, cecilia lo of the laboratory of developmental biology, nhlbi, nih, for providing an ultrasound image, takashimurakami and sam hwang of the dermatology branch, nci, nih, for providing a luciferase image, michael green and the imaging physics laboratory, nih, for providing a pet image, and afonso silva of the laboratory for functional and molecular imaging, ninds, nih, for providing images for this paper. we would also like to thank alan koretsky of the laboratory for functional and molecular imaging for helpful discussions. key: cord- -chwk bs authors: nan title: abstracts: poster session date: - - journal: ann neurol doi: . /ana. sha: doc_id: cord_uid: chwk bs nan an immune etiology has been postulated for acute cerebellar ataxia of childhood (acac) since it frequently follows viral infections. we analyzed serum and cerebrospinal fluid (csf) from acac patients for antibody cross-reacting with cerebellar neurons. serum and csf were obtained within days of onset of pancerebellar ataxia from subjects aged . to years. varicella infection preceded cases. results of enhanced cranial ct scans were normal; csf demonstrated - cells/mm with sterile cultures. serial dilutions from : of serum and undiluted csf were screened for antineuronal antibody by indirect immunofluorescence (iif) using frozen, unfixed normal human cerebellum. serum ( : ) was examined further for antineural antibody by western immunoblotting using purified cerebellar neuronal extracts as antigen. serum from age-matched, neurologically normal pediatric inpatients served as the control group for iif and immunoblot experiments. in acac patients, no antineuronal immunoreactivity was observed by iif. immunoblots demonstrated no consistent pattern of immunoreaction when comparing acac to controls, though patient exhibited distinct bands at kd (neurofilament protein) and kd. although antecedent infection suggests an immune etiology for acac, our preliminary results do not support a humoral mechanism for this disorder. ingrid taff; joseph zito, robert gould, and steven pavlakis, great neck and manhasset, ny in a -month period we studied patients between the ages of weeks and years with magnetic resonance angiography (mra). studies were performed on a . t magnet (siemens magnetom sp) with a circular polarized head coil. a three-dimensional time-of-flight technique was utilized. occasionally, images were obtained after gadopenetate dimeglumine infusion. two-dimensional projection images were calculated using a maximum intensity projection algorithm and recorded on laser film. sixty-seven patients also had routine mri. a sampling of vascular lesions was demonstrated. nineteen patients had clinical and mri evidence of stroke. mra revealed intracranial vascular occlusion in patients, diminished focal cerebral flow in the affected area in , and generalized ipsilateral underdeveloped cerebral circulation in . a moya-moya vascular pattern was found in and sickle-cell vasculopathy was found in patient. seven mras were normal. seventeen vascular hamartomas were demonstrated including vene of galen malformations, arteriovascular malformations, and venous angiomas. three aneurysms were found. thirty-one mras were normal. we find m u to be a valuable adjunct to routine mr imaging in the evaluation of pediatric patients with potential cerebrovascular disease. it demonstrates a spectrum of pathology, is noninvasive, and allows for serial follow-up examinations. angiography in pediatric cerebrovascular disease p . thalamic change in acute encephalopathy of adult rats. twelve weeks after grafting, clinical and histological studies were performed. we developed a protocol for evaluating functional deficits that follow spinal cord injury in the rat. the survival, growth, differentiation, and parenchymal integration of the graft were documented histologically on semi-thin section. animals that received the transplants demonstrated qualitative and quantitative improvements in several parameters of locomotion. donor tissue integrated most often with the host spinal cord at interfaces with host gray matter; however, some implants also exhibited sites of fusion with damaged host white matter. we suggest embryonic rat spinal cord transplantation may be a useful treatment of spinal cord injury and a possible therapeutic strategy in human spinal cord injury and amyotrophic lateral sclerosis. the basic neuropathophysiology of hemineglect after unilateral cerebral lesions is still not clear. one theory holds that degraded perceptual processing occurs in the damaged hemisphere due to intrahemispheric deficits. another holds interhemispheric interaction at fault, with the intact hemisphere actively inhibiting spatial cognitive processes in the damaged one. we tested adult macaca fascicuhris with acute neglect on a task in which the whole visual surround was restricted to degrees from central fixation, and a second in which an opaque lens occluded the eye either ipsilateral (ipsi) or contralateral (contra) to the lesion. using paired t tests, in the first task there were no differences in reaction time to the ipsi and contralesional hemifields. in the second, there was no change in extent of the ipsilesional field (obtained with the contralesional eye occluded), as compared to its extent without occlusion. the contralesional field, however, improved significantly ( p < . ) with the ipsilesional eye occluded. since reducing sensory input to both hemispheres leads to no worsening of hemineglect, but reducing sensory input to the intact hemisphere alone leads to improvement of hemineglect, we conclude that adverse interhemispheric interactions play a major role in the pathophysiology of hemineglect. we assessed the sensitivity and applicability of a new, cornbined cognitive and mood screening battery for multiple sclerosis (ms). sixty consecutive, untreated clinically active ms patients, each relapsing-remitting and chronic progressive, underwent the battery and head mri upon entering concurrent treatment trials. the battery combines the faust-fogel brief cognitive screen and visual analogue dysphoria scale, both previously validated in other neurological diseases. cognitive domains tested were immediate and delayed sentence and word-pair recall, verbal fluency, and conflicting response suppression. patients marked ''usual mood" along a "happy-sad" cartoon continuum. relapsing patients were program and abstracts, american neurological association younger ( . vs . yr mean), with shorter ms durations ( . vs . yr), and had lower kurtzke disability scores ( . vs . ). modified qualitative mri grading (lesion burden, confluence, localization) was compared. half as many relapsing patients ( % vs %) scored ''abnormal'' cognitively, despite similar "sadness" rates ( % vs %). subjective dys-~ phoria in both groups correlated with denser periventricular lesion burdens. the battery was well tolerated and easily administered within minutes without special equipment. this combined cognitive and mood screening battery is sensitive and convenient for clinically active ms. alternate forms of the battery are needed for repeatability. questionnaires may be reliable and valid supplements to laboratory tests for brain-damaged patients, as they can be applied to situations for which laboratory testing is not possible. we investigated the usefulness of informant-based data in alzheimer's disease (ad) by comparing caregivers' subjective evaluations of probable a d patients' performance on an abbreviated version of the memory self-report questionnaire to objective evaluations derived from an extensive battery of neuropsychological tests and to clinicians' evaluations. similar information was obtained from healthy agematched controls. caregivers' subjective appraisals of patients' memory correlated significantly with objective measures of secondary memory, with all cognitive variables, measures of activities of daily living, and clinicians' evaluations of dementia staging. scores were independent of clinical indicators of depression. the abbreviated memory questionnaire showed good reliability, internal consistency, and external validity. its positive predictive value is . and its negative predictive value is close to %. results suggest that ( ) informant-based questionnaires may be useful for obtaining valid information on cognitive ability outside of laboratory settings; ( ) the scale reflected more than just memory functions; and ( ) the scale may be promising for screening cognitive difficulties in epidemiological or clinical settings. although neglect along the horizontal dimensions of extrapersonal space is well recognized, there are only a limited number of observations documenting neglect along the vertical and radial spatial dimensions. we report an investigation of neglect along the principal dimensions of extrapersonal space in a patient with bilateral mesial temporo-occipital infarctions. neglect was assessed by asking the patient and controls to bisect lines of lengths oriented in directions with respect to the body: horizontal, vertical, and radial. our patient showed significant neglect of upper vertical and far radial space, as well as neglect of left hemispace. his line bisection errors were consistently in a direction opposite the slight directional biases shown by controls for all line orientations ( p < . ). the magnitude of the patient's bisection errors increased by moving the lines toward the neglected sectors of -dimensional space. neglect of upper vertical and far radial space was also evident on line cancellation tasks. our results suggest that following focal brain injury, neglect may be observed along all dimensions of extrapersonal space. these findings provide further empirical support for functional specialization within inferior and mesial temporooccipital regions for attending to upper vertical and far visual space (previc, ) . p . posterior cortical atrophy: degenerative disease with primary visuospatial and visuosemantic deficits a. kertesz, m . polk, and a. kirk, london, ontario, and saskatoon, saskatchewan, canada posterior cortical atrophy is a recent, and heidenhahn's disease is an old, label for a miscellaneous group of patients with imaging or pathological and clinical evidence of visuocognitive deficits and cortical atrophy localized to the posterior cortex. the extent of this cortical localization and the nature of the pathological findings are not fully agreed upon, but spongiform degeneration and alzheimer pathology have been described. detailed examination of patients who are representative of the problem and have uniquely specific deficits is presented. one patient had visual associative agnosia, prosopagnosia, and transcortical sensory aphasia. lexicosemantic experiments of categorization, word retrieval, and comprehension of auditory and visual stimuli showed a specific impairment of visuoverbal semantics. a striking preservation of phonological, orthographic and visual structural input, and intercategory dissociations was demonstrated. consistency of errors argued for specific loss of semantic knowledge. another patient with apraxia, primary visuospatial deficit, agraphia, and amnesia at the beginning had predominantly right-sided posterior cortical atrophy, demonstrating further fractionation of the entity and the striking specificity of visuospatial function. the behavioral specification of degenerative disease is clinically and theoretically important. permanent neurological deficits after ischemic stroke are mainly determined by the location and size of the infarct. clinical recovery also depends on the functional state of adjacent brain tissue, where both neuronal loss and deactivation without gross morphological damage may affect flow and metabolism to a varying degree (g. mies et al, stroke ; - ) , and where the ability to respond to stimulation by appropriate neuronal recruitment may be impaired. therefore, degree of resting hypometabolism and of responsiveness to functional activation may provide a measure of prognosis. in patients (age . . yr) with aphasia consequent to ischemic stroke of the dominant hemisphere, regional cerebral metabolic rate of glucose (rcmrgi) was measured at rest and in of them also during spontaneous speech, using positron emission tomography (pet) of -(f )-fluoro- -deoxy-~-glucose (fdg). the pet study and a standardized neuropsychological test battery to assess the main aspects of language were performed around the fourteenth day after the stroke, and the language functions were assessed again to months later. performances in various dimensions of language weeks and to months after stroke were related to rcmrgl in topographically meaningful areas at rest and during activation using wilcoxon-rank program and abstracts, american neurological association sum test and multiple regression analysis. severity of aphasia was assessed by the token test, which showed a bimodal distribution to slight and severe, and a lower representation of moderate cases. global and all regional cmrgl at rest and during activation were significantly correlated to scores in token test at first and second examination, with the highest correlation coefficients ( - . to - . ) for broca's, wernicke's, and left temporoparietal regions. for performance after to months, the relationships were still significant with lower coefficients. verbal fluency also was correlated to kmrgi, but with lower coefficients that slightly increased for the recovery state. language performance at different stages in the course after ischemic stroke was significantly related (r = . for token test, r = . for verbal fluency). however, there exists a high variability in recovery that may be explained by stepwise regression of metabolic values. significant effects were observed only for cmrgl of the left hemisphere outside the infarct (partial r' = . ) at rest and for cmrgl within the infarct ( . ), the contralat-era mirror region ( . ), and broca's region ( . ) during activation, with a sum of all partial weight factors of . at rest and . during activation. our results furnish indicators for recovery of aphasia: the resting metabolism of the left hemisphere outside the infarct, and the activated metabolism in residual tissue within the infarct and in languagerelated areas. although the hemispheric metabolism at rest might be related to neuronal loss and thereby to the brain's reserve capacity, the extent of metabolic activation indicates neuronal recruitment and the capability of neuronal networks for functional recovery. heparin therapy for acute myocardial infarction: the timi-i pilot and randomized trial combined experience m . a. sloan, t . r. price, m . l. tevrin, and s. forman for the timi investigators, baltimore, m d of , myocardial infarction (mi) patients treated with rt-pa and heparin, ( . %) developed ischemic cerebral infarcts (ci). all ci patients had detailed neurological evaluations and ( %) had c t scans. age range was to years (mean yr), were male, and were caucasian. electrocardiographic location of mi was anterior in ( %) and nonanterior in ( %). six cis occurred within hours; between and hours; between and hours; between and hours; during the second week; and others distributed over the weeks after study entry. six of cis did not involve cerebral cortex; ( %) had multiple cis. of cis thought to be embolic in origin, had at least cardiac abnormality (mural clot, wall motion abnormality, aneurysm, or transient atrial fibrillation) known to be associated more specifically with embolism than just the diagnosis of myocardial infarction. eight of ( %) with ct scans had hemorrhagic conversion of varying degrees. the time of occurrence and sites of ci after rt-pa and heparin therapy for acute mi are similar to those reported in the prethrombolytic area. nancy futrell andjeanne m. riddle, detroit, m i photochemical irradiation of the carotid artery of rats has been used to induce endothelial damage, producing a nonocc h i v e thrombus (that apparently embolizes spontaneously) thrombi and emboli and multiple cerebral infarcts. evidence for embolism generally has a presumptive component. to document further that cerebral infarcts in this model are indeed due to embolism, we studied the ultrastructure of the carotid thrombi and the presumed cerebral emboli using scanning and transmission electron microscopy (sem, tem). the right carotid artery of wistar rats was irradiated with a laser ( nm, mw/cm , min) following the injection of the photosensitizing dye photofrin , . mgikg. rats were sacrificed from to hours later. endothelial damage with formation of a fragmenting thrombus, composed mainly of platelets and erythrocytes (with no fibrin in most areas), was present in the carotid arteries of all rats by sem. sem was done on cerebral vessels, containing peripheral blood elements, with single ( ) and aggregated ( ) platelets (causing occlusion in ), single ( ) and aggregated ( ) erythrocytes (without occlusion), and single ( ) and aggregated ( ) leukocytes (without occlusion). tem demonstrated that the platelet aggregates did not adhere to the cerebral endothelium. the endothelial surface of all cerebral vessels was normal, which provided additional evidence that the mechanism of cerebral infarction in this model is embolism. model of repetitive ischemia: this effect is significantly enhanced when combined with mild hypothermia ashfaq shuaib and elisabeth sechocka, saskatoon, saskatchewan. canada there is considerable evidence that glutamate release resulting in activation of postsynaptic receptors (especially nmethyhaspartate) is a major mechanism of ischemic neuronal injury. in vivo experiments have shown that a more severe release of glutamate may be responsible for the excessive damage seen with repeated ischemic insults. we have shown that in cell cultures the effect of brief repeated insults is more severe than a single insult of similar duration. in the present study, we tested the protective effects of cgs- in a cell culture model of single ischemic and multiple-insult paradigm. in the multiple-insult paradigm, in some cultures cgs- was combined with mild hypothermia to see if this would offer additional protection. cgs- offered a dose-dependent protection in cell cultures exposed to a single ischemic insult. cgs- was protective to cultures exposed to repeated ischemic insults. the protective effects were enhanced significantly when they were combined with hypothermia, resulting in almost complete protection of the cultures. the combination of therapies appears to be a valuable strategy in neuronal protection during cerebral ischemia. toby i. gropen, i . prohovnik, t . k. tatemirhi, z. sharif; and m. hirano, new york, n y although a rare syndrome, mitochondria encephalomyopathy, lactic acidosis, and stroke (melas) may offer a unique insight into stroke mechanisms. we report novel observations in a patient with melas studied with serial and quantitative cerebral perfusion after stroke using """tc-ceretec spect and ' ixe rcbf. a -year-old man with melas presented with left-sided headache, generalized seizures, fluent aphasia, and right hemianopia. serial ct and mri showed infarction of the posterior left hemisphere in a multiterritorial distribution. spect performed days after stroke showed to % greater flow in the infarct than in normal brain, which reversed days after stroke. quantitative rcbf (m isi, reflecting mostly gray matter), when corpatients died. we recommend ct evaluation in all patients who have a seizure or lose consciousness during the peripar-tum period. despite intensive management, mortality is high. seizures should not be attributed to eclampsia without careful neurological assessment. when prenatal care is sought, women should be counseled about the dangers of cocaine to themselves as well as to their babies. changes in circulating blood volume following stephan a. mayer, matthew e. fink, laura lenniban, louise m. klebanoff; auis beckford, lsak prohounik, william young, and robert a. solomon, new york, n y reduction of blood volume (bv) has been implicated as a risk factor for delayed cerebral ischemia (dci) due to vasospasm after aneurysmal subarachnoid hemorrhage (sah). volume expansion guided by target filling pressures has gained popularity as a means of preventing or reversing dci; however, the adequacy of central venous pressure (cvp) as a reflection of bv in this setting remains unclear. we measured bv and cvp concurrently in patients ( males, females; mean age yr) day after craniotomy (mean . days after sah) and an average of . days later. the mean bv (mllkg) measured using chromium '-labeled red blood cells (rbcs) fell from . to . (normal range - ), a reduction of % ( p = . , paired student's t test). despite this, mean cvp (mm hg) remained unchanged ( . vs . ). similar reductions of plasma volume ( %) and rbc volume ( %) accounted for no change in mean hematocrit ( . vs . ). bv fell . % among grade iiiliv patients (n = ) compared to . % among grade / patients (n = ). a moderate correlation between bv and cvp ( r = . , p = . ) was found only with the first set of measurements. time-related alterations in venous capacitance, myocardial contractility, or systemic vascular resistance may explain our findings. axel rosengart, louis r. caplan, michael s. pessin, atherostenosis of the extracranial vertebral artery (ec-va) has rarely been studied systematically in series of patients with acute vertebrobasilar strokes or transient ischemic attacks. we identified by conventional angiography and neuroimaging (ct, mri, ultrasound, mr angiography) patients with ec-va disease among patients with posterior circulation ischemia. patients with cardiac sources of emboli were excluded. the probable etiologic mechanisms were: group a: vertebral artery origin (vao) atherostenosis with embolism- patients; group b: vao atherostenosis with hemodynamic spells- patients; group c: patient with vao atherostenosis and both intra-arterial embolism and hernodynamic spells; group d: ec-va dissection- patients ( unilateral, bilateral); patient had perioperative compromise of the ec-va with presumed intra-arterial embolism; group e: vao disease in addition to other distal vascular lesions- patients ( with intracranial va and with basilar artery [baf occlusive disease). ec-va disease is not always benign. vao atherostenosis and dissection of the ec-va are sources of intra-arterial emboli. hemodynamicrelated ischemia occurs with bilateral and unilateral va disease but is often transient. vao atherostenosis is often accompanied by severe occlusive disease of the intracranial va and ba. program and abstracts, american neurological association sebastian e. ameriso, vicky l. y. wong, andvas gruber, hidemi ishii, and mark fisher, los angeles and la jolla, c a , and kanagawa, japan hemostasis abnormalities are associated with ischemic stroke. these changes typically are demonstrated in antecubital venous blood samples and may not necessarily represent changes within the vasculature of the brain. the purpose of this study was to identify potential differences in hemostatic profile from samples of cranial versus noncranial venous sites in patients with acute ischemic stroke. eight patients were studied within days of acute brain infarction. some patients were studied on separate days. blood was drawn from the external jugular vein and immediately thereafter from an antecubital vein without the use of tourniquet. we measured hematocrit, leukocyte count, platelet count, fibrin d-dimer (cross-linked fibrin fragment), plasminogen activator inhibitor- (pai- , an important antifibrinolytic protein), and anticoagulant proteins thrombomodulin and activated protein c. a jugular-to-antecubital ratio was calculated for each paired blood sampling. thirteen paired samples were obtained from the eight patients. external jugular-to-antecubital ratios (mean to-antecubitat ratio for pal was significantly different from ( p < . ), with higher concentrations in jugular samples. in conclusion, levels of hemostatic proteins measured from cranial venous blood may differ from antecubital samples in patients with acute ischemic stroke. in animal models of transient cerebral ischemia, the effects of repetitive insults are more severe than a single ischemic episode of similar duration. we used the cell culture model of ischemia to determine if the effects of repetitive ischemia are similarly more severe in this model of ischemia. for cell culture, we used fetal mice cortical astrocytic and postnatal cerebellar (glutamatergic) granular neurons and cerebral gamma-aminobutyric acid (gaba)ergic cells. lactic dehydrogenase (ldh) (activity per gram protein) release in the medium was used as a measure of cellular damage. compared to a single insult, there was a large increase in ldh release during repetitive ischemia in astrocytes ( vs , p < . ) and granular cells ( vs , p < . ) (highly significant) and a modest (but significant) increase in the cortical neurons ( . vs . p = . ). the demonstration that repetitive ischemia produces more severe damage in cell culture would suggest that the mechanisms are not predominantly vascular. cell culture could prove useful to study the mechanisms of neuronal damage with repetitive ischemia. we studied the spontaneous recovery of neurological function after acute ischemic stroke using a standardized stroke nih stroke scale scale ( n i h stroke scale) to assess the extent of improvement, differences in stroke types, and early predictors of later outcome. we performed serial neurological assessments on admission; , , and hours after admission; and to days and > days after admission. twenty-six patients had presumed embolic occlusion of the middle cerebral artery (mca) and had a clinical diagnosis of lacune. admission score was better in the lacune group compared to the mca group. the mean scores for all patients improved by the to -day and the > -day examination, but the degree of improvement was greater in the mca group than in the lacune group at > days ( p < . ). the degree of change at to days correlated with the change in score at hours ( r = . , p < . ) and hours ( r = . , p < . ). most patients improve after acute ischemic stroke, but to variable degrees and at different rates. david w. desmond, thomas k. tatemichi, miguel figueroa, dew'itt t . cross, and yaakov stern, new yovk, n y to investigate the effects of lacunar infarction (li) on cognitive function, we examined li patients months after stroke (age = . ? . yr; education = . . yr) and stroke-free nondemented control subjects (age = . k . yr; education = . k . yr) with a battery of neuropsychological tests. li was defined as a presenting infarct of cc and a mean volume of any additional subcortical infarctions of cc on ct scan. using multiple regression analyses, with significance set at p < . to minimize the risk of type i error, we considered the role of li as a correlate of performance in multiple cognitive domains. controlling for the effects of demographic factors, vascular risk factors, alcohol use, and depression within the multivariate models, li was a significant independent correlate of deficits in memory (( = -. , p = . ), verbal (p = -. , p = . ), visuospatial (p = -. , p < .oool), abstract reasoning (p = -. , p = . ), and attentional skills (p = -. , p < . ). we further investigated the effects of infarct number, volume, and location, as well as atrophy, on global cognitive function within the li group. the only significant independent correlate of global cognitive performance was a preponderance of left-hemisphere infarctions (p = -. , p = , ). these results suggest that li may produce dysfunction in multiple cognitive domains, particularly when the left hemisphere is differentially involved. p . increased intracranial atherosclerotic stroke in hispanics and blacks from northern manhattan ralph l. sacco, christina zamanillo, t . shi, andj. p. mobr, new york, ny intracranial atherosclerosis has been found to be more frequent in blacks compared to whites, whereas hispanics have rarely been characterized. among consecutive patients from northern manhattan over age hospitalized at the presbyterian hospital from to , cerebral infarction occurred in whites, blacks, and hispanics. all patients had at least one c t scan, % had duplex doppler, % transcranial doppler, and % angiography. strokes were classified as atherosclerotic (ath), cardioembolism, lacunar, and as infarcts of undetermined cause. ath was further subdivided into extracranial (eath) or intracranial (iath) . overall, the frequency of ath was similar in the three racelethnic groups (white , black ' , hispanic ) . the distribution of the atherosclerosis, however, was different in whites compared to blacks and hispanics. whites had more eath stroke than blacks and hispanics (white %, black % , hispanic lo%), while iath was similar in blacks and hispanics and greater than in whites (white , black , hispanic %). nonwhites have more iath stroke than whites. the similarity in the distribution of atherosclerosis between blacks and hispanics argues for shared environmental risk factors, rather than genetic differences. ethnic differences in stroke risk factors may help explain differences in infarct subtype. we studied mild to moderate alzheimer's disease (ad) patients with a series of " water bolus positron emission tomographic (pet) activation studies, and compared them to similar studies in age-matched normal controls. for each group, pet images were mapped onto the subjects' mri scan, and results of a particular activation condition were averaged across the group. naming a series of pictures (line drawings of animals) minus counting abstract designs as a baseline produced strong activation of the anterior cingulate gyrus only in the ad group. silent reading of words minus viewing a baseline series of "xs" similarly showed strong activation of the anterior cingulate gyms in the ad subjects but not the normals. naming block (activation condition) of % unnamed pictures, minus a second block (baseline) of easily named pictures, demonstrated much greater cingulate activation in the ad patients, for naming of the more difficult pictures. we conclude that this cingulate activation may reflect the greater involvement of an attentional network (of which the anterior cingulate is a part) in tasks requiring a higher degree of "mental work" on the part of ad patients. dementia in alzheimer's disease j. w. pettegrew, k. panchalingam, w. e. klunk, and r. j alzheimer's disease (ad) predominantly affects the brain, resulting in the loss of multiple cognitive abilities. some studies suggest the membranes of peripheral cells are involved in the disease. to investigate erythrocyte membrane molecular dynamics in ad patients and age-matched controls, we investigated erythrocyte membrane molecular motion at the surface (fluorescamine), aqueous-hydrocarbon interface (dppe-ans), and hydrocarbon core ( j-as; ppc-dph) by steady-state fluorescence anisotropy measurements of probable ad patients ( males; females) and ( males; females) age-matched controls. cognitive function was assessed by the mini-mental, mattis, and blessed scales. we found that intergroup comparisons revealed decreased motion at the surface ( p = . ) and aqueous-hydrocarbon interface ( p = . ) and increased motion in the hydrocarbon core ( p = . ) of the moderately to severely impaired ad patients compared to the controls. in the ad patients, there were significant correlations between decreasing membrane surface motion and worsening blessed scores (males p = . ; r = . ; femalesp = . ; r = . ). these findings suggest that molecules are being produced in the brain of ad patients that gain access to the circulation. these molecules insert into the erythrocyte membrane and secondarily alter erythrocyte membrane molecular motion. the production of these molecules correlates with the dementia and could contribute to the molecular pathophysiology of the disease. parkinson's disease (pd) and alzheimer's disease (ad) are common disorders of old age and may therefore coexist. the prognosis in demented pd patients is poor and early recognition of such cases is therefore desirable. the objective of this study was to identify characteristics that distinguish pd + ad from pd patients during early stage. all patients were clinically evaluated over a -year period . clinical diagnosis of dementia was made only when unequivocal clinical evidence of progressive decline in memory and cognitive function was documented, and pathological diagnosis of ad and pd was made using standard criteria. twentysix patients who had only pd or pd + ad were identified; had no dementia and at autopsy had pd. six patients had clinical evidence of parkinsonism and dementia and at autopsy had distinct pathological findings-pd and ad. these cases could be classified as having simultaneous or sequential evolution of pd + ad. those with sequential onset had pd before age years but were inexplicably functionally disabled early on, whereas those with simultaneous onset manifested pd after age years. pd + ad patients had rapid disease progression, shorter survival, poorer drug response, and more side effects of levodopa than pd patients. to study the prevalence ofwhite matter lesions in the general elderly population, and to investigate whether white matter lesions were relatively frequent in subjects with classic vascular risk factors and with hemostatic risk factors, magnetic resonance scans were obtained of participants, aged to years, of the rotterdam elderly study. the subjects for the imaging study were a random sample from the general population, stratified by age and gender. t -weighted images were obtained in the axial plane. white matter lesions were considered present when moderate or severe periventricular hyperintensities or when more than small focal lesions or focal confluent lesions were found. overall, % of subjects had white matter lesions. the prevalence and severity of le-program and abstracts, american neurological association sions increased with age. history of stroke or myocardial infarction, presence of peripheral arterial disease, factor viic activity, and fibrinogen level were each significantly and independently associated with the presence of white matter lesions. significant relations with actual systolic as well as diastolic blood pressure, with a history of hypertension, and with plasma cholesterol were observed only for subjects between and years. this study suggests that white matter lesions in the elderly may be related not only to the classic cardiovascular risk factors. but also to hemostatic factors. joan m. swearer, paula nelligan, hanno muelher, beatrice woodward, and david drachman, worcester, ma although behavioral disturbances occur frequently in alzheimer's disease and other dementing disorders, little is known about the factors that predict their development or predispose to their occurrence. in the present study we examined sets of possible predictive/predisposing factors retrospectively for behavioral disturbances in mildly to severely demented, community-dwelling patients. the factors examined included: individual distinguishing features (age, gender, age of onset, premorbid personality traits, prior psychiatric history) and dementia severity (dependence in activities of daily living [adls) and self-care, duration of dementia, global disease severity). spearman correlations and t tests were used to assess the relative influence of these factors on the occurrence of types of aberrant behaviors: aggressive behaviors, disordered ideation, and motor abnormalities. forty percent of the patients exhibited aggressive behaviors, % exhibited disordered ideation, and % had motor abnormalities. neither a prior history of psychiatric disorders nor premorbid personality traits were associated with the occurrence of the target behaviors. dependence in adls and self-care and greater global severity were associated ( p < . ) with the frequency and severity of aggressive behaviors, disordered ideation, and motor abnormalities. these results suggest that severity of dementia is a consistent and reliable factor in the development of aberrant behaviors, whereas preexisting personality traits are not. dementia of the alzheimer t y p e w. j. burke, a. ranno, w. h . roccafrte, s. p. wengel. b. l. bayer, and n . k. willcockson, omaha, ne l-deprenyl is an irreversible inhibitor of mao-b that has been reported to cause modest improvements in short-term memory and behavioral symptoms in persons with dementia of the alzheimer type (dat). thirty-eight subjects meeting research criteria for mild d a t were enrolled in a placebo-controlled, double-blind trial of r-deprenyl at a dose of mg twice a day. subjects underwent extensive clinical and neuropsychological assessments at entry, and at and months. after months, subjects taking both l-deprenyl and placebo showed a significant decline in their scores on the mini-mental state examination, the clinical dementia rating (cdr) scale, and the sum-of-boxes score derived from the cdr. when the change in scores on these clinical measures was examined across the groups, there was no significant difference. there were no significant differences within or between groups on several behavioral measures including the brief psychiatric rating scale and the cornell rating scale for depression in dementia. neuropsychological testing demonstrated no significant differences berween groups based on mean score change. l-deprenyl did not affect cognition or behavioral symptoms of dat in this -month study. k. marder, m-x. tang, r. ottman, l. cote, y. stern, and r. mayeux, new york, n y the etiology of dementia in parkinson's disease (pd) is probably multifactorial but there may be a shared susceptibility for p d and alzheimer's disease (ad). reliable risk factor interviews were conducted with informants of nondemented p d patients (pd-d) and demented p d patients (pd + d) enrolled in a longitudinal community study of pd. p d + d were older ( . yr) than pd-d ( . yr) and had later age at onset of motor signs ( . yr) than pd-d ( . yr) ( p < , ). the frequency of smoking, alcohol use, head injury, and family history (fh) of pd did not differ but fh of ad was significantly more frequent in the pd + d group (or . , ci . - . ). using stepwise logistic regression, only age of onset of motor signs (or . ), education < years (or . ), and the interaction of age of onset of motor signs and fh of a d (or . ) were independent predictors of dementia in pd. to address variable years at risk for development of dementia, life table analysis revealed the cumulative risk of a d to age in first-degree relatives of p d + d was . , and . in pd-d relatives ( p < . ). cox proportional hazards analysis controlling for the differences in ages of the relatives of both groups yielded a rate ratio of . (ci . - . ) for the development of a d among p d + d compared to pd-d relatives. we conclude that a genetic susceptibility to a d may raise the risk for dementia in patients with pd. differentiated from alzheimer's disease? john c. mowis, elizabeth grant, rita canfield, eugene rubin, and daniel mckeel, jr, st louis. mo vascular dementia (vd) is believed to account for to % of all us cases of dementia; however, pathologically confirmed cases are quite rare. this discrepancy suggests that current diagnostic criteria lead to the clinical overdiagnosis of vd. twenty v d subjects (mean age . yr; men, women) were diagnosed solely on the basis of the presence of dementia, a history of stroke(s), and a documented relationship of stroke to onset andlor course of dementia; ischemic scores (is) and neuroradiographic findings were not used for diagnosis. compared with subjects (mean age . yr; men, women) with dementia of the alzheimer type (dat), there were no significant group differences for comparable clinical dementia rating stages of dementia for measures of language, activities of daily living, or general cognition. the vd group scored significantly higher than the dat group on the modified is (f [ , ] = . , p < , ). all autopsied d a t subjects had verified alzheimer's disease (ad); also had cerebral infarctions. the autopsied v d subjects had , , and cc of brain tissue affected by stroke; ( cc) also satisfied histological criteria for ad. we conclude that ( ) the clinical features of vd and a d overlap considerably; ( ) diagnostic criteria based on the temporal association of stroke with dementia may have predictive value for vd; and ( ) the frequent coexistence of a d and strokes indicates that refinement of criteria is needed to distinguish "mixed" and "pure" vd. clinicopathological correlation remains essential for any study of putative vd. left-handedness has been proposed as a marker for decreased survival in the general population, but possible effects of handedness on longevity in alzheimer's disease (ad) have not been examined. we hypothesized that left-handed ad patients would evince more rapid deterioration and therefore die at an earlier age than right-handed patients. subjects were demented patients consecutively confirmed at autopsy to meet nincds-adrda criteria for "definite" ad. handedness was determined from structured interviews with primary caregivers and validated for most subjects with the edinburgh inventory of handedness. age at onset of dementia symptoms retrospectively determined by caregivers was used to calculate the duration of illness at the time of death. because of reported gender differences with regard to longevity, we first partialled out effects of gender before using hierarchical regression procedures to test the hypothesis. four of men and of women with definite ad were left-handed. the mean age at onset did not differ significantly between handedness groups (f [ l,loo] = . ), but the mean duration of symptoms ( alterations in the optical properties of brain can be used to detect pathological changes in patients with alzheimer's disease (ad). using time-resolved spectroscopy (trs) and phase-modulation spectroscopy (pms), we measured the absorption (ua) coefficient, scattering (us) coefficient, and mean photon pathlength (pl) of red light directed through the base of the frontal lobes of patients with ad and age-matched control subjects. the measured values and the asymmetry index (ai) (an indication of the symmetry of the measurements between the left and right side of the brain) were correlated with the severity of disease as determined by mini-mental state score. there were significant differences between the ad and control group for ua, us, pl, and the standard deviation of ai. there was no correlation between the mms score and ua, us, or pl. however, the highest asymmetry index values were seen in moderately impaired patients , which suggests that the asymmetrical nature of the pathological process detected by optical spectroscopy is most marked during this stage of the illness. this noninvasive technique may provide a convenient method to detect and monitor the pathological changes that occur in the brain of patients with ad. disease p . memory impairment in very mild alzheimer's a memory impairment is often the earliest indication of alzheimer's disease (ad). we investigated components of disease learning and recall to determine which aspect of memory function is impaired the earliest in incipient ad. using the mayo clinic alzheimer's disease patient registry, which is a longitudinal prospective project on ad and normal aging, we identified patients with very mild ad (i.e., with a mini-mental state score of or greater) and age-and sex-matched controls. we assessed performance on memory measures: the rey auditory verbal learning test and the buschke free and cued selective reminding test (fcsrt). the parameters evaluated included a measure of acquisition, total learning over trials (tl), and delayed recall (dr). on the fcsrt, an index of facilitation of performance with semantic cues (sc) was assessed. results indicated that all indices, tl., dr, and sc, were capable of separating the mild ad group from the controls ( p < , ). using a linear discriminant analysis with stepwise variable entry, the measure that assessed the patient's ability to use semantic cues (sc) was the most sensitive parameter for separating the groups ( f = . , p < . ), and the acquisition parameter (tl) was also useful at adding some additional predictive power (f = . , p < . ). the delayed recall measure, however, did not add anything to the previous measures. it appears that very early ad can be detected using appropriately structured memory tasks, and these procedures can be helpful in identifying at-risk individuals. alzheimer's disease (ad) has an insidious onset that is difficult to date reliably. we developed a standardized interview to provide objective criteria for dating the onset of different symptoms (memory complainr, performance problems, language deficits, disorientation, depression, behavior problems, and psychosis), yielding an estimated disease onset date. inrerrater reliability (icc = . ;p < , ) and interinformant reliability (icc = ; p < . ) for the onset of first symptom was high. interrater agreement for the order in which symptoms appeared was high (icc = . - . ) as was interinformant reliability for all symptoms except memory complaint. the interview was administered to patients with ad. mean estimate duration of illness was . years k . years and correlated significanrly with problems in instrumental activities of daily living. sixty-six percent had memory complaint and % had performance problems as their initial symptom. this technique provides a reliable characterization of disease onset. longitudinal studies will determine if particular onset symptoms differentially predict disease progression. the purpose of this study was to determine whether there is an excess of white matter disease (wmd) in alzheimer's disease (ad). brun and englund ( ) reported an excess of wmd in brains of patients with ad vs age-matched controls. there have been reports both confirming (bowen et al, ; fazekas et al, ) and refuting (leys, ) these findings using ct and mri in patients with clinically diagnosed ad. postmortem t -weighted mri scans and program and abstracts, american neurological association neuropathology were graded on brains of pathologically confirmed ad subjects and brains of age-matched neuropathologically normal controls. white matter lesions were scored on a to scale (none, mild, moderate, severe) separately for periventricular (pvl) and deep white matter (dwm) areas in mri scans and lux fast blue (lfb)-stained brain sections. correlations between mri and neuropathology were good ( r = . for pvl, r = . for dwm). pvl scores were higher in ad than in normal subjects on mri (ad: . l . vs controls: . rfr . ; p < . ). on pathology the difference in scores did not reach significance (ad: . . vs controls: . * . ; p = . ). similarly, dwm scores were higher in ad subjects than normals on mri, but not neuropathology. in conclusion, ad brains have a significant excess of wmd on mri compared to controls. although the pvl and dwm scores for pathological sections are not different in the groups, mri is much more sensitive than lfb-stained sections for wmd. thirteen autopsy cases of progressive supranuclear palsy (psp) were investigated for clinical-neuropathological correlations and heterogeneity. we reviewed clinical records of men and women aged to years (mean age yr) with disease duration ranging from to years. most patients had classic features of psp including ophthalmoplegia, postural instability, and extrapyramidal signs. dementia was eventually observed in of the patients ( %). six of patients ( %) on whom adequate initial documentation was available presented with memory loss or behavior change. five of the patients ( %), including with an initial presentation of memory loss, were diagnosed clinically as having alzheimer's disease (ad) rather than psp; neuropathological diagnoses in these cases varied: i had combined ad-psp; had ad-psp combined with parkinson's disease (pd) changes; had psp-pd; and had "pure" psp. the patients with concomitant pd changes showed lewy bodies in the substantia nigra, locus coeruleus, nucleus basalis, and neocortex. the remaining patients were clinically diagnosed as having psp; neuropathological diagnoses in these cases included with "pure" psp and with psp that also met neuropathological criteria for ad (psp-ad). these findings emphasize the clinical and neuropathological heterogeneity in psp. the neuropsychological battery developed for the consortium to establish a registry for alzheimer's disease (cerad) is currently used in many research studies to index the cognitive impairments of alzheimer's disease. in spite of its widespread use, normative informarion on the battery, important for interpretation of performance, has not been available. we report norms for the cerad battery based on a large sample of elderly control subjects (n = ; white men and women; ages - yr) enrolled in the national study of cerad. performance on the neuropsychological measures was examined separately for subjects with high ( yr) and low (< yr) education. distribution of scores and basic descriptive information (means and sd) for each measure were determined. significant age and sex effects were observed on most cognitive measures in the highly educated group. in contrast, no significant age effects were observed in the low education group. effect of sex was not explored in this group due to the limited sample size (n = ). further exploration of cerad performance in normal controls from underrepresented groups including minorities, residents of rural communities, and individuals with low education is in progress. intraneuronal inclusions of cytoskeletal proteins appear in several neurological diseases; for example, the neurofibrillary tangles of alzheimer's disease contain a cytoskeletal protein, tau. because the previously described slowing of axonal transport in aged animals might lead to accumulation of cytoskeletal proteins in nerve-cell bodies and axons, we assessed the abundance of major cytoskeletal proteins in brain tracts of rats at age months or months. immunoassay was performed with monoclonal antibodies to alpha and beta tubulin and to nf-l (the core neurofilament protein) by published methods. samples were dissected in a standardized fashion and -mrn pieces of the following tracts were assayed: optic nerve, corticospinal tract (medulla), superior cerebellar peduncle, l dorsal root, and l ventral root. between months and months, the nf-l content approximately doubled in each brain site. tubulin substantially increased at of aged rats all sites except the fimbria-fornix. in contrast, tubulin did not change in the spinal roots. nf-l increased slightly in the ventral but not the dorsal root. this tendency of senescent brain neurons to accumulate cytoskeletal proteins in their axoplasm may predispose them to formation of intraneuronal inclusions in various degenerative diseases. we performed a prospective study of preoperative magnetic resonance imaging (mri) in consecutive patients with intractable partial epilepsy who underwent a stereotactic resection of an extrahippocampal temporal lobe foreign-tissue lesion, "lesionectomy," between june and january . interpretation of the mri studies was performed by an investigator blinded to the presurgical evaluation, surgical outcome, and pathology. hippocampal formation (hf) atrophy was assessed using mri-based volumetry (n = ) and visual grading of the h f (n = ). mri-detected hf atrophy has been shown to be a reliable marker of moderate to severe mesial temporal sclerosis (mts) (cascino gd, et al, ann neurol ; : - evidence from experimental animals indicates that endogenously produced platelet-derived growth factor (pdgf) is an important regulator of glial proliferation and differentiation. because of the striking degree of glial proliferation in chronic epilepsy, we sought to determine whether cultured glia from human epilepsy tissue would be responsive to pdgf. the effects of pdgf on dna synthesis, proliferation, and relative distribution of a b (+) glia were studied in a cell culture derived from temporal lobe white matter of adult epilepsy lobectomy tissue. by immunocytochemistry, glial fibrillary acidic protein (gfap) was detectable in % of cells in untreated or -day pdgf-treated ( ng/ml) cultures, which confirmed their astrocytic nature. in contrast, a b ( +) cells increased from to % in untreated cultures to % after pdgf treatment, which suggested that type astrocytes (a b [ + , gfap[ +]) had been elicited. dna synthesis of cells resembling oligodendrocyte-type astrocyte ( - a) progenitors occurred within hours after program and abstracts, american neurological association pdgf treatment as evidenced by nuclear incorporation of brdu in bipolar a b ( +) cells. these studies demonstrate that expansion of adult human gfap( +) astrocyte populations is sensitive to regulation by pdgf. further, these data imply the existence of pdgf-responsive - a progenitor cells in astrocyte-rich cultures derived from human epilepsy tissue. ( we have recorded vagal and esophageal-evoked potentials after electrical (e) and balloon (b) stimulation in epileptic patients who had vagal stimulators for the control of intractable epilepsy and the results were compared with esophagealevoked potentials in healthy controls and diabetic patients. the vagal and esophageal-evoked potentials showed similar configurations with major positive and negative potentials. the amplitudes of the responses habituated rapidly over trials at per second up to per seconds. latencies were shorter from the upper esophagus ( cm above lower esophageal sphinctereles]) cf. lower esophagus ( cm above les) yielding conduction velocities of to meters per second but conduction was significantly slower in the diabetics. the vagal-evoked potentials have validated the use of esophageal-evoked potentials as a practical method of assessment of the integrity and speed of conduction in vagal afferent pathways in man. ronald e. kramer and neil l. rosenberg, englewood. co seizure disorders were analyzed in patients in whom toluene was the sole or major drug of abuse. toluene abuse is increasing; therefore, physicians should gain experience with its neuropathological and ciinical sequelae. a retrospective chart review found patients meeting criteria. the average patient age was years; abuse onset averaged . years; abuse averaged . years; and patients were male. ten were daily, were weekly, and were intermittent users. seizures occurred in . one suffered a single generalized tonic-clonic seizure without recurrence and without treatment. his we characterized the clinical dose-response curves for relief of parkinsonism and production of dyskinesias as a function of plasma levodopa and - -methyldopa levels in patients with parkinson's disease (pd) and fluctuating responses to oral levodopa/carbidopa. dose response to graded intravenous levodopa was measured after overnight drug withdrawal on occasions, first after chronic, intermittent oral levodopa/ carbidopa and second after to days of continuous intravenous levodopa. continuous intravenous levodopa shifted the dyskinesia dose-response curve to the right, and reduced maximum dyskinesia activity, but did not significantly alter dose response for relief of parkinsonism. improvement in dyskinesia was apparent by the second day of continuous levodopa, during which ratios of plasma dopa/ - -methyldopa remained constant. our results support the hypothesis that relief of parkinsonism and production of dyskinesias occur by separate mechanisms. continuous dopamine-mimetic therapy should be sought as a therapeutic goal for advanced pd. dopa-responsive dystonia (drd) is a distinct subset of idiopathic dystonia with diurnal fl uctuation and a dramatically beneficial response to l-dopa. it has hitherto been considered an autosomal-dominant disease with reduced penetration (mckusick no. ) . we studied an arabic family of members with d r d spanning generations. we examined members and of their spouses. l-dopa was withheld for hours from patients in treatment. five family members had generalized dystonia with diurnal auctuation ( i male, in an arabic family females). dystonia started between the age of and years with gait difficulty and involvement of the legs. mri, eeg, evoked potentials, and screening for wilson's disease were negative. an excellent response to l-dopa was noted in all patients with continued long-term clinical stability for as long as years. the patients were the products of consanguineous marriages, and their siblings were normal. the patients were descendants of the same great-great-grandparents. this pedigree suggests an autosomal-recessive type of inheritance. we believe this is the first report of d r d with an autosomal-recessive type of inheritance. a. achiron, m . gornish, h . goldberg, i . ziv, r. djaldetti, y. zoldan, h. smka, and e. mekzmed, petah tiqva, israel freezing gait is an incapacitating symptom that occurs often in advanced parkinson's disease and also in other neurological disorders, eg., multiinfarct state, multisystem atrophies, and normotensive hydrocephalus. we evaluated, videotaped, and rated patients ( men, age k , - yr) who developed pure progressive freezing gait during . . , . - years. severity was mild in with sudden motor blocks mainly when confronted with obstacles; moderate in with gait arrests upon any attempt to initiate walking and changing direction, requiring a walking stick or partial external assistance; and severe in with total inability to start walking, requiring a walker, massive assistance, or a wheelchair. in all, freezing was associated with postural instability. they could mimic normal gait when seated or lying prone and could overcome arrests by the "walking over lines" maneuver. neurological examination was otherwise normal with no signs of dementia, parkinsonism, or pseudobulbar palsy. ischemic risk factors including ischemic heart disease, hypertension, and diabetes occurred in and previous strokes in . brain c t and mri were normal or showed mild cortical atrophy in and putative lacunae in only patients. none responded to levodopa or dopamine agonists. progressive pure freezing gait should be recognized as a separate nonparkinsonian neurological entity. it may be due to degenerative or ischemic non-nigral brainstem lesions. we describe patients with causalgia and dystonia, triggered by peripheral injuries in patients and occurring spontaneously in patients. the injury was often trivial. the mean age at presentation was . years. the legs were affected in patients, and the arm was affected in the remaining patients. all had burning pain, allodynia, and hyperpathia, along with vasomotor, sudomotor, and trophic changes. all developed typical dystonic muscle spasms in the affected part. the spasms typically were sustained, producing a fixed dystonic posture, in contrast to the mobile spasms characteristic of idiopathic torsion dystonia. dystonia always followed the causalgia and was painful. there was spread of the causalgia and of the dystonia from its initial site both in the affected limb and to other extremities, the latter in a hemiplegic, transverse, and triplegic distribution. all forms of conventional treatment failed to relieve either the pain or the dystonia. we suggest that functional changes in the corticobasal ganglia-thalamic system are responsible for this painful dystonic syndrome. program and abstracts, american neurological association holiday for parkinson's disease: a controlled clinical trial r. kurlan, c . m . tanner, c. g. goetz, j . sutton, p. carvey, c. deeley, l. cui, c. itvine, and m . mcdemzott, rochester, ny, chicago, il, and san jose, c a the efficacy and mechanisms of levodopa (ld) drug holiday for parkinson's disease (pd) remain controversial. we performed a double-blind, randomized study with advanced pd patients ( men, women; aged - yr) with entry criteria of inadequate response to ld plus dose-limiting ld-induced side effects (dyskinesias, hallucinations, and confusion). subjects were assigned to: ( ) % placebo for ld (complete drug holiday) or ( ) % ld and % placebo for ld ( % drug reduction) for days. after subsequent open-label ld dose optimization, subjects were followed to end point (defined as the time when entry criteria were again satisfied or a maximum of year). median survival time to end point was not significantly different for the complete drug holiday ( days) and % drug reduction ( days) groups ( p = ) . aspiration pneumonia occurred in complete drug holiday patients and no significant morbidity occurred with drug reduction. after a -mg dose of ld, clinical and pharmacological responses were no different before and after drug holiday ( p = . ) or reduction ( p = ). subject to the limitations of our small sample size, we conclude that complete drug holiday is associated with greater morbidity and confers no major advantage over % drug reduction. we found no evidence of significant alterations of pharmacokinetic or pharmacodynamic properties of ld after drug holiday or reduction. ( (pc) of the substantia nigra on t -weighted images. the narrowing of the pc signal has been attributed either to atrophy of the pc or to increased deposition of iron in this region. we have studied details of iron distribution in the midbrain of formalin-fixed human brains by scanning pixe analysis. three p d brains, juvenile pd brain, and control (amyotrophic lateral sclerosis) brains were studied. in the controls, the iron content of the pars reticulata (pr) was almost equal to that of the red nucleus (rn), but that of the pc was less than % of the pr. in parkinsonian brains, the iron content in the pc was significantly higher than in the controls. the iron content ratios of pc/pr and pc/rn in parkinsonian brains were significantly higher than in the controls. these findings suggest that iron deposition increases in the pc of parkinsonian brains. the difference in the pattern of iron content corresponds to the intensity profile pattern noted on mri. mri findings in parkinsonian patients may reflect a change in the iron distribution pattern. (jankovic and brin, nejm, ) . such resistance within exposures is not likely due to toxin antibody formation. of cd patients evaluated per protocol receiving or more botox tx under multichannel emg monitoring, ( . %) showed no benefit after the first and second tx, despite mild neck weakness on static muscle testing and, in some instances, emg signs of denervation. the responders ( men, women) had younger age onset cd (mean yr vs yr), but similar duration (mean yr vs yr) compared to the male and female nonresponders (in contrast to jankovic and schwartz, arch neurol, ) . both groups had similar degrees of severity and tx dose (mean iu, range . - ). although disparate group size prohibits statistical analysis, some interesting comparisons include: nonresponders were more apt to have extranuchal dystonic sites ( % vs %), antecollis ( % vs %), dark eyes ( % vs %), women with elevated antinuclear antibody titer ( % vs %), history of intracranial operation ( % vs o%), significant for age focal mri abnormality ( of vs of ). history of cervical operation ( patients) did not limit responsiveness. rates of prior remission, perinatal stress, antecedent trauma, left-handedness, and family history of movement disorder were similar for both groups. antecollis presents problems for optimizing tx to affected muscles, but central mechanisms may play a role in why some patients with focal dystonia do not improve with botox tx from the outset. enrico fazzini, new york, n y with parkinson's disease does deprenyl have a symptomatic effect on patients with untreated and l-dopa-treated parkinson's disease (pd)? once deprenyl is started, how long is it before another medication is needed to control symptoms of continued disease progression? there has been controversy over whether deprenyl has effects on delaying disease progression (nejm ; : ) and/or in alleviating the symptoms of pd. one hundred seventy-five patients already taking l-dopa (group ) and patients who had never taken l-dopa (group ) were treated with deprenyl mg/day. unified pd rating scale (updrs) scores were measured before and after deprenyl. patients were followed until pd symptoms progressed to the point of requiring additional medication. one hundred eighteen of ( %) patients in group (reduced updrs mean activities of daily living [adl) to , motor [mtr] to ) and / ( %) patients in group (reduced updrs mean adl to , mtr to ) reported symptomatic benefit. an average of months' duration was found in both groups before further medication adjustments were needed. deprenyl provides symptomatic benefit for an average of months in the majority of patients with p d regardless of whether or not they are being treated with l-dopa. yasuo iwasaki, masao kinoshita, toshiya shojima, and ken ikeda, tokyo, japan, and cleveland, oh in parkinsonian patients we measured fasting plasma amino acids in parkinson's disease patients and controls matched for age and sex. all patients were receiving l-dopa and they were free of any medications other than l-dopa. normal controls were free of any medication. there were no differences in diets between patients and controls. fasting blood specimens were collected in heparinized tubes and immediately were centrifuged at , g for minutes. analysis of plasma amino acids was performed by automated ion-exchange chromatography with lithium-based buffer and an amino-acid analyzer. parkinsonian patients had significant elevations of aspartate, glutamate, and glycine. the other amino acids were not significantly different from those in controls. n o correlation between severity or activity and degree of abnormality in plasma level of amino acids in patients was established. we conclude that excitatory amino-acid metabolism is altered in patients with parkinson's disease. bonnie e. levin, rachel tomer, and william weiner, miami, fl disease there is evidence linking obsessive-compulsive symptoms (ocs) to basal ganglia dysfunction. we investigated the presence and severity of ocs in a sample of patients with an unequivocal diagnosis of idiopathic parkinson's disease (pd) using the leyton obsessional inventory. ocs was found in the majority of the patients, with ( %) scoring above the normative cutoff for the symptom score and ( %) scoring above the normative cutoff for the trait score. when severity of oc symptoms was correlated with a battery of neuropsychological measures, significant relationships were observed between ocs and a preponderance of tests associated with right-hemisphere functions. these findings were observed especially on those tests with a strong frontal lobe component (block design: r = -. ; embedded figures: r = -. ; set shifting: r = -. ; and perseverative responses: r = . ; p < . for all measures). in all cases, the more severe oc symptoms, the poorer the performance. a similar trend was observed between the leyton trait scores and the cognitive measures. these findings suggest that ocs is present in a subgroup of pd patients, which may reflect greater compromise of right-hemisphere basal ganglia-frontal lobe pathways. intraclass correlations (iccs) were calculated for the total motor score and for each individual sign. results indicated excellent agreement (icc > . ) for the total motor score, resting tremor, gait, arising from a chair, and speeded, repetitive movements; good agreement (icc > . ) for rigidity, action tremor, posture, postural stability, and bradykinesia; and poor agreement (icc < . ) for speech and facial mobility. a factor analysis was then performed on updrs motor scores for pd patients from a community-dwelling cohort. three factors were extracted by principal components analysis with subsequent varimax rotation, accounting for . % of the total variance: factor -balance and stability (posture, postural stability, gait, arising from a chair, and bradykinesia); factor -rigidity and motor speed (rigidity, speech, facial mobility, rapid alternating movements, leg agility, hand movements, and finger tapping); factor -tremor (resting and action). these results indicate that the updrs motor examination is reliable between raters and measures the cardinal signs of pd. an open pilot study was performed to evaluate the efficacy of botulinum a toxin (botox) injections for disabling hand tremors. a previous report on the use of botox for hand tremors suggested that it was helpful, but relied on subjective clinical rating scales. the extent of normal clinical fluctuations or a placebo response could not be determined. to investigate these issues more objectively, patients with parkinson's disease and with essential tremor with refractory hand tremors underwent electromyographically guided intramuscular injections of botox into wrist flexors and extensors. patients without great medication-related tremor fluctuations were selected. results before and after botox were determined by comparing ( ) patient perceptions of functional improvement, ( ) clinical assessments using the unified pd rating scale for tremor and the webster rating scales, and ( ) physiological measurements using accelerometric analysis of hand tremors of tremor frequency, amplitude, and waveform characteristics. all patients reported some improvement, ranging from mild to marked with a mean of . on a to ( = marked) global rating scale. however, only / patients showed a significant improvement in the clinical rating scales, confirmed by > % reduction in tremor amplitudes. these findings show that most patients reported improvement not confirmed by the clinical or physiological measures. efficacy of botox injections for tremors is implied, but controlled trials are needed before this procedure can be generally recommended. christopher g. goetz and glenn t . stebbins, chicago, i l we tested whether hallucinations, motor disability, and cognitive decline were risk factors for nursing home placement in advanced parkinson's disease (pd) and whether these effects were independent or synergistic. between and , we identified patients admitted to long-term nursing homes. using case control methodology, we matched each for age, pd duration, and sex with control pd patients remaining at home. parkinsonism was assessed by the motor and activities of daily living subscales of the unified p d rating scale (updrs); hallucinations and dementia were determined by scores on the thought disorder and intellectual impairment items of the updrs. tests of synergy were based on a mantel-hentel model. hallucinations were a significant risk factor with odds ratio = . , x = . , p < , . motor impairment alone and cognitive impairment alone were not significant risk factors for nursing home placement (x for motor severity = , , p > . , and x for cognitive impairment = . , p > . ). furthermore, combined odds ratios for hallucinationslmotor severity and hallucinations/cognitive impairment showed no synergy of effect (x < . for both,p > . ). of the variables studied, hallucinatory behavior is the most prominent and independent risk factor for nursing home placement in these patients; the data suggest that aggressive control of hallucinations may be warranted to prevent nursing home admission. temperature-sensitive paramyotonia congenita phenotype* louis j . ptacek, philip mcmanis, hzrbert kwiecinski, alfred george, robert barchi, launce gouw. and mark leppert, salt lake city, u t , rochester, mn, warsaw, poland, and philadelphia, pa the periodic paralyses are a group of autosomal-dominant muscle diseases sharing a common feature of episodic paralysis. in one form, paramyotonia congenita (pc), the paralysis is temperature-sensitive, usually occurring with muscle cooling. electrophysiological studies of muscle from patients with pc have revealed temperature-dependent alterations in sodium channel (nach) function. this observation led to the identification of distinct mutations in an s segment of a skeletal muscle nach in unrelated pc families. we describe the use of the single-strand conformation polymorphism (sscp) technique to define a third allele specific to pc patients in an additional family. this aberrant pattern, though distinct from the first , occurs in the same exon of this nach gene. sequencing is currently underway to define the molecular alteration causing this aberrant pattern. two additional families with the pc phenotype have been sampled and do not demonstrate these sscp variants. we are currently searching for new mutations in these families to define further the molecular heterogeneity of this temperature-sensitive pc phenotype. parag mehta and roger w. kukz, brooklyn, n y abnormal accumulation of calcium (ca) in myofibers is thought to play a role in pathogenic myonecrosis. attempts at reducing intracellular ca content with ca channel blockers in duchenne muscular dystrophy (dmd) have been clinically unsuccessful. dantrolene, however, which acts at the sarcoplasmic reticulum to inhibit ca release from intracellular stores, has produced dramatic reductions in serum creatine kinase (ck) in dystrophic mice and more recently in dmd. we investigated the effect of low-dose dantrolene in a group of patients with limb girdle dystrophy (lgd), dmd, and other myopathic disorders. all subjects received dantrolene in incrementing doses from to mg daily over a to -week period. mean baseline ck was compared to ck with dantrolene treatment. dramatic reductions in serum ck levels averaging % were seen at to -mg doses in lgd patients ( ). dmd patients ( ) and patients with other myopathies ( ) showed a similar but less dramatic reduction in ck. three of the weakest patients complained of increased fatigue while taking mg, which suggests that higher-dose dantrolene may confound longer-term trials assessing clinical muscle strength and function. dantrolene in dosages well below conventional antispastic doses has a dramatic effect on serum ck and possibly myofiber necrosis in lgd, other dystrophies, and other muscle disorders. p . antigen-specific therapy in myasthenia gravis: myasthenia gravis (mg) is mediated by anti-acetylcholine receptor (achr) antibodies, believed to be t-cell dependent, and antigen-specific therapy would be preferable to current nonspecific immunosuppression. exposing mouse t-cell clones to mhc class i molecules complexed with relevant antigen on planar membranes induced proliferative unresponsiveness (quill and schwartz, ) , and soluble mhc class i molecules complexed with myelin basic protein (mbp) peptide resulted in unresponsiveness of specific tlymphocyte clones in vitro (sharma et al, ) . we have used our well-defined dr -restricted t-cell clone (ong et a [, ) isolated from an mg patient and specific for p - of the achr alpha subunit. overnight incubation of these t cells with a soluble p - : dr complex substantially inhibited the subsequent response to challenge with soluble antigen and presenting cells. in contrast, antigen response after preincubation with dr complexed to an irrelevant peptide (mbp - ), soluble dr alone, or an experimental approach studied in vitro p - alone (at equimolar concentrations) did not differ appreciably from that in untreated cells. the p - :dr complex had no effect on other non-achrspecific cell lines/clones. these results suggest that the use of soluble mhc-peptide complexes may be an approach to selective immunotherapy in mg patients. p . high-dose intravenous immunoglobulin in the shawke a. soueidan and marinos c. dalakas, bethesda, md inclusion body myositis (ibm) is a severe disabling inflammatory myopathy with characteristic clinical and histological features. it is commonly suspected when a patient with presumed polymyositis does not respond to available immunotherapies. the need for an effective treatment in patients with ibm prompted the present pilot study using high-dose intravenous immunoglobulin (hd-ivig), an apparently effective immunomodulating agent in several autoimmune neuromuscular disorders. we treated patients with muscle biopsy-proven ibm with up to monthly infusions of gml kg ivig. after the first infusion, of the patients showed definite functional improvement consisting of independent ambulation, fewer falls, and increased ability to lift weights. the muscle strength of the proximal and less atrophic muscle groups improved by one grade mrc scale (from to ), whereas the distal and atrophic muscles remained unchanged. the improvement, sustained up to months, was greater in patients with the most severe endomysial inflammation. we conclude that hd-ivig may be the first promising agent that can improve the strength of certain muscle groups in patients with ibm. because ivig is prohibitively expensive, the present encouraging results warrant a large-scale controlled therapeutic study. hays, and n . lutov, new york, n y , and milan, italy anti-myelin-associated glycoprotein (mag) antibodies from patients with neuropathy cross-react with the glycolipid -sulfated glucuronyl paragloboside (sgpg). among patients tested by enzyme-linked immunosorbent assay and western blot, had highly elevated antibody titers ( , ) to both mag and sgpg, had highly elevated titers to mag alone, and had highly elevated titers to only sgpg. immunostaining of normal nerve myelin by the antibodies correlated better with anti-mag than anti-sgpg activity. twenty-one of the patients, including patients in all groups, had predominantly sensory or sensorimotor neuropathy, and biopsy specimens revealed deposits of igm and complement on affected myelin sheaths. three patients presented with motor syndromes, all with antibodies specific for sgpg; had a predominantly motor demyelinating neuropathy, had upper and lower motor neuron signs and peripheral neuropathy, and had amyotrophic lateral sclerosis confirmed post mortem. all had deposits of complement on peripheral nerve myelin sheaths. these studies suggest the following: ( ) that anti-mag or sgpg antibodies may differ in their fine specificities and biological activities, ( ) that anti-sgpg antibodies also may occur in motor neuron diseases, complicating the clinical presentation, and ( ) that both mag and sgpg should be used as antigens in testing for autoantibody activity in peripheral neuropathy. david b. williams, john steele, ulla-katrina craig, sandra bryant, peter o'brien, and leonard kurland, newcastle, new south wales, australia, mangilao, guam, and rochester, m n continuing surveillance of neurodegenerative diseases in the mariana islands reveals changes in frequency and clinical characteristics since the s that resemble those in other known western pacific foci (kii peninsula, japan, and irian jaya, new guinea). recent surveys of patients years and older were conducted on rota, tinian, and yigo, guam. possible cases of dementia, parkinsonism, and amyotrophic lateral sclerosis (als) were identified by local trained personnel using a questionnaire, world health organization neurology test, and cognitive screening. those who failed the screening were examined by a neurologist. in the small populations of rota and tinian, there were no definite cases of als compared to i to cases present in previous surveys. the high prevalence of parkinsonism-dementia complex (pdc) was unchanged and dementia was increased compared to earlier surveys. in yigo, als and pdc continue to be prevalent; however, the als patients are predominantly long-term survivors (> -year disease duration). in areas of previous high prevalence of als/pdc, dementia (as pdc) was associated with extrapyramidal signs, whereas in areas of previously low prevalence of als/pdc, dementia alone, possibly of alzheimer type, predominated. these observations help to confirm previous reports of changing clinical patterns, but suggest that the geographic distribution of the (presumed) environmental etiological agent for als/pdc remains stable after almost years. p. v . fragokz, . frongillo, m. michisanti, g. antonini. derangements of the cardiac conducting system are the most common features of heart involvement in myotonic dystrophy (md). in view of chis patients with various grades of md ( males and females, mean age yr) underwent -lead ecg and holter monitoring. in patients ( %), almost all with a severe grade of md, or more conduction defects were found: first-degree atrioventricular block (i-avb) in cases, second-degree avb in case, right bundle branch block in cases, left anterior hemiblock in cases, left bundle branch block in cases, and trifascicular block in case (pacemaker implanted). an -year-old boy had a chronic atrial fibrillation with slow ventricular rate; he died suddenly while awaiting electrophysiological study. thirty-seven patients were followed over a mean period of months (range - mo). a -year-old woman experienced a myocardial infarction and was excluded from subsequent considerations. conduction defects de novo appeared in patients: i-avb in and i-avb plus -avb (mobitz i and i type) in . nine patients, all with i-avb at initial evaluation, showed deterioration of their defects' conduction: a bifascicular block was observed in cases and a trifascicular block in cases (pacemaker implanted). conduction defects may run a malignant course in md, mainly in patients with more severe grades of the neuromuscular disease; thus, a close cardiological evaluation is mandatory for a proper therapeutic approach in single cases. hiroshi mitsumoto, surest kumar, kevy h. levin, robert w. shields, jr, michelle secic, asa j . wilbourn, and rajendra g . desai, cleveland, oh, and santa ana, ca twenty patients with amyotrophic lateral sclerosis (als) entered a pretreatment study with monthly quantitative isometric muscle strength tests ( muscles in each extremity) and quantitative tufts scales including vital capacity, bulbar diadochokinetic rate, timed water drinking, timed rising from a chair, and timed walking meters. after to months of pretreatment observation, the patients received mg/kg intravenous immunoglobulin (ivig) (gamimune-n, miles) every month for up to months. during the study period, patients died and patients withdrew from the study. the slope of each variable's changes over time before and after the ivig treatment were compared statistically. none of the quantitative scales showed significant change with ivig. however, the slope of the upper extremity muscle strength revealed improvement with ivig treatment ( p = . and . , right and left, respectively). when all extremities were combined, the slope was also significantly improved with ivig ( p = . ). lower extremity muscle strength alone showed similar trends but no statistical significance. electrophysiological and immunological data were also analyzed. our results warrant a double-blind, controlled study with ivig for the treatment of als. leber's hereditary optic neuropathy (lhon) is a mitochondrial disorder with predominantly optic nerve abnormality. it can be associated with dystonia, ataxia, encephalopathy, cardiac abnormalities, and other less well-characterized neurological syndromes. we describe members of a family with lhon with a slowly progressive motor polyneuropathy. a -year-old man and his -year-old sister have had mild motor impairment since early childhood. a gait disorder and distal muscle weakness became evident at puberty. the girl, but not the man, also has blindness, distal numbness, type i diabetes mellitus, and short stature. physical examination showed in both: bilateral foot drop, limb hyperreflexia but absent ankle reflexes, distal sensory loss, and a slight brownish scaly skin discoloration over the forearms. only the girl had clonus and optic nerve atrophy. the man had peripapillary telangiectasias. the jaw jerk was normal in both. motor nerve conductions in both showed absent tibia and peroneal responses, whereas other motor and sensory nerve conductions were normal. emg revealed denervation, more so distally. muscle biopsy findings showed recent denervation and previous denervation followed by reinnervation. n o raggedred fibers were observed with the modified trichrome and sdh stains. brain mri was normal in both. cerebrospinal fluid in the girl was normal. blood samples from both patients and maternally related family members revealed a mitochondrial dna point mutation at position (d. c. wallace). in this family, only male had lhon; females had lhon and others, including the patients' mother, were asymptomatic carriers. this association of chronic motor neuropathy and hyperreflexia with lhon appears to be a distinct syndrome. the pathogenic mechanism by which the mitochondrial dna defect causes the neuropathy (and other neurological deficits) requires analysis. duchennelbecker muscular dystrophy henry j . kaminski, mazen al-hakim, r. john leigh, bashar katirji, and robert l. ruff; cleveland, oh fast-twitch extremity muscle fibers are preferentially affected in duchenne/becker muscular dystrophy (dbmd). since saccades are thought to be mediated by fast-twitch fibers, saccadic velocities would be expected to be decreased among these patients. to investigate involvement of extraocular muscle (eom) by dbmd, we studied with infrared oculography patients who were wheelchair-bound and able to perform only minimal activities of daily living. saccades were slightly slowed but were within % confidence limits of normal. all patients showed square wave jerk movements (swj). in patients, the frequency of the swj exceeded that of normal subjects, which suggested central nervous system dysfunction. clinical neuroophrhalmological examination of other dbmd patients was normal. this investigation is the first study of ocular motility in dbmd and demonstrates that eom function is relatively preserved even in far advanced patients. eom is composed of a heterogenous mix of fiber types that differ in anatomical and physiological characteristics from extremity muscle. study of eom in dbmd may prove to be useful in understanding why some muscles are resistant to dbmd and in characterizing properties that limit muscle degeneration. (supported by nih grants ey , ey , the department of veterans affairs, and the evenor armington fund.) since patients with myotonic dystrophy (mtd) exhibit a marked resistance to insulin effect on glucose uptake and an impaired handling of the insulin-sensitive amino acids, it is possible that muscle wasting in mtd may reflect a derangement of insulin action on muscle protein metabolism. increased muscle protein breakdown in mtd would be expected if the normal inhibitory effect of insulin on protein catabolism is impaired. the forearm perfusion technique combined with measurements of -methylhistidine ( -mh) arteriovenous (a-v) differences by high-performance liquid chromatography provides a unique method to investigate skeletal muscle myofibrillar protein degradation in vivo. we studied -mh (a-v) and efflux from the forearm muscles in men moderately affected with mtd and normal men. efflux values (q) were calculated as the product of -mh (a-v) times forearm plasma flow measured by the indicator dilution technique. forearm -mh release (estimated as {a-v} or q) of mtd patients did not differ significantly from normal controls. we conclude that myofibrillar degradation is not increased in mtd even when measured in a muscle compartment selectively affected by wasting. the possibility of an impaired anabolic action of insulin in mtd has yet to be determined. to study the relationship between the ragged red fibers (rrf) and age, we have reviewed muscle biopsy specimens prospectively. patients with well-established mitochondrial myopathy syndrome and with myopathies known to produce secondary rrf were excluded. the number of ragged red fibers (rrf) was counted under x (lpf) magnification. rrf were identified by the modified trichrome and sdh stain. for the final analysis, the sdh staining was used. the frequency of rrf was analyzed in relation to patients' ages. the frequency of cases with more than rrf increased with aging: % in the first decade, % in the fourth decade, and % in the eighth decade. the frequency of cases with more than rrf also increased with aging: % in the first three decades, % in the fourth decade, and % in the eighth decade. of patients with well-established mitochondrial myopathy syndrome, had more than rrf under lpf. the number of rrf in muscle increases with aging, indicating that mitochondrial activity in muscle is affected by aging. this finding may complicate the diagnostic criteria of mitochondrial myopathy in older individuals. ten rrf under lpf seems to be a reasonable cutoff point for the diagnosis of mitochondrial myopathy. schwartz-jampel, a rare autosomal-recessive syndrome characterized by short stature, myotonia, skeletal abnormalities, and peculiar facies, was reported by aberfeld in . the same sibship was earlier reported by schwartz and jampel in with emphasis on blepharophimosis. as of this writing about cases have been reported in the literature. most of the features of this syndrome are believed to be secondary to primary muscle disease. several peripheral electrophysiological studies showing features of myotonia have been reported. we describe patients with schwartz-jampel syndrome showing evidence of central conduction disturbance documented by somatosensory-evoked potentials (seps). median nerve seps showed normal latencies to erb's point and n- in all. interpeak latencies between n and n were prolonged in with complete block in . emg showed typical myotonic discharges in all. motor nerve conduction velocities, visual and brainstem auditory-evoked potentials, ct, and mri were normal in all. seps in the parents were normal. we believe this is the first report documenting evidence of central nervous system (cns) involvement in schwartz-jampel syndrome. schwartz-jampel syndrome and myotonic dystrophy may have similar cns ''lesion'' as sep abnormalities also have been shown in myotonic dystrophy. epidemiological studies have associated consumption of certain batches of l-tryptophan (lt) with development of the eosinophilia-myalgia syndrome (ems). , '-ethyledenebisltryptophan) (ebt or peak e), a derivative of lt, is a trace contaminant associated with implicated batches of lt. three female lewis rats received ebt, mg per gm daily, by intraperitoneal injection. four control rats received unimplicated lt. n o peripheral eosinophilia, rash, or weakness were observed in either group. one rat from each group died during the experiment (control-bowel infarct; ebt-death under anesthetic). after days, forelimb and hindlimb muscles of the remaining animals were frozen and fixed for program and abstracts, american neurological association ultrastructural and histological studies. two ebt rats had a myopathy involving soleus with a perimysial infiltrate containing lymphocytes, macrophages and sparse eosinophils, and necrotic fibers; the other showed few necrotic fibers in gastrocnemius. occasional eosinophils were seen in fascia in both animals given ebt but not in controls. fiber-type specific quantitative analysis of the microvasculature showed no decrease in the capillary index. ultrastructural examination revealed an increase in the size of microvessels in ebt animals. no denervation or reinnervation were demonstrated. the perimysial inflammation replicates an important feature of human ems and supports the epidemiological evidence that ebt is the causative agent of the disease. britta ostermeyer-shoaib, bernard m. patten, and tetsuo ashizawa, houston, t x five women (patients - ) developed motor neuron disease (mnd) years (range - yr) after receiving silicone gel-filled breast implants. at explant in patients, had both and had the left implant ruptured with silicone spilled into tissue. one woman (patient ) developed amyotrophic lateral sclerosis (als) years after numerous injections of free silicone into her face. biceps muscle biopsy specimens in all showed neurogenic atrophy. patient developed als with bulbar involvement and died years later of respiratory failure. she had anti-gm antibodies and autopsy findings confirmed the diagnosis of typical als. patient developed als, but also fatigue, myalgia, arthralgia, and skin rash. she had anti-gm antibodies, antisilicone antibodies, positive antinuclear antibodies (ana), and decreased serum igg, iga, and c , but increased igm and creatine phosphokinase (cpk) and chronic inflammation was revealed in muscle biopsy specimens. patient developed als, but also had hair loss, skin rash, fatigue, headache, sjogren's syndrome, and positive ana. patient developed als, but also had myalgia and arthralgia. patient developed lower mnd, but also fevers, arthralgia, and joint stiffness. she had anti-gm antibodies, positive ana, antimyelin antibodies, and decreased serum igg and iga with chronic inflammation shown in nerve biopsy findings. patient developed a steroidresponsive and steroid-dependent als with bulbar involvement. she had a monoclonal gammopathy in the cerebrospinal fluid and increased cpk. we suggest that silicone acts as an adjuvant that damages motor neurons via an indirect autoimmune mechanism. implants and silicone injections into the face p . silicone adjuvant breast disease: more forty-five women developed mixed sensory-motor neuropathy ( ), motor neuron disease ( ), multiple sclerosis ( ), multiple sclerosis-like syndrome ( ), or myasthenia gravis ( ) years (range mo- yr) after receiving silicone-gel breast implants ( ), saline-filled silicone-covered breast implants ( ), or direct injections of silicone into the breast ( ). most patients had, in addition, severe fatigability, myalgia, arthralgia, morning stiffness, skin rash, lymphadenopathy, sjogren's syndrome, and short-term memory problems. laboratory results revealed in most of the women decreased or increased serum immunoglobulins, autoantibodies, a serum monoclonal gammopathy, or oligoclonal bands in cerebrospinal fluid. at explantation in , had both and had implant neurological cases ruptured. biopsy of the fibrous implant capsule in most patients showed foreign-body giant cells containing refractile material consistent with silicone whether or not the elastomer shell was ruptured, indicating silicone bleed. the major finding on surd nerve biopsy was loss of myelinated fibers, on biceps muscle biopsy was neurogenic atrophy, and on pectoralis muscle biopsy was myositis with vasculitis and free silicone in some. we suggest that silicone may provoke damage to nerve and muscle, probably indirectly promoting autoimmunity. james f. howard, jr, m . kathleen donovan. and m. susan tucker, chapel hill, nc urinary symptoms of urgency and incontinence have been reported only rarely in patients with myasthenia gravis (mg) and then most often in association with myasthenic crisis. we report the case of a -year-old woman who in december had the onset of chest pain and was found to have a lymphocytic thymoma. in june she developed urinary incontinence, was found to have an open bladder neck. and underwent a suspension procedure for stress incontinence in january . eight months later she developed exertional fatigue and a diagnosis of m g was made. in july there was a recurrence of urinary incontinence. these symptoms clustered toward the end of the day and at trough mestinon dose. neuro-urophysiological studies demonstrated her previous open bladder neck, the inability to sustain a pelvic floor contraction, and increased bladder wall contraction. singlefiber electromyography (sfemg) recordings from the anal sphincter demonstrated a mean consecutive difference (mcd) of ysec, and % of fiber pairs had impulse blocking while recordings in the extensor digitorium communis muscle were normal. following a course of plasma exchange, there was significant clinical improvement with a reduction in the frequency of urinary incontinence, and improvement in anal sphincter sfemg studies (mcd, ysec with no blocking). this case demonstrates that in those myasthenic patients with predisposing bladder outlet dysfunction, urinary incontinence may be a manifestation of worsening mg. diana m. escolar, mohamed eldaly, and jaime rich, boston, m a debate still exists as to the role of antibody versus celmediated factors in the pathogenesis of guillain-barre syndrome (gbs). we describe a patient with increased proportion of circulating t cells and a t-cell lymphoma who developed gbs and responded to intravenous immunoglobulin (ivig). a -year-old man with t-cell lymphoma drveloped gbs by clinical, nerve conduction, and cerebrospinal fluid criteria. he had an elevated proportion of t cells and markedly reduced b cells with a normal cd /cd ratio. he responded rapidly to ivig, with return of nearly normal motor function in week. three weeks later, he relapsed and his vital capacity dropped. ivig was again administered and within hours he nearly recovered. a third relapse, days later, again responded to ivig. he has remained asymptomatic with ivig maintenance. the role of t-cell lymphocytes in initiating experimental autoimmune neuritis has been shown by adoptive transfer experiments. this patient with t-cell neoplasia may represent an analogous model in hu-guillain-barre syndrome mans supporting the role of t-cell (cell-mediated) autoimmunity in the pathogenesis of gbs. ivig therapy may act primarily by inhibiting the t-cell-mediated attack on myelin. p . sympathetic skin response: age effect it is frequently stated that the sympathetic skin response (ssr) can be elicited in all normal subjects, but the age of the investigated population usually is not considered to be a significant factor. we have examined the ssr in the upper and lower limbs of normal subjects, aged to years ( of them males). the ssr was elicitable in the lower limbs in all subjects under the age of years and in the upper limbs in all subjects younger than years. in contrast, it could be elicited in the lower limbs in only % and in the upper limbs in % of octogenarians. the amplitude of the response, though highly variable, showed a remarkable decline with age, both in the upper ( p < . , r = . ) and in the lower ( p < . , r = . ) limbs. these results indicate that age affects both the elicitability and the amplitude of the ssr. this has to be taken into consideration when evaluating the autonomic function in the elderly. we reviewed records of patients appearing to have motor neuron disease (mnd) to whom we recommended immunosuppression over years ( of m n d patients). atypical findings engendered hope rhat they might have treatable neuropathy. electrophysiological studies were mainly consistent with mnd, but also showed conduction block or other evidence of relatively mild peripheral nerve disease in . sensory symptoms were present in ; or more reduced or absent deep tendon reflexes in ; elevated cerebrospinal fluid protein in ; and nonspecific abnormalities on sural nerve biopsies in of . anti-gm levels were measured in (including who improved), but none was significantly elevated. immunosuppression included cyclophosphamide ( patients); prednisone ( ); plasma exchange ( ); intravenous gammaglobulin ( ); cyclosporine ( ); and total lymphoid irradiation ( ). seven treated patients died, worsened, remained stable for years, and improved. two patients declined treatment. one died and the other did not worsen in years. we conclude that immunosuppression by our methods is, at best, rarely effective in atypical mnd. we studied serum antiglycolipid antibodies by enzymelinked immunosorbent assay in patients with typical miller fisher syndrome (mfs), patients with atypical mfs who were lacking in some of the cardinal signs, patients with guillain-barrc syndrome (gbs) with ophthalmoplegia, patients with gbs without ophthalmoplegia, patients with multiple sclerosis (ms), and patients with other immunological disorders (oid) including systemic lupus erythematosus, polymyositis, and mixed connective tissue disorder. all patients with typical mfs had increased activity of igg antibody against ganglioside g q l b in the early phase, and it reduced with time. such anti-gqlb igg activity also was detected in of the patients with atypical mfs and in of the patients with gbs with ophthalmoplegia. in atypical mfs, the only patient without increased anti-gq b igg activity demonstrated normal eye movement with ptosis, whereas eye movement was impaired in the other patients. no patients with gbs without ophthalmoplegia, ms, or oid had increased anti-gqlb igg activity. these findings suggest the close association between increased anti-gql b igg activity and impaired eye movement in mfs and gbs. serum anti-gqlb igg activity possibly plays a role in impaired eye movement in mfs. our goal is to develop an assay that can be used to monitor a relevant immune effect of interferon p (ifnp) in multiple sclerosis (ms) patients during the course of ifnp immuno-' therapy, since recombinant ifnp is being tested in multicenter clinical trials. this report extends our prior studies of the inhibitory effect of ifnp on t-cell activation. peripheral blood mononuclear cells (pbls) from healthy donors and clinically stable ms patients were studied. pbl cultures were stimulated with cona, mab to cd , or with the phorbol ester pma in the presence of the calcium ionophore ionomycin. parallel cultures were studied in the presence of ifnp, uiml. t-cell activation was monitored by determining the percent cells positive for il- receptor (il- r) using facs analysis, or with a sensitive enzyme-linked immunosorbent assay for ifny. ifnp markedly inhibited il- r expression induced by cona, by mab to cd , or by pma and ionomycin, which activate t cells via different pathways. the results suggest that ifnp inhibits t-cell activation by actions independent of membrane receptors. we observed significant inhibition of cona-induced t-cell il- r expression in both ms patients ( . % inhibition, p < . ) and controls ( . % inhibition, p < . ). there was no significant difference in percent inhibition between ms and controls, but there was more variance among the ms patients. variability of biological effects of ifnp on t cells may relate to differential therapeutic responses to exogenously administered ifnp in ms patients. preliminary experiments suggested that ifnp inhibited ifn gamma secretion by pbl stimulated with cona. ifnp inhibits a number of events associated with t-cell activation, in both normal and ms t cells. response to ifnp appears more variable in the ms cases. immunological monitoring of t-cell activation in patients receiving ifnp may assist in understanding the observed therapeutic responses and planning clinical protocols. myelin destruction is associated with many central nervous system disorders, such as multiple sclerosis, head trauma, and ischemic injury. inflammatory cells, monocytes/macrophages, and polymorphonuclear leukocytes (pmn) may me-program and abstracts, american neurological association diate myelin injury, and lipid peroxidation may be an important mechanism. inhibiting myelin oxidation could have substantial benefit, so we evaluated the ability of a -minosteroid, u a, to inhibit myelin oxidation by monocytes and pmn. fresh rat brain myelin was harvested by multiple sucrose gradient, ultracentrifugation steps, and the final product was confirmed to be pure myelin by sds-page electrophoresis. human monocytes or pmn were obtained from healthy, unmedicated volunteers by gradient separation techniques. monocytes ( . x lo cells/ml) and pmn ( . x lo cells/ml), myelin ( pg protein/ml), and lipopolysaccharide ( pg/ml) were incubated for hours with or without wm u a in -ml wells. myelin oxidation was evaluated by a thiobarbituric acid reactive substance assay for production of malondialdehyde (nmol/ ml). myelin oxidation by monocytes was . +- . (mean standard error of mean) without u a and was reduced to . ? . by pm u a ( p < . ). pmn-mediated myelin oxidation was . _t . without drug and . ? . with drug ( p < . ). these results demonstrate that u a markedly inhibits monocyte-and pmn-mediated myelin oxidation and suggest that the aminosteroids may help disorders associated with inflammatory cell-induced myelin injury. microglia cells participate in the pathological reactions of the cns to multiple insults including trauma, inflammation, and neuronal degeneration. functional roles for these cells could include mediating tissue in jury, promoting repair, or modulating immune responses. with regard to the latter, we have observed that the majority of adult human-derived microglia express major histocompatibility complex (mhc) class molecules under basal culture conditions, in contrast to astrocytes derived from the same surgical biopsy specimens. all morphological subtypes of the microglia (ameboid, bipolar, and ramified) expressed mhc class i molecules, indicating a discordance between morphology and mhc antigen expression as markers of microglia activation. the microglia actively ingest myelin constituents, as assessed using fluorescein-labeled myelin basic protein and laser confocal microscopy. autologous t cells (e') freshly isolated from the systemic blood and cocultured with candida antigen underwent active proliferation in the presence of to % microglia, indicating the functional capacity of the microglia to serve as antigen-presenting cells. y-interferon augmented both mhc class expression and functional antigen-presenting capacity. these results indicate the potential of the adult human microglia to promote immune reactivity within the cns. protein (mbp) neutralize anti-mbp purified from multiple sclerosis cerebrospinal fluid active phases of multiple sclerosis (ms) are associated with increased titers of intrathecally produced antimyelin basic protein (anti-mbp). anti-mbp can be purified by antigenspecific affinity chromatography from csf igg of patients with acute relapses of ms. eighteen synthetic peptides of human myelin basic protein (h-mbp) containing between and amino-acid residues and covering the entire length of the molecule were synthesized by the fmoc method. purified anti-mbp was reacted with increasing amounts of h-mbp as well as each of the peptides in an initial liquid phase assay, and subsequently titers of f anti-mbp in all resulting mixtures were measured by a solid-phase radioimmunoassay . purified anti-mbp was neutralized by h-mbp and of the synthetic peptides containing overall residues corresponding to to of h-mbp. the remaining synthetic peptides covering both the amino and carboxyl terminals of h-mbp did not significantly react with purified anti-mbp from these patients. in conclusion, anti-mbp purified from csf of ms patients has affinity for epitopes located between residues and of h-mbp. in a double-blind study involving patients, we recently demonstrated that -aminopyridine ( -ap) is superior to placebo in the treatment of multiple sclerosis (ms) (ann neurol, in press). the related agent , -diaminopyridine (dap) also appears to be effective. to enable a preliminary comparison, patients, who in our previous study had not benefitted from -ap, were now treated ( wk) with dap (up to . mg/kg/day) for weeks in an open-label fashion. instruments for assessment and registration of side effects were the same as in the previous trial. the optimal dose of dap was . mg/day compared to . mg/day for -ap. significant changes in the edss ( . point or more) were not found, whereas significant improvements in neurophysiological parameters were found (no difference between -ap and dap, allp > . ). subjective side effects during -ap ( patients) mainly suggested cns-function disturbance (dizziness and gait disturbance) and during dap ( patients) mainly suggested peripheral nervous system-function disturbance (paresthesias). systemic tolerability clearly was diminished for dap compared to -ap, with patients withdrawing because of severe gastric complaints and developing liver function abnormalities. these data suggest that -ap is more valuable than dap in the treatment of ms. cy clophosphamide/methylprednisolone therapy in multiple sclerosis multiple sclerosis (ms) is a presumed autoimmune disease in which various forms of immunotherapy have been attempted. mri studies show the disease to be more chronically active than is clinically evident, thus a single treatment is unlikely to provide lasting benefit. recently, the northeast cooperative treatment group found that pulse cyclophosphamide ( mg/m every other month for years) slows progressive ms. we initiated a pilot study to determine the effect of a more intensive and prolonged pulse therapy regimen in both progressive and earlier stages of the disease. pulse therapy was given after induction with either iv cyclophosphamide/corticotropin ( mg/m x over days) or iv methylprednisolone ( gm x over days). patients received a single iv dose of cyclophosphamide ( - , mg/m ) adjusted to produce leukopenia plus gram of iv methylprednisolone monthly for a year, every weeks for the next year, and every months in the third year. another group received pulse methylprednisolone without cyclophosphamide. as of this writing, patients have been treated, of which have completed years. interim analysis shows that patients treated with pulse methylprednisolone were more likely to become treatment failures than those treated with pulse cyclophosphamide/methylprednisolone ( % vs %) independent of induction therapy. withdrawal due to toxicity, however, was higher in the pulse cyclophospharnide group. current regimens involve methylprednisolone induction alone followed by pulse cyclophosphamide/methylprednisolone, analogous to lupus nephritis pulse therapy. this regimen can be given solely on an outpatient basis, does not cause alopecia, and is more amenable for use in earlier stages of the disease. to determine the incidence of pathologically confirmed malignancy in multiple sclerosis (ms) patients in funded clinical trials of cyclophosphamide (ctx) and of azathioprine (aza), data were collected longitudinally using telephone interviews, written questionnaires, physical examinations, and medical records for ctx and aza patients from a community in-hospital and out-patient ms clinic in fargo, nd. in the ctx study (goodkin et al, arch neurol ; : - ) , clinically definite (cd), chronic progressive ms patients were enrolled. twenty-four were controls and received a mean induction dose of . grams. fourteen of the induced patients then received boosters every other month for months resulting in a mean total dose of . grams. no malignancies were detected. in the aza study (goodkin et al, neurology ; : - ) , c d relapsing ms patients participated. twenty-five were controls and received mgtkg of aza daily by mouth adjusted to maintain a white blood count of greater than , o/cmm for years (mean dose . mg/kg). two of aza patients developed resectable skin cancers: basal cell (bcc) at months and i squarnous cell (scc) at months. the incidence of developing a bcc or scc was not significantly increased after initiating therapies as compared to the untreated ms controls (aza: fisher exact testp value = . ). no other malignancy has been detected during to months of clinical follow-up. allergic encephalomyelitis paula dore-dufly, ruth washington, and robert h. swanborg, detroit, m i postcapillary endothelium at sites of inflammation undergoes many changes referred to as activation. activated endothelial cells (ec) exhibit increased surface expression of immunorelevant proteins (icam- ; ncam, elam, and mhc class i and class i antigens [ags)). the sequence of events that characterizes ec activation may be important in susceptibility, induction, and perpetuation of experimental allergic encephalomyelitis (eae). in this study we examine expression of ec activation antigens in central nervous system (cns) microvessels in response to interferon gamma (ifn-y). cns microvessels from sjl and bio.s mice were incubated for hours in ifn-y ( u/ml), fixed, permeabilized, and then stained with an antibody that recognizes class i, class i mhc antigens, icam- , and factor viii. relative fluorescence intensity was determined using a laser cytometer. results indicate that microvessels from all strains tested expressed no detectable icam- and class i ags. little class i antigen and transferrin receptors were expressed. upon stimulation with ifn-y, sjl microvessels exhibited increased surface expression of all ec activation ags. b o.s microvessels exhibited icam- and class i mhc but mhc class i ags were not upregulated. results indicate that there are strain differences in the ec response to ifn-y. resistance of b o.s mouse ec to activation by ifn may be a factor in decreased susceptibility or induction of eae, or both. protein-t-cell line-mediated experimental to investigate a possible pathogenic role of interferongamma (ifn-y) in experimental allergic encephalomyelitis (eae), an immunocytochemical study was undertaken to localize this cytokine in the spinal cord of lewis rats in which eae was produced by adoptive transfer of myelin basic protein-specific t cells. one pm-thick cryosections of spinal cord were labeled with monoclonal antibodies (mab) db- and db- recognizing different epitopes of rat ifn-y. in the spinal cord of naive rats, mab db-i, but not db- , stained processes of astrocytes, suggesting that astrocytes contain a protein with an epitope cross-reacting with ifn-y. in rats with at-eae, numerous ifn-y-positive cells stained with both mab db- -and db- -positive cells were present from days to after cell transfer and had disappeared on day . at day they entered the spinal cords predominantly through subpial vessels. ifn-y-positive cells could be identified as w / + leukocytes as well as ed -positive macrophages. as in naive rats, astrocytes in at-eae were labeled only with mab db- , but not db- . we never observed labeling of motor neurons with these mab. the transient presence of ifn-y in the rat spinal cord at the onset of at-eae suggests a pathogenic role of this cytokine in acute immune-mediated demyelination of the cns probably as a local stimulus for expression of mhc class i antigens and adhesion molecules, as well as for the release of tnf-a and toxic oxygen radicals from macrophages and microglia. immune responses to stress or heat shock proteins are implicated in the pathogenesis of several autoimmune diseases, including multiple sclerosis (ms). we examined the hypothesis that antigens in myelin cross-reacted with stress protein antigens. two techniques were used: immunocytochemistry and western blotting. frozen histological sections were prepared from normal human central and peripheral nervous system tissues. sections were incubated with murine monoclonal antibodies to different mycobacterial stress proteins. antibody binding was determined using avidin-biotin complexed antimurine antibody linked to alkaline phosphatase. program and abstracts, american neurological association a monoclonal antibody to the stress protein sp from m . leprae strongly stained both central and peripheral nervous system myelin. no myelin staining was noted with antibodies to sp or sp . proteins from purified central and peripheral nervous system myelin were separated by sds-page. western blots were prepared using a monoclonal antibody to sp and a polyvalent rabbit antibody to myelin basic protein (mbp) as primary antibodies. antibody binding was determined using antimurine or antirabbit igg antibody coupled to alkaline phosphatase. strong staining of central but not peripheral mbp by the anti-sp antibody was observed. the rabbit anti-mbp antibody stained both central and peripheral nervous system mbp. the presence of antigenic epitopes shared by a stress protein and the potential autoantigen, mbp, supports the hypothesis that immune responses to stress proteins may be involved in the pathogenesis of presumed autoimmune diseases such as ms. ( ). of patients with borderline or positive csf lyme titer, received parenteral ceftriaxone. all had later relapses consistent with ms. one patient received a month of oral doxycycline. the fifth patient had a negative western blot and was not treated. we conclude that an incidental borderline or positive lyme serology in an ms patient is unlikely to indicate neurological lyme disease. borderline serologies should be documented to rise on later testing; positive serologies should be confirmed by retest in a different laboratory or by western blot. csf abnormalities suggestive of neurological lyme disease (pleocytosis, protein elevation, intrathecal lyme antibodies) are distinct from those suggestive of ms (ogb, elevated igg index, mbp). in such patients antibiotic treatment may be appropriate, but will not alter disease course. when designing and analyzing therapeutic trials for multiple sclerosis (ms), investigators commonly compare the proportion of patients in the experimental and control groups who worsen one or more steps on the disability status scale (dss) or expanded dss during the study (typically years' duration). however, the intervals between the scores in the dss may not be equal. it may be easier to change by one or more steps in the lower end of the scale (e.g., dss = - ) than in the midportion of the scale (e.g., dss = - ). to evaluate this possibility, we compared the proportion of patients who worsened by one or more steps in the years after entering our program with dss = or with dss = . fifty-one percent ( ) natural history data may be useful for designing therapeutic trials for multiple sclerosis (ms). since , we have collected such data in a standard format on patients in the ucla multiple sclerosis research and treatment program. t o describe the course in our group, we have performed survival analysis (kaplan-meier) of patients with or more assessments who entered the clinic with disability status scale (dss) scores of to (n = ). an increase of one or more steps in the dss score persisting for more than months defines worsening. median times to worsening for a dds at entry of to were approximately years (range . - . ); but were . years for dss and . years for dss . for those starting at dss (n = ), only % worsened by year, % by years, and % by years. the percent worsening when starting at dss (n = ) were %, %, and %, respectively. these variable rates of worsening (i.e., time spent at each starting level) influence therapeutic trial design. including patients with dss or will increase the sample size and study duration. for testing nontoxic agents, we recommend enrolling patients with dss to . for more toxic treatments, we suggest dss to . (partially supported by usphs grant ns , the conrad n. hilton foundation, and various donors.) pi . cholinergic antagonists and p-adrenergic agonists inhibit experimental allergic encephalomyelitis in an additive manner mark a. jensen, avertano noronha, and bawy g. w. amason, chicago, il lymphoid organs receive a sympathetic (sns) and possibly a parasympathetic innervation. lymphocytes express padrenergic and cholinergic receptors and thus are sensitive to regulation by these neurotransmitters. the severity of experimental allergic encephalomyelitis (eae) is increased in sns-ablated animals. local parasympathectomy decreases plaque-forming responses in submandibular nodes. p,-adrenergic receptors are upregulated on cds t cells in progressive multiple sclerosis, as are m,-muscarinic acetylcholine receptors on cd t cells. we examined the effect of isoproterenol, a p-adrenergic agonist, and scopolamine, a cholinergic antagonist, on the course of eae in lewis rats. eae was induced by injection of . ml of incomplete freund's ad juvant containing guinea pig spinal cord ( % wlv) and m. tubercdosis ( mgiml) in one hind footpad. scopolamine ( . mglkg, twice daily) and/or isoproterenol(o. mglkg, twice daily) or saline were injected subcutaneously starting on the day of immunization. scopolamine or isoproterenol alone reduced severity ( p < . , t test) and duration ( p < . , t test) of disease compared to controls. the combination of scopolamine and isoproterenol further reduced disease severity compared to either agent alone ( p < . , x test), suggesting an additive protective effect of cholinergic antagonists and p-adrenergic agonists in eae. antigen-presenting cells a . conrad, v. sanders, p. schmid, and w. w . tourtellotte, los angeles, c a tissue is cryopreserved by the method of tourtellotte; this procedure minimizes or eliminates ice artifacts and preserves surface protein markers. the dissected plaques are lightly fixed in % paraformaldehyde and then suspended in % sucrose. blocks are mounted in oct, cryosectioned at p,m, and picked up on gelatinized slides. the activity of plaques is determined by the presence or absence of myelin debris (antimyelin basic protein stain or lux fast blue) or presence or absence of neutral lipids indicating myelin digestion as seen by oil red (oro) staining and the presence or absence of a class i major histocompatibility complex antigen (evidence for an antigen-presenting cell) on macrophages or microglia as seen by immunocytochemically staining for hla-dr (hb atcc). the following is our classification of the activity of multiple sclerosis (ms) plaques. type i, the most active, is defined as an area of hypercellularity, positive for hla-dr with no o r staining or staining for myelin debris. type , or active, is defined as an area of hla-dr-positive cells that stain mildly with o r at the plaque edge but positive for myelin debris; evidence for demyelinating activity < hours (prineas; raine). there is an inner area of plump cells that are positive for hla-dr and oro. type , or modestly active, is defined as a "shelf" of plump hla-dr-positive cells at the edge loaded with program and abstracts, american neurological association oro-stained neutral lipid but a paucity of or no myelin debris. a region of hypocellularity is observed at the center of plaque. type iv, least active or inactive, is defined as scattered hla-dr-positive cells at plaque edge with little or no o r staining and no evidence of myelin debris. the frequency of plaque types was determined from a random sample of ms tissue blocks from patients who died of ms. ten percent of the plaques were type i; %: were type ; % were type . the majority of plaques ( %) were inactive (type iv). accordingly, it is necessary to classify the demyelinating activity of ms plaques for protocols designed to investigate etiopathogenesis. do these results suggest that whatever causes ms can be eradicated in half of the demyelinating areas by the time of death? p . localization of g d l b ganglioside antigen in the human peripheral nervous system susumu kusunoki, atsuro chiba, tadashi tai, and lchiro kanazawa, tokyo, japan serum antibodies against ganglioside gm and/or g d l b frequently are detected in autoimmune neuropathies such as rnultifocal motor neuropathy, igm paraproteinemic neuropathy, and guillain-barre syndrome. some of them bind to gm or g d l b monospecifically but the others cross-react with both of the antigens. to investigate respective localizations of gm and g d l b antigens in the human peripheral nervous system (pns), immunohistochemical study of dorsal root ganglia (drg), dorsal roots, ventral roots, and sympathetic ganglia (sg), which were obtained from human autopsy specimens, was performed by using mouse monoclonal antibodies, each monospecific to gm and gdlb. ggr , monospecific to gd b, immunostained nerve cell somas and axons of drg, sg, and dorsal and ventral roots. ggrl also recognized some myelin, including paranodal areas. however, gmb , monospecific to gm , did not bind to either neuron or myelin. thus, serum anti-gdlb antibody can bind to neurons and some myelin in the human pns. further study is necessary to identify the localization of gm antigen, because previous biochemical studies have shown that gm is also present in the human pns. the purpose of this study was to compare t and t lymphocytes in migraine patients versus controls, and a review of the literature was done. fifty-six migraine patients, aged to , were tested, as were controls. the t :t ratio in migraine patients was : , compared to : for controls. suppressors (t ) were reduced from in controls to in migraine patients. helpers (t ) decreased from , in controls to in migraine patients, and total ?' lymphocytes decreased from , to , . previous studies have revealed similar differences in t lymphocytes, with higher t : t ratios being found in both migraine and tension-type headache patients. in food-induced migraine, an increase in circulating immune complexes was noted, with increased t levels. differences in serotonin binding to mononuclear cells have been noted in migraine patients. a decreased sensitivity of the lymphocyte beta-adrenergic receptor in migraine patients was suggested by one study. after lymphocyte incubation with il- , the natural cytotoxic response is augmented in cluster patients. the percentage of lymphocytes expressing receptors for il- was decreased in cluster patients in a fur-review of the literature ther study. this il- receptor defect was independent of whether the clusters were present. there is a loss of highaffinity binding sites for serotonin on lymphocytes in both episodic tension and chronic tension headaches. we used positron emission tomography (pet) to measure local cerebral blood flow in volunteer subjects while they performed tasks of memory-guided saccades and a visual fixation control. tasks were performed continuously for seconds during emission scans, after bolus injection of h lso. eye movements were verified with electrooculography. areas of significant increase in regional blood flow between tasks were matched to three-dimensional reconstructions of brain magnetic resonance images of each subject. compared to the visual fixation control, saccade tasks evoked bilateral activation in the posterior superior parietal lobule with extension into the inferior parietal lobule. activation was also seen bilaterally in an area of frontal cortex immediately rostra to the precentral gyrus extending from the superior frontal gyrus to the inferior frontal sulcus. the increased blood flow in the posterior parietal cortex most likely corresponded to enhancement of visual attention required during saccades, while that in the frontal lobe, which included the frontal eye fields, indicated activation for saccade motor output. pamela blake, alexander s. mark, martin kolsky, and jorge kattah, washington, dc fifty patients with third cranial nerve (cn) palsy underwent precontrast and postcontrast mri to assess the utility of this study in this clinical context. mri demonstrated an appropriate lesion in cases. six patients had brainstem lesions ( infarcts, mass lesion, cryptic vascular malformation, hemorrhagic shearing injury, with compound q toxicity). lesions of the cisternal segment of the nerve were present in patients ( aneurysms, lymphomas, ophthalmoplegic migraine, viral meningitis, coccidiodomycosis, nerve avulsion), with enhancement of this segment in patients. fourteen patients had cavernous sinus lesions ( lymphomas, nasopharyngeal carcinoma, tolosa-hunt syndrome, cavernous carotid aneurysms, pituitary apoplexy, aspergillosis). eighteen patients, all with history of diabetes or vascular disease, had normal mri results, suggesting microvascular infarction of c n . in patients with cn i palsy, mri can detect the presence of brainstem or cavernous sinus lesions and often can suggest their cause. mri with contrast enhancement can demonstrate involvement of the cisternal segment of cn i in patients with inflammatory or infiltrative processes that previously could not be radiographically demonstrated. our study suggests microvascular infarction does not cause nerve enhancement on contrast-enhanced mri. we describe patients with acute hyperglycemic, hyperosmolal, nonketotic stupor who had ocular flutter or opsoclonus clinically. these are the fourth and fifth adult patients reported with the acute onset of stupor and opsoclonus; all patients had nonketotic hyperglycemia and hyperosmolality (rapid eye movement sleep also causes stupor and saccadic eye movements). three of the patients had myoclonic jerks in addition to opsoclonus. in the , opsoclonus began when glucose and osmolality acutely increased, and completely resolved when glucose and osmolality became normal, showing that opsoclonus is a specific and reversible effect of the metabolic disorder and implying that either acute hyperglycemia or hyperosmolality directly causes opsoclonus. since acute hyperosmolality caused by nacl or sucrose can cause a similar syndrome in experimental animals (trans am neurol assoc ; : - ) and infants, hyperosmolality is probably more important. opsoclonus is thought to be due to abnormal activity of saccadic "burst" cells in the pons. acute hyperosmolality may cause spontaneous saccades by disinhibiting burst cells from normal "pause" cell inhibition or by directly activating burst cells. the combination of acute deterioration in mental status and either ocular flutter or opsoclonus should suggest acute hyperosmolality, in particular, nonketotic hyperglycemia. neural cell adhesion molecule (n-cam) and the related cell adhesion molecule l play significant roles in axon outgrowth and mediation of cell-cell contact in development, and after peripheral nervous system injury. to understand the role of these molecules after injury in the adult cns, we studied alterations in n-cam and l in the rat brain's response to entorhinal cortex (erc) lesion. post lesion, reactive synaptogenesis and axonal sprouting follow a well-defined temporal course in restoring the synaptic density of the dederented outer two-thirds of the hippocampal dentate gyrus molecular layer (ml) to near prelesion levels. we found striking regionand lamina-specific staining of n-cam and l in the normal hippocampus and marked alterations in these molecules after injury. embryonic n-cam, present in high amounts during development but expressed at very low levels in the adult hippocampus, was massively re-expressed in the denervated zone; the embryonic form was still heavily expressed days later, when synapse number returned to >so% of prelesion levels. l staining, normally evenly distributed through the ml of the dentate, was completely lost in the outer ml, which is denervated by the erc lesion. this staining had not returned by days after lesion. neural cell adhesion molecules play a role in specificity of neural connectivity both in development and after injury. in reactive synaptogenesis and axonal sprouting after injury, both ontogenetic (the reexpression of embryonic epitopes) as well as uniquely adult sequences of repair are utilized. following hemispherectom y" a. pascual-leone, h . t. chugani, l. g. cohen, j . p . brasil-neto, e. m . wassermann, j . and m. hallett, betbesh, md, and los angeles, ca we studied subjects, aged months to years, who underwent hemispherectomy months to years earlier for intractable epilepsy. all had a spastic hemiparesis contralateral to the resected hemisphere, which was present presurgically. we used focal transcranial magnetic stimulation to map the areas of the preserved hemisphere targeting the abductor pollicis brevis (apb), the biceps, and the deltoid ipsilaterally and contralaterally. in subjects who had hemispherectomy after age , the same area targeted ipsilateral and contralateral muscles. in the remaining subjects, who were more functional, areas targeted ipsilateral muscles. one area coincided with the contralateral representation, but stimulation induced motor-evoked potentials (meps) of lower amplitude and longer latency in the ipsilateral muscles. the other area, to cm anterolaterally, targeted exclusively ipsilateral muscles and stimulation induced meps of normal amplitude and latency. this separate ipsilateral representation was more distinct in subjects studied a long time after the hemispherectomy and in those who were younger at the time of the operation. these results show evidence of motor reorganization after hemispherectomy. better motor function is associated with topographically differentiated ipsilat-era and contralateral representations, which may depend on age at the time of hemispherectomy and the time since then. cynthia l. comella, glenn t . stebbins, nancy brown-toms, and christopher g. goetz, chicago, il in a single-blind, crossover study, we evaluated the effect of an intensive outpatient physical rehabilitation program (re-hab) on the severity of parkinson's disease (pd). the re-hab program consisted of -hour sessions per week for weeks. sixteen patients completed phases, a rehab phase and a control phase, separated by months. the order of participation in each phase was randomized. all patients were evaluated using the unified pd rating scale with subscales for mentation (ment), activities of daily living (adl), and motor function (mot) by an investigator blinded to the rehab phase of the patient. all patients were evaluated immediately before and after each phase. pd medications were not changed during any phase. following the re-hab phase, there was significant improvement in adl score (pre-rehab , post-rehab , p = . wilcoxon) and in mot score (pre-rehab , post-rehab , p = , wilcoxon), but no change in ment score. after the con-trol phase, there was no significant change in any outcome measure. this is the first controlled, crossover study of an intensive rehab program in pd. it demonstrates that re-hab improves objective motor function and adl scores. sensitive and quantitative measurements of leg weakness, one of the most common deficits in multiple sclerosis (ms) patients, can be made using specialized extremity testing equipment. to determine whether such determinations could be used in clinical trials, ms patients with leg weakness that had been stable for at least months were evaluated every days over a -month period. each testing session was carried out at the same time of day and medication dosages and schedules were kept constant (only patient was taking baclofen and his dosing remained constant). quadriceps and hamstrings strengths were measured in isometric contraction in a mechanical testing apparatus (kincom). variability for each series of determinations was expressed as the standard deviation of the mean as a percent of the mean. the overall variability then was expressed as the mean of the individual variabilities. the mean variability for the strength determinations over months was . k . , and only one series of determinations out of had greater than % variability. these results suggest that quantitative strength determinations might be useful in clinical trials, and early experience in trials of aminopyridines will be discussed. polymyositis (pm) is an inflammatory myopathy of unknown cause, but the accumulating data strongly suggest an autoim-mune pathogenesis. the histological picture is of muscle fiber necrosis and inflammation, whereas in postviral fatigue syndrome (pfs), a disorder characterized by severe fatigue with myalgia and psychiatric symptoms, the histological picture of muscle is essentially normal. enteroviruses have been implicated on epidemiological and serological studies in both. we have used the polymerase chain reaction (pcr) and an enteroviral-specific probe and found persistent enteroviral genomic material in both pm and pfs muscle biopsy specimens. furthermore, we used a radiolabeled full-length cdna probe derived from coxsackie b in an in situ technique to look for viral d n a in pcr-positive cases. coxsackie genome was clearly identifiable in the muscle biopsy specimens of patients with pm but negative in pcr enteroviral-positive cases of pfs. the virus excites an inflammatory reaction only in pm. a murine animal model for pfs developed in our laboratory showed positive muscle pcr using enterovirus probes and a conspicuous increase in interleukin within the brain. these results provide major clues in the search for the etiology of these two puzzling disorders. human t-lymphotropic virus type i (htlv-i) is a cause of adult t-cell leukemia and tropical spastic paraparesis. in a specific population of iranian jews originating from the city of mashad, there is a high incidence of htlv-i infection ( . %) and associated t-cell leukemia. we evaluated the incidence of possible correlation between htlv-i infection and spastic paraparesis in israeli mashadi-born jews. we have examined mashadi-born immigrants in a mashadi community center ( men, women, mean age t_ . yr) and non-mashadi iranian-born jews. blood samples were tested for htlv-i antibodies by particle agglutination test. the polymerase chain reaction (pcr) was used to amplify htlv-i sequences of d n a from peripheral blood mononuclear cells. twelve mashadi-born immigrants ( %) were seropositive for htlv-i. in of those serologically positive for htlv-i ( %), neurological examination revealed spastic paraparesis of varying severity. none of the non-mashadi iranian jews were seropositive for htlv-i or had clinical signs of spastic paraparesis. these results support other studies of htlv-i-associated myelopathy. the high incidence of htlv-i-associated spastic paraparesis in the mashadi community might be related to their unique history of a high rate of intermarriage among members of this ethnically segregated group. further epidemiological studies are underway to evaluate the incidence of htlv-i in mashadi families as well as in mashadi-originating jews born in israel, to identify whether infection might be genetically transmitted. lymphotropic virus t y p e i-associated acute t-cell leukemia/lymphoma william j . harrington, jr, william a. sheremata, susan snodgrass, and mark raven, miami, fl human t-cell lymphotropic virus type i (htlv-i)-associated acute t-cell leukernia/lymphoma (atl) is thought to produce important c n s disease infrequently. we wish to correct this impression by presenting neurological findings in patients seen between and the present. all had positive western blots to htlv with polymerase chain reaction confirmation of htlv-i infection. only had a concomitant human immunodeficiency virus infection. all were black, aged to years, were men and women. all but americans came from the caribbean nations of haiti ( , dominican republic (l), jamaica ( ), and trinidad ( ). sexual transmission was the risk factor for htlv-i for all except for intravenous drug user. all patients were systemically ill. three had preceding neurological abnormality ( , months, and yr) and had major neurological disease concomitantly. two of these had tumor masses demonstrated in brain and in the spinal canal. one had a minor facial sensory abnormality; only had no deficits. we conclude that cns disease is commonly associated with atl, and that in the us atl occurs principally in caribbean natives. a. nath, v . hartloper, and m . furer, winni$eg, manitoba, canada microglia and astrocyte cultures were established from human fetal brain. microglia were infected with human immunodeficiency virus (hiv) strains, hiv,, or hiv,,,, resulting in a rising titer of p antigen in the supernatants. multinucleated giant-cell formation, vacuolar changes, and rising levels of lactate dehydrogenase in the supernatants were seen, indicating a cytopathic infection of microglia. astrocytes were infected with free virus or cocultivated with an hiv-infected lymphocyte cell line (hut- ). after a productive phase (rising titers of p antigen and detection of hiv antigens by immunocytochemistry), the cells went into a latent phase where hiv could be detected only by dna polymerase chain reaction. a -fold increase in astrocytes staining for hiv antigens was seen after cocultivation with hut- cells. lymphocytes adhered to astrocytes by hours of cocultivation. no adhesion was seen to microglia. fusion of plasma membranes was seen on electron microscopy. infected astrocytes did not show cytopathic or morphological changes. cell-to-cell contact may be important in viral transmission to astrocytes. hszao-huei chen, steven b. stein, wing kong, and raymond p. roos, chicago, i l one of our goals is tq delineate molecular determinants for disease phenotypes produced by theiler's virus (tv), a mouse picornavirus. the identification of these genes and gene products may clarify viral pathogenesis and also lead to the identification of genes that are important in normal cns function and nonviral cns disease. members of the gdvii subgroup of tv cause an acute, fatal neuronal infection, whereas members of the to subgroup are less neurovirulent and produce a demyelinating persistent infection. our studies of infectious tv cdna clones have demonstrated that the gdvii b(vp )- c segment is critical for neurovirulence. several other areas of the genome, including the ' untranslated region (s'utr), also affect tmev-induced disease. the 'utr of poliovirus, another picornavirus, has a critical role in paralysis; this effect on neurovirulence is believed to result from an altered translational efficiency related to bind-region ing of neural cell proteins. tv 'utr has an unusual predicted secondary structure, even for picornaviruses. our studies demonstrate that the tv 'utr affects translational efficiency and has a distinctive protein-binding pattern. investigations of the tv 'utr may clarify features of translational regulation of cns genes in general. p . coronaviruses infect primate brain from g a y f. cabirac, ronald s. murray, galen cai, kristen hoel, and kenneth soike, englewood, co, and covington, la recently, we described finding coronavirus (cv) rna and antigen in active demyelinating plaques of multiple sclerosis (ms) brain tissue (murray et al, ann neurol, in press). molecular analysis showed the cv rna to be more closely related to murine cvs than to human cvs. we then demonstrated that, following intracerebral inoculation, the murine cv jhm and the putative ms isolate cv-sd could infect and cause demyelination in primate brain (murray et al, virology, in press). we now have data showing that murine cv can infect primate brain following intranasal or intravenous routes of inoculation. standard virology, histopathology, and the molecular analysis of viral cytotropism will be presented. we conclude that cvs related to murine cvs can infect primate cns from peripheral routes and warrant consideration as potential human pathogens. probes (gag, pol, or enw). eleven were white and were black. a history of transfusion was obtained in , and sexual risk of transmission was present in but not in others. fulminant disease occurred in transfused men months to years later but such disease was only seen in woman (in month). in contrast, of women with multiple sexual partners had rapid progressive disease. the male-to-female ratio was : for transfusion association and : for those at sexual risk but : for unknown risk, transfusion is an important risk for tsp/ham and the diagnosis must be considered in all gait problems, regardless of the "diagnosis."transfusion association should decrease with regular testing of blood donors, but this will not affect the risk of sexual transmission. spastic paraparedhtlv-i-associated myelopathy (tsp/ ham). it is unclear why htlv-i infection causes atl in some individuals and tsplham in others. differences in the genome of viral isolates or immunological and host factors have been hypothesized to play a role in disease expression. at present there are no animal models of tsplham and no suitable animal models of htlv-i infection that can address these issues. we transplanted severe combined immunodeficient (scid) mice with peripheral blood mononuclear cells (pbm) from tsplham patients in an attempt to produce htlv-i disease. two weeks after transplantation of pbm from tsplham patients, we detected anti-htlv-i igg in serum samples of of scid mice by enzyme immunoassay using sonicated whole virus. five weeks after transplantation, we detected anti-htlv-i igg to p , p , gp , or gp in serum samples of of scid mice by immunoblot of disrupted virus. these findings suggest that scid mice may be valuable in the study of molecular and pathological determinants of htlv-i-induced disease. theiler's virus produces an encephalomyelitis in susceptible mice. during the course of the disease, specific regions in the cns become infected. compared to the immunocompetent mouse, the nude mouse provides a useful model where viral dissemination can be studied in the absence of functional t lymphocytes and antibodies. we investigated the distribution and spread of the da strain of theiler's virus in the cns of nude mice. by immunohistochemistry, the hippocampus, arnygdaloid nuclei, entorhinal cortex, cingulate cortex, thalamus (anteroventral nuclei), midbrain, and spinal cord all contained viral antigens by weeks after infection. in addition, the olfactory nuclei, mamillary body, hypothalamus, basal ganglia, and nucleus raphe dorsalis often were involved. in the brain, the limbic system was the site commonly infected by theiler's virus. the time course of virus dissemination varied depending on the site of initial virus infection, though the final distribution of virus was the same. olfactory bulb injection, which is a direct inoculation into the olfactory pathway, resulted in more rapid spread than did cortex injection. we demonstrated the constant presence of viral antigen in the limbic system and a different kinetics of viral dissemination between the two different routes of intracerebral inoculations. these results suggest that limbic structures and their connections are important to the dissemination of theiler's virus. -associated myelopathy in a northwest native indian d. foti, d. werke, g. dekaban, g. p. a . rice, andj. oger, vancouver, bc, and london, ontario, canada a -year-old indian of the oweekeno tribe was admitted for investigation of a myelopathy. initially symptomatic with midthoracic radicular pain, she developed progressive spastic paraparesis over year with mild sensory symptoms and urinary retention. mri of the cord and brain were normal. csf showed elevated protein ( mgll), lymphocytes, and weak oligoclonal banding with evidence of intrathecal igg synthesis. antibodies to human t-lymphotropic virus type i (htlv-i) were positive by enzyme-linked immunosorbent assay and western blot on both serum and csf. presence of htlv-i was demonstrated by polymerase chain reaction of blood lymphocytes. htlv-i-associated myelopathy, or tropical spastic paraparesis, is endemic in southern japan, the caribbean basin, and several tropical islands but has not been reported in natives of northwest canada. this patient's only risk factors for htlv-i infection were blood transfusions years previously. ongoing familial and epidemiological studies as well as virus sequencing should indicate if this case represents an indigenous or an imported infection. caused by herpes simplex virus type lawy blankensbz) and herbert . newton, columbus, oh myeloradiculitis occasionally occurs secondary to herpes simplex virus type (hsv ) infection, but rarely has been reported after herpes simplex virus type (hsv ) infection without encephalitis. we describe a -year-old man who developed cervical myelopathy and radiculitis, never developed symptoms of encephalitis, and had positive hsvl spinal fluid cultures. h e initially developed extremity weakness and incoordination, numbness, paresthesias, and neck pain. evaluation was negative except for mri results, which showed a high-signal lesion centrally within the cervical cord. the weakness, sensory loss, and radicular pain progressed over several months. subsequent mri showed extension of the high-signal abnormality and mild enlargement of the cervical cord. symptoms stabilized briefly with dexamethasone but soon worsened, and were accompanied by paroxysmal kinesiogenic dystonic episodes of his arms and right leg. repeat evaluation was unrevealing except for the spinal fluid, which grew out hsv . the patient was treated with dilantin and a i-month course of intravenous acyclovir, with slow improvement of neurological status and resolution of the dystonic episodes. this case illustrates that hsvl can cause a myelopathy with a subacute and protracted course, requiring serial was more frequent in the middle-aged group ( p < . , p = . ). history of hypertension, previous strokes, diabetes mellitus, and antithrombotic treatment was similar, as were sex ratio, qualifying event type (transient ischemic attack or nondisabling stroke), and angiographic features; stenosis severity in either side and presence of ulceration were all similar. in elderly patients, ecad is associated with symptomatic cardiac disease (scad or af), whereas in middleaged patients it is associated with precursors of generalized atherosclerosis (smoking and hyperlipidemia). to identify the anatomic factors correlating with dementia in patients with lacunar infarctions, we examined digitized ct data on elderly patients (mean age = . yr; education = yr) who presented with acute lacunar infarction. dementia was diagnosed in patients ( . %) based on neuropsychological tests given months after stroke onset. the following ct variables were assessed: infarct location and number, total infarct volume, brain parenchymal and csf areas at levels, and width of the frontal horn, third ventricle (tvw), and lateral ventricle plus their ratio to the intracranial width. atrophy and leukoaraiosis were rated semiquantitatively using a standard scoring method. in the group overall, mean infarct volume was . cc and mean infarct number was . . in univariate analyses, dementia was significantly related to infarct volume, number, tvw, bilaterality, and infarct predominance on the left side, but not to leukoaraiosis or atrophy. in a regression model adjusting for demographic factors, the ct variables correlating independently with dementia status were infarct number (p = . , p = . ) and the presence of left cerebral infarcts (p = . , p = . ). we conclude that the most important ct variables related to dementia in lacunar stroke are lesion multiplicity and the presence of lesions on the left side. brain ischemia results in potassium (k+)-induced voltageregulated presynaptic calcium (ca") accumulation, which may contribute directly to neuronal in jury presynaptically, and also promote excessive release of excitatory neurotransmitters leading to cell damage postsynaptically. k+-induced depolarization of brain synaptosomes may be used as an in vitro model to study the therapeutic potential of pharmacological agents to alter ischemia-induced presynaptic ca + accumulation. we preincubated gerbil cerebral cortical synaptosomes in r (janssen pharmaceutical) at concentrations of to lo-' m, subsequently depolarized the synaptosomes with k + , at concentrations of to mm, and measured intrasynaptosomal ca ' ([ca +]) with the fluorescent indicator fura . r had no effect on ecaz'i in nondepolarized synaptosomes, but significantly (<. , student t ) depressed depolarization-induced {ca +] at to lo-' m in a dose-dependent fashion. the greater the degree of depolarization employed, the greater degree of depression in [ca +] was seen at each dose of r . since r had no effect on [ca +] when utilizing ca +-free incubation media, it was demonstrated that r prevents depolaritation-induced [ca ' ] increase by blocking voltage-regulated influx. because r appears to block voltage-regulated presynaptic ca ' accumulation, it should be further evaluated as a potential therapeutic agent after cerebral ischemia. sneddon's syndrome (ss) is a focal and diffuse arthropathy affecting mainly the vascular wall of the skin and cerebral arteries. etiology is not determined. we studied patients with ss ( females, males), aged to years. clinical, radiological, and immunological studies were done. all patients developed cerebrovascular disorders: ischemic stroke in %, transient ischemic attack (tia) in %, and ischemic stroke and tia in %. cerebral scan showed small and medium (less than cm) ischemic lesions in %. these lesions were superficial in the cerebral cortex ( %); deeper in the centrum semiovalis, internal capsule, and basal ganglia ( %); and both superficial and deeper ( %). ultrasound and angiogram studies revealed obstruction of intracranial arteries in %, and of extracranial arteries in %. partial or complete improvement of cerebrovascular symptoms was observed in %. immunological studies showed increased content of b-cell lymphocytes ( p < . ), increased levels of igm ( p < o.oool), and circulating immunocomplexes ( p < . ). anticardiolipin antibodies were increased ( %) and lupus anticoagulant detected ( %). cerebrovascular disorders in ss that lead to small ischemic cortical lesions have a good prognosis. pathogenesis of this syndrome may be related to antiphospholipid antibodies. the cheiro-oral syndrome is characterized by pure sensory deficit limited to the hand and mouth. this syndrome has been described in diverse lesions of the parietal operculum and brainstem, but occurs most commonly due to lesions of the contralateral thalamus, and suggests a humuncular representation of sensation in the ventral posterior lateral (vpl) and ventral posterior medial (vpm) nuclei. we describe a -year-old hypertensive woman who presented with sudden onset of numbness of the left side of her body. examination revealed a left hemisensory deficit to all modalities that spared the hand and peri-oral regions. cat scan and mri demonstrated an acute infarction of the posterolateral right thalamus, with a rim of preservation adjacent to the internal capsule. pure hemisensory loss with sparing of the hand and mouth ("inverse cheiro-oral syndrome") has not been reported previously, and complements previously published studies of the cheiro-oral syndrome in demonstrating somatotopic sensory representation in the thalamus. to examine the relationship between depression and dementia after stroke, we administered the -item hamilton depression rating scale (hdrs) and neuropsychological tests to elderly patients months after ischemic stroke. using dsm- -r criteria, we found dementia in ( . %). hdrs score was . -t . overall, and higher in demented compared to nondemented patients ( . . vs . t . , p = . ). the frequency of depression (total hdrs score > ) was also higher with dementia ( . % vs . %, p = . ). however, demented patients did not differ from nondemented patients on ratings of depressed mood. instead, hdrs items for psychomotor retardation, reduced work activities, and impaired insight best distinguished the groups. in multiple regression analysis, stroke severity (p = . , p = . ) was the most important correlate of hdrs score; dementia status was not correlated independently. mean scores on mini-mental state examination and neuropsychological tests assessing memory, orientation, verbal, spatial, attentional, and abstract reasoning skills did not differ by depression status. although weakly related to intellectual impairment, hdrs score in our stroke sample was most importantly associated with stroke severity. higher scores on hdrs in demented stroke patients may be explained by physical and cognitive symptoms that are expected with dementia. these findings do not support a causal link between depression and dementia, and argue against the importance of "depressive pseudodementia" as an explanation for intellectual decline after stroke. to investigate the pathophysiological mechanism of the white matter lesions in progressive subcortical vascular encephalopathy (psve) of binswanger type, we measured regional water partition coefficient (pc) (reflecting water content) and effective p h (pht) (weighted average of intra-and extracellular ph) with dynamic positron emission tomographic technique using - co,, o,, and c- co,. si-multaneously, regional cerebral blood flow (rcbf) and regional cerebral metabolic rate of oxygen (rcmro,) were evaluated. eight subjects ( normal, psve, multiple infarction) were examined. in the white matter lesions in psve, corresponding to high-intensity areas in t -weighted images of mr, the pc increased and pht was unchanged or decreased, whereas both rcbf and rcmroz declined. the ratio of white matter pc to gray matter pc was . in psve and . in normals. in the frontal gray matter, the pc decreased in psve, whereas rcbf and rcmroz also decreased. these results suggest that tissue water content increases in the white matter lesions in psve reflecting the edematous status of the damaged regions. elevated pht with high pc may reflect the increase of extracellular water of the tissue. measurement of pc and pht provides useful information about the pathogenesis of psve. stroke has been the second most common cause of death in korea but its risk factors (rfs) have not been studied intensively, so the rfs or causes were investigated prospectively in , consecutive stroke patients who were admitted to the chungnam national university hospital, taejon, korea, between and . they included cases of cerebral ischemia (ci) ( . %), cases of intracerebral hemorrhage (ich) ( . %), and cases of subarachnoid hemorrhage (sah) ( . %). control data were obtained from healthy spouses of the patients. multivariate analyses showed that hypertension (ht) was the strongest rf for all stroke types and was followed by old age, diabetes mellitus (dm), smoking, high-density lipoprotein cholesterol, and fibrinogen. the rfs for atherothrombotic ci included old age, ht, dm, smoking, fibrinogen, and cholesterol. for lacunar infarcts, ht, dm, old age, fibrinogen, alcohol abuse, smoking, and female sex were the significant rfs. ht was the cause of ich in ( . %) and alcohol abuse ( , . %) and vascular anomalies ( , . %) followed. most alcoholassociated ichs occurred characteristically in the posterior fossa. frequencies of hospital admission of ich patients correlated positively with diurnal variation of temperature ( r = . , p < . ). aneurysmal rupture was the cause of sah in patients ( . %). three major sites of aneurysms identified on cerebral angiograms were the anterior communicating artery ( , . %), the middle cerebral artery ( , . %), and the posterior communicating artery ( , . %). thirty-nine patients ( . %) had no identifiable cause of sah. in korea curvilinear subinsular lesions have been noted on ct but the underlying pathology is unknown. we reviewed the cranial mr scans ( . tesla ge machine) of serial patients over the age of who had no cause for mr hyperintensities (hi) other than age or vascular risk factors. seven ( %) had linear subinsular h i (sihi). four of ( %) patients with sihi and of ( %) without sihi had marked periventricular h i compatible with subcortical arteriosclerotic encephalopathy (pvhi) ( p < . ). patients with sihi were older ( . yr) than patients without sihi ( . yr) ( p < . ). four of ( %) patients with sihi had hypertension program and abstracts, american neurological association or vascular risk factors. a further patient with diabetes, hypertension, and the opercular syndrome (bilateral facial, pharyngeal, and lingual weakness) had subinsular lesions on ct. the brain arteries were injected postmortem with a lead/ gelatin suspension, and mr of the whole brain and x-ray films of the brain slices were taken. bilateral sihi were seen on mr and corresponded with linear cavitary infarction pathologically, which on microangiograms was found to lie in the border-zone between cortical and basal penetrating arteries. we conclude that sihi are associated with older age and pvhi, and can be due to infarction in a deep watershed territory and can be associated with clinical deficits. hemodilution-treatment results in consecutive cases james l. frey, phoenix, az because precipitous neurological deterioration occurred during blood pressure reduction in a seminal case of lacunar infarction, subsequent patients with partial or evolving lacunar deficits were treated with hemodilution and blood pressure nonintervention to test the hypothesis that lacunar strokes represent perfusion failure. isovolemic hemodilution was performed using hetastarch with target hematocrit of to . results of pretreatment ct brain scans, carotid ultrasound, and echocardiograms were normal. nine patients recovered normal neurological function, and regained complete functional independence in close temporal correlation with hemodilution. mri brain scans demonstrated appropriate single white matter lesions in cases. no specific risk factor combination could be identified. n o patient has had recurrent stroke in follow-up from to months. response to hemodilution suggests a hemodynamic pathophysiology. successful treatment requires ( } blood pressure nonintervention and ( ) hemodilution prior to severe clinical deterioration. the hemodynamic classification for the carotid-cavernous sinus fistula (ccf) is important for the implication of prognosis and therapy, but satisfactory objective criteria for such differentiation is still lacking. retrospectively, we studied the application of extracranial duplex sonography in cases of ccf with emphasis on the hemodynamic parameters of resistivity index and flow volume. a correlation was made with the angiographic findings in an attempt to evolve an objective hemodynamic classification by this noninvasive method. the alterations in membrane metabolism and structure could be the primary etiological event in alzheimer's disease (ad) that results in the clinical and neuropathological findings. to investigate in vivo brain membrane phospholipid and highenergy phosphate metabolism in probable ad patients and control subjects, the building blocks (pme) and breakdown products (pde) of membranes and the high-energy phosphates pcr and atp were measured noninvasively by in vivo brain p mrs in probable ad patients ( males; females) and controls ( males; females). all subjects were assessed by mini-mental, mattis, and blessed scales. we found that, at clinical onset, ad females had elevated pme ( p = . ), decreased pcr ( p = . ), and decreased atp ( p = . ). similar changes were not seen in ad males at clinical onset, but the severely demented ad males had increased atp ( p = . ). correlation analysis for the ad patients revealed that increasing dementia was associated with decreasing pme ( p = . ; r = . ), increasing pde ( p = . ; r = . ), increasing pcr ( p = . ; r = . ), and increasing atp ( p = . ; y = . ). similar metaboliccognitive correlations were not seen in the controls. these results demonstrate alterations in membrane and energy metabolism at the earliest clinical stages of ad. increasing dementia correlates with markers of membrane degeneration and decreased utilization of high-energy phosphates. both of these findings suggest the dementia in ad is secondary to membrane changes resulting in synapse loss. alzheimer's disease: postmortem mri and histological correlates fen-lei f. chang, j. e. purisi, c. r. jack+ jr, and r. c. petersen, rochester, mn hippocampal atrophy, defined by mri-derived volumetric measurement, has been useful in differentiating alzheimer's disease (ad) patients from normals. since several studies have demonstrated anatomical and functional gradients along the rostral-caudal (r-c) axis of the hippocampus, it is tempting to speculate on the existence of a differential distribution of morphometric changes along this axis. the hippocampi from patients with clinically and pathologically confirmed ad were studied by postmortem mri and by reconstruction of serial histological sections. there was good correspondence between these two methods. the r-c length of the hippocampus in ad was preserved compared to normal. this length was longer on the left, both in normals and ad. the adassociated atrophy was due primarily to the reduction of the coronal cross-sectional area of the hippocampus. with increasing hippocampal atrophy, volume reduction was more prominent in the rostral area (pes hippocampus). this nonuniform reduction in volume may be associated with different connectivity patterns between rostral and caudal hippocampus. the purpose of this study was to determine the neuropathological validity of nincds-adrda criteria (nac) for probable and possible ad. mckhann et al ( ) provided clinical criteria for the categories probable ad and possible ad. the validity of these categories has not yet been reported. a retrospective, blinded evaluation of the complete neurological history, examination, neuroimaging, laboratory, and psychometric data was done for subjects from the state of florida brain bank. pathological classification, which was blind to clinical diagnoses, was in categories: pure ad, ad + , and other dementias. ninety-three percent of probable ad (n = ), whereas only % of possible ad (n = ) patients, had ad or a d + ( p = . ). pure ad was found in % of probable ad and % of possible ad patients ( p = . ). pathological evidence of coexisting parkinson's disease was present in % of all ad brains. these results suggest differential predictive power of nac for probable and possible ad, as suggested by the labels. nac are, therefore, usefui for research and clinical purposes. our prior study of falls in the elderly had shown significantly more white matter low attenuation (wmla) on ct scan among fallers than nonfallers, but no association between wmla and cognitive impairment among nondemented subjects. as these subjects were followed over time, it appeared that fallers were becoming demented at a more rapid rate than nonfallers. as a result, we analyzed the relationship between wmla and rate of change on the blessed test of information, memory, and concentration (bimc) in a combined cohort of subjects from the falls study and from a longitudinal study of dementia and normal aging. we selected of these subjects whose initial bimc score was less than (i.e., not already severely impaired) and who had at least yearly bimc evaluations. ct scans were scored on an -point ordinal scale for hemispheric wmla. linear regression was used to summarize the rate of change for each subjects' test scores. the rate of change on bimc was . points per year with standard error (se) of . among subjects who eventually became demented; nondemented subjects declined at . points per year with se of . . multiple regression analysis was performed with initial bimc score and wmla as the independent variables and rate of change of bimc as the dependent variable. wmla accounted for % of the variance (partial r = . , t = . , p < . ). these data suggest that elderly subjects with wmla may be at increased risk for rapid cognitive decline. such as g proteins and adenylate cyclase. the activities of adenylate cyclase, and of the g protein-associated enzyme activity, low-km glutamyl transpeptidase (gtpase), were assayed in membranes prepared from the postmortem brains of alzheimer-diseased and age-matched control subjects. both basal and fluoroaluminate-stimulated adenylate cyclase activities were significantly reduced in ad frontal cortex compared to control subjects ( p < . ; two-tailed student's t test). in addition, a significant, though smaller, reduction in basal gtpase activity also was detected in ad frontal cortex ( p < . ). in contrast, no significant change in the activity of either enzyme was detected in the hippocampus. the stimulation of gtpase activity by muscarinic and gababreceptor agonists was not altered significantly by the presence of alzheimer's disease. however, the degree of stimulation was much lower in human tissue compared to that observed using fresh rat brain, suggesting that the ability of receptors to activate g proteins declines post mortem. these results suggest that alzheimer's disease causes alterations in some key components involved in signal transduction. the association of lobar hemorrhage (lh) with cerebral amyloid angiopathy (caa) and that of caa with alzheimer's disease (ad) are well known. to determine how frequently lh and caa occur in ad, we reviewed patients with cerebral or cerebellar hemorrhage and caa. five patients were treated surgically, none was demented, died, and came to autopsy. eight patients died of lh and came to autopsy. of the autopsied patients, had ad, both clinically and neuropathologically. they comprised . % of cases of autopsy-confirmed ad in our laboratory. none of the other patients were known to be demented. five had senile plaques, with or without neurofibrillary tangles, in the hippocampus, and occasional senile plaques in the cortex, but none met the consortium for establishing a registry for alzheimer's disease neuropathological criteria for ad. ad patients were , , and years old and the ages of the nondemented patients ranged from to (mean = . yr). seven were younger than years of age. despite the frequent occurrence of caa in ad, we found that lh was uncommon. in addition, most of our patients with lh and caa were not demented and tended to be younger than ad patients with lh. these results indicate that the hf is involved primarily in acquisition or leaning processes and less so in retrieval of previously learned information. these findings relate to memory and structural brain changes found in normal aging. alzheimer's disease y . stern, l. stricks, g. alexander, . prohovnik, and there is an inverse relationship between parietotemporal cerebral blood flow and years of education in alzheimer's disease (ad) patients matched for clinical severity, which suggests delayed clinical manifestation of ad in patients with higher education (stern et al, soc neurosci abs ). we classified the lifetime primary occupations of ad patients using the dictionary of occupational titles of the us department of labor and derived factor scores describing intellectual, interpersonal, and physical job demands. after controlling for age, education, age at onset, illness duration, and dementia severity (mental status and activities of daily living), relative perfusion in the parietotemporal region (assessed using -xenon inhalation) showed significant correlations with job complexity (pl: r = -. , p < . ) and interpersonal (p : r = -. , p < . ) factor scores. in a stepwise multiple regression, job complexity and interpersonal skills increased explained parietotemporal flow variance by . % ( f = . , p < . ) over that explained by demo-graphic and severity indices; physical demands then accounted for another . % of the variance ( f = . , p < . ). we conclude that occupational demands, similar to but independent of education, may provide a reserve that delays the clinical expression of ad. richard mayeux and ming-xin tang, new york, n y risk factors for alzheimer's disease (ad) were collected from patients with ad and healthy elderly controls in an urban community population consisting of ethnic groups: black, hispanic, and white. advanced age (> yr) (or = . ; % ci . - . ) and head injury with loss of consciousness (or = . ; . - . ) were associated with ad, controlling for all known putative risk factors. factors such as low education (< yr) (or = . ; . - . ) and family history of ad (or = . ; . - . ) were not found to be significantly related to ad. head injury occurred in . % of the patients and .?% of controls. most ( %) head injuries in the patients with ad occurred after age , prior to disease onset. in controls with head injury, had experienced a head injury before age . the duration of unconsciousness was consistently longer in patients with ad than in the controls. the overall effect in each ethnic group was similar (or,, . ; . - . ). these results confirm and strengthen the previously described putative relationship between head injury and ad. we also conclude that both the severity and the timing of the head injury as well as the frequency of head injury in the population at risk may be important factors in understanding the causal relationship between head injury and ad. the purpose of this study was to determine how native language affects the cutoff scores in screening tests for dementia. there is a paucity of data o n this issue at present. screening tests used in the study were: folstein mini-mental state (mms); clockdrawing (clock); preparing a letter for mailing (mail); -item grocery list (list); and hamilton depression scale (ham). the subjects included ( demented) native english speakers (eng) and ( demented) native spanish speakers (spa) with memory complaints. diagnosis of dementia was determined by neurological, neuropsychological, and psychiatric evaluation. age and gender were unrelated to mms. in spa only, education was positively related to mms. ham scores were higher in de- and . (spa); c d and list did not add discriminative power to mms for eng but did so for list in spa. mms discriminates between demented and nondemented far better in english than in spanish speakers. only mail adds discriminative power to mms. a. heyman, g. fillenbaum, s. mirra, and participating cerad neuropathologists, durham, nc, and atlanta, ga the clinical diagnosis of alzheimer's disease (ad) has become more accurate in recent years due to the application of specific clinical criteria, wider use of neuroimaging procedures, and greater expertise among physicians. we report the frequency of clinical misdiagnosis of ad among patients who at autopsy were found to meet the rigorous clinical diagnostic criteria imposed by the consortium to establish a registry for alzheimer's disease (cerad) study. these patients included men and women (mean ages and yr, respectively) who were among the group of patients who died in cerad medical centers in the us between and . the clinical diagnosis of ad was neuropathologically confirmed in ( . %) of the cases. of these cases, varying degrees of concomitant cerebrovascular disease were present in % and coexisting parkinson's disease changes were found in %. in of the patients without neuropathological evidence of ad, the diagnoses were: lobar atrophy, diffuse lewy body disease, nonspecific neurodegenerative changes, and mesocorticolimbic dementia, respectively. the fifth patient showed no morphological abnormalities. on the basis of these results, it would appear that application of strict diagnostic criteria, as well as the use of brain scans and detailed clinical and neuropsychological tests by experienced clinicians, cannot yet distinguish some types of primary degenerative dementias from alzheimer's disease. we designed a scale that measures an underexplored facet of functional decline in alzheimer's disease (ad): the patient's dependence on others for supervising or performing activities. two hundred twenty-three informants for patients with mild ad (clinical dementia rating [cdr] = for ; cdr = for ) were interviewed and dependence was staged from to . interrater reliability was assessed by separate interviews of informants; agreement was % for dependence stage. dependence stage differed significantly at the cdr levels (chi square = . , p < . ) and correlated significantly with modified mini-mental state (mmms) ( r = -. , p < . ) and blessed dementia rating scale-part (bdrs) ( y = . , p < . ). seventy-eight percent of patients in a health-related facility were at stage or higher vs % of patients living at home. in a multiple regression model, both the bdrs and dependence scale accounted for unique portions of the variance in mmms, suggesting that they assess unique aspects of functional ability. dependence increased significantly in patients retested at year. we conclude that the dependence scale is reliable and relates to both disease severity and progression. formal assessment of dependence should prove useful for studies of the natural history of ad as well as for clinical trials. cortical-basal ganglionic degeneration (cbgd) is a disorder characterized by an asymmetrical akinetic-rigid syndrome and cortical signs such as apraxia, alien limb phenomena, and cortical sensory loss. dementia has been present in many cases, but always as a late manifestation. we report cases pathologically consistent with cbgd, presenting as primary degenerative dementia, fulfilling nincds-adrda criteria for probable alzheimer's disease (ad). the first patient presented with changes in memory and personality, language dysfunction, decreased verbal output, and shuffling gait. follow-up examinations over years showed progressive dementia, wide-based gait, and frequent falls. the second patient presented with complaints of memory loss. neuropsychological examinations showed progressive deficits in memory, attention, calculations, and visuospatial functioning. no movement disorder developed over years of follow-up. at autopsy, both patients had typical changes of cbgd and lacked pathological features of ad. definitive diagnosis of cbgd rests on both clinical and pathological criteria. cbgd should be considered in the differential diagnosis of patients with dementia resembling that found in ad, especially if extrapyramidal signs are present. a quick, easily administered and scored test for praxis is desirable in evaluation of neurological patients. during months in , each patient seen in the outpatient setting by the principal investigator (e. k.) received of praxis screening batteries. thirty-six patients were tested with a short battery. eleven had normal cognition based on neurological history, examination, and a short test of mental status. twenty-five had cognitive decline (cd). handedness, male/ female ratio, education, and mean age were similar in both groups. mean time of completion of the test was seconds in normals and * seconds in patients with cd. total scores (maximum ) were . * . in the normals and . in the cognitively declined patients. twenty-five other patients, with cd and with normal cognition, were tested with a longer battery containing oral/ facial, upper and lower limb, axial, sequential, and imitation subtests (maximum score ). normals completed the battery in i , and cognitively declined patients completed the battery in ? seconds. of the various subtests, tests of sequential praxis were performed most poorly by patients with cd: . * . in normals vs . * . in patients with cd. oral/facial praxis was least affected by cd: olivopontocerebellar atrophy (opca) is generally understood to be a nondementing neurodegenerative disorder affecting the cerebellum, lower brainstem, and spinal cord. one of us (s. k.) recently reported that postmortem cerebral cortex from patients with dominantly inherited opca shows a widespread reduction of cholinergic markers similar to that observed in alzheimer's disease (ad). we were interested to determine the status of other neurotransmitter systems in opca postmortem cerebral cortex. samples of frontal, parietal, temporal, and occipital cortex were dissected from confirmed cases of opca and age-matched controls. after processing, neuropeptide levels were measured by radioimmunoassay. concentrations of somatostatin were significantly reduced by to % in of the cortical areas of opca brain that were examined. the area that was spared was the inferior temporal gyrus, a region in which somatostatin levels are markedly reduced in ad. levels of neuropeptide y were normal in all areas, while concentrations of cholecystokinin, vasoactive intestinal polypeptide, and substance p were significantly increased in of the areas. these data show widespread neuropeptide changes in the cerebral cortex of opca postmortem brain. in contrast to cholinergic markers, the pattern of neuropeptide changes is different from what is observed in ad. it has been postulated that demise of the corticomotoneuron is the initial event in amyotrophic lateral sclerosis (als) and that the anterior horn cell dies as the result of antegrade glutamatergic excitotoxicity (muscle nerve ; : ). excitability of the corticomotoneuronal system can be tested by measuring threshold-to-cortical magnetic stimulation and the motor-evoked potential (mep)/compound muscle action potential (cmap) ratio, which estimates the number of corticornotoneurons stimulated. cortical threshold and mep/ cmap ratio were measured in patients early in the course of als. the mean time interval from onset of first symptoms was . months. mean threshold and mepicmap ratio measured . f . % and . rfr . %, respectively. in ( . %) patients, threshold was paradoxically low (< %, mean . +. . %) and in ( . %) patients there was no response. there was a significant ( r z = . ) inverse power relationship between cortical threshold and mep/cmap ratio given by . x mep/cmap-'j. six months later, / ( . %) patients still had low thresholds but the mean mep/ cmap ratio had dropped to . ? . % and in . % there was no response. we conclude that early in als the corticomotoneuronal pathways are abnormally excitable. this may explain early cramping and fasciculation, which characteristically diminishes as als progresses. one of the distinct clinical features in patients with amyotrophic lateral sclerosis (als) is loss of elasticity of skin. however, little is known concerning the biochemical nature of skin elastin in als. in our study, cross-links unique to elastin, desmosine and isodesmosine, were measured and compared in skin tissue (left upper arm) from patients with als and from age-matched controls. the contents of desmosine and isodesmosine were decreased significantly ( p < . and p < . , respectively) in patients with als (mean * sd, . ? . and . * . nmol/mg dry weight; range . - . and . - . nmol/mg dry weight, respectively) as compared with those of controls (mean sd, . * . and . . ;range . - . and . - . , respectively), and were negatively and significantly associated with duration of illness in patients with with amyotrophic lateral sclerosis als ( r = - . , p < . , and r = - . , p < . , respectively). the ratio of desmosine and isodesmosine was constant ( : ) in all samples analyzed. the decline in skin desmosine and isodesmosine is more rapid in als than in normal aging. thus, cross-linking of skin elastin is affected in als. (supported in part by n i h grants de , de , de , ar , ar , and nasa grant nag- - .) pl . natural history of amyotrophic ( ) collection of large numbers of twin pairs in disease of low prevalence is difficult. to circumvent this, we devised a new approach termed the "death discordant twin pair" method. eleven thousand deaths from motor neuron disease (mnd) were extracted from the office of population censuses and surveys during to . birth indexes from onward were searched for possible twins. for each twin so identified ( pairs), the national health service central registry located the relevant family practitioner committee and thence the co-twin's general practitioner. the search produced: ( ) living co-twins; ( ) embarked; ( ) dying as adults or infants; ( ) not mnd; and ( ) validity of the accuracy, sensitivity, and specificity of the world federation of neurology (wfn) subcommittee on motor neuron disease working group criteria for the clinical diagnosis of amyotrophic lateral sclerosis (als) has been tested against neuropathological criteria in autopsied patients (neurology, in press). integration of clinical and electrodiagnostic data to meet wfn criteria for possible, probable, and definite als was studied in this samegroup. patients received . ifr . (mean * standard deviation) electromyograms (emgs) per patient and included . . emg levels (bulbar, cervical, thoracic, lumbar) per patient. proportionately fewer emgs were performed as the level of diagnostic certainty at presentation increased: suspected ( . %), possible ( . %), probable ( . %), definite ( . %). in only . % of all patients studied did the first emg alone change the level of diagnostic certainty of the diagnosis of als. only . % of patients presenting with suspected als alone or with possible or probable als were associated with a change in level of diagnostic certainty following or more emgs. however, although increasing the number of emgs performed per patient may be associated with an increasing chance of increasing the level of diagnostic certainty ( emgdpatient = . %; emgdpatient = . %), selection of the level of emg analysis was more crucial. the "el escorial" criteria emphasize the importance of emg evidence of lower motor neuron involvement in a limb with clinical upper motor neuron signs. our analysis of emg studies in autopsy-confirmed als patients suggests that complete evaluation of bulbar and thoracic levels for lower motor neuron changes and complete evaluation of motor unit recruitment patterns are important for the integration of emg data with clinical data in the application of the "el escorial" criteria for the diagnosis of possible, probable, and definite als. sibships on guam annette grefe, john steele, linda flares, and stephen waving, birmingham, al, and umatac and mangikao, guam reports in the s indicated that % of guamanian chamorro patients with amyotrophic lateral sclerosis (als) gave october a positive family history. subsequent investigators have inferred that purely genetic factors are not responsible for guamanian als or its clinical variant, parkinsonism-dementia complex (pdc). we report the first chamorro sibships selected in an ongoing study of familial aggregations. the basis for the initial selection was that the youngest patient in the sibship had als. age of onset was to years (mean yr). fourteen of persons in these sibships were affected. others in the sibship developed pdc, progressive supranuclear palsy, or pure dementia later in life (mean yr, range - yr). these cases developed to years (mean yr) after onset of disease in the first sibling. the age at onset of the first case and the intervals between earliest and latest cases in such sibships may help to determine minimal and maximal latency (i.e., interval between exposure to an exogenous agent and onset of symptoms). our observations suggest that exposure may have occurred early (before age ) with varying and often long latency (up to yr). we also find that variability of clinical expression may be correlated with the age at onset. concentrating on the study of familial cases on guam may enhance the identification of the etiologic agent(s) of this prevalent and tragic disorder. the spinocerebellar ataxias are an uncommon group of genetic disorders that have been well characterized in north america and europe. information concerning these conditions in africa and other parts is scant. to address this problem, a large-scale survey has been undertaken in the cape province of south africa. in this investigation, more than persons in affected families have been appraised and investigated and phenotypic features have been analyzed in detail. linkage studies have been undertaken in families with similar phenotypes in which the condition was transmitted as an autosomal-dominant trait. human lymphocyte antigen (hla) typing was carried out on members of the families and linkage analysis was undertaken using the liped program to analyze the data with a correction factor for age of onset. maximum lod scores were: family a: . ( = . ); family b: . ( = . ); family c: . ( = . ); family d: . ( = . ). these results indicate linkage to hla in out of families. these findings provide support for the concept of genetic heterogeneity in these phenotypically homogeneous families. pcr typing with the reportedly more closely linked d s locus is now being undertaken in these south african families. h.-p. hartung, g. f. hoffmann, and g. becker, wunburg, heidelberg, germany recently, l- -hydroxyglutaric acidemia has been described as a novel metabolic disorder in children. we report the occurrence of this disease in adults. one of brothers developed at the age of an abnormal gait and dysarthria; in the other , clumsiness and walking delay were noted at age . symptoms progressed and at the time of admission, when the patients were and years, neurological examination revealed a spastic ataxic gait, limb ataxia, dysmetria, dysarthria, dystonic posturing, and mental retardation. ct and mr imaging revealed subcortical white matter changes with loss of arcuate fibers, folial atrophy, and leakage in the cerebellar vermis, as well as atrophic changes in the cerebellar hemi-acidemia program and abstracts, american neurological association spheres. on biochemical screening, highly elevated concentrations of l- -hydroxyglutaric acid were found in csf, plasma, and urine. the pathological accumulation of l- hydroxyglutaric acid in these adults, along with the clinical picture characterized by cerebellar, extrapyramidal, and pyramidal symptoms and oligophrenia, and the neuroradiological findings of severe loss of myelinated arcuate fibers in subcortical white matter, conform with what previously has been described in the few neuropediatric cases. the biochemical abnormality underlying accumulation of this organic acid remains elusive. this study was undertaken to differentiate primarily affected areas from functionally suppressed areas due to remote effect in aphasic patients with focal brain degeneration, using an activation method with - water, in comparison with [sf] -fluoro- -deoxy-~-g~ucose (fdg) positron emission tomographic examination at rest. the subjects were patients with slowly progressive aphasia showing contrasted clinical symptoms (nonfluent type vs fluent type). regional cerebral metabolic rate of glucose (cmrglu) was measured with intravenous injection of mbq of f- fdg at rest. regional cerebral blood flow (cbf) was measured with intravenous bolus injection of . gbq of - water in different conditions: at rest, under repetition tasks, and under naming tasks. changes of cbf were evaluated between a resting condition and task-performing conditions. regional cmrglu was decreased focally in both broca's and wernicke's areas similarly in these cases in spite of the difference in clinical symptoms, whereas the patterns of regional cbf changes were different. the fluent patient showed prominent activation in the bilateral frontal areas on repetition tasks. the nonfluent patient showed, whereas the fluent patient did not show, focal activation in the left occipitoparietal area on a naming task. evaluation with an activation method can provide detailed information about the pathophysiological process and the location of primary lesion. defective complex i activity has been linked to huntington's disease (hd) and parkinson's disease (pd). intrastriatal injection of inhibitors of complex i reproduces the pathological features of hd, and the neurotoxin mpp+ kills dopaminergic neurons by inhibiting complex i. defects in complex i have been reported in hd and pd, but the distribution of this enzyme in the brain is unknown. to map complex i in brain quantitatively, we developed an assay using e h)dihydrorotenone to label the enzyme in tissue sections. this high-affinity binding is saturable and is displaceable by rote-in brain none and mpp+. using pm rotenone to define nonspecific binding, more than % of binding is specific. highest levels of binding are found in kidney, followed by myocardium. moderate levels of complex i are seen in striated muscle and some brain regions. within the brain, binding varies more than -fold and is heaviest in the cerebellar molecular layer and dentate gyrus. lower levels of binding are found in cortex and striatum and very low levels are located in substantia nigra. this assay may help to clarify the role of complex i in neurodegenerative disorders. ( in , patients with medically intractable parkinson's disease underwent autologous adrenal medullary-to-caudate transplants at the university of california-los angeles (ucla). these persons had been followed for several years before operation at -or -month intervals. at each visit, their disability had been rated on the quantified ucla scale and the hoehn and yahr stage of disease. these provided a longitudinal assessment of the progression of disease in each patient, which could be compared to the rate of progression in the cohort of cases followed at ucla for years. in addition, the unified parkinson's disease rating scale provided supplementary data for the immediate preoperative and subsequent postoperative evaluations. the hours "off" also were recorded for the preoperative and postoperative periods. after operation, the same evaluations were performed by the neurologist who previously had cared for the patients. the longitudinal postoperative data revealed that at to months after operation, all patients improved. after years, continue to be less disabled than their preoperative baselines. the progression of their disease, while still evident, is nonetheless proceeding at a slower rate than before transplant. the fourth patient had brief improvement shortly after operation, but then rapidly worsened to his previous level. his disease has continued to progress at a rapid pace, unchanged from progression before operation. individuals at risk for huntington's disease h . p. h . kremer, w. shtybel, b. snow, c. clark, j . theilmann, m . r. hayden, and w. in huntington's disease (hd), caudate hypometabolism as demonstrated by positron emission tomography (pet) is a well-established feature in symptomatic patients. in individuals at risk, however, conflicting findings are reported. since we have performed pet scans in asymptomatic persons at risk for hd (age - yr) . linkage analysis with independent dna probes or subsequent evolution to clinical hd (in patients) allowed a risk estimate for subjects. twenty were considered to be at increased risk (? %), at decreased risk (< %), and in individual no modification could be given. nine subjects were not tested. a pet scan was considered abnormal if either the caudate/thalamus ratio or the caudate/whole-brain ratio of rcmrglu was more than these criteria, scans in individuals were abnormal. none had received a decreased risk. comparison of the ratios of increased risk, decreased risk, unmodified risk, and control subjects failed to show statistically significant differences (analysis of variance). follow-up of persons with an abnormal scan showed conversion to symptomatic status within years after the first abnormal scan. this result suggests that an abnormal pet scan in a person at risk for h d heralds the onset of choreic movements. robitaille, m . el-awar, b. clark, l. scbut, m. ball, l. young, r. currier, and k. sbannak, toronto, ontario, and montreal, quebec, canada; pittsburgh, pa, minneapolis, mn, portkmd, or, and jackson, ms we measured the levels of dopamine in striatum of patients with end-stage dominantly inherited olivopontocerebellar atrophy (opca). on average, dopamine levels were reduced in putamen ( - , as compared with controls), caudate ( - %), and nucleus accumbens ( - %). however, individual patient values showed a wide variation (normal to - ), indicating that striatal dopamine loss is a common, but not constant feature of opca. seven patients had marked putamen dopamine loss (- to - ) but without corresponding severe substantia nigra cell damage; this suggests a "dying-back'' phenomenon in which nerve terminal loss precedes cell-body degeneration. in this regard, opca may offer the possibility of examining nigrostriatal dopamine neuronal degeneration at an early stage. although patients were found to have severe nigral cell loss with near total ( - to - %) striatal dopamine loss, none had depression in parkinson's disease (pd) has been correlated with low cerebrospinal fluid (csf) levels of -hydroxyindoleacetic acid ( -hiaa). l-dopa may precipitate or exacerbate depression in % of pd patients. to determine if l-dopa affects -hydroxytryptamine ( ht) metabolism, patients were studied. four had pd. of these, were taking l-dopa and both were depressed. the diagnoses in the remaining were progressive supranuclear palsy (psp), striatonigral degeneration (snd), normal pressure hydrocephalus, and pseudoseizures with depression. neuropsychological examinations and lps of all patients were done. three patients were started on l-dopa (the previously untreated pd patients and the psp patient) and retested days later. one pd patient started on l-dopa became depressed. mood in the others was unchanged. csf was analyzed for ht and -hiaa. ht could not be detected in the csf of patients who were not taking l-dopa, but was easily detectable in all of the patients who were taking l-dopa. -hiaa levels were low in the untreated pd patients, and also in the patients with psp, snd, and pseudoseizures with depression. -hiaa levels were even lower in the l-dopa-treated patients. the ratio of -hiaa: ht (an index of ht turnover) was lowest in the l-dopa-treated pd patients who were depressed. low csf -hiaa in untreated pd may reflect depletion of brain ht. l-dopa may induce depression by inhibiting ht turnover in ht-depleted brain. p . ventroposterolateral medial pallidotomy in the e. fazzani, m. dogali, a. ben;, d. eidelberg, j. gianutsos, t. kay, b. newman, s. loftus, d. samehon, and l. laitinen, new york, n y , and stockholm, sweden in patients with parkinson's disease (pd), as a consequence of low dopamine there exists an increase in inhibitory output from the globus pallidus. ten patients ( men and women) with pd received unilateral ( right, left) ventroposterolateral medial globus pallidotomies (vplmp). the average patient age was years (range - yr), and the average duration of disease was years (range - yr). patients fluctuated between "on" chorea and "off" parkinsonism. hoehn and yahr stage "on" was i in , in ; and "off" was i in , iv in , and v in patients. unified pd rating scale (updrs) score averages hours off medicines ( hom) were activities of daily living (adl): and motor (mtr): preoperatively (preop). capit score averages preop hom were pronation-supination (ps): seconds (s), finger tap (ft): s, board (b): s for the most affected contralateral side, and gait: s ( patients could not walk). re-examination was done to days after pallidotomy. updrs scores hom decreased an average of %. three patients had major bilateral improvement in bradykinesia. rest tremor, prominent in patients, also was diminished. capit scores hom decreased to ps: s, ft: s, b: s; the average gait of the patients who could walk preop improved to s. there were no side effects. vplmp leads to an immediate overall significant improvement in patients with pd. s. kish, y . there is a growing interest in the genetic aspects of parkinson's disease and other basal ganglia disorders. we have studied families whose ancestors immigrated to north america from contiguous regions of northern germany and southern denmark. the pedigrees contain , , and individuals spanning , , and generations with , , and affected members, respectively. autosomal-dominant inheritance is clearly present in families and probable in the third. typical levodopa-responsive parkinsonism with bradykinesia, rigidity, resting tremor, and impaired postural reflexes uniformly develops in affected individuals from all families. n o downgaze impairment, pyramidal signs, sensory disturbances, cerebellar dysfunction, or orthostatic blood pressure changes have been observed. dementia, however, has developed in a few elderly individuals, especially in family. laboratory studies are normal. mri shows moderately enlarged ventricles and cortical atrophy. -fd positron emission tomography demonstrated reduced striatal uptake in examined patient and normal uptake in l individual at risk. autopsy of only subject has been performed (in ). brain weight was , grams and there were no obvious gross abnormali- program and abstracts, american neurological association tuesday, october ties, but microscopic examination was limited. further research on these families is planned. electrophysiological study s. maurri, m . cincotta, a. ragazzoni, g. descisciolo, and f. barontini, florence, ltah many neurophysiological examinations were conducted of a -year-old woman with familial mirror movements. n o other neurological abnormalities were detected. examination included voluntary electromyographic (emg) activity from various muscles, f-wave as well as short-and long-latency reflex responses of the thenar muscles from electrical stimulation of the median nerve, mapping of motor-evoked potentials (meps) to transcranial magnetic stimulation, movement-related cortical potentials (mrcps), and somatosensory-evoked potentials (seps). emg documented mirror activity in the upper limbs, most marked in the muscles of both hands. onset latency of emg activity in response to an auditory stimulus was identical in active and mirror muscle. long-latency responses from median nerve stimulation were recorded on contralateral as well as ipsilateral thenar muscles. short-latency reflexes and f wave were strictly ipsilateral. unilateral scalp magnetic stimulation evoked bilateral responses at similar latencies in the thenar muscles; midline scalp stimulation activated no responses. scalp distribution of median nerve seps and of mrcps associated with self-paced thumb abduction were normal. our findings suggest that congenital inherited mirror movements in otherwise normal subjects can be generated by corticospinal fibers pro jecting to ipsilateral motoneurons of the spinal cord. we have previously identified dysphagia and constipation (both slow transit and defecatory dysfunction types) as common gastrointestinal (gi) problems in parkinson's disease (pd). since apomorphine has been shown to be capable of terminating off-periods when injected subcutaneously, we have evaluated the effects of apomorphine injection on objective parameters of dysphagia and bowel dysfunction in pd patients. nine subjects underwent the following battery of studies to characterize their pd features, swallowing, and bowel function: gi assessment survey, unified pd rating scale, videoesophagram, colon transit study, defecography, and anorectal manometry. specific abnormalities on the studies were noted and the most abnormal study was repeated after subcutaneous administration of mg apomorphine. all individuals were pretreated with domperidone mg four times daily for days prior to apomorphine administration. improvement in both esophageal motility and deglutition was noted in the individual in whom videoesophagram was repeated. for the other patients, defecography or anorectal manometry was performed. significant improvement in specific parameters was demonstrated after apomorphine administration, but individuals experienced syncope during radiographic procedures. we conclude that subcutaneous apomorphine administration holds promise as a potential therapeutic approach to dysphagia and, especially, bowel dysfunction in pd, but that further investigation and refinement are necessary. asymmetrical effect of unilateral thalamotomy or subthalamotomy on tremor in parkinson's disease nico diedericb, christopber g. goetz, glenn t . stebbins, harold l. klawans, k. nittner, a. kozrlosakis, p. sanker, and v . strum, cologne, germany, and chicago, il in the past, stereotactic operation was a regular treatment for unilateral tremor in parkinson's disease (pd). however, follow-up studies were usually short term and always unblinded. we examined pd patients in long-term follow-up (mean . yr after operation) who underwent unilateral thalamotomy for parkinsonian tremor. we used videotapes and the unified parkinson's disease rating scale to blindly compare tremor ipsilateral and contralateral to the side of operation. since the patients were specifically selected for stereotactic operation because of asymmetric tremor, we reasoned that a sign of long-term efficacy would be current postoperative reversal of tremor side predominance. upper extremity tremor was significantly better contralateral to the side of operation compared to the ipsilateral side ( z = . ; p < . ). for the lower extremities the difference was not statistically significant. in chronic follow-up, stereotactic operation improved the absolute magnitude of arm tremor or ameliorated its rate of progression. since asymmetric bradykinesia and dyskinesia were not prerequisites for the choice of surgical side, we cannot make any conclusion about longterm impact of operation on these features. subtle extrapyramidal signs resembles that of patients with parkinson's disease m . richards, k. marder, l. cote, y . stern, and r. mayeux, new york, n y to investigate the relationship between extrapyramidal signs (eps) and cognition, eps severity and neuropsychological function were assessed in normal elderly individuals and nondemented patients with idiopathic parkinson's disease (pd) from a community-dwelling cohort in new york city. multivariate analysis of variance (manova) indicated poorer neuropsychological performance ( p = . ) in pd patients on verbal memory, orientation, verbal fluency, visuomotor construction, and psychomotor speed, but not naming, abstract reasoning, or matching. controlling for eps severity abolished these differences. one hundred fourteen ( %) of the normal individuals had subtle eps (mostly postural abnormality, bradykinesia, or rigidity) but no identifiable neurological disorder. manova indicated poorer neuropsychological test performance ( j = , ) in these individuals than in normals without eps on verbal memory, orientation, abstract reasoning, naming, verbal fluency, matching, and psychomotor speed but not visuomotor construction. we conclude that: ( ) cognitive impairment in pd is specifically associated with eps, and ( ) a similar association occurs in individuals with subtle eps but no neurological disorder. whether this represents a preclinical stage of pd or ad is yet to be determined. disease in olmsted county, minnesota emre kokmen, fatma sibel ozekmekci, c. mary beard, and peter c. o'brien, rochester, m n , and istanbd, turkey there have been many studies of prevalence of huntington's disease (hd) in diverse populations around the world. to study the incidence, we took advantage of the availability of detailed health care records for the population of olmsted county, mn, from mayo clinic, its affiliated hospitals, olmsted medical group, county hospital, state hospital, records of solo practitioners, nursing homes, death certificates, and autopsy records. we reviewed all records with a diagnosis of hd, huntington's chorea, chorea major, and chorea otherwise unidentified, and sought evidence for progressive chorea, progressive cognitive and/or behavioral dysfunction, and family history compatible with autosomal-dominant inheritance with onset of symptoms in the period between january , , and december , , while the patient lived in the geographic boundaries of olmsted county. we found males and females who met these criteria. average annual incidence rate (age/sex adjusted to us white population) for hd for this -year period was . cases/ year/ , population. we also estimated prevalence by taking account of in-migration, out-migration, and deaths. the agelsex adjusted ( ) prevalence for - - was . , and for - - it was . / , . the small number of cases caused the instability of the prevalence rates, but our rates are similar to rates reported in other populations. alton e . btyant, , l. breeden hollis, john a. hamjian, john d. wooten, ill, and francis . walker, nc we described patients with unusual episodic movement disorders and normal diagnostic work-ups: a -year-old woman who had recurrent episodes of tonic jaw deviation and forced right-eye closure; a -year-old woman who developed unexplained pain and subsequent spells of tonic inversion of the left leg; a -year-old man who presented with a bizarre episodic right-arm tremor; and a -year-old woman who experienced intermittent abdominal undulations. examination of the affected body part provoked or enhanced symptoms in all patients. using suggestion and placebo activation in the form of a medicated patch, intravenous saline, or cervical massage, we first induced and then aborted typical episodes of their abnormal movements. postinduction discussions of the procedure led to a marked reduction in the frequency of attacks in patients. activation procedures are useful in diagnosing psychogenic disorders because they demonstrate that situational, not medical, factors govern the expression of the abnormal behavior. we speculate that patients who are refractory to simple suggestion may respond to induction because it offers the potential of validating their symptoms. as in the case of psychogenic respiratory distress or pseudoseizures, positive induction can assist in counseling and symptom control. had alzheimer's disease with parkinsonism (adp), had essential tremor (et), had cerebellar tremor in multiple sclerosis (ms), and had tardive dyskinesia (td). clozapine was used either to treat psychosis ( pd, adp, dys, td) or tremor ( pd, et, ms). two pd patients were retrospective analysis of patients counted twice, who was treated for psychosis and then tremor and who was treated on separate occasions for psychosis with different responses. all dys patients improved, with complete resolution of their dystonia on changing antipsychotic drugs. the patients with et ( mg) and ms ( mg) improved mildly but sedation and clumsiness caused drug discontinuation in the ms patient. one adp patient ( . mg) responded well and the other became sedated and confused ( mg). the p d responses for psychosis at a dose range of . to mg daily were good ( ), very good ( ), and excellent ( ), whereas were intolerant. pd tremor responses were good ( , very good ( ), excellent ( ), and poor ( ) at doses of . to mg daily. one patient died of unrelated causes shortly after initiation of the drug. adverse effects included sedation, weight gain, hypersalivation, fainting, clumsiness, transient granulocytopenia, and "spasms" necessitating discontinuation in patients ( pd, l td, and l ms). tourette's syndrome and attention-deficit disorder patients s. m. silverstein, p. g. coma, d. palumbo, l. west, and r. kurlan, rochester, n y impaired attention is a common comorbid behavioral feature of tourette's syndrome (ts) and a key clinical feature of attention-deficit hyperactivity disorder (adhd). however, the pattern of attentional impairments reported in adhd has not been observed in ts. we therefore compared ts patients ( male, female; mean age ? yr), adhd patients ( male, female; * yr), and normal controls ( male, female; ? yr) on specific neuropsychological (np) and computer-administered tasks of attentional ability. adhd, but not ts, subjects performed significantly worse than controls on the n p tasks (digit symbol, perceptual speed) and had a trend toward poorer performance on a computerized measure of attention. however, both the adhd and ts groups had significantly greater test performance variability on some, but not all, tasks and had more subjects with deviant scores. among ts patients, higher scores on an obsessive-compulsive disorder (ocd) inventory and a greater number of adhd symptoms correlated significantly with poorer performance on the attentional tasks. moreover, ts patients with observed tics during testing had greater attentional impairment than those without tics. these results suggest that: ( ) many adult ts patients do not have impaired attention; ( ) attentional impairment in ts differs from that observed in adhd; and ( ) attentional impairment in ts is associated with the full neurobehavioral spectrum of ts (i.e., tics, ocd, and adhd). frank r. sharp, cathleen miller, thomas rando, and steven greenberg, san francisco and palo alto, c a six patients are described with choreoathetoid movements and marked proprioceptive sensory loss. one patient had a traumatic injury to the right parietal cortex that produced severe proprioceptive sensory loss and choreoathetosis in the left arm. another patient had a left thalamic infarction that resulted in profound proprioceptive sensory loss and chorea on the right side of the body. two patients had cervical spinal cord disease, proprioceptive sensory loss, and diffuse choreoathetosis. another patient had dorsal root ganglionitis associ-a hypothesis program and abstracts, american neurological association ated with small-cell lung carcinoma that produced diffuse loss of all sensory modalities and chorea. the last patient had an ulnar sensory neuropathy and choreic movements of the fifth finger. lesions anywhere along the pathway that transmits limb proprioception may cause pseudochoreoathetosis. furthermore, choreoathetosis without sensory loss caused by focal lesions of striatum may occur because of disruption of cortical proprioceptive inputs to striatum-perhaps explaining why most focal lesions of striatum do not produce chorea. sporadic inclusion-body myositis (s-ibm) and autosomalrecessive hereditary inclusion-bod y myositis (h-ibm) are of unknown cause and pathogenesis. in both there are muscle fibers with rimmed vacuoles containing to -nm cytoplasmic tubulofilaments (ctfs) and denervation atrophy; in s-ibm, but not h-ibm, there is a varying degree of inflammation. vacuolated fibers contain ubiquitinated inclusions (askanas ) and congo-red positivity indicating amyloid (mendell ). because immunoreactive p-amyloid precursor protein (app) and p-amyloid protein (p-ap) are constituents of ubiquitinated senile plaques in alzheimer's disease (ad) brain, we studied immunolocalization of app and p-ap fibers in ibm muscle using antibodies against: ( ) non-p-ap fragments of app, viz. (a) c-terminus (residue - courtesy d. selkoe) and (b) n-terminus (residue - courtesy b. frangione and d. levartovsky); ( ) p-ap (sequence - , courtesy g. glenner, and sequence - courtesy d. selkoe); ( ) ub (chemicon). in of ibm patients, including one h-ibm, % of the vacuolated muscle fibers contained large or several small app and p-ap immunoreactive (ir) inclusions, which by double-labeling fluorescence were closely colocalized with each other and with ub-ir. none of control muscle biopsy specimens (including polymyositis) contained app-ir, p-ap-ir, or ub-ir inclusions characteristic of ibm. control experiments utilizing omitted, replaced, or absorbed primary antisera were negative. p-ap, a product of proteolytic cleavage of app, is receiving attention regarding the pathogenesis of ad. our study provides ( ) the first demonstration of app and p-ap accumulations in abnormal human muscle, and ( ) raises the possibility that in ibm muscle and ad brain rhey may form from similar cellular events. jeffrrey d. rothstein, lin jin, and ralph kuncl, baltimore, m d the pathogenesis of motor neuron death in amyotrophic lateral sclerosis (als) is unknown. accumulating evidence suggests that the disease is characterized neurochemically by a derangement in the control of neurotransmitter glutamate metabolism: csf levels of glutamate and aspartate are ele-of motor neuron degeneration vated and their high-affinity transporter is defective in brain and spinal cord. inefficient glutamate transport, and subsequent chronic increase in extracellular glutamate, could be responsible for selective motor neuron death. to test the hypothesis that chronic defects in glutamate uptake can produce motor neuron toxicity, we developed a tissue culture model employing organotypic rat spinal cord maintained under conditions of chronic glutamate uptake inhibition. slices ( pm) of lumbar spinal cord from -to -day-old rat pups were cultured on millicell membranes. chronic uptake inhibition was produced by culturing tissue in the presence of threohydroxyaspartate (tha) or pyrrolidine-dicarboxylic acid, both known to be specific inhibitors of glutamate transport. tha produced chronic elevation of glutamate in the medium and produced motor neuron toxicity after to days in culture using pm tha, and after days using pm tha, as determined by assay of tissue choline acetyltransferase (chat) activity and by histological analysis of -micron plastic sections. motor neuron toxicity was completely blocked by the non-n-methybaspartate (nmda) antagonists cnqx or nbqx, but not by the nmda antagonist mk- . this model demonstrates that the chronic loss of glutamate transport in als can produce motor neuron degeneration and that motor neurons appear to be susceptible to non-nmda-mediated glutamate toxicity. guillain last year, we described a distinct acute paralytic syndrome in children and young adults from northern china and differentiated it from guillain-barre syndrome (gbs) by epidemiological, clinical, and nerve conduction (nc) features. to distinguish chinese paralytic syndrome (cps) from gbs more clearly, we measured nc in cps patients (mean yr, range . - yr) and in gbs patients from johns hopkins (mean yr, range - yr). sensory nc was normal in all (n = ) but nerve of cps patients, whereas sensory nc was frequently abnormal in gbs patients: median nerve, %; ulnar nerve, %; and sural nerve, %. motor n c also differed between the groups. in all nerves, distal latency (dl) was significantly longer in gbs than in cps. for example, in the median nerve, mean dl was . ms (se ) in gbs and . ms ( . ) in cps ( p < . ). motor conduction velocity was significantly reduced in gbs median and ulnar nerves compared with cps nerves. f-wave latency was significantly longer in gbs median nerves than in cps nerves. these data support the distinction both clinically and electrodiagnostically between cps and north american gbs. the use of n c may be especially important in field epidemiological studies in separating the disorders. clinical manifestations and gene analysis of the first japanese kindred yoshihide sunada, teruo shimizu, lchiro kanazawa, and toru mannen, tokyo, japan familial amyloidotic polyneuropathy type iv (fap iv) has been clustered in the finnish population and only a few cases have been reported from the netherlands. denmark, and united states. we describe the first japanese family with fap iv. the family originates from nagano prefecture, a mountainous district in the middle part of japan, and has no relationship to the finnish population. this family has members in generations, and individuals are affected with slowly progressive cranial neuropathy and corneal lattice dystrophy. the genetic trait is autosomal-dominant. polarizing microscopy and immunohistochemistry show abundant amyloid deposits reactive to an anti-gelsolin monoclonal antibody. direct sequence analysis of a dna fragment spanning codon of the plasmagelsolin cdna from the propositus, and restriction analysis using a modified pcr from other family members demonstrate a single base substitution, g to a at the first base of codon , which is identical to the mutation of finnish fap iv. this suggests that the mutation causes the fap iv phenotype regardless of ethnic background. gene expression focal puncture injury has been used as a model to study degenerative and regenerative responses of skeletal muscle. previous studies have demonstrated the ultrastructural and metabolic effects of muscle injury. however, the early genomic response to focal injury is presently unknown. we asked whether the immediate early genes (iegs) or early response genes-~$ , c-jun, nur , and junb-are responsive to muscle injury. these iegs encode transcription factors and are expressed rapidly after cell-surface stimulation. we have previously shown that surgical denervation and neural stimulation of muscle induced differential patterns of ieg expression. in this study, we produced injury of mouse gastrocnemius muscle by injection of c . of normal saline. we used the contralateral (uninjected) muscle as a control and examined the milna levels of each of these iegs. we found that ~$ and junb levels were increased at and hours and returned to basal levels by hours. in contrast, mrna levels of nur and cjun remained unchanged. this pattern of ieg response is distinct from that seen after muscle stimulation or denervation. the selectivity of this pattern suggests that ieg expression may play a role in the response of muscle to injury. amyotrophic lateral sclerosis (als) is a degenerative disease that leads to the restricted loss of motor neurons (mn). the reason for the selective death of mn remains unknown. we hypothesize that mn-enriched or mn-specific genes are important for normal m n function and that their disturbance may play a role in the pathogenesis of als. we have produced clonal hybrid cells derived from embryonic and neonatal spinal cord m n for the study of m n gene properties. some of these hybrid mn clones express traits typical of mn, such as high levels of choline acetyltransferase enzyme activity and message, glycine receptor message, and neurofilament and neural cell adhesion molecule proteins. we are using molecular techniques to identify novel mn-enriched or mn-specific genes in these cells. with this strategy, we have identified several cdna clones preferentially expressed in mn hybrid cells but not in the parental neuroblastoma cells by differential hybridization of an embryonic mn hybrid cdna phage library. we are extending these observations by performing subtraction hybridization experiments. these results suggest that mn-enriched or mn-specific genes can be identified, and may lead to a greater understanding of the etiology of als. there is a syndrome of slowly progressive, mid-adult-onset fasciculating progressive muscular atrophy (pma) affecting upper more than lower limbs, without bulbar or corticospinal signs, more often in males, associated with igm monoclonal gammopathy, and no nerve conduction block. two such men, ages (a) years and (b) years, duration and and one-half years, csf protein and , had failed to achieve sustained improvement with: prednisone, cyclophosphamide, total-body irradiation, and multiple lymphoplasmaphereses in a; and interferon alpha a in b. intravenous immunoglobulin (ivig), . gm/kg/day, has provided dramatic benefit, sustained and increasing for > and > months to date. (there is a continuing base of depotestosterone, mg weekly, which initially alone provided very minimal improvement.) strength increase was evident at and days after the first course of daily ivig infusions. it further increased for to and one-half weeks after treatment, and then began to diminish. repeat -day treatment weeks after the first course resulted in summated improvement, now sustained and enhanced by an average of treatment per week. quantitated strength testing by a blinded observer has shown a -fold to >loo-fold gradually increasing muscle function in all limbs. patient a regained the ability to feed himself, get out of a chair, walk unaided, and go up steps; quantitated hip flexors increased -and -fold. patient b regained the ability to feed himself, take care of personal toilet needs, walk securely, and drive miles; quantitated hip flexors increased -fold, and biceps flexions increased from with no weight to > reps while holding -pound weights. bukhara jews: a new cluster with typical oculopharyngeal muscular dystrophy (opmd) is a rare, late-onset myopathy with autosomal-dominant inheritance. its ultrastructural hallmark is the finding in muscle fibers of intranuclear tubular filaments of . -nm outer diameter. most opmd cases were described among french canadians; in france, the homeland of their ancestors, the prevalence is / , (brunet et al, ) . in israel's central area live approximately , jews who have immigrated from the bukhara and samarkand regions in uzbekistan. they represent a homogeneous ethnic group with its own language and community life. among them we have identified opmd in families ( affected individuals). the inheritance, clinical, electrophysiological, and histological features of these pa-tients are similar to those described in other pdts of the world, with typical intranuclear inclusions seen on electron microscopy. the minimal estimated prevalence of opmd in this population is approximately : . this cluster of opmd among bukhara jews is the second largest in the world. because many bukharian families are large, they may be suitable for linkage genetic studies. human muscle during ontogenesis e . scarpini, g. conti, p. l. baron, and g. myoblast transfer has been proposed recently as a possible therapy for duchenne muscular dystrophy patients. because immune rejection can represent a major problem in myoblast implantation, immunological characteristics of human muscle should be investigated. previous studies showed that human muscle cells cultured in vitro can constitutively express human lymphocyte antigen (hla) class i, but not hla class . furthermore, human y-interferon induces the surface expression of hla class i on mononuclear myoblasts, but not on multinucleated myotubes. however, whether the cells produce and present the antigen by themselves or take this material from the environment, where it could be released by infiltrative cells, is not yet clear. in this study, we analyzed hla molecules at the protein level by immunocytochemistry with monoclonal antibodies against different hla-dr epitopes and hla-abc molecules on frozen serial sections of human muscle during development and at the adult stage. human muscle infiltration by macrophages and monocytesmacrophages also were studied with m and leum specific monoclonal antibodies at the same stages of development. our results show that during muscle development and maturation, hla-dr and hla-abc antibodies do not label muscle fibers but some m -and leum -positive cells within the muscle. these data can be useful to understand the role of infiltrating monocytes-macrophages in the muscle immune response. mounting evidence suggests that excitotoxicity, mediated via the glutamate receptor, is involved in the pathogenesis of amyotrophic lateral sclerosis (als), as well as in other neurological diseases. we therefore initiated an open label, phasen i trial of highdose dextromethorphan (dm), a noncompetitive, selective n-methybaspartate antagonist, in als. patients began with mg/kg/day, divided into doses, and incrementally escalated their medication to mg/kg/day or their maximum tolerable dose. thirteen patients, all extensive metabolizers of dm, were enrolled. total daily doses ranged from . to mg/kg. major side effects were lightheadedness ( ), slurred speech ( ), and fatigue ( ). no biochemical, hematological, or neuropsychiatric abnormalities occurred after up to months of maximal therapy, except for depression in patient. plasma kinetics of dextrorphan (dt) (the major metabolite of dm) were studied after an acute oral dose of . mg/kg dm. median elimination halflife was . hours. plasma dt concentration peaked at a median of hours, with a median cmax of . pm. median amyotrophic lateral sclerosis cerebrospinal fluid/plasma dt ratio was . . this study demonstrates the feasibility of long-term, high-dose dm therapy. we are now conducting a phase i study of highdose dm in als, designed to assess its efficacy. polyneuropathy: a chronic inflammatory demyelinating polyradiculoneuropathy variant? d. cros, k. h. chiappa, s. patel, and s. gominak, boston, ma, we describe patients ( men, woman) with a pure, adultonset sensory neuropathy. the course was chronic in all cases. three patients had a relapsing-remitting course over to years with several attacks every year; the onset was gradual and followed by a plateau in the fourth patient. all patients had positive and negative sensory symptoms, and had positive motor symptoms (fasciculations). in all patients, muscle power was normal at the time of peak deficit. all were areflexic and had large fiber sensory deficits, and patients had sensory ataxia. three patients had elevated csf protein, whereas the csf was normal in patient. mri demonstrated marked thickening of the lumbosacral spinal roots in patient. motor conduction studies were normal in all patients, and mild f-response abnormalities were noted in . neurophysiological investigations of the sensory pathways were abnormal in all. three patients had several studies over a -year period. sensory nerve action potentials were unobtainable in patients, and normal in the others. median and tibial somatosensory-evoked potentials showed conduction slowing consistent with demyelinating lesions affecting the peripheral sensory pathways, either globally or focally in the proximal segments. two patients appeared to respond to plasma exchange or intravenous immunoglobulin therapy, or both. glial fibrillary acidic protein cells in experimental motoneuron disease raul n . mandler, pam c. allgood, and james a. wallace, albuquerque, nm neuronal degeneration in human and animal motoneuron disease has been emphasized, but glial phenotype alterations have not been studied as extensively. we carried out a developmental and topographic study of astrocyte expression in the wobbler mouse model of motoneuron disease. wobbler mice and normal littermates were studied at , , , and weeks of postnatal development. anesthetized animals were perfused intracardially with paraformaldehyde. spinal cords were dissected and landmarks were identified carefully for systematic study. sections were stained with monoclonal antibodies against glial fibrillary acidic protein (gfap) neurofilament and neuron-specific enolase. cell quantitation was done with video-enhancing microscopy. in symptomatic animals, marked increases in gfap staining were found in rostral and caudal spinal cord areas. quantitation studies revealed a to -fold increase in gfap+ cells in the wobbler. we conclude that gfap+ cells are markedly increased in the wobbler mouse at cervical, thoracic, and lumbar areas. this cell may also be relevant in motoneuron disease pathogenesis. ( indirect evidence suggests that polio virus may persist in the human cns years after initial infection and may be a cause for the post-polio syndrome. to evaluate whether the polio virus genome can be detected in the cns of patients with previous polio infection, we identified patients who had died with autopsy findings and clinical history consistent with poliomyelitis. rna was extracted from paraffin-embedded sections of brain or spinal cord and subjected to reverse transcription followed by dna amplification by polymerase chain reaction (rt-pcr) using primers specific for heat shock protein (hsp ) and a conserved region of the polio viruses. hsp mrna could be detected in all specimens, indicating that amplifiable rna had been isolated. in no specimens could polio virus rna be detected. this study suggests that polio virus does not persist in the human cns in quantities detectable by the sensitive pcr method. with cmt type , seen at mayo clinic rochester between and , for the frequency of selective calf weakness in cmt type , the form of cmt most similar clinically to distal sma. anterior compartment weakness exceeded calf weakness in patients ( %); anterior and posterior involvement was equal in ( %). calfweakness exceeded anterior compartment weakness in patient ( %). selective calf weakness in distal sma thus helps distinguish this disorder from cmt type , and similarly from distal sma with weakness resembling cmt, in that we are unaware of the distributions in distal sma occurring in the same family. given the possibility of genetic heterogeneity, linkage studies of distal sma probably should include patient selection criteria such that the distribution of leg muscle weakness is homogeneous. p . conjugal amyotrophic lateral sclerosis: amyotrophic lateral sclerosis (als) is a sporadic neurodegenerative disorder of unknown cause. unusual cases may provide etiologic clues. we report a married couple, both of clue to etiology? whom developed als in year. the couple grew up in southeastern pennsylvania and attended the same schools. they married after high school and have healthy children. in september , a -year-old woman noted right-hand weakness and associated fasciculations that progressed to the entire right upper extremity. by january , the lower extremities were asymmetrically weak and fasciculating. she then developed left-arm weakness, d ysarthria, dysphagia, and emotional incontinence. she had hyperreflexia and bilateral extensor plantar responses. then, in may , her husband, aged , noted difficulty whistling, which progressed to frank dysarthria. later, he developed dysphagia, emotional incontinence, and weakness, wasting, and fasciculations in the upper extremities. hyperactive gag, jaw, and limb reflexes were present. in both, electrodiagnostic testing revealed widespread evidence of lower motor neuron degeneration. numerous laboratory tests were normal. although these cases may represent a chance association, the development of als in a young husband and wife suggests a possible environmental cause. the authors welcome suggestions about these cases from the neurological community. conduction block in demyelinating neuropathies usually is assessed from differences in the sizes of surface-recorded maximum m-potentials evoked by supramaximal stimulation at successively more proximal sites along the course of motor nerves. as the maximum m-potential is comprised of many bitriphasic surface-recorded motor unit action potentials (muaps), differences in the relative latencies between muaps may lead to phase cancellations, reducing the m-potential size and rendering any quantitative assessment of the extent of conduction block relative to phase cancellation difficult. cooling a muscle (not the nerve), however, by as much as °c increases the negative peak durations of muaps by as much as to times and moves the point at which maximum phase cancellation might occur to some theoretical point well proximal to the spinal roots. in cases of guillain-barre syndrome (gbs) studied to date, cooling produced little change in percent reductions in m-potential negative peak areas between successively more proximal sites of stimulation. this finding suggests that "true" conduction block rather than interpotential phase cancellation best explains reductions in m-potential size at successively more proximal sites of stimulation in gbs. associated with trimethoprim-sul famethoxazole rare cases of primarily motor polyneuropathy have been associated with the use of sulfonamides. the incidence of polyneuropathy has diminished substantially with the abandonment of earlier methylated compounds. we describe patients who developed allergic phenomena, including a skin rash and debilitating, painful sensory and autonomic polyneuropathy within days of receiving trimethoprimsulfamethoxazole. in patient, examination revealed resting tachycardia, marked blood pressure orthostasis and near-program and abstracts, american neurological association syncope, hyporeffexia, urinary incontinence, and reduced sensation distally in the lower extremities. his cerebrospinal fluid was acellular with a protein of mg/dl. the other patient showed a resting tachycardia, sluggish pupils, reduced distal vibration perception, and hyperpathia of hands and feet. conventional nerve conduction studies demonstrated normal motor results in both patients, absent or reduced sensory amplitudes in the first patient, and normal sensory results in the second. autonomic studies identified profound abnormalities in testing of sympathetic skin potentials, sinus arrhythmia, and valsalva's ratio. in both cases, nerve biopsy was not performed for fear of exacerbating the patient's hyperpathia. subsequent hemodynamic and electrophysiological testing showed improvement in autonomic function, paralleling the patients' clinical amelioration. although uncommon, a painful, sensory and autonomic, partially reversible polyneuropathy may develop after the use of trimethoprim-sulfamethoxazole. the remote effects of botulinum a toxin injections into vocalis muscles for treatment of focal laryngeal dystonia were investigated using single-fiber electromyography (sfemg). botulinum a toxin injections have been proven effective therapy for various dystonic disorders including focal laryngeal dystonia, blepharospasm, and torticollis. previous sfemg studies have demonstrated remote effects of the toxin in noninjected muscles after treatment for both blepharospasm and torticollis. these effects include an increase in fiber density, mean jitter (mcd), and percentage of fiber pairs with increased jitter. other researchers have postulated that the distant effects of this toxin may be related in part to the dose of botulinum toxin injected. to investigate this hypothesis we have studied patients treated for focal laryngeal dystonia because the amounts of toxin required are / th to / ooth of the doses used to treat other dystonias. using electromyographic (emg) guidance, bilateral injections of . or . mouse units of botulinum a toxin were injected into each vocalis muscle of patients. each patient had significant improvement in phonotory function within hours after injections and have been followed serially (usually within weeks and again at mo) after injections, with sfemg recordings of the left extensor digitorum communis and sternocleidomastoid muscles. five patients have had more than series of injections over the months since we began this study. sfemg studies have revealed no significant change in the fiber density, mean mcd, or percent of fiber pairs with normal jitter in either muscle. in conclusion, our studies support the hypothesis that the presence of remote effects of botulinum toxin may be related, in part, to the amount of toxin used. the c bl/ / a mouse exhibits the remarkable characteristic of prolonged survival of axons separated from their cell bodies (slow wallerian degeneration). previous work has demonstrated that the axon itself is responsible for the phenotype of prolonged survival. we investigated whether the lack of rapid axonal degeneration after axotomy in this substrain is due to an inability to break down cytoskeletal components, a process that is normally accomplished by activation of intrinsic calcium proteases. segments of desheathed sciatic nerves from normal and ola mice were incubated for hours under conditions that disrupt the axolemma (freeze/ thaw or in % triton x-loo), allowing external calcium free access to axoplasm. nerves were analyzed by western blot for neurofilament (nf) proteins and by electron microscopy. in high-calcium media ( mm caci,), nf immunoreactivity was lost and axoplasm was reduced to watery debris in both substrains, whereas in egta-buffered media, axoplasm was preserved. these results demonstrate that calcium-activated proteases are present and can be activated in ola nerves. the defect in these mice that allows for prolonged survival of transected axons is likely in the mechanism for calcium entry into the distal stump. the mechanism by which the analogue of adrenocorticotrophic hormone, acta - , prevents cisplatinum (cp) neurotoxicity is unknown. murine n e. neuroblastoma cells and neural crest-derived, squirrel fish erythrophore cells tuesday, have similar vesicular transport mechanisms to human neural cells. they were used to study the effects of cp and acth , on cellular transport. differentiated n e. cells were treated hour prior to observation with serum-free media (sfm, control); sfm/cp pg/ml; or sfm/cp pg/ml and ng/ml acth -,. organelle transport was studied ( neurites and - organelles per condition) using computer-enhanced video microscopy. mean fast anterograde ( . k . pmsec-' vs . * . pmsec-') and retrograde ( . . pmsec-' vs . +- . pmsec-') transport were decreased in cp-treated compared to control cells ( p < . ). in cp/acth ,-treated cells, mean anterograde ( . +_ . pmsec-') and retrograde ( . . pmsec-') velocities were greater than in cp cells ( p < . ). velocities in control and cp/acth , cells were not statistically different. erythrophore pigment granule transport was observed in a blinded study, using similar techniques. mean aggregation velocity was greater in control ( . k . msec-') and cp/acth , ( . f . msec-')-treated cells compared to cp ( . * . msec-') cells ( p < . ). incubation with cp for or hours affected velocities equally, but acute exposure was more easily reversed by control or acth,, containing media. there is striking inhibition by cp in cross-species models of organelle transport. this can be prevented by acth ,. erythrophores allow future study of individual transport components. neurotrophin to investigate signal transduction pathways involved in neurite growth, the cytoplasmic regions of p sngfr, the common neurotrophin receptor monomer, were searched for a motif analogous to the predicted secondary structure of the tetradecapeptide mastoparan. potential sequences were modeled using a semi-empirical molecular mechanical force field approach. the sequence rat ~ ~~~ - represents a highly conserved amphiphilic domain predicted to be involved in neurotrophin signal transduction via g-protein mechanisms. to test this prediction, peptides containing sequences homologous to p ngfr - were examined for effects on trophic factor-induced survival/differentiation responses of rat pc pheochromocytoma cells, chick embryo drg neurons, and chick embryo ciliary neurons. a peptide identical to ~ ~~~ - accelerated the neurite growth response to nerve growth factor (ngf) of pc cells and drg neurons in a time frame that paralleled uptake into cells, but mastoparan did not influence ngf-mediated neurite growth. millimolar mg+ + and benzalkonium chloride, known to block the actions of mastoparan, blocked the effect of the peptide on ngf-mediated neurite growth by pc cells. peptides mutated to alter cationic amino acid relationships or amphiphilicity were less effective than the peptide in accelerating ngf-mediated neurite growth. these observations complement and extend evidence suggesting a pivotal role of ~ ~~~ in ngf-mediated signal transduction. these studies complement and extend evidence suggesting a pivotal role of p sngfr in neurotrophin signal transduction and evidence that activation of intracellular signalling processes involving specific g-protein mechanisms are involved in neurotrophin-mediated neurite growth. crushing the hypoglossal nerve causes hypoglossal motor neurons to decrease expression of choline acetyltransferase (chat) and begin expressing p ngfr, the low-affinity ngf receptor. these changes are evident within days after the injury and continue for several weeks. inhibition of axonal transport by vincristine applied to uninjured nerves causes loss of chat expression without induction of ~ ~~" . we sought to determine if topical vincristine would alter p sngf' expression after nerve injury. hypoglossal nerves were surgically exposed unilaterally in anesthetized rats and crushed. one week later, rats were reanesthetized and the same nerves were re-exposed. vincristine or saline was applied at the crush sites by soaking a strip of cotronoid wrapped around the nerves. one week later, rats were anesthetized and perfused with aldehydes. frozen sections from the brainstems were stained by indirect immunoperoxidase to demonstrate chat and ~ ~~~' . saline-treated controls showed decreased chat and abundant ~ ~~" in hypoglossal motor neurons ipsilateral to the crush injury. vincristine-treated animals showed no chat and no p tngf'. we interpret these results as indicating that a signal originating from the injury site maintains ~ ~~" expression after nerve injury. catecholamines have been reported to be toxic to embryonic-derived rat neurons and glia via the formation of reactive oxygen species (rosenberg, ) . we tried to determine whether oligodendrocytes (ol) from adult -month-old rat brain are similarly susceptible. toxicity to ol was examined using light microscopy and galactocerebroside immunohistochemistry where the relative number of surviving ol and their extent of process formation were graded. five days of exposure to norepinephrine (ne) and epinephrine (epi) at and fm produced significant toxicity ( p < . , analysis of variance [anova)) to adult rat ol; this toxicity was evident by hours of exposure. treatment with catalase ( p,g/ml), a free-radical scavenger enzyme, completely prevented the toxicity of catecholamines. to ascertain whether astrocytes, which have free-radical scavenging capacity, could prevent the catecholamine-induced injury to ol, rat ol were seeded on neonatal rat astrocytes. under such conditions, the toxicity of n e and epi was reduced significantly ( p < . , anova). these findings suggest that impairment of this protective function of astrocytes may render ol and its myelin membrane susceptible to free-radical-mediated damage. lyme neuroborreliosis is an increasingly prevalent disorder, but the diagnosis generally has been indirect. thus, the pres-ence of other manifestations of the infection, consistent findings on neurological exam or lumbar puncture, or presence of csf antibody have been used rather than direct isolation or identification of the organism from the csf. we have previously developed polymerase chain reaction with hybridization (pcr/h) to identify borrelia burgdorferi in the blood and organs of infected mice, and found that the assay was equivalent or, in some cases, preferable to culture (ann neurol ; : ) . the assay used for primers oligos derived from a sequence of genomic b. burgdovfri d n a expressed on a plasmid by rosa and schwan. a two-stage nested pcr was performed on csf samples in which the d n a was isolated in a variety of ways. pcr products were subsequently hybridized with a digoxigenin-labeled internal probe by slotblot hybridization. the sensitivity of the assay was excellent, being mg), with higher single doses of taxol(> mg/m ), or with a preexisting neuropathy. we conclude that sensorimotor neuropathy and myopathy are dose-limiting neurotoxicities of combined cisplatin and taxol use, now that neutropenia can be controlled with neuropathy and myopathy g-csf. central nervous system lymphoma casilda balmacedz and lisa deangelis, new york, ny ally periventricular and may seed the csf by direct growth through the ependyma. we reviewed the csf profile of non-acquired immunodeficiency syndrome (aids) patients (pts) with pcnsl. all pts had lumbar puncture (lp) and had multiple samples from an ommaya reservoir. definite lm involvement was identified with a positive csf cytology, lymphomatous lm infiltration on a surgical specimen, or mri with gadolinium showing lm tumor. probable lm lymphoma was diagnosed in pts with suspicious or atypical csf cytology. there were women and men with a median age of (range - yr). at diagnosis, mean white blood cell count was /mm (range - , ); mean lumbar csf protein was mgldl (range - , ); and mean ventricular csf protein was mgldl (range - ). glucose was always normal. nineteen of pts sampled had oligoclonal bands, and / had elevated pz microglobulin. at diagnosis ( %) had an abnormal csf cytology: positive, suspicious, and atypical. one pt had pathological infiltration of the lm and had lm tumor on spine mri for a total of ( %) pts with definite or probable lm lymphoma. in pts with abnormal cytology, the abnormality was found in ( %) lps and / ( %) of the ommaya and ventricular specimens. in pts the lumbar cytology was the only abnormal specimen despite multiple ventricular samples, and in only the ventricular csf was abnormal. thirty-six of ( %) pts developed recurrent tumor afrer treatment. forty-two percent ( ) of all patients with relapse had lm recurrence. lm recurrence was accompanied by brain recurrence in pts, systemic in , ocular in , both systemic and ocular in , and isolated in . at diagnosis / patients received treatment directed against the lm. of these, ( %) had meningeal recurrence whereas of the ( %) patients who did not receive this treatment had lm recurrence. lm involvement by pcnsl is frequent, may be missed on a single csf sample, and requires specific therapy at diagnosis. sixty-three solid cancer patients with a single brain metastasis were prospectively randomized for neurosurgery and radiotherapy combined (arm ) or radiotherapy alone (arm ). they were stratified for lung or nonlung cancer and for active versus stable or absent extracranial disease. world health organization performance status was . age, sex, performance status, and location of brain metastasis were divided evenly over both groups. one-month mortality was % in arm and % in arm . median survival of months after combination therapy was significantly better compared to months after irradiation alone ( p < . ). it made no difference whether they had lung or nonlung cancer. the largest difference between both treatment arms was observed in patients with stable or absent extracranial disease ( vs mo, p < . ). when systemic disease activity was present, median survival was months irrespective of treatment arm. functional independent survival was to months shorter than overall survival and was significantly better for patients with stable extracranial disease after combined therapy. multivariate analysis showed that age was also an independent prognostic factor. patients older than years had a hazard ratio for dying of . (p. ). we will detail the type and pattern of neurological complications in t-cell non-hodgkin's lymphoma (nhl), and review how they differ from those associated with b-cell nhl, and the lymphomas in general. this study is the first step in a process to characterize these tumors to determine if special staging or cns prophylaxis are indicated in any of the subtypes of t-cell lymphoma. we recently have encountered women with breast cancer and an unusual sensorimotor neuropathy. the neuropathy was the major clinical problem. in women the initial symptom was severe itching, generalized and first localized to the involved breast and then generalized. all developed distal extremity numbness and burning that very slowly progressed proximally, and in became generalized. four complained of painful muscle cramps in the extremities ( ) and jaw ( ). all had mild extremity weakness, distal ( ) and proximal ( ) . three women developed symptoms up to months prior to cancer diagnosis, shortly after diagnosis, and years after diagnosis. four women had disease confined to the breast and regional lymph nodes, and had metastatic disease in remission. although annoying, symptoms were generally not disabling. three women stabilized or had slight improve-associated with breast cancer ment with cancer treatment, and continue to gradually progress while in cancer remission; required a cane to ambulate after years due to sensory ataxia. one who developed cancer relapse had concurrent neurological relapse. one woman treated with high-dose immunoglobulin did not improve. none had significant weight loss. laboratory abnormalities included elevated erythrocyte sedimentation rate ( - ) in , antinuclear antibody : in , csf with lymphocytic pleocytosis ( - white blood cellslmm) in / and elevated protein ( - mg/dl) in available. emgi ncv showed mild sensory-to-motor polyneuropathy in available. none had detectable antibodies against peripheral nerve or dorsal root ganglia. the etiology of sensorimotor neuropathy in these patients is unknown, but it may represent a distinct paraneoplastic syndrome that can herald the onset of, and parallel the course of breast cancer. our objective was to determine whether ceramide induces differentiation of anaplastic glioma cells. sphingomyelin hydrolysis resulting in ceramide production has been linked to differentiation of leukemia cells. t rat anaplastic glioma cells, seeded at x lo cells per well, were grown in serum-a glioma cell line program and abstracts, american neurological association free media. on day , cells were photographed, scored for processes longer than one cell body, and counted. c ceramide changed plump cells to flattened cells with many long processes: ceramide treatment increased the percentage of cells with processes from % (sd) to * % (n = , p < . ). control cells grew to . x lo cells/well . x lo cells; ceramide-treated cells grew to . x lo ? . x los (n = , p < . ). although one ceramide analog reproduced the c ceramide-associated changes, the optical isomer of this analog did not, demonstrating stereospecificity. cerarnide did not decrease cell viability by trypan blue. ceramide inhibits proliferation and induces process formation in a glioma cell line, causing it to assume a more differentiated phenotype. cerarnide or its analogs represent possible future therapeutic agents that would inhibit the growth and affect differentiation of anaplastic gliomas. [bashir, mod pathol ; ( ) : - )). this is similar to the pattern seen in ebv-infected human b cells and unlike the uniform latent infection seen in burkitt's lymphoma. we tested the hypothesis that long-term passaging of ebv-immortalized human b cells in immunodeficient mice leads to emergence of a uniform nonlytic pattern of ebv infection associated with appearance of the malignant profile. ebv-infected normal human b cells were serially passaged intracerebrally in severe combined immunodeficient cb mice ( x ' cells per mouse, mice per passage for a total of passages). frozen mouse brain sections from each passage were stained with vca antibody (ebv lytic cycle) and hybridized with biotinylated bamh -w sequence of ebv. all injected animals developed tumors as previously described (bashir, lab invest ; ( ): - ) . tumor cells continued to express vca and showed latent and lytic hybridization patterns with bamh,-w after passages despite exhibiting monoclonality (surface immunoglobulins) and random chromosomal changes. lytic infection of immortalized b cells with ebv is stable, resembling brain lymphomas in aids, and unlike the latent infection seen in burkitt's lymphoma. a previously healthy -year-old man developed diplopia and incapacitating, diffuse weakness over a period of weeks. examination showed a "one-and-a-half'' syndrome of horizontal gaze paresis, patchy severe weakness with atrophy and fasciculations, absent tendon reflexes in the legs and right biceps, and decreased vibration sense in the feet. csf contained a mild pleocytosis, elevated protein, and oligoclonal igg bands. electrophysiological testing indicated a generalized sensorimotor axonal neuropathy with diffuse denervation. small-cell lung carcinoma was diagnosed by bronchoscopy. prednisone produced mild subjective improvement. chemotherapy was begun but the patient developed fatal septicemia. serum was negative for anti-hu or anti-gm with paraneoplastic encephalomyeloneuritis antibodies. serum and csf contained high titers of igg antibodies reacting specifically with a protein antigen of approximately kd in immunoblots of human cerebral cortical neuronal nuclei or of human purkinje cells. this pattern of autoantibody reactivity was not present in sera from any of other patients with small-cell lung carcinoma, of whom had paraneoplastic encephalomyeloneuritis and anti-hu antibodies, nor was it present in many patients with other neurological disorders. the patient's serum has been used to probe a human cerebellum expression library and to isolate a cdna clone that is being characterized. acute encephalopathy is the problem in % of neurology consultations reported at mskcc. we studied patients ( prospectively and retrospectively) to determine clinical findings, causes, and outcome. fifty-five were women and were men, and the average age was years. all patients had cancer: lung ( %), gastrointestinal tract ( %), breast ( %), and others ( %), forty-two patients ( %) were delirious on admission and delirium developed an average of days later in %. encephalopathy occurred postoperatively in %. symptoms included confusion ( %), lethargy ( %), agitation ( %), hallucinations ( %), and seizures ( %). signs included deficits in attention ( %), memory ( %), language ( %), lateralizing signs ( %), and asterixis ( %). the average mini-mental status test (mms) score was ( = normal). a single cause for delirium was found in only % of patients with an average of etiologies per patient. metabolic abnormalities were found in % of patients, and were a primary cause in %; disseminated intravascular coagulation contributed to delirium in %. cns metastases were found in % and were a major cause of delirium in all. fifty percent of the patients had fever/ systemic infection, but sepsis was present in only %; only patient had cns infection. medication contributed to delirium in % but was a primary cause in only %. the -day mortality rate was % and delirium improved in % (average mms = ). patients with cancer have multiple, potentially treatable causes of delirium. delirium is associated with a high death rate, though patients generally improve. radiation therapy for brain tumors d. w. dodick, b. mokri, k. k. unni, g. m. miller, and e. g. shaw, rochester, m n osteosarcoma in a previously normal bone is a rare but recognized remote effect of radiation therapy. any bone in the field of radiation can be affected. involvement of cranial bones is exceedingly rare. we could identify only patients ( men and women) with postirradiation osteosarcoma of the calvarium seen at the mayo clinic over a -year period, from to . all had received radiation for brain tumor, osteosarcoma had appeared in the field of radiation in all, the interval from radiation therapy to the appearance of sarcoma ranged from to years, and diagnosis of sarcoma was confirmed histologically in all cases. the patients' age at the diagnosis of the brain tumor ranged from to years. the nature of the brain tumor was unverified in cases, was a low-grade ependymoma in the third case, and a pilocystic astrocytoma in the fourth case. one patient is still alive months after the diagnosis of the sarcoma. she received chemotherapy and subsequently underwent resection of the osteosarcoma. one patient died postoperatively after partial resection of the sarcoma. the other patients died months and months after the diagnosis of the osteosarcoma despite additional radiation therapy in the former and aggressive chemotherapy in the latter. element-la fusion gene as a potential marker of neural tumor differentiation lawrence recht, chiffon wu, and louis j. degennam, worcester, ma inducing cancers to differentiate into more benign differentiated tumors represents a novel oncological strategy. to establish a model that would permit assessment of this phenomenon at a molecular level, we created and have partially characterized a murine neuroblastoma line that has been stably transfected with a synthetic fusion gene containing the promoter element of the rodent synapsin i gene (synapsin i regulatory element isre)). in vivo, this promoter directs the neuron-specific expression of the synapsin i gene in normal adults. the gene also is expressed in varying amounts in neuronal tumors including neuroblastoma. in the synthetic fusion gene, the sre has been linked to the lacz gene that encodes bacterial p-galactosidase. a simple histochemical assay for p-galactosidase therefore provides a specific marker of the expression of the fusion gene. our preliminary experiments as of this writing have shown that it is possible to detect p-galactosidase activity in the transfected neuroblastoma cells both in vitro and in transplanted tumors. it appears possible therefore that this transfected neuroblastoma cell line can provide a useful model system with which to assess the effects of differentiation therapies. larger lesions (> cm ), and larger midline shifts (> mm). twenty-eight of ( %) patients with prior has had bt has compared to of ( %) patients without prior has. in patients, their bt h a was similar to their previous ha but was more frequent or severe. we conclude that has in bt patients are common but usually not severe. nausea, vomiting, an abnormal neurological examination, or a change in prior headaches warrant further investigation. cairncross and macdonald showed that procarbazine, lomustine, and vincristine (pcv) are effective for recurrent anaplastic oligodendrogliomas (ao) (ann neurol ; : - ) . pcv now has a major role in management of all forms of oligodendrogliomas ( ), but the biological basis for this response is unknown. to evaluate one subset of possibilities, we studied patients ( ao, ) with a ct method that permits measurement of blood-to-tissue transport (kj, tumor-to-blood transport (k ), and vascular volume (v,) (ann neurol ; : - ) . pcv was used to treat of the patients. k, (~ grr-' min-') values were highly variable for whole tumor, ranging from . to . (mean . k . ) with no difference between a and . k and v, were also highly variable. k, of tumor-free brain was . to . (mean . ? . ). in comparison to malignant astrocytomas, which have a mean k, in the range of . with some as high as . , a and appear to be much less permeable. this suggests that the efficacy of pcv may be due to factors other than capillary transport, such as tumor-cell sensitivity. frameless stereotactic localizer gene h. barnett, donald w. komos, and charles p . steiner, cleveland, oh extent of tumor resection has been shown to correlate with prognosis in malignant gliomas. although frame-based stereotactic techniques can provide information regarding tumor margin, they are often unwieldy and require expensive and elaborate computing systems. a frameless stereotactic neurosurgical localizing system was designed that overcomes these liabilities. this armless, frameless, stereotactic pointing device provides real-time three-dimensional localization information during operation. in addition to assisting in placement of a trephine craniotomy, it allows volumetric resection of the tumor with virtually complete excision of even large irregularly shaped tumors. mean error on localizing a point in space using this system has proven to be less than mm. a technical description of the system as well as surgical results are presented. to investigate the effect of age on response rate to chemotherapy and time to progression (ttp) and death ('itd) in patients with recurrent astrocytomas and malignant astrocytomas, we reviewed case records and scans of patients who received chemotherapy at the university of michigan with bischloroethylnitrosourea or procarbazine. three age groups were studied: ( ) < yr (n = ); ( ) - yr (n = ); ( ) > yr (n = ). tumors were grouped as grade r+ (recurrent grade plus grade , n = ) or grade (n = ). serial computed tomographic or magnetic resonance scans were analyzed in a blinded fashion and graded as progressive disease (pd), stable disease (sd), or partial response (pr, > % decrease in size). the pr rates for the age groups were %/ %/ % for grade r+ tumors ( p = . ) and %/ %/ % for grade tumors ( p = . ). median 'itp was weeks for grade r + and / weeks for grade . median ltd was / / weeks for grade r+ and / / weeks for grade . we conclude that age is an important prognostic factor with respect to likelihood of response to chemotherapy, duration of response, and survival irrespective of grade. cheryl p. harris and kurt a. jaeckle, salt lake city, ut intravascular malignant lymphomatosis (iml), a b-cell lymphoma confined to small venules and capillaries, often presents with neurological symptoms. this disease is uniformly fatal ( -month mean survival); no successful treatment has been identified. we observed marked reproducible neurological improvement after plasmapheresis in a -year-old woman with iml. presenting with a cauda equina syndrome, she progressed over year with neurological, hepatic, and hematological disease. persistent laboratory abnormalities included a high sedimentation rate ( mm/hr), coagulopathy, hemolytic anemia, and elevated liver enzymes. extensive evaluations for infectious, autoimmune, and neoplastic processes, including bone marrow examination, were inconclusive. because of neurological progression, empiric therapy with high-dose steroids followed by cyclophosphamide was initiated without response. plasmapheresis ( ml/kg in exchanges) effected resolution of encephalopathy and normalization of the coagulopathy and sedimentation rate. neurological progression recurred within weeks of pheresis; repetitive courses reproduced neurological response. finally, progressive dementia ensued, and a decision was made to cease pheresis; the patient died days later, months after presentation. autopsy disclosed diffuse intravascular cd- positive malignant lymphoma cells in small vessels of all organs. although the mechanism is unknown, the serendipitous discovery of response to plasmapheresis in this patient warrants further consideration. morphine is an effective analgesic in the rat after injection into a number of discrete brainstem regions, including the periaqueductal gray (pag), the locus coeruleus (lc), and the nucleus raphe magnus (nrm). early work with morphine gray and the nucleus raphe magnus established the existence of synergy between the brainstem and the spinal cord in rats. more recently, studies from our laboratory revealed synergy between two brainstem structures, the pag and the lc. in the current study, we explored the analgesic interactions between the pag and the nrm using indwelling cannulae. first, we established morphine dose-response curves and calculated the ed,, independently in the pag ( . pg) and the nrm ( . pg). we then simultaneously injected various morphine doses into both regions. injecting morphine at pg into either the pag or the nrm did not elevate tailflick latencies above baseline values. however, administered into both regions simultaneously, the -pg doses produced an % maximal response, corresponding to more than a threefold increase of baseline latencies. a fixed morphine dose of pg in the pag shifted the morphine dose-response curve fivefold in the nrm (ed,, . pg), whereas a fixed nrm dose of fg shifted morphine's dose-response in the pag approximately twofold. together, these results clearly show synergistic interactions for morphine between the pag and the nrm. the presence of synergistic interactions between brainstem nuclei as well as between the brainstem and the spinal cord underscores the complexity of opioid analgesic systems. p . the glutamate uptake inhibitor ~-trans- , -pyrrolidine dicarboxylate is neurotoxic in neonatal rat brain john d. e. barks and faye s. siloerstein, ann arbor, m i important evidence of the neurotoxicity of endogenous glutamate (glu) in mammalian brain was provided by the observation that dl-threo- -hydroxyaspartate, a high-affinity glutamate uptake (hagu) inhibitor, was neurotoxic in adult rodent striatum (j neurochem ; : ) ; however, the absence of neurotoxicity in neonatal brain was interpreted as evidence that immaturity of glutamatergic innervation limited the potential role of endogenous glu as a neurotoxin in the immature brain. yet, considerable data provide indirect support for the hypothesis that glu can be neurotoxic at this stage. to resolve this issue, we assessed the neurotoxicity of a novel, selective hagu inhibitor, ~-trans- , -pyrrolidine dicarboxylate (l-pdc) (j med chem ; : ), in postnatal day (pnd) rats (n = ). l-pdc (ph . ) was stereotaxically injected into right anterior striatum (str) ( nrnol, n = ) or through dorsal hippocampus into posterior str ( nmol, n = ; nmol, n = ). animals were killed days later, and neuropathology was assessed in cresyl violet-stained sections. after anterior injections, focal neuronal necrosis was evident in dorsal str; high-dose posterior injections caused prominent hippocampal lesions with pyramidal layer thinning and focal necrosis in dorsal thalamus, while nmol produced small foci of pyramidal cell loss. in both groups, focal cortical necrosis and callosal cysts were apparent adjacent to the injection track. l-pdc-induced brain injury provides direct support for the hypothesis that endogenous glu may be neurotoxic in the developing brain. (sax et al, ann neurol ; : a) . the signs and symptoms of of these patients lessened for to months. furthermore, a patient with a severe oral-lingual biting dyskinesia improved when taking doses up to milligrams per day for months. we noted no-significant adverse reactions, although patients had mild but labile elevations in sgop and sgpt. one patient receiving opioid analgesics for pain inadvertently failed to discontinue the naltrexone but noted no reduction in the pain-alleviating effects of the analgesic. although hyperkinesia, especially of midline functions, as well as quality of life improved for the hd patients, their cognitive deficits remained unaffected. these observations suggest that chronic naltrexone is a safe and effective agent to treat chorea, dysphagia, and oral dyskinesia in hd for periods longer than a year. furthermore, they indicate that naltrexone can be effective in ameliorating oral-lingual biting tardive dyskinesia. these findings support our previous hypothesis that endogenous opioids play a role in rhe modulation of the dopamine system in hyperkinetic stereotypic movement disorders. a. jon stoessl, elizabeth szczutkmuski, and hanna fydvszak, london, ontario, canada we previously have demonstrated (psychopharmacology ; : - ) that intraperitoneally (ip) administered cholecystokinin (cck)- s suppresses vacuous chewing mouth movements (vcms, a putative mode of tardive dyskinesia) in rats exposed to chronic neuroleptics. as cck is not thought to cross the blood-brain barrier in significant amounts, its site of action in this paradigm is unclear. other behavioral and neurochemical effects of ip cck are blocked by vagotomy. male sprague-dawley rats were administered fluphenazine decanoate (flu; mg/kg im) or its vehicle every weeks for approximately weeks. cck ( , , or ng intracerebroventricularly) had no effect on neuroleptic-induced vcms. another group of neuroleptic-treated rats was subjected to bilateral subdiaphragmatic vagotomy or a sham procedure. cck- s ( , , or pg/kg intraperitoneally) suppressed neuroleptic-induced vcms in shamoperated animals, which confirmed our previous results. in vagotomited animals, chronic flu failed to induce vcms and cck was without effect in vehicle-or neuroleptictreated animals. these data suggest that the effects of cck on flu-induced vcms may be mediated peripherally, and that vagal pathways may be important for generating this response. (supported by the ontario mental health foundation and the ontario ministry of health.) p . excitotoxic amino acids are not involved in dopaminergic neurotoxicity of m p t p eldad mehmed, jutta rosenthal, and avinoam reches, petah tiqva, tel aviv, and jerusalem, israel the dopaminergic (da) neurotoxicity of -methyl- phenyl- , , , -tetrahydropyridine (mptp) is mediated via its oxidation in cns to mpp + , which enters da neurons and poisons mitochondrial complex i. da neuronal damage induced by direct nigral mpp+ injection is prevented by pretreatment with n-methyl-d-aspartate receptor antagonists, which suggests that excitatory amino acids are involved in mptp toxicity. since local mpp + application may produce nonselective nigral damage, we examined whether excitotoxins have a role in toxicity of systemically administered mptp. c black mice were injected intraperitoneally, once, with mptp.hci( mg/kg) and decapitated days later. groups of animals underwent the following pretreatments: (i) decortication week prior to mftp; ( ) intracerebroventricular injections of the excitatory amino acid receptor antagonists -amino-phosphonoheptanoate and d-glutamyl-glycine; and ( ) intraperitoneal injections of the calcium channel antagonists nimodipine, diltiazem, and flunarizine minutes prior to mptp. mptp produced marked striatal da depletions. decortication, destroying glutamatergic corticostriatal projections, intracerebral amino acid receptor antagonists, and systemic calcium channel antagonists did not protect mice against mptp toxicity; mptp-induced striatal da decreases were similar to those given the neurotoxin alone. this study suggests that excitotoxins are not involved in the mechanism of mptp toxicity. scopolamine-induced cognitive deficits k . j . meador, m . e. allen, p. franke, e. e. moore, and d. w. loring, augusta, ga a unique neurophysiological role for thiamine in cholinergic systems has been suggested. total thiamine content in cholinergic nerve terminals is comparable to that of acetylcholine, and the phosphorylation state of thiamine changes with release of acetylcholine. thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. based on these observations, we investigated the effects of pharmacological doses of thiamine on the cognitive deficits induced by the anticholinergic scopolamine in healthy young adults using a randomized, double-blind, placebo-conrrolled, double crossover design. cognitive tests included the p eventrelated potential and free recall memory for a verbal paragraph. conditions included baseline (bl), thiamine gm by mouth and scopolamine . mg/kg intramuscularly (b + scop), and lactose by mouth and scopolamine (plac + scop). testing was performed hours post thiamine or placebo, and . hours post scopolamine. thiamine significantly reduced the adverse effects of scopolamine on p latency (f [i, = . , p . ) and percent recall memory ( f el, ) = . , p . ). means (+sd) and p latency (ms) were bl = ( ), b + scop = ( ), and plac neurol ; : - ) . we previously reported that cff improved in of ms patients ( %) given el- orally in divided daily doses ranging from . to . mg (stefoski et al, neurology ; : - . subsequent analysis revealed that in of the patients cff improvements and reversals followed in a phase-locked trend the rising and falling serum concentrations of el- , including patients whose changes remained below the % increase needed to qualify for the improved category. these results resemble the phase-locked effects of temperature on neurological function in ms. the cff changes, because they so closely reflect variations in serum concentration, suggest that el- tissue levels closely follow those in serum and that el- rapidly crosses the blood-brain barrier. efficacy of el- in ms is also predicted to have a close relationship to serum levels. p . development of a n internal standard detectable by proton and phosphorus- nmr and hplc w. e. klunk, k. panchalingam, r. j . mcclure, and j . w. pettegrnu, pittsburgh, pa comparison of quantitative results from different analytical techniques can prove difficult due to the peculiarities of the particular techniques and the lack of a common standard applicable to all of the techniques. recently, both in vivo and in vitro nuclear magnetic resonance (nmr) have been applied to the quantification of a large variety of metabolites. although nmr can be applied to the study of living tissue, the question arises of how this technique compares with more traditional techniques such as high-pressure liquid chromatography (hplc). although this question can be addressed partly by studying perchloric acid (pca) extracts, it is difficult to directly compare this in vitro nmr data with results from hplc. to address this question, we have developed an internal standard that can be quantified directly by in vitro phosphorus- nmr, proton nmr, and by -fluorenylmethyl chloroformate (fmoc) derivatization followed by separation by hplc. a variety of aminophosphonic acids were studied by 'p nmr, 'h nmr, and hplc. promising compounds were added to pca extracts of human brain. the optimal compound was found to be -aminopropylphosphonic acid (app, ho p-ch -ch,-ch -nh ). app is easily detectable by all techniques, falls well outside of the region of interest in phosphorus- nmr, and is well resolved by proton nmr at mhz. it is easily separable from the phosphomonoesters and phosphodiesters observable by hplc and from the amino acids that occur in brain in significant concentrations. app appears to be a useful internal standard in the study of phosphorus and amino acid metabolites by in vitro p nmr, 'h nmr, and hplc. theories of sentence comprehension hypothesize at least a grammatical component that establishes the relationship among words in a sentence, and a semantic component that determines the meanings of these words. we used positron emission tomography (pet) to quantify regional cerebral blood flow (rcbf) in neurologically intact subjects during their detection of a letter target, a grammatical target, or a semantic target in the same written sentences. a mixedmodel analysis of variance (anova) revealed significant main effects for region (f e , ) = . ; p < . ), condition (f , = . ;~ < . ), and a significant region times condition interaction ( f {go, = . ; p < . ), but there were no differences between individual subjects. subsequent anovas revealed increased rcbf in a unique set of brain regions during the subjects' response to a grammatical probe when compared to their response to a letter probe of the same sentences. a unique distribution of rcbf also distinguished response to the semantic probe from response to the grammatical probe and the letter probe. other brain regions apparently contributed to performance for several activation conditions. these findings support the hypothesized dissociation of specific linguistic components based on their unique cerebral topographical representation, and that a distributed network of brain regions subserves sentence comprehension. cerebral music processing-a comparison study of musically trained and naive individuals louis s. russo, jr, jachonville, fl we performed topographical mapping of brain electrical activity in right-handed symphony musicians and righthanded, musically naive individuals during various musical tasks; namely, listening to solo piano music, silent singing of familiar music, and silent reading of unfamiliar music. fast-fourier transform ( f r ) of electrocortical activity was carried out during task performance and the eyes-open resting state. data were analyzed using a computer-assisted model. increases in regional beta activity of greater than standard deviations from the resting state were considered significant of activation. during audition, the musicians showed activation in the right posterior parietotemporal region; the naive showed no change from the resting state. during silent singing, the musicians showed bitemporal activation, r > l; the naive showed activation in the right mid-and posteriortemporal regions alone. during silent sight reading, the musicians showed a major activation in both temporal regions, l > > r, the naive showed only a marginal change in the posterior temporal-occipital regions. these data suggest that music processing is primarily a right cerebral function in untrained individuals and a bilateral function in musicians. musicians, in contrast to the naive, show progressively more left brain activation as task complexity increases. the present study analyzes language profiles in patients who presented with primary progressive aphasia (ppa) without global dementia for at least years. language and cognitive impairment were evaluated using the western aphasia battery (wab) and the mattis dementia rating scale (drs). expressive language disability with reduced speech fluency and anomia, but preserved language comprehension and nonverbal cognition, were typical features in early stages. spontaneous speech was significantly more impaired in ppa than in anomic aphasia after left-hemisphere stroke and in language impairment in probable alzheimer's disease (ad) ( p = . ). the profile of aphasia suggests that ppa tends to affect anterior parts of the language-dominant cortex first. neuroimaging generally showed mild to moderate brain atrophy. in patients atrophy involved especially the left frontal progressive aphasia cortex. follow-up examinations that were done in patients or several years after the first assessment revealed continuous, most often rapid deterioration of language impairment. two patients died and years after the onset of ppa. neuropathological examination showed ad in patient and pick's disease in the other patient. beverly clarke, adrian upton, markad kamath, and helene griff;., hamilton, ontario, canada eight patients implanted with a cyberonics neurocybernetic prosthesis model to stimulate the vagus nerve were assessed for changes in cognitive performance. the patients had complex partial seizures for more than years, with more than per month. patients were years * . sd old. cognitive evaluation included response time to a randomized light signal appearing on a switch box (test a); test b, in which the signal appeared bilaterally; and test c, in which a response to the signal was required while the patient simultaneously ignored a second signal. data were collected and analyzed using an apple i e computer and switch pad. all patients were taking therapeutic levels of anticonvulsant medications and dosages were constant. testing occurred times during a day preoperatively (day l), weeks postoperatively with the stimulator on (day ), and months after turn-on (day ). patients were randomized into high-and low-frequency stimulation groups (hfg and lfg). hfg parameters were hz, so msec pulse width (pw), and lfg hz, msec pw. examiners were blinded as to group. student's t-test analyses of mean differences between groups and individual measurements showed a significant difference between hfg and lfg for test c ( p < . ). lfg showed a significant improvement for tests a, b, c between day and , and for test c between day and . no group effect was seen between day and in the lfg. individual measurements showed improvement for test b ( p < . ) for the hfg between day and , test b ( p < . s) between day and , and tests a and b ( p < . ) and ( p < . ) day vs . the lfg group improved between days and and and . between day and day , the lfg showed improvement only for test b ( p < . ). chronic stimulation of the vagus nerve improves cognitive function in epileptic patients and this improvement is more marked with low-frequency stimulation. a. guidotti, and j. d. rothstein, bologna, itah, washington, dc, and baltimore, m d we reported idiopathic recurring stupor (irs) in a patient with stuporous episodes without known causes and reversed by flumazenil, a specific benzodiazepine (bz) antagonist. ictal plasmdcerebrospinal fluid (csf) showed increased bz-like activity (ann neurol, in press). recently, an endogenous bzreceptor ligand (endozepine [ez]) has been purified from mammalian brain with properties similar to diazepam. it acts like diazepam to potentiate gamma-aminobutyric acidmediated postsynaptic inhibition. we hypothesized that irs might be due to an excess of this substance. irs was diagnosed in patients, and years old, who had recurring stupor or coma episodes lasting hours to days. ictal brain ct/mri, kidney, liver, heart, blood glucose, ammonia, and osmolality were normal. eeg showed fast -hz background activity while the patients were unreactive to stimuli, reversed by flumazenil. ictal serum or csf revealed an enormous increase of the ez in both patients, with levels as high as nm, compared to to nm in control serum/csf. interictal csf or serum in irs contained ez levels similar to control csf and serum. irs may be due to excess ez. the cause for increased ez is unknown. parkinson's disease: evidence from word learning murray grossman, jenger mickanin, barbara schaefr, kris onishi, matthew b. stern, steven gollomp, and howard hurtig, philadelphia, pa several reports have suggested that patients with parkinson's disease (pd) have intellectual impairments in several domains such as memory, but few studies have explored difficulties in language processing. we investigated the ability of nondemented pd patients with mild motor impairments to learn about the grammatical and semantic information represented in a new verb. the new verb was presented to patients in a sentence-picture matching context, and we probed their recall of the verb minutes later. a sentence judgment task assessed grammatical knowledge by asking patients to judge the new verb, known verbs, and pseudowords used appropriately or incorrectly in a sentence. we found that % of pd patients were significantly impaired in their grammatical appreciation of the new verb (f [i, = . ;p < . ). this was not related to their motor disorder or neuropsychological performance. a picture classification task used pictures illustrating specific aspects of the new word's meaning to evaluate semantic knowledge. pd patients were as accurate as controls at deciding whether a picture illustrated the meaning of the new verb (f ( , = .lo;p > . ). only pd patient ( %) had difficulty sorting pictures. selective difficulty recalling only grammatical aspects of a new word suggests that the word learning impairment in pd cannot be entirely explained by poor memory. instead, in agreement with other recent findings, pd patients may be impaired in some aspect of grammatical processing in language. we discuss the hypothesis that defects in the frontocaudate axis in pd underlie this impairment. neuropsychological performance on both verbal and nonverbal tasks is reported to differ between healthy men and women. some of these cognitive differences are postulated to reflect differences in interhemispheric and intrahemispheric cerebral organization. our preliminary study indicated that women with alzheimer's disease (ad) performed worse than men on a composite neuropsychological battery, even after effects of potentially confounding variables were considered (buckwalter et al, j clin exp neuropsychol ; : ) . to explore further the nature of gender-associated differences in ad, we analyzed data from a verbal and a nonverbal task (the boston naming test and drawings from the spatial quantitative battery supplement to the boston diagnostic aphasia examination) for men and women who met nincds-adrda criteria for "probable" ad. prior to ana-grip strength kg [range . - kg]). the electrophysiological examination showed improvement with reversal of conduction block in patients and was unchanged in . an apparent response to the placebo was seen in patients. improvement after ivig therapy was maintained for variable durations ( - wk) and reoccurred with subsequent infusions. an equally effective response was documented after infusion of a single ivig dose of gm/kg. we conclude that ivig therapy is effective in some patients with cidp, even after long duration of illness. the best responses were observed in patients with recent relapse. a single high-dose treatment may be equally effective. the object of this study was to examine whether borrelia burgdorjeri antigens could be detected in csf in the absence of detectable antibodies to b. burgdorjeri (the etiological agent of lyme disease). osp a is a -kd antigen that is specific for . duvgdorferi osp a was probed using western (immuno) blot and specific mouse monoclonal antibodies. polyclonal lyme antibodies were detected in csf using standard micro enzyme-linked immunosorbent assay. seven patients had osp a in csf without detectable lyme antibodies. there were men and women aged to years (mean yr). disease duration ranged from weeks to years. neurological syndromes included confusion with acute flulike illness, optic neuritis, hemiparesis with inflammatory brain lesion, encephalitis, headache with erythema migrans, bilateral facial nerve palsies, and encephalomyeloradiculitis. three patients had csf abnormalities. in patients csf parameters were otherwise completely normal. possible explanations for undetectable csf lyme antibodies included early infection ( patients), prior antibiotics ( patients), and prior steroids plus antibiotics ( patient). in patient there was no obvious explanation. we conclude that osp a, a specific antigen of b. burgdorferi, may be present in csf without a detectable humoral response. the diagnosis of neurological infection with b. bwgdorjeri should not require a positive csf serology. mollaret's meningitis: demonstration by polymerase chain reaction a -year-old man was seen in september for his fourth episode of aseptic meningitis over a -year period. the episodes conformed to criteria for mollaret's meningitis as published by bruyn, straathof, and raymakers, and subsequently by others; they lasted about week, and were characterized by fever, headache, meningismus, lymphocytic pleocytosis, elevated protein in cerebrospinal fluid (csf), and spontaneous resolution without residua. extensive prior evaluations had failed to uncover a cause. the patient was otherwise well and neither he nor his wife had any history of sexually transmitted diseases. suspicion of herpes simplex virus (hsv) arose due to a single transient, raised skin rash several weeks earlier that failed to yield virus on culture. the patient was treated with acyclovir, which resulted in rapid resolution of symptoms. though culture and immunological studies of csf and blood again were unrevealing, polymerase chain reaction (pcr) studies of csf confirmed the presence of hsv type . we suspect that herpes simplex virus is a more common cause of recurrent aseptic meningitis than current culture and immunological techniques would suggest. pcr offers increased diagnostic sensitivity for neurotropic viruses and should be considered in patients with recurrent meningitis of cryptic etiology. differentiation by inorganic lead: a role for protein kinase c j. lutewa, j. p. bressler, r. r. indurti, l. belloni-olivi, and g. w . goldstein, baltimore, m d microvascular endothelial function in developing brain is altered by inorganic lead. this may result from changes in protein kinase c (pkc) modulation. we examined the effects of inorganic lead on an in vitro model of neural endothelial differentiation. astroglial-induced endothelial differentiation into capillary-like structures was inhibited by lead acetate with % maximal inhibition occurring at . pm lead. inhibition was independent of effects on cell viability or growth. we examined the effects of lead on cellular pkc pools under conditions that inhibited capillary-like structure formation. membranous pkc increased in c astroglial and neural endothelial cells after exposure to lead acetate. exposing c cells to p,m lead for hours increased membranous pkc by % as determined by immunoblotting. membranous pkc increased in response to as little as nm lead and saturated at pm. phorbol esters were used to determine if pkc modulation was mechanistically related to lead's inhibition of capillary-like structure formation. -myristate -acetate ( nm) inhibited endothelial differentiation by * %, whereas -alpha-phorbol , didecanoate was without effect. these findings demonstrate that inorganic lead may induce cerebral microvessel dysfunction by interfering with pkc modulation in microvascular endothelial or perivascular astroglial cells. w. f. brown, b. v . watson, j . garland, g . c. ebers, and n . desai, london, ontario, canada gait difficulties in multiple sclerosis (ms) are commonly accompanied by fatigue and dyspnea. possible explanations for the latter include weakness andlor dyssynergia of the respiratory muscles, including possible abnormalities in central pathways regulating respiration. this study examined central and peripheral motor conduction to the diaphragm in ms patients whose gait was notably labored and accompanied by breathlessness. peripheral conduction was assessed by measuring the latency and size of the surface-recorded diaphragmatic maximum m-potential responses to supramaximal stimulation of the phrenic nerve in the neck, and central motor conduction by comparable measurements in response to magnetoelectrical stimulation over the vertex. peripheral motor conduction was normal. the most striking abnormalities were in central motor conduction. cortical stimulus-evoked diaphragmatic responses were absent on both sides in patients, and unilaterally in l patient, whereas in others the latency of the cortical stimulus-evoked response was increased and the size clearly reduced and entirely normal in only patients. these studies show that central conduction program and abstracts, american neurological association to the diaphragm is commonly abnormal and may play a role in the fatigue and dyspnea experienced by ms patients. six men ( - yr) developed myelopathy that progressed slowly over several months and was characterized by asymmetrical, incomplete spinal cord syndrome manifested at the sensory level at the trunk, mild spastic paraparesis, and urinary incontinence. the spinal cord lesions at appropriate levels were recognized by mri as enhancing lesions in of the men. coxiella burnetii infection was confirmed in the blood of all patients by immunofluorescence microscopic assay (ifa) and transmission electron microscopy (tem). in patients, we detected c. burnetti by tem and ifa using csf of the patients inoculated onto fresh peripheral blood lymphocytes. four patients who were treated with appropriate antibiotics responded with either partial resolution of symptoms or arrest of further neurological progression. in patients the lesion was shown on mri to have decreased in size. in summary, we report cases of transverse myelopathy associated with c. barnetti infection. this is the first report, to our knowledge, of coxiella-related chronic myelopathy. we present a series of patients with different labyrinthine lesions diagnosed by mri. twelve patients with sensorineural hearing loss were studied by gadolinium-enhanced mri, including -mm contiguous t -weighted images through the labyrinth. ten patients had enhancement of the cochlea or vestibule, or both. all patients with cochlear enhancement had severe neural sensory hearing loss. all patients with vestibular enhancement had severe vestibular symptoms. the patients' final diagnosis included viral labyrinthitis ( patients), syphilitic labyrinthitis ( patients), bacterial labyrinthitis ( patient), and vestibular neuromas ( patients). one patient had an acoustic neuroma extending in the basal turn of the cochlea. the enhancement in patients with vestibular neuromas was brighter and there was slight mass effect in comparison with the patients with inflammatory labyrinthine lesions. one patient had hemorrhage within the vestibule from an adjacent temporal bone hemangioma. one patient with ct-proven cochlear otosclerosis had pericochlear areas of enhancement on gadolinium mri. mri can diagnose a variety of labyrinthine lesions that correlate very well with the patient's clinical symptoms. gadolinium should be used routinely in patients with suspected labyrinthine disease. the diagnosis of meniere's disease and endolymphatic hydrops remains a diagnosis of exclusion. few radiographic findings have been correlated with the clinical symptoms of this entity. we describe patients with symptoms of hearing loss or vertigo, or both, who demonstrated enhancement of the endolymphatic sac on gadolinium-enhanced mri. no enhancement was noted in a series of controls with no symptoms of hearing loss and vertigo. enhancement in the brain correlates with inflammatory or neoplastic conditions. we thus can speculate that enhancement of the endolymphatic sac reflects an inflammatory process in this location that may interfere with the normal resorption of indulin and secondary hydrops. in addition to excluding an acoustic neuroma and a labyrinthine schwannoma (which clinically may be confused with meniere's disease), contrast-enhanced mri may provide objective evidence in favor of labyrinthine hydrops. it was intermittent ( %) but progressive. the ha was mild to moderate in severity; it was the worst symptom in only ( %) and the first symptom in ( %) patients. has were worse in the morning in ( %) and interfered with sleep in ( %) patients. unlike true tension-type has, bt has were worse with bending over in ( %), with valsalva's maneuver in ( %), and nausea or vomiting were present in ( %) patients. an abnormal neurological exam was found in ( %) patients with has and ( %) patients without has lyzing the effects of gender, we used a hierarchical regression procedure to control for possible effects of subject age, education, age at onset of dementia symptoms, dementia duration, and family history of dementia. significant gender effects were found for the verbal task ( p < . ) (mean boston naming test score of . for women and . for men), but not for the drawing task. we conclude that verbal abilities are more severely affected in women than in men with ad, a difference that may in part reflect premorbid gender-associated differences in cerebral hemispheric organization. hemispatial placement is known to affect line bisection in patients with neglect. whereas placing stimuli in neglected space increases bisection error, placing stimuli in nonneglected space attenuates error. the effects of hemispatial placement on line bisection were examined in patients with chronic neglect (over months after stroke). all patients had large (frontotemporoparietal), unilateral, right-hemisphere lesions. each patient bisected lines of different lengths ( , , , and cm) in hemispatial conditions ( cm left of midline, midline, and cm right of midline). like previous reports, when patients bisected lines in left hemispace, a consistent ( / trials) left-sided neglect was observed ( . cm). however, when lines were bisected in center space, misbisections occurred on either side of the midline; and, unlike previous studies, when lines were bisected in right hemispace, a consistent ( / trials) right-sided neglect was observed ( . cm). the magnitude and directional consistency of line bisection errors were significant. neither visual field defects nor limitations in reaching accounted for the results. recovery in chronic neglect may involve a realignment of limited attentional resources favoring the body's midline. consequently, performance in both hemispatial fields can be biased toward midline, resulting in neglect of opposite directions. despite agreement that depression is the most common neuropsychiatric symptom associated with multiple sclerosis (ms), many aspects of this emotional change are unclear. one of the more controversial issues concerns the relationship between severity of ms and depression. this relationship is used to evaluate whether depression is an integral or reactive symptom of ms. examination of this relationship is complicated by the presumed overlap between somatic features of depressive and neurological symptoms in ms. to clarify this situation, we examined the relationship between severity of ms and categories of depressive symptoms using the beck depression inventory (bdi). eighty-nine patients and normal controls were examined. for certain comparisons, patients were classified as mild (extended disability status scale of - ) or moderatelsevere ( ) ( ) ( ) ( ) ( ) ( ) . results indicated that total bdi scores and the depressive symptom categories (mood, self-reproach, vegetative, and somatic features) were elevated in patients with ms, but the extent of these elevations was not related to severity of disease. these results suggest that depression in ms is not a simple reaction to physical disability. furthermore, clinical examination of depressive symptoms is straightforward and not confounded by severity of ms. neurological involvement in wegener's granulomatosis was studied in consecutive patients diagnosed at the mayo clinic. one hundred and nine patients ( %) had neurological involvement. peripheral neuropathy was seen in ( . %), cranial neuropathy in , external ophthalmoplegia in , cerebrovascular events in , seizures in , and miscellaneous involvement in . the mean age and sex ratio did not differ in those with or without neurological involvement. among the patients with peripheral neuropathy, had multiple mononeuropathy, had distal symmetric polyneuropathy, and had unclassified peripheral neuropathy. multiple mononeuropathy was one of the major presenting symptoms in patients. kidney involvement was significantly higher in the patients with peripheral neuropathy compared to those without it (p < . ). among the cranial nerves, the second, sixth, and seventh nerves were affected most frequently. multiple cranial nerves were affected in patients. unusual neurological manifestations among the miscellaneous group included spastic paraparesis, temporal arteritis, homer's syndrome, and papilledema. this is the first comprehensive study on the frequency and distribution of neurological involvement in wegener's granulomatosis. chronic inflammatory demyelinating polyneuropathy: a double-blind placebo-controlled crossover study treatment with high-dose intravenous human immunoglobulin (ivig) has been reported to be beneficial in some patients with chronic inflammatory demyelinating polyneuropathy (cidp), yet most observations have been nonblinded. we examined the effect of ivig therapy in patients ( men, women) with cidp in a double-blind, placebo-controlled crossover study. disease was chronic progressive (n = ) or chronic relapsing (n = ) and of variable duration ( mo to yr). the diagnosis was confirmed by electrophysiological ( ) and nerve biopsy ( ) examinations. the trial consisted of two -day periods each. patients were randomly treated with ivig ( . mg/kg/day) or placebo on consecutive days and followed. function was assessed by a quantitative neurological disability score, functional grade, grip strength measurement, and electrophysiological examinations at the beginning and end of each treatment period. with ivig therapy, significant improvement was documented in / patients (improvement in neurological disability score mean key: cord- -j gpww q authors: sun, wei; shi, zhencai; gao, fuqiang; wang, bailiang; li, zirong title: the pathogenesis of multifocal osteonecrosis date: - - journal: sci rep doi: . /srep sha: doc_id: cord_uid: j gpww q our objective was to study the incidence, etiology, and diagnosis of multifocal osteonecrosis (mfon) and its treatment options to facilitate an earlier diagnosis and to optimize treatment. a radiological investigation was performed in osteonecrosis patients with a high risk of mfon for a more accurate diagnosis between january and june . for patients with osteonecrosis of both the hip and knee joints or for patients with a history of corticosteroid use or alcohol abuse who had osteonecrosis of one or more joints in the shoulder, ankle, wrist or elbow, magnetic resonance imaging (mri) was also performed on other joints, regardless of whether these joints were symptomatic. furthermore, we performed a radiological screening of patients who had a negative diagnosis of mfon but were at a high risk; among them, another mfon cases were successfully identified ( . %). thus, the incidence of mfon during the study period increased from . % to . %. patients diagnosed with osteonecrosis and who are at a high risk of mfon should have their other joints radiologically examined when necessary. this will reduce missed diagnosis of mfon and facilitate an earlier diagnosis and treatment to achieve an optimal outcome. between january and june , only of the osteonecrosis patients under our care were diagnosed with mfon ( . %) upon admission. after the comprehensive evaluation of the joints of patients who had a negative diagnosis of mfon but who were at a high risk, another cases of mfon were successfully identified ( . %). consequently, the incidence of mfon during the study period increased to . %. the mfon patients admitted to our center had a mean number of . osteonecrotic lesions, similar to the mean number of lesions ( . ) found in post-sars mfon patients. the associated factors, diseases, and comorbidities are listed in table . of the patients diagnosed with mfon on admission between and , were male and were female. forty-seven of the mfon patients had a history of corticosteroid use, and the remaining one patient had a history of alcohol use. of the patients with a history of corticosteroid use, had sle, nine had chronic nephropathy, five had hematological diseases (four had acute lymphoblastic leukemia and one had non-hodgkin's lymphoma), five had an organ transplantation (four had a renal transplantation and one had a cardiac transplantation), three had sjogren's syndrome, two had dermatomyositis, two had multiple sclerosis and three received steroid therapy for trauma emergency. of the newly diagnosed mfon patients, were male and were female. all of them had a history of corticosteroid use. fifteen patients had sle, eight had acute lymphoblastic leukemia, five had chronic nephropathy, and three had an organ transplantation (two had a renal transplantation and one had a hepatic transplantation). the mfon patients most commonly had osteonecrosis of the femoral head, followed by the knee, shoulder and ankle bones. the majority of patients had bilateral lesions (hips, knees and shoulders) (fig. , table ). there was a significant difference in the number of mfon patients identified after the radiological screening based on risk factors compared with that before the screening (p < . ). incidence of mfon. there have not been any journal articles in china concerning mfon, and such reports were also limited in other countries. mont et al. studied mfon cases diagnosed between and from centers in the united states. according to the available data from centers concerning their total number of patients with osteonecrosis, patients had mfon of the patients ( . %) diagnosed with osteonecrosis. in , we screened post-sars medical workers with corticosteroid use and found patients had mfon of the patients ( %) with a diagnosis of osteonecrosis. by contrast, between and , we found only patients with mfon of the patients ( . %) diagnosed with osteonecrosis who were admitted to our center. the incidence of mfon in post-sars osteonecrosis patients was obviously higher than that in daily clinical practice. this is because the lesions found in joints, such as the knees, shoulders and ankles, in the early stages of mfon cases may not have any signs or symptoms. in our screening of post-sars patients, all of them had a comprehensive mri evaluation of their bilateral hips, knees, shoulders and wrists or ankles, which revealed the asymptomatic osteonecrosis. however, in daily clinical practice, we often focus on the osteonecrosis diagnosis of the femoral head without performing an mri on the other joints. this implies that there are possible missed diagnoses of asymptomatic mfon patients. a recent study also showed a higher incidence of mfon than that typically reported in literature . dose of corticosteroids is the main risk factor for mfon. in france, hernigou reported on mfon cases diagnosed between and , all of which were associated with corticosteroid use. in the cases reported by mont et al. , % had a history of corticosteroid use, and the rest had a coagulation disorder. our study showed that of the ( %) mfon patients admitted to our center had a treatment history of high-dose corticosteroids, and the two remaining patients had a history of alcohol use. moreover, the dosage and route of administration of the corticosteroids were obviously related to the incidence of mfon. a study by hernigou demonstrated that the total dose and the daily dose of venous injection were closely related to the occurrence of mfon. this was also found in our study of post-sars osteonecrosis patients caused by the use of corticosteroids . there have been a limited number of mfon case reports and a high occurrence of mfon in asymptomatic patients. therefore, the exact incidence of mfon in patients with various diseases remains unclear. the incidence of mfon in patients with sickle cell disease was reported to be % ( of ) as a complication in the maintenance treatment of acute lymphocytic leukemia and non-hodgkin's disease, and its incidence in these diseases is also higher than that reported in the literature. solarino et al. performed mri screening in patients with acute lymphoblastic leukemia after chemotherapy and found that % of them had mfon . in the mfon cases presented in this study, most were sle, followed by hematological diseases, nephropathy, organ transplantation, dermatomyositis and multiple sclerosis. mfon was especially prevalent in leukemia patients; of the osteonecrosis patients with leukemia under our care were found to have mfon. three of the four patients who received pulse steroid therapy for trauma emergency had a spinal cord injury, for which steroid therapy was considered appropriate. however, one patient received pulse steroid therapy for only an eye injury and was found to have osteonecrosis in eight joints, including the hips, knees, shoulders and ankles. caution should be taken for such cases in the future. mfon patients most commonly had osteonecrosis of the femoral head, followed by the knee, shoulder and ankle bones. osteonecrosis of the shoulder, ankle and wrist never occurred aloneand was always accompanied by osteonecrosis of the hip and knee. among the three populations of mfon patients presented in this study, - % had femoral head involvement, - % had knee involvement, and - % had humeral head involvement. the average number of osteonecrotic lesions was . per patient. to date, mri is the most sensitive and specific tool to diagnose mfon. initial studies found that low field mri was as sensitive as a radionuclide scan in diagnosing osteonecrosis. nevertheless, recent studies have demonstrated that high field ( . - t) mri has a higher sensitivity, specificity and accuracy in diagnosing osteonecrosis. mont et al. compared the sensitivity of radionuclide scans with mri, and found that mri has a sensitivity of %. by contrast, the sensitivity of radionuclide scans is only %. radionuclide scans have a higher sensitivity in detecting advanced stage osteonecrosis of the hip and knee than of the shoulder and ankle. although the diagnosis of osteonecrosis by mri has its advantages, the screening for mfon with mri is faced with a long scanning time and high cost. there have been debates regarding the optimal method to screen symptomatic and asymptomatic mfon , . plain film x-ray is not sensitive enough to diagnose asymptomatic mfon, but there is still an advantage to carrying out an x-ray examination. even if the x-ray result of a joint with pain is negative for osteonecrosis, it provides a preliminary examination of the local bone structure, which serves as a reference for further investigation by mri. other methods include a short time inversion recovery (stir) mri test followed by mri or a radionuclide scan of specific joints. nevertheless, further studies are required to determine the optimal method for early detection of osteonecrosis. moreover, as the majority ( - %) of osteonecrosis cases reported in the literature are bilateral, patients diagnosed with osteonecrosis of a joint on one side should be radiologically examined on the other side. missed diagnoses of mfon have frequently occurred in clinical practice. to reduce this, we recommend the following measures. ) patients with associated diseases and long-term use of high-dose corticosteroids should have their hips and knees evaluated by mri within six to twelve months after the medication. ) patients diagnosed with osteonecrosis of the hip and knee should have their bilateral shoulders evaluated by mri. ) patients with corticosteroid use or alcohol abuse and who are diagnosed with osteonecrosis of one or more joints in the shoulder, ankle, wrist and elbow should have their hips and knees evaluated by mri. mfon patients usually start with silent lesions. as the disorder gradually progresses, patients will experience joint pain. at first, the pain is mild and patients may only experience increased pain during movement or weight bearing on the affected bone or joint. as significant damage develops in the joints, patients will experience severe pain. the period of time between the first symptoms and the loss of joint function varies for each patient and ranges from several months to several years. in the late stages of mfon, patients often have symptoms at rest and reduced joint activity, resulting in severe joint dysfunction. the treatment of mfon remains controversial. the general principle is to estimate the prognosis of each lesion. in addition, predicting the presence of collapse of the joint surfaces is the basis for determining the order of treatment. the progress of osteonecrosis is often different for each joint. osteonecrosis of the femoral head progresses the fastest and attention should be paid to the early appearance of symptoms. this is followed by the progression of osteonecrosis to the knees and shoulders. patients who have osteonecrosis of multiple weight-bearing joints and a large necrotic lesion area may develop joint destruction, and early intervention should be used. the progression of osteonecrosis to the elbow and wrist is relatively slow; however, we still lack experience regarding the appropriate treatment method for this area. bone infarction often leads to calcification and self-repair. hence, osteonecrotic elbows and wrists should mainly be managed by monitoring, and over treatment should be avoided if there are no clinical symptoms. in addition, an appropriate treatment strategy should be selected according to the stage of osteonecrosis in each joint involved . for symptomatic patients at an early stage (i.e., arco stages i, ii or china stages i-iii), joint-preservation treatment options are commonly used, such as extracorporeal shock wave, core decompression, and vascularized and nonvascularized bone grafting. when > mm of the articular surface has collapsed or the necrotic lesion area is > %, joint-preservation treatments may not provide good efficacy. in the advanced stages of the disease (i.e., arco stages iiic and iv, or china stages v-vi), arthroplasty is required when joint preservation is not possible. there are some limitations of this study. this study is limited by virtue of the retrospective analysis at only one center. and there was no randomized and blinded control group with conservative treatment in this study. the incidence of mfon was high when clinical risk factors were present, such has high-dose steroid use, alcohol abuse, sle, chronic nephropathy and leukemia. for a highly suspected case of mfon, a radiological screening of multiple joints is necessary, and mri is still the gold standard for diagnosing mfon. such screening can help to effectively reduce missed diagnoses. the goals of the treatment should be to take measures to delay the progress of the disease, to preserve the joint function and to avoid joint surface collapse and destruction by diagnosing the disease early. in addition, an appropriate treatment strategy should be selected according to the stage of mfon. conservative treatment and joint-preservation treatment options should be adopted during the early stages, while arthroplasty should be performed during the advanced stages. this study was performed in accordance with the principles expressed in the declaration of helsinki and approved by the ethics committee of the china-japan friendship hospital. informed consent was obtained from all patients. a standardized mri was taken of patients, including their bilateral joints. the apparatus was a ge sigma profile/gold, and t weighted, coronal stir, and transverse t wi sequences were used. the parameters of the scan included a layer thickness of mm and a distance between layers of mm. the t wi were obtained with a tr from ~ ms and a te of ms, and the stir images were obtained with a tr of ms and a te of ms. if an abnormal signal was found, then a t weighted scan was added, and for some of the patients, we also performed fat suppression and water-fat separation sequences. we only used t and t sequences for the other joints of the patients. osteonecrosis was defined as either a subchondral or an intramedullary area demarcated by a distinct marginal rim with low signal intensity that encompassed the medullary fat on the mri images. in addition to the mri, all patients were subjected to an x-ray that included the affected joints. our general survey on the bones and joints of post-sars medical workers who used corticosteroids revealed that the corticosteroid dose was approximately mg in unifocal osteonecrosis patients. by contrast, the dose was > mg in all mfon patients except for one patient who received mg, with the highest dose at , mg. the mfon patients also had prolonged corticosteroid treatment (≥ days) . of the mfon patients diagnosed between january and december , one had a -year history of alcohol abuse (average daily alcohol consumption of g). the remaining patients had a history of intensive steroid use for the following diseases: sle ( patients), acute lymphoblastic leukemia ( patients), chronic nephropathy ( patients), anaphylactoid purpura ( patient) and pulse steroid therapy for traumatic shock ( patient). therefore, we summarized the high risk factors for mfon to include: a medical history of sle, chronic nephropathy, hematological diseases or coagulation abnormalities (especially leukemia); total corticosteroid (methylprednisolone) dose > mg, especially for patients with a history of intravenous pulse therapy; and a total corticosteroid administration time of > days. between january and june , a total of osteonecrosis patients were admitted to our center, and only of them were diagnosed with mfon ( . %) upon admission. a radiological investigation was performed in patients with a negative diagnosis of mfon but who had a high risk of mfon and complaints of pain in other joints. for patients found to have osteonecrosis of both the hip and knee, mri was performed on their bilateral shoulders and ankles, and also their bilateral wrists and elbows when necessary, regardless of whether other joints were symptomatic. for patients with a history of corticosteroid use or alcohol abuse and who were found to have osteonecrosis of one or more joints in the shoulder, ankle, wrist and elbow, mri was performed on their hips and knees and their other joints when necessary. the results were analyzed by a chi-square test the using spss software. a p value < . was considered statistically significant. symptomatic multifocal osteonecrosis. a multicenter study. collaborative osteonecrosis group clinical research of correlation between osteonecrosis and steroid multifocal joint osteonecrosis in sickle cell disease thrombophilia, hypofibrinolysis, the enos t- c polymorphism,and multifocalosteonecrosis multifocal osteonecrosis in systemic lupus erythematosus: case report and review of the literature multiple site osteonecrosis in hiv infection osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the children's cancer group on a case of multifocal osteonecrosis in a patient suffering from acute lymphoblastic leukemia multifocal avascular necrosis after liver transplantation: an unusual presentation of the antiphospholipid syndrome multifocal osteonecrosis associated with human immunodefi ciency virus infection symptomatic steroid-induced multifocal diaphyseal osteonecrosis in a patient with multiple sclerosis widespread osteonecrosis in children with leukemia revealed by whole-body mri vibration-induced multifocal carpal osteonecrosis in a -year-old man a rare cause of peripheral arthralgia in inflammatory bowel disease: multifocal osteonecrosis non-traumatic osteonecrosis of the femoral head: ten years later bone scanning of limited value for diagnosis of symptomatic oligofocal and multifocal osteonecrosis detection of multifocal osteonecrosis in an adolescent with dermatomyositis using whole-body mri fast sequences mr imaging at the investigation of painful skeletal sites in patients with hip osteonecrosis chinese specialist consensus on diagnosis and treatment of osteonecrosis of the femoral head this study was supported by the national natural science foundation of china ( ) and the china-japan friendship hospital youth science and technology excellence project ( -qnyc-a- ). the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the paper. w.s., z.c.s. and z.r.l. conceived the experiments. w.s., z.c.s., f.q.g. and w.b.l. performed the experiments. w.s., z.c.s., f.q.g. and w.b.l. analyzed the data. w.s., z.c.s. and z.r.l. wrote the manuscript. all authors reviewed the manuscript. competing financial interests: the authors declare no competing financial interests. this work is licensed under a creative commons attribution . international license. the images or other third party material in this article are included in the article's creative commons license, unless indicated otherwise in the credit line; if the material is not included under the creative commons license, users will need to obtain permission from the license holder to reproduce the material. to view a copy of this license, visit http://creativecommons.org/licenses/by/ . / key: cord- - g owogs authors: sharma, suvasini; dale, russell c. title: acute disseminated encephalomyelitis date: - - journal: acute encephalopathy and encephalitis in infancy and its related disorders doi: . /b - - - - . -x sha: doc_id: cord_uid: g owogs acute disseminated encephalomyelitis (adem) is an inflammatory demyelinating syndrome with encephalopathy. adem typically affects young children, is often postinfectious, and is typically monophasic. mri neuroimaging, which shows new lesions with poorly demarcated borders, but not old and established lesions, is essential to diagnosis. autoantibodies against myelin oligodendrocyte glycoprotein (mog) are found in ∼ % of adem patients, and these patients have different clinical and neuroimaging features to seronegative patients. treatment in the acute phase is typically with high-dose corticosteroids and intravenous immunoglobulin or plasma exchange for refractory patients. outcome is usually good, but residual cognitive, inattentive, and executive issues are likely underestimated. in patients who have a relapse, biomarkers and imaging should help differentiate multiphasic adem, neuromyelitis optica spectrum disorder, anti-mog antibody–associated relapsing demyelination, and multiple sclerosis. acute disseminated encephalomyelitis (adem) is an acute immune-mediated inflammatory demyelinating condition involving the brain and spinal cord, which presents clinically with new-onset polyfocal neurologic features, which by definition include encephalopathy. the mri shows characteristic multifocal demyelinating abnormalities. there is often a history of infection or immunization, and adem is considered a postinfectious/parainfectious condition. this condition is a common cause of encephalitis in children and must be considered in the differential diagnosis of a child presenting with acute febrile encephalopathy and altered sensorium with or without fever. children with adem respond well to immunosuppressive treatment (steroids) with the majority having a single event, i.e., a monophasic course. a small proportion of children with adem may have relapses, and in this subset, multiple sclerosis (ms) is a diagnostic consideration. in this chapter we discuss the epidemiology, pathophysiology, clinical features, investigations, treatment, and outcome of adem in children. adem is a clinicoradiological diagnosis because there are currently no diagnostic blood or csf abnormalities or biomarkers (apart from anti-myelin oligodendrocyte protein [anti-mog] antibodies, discussed later). therefore in earlier studies there was a marked heterogeneity regarding the criteria for diagnosis. in , the international pediatric multiple sclerosis study group (ipmssg) proposed consensus definitions for pediatric acquired demyelinating disorders of the central nervous system (cns) to improve consistency in terminology. these criteria were revised in . for the diagnosis of adem, all of the following criteria are required : . a first polyfocal, clinical cns event with presumed inflammatory demyelinating cause. . encephalopathy that cannot be explained by fever. encephalopathy refers to an alteration in consciousness (e.g., stupor, lethargy) or behavioral change unexplained by fever, systemic illness, or postictal symptoms. or more after the onset. this implies that the confirmation of the monophasic course requires followup and can only be done retrospectively. . brain mri is abnormal during the acute ( months) phase. . typically on brain mri, there are diffuse poorly demarcated, large (> - cm) lesions involving predominantly the cerebral white matter. t hypointense lesions in the white matter are rare. deep gray matter lesions (e.g., thalamus or basal ganglia lesions) can be present. if a child has a first monofocal or polyfocal clinical cns event with presumed inflammatory demyelinating cause in the absence of encephalopathy and the mri criteria for ms are not met, this is known as clinically isolated syndrome (cis). examples of cis include optic neuritis, transverse myelitis, hemiparesis, monoparesis, and brainstem syndromes. cis has a higher likelihood of progression to ms as compared with adem. the clinical symptoms and radiologic findings of adem can fluctuate in severity and evolve in the first months after onset. accordingly, a second event is defined as the development of new symptoms more than months after the start of the incident illness. there is no strong biological rationale of the use of months as a cutoff, although it is hypothesized that monophasic immune dysregulation is usually resolved within a -month period. a small proportion of children with adem ( %) will have a relapse of an inflammatory demyelinating event with encephalopathy. in the criteria, two terms were used for relapses of adem: recurrent and multiphasic adem. recurrent adem was defined as acute disseminated encephalomyelitis suvasini sharma, md, dm • russell c. dale, mbchb, msc, mrcphch, phd a new event of adem with a recurrence of the same symptoms and signs, or more months after the first adem event. multiphasic adem was defined as a new event of adem involving new anatomic areas of the cns and occurring at least months after the onset of the initial adem event and at least month after completing steroid therapy. in the revision, the term recurrent adem has been dropped. multiphasic adem now encompasses both new as well as reemergence of previous clinical and mri findings. also, the timing criterion in relation to steroids for recurrent/ multiphasic adem has been removed. a third adem-like event is not consistent with a diagnosis of multiphasic adem but indicates a chronic relapsing demyelinating disorder, such as relapsing optic neuritis, neuromyelitis optica spectrum disorder associated with antiaquaporin- antibodies, relapsing anti-mog antibody-associated demyelination, or ms depending the clinical phenotype, biomarker, and neuroimaging findings. epidemiology population-based studies have shown varying incidence rates of adem: . per , children per year (germany), . per , children per year (china), . per , children per year (san diego), and . per , person years (japan). the varying incidence may be influenced by factors such as genetic predisposition, latitude, environmental and socioeconomic factors, and study methodology. , the median age at presentation of adem is - years, with male predominance. a recent study from a single center showed that adem was the most common cause of encephalitis ( % of all encephalitis). adem is preceded by infection or vaccination in %- % of cases. common antecedent infections include flu-like illnesses ( %- %), followed by nonspecific upper respiratory tract infections ( %- %) and gastroenteritis ( %). , , in children, exanthematous diseases are also reported as an infectious antecedent. adem has been reported more commonly in winter and spring. this seasonal distribution is likely due to seasonal viral illnesses and epidemics. viruses (coronavirus, coxsackie b, dengue, hepatitis a virus, hepatitis c virus, herpes simplex virus, varicella zoster virus, epstein-barr virus, human herpesvirus- , human immunodeficiency virus, measles, mumps, rubella, and parainfluenza) are the infectious agents most frequently associated with adem. bacteria (streptococcus, mycoplasma, legionella, chlamydia, borrelia, rickettsia, campylobacter) and parasites (plasmodium vivax, toxoplasma gondii) may be rarely involved. the mean latency between the infectious prodrome and the onset of neurologic symptoms varies, often being between and days (range: - days). postimmunization adem accounts for only % of cases of adem. postvaccination adem has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, japanese b encephalitis, pertussis, influenza, hepatitis b vaccine, and human papillomavirus vaccine. in a recent retrospective review of vaccine adverse event reporting system (vaers) database and the eudravigilance postauthorisation module (evpm) from to , a total of cases of postvaccination adem were reported, and half of the patients were less than years of age and with a slight male predominance. the time interval from vaccination to adem onset was - days in % of the cases. vaccine against seasonal flu and human papillomavirus vaccine were those most frequently associated with adem, accounting for almost % of the total cases. the risk of developing adem following vaccination is relatively low, compared with the risk of adem following infections against which the vaccines are aimed to protect. the benefits of vaccinations are considered to far surpass the potential risk of postvaccine adem. the exact pathogenesis of adem is unclear. postinfectious immune-mediated mechanisms are implicated. molecular mimicry with t cell-mediated cross-activation and response against myelin proteins, such as myelin basic protein, proteolipid protein, and mog plus b cell activation and autoantibody production, may play a role. this hypothesis is supported by studies showing the presence of anti-mog antibodies in the serum and cerebrospinal fluid (csf) during the acute phase and their progressive decline along with disease resolution. in a single study comparing the profile of myelin peptide autoantibodies in children with adem versus ms, adem was characterized by igg autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and α-b-crystallin. in contrast, ms was characterized by igm autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and oligodendrocyte specific protein. there may also be a nonspecific self-sensitization of reactive t cells (bystander activation) against myelin proteins secondary to infections. in a recent study comparing the csf cytokine profiles in children with adem, enterovirus encephalitis, and anti-nmda receptor encephalitis, patients with adem showed predominant elevation of th (ifn-γ, tnf-α, cxcl , cxcl ), th (il- , eotaxin, ccl , il- ), th (il- , g-csf, il- , il- , and il- a), b cell (cxcl , baff, ccl ), and other cytokine (cxcl , ifn-α , il- ra) molecules, which supports the hypothesis that both cell-mediated and humoral effector mechanisms may play a role. in a recent study comparing the cytokine profile of anti-mog positive versus anti-mog negative demyelinating disorders it was found that the csf in anti-mog antibody positive patients showed predominant elevation of b cell-related cytokines/chemokines (cxcl , april, baff, and ccl ) as well as some of th -related cytokines (il- and g-csf) compared with anti-mog antibody seronegative patients. these findings suggest that patients with anti-mog antibodies have a more pronounced cns inflammatory response with elevation of predominant humoral-associated cytokines/chemokines, as well as some th -and neutrophil-related cytokines/chemokines, suggesting a differential inflammatory pathogenesis associated with mog antibody seropositivity. these findings also suggest that there is a considerable pathophysiologic heterogeneity in patients with adem, suggesting a spectrum of inflammatory demyelination rather than a single disease entity. histopathologically, the hallmarks of adem include perivenular sleeves of demyelination, perivenous inflammation with infiltrates of myelin-laden macrophages, t and b lymphocytes, plasma cells and granulocytes, axonal injury, and edema. , the axonal damage is demonstrated by the increased level of a phosphorylated microtubule-associated protein, primarily located in neuronal axons, known as tau protein, in the csf, indicative of the clinical severity of adem. moreover, the csf tau protein concentration in patients with partial lesion resolution in follow-up brain mri has been shown to be significantly higher than in patients with complete lesion resolution. in addition, there are diffuse cortical microglial alterations (multifocal microglial aggregates), which may be partly responsible for the encephalopathy seen in children with adem. adem clinically presents as an acute onset encephalopathy along with polyfocal neurologic deficits. the neurologic symptoms are preceded by prodromal symptoms such a fever, malaise, irritability, somnolence, headache, nausea, and vomiting. encephalopathy presents as a change in behavior and/or consciousness, varying in severity from lethargy to coma. commonly headache/ vomiting ( %- %), seizures ( %- %), and meningismus ( %- %) may be associated. the patient may also have focal or multifocal neurologic deficits such as hemiparesis, ataxia, aphasia, diplopia, and rarely dystonia and choreiform movements. multiple cranial nerve involvement may occur. spinal cord involvement may be present in up to % of cases, with clinical features of flaccid paralysis, constipation, or urinary retention. , myelitis is significantly more common in anti-mog antibody-associated adem and is associated with longitudinally extensive lesions on the mri. the clinical course of adem is rapidly progressive, with the development of maximal deficits within - days. rarely, respiratory failure occurs because of brainstem involvement. fever and seizures are described more frequently in adem compared with other acute demyelinating syndromes. combined central and peripheral demyelination has been reported but is very rare in children. clinical manifestations of peripheral neuropathy may occur simultaneously along with the cns manifestations or after them. the diagnosis of adem is clinicoradiological. the characteristic mri lesions are t -weighted and fluidattenuated inversion recovery hyperintense multifocal, irregular, poorly marginated areas with diameters between mm and cm. adem lesions typically involve the subcortical and central white matter and cortical gray-white matter junction, thalami, basal ganglia, cerebellum, and brainstem (figs. . - . ) . the reported frequency of gadolinium-enhancing lesions is highly variable between studies ( %- %), perhaps depending on the timing of obtaining mri in the course of the illness. spinal cord involvement is seen in %- % of patients. five radiologic patterns have been described in adem : ( ) adem with small lesions (< mm), ( ) adem with large confluent white matter asymmetric lesions, ( ) adem with symmetric bithalamic involvement, ( ) adem with a leukodystrophic pattern with diffuse bilateral and usually nonenhanced white matter-sited lesions, and ( ) adem with acute hemorrhagic encephalomyelitis. the latter two phenotypes are uncommon. mri abnormalities may appear later than the clinical symptoms, and progression of mri lesions has been reported during the course of illness despite clinical improvement. mri at presentation can even be normal, and delays of between days and weeks between symptom onset and the appearance of mri alterations have been reported. in a recent study on the evolution of mri during adem episodes, it was noted that new lesions and enlargement of existing mri lesions occurred in the first months in about % of the performed mris, despite clinical recovery. however, this was not noted months after first onset of adem. therefore it should be recommended that convalescent mri scans performed during the first months after adem that show new lesions should not necessarily infer the patient has ms. to differentiate from ms, lesions of ms tend be smaller, discrete and ovoid, and periventricular, especially perpendicular to corpus callosum (dawson fingers), in contrast to the fluffy poorly marginated subcortical lesions in adem. the main differentiating features of adem compared with ms are periventricular sparing and the absence of periventricular dawson finger lesions and black holes on t sequences, which are typical of ms (fig. . ) . follow-up imaging is important to demonstrate resolution of lesions and confirming that no new lesions have developed. in asymptomatic children, repeat imaging is recommended - months after the episode of adem. an earlier repeat imaging at months would be optimal. in children with new symptoms, imaging should be considered earlier. advanced neuroimaging techniques such as diffusion-weighted imaging (dwi) and magnetic resonance spectroscopy appear useful to exclude other diseases, such as strokes and neoplasms, to discriminate between acute and chronic lesions, and to add information about the extent of the affected areas. in a recent study of dwi in children with adem, vasogenic edema was demonstrated on dwi and corresponding apparent diffusion coefficient (adc) maps in of patients; cytotoxic edema was identified in patients while the other patients displayed no changes on dwi/adc. because the presentation of adem frequently mimics acute encephalitis, csf studies are often done, and although they may confirm an inflammatory process, they are nondiagnostic in adem. csf examination is, however, important, especially to exclude an infectious pathology, which is a common differential diagnosis. csf examination in adem reveals inflammatory findings in most patients, consisting of elevated protein levels, up to . g/l (seen in %- % of patients) and lymphocytic pleocytosis, which is typically mild (seen in %- % of patients). , the csf may be normal in %- % of patients. , , intrathecal oligoclonal bands are rare, and if present should raise consideration of ms. in three recent series, of patients, oligoclonal bands were reported in only patient ( . %). [ ] [ ] [ ] recently, it has been shown that serum igg antibodies to mog are present in up to % of children with adem. high-titer anti-mog antibodies have also been found in children with bilateral often relapsing optic neuritis and aquaporin- seronegative neuromyelitis optica. although some relapsing patients with positive anti-mog antibodies can fulfill consensus criteria for ms, anti-mog antibodies generally do not associate with ms and, instead, suggest anti-mogassociated autoimmune demyelination. , these antibodies are seen almost exclusively in demyelinating illnesses and may help to differentiate from viral encephalitis. in patients with adem, the majority of children with anti-mog antibodies have a monophasic course with a rapid decline of anti-mog antibodies. the presence of anti-mog antibodies is likely to be a negative predictor for a future diagnosis of ms. in a study comparing children with adem with and without positivity for anti-mog antibodies, children with adem who were seropositive for anti-mog antibodies had mri characterized by large, bilateral, and widespread lesions with an increased frequency of longitudinal extensive transverse myelitis and a favorable clinical outcome in contrast to children lacking mog antibodies. corpus callosal lesions have been found to be uncommon in children with anti-mog antibodies. csf pleocytosis is more common in children with anti-mog antibodies, suggesting more inflammatory burden in the acute phase as compared with seronegative patients. some children with adem and seropositivity for anti-mog antibodies may have a relapsing course with future development of optic neuritis or myelitis, or multiphasic adem, but development of ms is rare. the diagnosis of adem is based on the clinical features and suggestive mri findings. the clinical picture mimics acute meningoencephalitis, and excluding infectious causes is the first priority. this is done by csf examination for gram stain, bacterial culture, and viral studies. peripheral smear should be obtained for malarial parasites in endemic areas. the mri obtained should be a gadolinium-enhanced image to look for any leptomeningeal enhancement or any other feature of infection (e.g., basal exudates, brain abscess). in a child with unexplained altered sensorium and neurologic deficits, other possibilities include autoimmune encephalitis (especially anti-nmda receptor encephalitis), viral-associated encephalopathies such as acute necrotizing encephalopathy, hashimoto encephalopathy, cns vasculitis, primary and secondary (systemic lupus erythematosus, anti-phospholipid antibody syndrome), metabolic (both inherited and acquired) disorders, and rarely toxins and nutritional deficiencies. anti-nmda receptor encephalitis must be suspected if the patient has behavior problems, psychosis, sleep disturbances, and movement disorders (especially orofacial dyskinesias) along with encephalopathy. other inflammatory demyelinating conditions must also be considered in the differential diagnosis. if the patient has monofocal or polyfocal symptoms in the absence of encephalopathy, then clinically isolated syndrome is diagnosed. if the predominant presentation is optic neuritis and myelitis, then neuromyelitis optica must be considered, and testing for aquaporin antibodies must be done if possible. neuromyelitis optica with anti-aquaporin- antibodies is an uncommon form of cns demyelination in children; therefore autoantibody testing for aquaporin antibodies should probably be done only with optic neuritis, myelitis, and brainstem symptoms with typical aqp antibody-associated features. the diagnosis of ms is not made during the first event but may be considered if the mri findings are suggestive, such as the presence of old and new lesions, and fulfillment of mcdonald or other criteria. , treatment the treatment of adem is based on observational studies and expert guidelines, because there are no randomized controlled trials. high-dose intravenous corticosteroids are generally considered the first-line treatment. the treatment regimen consists of iv methylprednisolone at a dose of mg/kg/day (maximally mg/d) for - days, sometimes followed by an oral taper over - weeks with a starting dose of prednisone of - mg/kg/day. the risk of relapse is increased if the steroid tapering period is less than weeks, although not all experts use tapered prednisolone. the aim of steroid treatment is primarily to reduce the cns inflammatory reaction and accelerate clinical recovery. recovery rates with steroid treatment are generally good, with full recovery reported in %- % of the patients. , a repeat pulse of intravenous steroids may be considered in the case of unsatisfactory clinical improvement or early relapse. iv immunoglobulin (ivig) treatment has been described in case reports and small case series, mostly in combination with corticosteroids or as a second-line treatment in steroid unresponsive adem. the usual total dose is g/kg, administered over - days. treatment with ivig has proven effective in about %- % of steroid-resistant patients. , ivig presumably acts by binding and neutralizing autoantibodies, inhibiting cytokine release, and modulating lymphocyte activation. plasmapheresis may be considered in therapyrefractory patients with fulminant disease, with an estimated efficacy of %. the usual regimen is five to seven exchanges but there are not infrequent complications in the form of anemia, hypotension, hypocalcemia, thrombosis, and line infections. moreover, plasmapheresis is technically difficult to perform in young children. rarely, patients with fulminant adem and cerebral edema have been treated with hypothermia in which the body temperature is reduced to °c and intracranial pressure and cerebral perfusion pressure levels are maintained low using mannitol and dopamine. , decompressive craniectomy may be considered in cases of refractory intracranial hypertension. in pediatric series, adem has a favorable prognosis, with a good functional recovery reported in %- % of patients. neurologic improvement is usually seen within days following initiation of treatment, and recovery to baseline usually occurs within weeks. mortality has been reported in %- % of affected patients in recent series. , residual severe disability is rare, reported in % of children in recent studies. about %- % of children are reported to experience residual cognitive impairment or changes in mood and behavior, and the neurocognitive burden of adem is probably underappreciated. , , few studies have analyzed the neuropsychological profile of monophasic adem patients. although, overall, these patients showed a satisfactory global performance, a number of children demonstrated isolated deficits in one or more cognitive domains, most frequently the attentive and executive domains. greater vulnerability to cognitive dysfunction and behavioral problems has been noted in adem patients diagnosed before the age of years. optic nerve involvement at presentation and antecedent viral infection have also been suggested as indicative of a poor outcome. in a recent study of the long-term neurocognitive outcome of children with adem, the most common residual symptoms were concentration difficulties ( %), behavior problems ( %), and learning difficulties ( %). on the kaufman intelligence test, a full-scale iq of more than was found in only % of patients, and % of patients fulfilled the criteria for adhd. male gender was a predictor for a worse neurocognitive outcome in this study. the attention and behavioral impairment in adem may be attributed to the cerebral white matter damage that may interfere with information processing and attention skills, which are critical for emotional functioning and behavioral regulation. when persisting symptoms continue after adem, persisting chronic immune activation should be considered, and a retrial of immune therapy can be used to determine if there is a reversible cause for ongoing symptoms. although in most cases adem has a monophasic course, a variable number of patients ( %- % in previous studies) experience relapses. because of the high interstudy variability and inconsistency of definitions in the past studies, it is difficult to have conclusive findings on relapsing patients from the current literature. latency from first episode to relapse is variable, ranging from months to years, and even after years in one case. relapses have been reported to be more common in the first months after the first episode, mostly occurring in children who underwent oral steroid tapering for weeks or less. most children experience a single relapse, but as many as three relapses are reported in some studies. , an increased risk of relapse after adem has been associated with coexistent optic neuritis, familial history of cns inflammatory demyelination, the presence of ms findings criteria on mri, and the absence of sequelae after the first attack in one study. multiphasic adem is uncommon. in literature, multiphasic adem was diagnosed in only of ( . %) children in one series, and in of ( . %) children in another series. after the initial episode of adem, a subsequent diagnosis of ms is not common. a long-term follow-up study using the international pediatrics multiple sclerosis study group criteria evaluated the parameters at initial diagnosis and eventual conversion to ms in a cohort of children with a first episode of acute cns demyelination. of the patients initially diagnosed with adem, only ( . %) were eventually diagnosed with ms at follow-up versus . % of those initially diagnosed with clinically isolated syndrome had ms. on multivariate analysis, the following predictors for developing ms were identified: female gender, clinical presentation with monofocal brainstem or hemispheric dysfunction, and fulfillment of the mri criteria for ms. in a patient with first episode of adem, criteria for ms are met, if after the initial adem, a second clinical event ( ) is non-encephalopathic, ( ) occurs or more months after the incident neurologic illness, and ( ) is associated with new mri findings consistent with revised radiologic criteria for dissemination in space. patients with anti-mog antibodies who relapse typically have further episodes of adem or optic neuritis, and typically do not have new lesions on mri during asymptomatic periods. adem is a polyfocal immune-mediated inflammatory demyelinating disease of the cns that involves multiple areas of the white matter, which mostly affects children under years of age. common antecedents include a recent viral or bacterial infection or more rarely immunization. the diagnosis is made in the clinical setting of acute onset of encephalopathy with other neurologic deficits and mri findings of multifocal demyelination after excluding cns infections. commonly, adem has a monophasic course in %- % of cases, with most children having a good recovery with high-dose intravenous steroid pulse treatment. ivig and plasmapheresis may be considered as second-and third-line therapies. adem overall has a good prognosis, but %- % of children may have neurocognitive dysfunction on follow-up. relapses may occur in %- % of patients in the form of multiphasic adem, optic neuritis, myelitis, or ms. there is need for further evaluation of biomarkers such as anti-mog antibodies for prediction of relapses and prognosis. acute disseminated encephalomyelitis: updates on an inflammatory cns syndrome consensus definitions proposed for pediatric multiple sclerosis and related disorders international pediatric multiple sclerosis study group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the definitions a long-term follow-up study using ipmssg criteria in children with cns demyelination paediatric multiple sclerosis and acute disseminated encephalomyelitis in germany: results of a nationwide survey 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acute osteomyelitis: a case report of methicillin resistant staphylococcus aureus acute tibial osteomyelitis with conventional radiography, computed tomography, and mri date: - - journal: radiol case rep doi: . /j.radcr. . . sha: doc_id: cord_uid: s scr r the tibia is an atypical site of osteomyelitis (om) in adults, and patients with this infection experience a significant degree of morbidity as well as the need for prolonged aggressive antibiotic therapy. the early diagnosis of om remains challenging, and often relies on imaging modalities which are of variable sensitivity. we present a case of a -year-old male with a methicillin resistant staphylococcus aureus (mrsa) left tibial om, contiguous left knee septic arthritis, and concurrent bacteraemia. eight days after the onset of pain in the left knee and lower limb, conventional radiography and computed tomography (ct) imaging had only subtleties of a soft tissue collection and a knee effusion. a mri demonstrated significant involvement of his tibial bone with a collection, from which surgical specimens confirmed mrsa. this case demonstrates the difficulty of diagnosing early acute om with conventional radiography and ct imaging, even after a week of symptoms in the affected limb. given the poor sensitivity of conventional radiography and ct in the diagnosis of early acute om, this case report illustrates how mri is the imaging modality of choice in this setting. mrsa. this case demonstrates the difficulty of diagnosing early acute om with conventional radiography and ct imaging, even after a week of symptoms in the affected limb. given the ✩ informed consent was gained from the patient for the manuscript. ✩✩ acute osteomyelitis (om), a bacterial infection of the bone, is a serious condition which has the potential to result in significant morbidity and high economic impacts on both the individual and the health care systems. it can develop as a complication of contiguous spread from an overlying soft tissue or joint infection, direct inoculation via an open fracture, following surgical or other procedures, or via haematogenous seeding [ ] . om has a bimodal age distribution, with acute and subacute haematogenous om more common in children and the metaphysis of long bones being the primary site of pediatric infection [ ] . in adults, direct inoculation of bone is the more common mechanism of bone infection, typically associated with open trauma in young adults, with contiguous soft tissue infection in diabetics, and with implant surgery such as hip and knee replacements in older adults. typical sites of nonimplant-associated adult om are the tarsal, metatarsal, toe and vertebral bones. adults at increased risk for hematogenous om include intravenous drug users, patients with indwelling catheters, the immunosuppressed, and those with compromised vascular supply [ , ] . the majority of acute om cases are monomicrobial and usually caused by staphylococcus aureus, both methicillin sensitive and methicillin resistant. polymicrobial infections are more likely to be seen on om complicating a contiguous focus of sepsis or open trauma. in this setting, common microorganisms including coagulase negative staphylococci, streptococci, enterococci, pseudomonas aeruginosa, the enterobacterales (enteric gram-negative rods), anaerobes, and in some epidemiological contexts mycobacterium tuberculosis [ , - ] . goals of om therapy includes eradication of infection, minimization of complications, and the restoration of functionality. for this to occur, many patients require a combination of both medical treatment and surgical intervention to ensure adequate drainage of all infected tissue and removal of any hardware present. however, the diagnosis of acute om remains a challenge in clinical practice. along with the assessment of history, clinical examination, microbiological and biochemical laboratory results, the use of imaging is central to the diagnosis of om. plain x-rays are the initial imaging modality of choice and are useful in detecting noninfectious bony disease and more advanced sequelae of om, such as destructive changes of the bone. however, plain films are of variable sensitivity and early infection may not be evident on the initial images [ ] . computed tomography (ct) also has utility in the setting of om, where it is particularly useful in detection of sequestrum in the setting of chronic om [ ] . as with plain x-rays, though, ct is limited in its ability to demonstrate bone marrow oedema which is a key feature of acute om [ ] . hence ct scans are often not diagnostically useful in the acute setting. magnetic resonance imaging (mri) on the other hand, appears to be the most sensitive imaging modality in acute om and can demonstrate early features of infection such as bone marrow oedema just days after infection onset [ , ] . in a meta-analysis of the accuracy of diagnostic tests for om in diabetic patients with foot ulcers, dinh et al. showed that plain radiography had a sensitivity of . and a specificity of . whereas mri had a sensitivity of . and a specificity of . [ ] . furthermore mri has the ability to detect associated soft tissue changes and micro-abscesses whether intraosseous or extraosseous which can assist in surgical drainage targets and source control [ ] . in this case report, we describe a patient with acute tibial om secondary to haematogenous dissemination who did not have diagnostic features of om on conventional radiographs or ct. he had vivid features of om on mri, supporting the notion that acute om may often require mri for diagnosis when initial conventional imaging is unremarkable. a -year-old caucasian male who presented with a -day history of fevers, progressive knee pain, and limited range of motion in his left lower limb. presentation for medical review was delayed due to concerns regarding coronavirus disease infection (covid- ). he had a background history of intravenous injecting drug use years prior, current oral opioid maintenance, and a recent prolonged hospital admission for a left sacroiliac om and a right wrist septic arthritis caused by bacteroides fragilis and streptococcus agalactiae . this had required removal of metal hardware and multiple washouts. the patient further reported a right dorsal foot injury months prior to admission where he sustained a cut from an oyster which had developed into a chronic wound which was described to have had purulent discharge in the weeks prior to admission. other relevant history included a long history of motocross sporting injuries with multiple long bone fractures in his upper limbs and previous skin grafts to these sites. the patient's vital signs were all within normal limits and he was afebrile. physical examination revealed warmth over the left lower limb at the tibial plateau and the left knee. the knee had no clinically evident effusion and preserved passive range of motion. the patient had mild peripheral oedema of the left leg in comparison to the right. there was no erythema, overlying skin lesion or indication of recent trauma in the left leg. he had an ulcerated ovoid wound ( × cm) over his right foot (see fig. ) with minor purulent discharge. there was no erythema, pain, warmth or tenderness over his left sacroiliac area or right wrist, the sites of his previous infection. his cardiorespiratory and gastrointestinal tract examination were unremarkable. admission investigations revealed that he had a raised white cell count of × /l with a neutrophilia of . × /l. his hemoglobin was with a microcytosis, his platelet count was and his c-reactive protein was . he had normal renal function and only trivial derangement of liver function tests. blood cultures taken on admission grew a nonmultiresistant methicillin resistant s. aureus with a vancomycin minimal inhibitory concentration of μg/ml. a swab of the right foot wound grew mrsa sensitive to rifampicin, fusidic acid, trimethoprim/sulfamethoxazole, doxycycline and clindamycin. surgical specimens from the left knee and tibial washout grew an identical mrsa. x-ray imaging of the patient's left knee demonstrated a small joint effusion (see fig. ). there were no erosive or destructive changes. x-ray of the right foot was noncontributory. on ct of the left leg there was no bony erosion, periostitis, acute fracture, or left knee effusion identified (see fig. ). there was a small volume of complex fluid between the medial head of the gastrocnemius and soleus muscles, which was suggested to be an acute rupture of the plantaris tendon, although clinically this was unlikely in the absence of acute onset pain. with the patient's ongoing pain, raised inflammatory markers and the identification of mrsa bacteraemia, there was a suspicion of tibial om. mri performed on day after symptom onset demonstrated heterogeneous marrow signal with areas of t weighted hyperintense confluent change and patchy enhancement following gadolinium administration in the proximal tibia, as well as a multilobulated collection extending along the posterior cortex (see fig. ). there was a small infected suprapatellar joint effusion and increased oedema in hoffa's fat pad. on subsequent mri imaging a week later, a focal defect in the posterior cortex of the tibia at the proximal metaphysis was visualized, highlighting the anatomical path of contiguous spread from the tibia into the left knee joint. following diagnostic confirmation of the patient's acute om by the mri scan, he underwent an operative washout of the areas of bony infection. intravenous vancomycin and oral clindamycin mg times daily were administered. the infected right foot wound, which presumably represented the original portal of entry of his bloodstream infection, was treated with bedside debridement, microdacyn spray and compression bandaging. following these interventions, the patient improved significantly, and further blood cultures were negative for mrsa. a minimum of weeks aggressive antimicrobial therapy was planned. this case illustrates the diagnostic challenges often encountered in a patient clinically suspected to have acute haematogenous om. despite clinical features, microbiological and other laboratory findings that supported a diagnosis of fig. -selected sagittal and axial slices, t spectral presaturation with inversion recovery following the administration of gadolinium (a and b), and t fat saturation (c and d) sequences demonstrate marked marrow oedema in the proximal tibia with patchy gadolinium enhancement. there is a focal area (x) of cortical thinning with possible breach. no intraosseous abscess is visible. there is an adjacent fluid collection (short arrows) with peripheral enhancement consistent with abscess formation (arrowheads). oedema and enhancement extend to the soft tissues, involving hoffa's fatpad, the adjacent musculature, and subcutaneous tissues. there is also a small enhancing suprapatellar effusion (long arrow) suggesting articular involvement. om, the patient's initial tibial imaging results by conventional radiography and ct were unconvincing. further assessment by mri was required before a definitive diagnosis could be made and hence appropriate medical and surgical treatment initiated. this underscores the importance of pursuing bone imaging in the form of mri in the setting of suspected early acute om, particularly when the clinical concern for bone infection presentation is unsupported by the conventional radiography and ct findings. despite its demonstrable utility, the limited availability of mri and contraindications to using this modality make the appropriate imaging pathway for acute om an ongoing challenge. while mri confers several advantages in the diagnosis of om, there are several instances and settings where mri may not be practicable or possible, placing significant limitations on its utility [ ] . some contraindications include devices, such as permanent pacemakers not compatible with mris, or metallic foreign objects in certain locations, such as in the eye, and even aneurysm coils that have been inserted previously. in addition, imaging artifacts from metallic hardware or prostheses may obscure findings despite the use of modern artifact suppression techniques. similarly, hardware artifacts may also complicate ct interpretation in suspected prosthesis-associated infections. mri is still not widely available in certain practice settings, particularly in remote and rural healthcare environments. in certain patient populations assessment with mri may also be difficult, such as patients with claustrophobia or those who may require general anesthesia, such as those with movement disorders or young children. alternative imaging methods for acute om may also be considered in settings where mri may not be practicable, such as the use of nuclear imaging modalities and dual energy-ct. several nuclear imaging techniques may be considered, including positron emission tomography (pet) scans, -phase bone scans, and tagged white blood cell scans. in these scans, areas of increased uptake of injected radionuclide can be detected by a gamma camera, and correspond with areas of abnormal bone metabolism suggesting the presence of om [ ] . a recent meta-analysis by treglia et al. suggested that fluorine- -labeled fluorodeoxyglucose pet imaging and pet/ct imaging were useful in the suspected om related to diabetic foot with high specificity [ ] . however, several other pathological processes can also result in abnormal bone metabolism, such as degenerative bone disease or tumors. there may also be poor anatomical localization of disease, even when ct co-registered images are produced, usually inferior to that achieved with mri [ ] . there has also been interest in the applications of dual energy-ct (dect), where it has several uses, such as in the detection of monosodium urate deposition in gout, and in the detection of bone marrow oedema, particularly in the setting of fractures [ ] . a systematic review by suh et al., which included studies, that assessed the sensitivity and specificity of dect in detecting bone marrow oedema found that dect had excellent sensitivity and specificity for bone marrow oedema detection, with a pooled specificity of . and a pooled sensitivity of . [ ] . more recently, muller et al. investigated the utility of dect, in comparison to mri, in assessing bone marrow oedema and fracture in those with wrist trauma and suspected wrist fracture who had negative radiographs, and found that in terms of detection of bone marrow oedema, dect had a high specificity and moderate sensitivity [ ] . however, despite increasing evidence in the use dect in bone marrow oedema detection, whether this translates to better diagnostic utility in acute om compared to other more established imaging modalities remains uncertain and hence should be the subject of further future research directions. acute haematogenous long bone om with contiguous spread into an adjacent joint is a rare occurrence in adults in modern times, although it was well described in the preantibiotic era. at the onset of om, imaging studies including conventional radiography and ct may appear unremarkable, lacking features suggestive of acute active infection. this case report highlights the significant disease severity that can be demonstrated on a mri in the setting of a normal conventional radiography and computed tomography imaging. whilst there are several practical limitations to the use of mri that may preclude its universal use, this case underscores its potential utility in the early diagnosis of acute om in order that timely and appropriate management and treatment can be initiated in such patients. the host and the skeletal infection: classification and pathogenesis of acute bacterial bone and joint sepsis mandell, douglas, and bennett's principles and practice of infectious diseases osteomyelitis-a historical and basic sciences review bacterial osteomyelitis: microbiological, clinical, therapeutic, and evolutive characteristics of episodes microbiology and management of joint and bone infections due to anaerobic bacteria trends in the epidemiology of osteomyelitis: a population-based study diagnostic accuracy of the physical examination and imaging tests for osteomyelitis underlying diabetic foot ulcers: meta-analysis radiographic imaging in osteomyelitis: the role of plain radiography, computed tomography, ultrasonography, magnetic resonance imaging, and scintigraphy. seminars in plastic surgery. © thieme medical publishers the imaging of osteomyelitis radiologic approach to musculoskeletal infections infection: musculoskeletal soft-tissue infections and their imaging mimics: from cellulitis to necrotizing fasciitis diagnostic performance of fluorine- -fluorodeoxyglucose positron emission tomography for the diagnosis of osteomyelitis related to diabetic foot: a systematic review and a meta-analysis current concepts in posttraumatic osteomyelitis: a diagnostic challenge with new imaging options dual-energy ct: a promising new technique for assessment of the musculoskeletal system diagnostic performance of dual-energy ct for the detection of bone marrow oedema: a systematic review and meta-analysis dual-energy ct for suspected radiographically negative wrist fractures: a prospective diagnostic test accuracy study key: cord- -z k wuhm authors: bonardel, claire; bonnerot, mathieu; ludwig, marie; vadot, wilfried; beaune, gaspard; chanzy, bruno; cornut, lucie; baysson, hélène; farines, magali; combes, isabelle; macheda, gabriel; bing, fabrice title: bilateral posterior infarction in a sars-cov- infected patient: discussion about an unusual case date: - - journal: j stroke cerebrovasc dis doi: . /j.jstrokecerebrovasdis. . sha: doc_id: cord_uid: z k wuhm in time of sars-cov pandemic, neurologists need to be vigilant for cerebrovascular complications of covid- . we present a case of bilateral occipito-temporal infarction revealed by a sudden cortical blindness with haemorrhagic transformation after intravenous thrombolysis in a diabetic patient infected by covid- . differential diagnoses are discussed in front of this unusual presentation and evolution. bilateral posterior infarction in a sars-cov- infected patient: discussion about an unusual case abstract in time of sars-cov pandemic, neurologists need to be vigilant for cerebrovascular complications of covid- . we present a case of bilateral occipito-temporal infarction revealed by a sudden cortical blindness with haemorrhagic transformation after intravenous thrombolysis in a diabetic patient infected by . differential diagnoses are discussed in front of this unusual presentation and evolution. a -year-old-man presented with one-week history of cough, dysgeusia and diarrhea. the patient complained of moderate headache without fever. the patient had a history of diabetes mellitus, hypertension and obesity. blood investigation showed a lymphocytopenia ( . giga/l), an increased fibrinogen ( . g/l), ferritin ( µg/l), creatin-kinase ( ui/l), c-reactive protein ( g/l), asat ( ui/l) and glycated hemoglobin ( . %) concentrations. prothrombin ratio was low ( %). antiphospholipid, platelets and partial thromboplastin time were normal. the rt-pcr for sars-cov- using a nasopharyngeal swab was positive. a chest scan showed bilateral ground glass opacities concerning more than % of the parenchymal lung ( figure ). six days after arrival and minutes after the fourth injection of remdesivir (loading dose: mg iv, mg iv per day thereafter), he presented an abrupt cortical blindness and disorientation (nihss score: ). an atrial fibrillation (af) was recorded. a first brain mri performed one hour after clinical onset showed bilateral and asymmetric acute occipito-temporal infarction without visibility of the p segments of the posterior cerebral arteries (pca) (figure a to c). fluid-attenuated inversion recovery (flair), t *, mr venography and mr angiography of the supra-aortic trunks were normal. no pathological enhancement in leptomeningeal spaces was observed. alteplase was injected min after symptom onset. the following morning, blindness was unchanged and anterograde memory disorders with anosognosia were noticed. the -hour control multimodality mri showed a haemorrhagic transformation of the previous lesions ( figure e -f). dynamic susceptibilityweighted contrast-enhanced magnetic resonance perfusion imaging (dsc-mri perfusion) showed an increase of cerebral blood volume (cbv) and flow (cbf) in the right thalamus and an increase of the mean transit time (mtt) and cbv in the right hemisphere ( figure h ). distal segments of the pca were permeable ( figure d ). nine hours later, the patient died due to a rapid respiratory breakdown, without neurological worsening. this bilateral cerebral posterior stroke may be secondary to an embolic event (af). stroke could also be explained by the state of hypercoagulability induced by sars-cov- infection . severe patients are more likely to have neurologic symptoms and bilateral frontotemporal hypoperfusion has been reported. in our case, mtt and cbv were increased in the right hemisphere which may reflect reduced cerebral perfusion pressure. the increase value of the cbf in the right thalamus may correspond to a post-recanalization hyperperfusion . other stroke mechanisms can be suggested. infection may have induced cerebral vasculitis, explaining the stroke and the perfusion's anomalies. severe reversible cerebral vasoconstriction syndrome (rcvs) cases with cerebral infarction and intracranial haemorrhage have been reported but the absence of thunderclap headache is unusual in rcvs . the absence of rapid increase in blood pressure and the presence of an initial cytotoxic oedema instead of vasogenic is less in favour of posterior reversible encephalopathy syndrome (pres) . an adverse effect of remdesivir is also to be discussed, but no neurological adverse effect potentially related to remdesivir have been reported . finally, the absence of thalamus involvement makes the diagnosis of acute necrotizing encephalitis unlikely . in conclusion, the origin of the stroke is probably multifactorial: the cytokine storm syndrome and hypercoagulability may have induced blood flow dysregulation, associated with an embolic event that may finally induce arterial thrombosis. a cerebral artery vasculitis or a rvcs are not excluded. this unusual case confirms the increased risk of thrombotic events in sars-cov infected patients. figures legend figure . axial ct scanner shows focal subpleural ground-glass opacities in the left and right lobes. the right lower lobe lesion is accompanied by air bronchogram (arrow). second mri (d to f). tof shows better visualisation of distal segments of bilateral pca (arrows) (d). fluid--attenuated inversion recovery (flair) shows a hypersignal in the initial ischemic lesions (initial flair was normal) (e). susceptibility-weighted imaging (swi) shows hypointensity (haemorrhage) concerning the totality of the ischemic lesion (f). mri perfusion shows an increase cerebral blood volume (cbv) in the right thalamus (arrow) (g) and an increase of mtt in the right hemisphere (h). annecy hospital annecy hospital * corresponding author: fabrice bing imaging unit, annecy hospital, metz-tessy, france email : fabricebing@yahoo.fr phone number author contact information: claire bonardel: cbonardel@chu-grenoble.fr mathieu bonnerot: mbonnerot@ch-annecygenevois.fr wilfried vadot: wvadot@ch-annecygenevois.fr gaspard beaune: gbeaune@ch-annecygenevois.fr lucie cornut : lcornut@ch-annecygenevois.fr hélène baysson : hbaysson@ch-annecygenevois.fr magali farines : mfarines@ch-annecygenevois.fr isabelle combes : icombes@ch-annecygenevois.fr gabriel macheda : gmacheda@ch-annecygenevois.fr keywords: infarction; mr perfusion; covid- ; visual loss; sars-cov running title: stroke in a sars-cov- infected patient conflict of interest: the authors report no disclosures difference of coagulation features between severe pneumonia induced by sars-cov and non-sars-cov neurologic manifestations of hospitalized patients with coronavirus disease neurologic features in severe sars-cov- infection diffusion-perfusion mri characterization of postrecanalization hyperperfusion in humans severe reversible cerebral vasoconstriction syndrome with large posterior cerebral infarction posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome: clinical and radiological considerations controlled trial of ebola virus disease therapeutics covid- -associated acute hemorrhagic necrotizing encephalopathy: ct and mri features key: cord- -efb j u authors: zheng, li-zhen; liu, zhong; lei, ming; peng, jiang; he, yi-xin; xie, xin-hui; man, chi-wai; huang, le; wang, xin-luan; fong, daniel tik-pui; xiao, de-ming; wang, da-ping; chen, yang; feng, jian q.; liu, ying; zhang, ge; qin, ling title: steroid-associated hip joint collapse in bipedal emus date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: efb j u in this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. five adult male emus were treated with a steroid-associated osteonecrosis (saon) induction protocol using combination of pulsed lipopolysaccharide (lps) and methylprednisolone (mps). additional three emus were used as normal control. post-induction, emu gait was observed, magnetic resonance imaging (mri) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. emus were sacrificed at week post-induction, bilateral femora were collected for micro-computed tomography (micro-ct) and histological analysis. asymmetric limping gait and abnormal mri signals were found in steroid-treated emus. saon was found in all emus with a joint collapse incidence of %. the percentage of neutrophils (neut %) and parameters on lipid metabolism significantly increased after induction. micro-ct revealed structure deterioration of subchondral trabecular bone. histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in saon group as compared with the normal controls. scanning electron microscope (sem) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in saon group. the combination of pulsed lps and mps developed in the current study was safe and effective to induce saon and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. in conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of on-induced hip joint collapse in patients. steroid-associated osteonecrosis (saon) is a common orthopaedic problem although steroids are initially prescribed for many non-orthopedic medical conditions, such as systemic lupus erythematosus (sle), organ transplantation, asthma, rheumatologic arthritis (ra), and severe acute respiratory syndrome (sars) [ ] [ ] [ ] [ ] [ ] . part of saon patients even evolved to hip joint collapse with subsequent total joint replacement [ , ] , and its long-term durability however still remained a big challenge [ ] . how to prevent accumulation of saon lesions is the first-line strategy for avoiding joint collapse. therefore, establishment of appropriated saon animal models that mimic clinical etiology and even evolves to joint collapse is desirable prior to translating prevention and treatment experimental protocols into clinical validation and applications. up to now there is lack of ideal animal models to exam the treatment efficiency or therapeutic strategy for saon-associated joint collapse. the limitation of the existing animal models, such as rabbit [ ] [ ] [ ] [ ] [ ] , rat [ ] [ ] [ ] [ ] , mouse [ , ] , pig [ , ] and chicken [ ] is that they fail to progress to the end-stage of saon, i.e. structural collapse of the weight-bearing joints. with bipedality, high activity level and large enough bodyweight similar to that of human beings, on model to be developed in emu femoral head could provide a unique opportunity to progress to human-like femoral head collapse [ , ] . focal cryogenic (liquid nitrogen) insults [ , ] and alternative cooling and heating insults [ ] have also been tested to induce on in emus with femoral head collapse. however, these models are not etiology-and or pathophysiology-orientated for saon research. accordingly, the aim of the current study was to establish a saon model in bipedal emus, with potentials to bone structural deterioration with subsequent femoral head collapse, a condition seen in saon patients attributed to similar biomechanics or loading ratio imposed onto the hip joint [ , ] . such a model would be essential for testing strategies to be developed for potential clinical applications for prevention and treatment of steroid-associated joint collapse. of all available animal models, rabbits were intensively used for establishing on model where either lipopolysaccharide (lps) [ ] or methylprednisolone (mps) [ , , ] or their combination (lps+mps) [ , ] were tested. all of them showed effectiveness in on induction, yet with varying degrees of on lesions and mortality of animals. based on our established saon rabbit model with a high incidence of on and low or no mortality that was induced by a combination of lps and mps [ , ] , we hypothesized that such a combination of pulsed lps and mps injections might also be able to induce saon in bipedal emus with subsequent hip joint collapse. the research ethics committee of shenzhen second peoples' hospital reviewed and approved the experimental protocols [licence no. - ] (appendix s ). both the guide for the care and use of laboratory animal ( ) [ ] and the arrive (animals in research: reporting in vivo experiments) guidelines [ ] were followed. eight months old young adult male emus were used for this study. they were kept in shenzhen emu institute and received food and water ad libitum. five emus assigned to the saon group were treated with a combination of lps and mps. three emus were used as controls without receiving either lps or mps. the emus were euthanized by intravenous injection of overdose of pentobarbital via jugular vein at weeks post injection. the details of this combined protocol were described as follows: each emu was intravenously injected with lipopolysaccharide (escherichia coli o :b ; sigma-aldrich, st. louis, mo, usa) twice via jugular vein with mg/kg body weight at an interval of days from day . thereafter, three injections of methylprednisolone (pharmacia & upjohn, peapack, nj, usa) with mg/kg body weight were given intramuscularly at gluteus muscle at an interval of days. in addition, each emu was intramuscularly injected at gluteus muscle with mg omeprazole sodium and orally with mg amoxicillin dispersible per day for days immediately after induction to prevent potential stomach ulcers and systemic infection ( figure s ). mri was performed with a . t mr unit (magnetom harmony; siemens, erlangen, germany) at baseline, week and then at monthly basis on saon induced emus for in vivo examination on bilateral proximal femora until weeks post induction. for facilitating in vivo bioimaging examination, a specific posture fixture was designed to obtain a highly reproducible image during mri scanning ( figure s ) . a phased-array body coil was used for mri scanning. coronal turbo spin-echo fatsaturated t -weighted images ( ms repetition time, ms echo time) were obtained with a slice thickness of mm and interslice gap of . mm from a field of view of mm mm with a matrix of pixels. blood was sampled at baseline, week , and post induction for routine blood examination and serum was prepared for examination of both coagulation and lipid metabolism. the serum parameters related to lipid metabolism, including total cholesterol (tc), total glycerin (tg), low-density lipoprotein (ldl) and high-density lipoprotein (hdl), and the serum parameters related to coagulation, including prothrombin time (pt), prothrombin time and international normalized ratio (pt/ inr), fibrinogen (fbg) and thrombin time (tt), were tested using standard clinical laboratory protocols for blood chemistry in shenzhen second peoples' hospital. gait of emus with saon was observed regularly after induction by recording abnormal gait pattern using a video camera. normal gait of the control emus was also recorded for comparison (video s and s ). emus walked or ran on a -meter walkway, and the sagittal plane motion was videotaped at hz by a highspeed video camera (casio ex-f , japan). the videos were analyzed by a motion analysis system (kwon d xp, korea) to obtain the included ankle joint angle during a gait stride cycle with respect to the time presented in term of percentage stride. gait pattern was defined abnormal when there was a deviation of the included ankle joint kinematics (more than degrees at any time) or the proportion of the stance and swing time (more than % deviation from control case). bilateral proximal femora from both control group and saon group were sampled and fixed in % buffered neutral formalin solution for days, and then soaked in % ethyl alcohol for measurement of trabecular morphology within and around on lesions. in brief, the proximal femur was scanned using a highresolution peripheral ct (hr-pqct) (xtreme ct, scanco medical, brüttisellen, switzerland) at a voltage of kv and a current of ua, with entire scan length of mm in a spatial resolution of mm used for animal experimental studies [ , ] . after the initial scanning, -dimentiaonal ( -d) images were realigned in the z-axis along the direction of femoral neck for further evaluation. for separating the signals of the mineralized tissue from the background signal, noise was removed using a lowpass gaussian filter (sigma = . , support = ) and mineralized tissue was then defined at a threshold of . -d structures of entire femoral heads were then reconstructed. the collapse was identified when fracture and/or clear deformation appeared in femoral head. a mm mm mm region in the centre of femoral head was defined as the region of interest (roi) for analysis and comparison. roi was defined within subchondral region centered in the collapsed region or the corresponding region of the non-collapsed femoral heads, where the largest thickness of this roi was / diameter of the femoral head. bone mineral density (bmd), bone tissue volume fraction (bv/tv), trabecular number (tb. n), trabecular thickness (tb. th) and trabecular separation (tb. sp) in the roi were measured separately by the workstation with the built-in hr-pqct software. after micro-ct scanning, femoral heads were sawed in half longitudinally along the coronal plane. halves were decalcified and embedded in paraffin; and halves were embedded in methyl methacrylate (mma) without decalcification. . decalcified sections. for paraffin embedded samples, sections were sliced along the coronal plane for hematoxylin-eosin (h&e) and fast green and safranin o staining, respectively. a microscope imaging system (leica q mc; leica microsystems, wetzlar, germany) was used to digitalize the histological sections for histomorphometric evaluation. ) examination of on: the entire area of each h&e stained section was examined for the presence of on with the established criteria, i.e. diffuse presence of empty lacunae or pyknotic nuclei of osteocytes in the trabeculae, accompanied by surrounding necrotic bone marrow [ , ] . the femoral head with at least one on lesion was considered as on+, while that with no on lesion was considered as on- [ , ] . ) quantification of fat cells in bone marrow: fat cells were quantified for both average of fat cell size and fat cell area fraction. the total bone marrow in subchondral bone was fold magnified and captured. the fat cells were manually traced and then quantified. the fat cell size was interpreted by fetet's diameter, i.e. the longest distance between any two points along a region of interest (roi) boundary [ ] . the fat cell area fraction was defined as total marrow fat cell area normalized by total marrow tissue area [ ] . ) histomorphometry of the subchondral plate: the thickness of subchondral bone plate of the femoral head was measured on the images. at least views per section were randomly selected for measuring. the thickness was examined by measuring point-to-point distance from the top of the calcified cartilage to the deep surface of the subchondral bone plate [ ] . ) examination of articular cartilage: the average thickness of cartilage were examined by the total area of cartilage divided by the length of cartilage band measured from the manually traced region on the entire frontal sections for evaluation under magnification. the thickness of cartilage at the collapsed region or the corresponding region of the non-collapsed femoral head was also examined. the proteoglycans content was quantified by measuring the thickness of safranin o stained articular cartilage. ) calculation of osteoblasts: the osteoblast perimeter percentage (%ob.pm) was calculated as the ratio of the total perimeter of the trabecular surface covered by osteoblasts to the whole perimeter of the trabecular surface [ ] . ) blood vessel quantification: the number of blood vessels within the collapsed region or the corresponding region of the non-collapsed femoral head was quantified on h&e sections [ ] . . undecalcified sections. the mma embedded femoral heads were sectioned along the sawed plane using a diamond saw (isomet, buehler). the cut surface was polished on a soft cloth rotating wheel [ ] . the surfaces were acid-etched with % phosphoric acid for - seconds, followed by % sodium hypochlorite for minutes. the samples were then sputtercoated with gold and palladium, as described previously [ , ] and examined for bone matrix and features of osteocytes in the scanning electron microscope (sem) (jsm- , jeol, japan). statistical power was set . . and the type i error probability was set , . for calculating sample size (n = ) using ps (power and sample size calculations version . ) for establishing saon model based on our previous rabbit model with a saon incidence of % [ ] . the incidence of collapse was defined as the number of collapsed hips divided by total number of hips in each group. the incidence of saon was defined as the number of saon emus divided by total number of emus in each group, and analyzed with fisher's exact test. the serum parameters were expressed as mean sd, and analyzed by one way analysis of variance (anova) with a post hoc bonferroni's multiple comparison test to compare the differences between every time point and baseline. micro-ct and histomorphometry data were expressed as mean sd, and analyzed with mann whitney test to compare the differences between the control group and saon group. spss . was used. the significance for comparison was set at p, . . in t weighed mri images, intense signals of edema in the proximal femur were found at week post-induction when compared to the baseline. the edema signals in proximal femur decreased in t weighed mri image at week post induction ( figure ). no collapse was found from mri images in the first weeks after induction. the results of routine blood examination showed abnormal increase in percentage of neutrophils (neut %) at weeks post induction (figure a ). for the time course changes in serum parameters related to lipid metabolism, tc was significantly increased at each time point post-induction, and ratio between ldl and hdl as well as ldl was also significantly increased at each time point post-injection (p, . for all) while tg did not show significant increase post-induction ( figure b ). however, as compared with baseline, no significant difference was found for the time course changes in serum parameters related to coagulation post-induction ( figure c ). all emus were observed to be less active but with normal gait in the next day after the first lps injection; while an asymmetric limping gait pattern was firstly observed at week post induction during loading and unloading gait cycle ( figure ). in the early post-induction phase the asymmetric limping gait was only observable when the emus were running. with time the asymmetric limping gait was observed when emus were walking; closing to week post induction some of the emus were observed no more active and kept sitting most of the time. no emus died during the experiment period over weeks. all five emus in saon group developed edema, an early stage sign of on at bilateral hip based on mri observations as described above, in part also shown by gross morphology after sample harvesting ( figure a and b) , and confirmed histologically as described below. the incidence of hip joint collapse was % ( out of hips from emus) found in the saon group, including emus with bilateral collapse, emu with unilateral collapse, and without hip joint collapse ( figure a-f) . there was no collapse of the hip found in control group. micro-ct analysis was performed for the trabecular bone microarchitecture in the subchondral region ( figure e and f) and in the center of the femoral head ( figure g and h) , respectively. within the subchondral region, the bmd, bv/tv, tb. n and tb. th in the saon group were found significantly lower than those in the control group (p, . for all), while the tb. sp in the saon group was significantly higher than that in the control group (p, . ) ( table ) . however, no statistically significant difference was found for all micro-ct indices of trabecular bone in the centre of the femoral head between the control and saon group (table ) . gross coronal view of h&e stained femoral head in the control group showed well-arranged trabecular bone supporting the subchondral plate and the articular cartilage ( figure a ); while the collapsed femoral head in saon group was lack of vertical arranged trabecular bone to support the subchondral plate and the articular cartilage, and bone fracture shown at collapsed site ( figure a ). though % of hips from emus in the saon group developed hip collapse, % of hips from all emus in the saon group developed on at bilateral hips as confirmed histologically while as expected no on lesion was found in the control emus (p, . ) ( figure b , c, d, e). osteonecrosis was distributed in whole femoral head, including subchondral bone ( figure b , e) , middle of the femoral head ( figure c ) and femoral neck ( figure d ), with numerous empty lacunae in the trabeculae and marrow tissue degenerated. compared with the control group, the marrow fat cell size (fetet's diameter of fat cell) and fat cell area fraction in the saon group were increased significantly with decreased number of mononuclear cells (p, . for both, figure b and figure a , b). the thickness of subchondral plate of femoral head of saon emus was decreased significantly (p, . , figure c ). the articular cartilage of saon emus also showed pathological alteration with significantly thinner thickness (p, . , figure f , g and figure d ). the proteoglycans content as interpreted by maximum thickness of safranin o staining was decreased significantly in saon group (p, . , figure e ), with osteonecrosis located at the collapsed region ( figure e ). the osteoblasts perimeter percentage (% ob. pm) of the saon group was significantly lower than those in the control group (p, . , figure f ). the blood vessels at subchondral region of saon group were surrounded with enlarged and compacted arranged fat cells, with some blood cells effused out of the vessel (figure b ). at the collapsed region or the corresponding region of the non-collapsed femoral head, the number of blood vessels of saon group was significantly less than that of the normal group (p, . , figure g ). sem images showed that in the collapsed region there was no osteo-like structure; instead, there were more osteo-lacunae outline, with more removal of bone mineral or less matrix; and that in the normal control, there was osteon-like structure and there were few osteo-lacunae outline with much solid bone matrix (figure ). using a combined pulsed lps and mps induction protocol previously established for saon quadrupedal rabbits [ , ] , the present study established a saon model in bipedal emus characterized with subchondral bone deterioration and hip joint collapse, an experimental model mimicking human on often developed at hip joint with femoral head collapse. as bioimaging evidence, we used mri to evaluate in vivo alteration of mri signals in the first weeks post induction as mri could diagnose early-stage on, even presymptomatically [ ] . abnormal signals were firstly detected at week postinduction, showing large scales of edema at the proximal femora. this phenomena is similar to clinical on where the bone marrow edema was found from mri earlier than either formation of the necrotic lesion or the collapse of the necrotic fragment [ ] . however, mri of emu hips merely shows bone marrow edema without typical band pattern shown in initial mri signaling of on patients [ , ] . this could be explained by the differences in anatomy and physiology of human (mammals) and emu (aves), such as that the bone marrow of emu hip mainly presented in subchondral bone in a shell-shaped region and there was hollow structure in emu's bone marrow cavity at both femoral neck and head. irrespective such differences, there were common structural features, i.e. on lesion and hip joint collapse found in saon emus and this would provide a platform, i.e. a large bipedal animal model for testing biomaterials developed for bone defect repair, including for that after surgical core-decompression in hip joints, a condition indicated for patients with early stage of on. for functional evidence, asymmetric limping gait was observed at week post-induction, suggesting that emus might suffer from joint pain caused by the on lesion formation and structural damage confirm histologically after harvesting the samples for detailed analysis. this symptom was also common in patients at early stage of on [ ] . the asymmetric limping gait shown in bipedal emus was similar to the low limb dysfunction in saon patients with subchondral lesions [ ] . for biochemical evidence, the current study suggested hyperlipidemia occurred after saon induction, which was evidenced by a significant increase in tc at all examined time point postinduction. in addition, abnormal higher lipid transportation to the peripheral tissues also occurred after induction, as evidenced by a significant increase in ldl/hdl, which was consistent with the results found in both saon rabbit model [ , ] and on patients [ ] . however, there was no significant difference in coagulation- related parameters after induction as compared with baseline, while hypercoagulable and hypofibrinolysis state were reported in saon rabbit model [ , ] and sars on patients [ ] . this inconsistency suggested that the pathogenesis of saon in emu might be explained by the dominant disorder in lipid metabolism. histological and histomorphometric analysis was performed in three rois of the femoral head, including the articular cartilage, subchondral bone region and the central part of the femoral head. under higher magnification of the subchondral bone region where edema was shown in mri images, remarkable necrotic changes were observed in emu after induction, including ) avascular zone at load bearing region, referring to the blood vessels quantification within the collapsed region; ) extravascular adipogenesis (fat cell enlargement); ) apoptosis of osteocytes in regions next to the marrow region packed with fat cells; and ) thinning of subchondral bone, poor quality of bone matrix and more osteolacunae that weakens the mechanical integrity of the femoral head, which could also be weakened by the necrosis and thinning of articular cartilage. these were essential indices of later joint collapse, typically seen in saon patients [ , ] that were substantiated in our histomorphometric analysis. on the contrary, our micro-ct evaluation for the central region of the femoral head, where no bone structural collapse was demonstrated, implied that the pulsed lps-mps induction protocol did not result in general osteoporosis as no difference in boney structural and bmd was found between saon emus and normal controls in regions away from the subchondral bone. this finding was also similar to a bone densitometry study in sars patients who underwent pulsed steroid treatment in hong kong [ ] . no obvious osteoporosis found in saon patients with joint collapse or animals were mainly explained by short-term effects of pulsed corticosteroid administration that resulted in local damage of vasculature in the subchondral bone region and impairment of bone marrow mononuclear cells, which triggered up-regulation of osteoclastic activities and inadequate bone formation known as destructive repair [ , , , , , ]. yet, long-term steroid administration was known to be able to induce secondary osteoporosis in patients [ ] or animals [ ] . in spite of the presence of difference in hip anatomy, the similarity in biomechanics of the hip joint with regard to proportion of joint loading between human and bipedal emu was well characterized by iowa biomechanics research group [ , ] . the contact stress of femoral head was reported with a maximum hip contact force of approximately . times of body weight in emus, directed axially along its femoral neck, which was moderately larger than that of humans [ ] and the contact stress magnitude and the sites of habitual loading on the femoral head was also comparable between emu hip and the human hip [ ] . that the joint biomechanics plays a crucial role for no-induced hip joint collapse was also well supported by findings obtained from bipedal and quadrupedal animals. in fact, the on-induction protocol with a combination of lps and mps successfully induced saon in quadruped animals, yet without resulting in subchondral collapse [ ] , although inadequate repair was also demonstrated in quadruped saon animals [ ] . besides emu study, another report showed that the chicken was also bipedal animal suitable for building up saon animal model [ ] , yet their induction protocol did not result in hip joint collapse. in order to mimic on and hip joint collapse, we tested large bipedal emus not because of its similarity in hip joint biomechanics to that of human but mainly that emu hip was sizeable to perform core decompression and testing porous scaffold biomaterials developed for potential clinical applications [ ] [ ] [ ] . the saon induction protocol tested in the present study successfully induced hip joint collapse in large bipedal emus. the occurrence of hip joint collapse in emus was apparent more ( out of hips from emus) than clinical data, such as . % saon incidence reported by li zr and co-workers in their welldocumented clinical study in sars patients who were treated with a high dose of corticosteroid for life-saving [ ] . as saon incidence is often dose-dependent and the purpose of the current preclinical study is to establish a saon bipedal large animal model with high incidence of on and hip joint collapse, we tested much higher dose of mps as compared with clinical recommended dose for sars patients [ ] . differ to human situation where only mps was used, we used both lps and mps pulsed treatment, where lps served the purpose to mimic clinical conditions, i.e. disease-related tissue inflammation [ , ] , in addition to higher mechanical loading imposed to the hip joint in emus where emu hip joint share - % of the body weight as compared with around % of body weight in human [ ] . in present emu study, we selected two lps injections with days interval that showed safe and effective to induce saon. neut % increased weeks post induction and decreased gradually to baseline level from weeks to weeks post induction which indicated inflammation reaction induced by lps. no typical clinical shwartzman reaction was observed in emus as we did not systemically study the non-skeletal tissue thrombosis or reticuloendothelial blockage for comparison with that in saon patients. it would be of interest to study in details the differences in physical or immune responses between human and birds in saon in future. in our previous study, we established saon in rabbit with lps ( mg/kg) + mps ( mg/kg) [ ] . as emu was estimated with similar body surface area to that of human, we calculated the current experimental dose based on the conventional human-rabbit dose conversion. however, the dose for the initial experiment for emu was . mg/kg. as we found that emus could tolerate larger dosage from our pilot study, we increased mps dose to mg/kg for the current study at a time interval of days for avoiding potential side-effect of mps injection. specific design for studying dosing effects (amount and frequency of lps and mps treatment) would also be of interests for further studies. the limitation of the current experimental study is that we are not able to delineate if the cause of joint collapse is attributed to saon and/or cartilage and subchondral bone thinning as we did not observe typical destructive repair by uncoupling of osteoclasts and osteoblasts as well as extensive local fibrosis found within necrotic regions reported in both quadrupedal rabbit model [ ] or patients [ , ] . future studies shall be designed to monitor such pathological changes at various time points after oninduction. larger sample size would also be appreciated although our findings did reach statistical significance where we estimated sample size using ps (power and sample size calculations version . ) for establishing our current emu saon model based on our previous rabbit model with a saon incidence of % [ ] . in conclusion, this was the first experimental study to confirm that a combined injection protocol of pulsed lps and mps was able to induce on and deterioration of subchondral bone microarchitecture in bipedal emus, with subsequent femoral head collapse. the establishment of this bipedal emu model with hip joint collapse provided a platform for evaluation of potential treatment protocols to be developed for prevention of steroidassociated hip joint collapse. pathogenesis and natural history of osteonecrosis steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy the functional capacity of healthcare workers with history of severe acute respiratory distress syndrome (sars) complicated with 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experimental induction of osteonecrosis in rabbits with shwartzman reaction protective effect of genistein aglycone on the development of osteonecrosis of the femoral head and secondary osteoporosis induced by methylprednisolone in rats glucocorticoid inhibits bone regeneration after osteonecrosis of the femoral head in aged female rats femoral artery constriction by norepinephrine is enhanced by methylprednisolone in a rat model femoral head osteonecrosis can be caused by disruption of the systemic immune response via the toll-like receptor signalling pathway a mouse model for glucocorticoid-induced osteonecrosis: effect of a steroid holiday pluripotential marrow cells produce adipocytes when transplanted into steroid-treated mice selective reduction of bone blood flow by short-term treatment with high-dose methylprednisolone. an experimental study in pigs femoral head blood flow reduction and hypercoagulability under h megadose steroid treatment in pigs the otto aufranc award. 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in patients with severe acute respiratory syndrome treated with steroids investigation of proximal femoral marrow with magnetic resonance imaging in recovered patients with severe acute respiratory syndrome reduced bone mineral density in male severe acute respiratory syndrome (sars) patients in hong kong relationship between bone marrow edema and development of symptoms in patients with osteonecrosis of the femoral head decrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid-induced osteonecrosis osteoporosis management in patients with rheumatoid arthritis: evidence for improvement hip joint contact force in the emu (dromaius novaehollandiae) during normal level walking contact stress distributions on the femoral head of the emu (dromaius novaehollandiae) comparative study of osteogenic potential of a composite scaffold incorporating either endogenous bone morphogenetic protein- or exogenous phytomolecule icaritin: an in vitro efficacy study exogenous phytoestrogenic molecule icaritin incorporated into a porous scaffold for enhancing bone defect repair plga/tcp composite scaffold incorporating bioactive phytomolecule icaritin for enhancement of bone defect repair in rabbits magnetic resonance imaging and histology of repair in femoral head osteonecrosis osteonecrosis of the jaws in patients treated with bisphosphonates -histomorphologic analysis in comparison with infected osteoradionecrosis the authors would like to thank medical staff from shenzhen second people's hospital, including dr. j xia for mri scanning and dr. jy xiong for providing anesthesia materials for animal experiments and dr. xh pan from the first peoples' hospital (shenzhen, china) for providing technical support. key: cord- -purunxce authors: waldman, amy; o'connor, erin; tennekoon, gihan title: childhood multiple sclerosis: a review date: - - journal: ment retard dev disabil res rev doi: . /mrdd. sha: doc_id: cord_uid: purunxce multiple sclerosis (ms) is an autoimmune demyelinating disorder of the central nervous system (cns) that is increasingly recognized as a disease that affects children. similar to adult‐onset ms, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. a lumbar puncture can be helpful in diagnosing ms when csf immunoglobulins and oligoclonal bands are present. white matter demyelinating lesions on mri are required for the diagnosis; however, children typically have fewer lesions than adults. many criteria have been proposed to diagnose ms that have been applied to children, mostly above years of age. the recent revisions to the mcdonald criteria allow for earlier diagnosis, such as after a clinically isolated event. however, children are more likely than adults to have monosymptomatic illnesses. none of the approved disease‐modifying therapies used in adult‐onset ms have been approved for pediatrics; however, a few studies have verified their safety and tolerability in children. although children and adults with ms have similar neurological symptoms, laboratory (cerebrospinal fluid) data, and neuroimaging findings, the clinical course, pathogenesis, and treatment of childhood onset ms require further investigation. mrdd research reviews ; : – . © wiley‐liss, inc. m ultiple sclerosis (ms) was first described more than years ago in adults. although rare, ms was recognized in children as early as [wechsler, ] . nevertheless, ms is still thought to be a disease of young adulthood, typically presenting between the ages of and years, and the diagnosis is rarely considered in children. physicians have questioned whether or not childhood ms is the same entity as seen in adults. in , gall et al. published one of the earliest retrospective studies on pediatric-onset ms [gall et al., ] . between and , children met inclusion criteria for the study. the patients demonstrated neurological signs and symptoms due to scattered lesions within the cns separated by time and space and supported by objective evidence. the study concluded that children and adults with ms have similar clinical profiles, including mode of onset, symptoms, and physical and laboratory (cerebral spinal fluid [csf]) findings. nevertheless, diagnosing ms in children is often difficult and controversial. the estimated prevalence of ms worldwide is per , with . - . % of patients presenting before the age of - years [ sindern et al., ; gadoth, ]. the calculated frequency of childhood-onset ms is . - . per , [gadoth, ] . ms has been diagnosed during infancy and early childhood (younger than years of age) accounting for . - . % of all cases [ruggieri et al., ] . there are reports of children presenting before the age of years, even as early as months [cole et al., ] . as seen in the adult population, there is a female predominance in childhood ms ranging from . - : [gall et al., ; duquette et al., ] . the presenting symptoms of ms in children are similar to those reported by adults. in , duquette et al. reviewed pediatric patients with ms who presented most commonly with either pure sensory symptoms or optic neuritis [duquette et al., ] . diplopia, pure motor symptoms, abnormal gait including ataxia (cerebellar or vestibular), mixed sensory and motor symptoms, and sphincter disturbances were also reported. in , sindern et al. identified patients with ms using poser's criteria (see diagnosis section) who presented before the age of years and compared them to sex-matched control patients diagnosed with ms between the ages of and years [sindern et al., ] . the most common finding at the onset of disease for both children and adults was optic neuritis, accounting for % and %, respectively. the second most common presenting symptom in children was sensory disturbance, seen in % of children and % of adults. transverse myelitis was more common in children, whereas motor symptoms were more common in adults ( %) than in children ( %). furthermore, in % of children, the initial presentation was rapid, resulting in admission to the hospital within a few hours to days. a longitudinal study by boiko et al. confirmed duquette's and sindern' s findings that sensory symptoms and optic neuritis were the most common initial manifestations in patients with the clinical onset of ms before the age of years [boiko et al., ] . in , poser et al. characterized the presentation of ms in adults (table ) [poser, ] , and the diagnosis of ms should be considered in children presenting with similar symptoms. the clinical course of ms is divided into four subtypes: relapsing-remitting (rrms), primary progressive (ppms), secondary progressive (spms), and progressive-relapsing (prms). rrms is the most common subtype in both adults and children. there are no diagnostic tests for ms. however, a lumbar puncture is routinely performed to obtain supportive evidence of cns inflammation. in approximately % of patients with childhoodonset ms, the routine analysis (cell count, protein, and glucose) of csf is normal [duquette et al., ; dale et al., ] . the remainder of patients has a lymphocytic pleocytosis (typically Ͻ cells/mm ) and/or elevated protein (typically Ͻ mg/dl) [dale et al., ] . intrathecal synthesis of immunoglobulin (ig), predominantly igg, is also seen in patients with ms. approximately % of children with ms have increased csf igg synthesis [jones, ] . furthermore, oligoclonal bands (ocb), markers of antibody synthesis in the cns, are present in about - % of adult patients with ms [olek and dawson, ] . in children, ocb were present in - % of patients and may appear later during disease convalescence or relapse [sindern et al., ; selcen et al., ; dale et al., ; jones, ]. ocb are not specific to ms [poser, ; olek and dawson, ] . they can be found in chronic cns infections, such as subacute sclerosing panencephalitis, viral infections of the cns, autoimmune neuropathies, cervical myelopathies, and cns tumors [ cohen et al., ] . magnetic resonance imaging (mri) reveals asymmetric, multifocal white matter lesions on t -weighted sequences and fluid-attenuated inversion recovery (flair) images [miller et al., ] . the lesions are most commonly located in the periventricular and subcortical white matter where they appear ovoid with extensions called dawson fingers [barkhof et al., ] . additional lesions can be seen in the cerebellum, spinal cord, basal ganglia, and thalami [dale et al., ] . new lesions may enhance with gadolinium administration. there are no longitudinal mri studies in childhood ms to establish whether there is progressive atrophy of the brain or the appearance of "black holes" (chronic inactive lesions). furthermore, unlike in adults, diffusion tensor imaging (dti) and magnetization transfer ratios (mtr) have not been systematically performed. finally, magnetic resonance spectroscopy (mrs) shows similar changes to those reported in adult ms patients with decreases in nacetyl aspartate (naa) reflecting neuronal loss, increases in choline reflecting remyelination, and increases in myoinositol reflecting gliosis [wolinsky and narayana, ] . ms remains a clinical diagnosis. in , poser et al. published guidelines incorporating laboratory, neuroimaging, and neurophysiologic data into the diagnostic criteria with four proposed subtypes: clinically definite ms, laboratory-supported definite ms, clinically probable ms, and laboratory-supported probable ms (see table ) . in , the mcdonald criteria were introduced to facilitate and simplify the diagnosis of ms for patients between and years [mcdonald et al., ] . the authors further defined mri criteria and included both monosymptomatic disease and ppms in the clinical presentations. caution was suggested in applying these guidelines to children younger than years. in fact, the sensitivity in diagnosing pediatric cases was questioned by a second panel that revised the mc-donald criteria in (see table ) [polman et al., ] . furthermore, hahn et al. reported that many pediatric patients did not meet the mcdonald mri criteria for dissemination in space (see table ) [hahn et al., ] . demonstrating dissemination in time (see table ) is also challenging in pediatrics due to the possibility of relapses in a monophasic disease (see differential diagnosis section). nevertheless, a repeat mri performed three months after the initial study is recommended to show dissemination in time. acute disseminated encephalomyelitis (adem), multiphasic disseminated encephalomyelitis (mdem), and ms share similar clinical presentations, laboratory data, and neuroimaging abnormalities. subtle differences between the [dale et al., ; hynson et al., ; stonehouse et al., ]. in addition, hepatitis b; measles, mumps, rubella (mmr); bacille calmette-guérin (bcg); meningitis a and c; rabies; influenza; smallpox; and japanese b encephalitis vaccines, given within the six weeks prior to the onset of adem, have been suspected in triggering an autoimmune response [dale et al., ] . clinically, adem is more likely to present with ataxia, encephalopathy, bilateral optic neuritis, and seizures [hynson et al., ] . children typically have a polysymptomatic presentation with sensory, pyramidal, cerebellar, and bulbar symptoms [dale et al., ] . headache, fever, meningismus, and vomiting are more often associated with adem [brass et al., ] . unilateral optic neuritis and internuclear ophthalmoplegia are more common in ms [dale et al., ] . in adem and ms, the csf can be normal, although many patients have a lymphocytic pleocytosis or elevated protein. in adem, the csf white blood cell (wbc) count can be as high as cells/mm , with a mean around cells/ mm . in ms, the cell count is lower (range, - cells/mm ; mean, cells/ mm ) [dale et al., ] . the csf protein varies from . to . g/dl (mean, . g/dl) and . to . g/dl (mean, . g/dl) in adem and ms, respectively [dale et al., ] . ocb are seen in the csf in more than half of patients with childhood ms but can be seen in adem [dale et al., ; brass et al., ] . with considerable overlap between clinical and laboratory findings, mri is an important tool in determining the difference between adem and ms. both can affect the periventricular, sub-cortical, and deep white matter; deep gray matter; brainstem; cerebellum; and spinal cord. cortical white matter lesions are typically bilateral but asymmetric. in adem, lesions are less likely to be periventricular. also, adem more com- yr of disease progression (retrospectively or prospectively determined) and two of the following: a) positive brain mri ( t lesions or or more t lesions with positive vep) f b) positive spinal cord mri (two focal t lesions) c) positive csf d note: if criteria indicated are fulfilled and there is no better explanation for the clinical presentation, the diagnosis is ms; if suspicious, but the criteria are not completely met, the diagnosis is "possible ms," if another diagnosis arises during the evaluation that better explains the entire clinical presentation, then the diagnosis is "not ms." a an attack is defined as an episode of neurological disturbance for which causative lesions are likely to be inflammatory and demyelinating in nature. there should be subjective report (backed up by objective findings) or objective observation that the event lasts for at least hr. b no additional tests are required; however, if tests (mri, csf) are undertaken and are negative, extreme caution needs to be taken before making a diagnosis of ms. alternative diagnoses must be considered. there must be no better explanation for the clinical picture and some objective evidence to support a diagnosis of ms. c mri demonstration of space dissemination must fulfill the criteria derived from barkhof et al. [ ] and tintoré et al. [ ] as presented in table . d positive csf determined using ocb detected using established methods (isoelectric focusing) different from any such bands in serum, or using an increased igg index. e mri demonstration of time dissemination must fulfill the criteria in table . f abnormal vep of the type seen in ms. abbreviation: vep, visual-evoked potential. three of the following are required for demonstrating dissemination in space . at least one gadolinium-enhancing lesion or nine t hyperintense lesions if there is no gadolinium-enhancing lesion . at least one infratentorial lesion . at least one juxtacortical lesion . at least three periventricular lesions there are two ways to show dissemination in time: . detection of gadolinium enhancement at least three months after the onset of the initial clinical event, if not at the site corresponding to the initial event . detection of a new t lesion if it appears at any time compared with a reference scan done at least days after the onset of the initial clinical event note: a spinal cord lesion can be considered equivalent to a brain infratentorial lesion, an enhancing spinal cord lesion is considered to be equivalent to an enhancing brain lesion, and individual spinal cord lesions can contribute together with individual brain lesions to reach the required number of t lesions. based on data from barkhof et al. [ ] and tintoré et al. [ ] . monly affects the thalami and basal ganglia, with a greater tendency for symmetry in the latter [dale et al., ] . in adem, a repeat mri scan performed more than two months after the onset of symptoms often shows partial or complete resolution of lesions with no new lesions. enhancement after the administration of gadolinium can be seen on the initial scan; however, no lesions enhance on the follow-up mri in adem. in ms, both new and enhancing lesions may be present when the scan is repeated, although the time to develop new lesions is unpredictable. in the absence of clinical symptoms, new findings on mri are useful in differentiating ms from adem. mdem presents a challenging dilemma in diagnosing childhood-onset ms. the clinical presentation, laboratory data, and neuroimaging features of mdem resemble adem, both of which are monophasic illnesses. however, patients with mdem have a clinical relapse after their initial illness or develop new lesions on mri, suggestive of a chronic demyelinating disease or ms. despite the presence of new lesions on mri, suggesting dissemination in time, some investigators believe that mdem and ms are separate entities. a diagnosis of mdem should be reserved for patients whose relapses are caused by the same trigger responsible for the inciting event and occur shortly after presentation or within two months of discontinuing steroids [dale et al., ] . ms is a neurodegenerative disease that affects young adults and children, often women. linkage and twin studies demonstrate that individuals carry a genetic susceptibility to this disease [rice, ] . a susceptibility locus for ms has been identified on chromosome , specifically the major histocompatability complex (mhc) class ii alleles human leukocyte antigens (hla) dr and dq . this association is seen in all populations. in sardinians, there is an additional association with dr , and, in turks, there is an association with dr and dr . in finns, there is an association of ms with myelin basic protein (chromosome ); however, neither this association nor an association with any other myelin genes has been noted in non-finnish populations [kenealy et al., ] . aside from the mhc locus, other regions of interest identified from the united kingdom study for ms susceptibility are located on chromosomes , , p, p, q, q, q, and xp [chataway et al., ] . some of the genes in these regions include tumor necrosis factor [tnf]␣, interleukin [il]- ra, il- , and cytotoxic t-lymphocyte-associated protein (ctla- ). aside from the genetic predisposition for ms, epidemiological data indicates that an environmental factor also plays a role [compston, ] . for some time, an infectious agent has been suspected in triggering an autoimmune response. this theory was supported by apparent epidemics that occurred in the faroe islands and iceland following world war ii [rice, ] . additional support for an infectious etiology was provided by further studies that showed elevated antiviral titers (measles, rubella, mumps, varicella/zoster, ebv, influenza/parainfluenza,coronavirus, htlv- , borna, etc) in the csf of ms patients during an acute exacerbation [ sibley et al., ; panitch, ] . presumably, the elevated titers represent nonspecific activation of b cells in the nervous system. in addition, the ms literature is replete with the isolation of viruses from the brains of patients with ms including measles, coronavirus, retroviruses, htlv- , hhv- , and scrapie agent. current focus on infectious agents includes ebv, hhv- , endogenous retroviruses such as herv-w, and chlamydia pneumoniae [johnson and major, ] . oldstone postulated that an environmental trigger activates the immune system by "molecular mimicry" in which an infectious agent has sequence homology to a myelin protein. following the infection, tolerance is broken and an immune response ensues with the appearance of autoreactive t cells (cd and cd ) [oldstone, ] . alternatively, the pathogen activates toll receptors that then initiate the cellular immune response with the production of il- and il- [vasselon and detmers, ; frohman et al., ] . the earliest pathological change seen in an ms lesion is oligodendrocyte apoptosis with microglial activation but lacking infiltrating lymphocytes [barnett and prineas, ; matute and pérez-cerdá, ] . older lesions have perivascular infiltration by lymphocytes, plasma cells, and macrophages; loss of myelin and oligodendrocytes; axonal damage; and reactive astrocytes. chronic lesions are sharply demarcated with a hypocellular center and axonal loss, perivascular infiltration by lymphocytes, and increased number of oligodendrocytes. in chronic silent lesions, there is a loss of axons and oligodendrocytes. lucchinetti et al. have grouped the neuropathological lesions into four types, each containing t cells [lucchinetti et al., [lucchinetti et al., , [lucchinetti et al., , . type is characterized by a predominance of macrophages, type ii by the deposition of immune complexes, type iii by oligodendrocyte malfunction, and type iv by oligodendrocyte death. there is insufficient data to describe the pathology of ms in children. ms is an organ-specific autoimmune disease mediated by type helper t cells (t h ) that recognize components of myelin and induce an inflammatory process by recruiting other inflammatory cells such as macrophages. in patients with ms, myelin-reactive t cells found in the blood stream produce a cytokine profile consistent with t h cells. in demyelinating lesions, t h cytokines, such as interferon ␥, tnf-␣, and il- , are expressed by these leukocytes. the chemokine profile also suggests a t h -mediated inflammatory process. nevertheless, ms is likely to be more than a purely t h -mediated disease because it is likely that cd cells, macrophages, b cells, and a paucity of regulatory t cells also play a role [merrill, ; sorensen et al., ; frohman et al., ] . therapy in ms targets four different aspects of a child's illness. first, disease-modifying drugs, or immunomodulators (id), are used to alter the biological activity of the disease, thereby preventing neurological disability. second, additional medications help alleviate symptoms such as fatigue, spasticity, bladder dysfunction, and depression. third, neuroprotective agents are being studied to prevent and repair nerve injury. finally, rehabilitation is needed to overcome physical handicaps. disease modifying, symptomatic, and neuroprotective therapies will be described in this review. in evaluating effectiveness of therapies that modify the biological activity of the disease in children, a major challenge is the inability to predict the outcome of the disease and the lack of good outcome measures. the goal of any disease-altering therapy is to prevent longterm disability which evolves over many years [goodin et al., ] . the efficacy of the newer therapies has predominantly been studied over a short time period. moreover, the expanded disability status scale (edss) that is used as an outcome measure in adult studies has not been validated for use in children. children with ms may have cognitive dysfunction, which has not been evaluated as an outcome measure, although the ms functional composite (msfc) places some weight on mental functioning. once again, the utility of this scale has not been established in children. currently, most studies use the short-term attack rate as an outcome measure as well as mri data to assess t disease burden, cerebral atrophy, and the appearance of t black holes. although there are very few trials that have included children, in this article we review therapies that are recommended for adults and, where data is available, highlight the pediatric studies. glucocorticoids, such as intravenous (iv) methylprednisolone, are the mainstay of treatment for acute attacks or relapses in ms [goodin et al., ] . they suppress the immune system in many ways, such as altering cytokine profiles, inhibiting the synthesis of matrix metalloproteinases, and reducing csf antibodies to mbp and ocb [kupersmith et al., ] . in , a multicenter trial compared adrenocorticotropic hormone (acth) ( u/day given intramuscularly [im] for four days with a -day taper) against placebo in patients with acute ms [rose et al., ] . after four weeks, the authors found that acth accelerated clinical improvement, although there was no significant difference in the outcome. in another study, acth ( u/day for one week followed by a taper) was compared with g of iv methylprednisolone for three days. in this study, there was no significant difference between the two treatment arms [thompson et al., ] . subsequently, a number of studies have been published using glucocorticoids for optic neuritis, most notably the optic neuritis treatment trial. this multicenter study compared iv methylprednisolone for three days followed by oral prednisone for days against a -day course of oral prednisone and a placebo group. for both primary (visual fields and contrast sensitivity) and secondary (visual acuity and color vision) endpoints, the group that received iv methylprednisolone had an accelerated recovery of visual function compared to the placebo group. the rate of recovery for the group receiving oral prednisone was in between the iv and placebo groups. at six months, there was no difference between the treated and the placebo groups [beck, ] . furthermore, the group receiving oral steroids had an increased number of recurrences of optic neuritis. in addition to their use in optic neuritis, high-dose ste-roids are also known to enhance the resolution of gadolinium-positive mri lesions [barkhof et al., ; burnham et al., ] . finally, abrupt discontinuation of steroids can lead to severe clinical, radiographic, and histopathologic relapses; therefore, an oral taper is recommended. although these studies were performed in young adults with rrms and cis, iv steroids ( - mg/kg/day given daily for - days followed by an oral taper over days) are used in children with acute attacks that impair function. interferons (ifn␤- a and ifn␤- b) are recombinant proteins, which inhibit the adhesion and the migration of wbc across the blood-brain barrier, thereby blocking antigen presentation and the synthesis and transport of matrix metalloproteinases [harris and halper, ] . in addition, they may cause a shift from a t h to a t h response. in adultonset ms, ifn-␤ has a beneficial effect on the clinical and radiological outcome measures. because the drug is not marketed for the pediatric population, there are no recommendations available for dosing children. for older children and adolescents, adult doses are most often used. interferon ␤- a (inf␤- a) is available in a weekly im injection (avonex, g) or a subcutaneous (sc) injection given three times a week (rebif, g or g). interferon ␤- b (inf␤- b, betaseron, million international units (miu) or g) is given sc every other day. for smaller teens or children younger than years, the doses are often adjusted to minimize adverse events and increase tolerability, such as starting with a half-dose of avonex or betaseron or using the lower dose for rebif. in , banwell et al. retrospectively studied dosing, safety, and tolerability of ifn␤- b in children diagnosed with ms who had been treated for an average of . months [banwell et al., ] . treatment was initiated at full dose ( miu or g) in children, all of whom were older than years of age. younger children were started at - % of the full dose and slowly increased; two children, both under the age of years, were unable to tolerate the dose escalation. none of the children had any serious adverse events. therapy was discontinued in of patients after being treated for a mean duration of weeks for various reasons, such as perceived lack of efficacy, cost of medication, lack of adherence, injection pain, and change in diagnosis. nevertheless, of the patients with confirmed ms, the annualized relapse rate was reduced by a mean of %. the side effects of inf␤ in children are similar to those reported by adults. fever is the most common side effect, reported in % of the patients [ghezzi et al., ] . additional side effects include headache, myalgia, flu-like symptoms, injection site reactions, fatigue, nausea, and asthenia [waubant et al., ; banwell et al., ] . the majority of these symptoms are transient. to alleviate side effects, children may be pretreated with acetaminophen, ibuprofen, or naproxen. laboratory abnormalities, such as elevations of liver function tests, can also occur. when present, a temporary discontinuation of the medication is recommended. often, the inf␤ can be restarted without a recurrence of the elevated transaminases [banwell et al., ] . ga is a random polypeptide composed of four amino acids (l-glutamic acid, l-lysine, l-alanine, and l-tyrosine) resembling myelin basic protein (mbp). this drug has a number of effects on the immune system including inhibition of antigen presentation, competition and displacement of bound mbp, conversion of cd t cells from t h to t h type cells, and induction of brain-derived neurotrophic factor (bdnf) expression [teitelbaum et al., ; neuhaus et al., ; aharoni et al., ; azoulay et al., ] . it also induces antigen-specific suppressor t cells which release anti-inflammatory cytokines thereby generating tolerance to self-antigens [harris and halper, ] . there are no trials similar to those conducted in adults that have primarily focused on the efficacy of this drug in children with ms. there are, however, reports of using this drug in children who were given mg sc daily, the standard dose for an adult. in one child treated with ga, chest pain was reported; however, no other clinical or laboratory abnormalities were identified [ghezzi et al., ] . although inf␤ and ga have been used in practice, the long-term tolerability, side effects, and overall efficacy in the pediatric population is not yet known. in a multicenter italian study published in , ghezzi et al. focused on effectiveness and tolerability of interferons and glatiramer acetate in patients treated before the age of [ghezzi et al., ] . sixty-five cases were reviewed. the majority was treated with avonex ( ), followed by rebif ( ), betaseron ( ), and copaxone ( ). relapses were defined as the occurrence of new symptoms lasting more than hr with objective findings of cns involvement in a previously unaffected patient or the acute worsening of preexisting symptoms lasting more than hr and causing an increase of at least on the edss. all four of the drugs substantially reduced the relapse rate with combined data showing a decrease from . to . relapses per year and similar results for the individual medications. the change in edss was not significantly different when comparing the first and last visit in the inf␤ subgroups; however, a statistically significant difference was seen in the ga subgroup (baseline: . Ϯ . , posttreatment: . Ϯ . , p ϭ . ). it should be noted that the patients on ga had overall lower disease duration when compared to the other groups and edss at entry was lower than that in the avonex and rebif/betaseron groups. natalizumab is a recombinant monoclonal antibody directed against ␣ -integrin. in experimental autoimmune encephalitis (eae), the animal model for ms, the expression of t-cell surface receptors (integrins) promotes adhesion and transport of these cells through capillary endothelial cells. this antibody against ␣ -integrin blocks the adhesion of activated t lymphocytes to endothelial cells thereby preventing these cells from entering the nervous system. this is the only selective immunomodulating drug for the treatment of ms. the results from the natalizumab safety and efficacy in relapsing remitting multiple sclerosis (affirm) and safety and efficacy of natalizumab in combination with interferon ␤- a in patients with relapsing remitting multiple sclerosis (sentinel) studies in adult patients indicate that the annualized rate of clinical relapses was reduced by %, the number of new and enhancing mri lesions was reduced by %, and a decrease occurred in progression and prolongation of the interval before neurological deterioration, demonstrating the usefulness of the drug [polman et al., ; rudicket al., ] . although natalizumab had significant short-term beneficial effects, unfortunately, three patients who received this drug developed progressive multifocal leukoencephalopathy (pml). the relative risk of developing pml in ms patients on natalizumab is in , [ropper, ]. moreover, the use of this drug may have other long-term effects, such as unmasking latent viral infections as well as other diseases that are dampened by immune surveillance. in children who have a malignant course of ms, the use of this drug on a short-term basis may be warranted. campath- h binds cd antigen, which is present on the surface of all b and t lymphocytes, as well as some monocytes. it is a lympholytic antibody that has been shown to prevent relapses and the formation of new mri lesions in ms; however, it does not seem to have any effect on disease progression [paolillo et al., ] . furthermore, when campath- h was initially used in patients with ms, a transient worsening of symptoms occurred due to the release of cytokines and nitric oxide (no) [moreau et al., ] . in vitro studies demonstrated that no can cause conduction blocks that could account for the transient worsening of symptoms with treatment initiation. pretreating with steroids can avert the cytokine release. rituximab is a humanized monoclonal antibody directed against cd and antigens found on b lymphocytes [valentine et al., ]. b-cell proliferation, as well as an increase in the mutations of their receptors, has been shown in the csf of ms patients. the b-cell response reflects the presence of a specific antigen in the cns. thus, the b cells have become another therapeutic target in ms. rituximab, a drug that depletes b cells, is currently being investigated in the treatment of ms [reff et al., ; frohman et al., ] . mitoxanthrone is an anticancer drug that acts by intercalating into dna thereby producing dna strand breaks and interstrand crosslinking. in the immune system, it causes the elimination of lymphocytes and reduction of t h cytokines. the major side effects include cardiac toxicity, presenting as a cardiomyopathy with irreversible congestive heart failure, and increased risk of developing malignant tumors. nevertheless, this drug reduced the attack rate of patients with rrms by %, reduced the number of gadolinium-enhancing and new lesions on the mri, and reduced the clinical rate of progression of the disease [millefiorini et al., ] . given the toxicity profile, this is not a first-line drug for the treatment of ms in children. cyclophosphamide is a powerful immunosuppressive agent that has been used to treat relapsing-remitting and progressive forms of ms. side effects include alopecia, nausea and vomiting, hemorrhagic cystitis, sterility, and long-term risk of malignancy. the use of iv cytoxan ( - mg/day with wbc counts about , per microliter) did not show any benefit for patients with progressive ms at -and -year follow-up after the initiation of therapy [hauser et al., ; likosky et al., ] . in a canadian study using , mg of cytoxan with a -year follow-up of patients with progressive ms, there was no significant benefit from use of this drug [canadian cooperative ms study group, ] . nevertheless, in a study of patients with progressive ms, younger patients derived some benefit from the use of cytoxan [weiner et al., ] . methotrexate acts as a folate antagonist, thereby affecting dna synthesis in immune cells. it decreases proinflammatory cytokines and enhances suppressor t-cell function. the major side effects are nausea, headache, diarrhea, liver damage, and the risk of developing non-hodgkin's lymphoma. a small, doubleblinded study of low-dose methotrexate revealed a benefit for patients with rrms but not for patients with the progressive forms of the disease [currier et al., ] . however, in another study of patients with chronic progressive ms, low-dose methotrexate was found to be beneficial and showed a reduction in the t diseased burden [goodkin et al., ] . azathioprine is an analog of -mercaptopurine that inhibits purine synthesis, thereby impairing dna and rna synthesis in b cells, t cells, and macrophages. its side effects are anemia, lymphopenia, alopecia, liver dysfunction, pancreatitis, reactivation of latent infections, and the risk of developing malignancies. in a retrospective analysis of seven studies that had enrolled patients, use of imuran reduced the number of relapses; however, the drug did not seem to affect the course of patients with progressive ms or their disability [yudkin et al., ] . cyclosporine is a potent immunosuppressive agent that selectively inhibits helper t cells. side effects include hirsutism, headaches, nausea, hypertension, edema, paresthesias, nephrotoxicity, and abdominal pain and discomfort. studies conducted in london and amsterdam showed no benefit on the relapse rate but did show some effect on slowing the progression of the disease [rudge et al., ] . given the side effects of this drug, its use in ms is very limited [goodin et al., ] . cladribine, an adenosine deaminase-resistant purine nucleoside, is a potent immunosuppressive drug that is selective for lymphocytes. side effects include nausea, diarrhea, fever, fatigue, and leukopenia. although cladribine does not have a significant effect in reducing the relapse rate, it may slow the degree of disability. in addition, it reduces the appearance of gadolinium-enhancing lesions on mri [beutler et al., ; rice et al., ] . -hydroxy- -methylglutaryl coenzyme a (hmg-coa) reductase inhibitors, also called statins, have been recently studied in a variety of cns disorders, including ms. statins disrupt the activation of proinflammatory t-cells by inhibiting signals from mhc class ii molecules [neuhaus et al., ] . they also decrease migration of leukocytes into the cns, expression of inflammatory mediators by t-lymphocytes and in the cns [stüve et al., ] . statins, such as simvastatin (zocor) and atorvastatin (lipitor) have been shown to inhibit and reverse chronic and relapsing eae [stüve et al., ] . atorvastatin induces stat phosphorylation and enhances the secretion of t h cytokines (il- , - , and - and transforming growth factor [tgf] ␤) while inhibiting stat phosphorylation and secretion of t h cytokines (il- , - , ifn-␥, and tnf␣) [youssef et al., ] . in small, shortterm studies, zocor decreased the number and size of gadolinium-positive lesions on mri scans without effect on progression and disability [vollmer et al., ] . the immunomodulatory effects of the statins offer promise in the treatment of ms, and their usefulness is being further investigated [neuhaus et al., ] . vaccination therapies are currently being developed that would alter the treatment of ms. vaccinations that promote the development of tolerance have been effective in eae [robinson et al., ]. in addition, t cell and t cell receptor peptide vaccinations have been studied in humans with ms [correale et al., ; bourdette et al., ] . none of the vaccines have been studied in children. iv immune globulin (ivig) blocks fc receptors on macrophages, alters the cytokine profile, and has antiidiotypic effects. ivig is typically used as an adjunct for acute relapses; however, its recurrent use has been studied in rrms. in a multicenter, double-blind, placebo-controlled study of rrms patients given ivig ( . - . g/kg) monthly for two years, a reduction in the clinical attack rate (Ϫ %) with a possible reduction in the degree of disability (not significant) was observed [fazekas et al., ] . in a separate study, the number of total and enhancing lesions seen on mri was decreased by more than % in patients treated with ivig compared with placebo [sorenson et al., ]. thus, it appears that ivig may reduce the attack rate in rrms but probably has little effect in slowing the progression of the disease. although it does not alter the long-term course in ms, plasma exchange has been used to treat acute relapses, presumably by removing harmful antibodies. several groups have investigated this particular therapeutic modality for treatment of patients with progressive ms [hauser et al., ] . for some patients who had not responded to iv steroids, plasma exchange performed every other day for a total of days provided a greater degree of improvement when compared with a sham-treated group [weinshenker et al., ] . some patients receiving plasma exchange improve very rapidly, which is unlikely due to the repair of the injured tissue. instead, the rate of recovery may be due to the rapid shifts in electrolytes that result in improved axonal conduction or the possible removal of an antibody that affects transmission of electrical impulses. although fatigue is a common and debilitating symptom is adults, children rarely complain of this symptom. the mechanism for fatigue is multifactorial and includes depression, excessive effort due to muscle weakness or spasticity, re-lease of cytokines, and sleep disturbance. therapies for fatigue in ms include the use of amantadine, modafanil, and pemoline. all have been shown to have modest beneficial effect in adults. when patients have involvement of the corticospinal tracts, whether it be due to lesions in the spinal cord or higher, treatment should include physical therapy, splints to prevent contractures, and stretching exercises combined with pharmacological treatments, such as diazepam (valium), tizanidine (zanaflex), baclofen (lioreseal), and dantroline (dantrium). less well established is the use of tetrahydocannabinol. for contractures that do not respond to stretching, alternatives include serial casting, botox injections, and tenotomy. in more severe cases, a baclofen pump, or rhizotomy or myelotomy, may be considered. hemiplegia in children is disabling, particularly because of the loss of dexterity. sensory impairment further aggravates movements of the hand. such children do not use the affected hand, which results in learned nonuse of that hand. recent studies indicate that such children benefit from intensive practice and forced use; restraint of the noninvolved arm appears to improve function of the affected hand, probably due to functional reorganization of the nervous system. patients with ms have a variety of paroxysmal symptoms that last seconds to minutes and are not associated with alterations in consciousness or any electroencephalogram correlate for seizure. paroxysmal sensory symptoms and motor symptoms, such as ataxia and lhermitte's sign, respond to low doses of carbamezapine, phenytoin, and acetazolamide. heat-sensitive symptoms can respond to potassium channel blockers with the caveat that these drugs can induce seizures. this is not an uncommon symptom in some children. nonsteroidal antiinflammatory agents are recommended. if they are not sufficient, gabapentin (neurontin), carbamezapine (tegretol), or amitriptyline (elavil) can be beneficial. in ms, axonal injury occurs early in the course of the disease with eventual transection of axons. factors that have been associated with axonal injury are cytokines, no, superoxide radicals, proteases, cd t cells, cholesterol breakdown products, abnormal expression of sodium channels and function of the sodium-calcium exchanger, and glutamine excitotoxicity [waxman et al., ] . when an axon is demyelinated, there is abnormal expression of voltagegated sodium channels with increased influx of sodium in an attempt to restore conduction. to compensate for this, there is a reversal of the sodium/calcium exchanger with efflux of sodium and an influx of calcium. this could result in calcium-mediated neuronal degeneration. this hypothesis has received some support from work on eae models where sodium channel blockers, such as flecainide and phenytoin, help preserve axons [lo et al., ; bechtold et al., ] . in patients with ms, mrs has demonstrated increased glutamate concentration, providing the underpinning for considering glutamate excitotoxicity. the increased glutamate could result from a decrease in glutamate transporters in glial cells and elevation of glutaminase, a glutamate-synthesizing enzyme, in microglia [werner et al., ] . however, increased glutamate acting through the ␣-amino- -hydroxy- -methyl-isoxazole- -propionic acid (ampa) and/or nmethyl-d-aspartate (nmda) receptors, which are present on neurons and oligodendrocytes, can result in calcium-mediated cell death. riluzole, a glutamate antagonist that has been used in infants with spinal muscular atrophy, blocks nmda and sodium channels and reduces the number of t -weighted hypointense lesions on the mri scans of patients with ms [frohman et al., ] . because axonal damage is a feature of ms, promoting neurite outgrowth could be beneficial. however, axonal sprouting is inhibited by activation of the nogo receptor by agonists such as nogo, oligodendrocyte-myelin glycoprotein (omgp), and myelin-associated glycoprotein (mag). thus, blocking the nogo receptor could represent a therapy that would be of value in promoting axonal sprouting [wang et al., ] . in acute ms plaques, there is clearcut evidence for remyelination; however, this is minimal in chronic lesions. the recruitment of oligodendrocyte precursor cells to areas of demyelination is mediated via chemokine and cytokine receptors, a pathway that appears to be intact. once attracted to areas of damage, these precursor cells recapitulate the differentiation process; however, full differentiation of these cells may be dampened by macromolecules that are negative regulators of this process, such as activation of the notch pathway due to reexpression of the ligand jagged or the nogo receptor interacting protein. in the future, both of these targets may be sites for therapeutic intervention that will aid the process of remyelination. in addition, transplantation of stem cells or oligodendroglial progenitor cells may be a consideration [john et al., ; mi et al., ; frohman et al., ]. ms is best recognized for its relapsing and remitting clinical course. in fact, in both children and adults, rrms is the most common form, followed by the secondary and primary progressive forms. however, the prognosis for pediatric ms remains controversial. the edss has been used to quantify the disability associated with ms by assigning a functional score for multiple systems (pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral) [kurtzke, ] . patients with a score of have a normal neurological exam. scores between . and . are fully ambulatory, whereas . - . are ambulatory for short distances without aid or rest. patients with scores greater than require assistance with ambulation as well as other activities of daily living. in , boiko et al. compared the time to edss of . (mild disability in at least three domains or moderate disability in one area) and . (requiring intermittent or constant unilateral assistance to walk meters with or without resting) in adult-and pediatric-onset ms [boiko et al., ] . on average, adults had a % risk of reaching edss scores of . and . in and years, respectively, after onset whereas disability in children was much slower, taking and years, respectively. in addition, . % of children with rrms progressed to spms after an average of . years (sd . years). the % risk for conversion from rrms to spms was years in children, whereas it was years in adults. although this data suggests a slower disease course in children, the overall morbidity is typically greater when children reach adulthood. children have higher edss scores when compared to adults with ms of the same age [ghezzi et al., ] . ms is under-recognized in the pediatric population and presents new challenges in diagnosis and treatment. despite significant advances in neuroimaging, ms remains a clinical diagnosis. new guidelines allow earlier diagnosis, 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associated with cytokine release in patients with multiple sclerosis mechanisms of action of glatiramer acetate in multiple sclerosis statins as immunomodulators: comparison with interferon-␤ b in ms are statins a treatment option for multiple sclerosis? molecular mimicry and immune-mediated diseases multiple sclerosis and other inflammatory demyelinating diseases of the cns influence of infection on exacerbations of multiple sclerosis quantitative mri in patients with secondary progressive multiple sclerosis treated with monoclonal antibody campath h a randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis diagnostic criteria for multiple sclerosis: revisions to the "mcdonald criteria multiple sclerosis: a guide for patients and their families onset symptoms in multiple sclerosis new diagnostic criteria for multiple sclerosis: guidelines for research protocols depletion of b cells in vivo by a chimeric mouse human monoclonal antibody to cd the genetic epidemiology of multiple sclerosis cladribine and progressive ms: clinical and mri outcomes of a multicenter controlled trial protein microarrays guide tolerizing dna vaccine treatment of autoimmune encephalomyelitis selective treatment of multiple sclerosis cooperative study in the evaluation of therapy in multiple sclerosis. acth vs. placebo-final report randomised double blind controlled trial of cyclosporin in multiple sclerosis natalizumab plus interferon ␤- a for relapsing multiple sclerosis multiple sclerosis in children under years of age multiple sclerosis in childhood: report of cases clinical viral infection and multiple sclerosis early onset ms under the age of : clinical and paraclinical features intravenous immunoglobulin g reduces mri activity in relapsing multiple sclerosis expression of specific chemokines and chemokine receptors in the cns of multiple sclerosis patients acute disseminated encephalomyelitis: recognition in the hands of general paediatricians statins as potential therapeutic agents in neuroinflammatory disorders synthetic copolymer inhibits human t-cell lines specific for myelin basic protein relative efficacy of intravenous methylprednisolone and acth in the treatment of acute relapse in ms isolated demyelinating syndromes: comparison of different mr criteria to predict conversion to clinically-definite multiple sclerosis phosphorylation of the cd phosphoprotein in resting b lymphocytes. regulation by protein kinase c toll receptors: a central element in innate immune responses oral simvastatin treatment in relapsing-remitting multiple sclerosis p interacts with the nogo receptor as a co-receptor for nogo, mag and omgp interferon ␤- a in children with multiple sclerosis is well tolerated na ϩ channel expression along axons in multiple sclerosis and its models statistics of multiple sclerosis including a study of the infantile, congenital, familial and hereditary forms and the mental and psychic symptoms intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the northeast cooperative multiple sclerosis treatment group a randomized trial of plasma exchange in acute cns inflammatory demyelinating disease multiple sclerosis: altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage magnetic resonance spectroscopy in multiple sclerosis: window into the diseased brain the hmg-coa reductase inhibitor, atorvastatin, promotes a th bias and reverses paralysis in cns autoimmune disease overview of azathioprine treatment in multiple sclerosis key: cord- -fx gcd authors: pirko, istvan; noseworthy, john h. title: demyelinating disorders of the central nervous system date: - - journal: textbook of clinical neurology doi: . /b - - . - sha: doc_id: cord_uid: fx gcd nan demyelinating disorders of the central nervous system istvan pirko and john h. noseworthy multiple sclerosis (ms) is now known to be a common malady even though it was first recognized as a distinct clinicopathological entity less than years ago. the lack of clear medical reports before the early s is sometimes interpreted as evidence that ms is a relatively new disease. however, it is more likely that the evolution of medicine into science led to more precise observation and description of human diseases, including ms. saint lidwina of schiedam ( - ) developed a relapsing neurological disorder at the age of and may be the first case of clinically described ms. ollivier was the first to report a clinical case in the medical literature in . shortly thereafter, carswell illustrated a case of what is now clearly recognizable as ms in his atlas of anatomical pathology. cruveilhier published gross pathological and clinical descriptions of ms. vulpian first suggested the rubric of "sclerose en plaque" in . charcot was primarily responsible for establishing ms as a unique and recognizable syndrome. he also described the clinical spectrum and the histological appearance. pierre marie was the first to suggest an infectious cause of ms in , a hypothesis that is still debated. toxins were also considered to be responsible in the early s. a major advance toward the understanding of demyelinating diseases was the discovery of experimental allergic encephalomyelitis (eae) by rivers in . a variety of different demyelinating diseases have subsequently been described (table - ). myelin provides insulation for axons and is necessary for saltatory conduction. it is composed of tightly wrapped lipid bilayers with specialized protein constituents. peripheral nervous system (pns) myelin is formed by the extension of schwann cells, and central nervous system (cns) myelin is produced by oligodendrocytes. the myelin coating is interrupted at regular intervals (nodes of ranvier) where the axon membrane with its concentration of voltagegated sodium channels is exposed to the extracellular environment ( fig. - ) . the presence of myelin is essential to maintain conduction velocity; its loss or damage can lead to significantly slower conduction or conduction block. other factors affect conduction velocity including certain antibodies and chemicals like nitric oxide. in certain cases, blockade may be the initial event in the cascade of events leading to demyelination. cns and pns myelin differ in a number of important ways. schwann cells myelinate only one internodal segment from a single pns axon, whereas oligodendrocytes myelinate multiple cns axons. the proteins also differ. proteolipid protein (plp) accounts for approximately % of the cns myelin proteins. mutations in this highly conserved protein cause pelizaeus-merzbacher disease. protein zero is the major pns myelin protein and performs a function similar to plp in compacting the intraperiod line. myelin basic protein (mbp) makes up % of cns and % of pns myelin proteins. mbp is not an integral protein but binds to the cytoplasmic surface and is responsible for compaction at the major dense line. myelin associate glycoprotein accounts for about % of both peripheral and central myelin. myelin oligodendrocyte glycoprotein and cyclic nucleotide phosphodiesterase are minor constituents of cns myelin and are not found in the pns. peripheral myelin protein is a minor component of pns myelin. ms is an inflammatory relapsing or progressive disorder of cns white matter and is a major cause of disability in young adults. pathologically, it is characterized by multifocal areas of demyelination, loss of oligodendrocytes, and astrogliosis but with relative preservation of axons. while demyelination is the classic hallmark of ms, axonal and neuronal injury are important aspects of the disease and are gaining more recognition. although certain clinical features are characteristic of ms, investigative studies are often needed to confirm the clinical suspicion and exclude other possibilities. recently, there have been advances in understanding the etiology, mechanisms of myelin injury, and potential for repair, and several partially effective agents are now approved for use in relapsing-remitting and secondary progressive ms. the pathogenesis and pathophysiology of ms remains incompletely understood. several mechanisms may be important to ms plaque formation: autoimmunity, infection, bystander demyelination, and heredity. although convincing proof is lacking, dietary factors and toxin exposure have been hypothesized to contribute as well. these mechanisms are not mutually exclusive, and the true pathophysiology is likely to depend on more than one of them. autoimmunity. during ontogenesis, autoreactive lymphocytes normally undergo clonal depletion, but some escape and are merely suppressed, becoming tolerant to their antigens. low levels of autoreactive t and b cells persist even in normal individuals. autoimmune disorders occur when the tolerance of these cells toward their antigen is broken. the decreased suppressor activity of circulating lymphocytes from patients with ms and other presumed autoimmune diseases may reflect loss of tolerance. one potential mechanism that may break tolerance is molecular mimicry between self and foreign antigens. autoreactive t lymphocytes may become activated on exposure to structurally similar foreign antigens. some evidence suggests that molecular mimicry is relevant in ms. not only do several viral and bacterial peptides share structural similarities with mbp, but it has also been demonstrated that these antigens may activate mbp-specific t-cell clones derived from ms patients. blood-brain barrier leakage alone may break tolerance because it gives cnsreactive lymphocytes easy access to otherwise inaccessible antigens. alternatively, a primary event such as an infection or injury may release cns antigens into the periphery, where they may activate corresponding autoreactive cells. the major support for autoimmunity in the pathogenesis and pathophysiology of ms is by analogy to eae, the major animal model for ms. eae is, however, an artificial situation and there is no spontaneous autoimmune animal model of ms. while eae is the most commonly studied model of ms, several features of human ms can not be adequately captured by this model. , over a hundred different effective treatments have been described for eae; however, almost all of them are ineffective and some are harmful in human ms. a recent editorial discusses the merits and important limitations of eae as a model for ms. in eae, just like in classic human autoimmune diseases such as systemic lupus erythematosus (sle) or rheumatoid arthritis, the main target antigens are known. however, despite the discovery of several "weak" antigens in human ms, no dominant antigens have been identified to date. the only human demyelinating disease with an identified specific antigen is devic's disease (neuromyelitis optica), which appears to be a novel autoimmune chanellopathy with an antigen that is neither neuronal nor myelin related (see later discussion of devic's syndrome under neuromyelitis optica). infection. the role of viral infections in the initiation and maintenance of ms has been debated for some time. several viral infections are known to cause demyelination in animals, including visna virus of goats and sheep, canine distemper virus, and theiler's murine encephalomyelitis virus. viral infections in humans can also cause demyelination (progressive multifocal leukoencephalopathy [jc papillomavirus], subacute sclerosing panencephalitis [measles virus], and human t-cell lymphotropic or leukemia virus type [htlv- ]-associated myelopathy). the epidemiology of ms suggests that environmental factors may promote the disease state, possibly due to one or more viruses. a virus may be involved in the pathogenesis of ms in several ways: . transient or persistent infection outside the cns may activate autoreactive t cells by means of molecular mimicry or by other nonspecific means (as superantigens do). . transient cns infection may initiate a cascade of events that fosters autoimmunity (breach the blood-brain barrier, release cns antigens). . recurrent cns infections may precipitate repeated inflammation and demyelination. . persistent cns viral infection could either incite inflammatory reactions detrimental to oligodendrocytes or directly injure them. beyond speculation and epidemiological observations, there is insufficient evidence for a viral infection playing a causative role in ms. early serological studies are difficult to interpret because of nonspecific immune activation and resulting elevation of titers to many different viruses. many ms patients have elevated cerebrospinal fluid (csf) titers to measles and herpes simplex (hsv) viruses, but this finding appears nonspecific. virus has rarely been cultured from csf of ms patients, but a new strain of hsv (the ms strain) and a new virus (inoue-melnick virus) were first isolated from the csf of ms patients. , newer molecular techniques to search for a viral genome in csf and brain have rejected the claim that htlv- is associated with ms. the finding that human herpesvirus (hhv ), although present in % of brains from both control subjects and ms patients, is localized to the oligodendrocyte nuclei near plaques of ms patients and to oligodendrocyte cytoplasm in control subjects indicates that persistent cns viral infection is common. this raises the possibility that ms may depend on an aberrant host response to this normal condition or that a defective virus that lacks the ability to evade immune detection may be to blame. more recently, measles and canine distemper virus antibodies were found elevated in blood and csf samples of ms patients, although their relationship is not clear to the disease process. in a study from denmark, patients with serological markers for late-stage epstein-barr virus (ebv) infection had a threefold increase in the likelihood of developing ms. a follow-up study from sweden failed to reach this conclusion. in general, serum samples of ms patients may contain higher titers of antibodies to the following infectious organisms: adenovirus, canine distemper virus, hsv, hhv , and influenza, measles, mumps, parainfluenza, rubella, vaccinia, and varicella zoster virus (vzv). similarly, csf samples from ms patients may show higher titers of adenovirus; chlamydia pneumoniae; cytomegalovirus (cmv); ebv; hhv ; coronavirus; influenza viruses a and b; measles or mumps virus; mycoplasma pneumoniae; parainfluenza viruses , , and ; respiratory syncytial virus; rubella virus; vaccinia; and vzv. there has been an interest recently in a potential link between c. pneumoniae infection and the development of ms. no direct cause-and-effect relationship has been observed between any of these infections and ms. "bystander" demyelination. immune actions may mediate myelin injury in a nonspecific manner. many soluble products of the immune response other than immunoglobulins are known or suspected to be toxic to myelin and oligodendrocytes. activated complement is capable of lysing oligodendrocytes in an antibody-independent fashion. the proinflammatory cytokine tumor necrosis factor-a causes myelin disruption and oligodendrocyte apoptosis in vitro. arachidonic acid metabolites may also participate in myelinolysis, and reactive oxygen species released by macrophages cause lipid peroxidation that can damage myelin. other soluble substances that are potentially toxic to myelin include nitric oxide and vasoactive amines. histological subtypes of ms lesion development. through the groundbreaking work of lucchinetti and associates in the ms lesion project, it is postulated that the formation of ms lesions follows one of four patterns. patterns i and ii are related to immune-mediated damage to myelin sheaths. in pattern i, cellular mechanisms of injury seem to prevail (macrophages and t-lymphocytes) whereas in pattern ii humoral mechanisms of injury predominate (e.g., antibody and complement-mediated mechanisms). patterns iii and iv are related to oligondendrocye pathology: in pattern iii, a distal oligdendrogliopathy and apoptosis have been reported, whereas in pattern iv, primary oligodendrogliopathy and degeneration of oligodendrocytes have been described. currently these subtypes can be diagnosed only by biopsy; serum and magnetic resonance imaging (mri) markers are not yet known, although lesional t hypointense rims and response to plasma exchange may correlate well with pattern ii pathology. it is important to note that the patterns do not correlate with clinical subtypes of ms, with the exception of pattern iv, which has been identified only in primary progressive (ppms) patients. evidence to date suggests that the pattern of lesion formation remains the same within an individual patient; patients do not "switch" from one pattern to the other. also, the patterns do not seem to represent different chronological stages of lesion formation. gray matter involvement. it has been known since the late th century that ms affects both gray and white matter structures. the importance of gray matter involvement has received little attention until recently, largely due to the development of advanced mri techniques (see later) that indicate neuronal and axonal involvement even in the earliest stages of this disease. a classification system of gray matter plaques was proposed by peterson and associates they described three patterns of cortical demyelination: type i lesions are contiguous with subcortical white matter lesions; type ii lesions are confined to the cortex, and are often perivascular; type iii lesions extend from the pial surface to cortical layer or . besides cortical gray matter involvement, there is also evidence for prominent basal ganglia involvement, which can be seen in the early stages of ms, and may correlate better with motor outcome and cognitive measures than measures of white matter involvement. lucchinetti and associates demonstrated that biopsy samples from newly diagnosed demyelinating cases contain numerous infiltrating immune cells, and can be destructive. the pathological classification of cortical lesions as described by petersen can also be found in these early ms biopsy samples. approximately % of biopsy cases in which gray matter was also sampled had evidence of clear cortical demyelination. in , an extensive histological study by kutzelnigg and associates investigated the role of cortical demyelination in all clinical subtypes of ms. in this study, brains of ms patients (relapsing-remitting [rr], secondary progressive [sp], and ppms) and control subjects were studied using advanced quantitative morphological techniques. cortical demyelination and diffuse axonal injury in the normal appearing white matter (nawm) were reported as hallmarks of progressive forms of ms. cortical demyelination was mainly seen in the subpial layer of cortex, and was associated with significant inflammatory infiltrates in the surrounding meninges. diffuse inflammation was also found throughout the white matter of the progressive cases, associated with activation of microglia. no significant correlation was shown between focal white matter lesion load and cortical demyelination. this study defines three crucially important pathological hallmarks of ms-focal demyelinated white matter lesions, diffuse injury in the white matter, and cortical plaque formation-and concludes that white matter lesion formation predominates in active forms of ms, while cortical pathology and diffuse white matter injury characterizes the progressive forms. the authors of this landmark paper also established that these three processes are potentially independent of each other. heredity. epidemiological findings support a polygenic hereditary predisposition to ms. a number of candidate genes have been investigated, often with conflicting results. the only definitive genetic association in ms is with the serologically defined human leukocyte antigen (hla) dr , dq . this is one of the dr haplotypes, also known as dw in cellular terminology and drb * , dqa * , dqb * in molecular nomenclature. though its link to ms is well established, the risk conferred by this haplotype is small (relative risk of to ), and it is neither necessary nor sufficient for the development of ms. linkage to this locus has not been proved, indicating that it plays only a minor role in familial susceptibility. other susceptibility genes likely contribute, possibly the t-cell receptor variable b region and the igg heavy-chain variable region (especially the vh - gene). but their specific roles have not been established. other genes under study have been the mbp coding gene, the ctla- gene on chromosome q , and the interleukin- ra associated gene, in concurrence with the hla-dr haplotype. mitochondrial mutations are also under investigation, and an lhon-associated mtdna mutation may be an important cofactor in developing ms in some patients. the apoe gene, as in alzheimer's disease, has been associated with a higher incidence of ms. on the other hand, apoe is considered to have neurotropic, immunomodulatory, and antioxidant properties. these findings are yet to be confirmed by larger studies. twenty percent of ms patients have at least one affected relative. only about % of first-degree relatives of patients develop ms, but this represents a -to -fold increase in risk compared with the general population. unaffected family members sometimes have abnormal findings on cranial mri, implying that this risk is even higher. one study of ms rates in adopted relatives of ms patients verified that the familial distribution is due to genetic factors rather than shared environment. twin studies lend support to both genetic and environmental influences on ms development. genetically identical monozygotic twins are more often concordant for ms than dizygotic twins ( % and . %, respectively), indicating a genetic component; however, even after following monozygotic twins past age or using mri data, less than % are concordant, suggesting a role for environmental factors. epidemiology and risk factors. ms is not a rare disease. it affects millions worldwide and approximately , in the united states alone. symptoms usually begin during young adulthood, with the peak onset at age . approximately . % of ms cases are diagnosed before age . women are affected nearly twice as often as men. ms has a predilection for whites, especially those of northern european heritage. other races and ethnic populations are resistant to a variable extent. ms is virtually unknown among black africans but occurs in african-americans at half the rate of whites, possibly due to racial admixture or environmental factors. ms is rare in tropical areas, and the prevalence increases proportionally to the distance from the equator, excluding polar regions. the prevalence is less than cases per , in tropical areas; in high prevalence areas it can be higher than per , , reaching up to per , in selected areas. although usually interpreted as the effect of environmental factors, the prevalence gradient is at least partially due to racial susceptibility. perhaps the most incriminating evidence for the role of environmental factors in the development of ms is the changing risk with migration and the occurrence of ms clusters and epidemics. immigrant populations tend to acquire the ms risk inherent to their new place of residence. migration from high to low prevalence before the age of lowers the ms risk, whereas migration after this age does not affect risk. migration from low to high prevalence areas increases the risk of ms, but the effect of age is less clear. many clusters of ms have been reported. , the occurrences of ms epidemics in iceland and the faroe islands have been proposed to be the result of exposure to a pathogen brought by british troops during their occupation in world war ii. other environmental factors associated with the development of ms include cigarette smoking (odds ratio of . , ci: . - . ), animal fat intake, and deficiency of vitamin d. , epidemiological data support the view that ms is caused or triggered by an environmental factor in persons who are genetically susceptible. the familial frequency and distribution implies that several genes contribute to susceptibility, and this is consistent with the low relative risk conferred by the genetic loci studied so far. data from clusters, migration studies, and family studies reveal that there is a latent period of some years between exposure to the environmental factor and the development of clinical symptoms and that the age at exposure is around , the putative age at acquisition. the precise environmental events that lead to cns demyelination are uncertain. viral infection is the most plausible, but because of the nonspecific elevation of viral titers and long latent period, there is little direct evidence. minor respiratory infections precede % of relapses in patients with established ms. measles infection was found to have occurred at a later age in ms patients than control subjects, although the incidence of ms has not been reduced by immunization against measles. head injury and trauma have received attention as putative triggering events, but cohort studies have not verified any link. pregnancy does not alter the risk of developing ms, but it does seem to influence disease activity. the annualized relapse rate drops from approximately . to . by the third trimester, but this is offset by an increase to . in the first postpartum months. most studies have found no longterm effects of pregnancy on the prognosis for progression or disability, although one did report a favorable effect. a multitude of other environmental factors have been suspected to alter the risk for ms (cold climate, precipitation, amount of peat in the soil, exposure to dogs, and consumption of meat, processed meat, and dairy products), but none has been verified to be an independent risk factor. ms can cause a wide variety of clinical features. many signs and symptoms are characteristic, and a few are virtually pathognomonic for the disorder. conversely, some symptoms are atypical and some are so rare as to suggest a different diagnosis (table - ). the course of the illness is also variable, but it remains a critical consideration in the diagnosis of ms. sensory symptoms are the most common presenting manifestation in ms ( % to %) and ultimately develop in nearly all patients. loss of sensation (numbness), paresthesias (tingling), dysesthesias (burning), and hyperesthesias are common. these symptoms may occur in practically any distribution: one or more limbs, part of a limb, trunk, face, or combinations. the more distinctive sensory relapses of ms consist of the sensory cord syndrome and the sensory useless hand syndrome. a common scenario is that of numbness or tingling beginning in one foot, ascending first ipsilaterally and then contralaterally. the sensory symptoms may ascend to the trunk, producing a sensory level, or may involve the upper extremities. associated symptoms commonly include poor balance, weakness, urinary urgency, constipation, and lhermitte's sign (see later). brown-séquard syndrome may occur with sensory disassociation and hemiparesis. the sensory cord syndrome reflects an evolving demyelinating lesion that begins in the medial posterior column ipsilateral to the first symptoms. sensory cord syndromes are common in ms and suggest the diagnosis when they occur in young persons and remit spontaneously or in response to corticosteroids. patients with the sensory useless hand may note subjective numbness and lose discriminatory and proprioceptive function, resulting in difficulty writing, typing, buttoning clothes, and holding onto objects, especially when not looking at the hand. this problem can occur bilaterally even without lower extremity symptoms. the responsible lesion is in the lemniscal pathways either in the cervical spinal cord or in the brain stem. this syndrome usually remits over several months. the useless hand syndrome is a very specific symptom and is only rarely caused by other disorders. a large portion of ms patients have persistent sensory loss, usually consisting of diminished vibratory and position sensation in distal extremities (video , sensory ataxia). itching may occur in a dermatomal distribution with relapse or in paroxysms. pain is not a major manifestation of ms, but distressing lower extremity dysesthetic pain associated with spinal cord involvement, radicular pain from lesions at the root entry zone, paroxysms, and an uncomfortable sensation of pressure or tightness surrounding a leg or the trunk may be present. pyramidal tract dysfunction is common in ms and causes weakness, spasticity, loss of dexterity, and hyperreflexia (video , hyper-reflexia). motor deficits can occur acutely or in a chronic progression with weakness of one or more limbs and facial weakness, leg stiffness that impairs gait and balance, or extensor and flexor spasms (video , spastic gait). exercise or heat frequently worsens subtle deficits. muscle atrophy is usually due to disuse, but lesions of lower motor neuron fibers or of the anterior horn itself can cause a pseudoradiculopathy with segmental weakness, atrophy, and diminished reflexes. motor symptoms are presenting manifestations of ms in % to % of all cases; their prevalence is higher than % in long-standing ms. the initial symptom of ms is optic neuritis (on) in % to % of patients, and more than % experience a clinical episode of on during their lifetime. the most common manifestation is visual loss in one eye that evolves over a few days. periocular pain, especially with eye movement, usually accompanies and may precede the visual symptoms. bilateral simultaneous on is uncommon in adults, but formal visual field testing reveals unexpected defects in the clinically normal eye in a substantial number of patients. children and asian patients are more likely to have bilateral simultaneous on; it may also be seen in neuromyelitis optica (nmo) patients. examination shows an afferent pupillary defect, diminished visual acuity, subdued color perception, and often a central scotoma (video , afferent pupillary defect). funduscopic examination is usually normal but occasionally will reveal papillitis (more common in children) or venous sheathing. most patients begin to recover within weeks, and significant visual patients with frequent and severe on events in the first years were more likely to convert to nmo; they also had a higher likelihood for significant persistent vision loss. cerebellar pathways are frequently involved during the course of ms, but a predominately cerebellar syndrome is uncommon at onset. the manifestations include dysmetria, dysdiadochokinesia (video , dysdiadochokinesis), action tremor with terminal accentuation, dysrhythmia, breakdown of complex motor movements, and loss of balance (video , tremor with ataxia). patients with long-standing ms may develop a "jiggling" gait and an ataxic dysarthria with imprecise articulation, scanning speech, or varying inflection, giving it an explosive character. urinary urgency, frequency, and urge incontinence (due to detrusor hyper-reflexia or detrusor-sphincter dyssynergia) result from spinal cord lesions and are frequently encountered in ms patients. the combined incidence of bowel and bladder dysfunction in ms is thought to be higher than %. symptoms of bladder dysfunction may be transient and occur with an exacerbation but are commonly persistent. impaired vesicular sensation causes a high capacity bladder and may lead to bladder atonia with thinning and disruption of the detrusor muscle. incontinence results in constant dribbling of urine in this irreversible condition. interruption of brain stem micturition center input sometimes leads to cocontracture of the urinary sphincter and detrusor muscles (detrusor-sphincter dyssynergia). the resulting high pressure may lead to hydronephrosis and chronic renal failure if untreated. constipation is a common problem, occurring in % to % of ms patients, especially with limited activity and spinal cord involvement. fecal incontinence is a socially devastating symptom that is often associated with perineal sensory loss in ms patients. sexual dysfunction is seldom mentioned, even though it is a frequent problem in ms. nearly two thirds of patients report diminished libido. one third of men have some degree of erectile dysfunction, and a similar percentage of women have deficient vaginal lubrication. besides direct neurological impairment, sensory loss, physical limitations, depression, and fatigue additionally contribute to sexual difficulties in ms patients. in addition, the partner's attitude and psychological factors dealing with self-image, self-esteem, and fear of rejection may also lead to impotence or loss of libido. intense vertigo associated with nausea and emesis is an occasional manifestation of ms relapse. in the absence of a clear diagnosis of ms, these symptoms are often attributed to vestibular neuronitis. patients may also develop a persistent but mild vertigo that is precipitated by movement, or this may be a residual finding after an acute relapse. internuclear ophthalmoplegia, caused by a lesion in the medial longitudinal fasciculus, is the most common cause of diplopia in ms patients (video , afferent pupillary defect). when symptomatic, it produces horizontal diplopia on lateral gaze that usually remits. examination discloses incomplete or slow adduction of the eye ipsilateral to the lesion and nystagmus of the contralateral eye during abduction (see chapter ) . dissociated nystagmus may be the only finding of an old or subtle internuclear ophthalmoplegia (video , internuclear ophthalmoplegia). bilateral internuclear ophthalmoplegia is strongly suggestive of ms, although this rarely may occur with tumor, infarct, mitochondrial cytopathy, wernicke's encephalitis, and chiari malformation (video , wernicke's encephalopathy). vertical and diagonal diplopia usually results from skew deviation. nystagmus, slow saccadic movements, broken ocular pursuits, and ocular dysmetria are other eye findings produced by lesions of cerebellar and vestibular pathways (see chapters and ; video , saccadic dysmetria). abducens paresis occurs on occasion, but oculomotor and trochlear nerve impairment is rare. corticospinal, spinothalamic, lemniscal, vestibular, and cerebellar pathways can all be affected. cranial nerve impairment may be seen with lesions that affect brain stem nuclei or exiting and entering fibers. usually this occurs in association with other symptoms. because of the long spinal tract and nucleus, the trigeminal nerve is frequently involved (video , trigeminal neuralgia). facial nerve paresis does occasionally occur, but ms is an extremely rare cause of bell's palsy in patients without previous symptoms. acute unilateral hearing loss is an uncommon manifestation. dysphagia is often due to impairment of cranial nerves ix, x, and xii and generally appears late in the course of some patients. once thought uncommon, cognitive disorders are now known to be present in % to % of ms patients. age, duration of ms, and physical disability do not completely predict the presence of cognitive dysfunction, but classic mri measures like the total t -weighted lesion load does not seem to correlate well with the degree of cognitive decline. measures of cortical atrophy, venticular enlargement, and neuronal integrity seem to correlate better with the cognitive aspects of ms. the problems are often subtle and may not be detected on standard mental status evaluation. the pattern of cognitive decline is typified by decrease of episodic memory, processing speed, verbal fluency, and difficulty with abstract concepts and complex reasoning. to a lesser extent, executive functioning and visual perception, semantic memory, and attention span may also be also decreased. general intelligence is not typically affected. as expected, cortical symptoms such as aphasia, apraxia, and agnosia are unusual. homonymous hemianopia, which can be caused by cortical or subcortical lesions, is also uncommon. despite prominent cerebral white matter involvement, many of the disconnection syndromes such as alexia without agraphia, conduction aphasia, and pure word deafness have not been reported in ms patients. affective disorders are more frequent in ms patients than in the general population. these include both anxiety and depression. in long-term studies, the incidence of depression in ms patients is close to %. neither depression nor anxiety is related to physical or cognitive disability or mri lesion load. patients sometimes experience uncontrollable weeping or less commonly laughter incongruent with their mood. interruption of inhibitory corticobulbar fibers is responsible for these symptoms (pseudobulbar affect). fatigue is a pervasive symptom among ms patients that is not related to disability or depression. over % of ms patients experience fatigue during their disease course. a diurnal pattern is characteristic and follows the normal circadian pattern of body temperature fluctuations, with the worse symptoms occurring in afternoon hours (peak core body temperature) often giving way to improvement in the late evening. ms symptoms may fluctuate in a predictable fashion. transient worsening of symptoms frequently follows exercise or elevation of body temperature. one example is uhtoff's phenomenon, in which visual blurring occurs during strenuous activity or with passive exposure to heat. these episodes resolve when the body temperature cools to normal or after a period of rest. an intercurrent infection with fever can induce worsening of symptoms and may be confused with a relapse. heat sensitivity is presumably related to conduction block, as demyelinated axons are more prone to failed conduction than normal, myelinated fibers. paroxysmal symptoms are characteristic of ms and are believed to be due to the lateral spread of excitation (ephaptic transmission) between denuded axons in areas of demyelination. symptoms are typically brief (seconds to minutes) and recur frequently, occasionally dozens of times per day. they may be precipitated by hyperventilation, certain sensory input, or particular postures. tonic spasms (paroxysmal dystonia) most often affect the arm and leg on one side, but the face, one limb, or bilateral limbs are sometimes involved (video , tonic spasms). these spasms may result from lesions anywhere along the corticospinal tract. they often begin during the recovery phase after an acute relapse and remit after a few months. intense pain and ipsilateral or crossed sensory symptoms may accompany them. paroxysmal weakness occurs, but it is uncommon. a wide variety of paroxysmal sensory symptoms may occur with ms, including tingling, prickling, burning, or itching, and sharp neuralgic pain is common. trigeminal neuralgia may appear in patients with ms (video , trigeminal neuralgia). the occurrence of trigeminal neuralgia in a person younger than age is suggestive of ms. lhermitte's sign (transient sensory symptoms usually precipitated by neck flexion) is usually described as an electrical or tingling sensation that travels down the spine or into the extremities. although quite common in ms, lhermitte's sign can also occur with a wide variety of other disorders, such as vitamin b deficiency, spondylosis, chiari malformation, and tumors, and after cisplatin chemotherapy. several other paroxysmal symptoms are occasionally encountered, including paroxysmal dysarthria and ataxia, paroxysmal diplopia, and combinations of these symptoms. facial myokymia and hemifacial spasm are additional transient (lasting months) phenomena sometimes due to brain stem demyelination (video , facial myokymia; video , hemifacial spasm). trismus, kinesigenic dystonia, paroxysmal kinesigenic choreoathetosis, and segmental myoclonus have also been described in case reports of ms patients as rare and unusual examination findings. seizures occur in a larger proportion of ms cases compared to normal control subjects. a recently published review of case series of ms patients with epileptic seizures yielded a prevalence of . %. this represents an approximately three-to sixfold increase compared to the general adult population. cortical and juxtacortical lesions may be responsible for the increased incidence of seizures in ms patients. however, such plaques are common and seizures in ms are not, which suggests that other factors may also contribute to the relationship between epilepsy and ms. focal motor seizures, possibly with secondary generalization, are the most frequent. the occurrence of seizures usually follows one of two patterns. on occasion, focal onset seizures begin early in the course of ms and later remit. the start of seizures late in the course of ms more often poses a chronic problem and may be difficult to control. the eye is the only organ outside the nervous system that is sometimes involved in ms. uveitis and retinal periphlebitis each occur in at least % of ms patients. in a recent study, most patients with ms-associated uveitis were white females between and years of age. the diagnosis of ms preceded the onset of uveitis in %, followed it in %. in over % of the cases, the uveitis was bilateral. pars planitis was found to be the most frequent form of uveitis (over %), and concomitant anterior chamber inflammation was also common. usually ms-associated uveitis is benign from the standpoint of visual acuity. uveitis can involve the posterior, intermediate (pars planitis), or rarely anterior portion and resembles that seen in other inflammatory (e.g., sarcoid, reiter's syndrome, behçet's syndrome, inflammatory bowel disease, systemic lupus erythematosus) and infectious (e.g., syphilis, tuberculosis, lyme disease) conditions. periphlebitis is seen as venous sheathing on funduscopic examination and is histologically identical to the perivascular inflammation present in brain white matter. it is interesting that inflammation commonly occurs in the retina, which has a peripheral type of myelin produced by schwann cells. there are occasional reports of peripheral nerve or nerve root demyelination in ms patients as well as central demyelination in acute inflammatory demyelinating polyradiculoneuropathy and chronic inflammatory demyelinating polyradiculoneuropathy (see chapter ) . some of these cases may be due to the incidental occurrence of two unrelated disease processes. however, because the pns and cns share many antigens, including mbp, it is possible that an autoimmune reaction or a viral infection could involve both the cns and pns. persons with one autoimmune disorder generally have an increased risk of others. even though there are several reports of systemic and organ-specific autoimmune diseases in ms patients, population-based studies have not confirmed any increase in prevalence of these disorders among ms patients. in fact, there appears to be a negative association between ms and rheumatoid arthritis. multifocal cns involvement and acute relapses, remissions, and slow progression of neurological deficits typify ms. a single episode of neurological dysfunction can be suggestive of ms if it follows the typical time course of a relapse: progression over less than weeks (usually days), with or without a period of stabilization, and improvement or resolution (often over months). insidious progression of deficits localized to a single site in the cns can also be due to ms, but other causes must be excluded. the temporal course of ms can be described by one of four categories: relapsing-remitting (rr), secondary progressive (sp), primary progressive (pp), and progressive relapsing (pr). many physicians use the term relapsing progressive, which encompassed patients with spms, prms, and even those with rrms who have stepwise relapse-related worsening disability. this term has recently been abandoned. other terms that relate to the course of ms but have no consensus regarding their definition are sometimes encountered. benign ms generally refers to patients who have had ms for a long time but have little or no disability. malignant ms is sometimes used to describe patients with frequent relapses and incomplete recovery but is also used in reference to patients with acute fulminant demyelinating syndromes (see later). the term clinically isolated syndrome (cis) refers to patients presenting with their first episode of region-restricted episodes of cns inflammatory demyelination. this may remain an isolated syndrome (no recurrence), it may remain a forme fruste of acute disseminated encephalomyelitis (adem), or it may be the harbinger for one of the relapsing forms of ms. the probability of recurrent demyelinating episodes (e.g., clinically definite ms) has been the subject of several important investigations, and several clinical features and test results are of predictive value. optic nerve, spinal cord, and brain stem are the most common sites of these recurrent monosymptomatic events, and the time profile follows that of ms relapses. the pathogenesis, pathophysiology, epidemiology, clinical features, associated disorders, differential diagnosis, evaluation, and management are the same as in ms. the prognosis for visual recovery after each episode of on is good, and most patients regain normal visual acuity. profound visual loss, recurrent on, and age older than are associated with a higher risk for poor recovery. investigators have concluded that recurrent multifocal demyelinating episodes, fulfilling the diagnostic requirements of clinically definite ms, develop in % or more of patients after isolated on when follow-up is extended beyond years. most of this risk is incurred within the first few years, although significant risk may continue into the fourth decade after the event. children much more often develop simultaneous bilateral on and have a lower risk for subsequent ms than adults. factors that are associated with an increased risk of developing ms as a disseminated illness are the presence of venous sheathing, recurrent on, family history of ms, white race, previous vague or nonspecific neurological symptoms, and the presence of oligoclonal bands (ocbs), elevated igg index, or igg synthesis rate in csf. the severity of acute transverse myelitis is inversely related to the risk of acquiring further symptomatic demyelinating lesions. complete transverse myelitis with profound loss of motor, sensory, and sphincter function imparts a relatively low risk of to for the later diagnosis of ms. partial transverse myelitis with preservation of significant motor function at peak is associated with a much higher incidence of ms. although monosymptomatic brain stem demyelination is not as common as either on or acute transverse myelitis, similar conclusions have been reached. in the only study available, two thirds of these patients with cerebral white matter lesions detected on mri developed ms within years, compared with none of patients with normal head mri. , a recently published -year follow-up of the original queen square series continues to demonstrate the value of the baseline cranial mri study in determining risk of recurrence (ms risk). in this cohort study of cis patients, approximately two thirds had at least one asymptomatic lesion ( of , %) at baseline. after years of follow-up, slightly more than half with one to three asymptomatic baseline cerebral lesions had developed ms ( of ) compared with the majority of cases presenting with at least four baseline lesions ( of , %). after years of follow-up, the majority of patients with any asymptomatic cerebral lesions had developed definite ms ( of , %). the recently published -year follow-up data on this group of patients reveals that % of the initially mri positive patients developed ms versus % of the mri negative subgroup. this information is helpful for treating patients in the setting of cis. differential diagnosis. only a few diseases cause neurological deficits that regress spontaneously and relapse in different areas of the cns over the course of many years. however, because of the remarkable heterogeneity of ms, many disorders may resemble ms (table - ) , especially in the first years of active disease. other primary idiopathic inflammatory demyelinating cns disorders may be mistaken for ms. adem usually causes monophasic cns demyelination. although it frequently involves multifocal areas of white matter simultaneously, adem cannot be reliably differentiated from the initial clinical episode of ms. fulminant brain demyelination in persons without previous symptoms of ms is more likely due to adem or other conditions (schilder's myelinoclastic diffuse sclerosis, balo's concentric sclerosis, marburg's variant of ms). neuromyelitis optica differs from ms primarily in the topography and intensity of the lesions. several systemic or organ-specific inflammatory conditions can involve the cns white matter. on, myelitis, and other syndromes sometimes occur with systemic lupus erythematosus. whether this autoimmune disease increases the risk of developing ms or causes similar syndromes by a different pathological process is unknown. sarcoidosis can affect the nervous system in several ways, including multifocal, corticosteroid-responsive white matter lesions. sjögren's syndrome sometimes occurs with ms, but this may only represent a chance association. neuro-behçet's disease has a predilection for the brain stem. occasionally, isolated demyelinating syndromes are associated with inflammatory bowel disease. a wide variety of vasculitic syndromes (e.g., primary angiitis of the cns, periarteritis nodosa, wegener's granulomatous angiitis, vasculitis associated with rheumatoid arthritis, susac's syndrome, eales'disease) may mimic ms. however, these syndromes can usually be distinguished by involvement of the cortex, seizures, early dementia, personality changes, psychosis, infarcts involving large vessel territories on mri, and lack of improvement. findings characteristic to the particular vasculitis (uveitis and vitreal hemorrhage in eales' disease, retinal and cochlear involvement in susac's syndrome, upper and lower respiratory tract involvement in wegener's granulomatosis) also aid in the correct diagnosis. a few infections must also be considered in the differential diagnosis of ms. both lyme disease and syphilis may cause multifocal white matter lesions. htlv- causes a chronic progressive myelopathy (htlv- -associated myelopathy/tropical spastic paraparesis). acute or recurrent myelitis can be caused by vzv. progressive multifocal leukoencephalopathy and toxoplasma abscesses should be considered in immunocompromised patients with progressive neurological decline. bacterial endocarditis with brain abscess formation, subacute sclerosing panencephalitis, or chronic rubella encephalomyelitis may need to be considered in the appropriate circumstances. cerebrovascular disease is only rarely mistaken for ms. occasionally, an ms relapse has an abrupt onset that may mimic an infarct, especially in those not previously diagnosed with ms. the usual circumstance is that of a hemisensory or hemimotor deficit imitating a lacunar infarct. disorders with multiple cerebral infarcts (emboli, hypercoagulable states, sneddon's syndrome, cadasil, vasculitis) may produce an mri appearance and course resembling ms. vascular malformations may also produce symptoms similar to ms. additional neurological illnesses capable of producing multifocal lesions rarely mimic ms. metastatic tumors and multifocal gliomas are often cited examples, but rarely is this distinction difficult for an experienced clinician. lymphoma more commonly masquerades as ms because the lesions may involve the white matter, may be multifocal, and are corticosteroid responsive. in addition, demyelination sometimes presents as one (or a few) mass lesion(s). in this situation, biopsy may be needed for diagnosis. neoplasms can cause paraneoplastic syndromes that may be confused with ms. a high index of suspicion must be kept for older age at presentation, subacute ataxia, early dementia, and personality changes. a few metabolic disorders may resemble ms, such as vitamin b deficiency, vitamin e deficiency (seen in bassen-kornzweig syndrome, hypobetalipoproteinemia, and refsum's disease), and central pontine or extrapontine myelinolysis (video , pontine myelinolysis). leukodystrophies are usually not difficult to distinguish from ms. krabbe's disease (galactocerebroside-b-galactosidase deficiency), metachromatic leukodystrophy (mld; arylsulfatase a deficiency), and the usual adult form of adrenoleukodystrophy (ald) and adrenomyeloneuropathy (amn) exhibit both central and peripheral dysmyelination. blood leukocyte or fibroblast culture enzyme activity levels will confirm the diagnosis of krabbe's disease and mld, and elevated levels of very long chain fatty acids occur in ald/amn. mitochondrial disorders should also be given consideration because symptoms and mri appearance may be similar to ms. a relapsing remitting disorder identical to ms is sometimes seen in patients with the mutations responsible for leber's hereditary optic neuritis (lhon). this usually occurs in female patients, and there may not be a family history of visual loss. a number of rare biochemically defined illnesses and other genetic disorders may occasionally merit consideration (including cobalamin and folate dysmetabolism, adult polyglucosan body disease, hereditary spastic paraparesis, spinocerebellar degeneration, and hereditary cerebroretinal vasculopathy). several additional disorders must be excluded before diagnosing primary progressive ms (ppms). spinal cord compression from spondylosis or tumor may produce chronic progressive myelopathy. chiari malformations, syringomyelia, syringobulbia, other foramen magnum lesions, spinal arteriovenous malformations, and dural fistulas may also need consideration. careful imaging readily identifies these structural abnormalities. degenerative diseases such as olivopontocerebellar atrophy may mimic ppms. mri and csf examination will help distinguish between the two. conversion reactions and somatization disorders are commonly encountered in a busy referral practice and must be accurately diagnosed to afford optimal patient management. evaluation. the diagnosis of ms is based on the demonstration of white matter lesions disseminated in time and space in the absence of another identifiable explanation. ms remains a clinical diagnosis, although mri, evoked potentials, and csf examination can help clarify less certain cases. for research purposes, various categories of ms have been defined based on the certainty of the diagnosis. at least two attacks and evidence of two separate cns lesions (clinical or paraclinical) are required for the designation of clinically definite ms (cdms). two attacks and evidence of one cns lesion or one attack and evidence of two cns lesions (clinical or paraclinical) is considered clinically probable ms. cases that fulfill the criteria for clinically probable ms and have supportive csf findings are labeled as laboratory-supported definite ms. patients with a clear history of at least two attacks and supportive csf but a normal neurological examination and no paraclinical evidence of cns lesions are categorized as having laboratory-supported probable ms. suspected cases that do not fit any of these criteria may be regarded as possible ms. paraclinical evidence generally refers to abnormalities on evoked potential studies or imaging procedures. as a result of increasing availability of refined paraclinical diagnostic modalities (especially mri) and an overall better understanding of the disease process, new diagnostic criteria for ms were proposed by an international expert panel in . three out of four of the following findings should be present on mri: ( ) one gadolinium enhancing lesion, or nine t hyperintense lesions; ( ) at least one infratentorial lesion; ( ) at least one juxtacortical lesion; and ( ) at least three periventricular lesions. according to the clinical diagnostic criteria, if a patient had two or more attacks with objective evidence on examination of two or more anatomical areas involved, no additional data is required to make the definite diagnosis. however, if such diagnostic studies were done and are not supportive of a diagnosis of ms, then the diagnosis should be reconsidered. if a patient presents with a history of two or more attacks, but objective clinical evidence only suggests one lesion, the following additional data is needed to confirm the diagnosis: the disease process has to be disseminated in space as demonstrated by mri; alternatively, two or more mri-detected lesions consistent with ms plus positive csf would suffice to meet the newly defined criteria. the clinician also may elect to await a further attack implicating a different anatomical site. in case a patient had one attack, with objective clinical evidence of two or more lesions, dissemination in time as demonstrated by serial mris separated by at least months or a second clinical attack would clarify the diagnosis. if a patient has a clinically isolated syndrome, or "monosymptomatic" presentation, the following criteria should be met: dissemination in space as demonstrated by mri (again separated by at least months), or two or more mridetected lesions consistent with ms plus positive csf and dissemination in time on serial mri scans, or a second clinical attack. in case the patient presents with a progressive course, the presence of positive csf is required, and dissemination in space should be present, as suggested by nine or more t -weighted brain lesions, or two or more cord lesions, or four to eight brain lesions plus one cord lesion on mri. alternatively, abnormal visual evoked potentials (veps) with four to eight brain lesions, or fewer than four brain lesions plus one cord lesion, and dissemination in time on serial mri scans, or continued progression for a year would meet the diagnostic criteria. "positive csf" according to this set of criteria is defined by either the presence of oligoclonal bands detected by established methods (preferably isoelectric focusing on agarose gel followed by immunoblotting) different from any such bands in serum, or by a raised igg index. the presence of both enhancing and nonenhancing white matter lesions on a single mr image must not be used as evidence of dissemination in time as well as space, because these can also be seen in adem. oligoclonal bands (ocbs) and an elevated igg index provide supportive csf findings. ancillary tests are frequently required to confirm the diagnosis of ms and to exclude other possibilities in uncertain cases. laboratory tests on peripheral blood can help to exclude many of the infectious and other inflammatory disorders. a chest x-ray is generally needed to assess for sarcoid or paraneoplastic disorders if these are under consideration. an ophthalmological examination may be needed to search for alternative causes of visual loss. imaging studies, csf examination, and evoked potentials are often helpful because characteristic abnormalities are frequently present. mri of the head is the most sensitive imaging study for ms ( fig. - ). focal areas of increased t -weighted and decreased t -weighted signal reflect the increased water content associated with demyelinated plaques. the mri appearance of ms lesions, however, is not specific and similar abnormalities may be seen in normal aging, small penetrating vessel infarcts, lyme disease, tropical spastic paraparesis/htlv- -associated myelopathy, sarcoid, systemic lupus erythematosus, sjögren's syndrome, mitochondrial cytopathies, vasculitis, and adem. the specificity for ms can be increased by consideration of lesion number, size, location, and shape. this is especially important in persons older than age . mri characteristics, other than the ones suggested by the international criteria outlined previously, are size larger than mm, oval shape (often with the long axis directed perpendicular to lateral ventricles), and locations in the periventricular area, corpus callosum, and posterior fossa. longitudinal mri studies have shown the evolution of ms lesions. gadolinium enhancement, indicating blood-brain barrier disruption, sometimes precedes the development of t -weighted lesions and typically lasts for weeks in the brain (occasionally longer, especially in larger hemispheric lesions), and perhaps somewhat longer in the spinal cord. flair imaging is especially helpful for evaluating periventricular lesions that may go unnoticed on regular t -weighted scans. the disadvantage of the technique is its relative insensitivity to posterior fossa lesions. proton density weighted images are also part of the usual sets of images used in the mr diagnostics of ms. these images can be evaluated similarly to t -weighted images. technically, they are usually acquired together with the t -weighted datasets, as a first echo in conventional fast spin echo sequences, where the subsequent echoes can be used for generating the t -weighted images. new t weighted lesions have a fuzzy border and enlarge over a few weeks. after a period of stabilization, the t -weighted lesion regresses and becomes more sharply delineated from the surrounding white matter as edema resolves. most of the time, a residual abnormality with increased t weighting and decreased t -weighted signal remains, reflecting demyelination and gliosis. the low attenuation t signal, or "t black hole," is more often seen in secondary progressive ms and is thought to represent actual tissue loss. in several well-documented cases, hypointense lesions on t -weighted scans were described in subcortical gray matter structures in ms patients. on a molecular level these areas are thought to represent iron deposition; their significance in ms is not fully understood. the mri activity of disease, defined as either the number of new, recurrent, and enlarging lesions or the number of gadolinium-enhancing lesions, is usually higher than the clinical activity. this may be either because of the involvement of asymptomatic areas of the cns or because of a pathophysiological difference between symptomatic and nonsymptomatic lesions based on the presence or absence of axonal dysfunction. there is only poor correlation between disability and lesion load (volume of white matter abnormalities) determined by head mri. sometimes individuals have severe impairment and few mri abnormalities, and the converse may occur. this disparity is partially explained by variable spinal cord involvement, but a pathophysiological difference may account for some of the discrepancy. several mri markers of gray matter involvement correlate better than measures of white matter pathology with clinical functional outcome measures in ms. in a recent study edss showed the strongest correlation with gray matter volume loss and with t black hole volume increase (p < . ); both are considered to reflect neuronal and axonal pathology. ambulatory function, assessed as the -feet timed walk, also correlated well with gray matter volume loss and t black hole volume. on normal appearing gray matter magnetization transfer ratio (mtr) histograms, normalized peak heights inversely correlated with edss in rrms patients (r ¼ À . , p ¼. ). in a study evaluating a number of mri parameters (including brain t -hypointense and flair-hyperintense lesion volume, third ventricle width, brain parenchymal fraction and t hypointensities in the dentate nucleus), the best correlation with edss (and the only correlating parameter with -feet timed walk) was t hypointensity in the dentate nucleus. in ms patients, an mri study concluded that gray matter atrophy correlated with clinical status (edss, -feet timed walking and disease duration). a study of patients with ppms and rrms showed that neocortical volume as determined by mri correlated with edss scores across all the patients, but the strength of the correlation was stronger (p < . ) in the ppms (r ¼ À . , p < . ) than in the rrms group (r ¼ À . , p ¼ . ). mr spectroscopy is increasingly becoming an accepted diagnostic modality, where information can be obtained about the biochemical constituents of selected voxels of interest. with this technique, a cubic volume of interest is defined based on a regular mr image set. simultaneous acquisition of multiple volume units is possible. with long echo time (te) studies, naa (n-acetylaspartate), choline, creatinine, and lactate peaks can be identified on the mr spectrum. with short te studies, myoinositol, lipids, and some neurotransmitters may be identified. the resolution of the mr spectrum (the "number of lines" in the spectrum) is proportionate to the magnetic field strength used. naa is the second most abundant amino acid constituent in the brain after glutamate. it is localized almost exclusively in neurons and axons. creatinine is used as the "constant" peak in a mr spectrum, since it is the least likely to be altered by cns-specific processes. therefore, numeric mrs data are usually presented as ratios related to creatinine. the naa/creatinine ratio is decreased in areas of axonal or neuronal loss. it correlates well with disability. it can be decreased in normal appearing white matter, also in early stages of lesion formation, thus representing a challenge to the usual dogma of axonal loss being secondary to myelin damage. the decrease of the naa/creatinine ratio may return to normal following the resolution of the acute phase. this process may be related either to reversibility of neuronal injury or to disappearance of edema in the involved areas. in general, more reduced naa peaks are seen in progressive forms of ms with more profound tissue loss. if a relatively large hemispheric lesion shows decreased naa content, similar findings may be seen in the other hemisphere in a "mirror" location. the lactate peak can be elevated in a variety of acute processes, and as such, carries relatively low specificity. the short te spectrum is used less frequently; the "mobile lipid" peak (which is thought to represent macromolecular protein fragments) is increased in areas of acute demyelination. another newer mri technique used in ms research is magnetization transfer imaging. the principle behind this imaging modality is relatively simple. in complex macromolecular systems, there is a baseline magnetization exchange in equilibrium between macromolecular protons and mobile protons. if the macromolecular protons are saturated before each excitation (and subsequent data acquisition) with a prolonged off-resonance broadband pulse, then the signal intensity of the image will be reduced owing to magnetization transfer exchange between the saturated ("bound") and free ("mobile") protons. by obtaining duplicate sets of images (with and without magnetization transfer pulse), a magnetization transfer ratio can be calculated. the ratio reflects the integrity of the macromolecular environment. it is reduced by approximately % to % in areas of edema, but it is more significantly reduced in areas of demyelination or axonal loss. if the ratio "normalizes" in a lesion, no subsequent tissue loss is usually seen on other imaging modalities. despite these advantages, the magnetization transfer imaging is technically difficult because it produces variable findings depending on the technical environment and is not universally available. it has not become an accepted and standard technique for evaluation of ms patients. it may be very useful as a marker for remyelination and tissue repair in future neuroprotective or tissue restorative trials. diffusion-weighted imaging is well known from its widespread use in the diagnosis of ischemic stroke. this technique can show early stages of ms plaque formation. the increase in apparent diffusion coefficient correlates with acute plaques, and seems to best correspond with t -enhancing lesions; this technique may show the lesions at an even earlier stage. mri has become an important component of clinical trials in ms. because of the high sensitivity of mri for disease activity, it is reasoned that periodic mri may determine treatment efficacy more quickly than monitoring relapse rate or disability level. many studies have used mri as a secondary outcome, but clinical outcomes are still used as the primary outcome for definitive trials. additional mri techniques have also proved useful in the diagnosis of ms. mri of the spinal cord shows discrete lesions in about % of cdms patients. several semiautomatic methods exist to determine lesion volume, ventricle volume, or hemispheric volume. these are generally applied for research purposes only, and are not part of the usual workup or diagnostic follow-up of ms. csf evaluation remains a valuable diagnostic tool for ms. a lymphocytic pleocytosis occurs during acute exacerbations in about one third of patients, but this seldom exceeds cells. eighty percent of the lymphocytes are cd positive. the ratio of cd to cd cells is : . less than % of the cells are b cells. csf protein is normal in up to %; levels above mg/dl are unusual and may suggest a different disorder. the proportion of g globulin is high owing to the synthesis of immunoglobulins within the blood-brain barrier. the majority of csf immunoglobulin is igg, although igm and iga may also be elevated. measures of intrathecal igg production have been devised that are more useful than simple g-globulin levels. the igg index and synthesis rate are elevated in % to % of cdms patients and occasionally in other disorders. agarose gel electrophoresis, or the more sensitive isoelectric focusing of csf proteins, often reveals discrete bands of immunoglobulin, each a monoclonal antibody. it is pertinent to compare serum and csf banding patterns because peripheral monoclonal gammopathies may produce csf bands. to reduce false-positive results, only unique csf ocbs should be reported. between % and % of clinically definite ms patients have ocbs; however, early in the course they are not as prevalent. once present, ocbs persist and the pattern does not vary, although new bands occasionally appear. unlike subacute sclerosing panencephalitis, in which the majority of ocbs are antibodies specific for measles virus, the antigenic specificity of ocbs in ms is unknown; they are unlikely to be pathogen specific or autoantigen directed; there is some evidence that they may be genetically determined germline antibodies. five percent to % of noninflammatory cns samples and % of inflammatory samples are also positive for ocbs. more detailed recommendations about the inclusion of csf parameters to the diagnosis of ms were recently published suggesting that the cell count and differential should be completed within hours. the new and recommended method for the detection of ocbs includes immunoelectophorsesis on agarose gel followed by immunoblotting. the reported sensitivity of this technique is above %, with a specificity of % to %. in other inflammatory or infectious illnesses, ocbs are often transient features. their persistence is more suggestive of ms. the presence of myelin components, antimyelin antibodies, and kappa light chains in csf has also been used in the diagnosis of ms. however, the sensitivity and specificity of these products is less than that of ocbs. in late , a new set of recommendations were published based on the first years of using mcdonald's criteria in diagnosing ms. the original mcdonald criteria have been incorrectly interpreted by some as mainly relying on mri for making a diagnosis of ms. in reality, the mcdonald criteria cannot even be applied without careful clinical evaluation of the patient. neurological deficits must be evident to the examiner, and must be suggestive of ms. scans that "look like" ms (and meet the criteria of barkhof and tintore) but have never been accompanied by an obvious and documented neurological examination finding do not fulfill the mcdonald criteria. there was some sympathy among the international panel members revising the mcdonald criteria to allow selected symptoms that are clearly and specifically enunciated by the patient (e.g., lhermitte's symptom, trigeminal neuralgia, numbness ascending to the waist or higher) coupled with objective paraclinical (such as imaging and csf) findings to be sufficient as an indicator of a prior or current attack needed for an ms diagnosis. however, the panel was reluctant to endorse the diagnosis of ms in the absence of any objective clinical findings, even if objective paraclinical findings are in place, at least until such a scheme is tested in prospective settings. patients with imaging and csf findings suggestive of ms but not showing any objective evidence for neurological deficits commonly seen in ms require careful clinical and radiological monitoring. until objective evidence for neurological deficits are found, ms can not be diagnosed. ms may be the correct diagnosis with less stringent imaging criteria than originally proposed; however, the panel was uncomfortable making changes that would allow mri confirmation of dissemination in space based on lower stringency imaging criteria without appropriate prospective data. most studies performed to date have been inadequately designed to address this issue. advanced imaging technologies are constantly evolving and will likely one day be shown to aid in making the diagnosis of ms. visualization of intracortical lesions, use of higher field strength magnets, and analysis of "normal appearing brain tissue," may be conrnerstones of a future mri criteria for ms. preliminary evidence suggests that "occult" damage in normalappearing white and gray matter seen with magnetization transfer, diffusion tensor imaging, or spectroscopy is an early feature of ms, whereas it likely does not occur in other demyelinating conditions such as acute disseminated encephalomyelitis and nmo. important changes have been made to the original definition of "dissemination in time" by mri. in keeping with the definition that clinical relapses must be separated by at least month, it was agreed that new t lesions on mri should occur at least days after disease onset. this means that any new t lesion occurring at any time point after a so-called reference scan performed at least days after the onset of the initial clinical event is useful in meeting imaging diagnostic criteria for dissemination in time. it should be noted though that a new t lesion must be of sufficient size and location to exclude lesions that could have been missed previously for technical reasons of slice orientation, thickness or spacing, tissue contrast, patient motion, or other artifacts. this requires standardized scanning procedures with emphasis on careful repositioning, as well as input from qualified evaluators experienced in ms imaging. with the new revision, there are two ways to show dissemination in time using imaging: ( ) detection of gadolinium enhancement at least months after the onset of initial clinical event, if not at the site corresponding to the initial event; or ( ) detection of a new t lesion if this appears at any time compared with a reference scan done at least days after onset of the initial clinical event. spinal cord lesions can be important in differentiating ms from other white matter diseases; however, the original mcdonald criteria did not provide sufficient guidelines for the use of cord imaging in ms. spinal cord imaging that detects typical ms cord lesions (minimal or no swelling of the cord; clearly hyperintense on t -weighted imaging; at least mm in size, but less than two vertebral segments long; and occupying only part of the cord cross section) is particularly helpful if brain imaging does not detect dissemination in space in a patient suspected to have ms. for dissemination in space, a spinal cord lesion is equivalent to, and can substitute for, a brain infratentorial lesion, but not for a periventricular or juxtacortical lesion. an enhancing spinal cord lesion is equivalent to an enhancing brain lesion, and an enhancing spinal cord lesion can "count" doubly in fulfilling the criteria (e.g., a single enhancing spinal cord lesion can "count" for an enhancing lesion and an infratentorial lesion). individual cord lesions can contribute together with individual brain lesions to reach the required nine t lesions to satisfy the barkhof-tintore criteria (the mri criteria incorporated in the original mcdonald's criteria). the panel recognized that diffuse cord changes may occur in ms, especially in the progressive forms; however, these changes are not sufficiently reliable to allow for their incorporation into the diagnostic criteria at this time. repeat spinal cord imaging in patients without new symptoms of myelitis has a low yield in efforts to demonstrate dissemination of lesions in time. in other words, while it is common to see asymptomatic new brain lesions on repeated scans, new cord lesions generally do result in new neurological symptoms. therefore, repeat cord imaging is recommended only to support an ms diagnosis when there is a clinical reason to suspect a new cord lesion. important changes have been proposed in diagnosing primary progressive ms. these revised criteria stress clinical and imaging (brain or spinal cord) evidence for diagnosis and place less emphasis on csf findings. the new criteria for ppms is as follows: ( ) at least year of disease progression (retrospectively or prospectively determined) ( ) plus two of the following: (a) positive brain mri (nine t lesions or four or more t lesions with positive vep), (b) positive spinal cord mri (two focal t lesions), (c) positive csf (isoelectric focusing evidence of oligoclonal igg bands or increased igg index, or both). evoked potentials are summed cortical electrical responses to peripheral sensory stimulation that can be used to localize sites of disease and measure conduction velocity along sensory pathways. vep and somatosensory evoked potentials (sseps) may detect subclinical sites of demyelination, thus providing evidence of multifocality. brain stem auditory evoked potentials (baeps) are occasionally informative. more than % of persons with a history of on have an abnormal vep, and % of cdms patients have abnormalities on veps even when the history of on is absent. slowed conduction is present on ssep in nearly three fourths of patients with cdms. baes are the least sensitive, with abnormalities in less than %. mri has largely supplanted the use of evoked potentials in ms because of the greater sensitivity in the diagnosis and the detailed anatomical information it provides. in , the american academy of neurology released practice parameters regarding the usefulness of evoked potential studies in ms. according to these recommendations, veps are considered probably useful (class ii evidence) to identify patients at increased risk for developing clinically definite ms. sseps are possibly useful, whereas the evidence for baeps supporting the diagnosis of cdms is insufficient. management. there is no available prevention or cure for ms. treatments focus on three areas: treating acute exacerbations and hastening their recovery; altering the natural history of ms; and providing symptomatic relief of current symptoms by enhancing physical abilities and preventing or treating complications. a fourth management topic concerns special treatment issues related to pregnancy. acute exacerbations. corticosteroids are the most commonly used treatment for ms, although there have been few studies to address their efficacy. adrenocorticotropic hormone (acth) was shown to speed recovery from an exacerbation but had no effect on the ultimate degree of recovery. because of the unpredictable cortisone response to acth, oral prednisone and later intravenous methylprednisolone became the preferred treatments. the optic neuritis treatment trial verified that intravenous methylprednisolone but not prednisone increased the recovery rate and unexpectedly increased the time to the next relapse, thus delaying the diagnosis of cdms. moreover, the prednisone-treated group had twice as many recurrences. the finding was not replicated in a second study, but it has affected the practice of treating acute ms exacerbations. the current recommendation is to treat disabling attacks with to mg of intravenous methylprednisolone per day for to days with or without a short tapering dose of oral corticosteroids. according to the practice parameters for steroid treatment of acute on attacks released by the american academy of neurology in , oral prednisone in doses of mg/kg/day has no proven value. higher dose of oral or parenteral methylprednisolone may result in quicker and more thorough recovery of visual function. there is no evidence of long-term benefit for visual function. a study suggested that intravenous steroids may also have long-term effects on disease progression when given regularly. in this study, rrms patients randomized to receive regularly scheduled pulses of iv methylprednisolone (every months for years, then every months for years) demonstrated stability or improvement in disability measures, fewer "t black holes," and less brain atrophy than did control patients randomized to receive steroids only with relapses. these findings suggest a possible long-term benefit of pulsed iv methylprednisolone therapy on brain atrophy and disability. this as yet unconfirmed approach to long-term therapy might be considered a reasonable "control arm" in future phase iii trials of experimental therapies. up to one third of patients do not have an adequate recovery after a relapse despite the use of corticosteroids. plasma exchange (plex) alone was found beneficial in a substantial proportion of patients with severe inflammatory demyelinating episodes who had failed to improve following treatment with high-dose iv methylprednisolone. , a randomized, sham-controlled, double-blind trial in patients (seven exchanges over days) without concomitant use of immunosuppressants in acute demyelinating events confirmed these findings. moderate or greater clinical improvement was observed in over % of participants. a trial of seven plex treatments (alternate days) is a reasonable option for patients who fail to respond to conventional iv methylprednisolone therapy in acute, severe episodes of demyelinating diseases. the response to plex is stongly associated with the histological ms subtype. antibody and complement plays a crucial role in pattern ii lesion formation. in a study of biopsy-proven ms cases by keegan and associates, pattern ii cases showed good response to plex, whereas cases of pattern i or iii did not respond at all to plex. neuromyelitis optica, which is now considered an antibody-mediated condition with a known serological marker, also shows good response to plex: in a study by the mayo group, % of nmo patients showed moderate or marked improvement to plex, and an additional % showed mild improvement. alteration of the natural course. the primary goal of drug treatment is to alter the natural course of the disease (e.g., reducing the frequency and severity of relapses, preventing the chronic progressive phase, and slowing the progression of disability). the disease activity seen on mri is often used as a secondary outcome, although mri measures currently correlate imperfectly with clinical outcome. knowledge on altering the course of ms is largely restricted to three patient groups, those with clinically isolated syndromes, those with rrms, and those with secondary progressive ms. before we discuss the known data in each of these demyelinating disease categories, it may be worth while to review the use of the most important evidence-based medicine (ebm) statistics that are applied to measure the magnitude of treatment effect. relative risk reduction (rrr) is the metric most commonly cited in publications and promotional materials about clinical trials. the rrr is the degree that the treatment reduced the frequency of the outcome measure (experimental event rate, e.g., relapse, progression) compared with the control treatment (control event rate). the rrr is a ratio, not an absolute number, and is calculated as follows: rrr ¼ ðcontrol event rate À experimental event rateÞ= control event rate if the control event rate is low (making the denominator smaller), it will obviously inflate the rrr. an "impressive" % rrr may have a low biological significance if the outcome occurs infrequently. therefore, the absolute risk reduction (arr) should be calculated as this corrects for the frequency of the outcome. for most of the approved ms agents, the calculated arr is considerably less than rrr. this metric is usually not cited in reports of clinical trials of disease-modifying agents. to calculate risk reduction, one must have access to the data citing comparisons of proportions (ratios), and this is not always immediately available in publications. another useful measure of treatment effect is the "number needed to treat" (nnt). it is calculated as the inverse of the arr: overall, the nnts for the disease-modifying agents in ms are in the to range for treatment periods of to years. however, these nnts are for outcomes that have limited predictive value for long-term outcomes (e.g., relapse behavior does not precisely predict long-term disability) and the agents are expensive, inconvenient to use, and not without risk. we must also remember that clinical trials typically enroll patients with very restricted eligibility criteria (often a history of considerable recent disease activity or progression), and considerable efforts are in place in trials to optimize compliance with the treatment plan. as such, the nnt experienced in a practice setting (effectiveness) may considerably exceed what was reported in the trial setting. altering the course of a clinically isolated syndrome. when should treatment be initiated in patients with very early demyelinating disease? two recently published multicenter studies have addressed this issue in persons at high risk of developing ms. in the champs study, patients with their first episode of presumed demyelinating disease ("clinically isolated syndrome") in the setting of an abnormal, asymptomatic baseline cranial mri scan, were randomized to receive either weekly interferon-b a mg im or placebo after an initial course of steroid therapy. this study was terminated early when the primary outcome measure of conversion to "clinically definite ms" (cdms) status was reached in a greater number of placebo-treated patients. these findings were not unexpected given the known effect of interferons on reducing relapse rate but do provide some support for early treatment. the duration of follow-up in this study ( % year, % years, % years) is insufficient to determine long-term benefit from early intervention, however. it is also clear that the treatment is only partially effective, as % of interferon (ifn)-treated patients in the champs trial had clinical or mri evidence of recurrent disease within months of starting treatment. the analysis of treatment effect related to the champs trial reveal a rrr of %, an arr of . %, and an nnt of patients over years to prevent one conversion to "clinically definite ms." in a second placebo-controlled study of patients with either monosymptomatic ( %) or multifocal onset ( %) early demyelinating disease, early treatment with interferon-b a in an unusually low dose ( mg subcutaneously once weekly), reduced conversion to cdms ( % versus %) at years. again, there is no data on whether these treatments offer long-term benefit. the ebm calculations regarding this trial show an rrr of %, and arr of %, and an nnt of patients over years in order to prevent one conversion to "clinically definite ms." these two studies provide support for considering early treatment in patients presenting with first attack, in the presence of multiple asymptomatic mri lesions, but further studies are needed to determine whether this approach will provide a prolonged benefit on disease course. it is important to note that these studies do not provide guidance about clinically isolated syndromes that present with a brain mri that is not suggestive of ms (i.e., only one optic nerve lesion, or one brain stem or cord lesion explaining the cis symptoms). we do not recommend that cis patients with fewer than two asymptomatic mri lesions receive treatment with interferons. please see the discussions under "summary of recommendations for the treatment of rrms patients" for further advice on patient counseling and decision making about the use of the disease-modifying medications. altering the course of relapsing-remitting multiple sclerosis b-interferons. interferons are a class of peptides that have antiviral and immunoregulatory functions. both interferon-a and interferon-b are part of the anti-inflammatory t h response. interferon-b b (betaseron) was the first drug approved by the u.s. food and drug administration (fda) specifically for the treatment of ms. a large clinical study in rrms patients demonstrated a reduction in the frequency of relapses by about one third with subcutaneous injection every other day. the severity of relapses was also lessened. interferon-b b had a striking effect on mri measures of disease activity. the placebo-control group continued to accumulate white matter lesions, whereas patients in the high-dose arm ( million iu) had stabilization of their mri lesion load. no difference was found in the disability levels, however. side effects include injection site reactions, flu-like symptoms (low-grade fever, myalgias, headache; these lessen in frequency after treatment for a few months), mild liver enzyme elevation, and lymphopenia. depression and attempted suicide were more common in the treated groups. to illustrate the magnitude of treatment effect of the pivotal interferon-b b trial, the rrr was %, the arr was %, and the nnt analysis showed that patients are needed to be treated over years to increase the number of those who were relapse free by one. one particularly disturbing result was the production of neutralizing autoantibodies (nabs) in % of patients after years of treatment. not only do patients with these antibodies thereafter fail to respond to this drug, but there is also a concern that nabs may cross-react with natural interferon-b and interfere with its function. all positive sera for nabs seem to cross-react with both interferon-b a and b. switching from one preparation to the other does not change the pattern of antibody response. the long-term effects of nabs are unknown. recent studies seem to support that nab formation reduces clinical and mri effects although often nab formation subsides with time. there are no firm guidelines for monitoring nab formation. most physicians do not measure nabs but rather change therapies empirically when patients appear to be failing treatment. low titer nabs may be just transient phenomenon related to ifn treatment; persistent high titer nabs on two consecutive tests at least months apart is likely associated with poor treatment response to inf. interferon-b a (avonex) has the same amino acid sequence as natural interferon-b and differs from interferon-b b by one amino acid as well as by the presence of carbohydrate moieties. once-weekly intramuscular interferon-b a has been found to have effects similar to that of interferon-b b in reducing the frequency of ms relapses. in addition, a favorable effect on disability was also demonstrated and side effects were less common. in the original interferon-b -a intramuscular trial, the primary outcome measure was time to edss progression. the rrr was %, the arr was %, and the nnt was for years to prevent one patient from developing edss progression. the calculations for "proportion relapse free" show an rrr of %, and arr of %, and an nnt of over years ( patients need to be treated for years to increase the number of patients who were relapse free by one). nabs occurred half as often as with interferon-b b. interferon-b a has been approved by the fda for treatment of "relapsing ms." the "correct" dose of interferon continues to be debated. in a recent placebo-controlled trial, patients randomized to a high dose of interferon-b a ( mg three times per week) did better than those receiving half this weekly dose. both groups outperformed placebo and the high dose seemed to have more effect on relapse severity, hospitalizations, mri activity, and lesion volume accumulation, and possibly on delaying disability in the most severely disabled patients. at the end of the years of follow-up, placebo-treated patients were randomized to or mg subcutaneously three times weekly; patients on active treatment were continued on their original dose. the authors reported a benefit for the higher dose and for those treated for the full years, again suggesting that early treatment and perhaps higher doses of interferons may be beneficial. the primary outcome, however, was relapse count per patient per years and, as such, patients treated early had a significant advantage using this outcome measure. there were trends favoring the higher dose (relapse rate, mri volumes; not for time to first confirmed progression, however). the authors did not make statistical adjustments for multiple comparisons and there were many dropouts in the high-dose groups, making it difficult to draw firm conclusions. again, the answer to the question about the benefit of early treatment can best come from long-term (perhaps to years) studies using "hard outcomes" (e.g., time to progression, major milestones in disability). the ebm calculations based on the "proportion relapse free" data for the original interferon-b a (rebif) study show an rrr of %, and arr of %, and an nnt of over years to increase the number of relapse free by one. relative treatment advantages of interferon-b a and b have not been clearly established but are under study. , a pilot study in rrms patients suggests that interferon-a may also have a therapeutic effect. a study of interferon responders showed that younger patients with frequent relapses, and higher edss scores upon entry may be associated better response. laboratory monitoring of interferon products. it is important to note that even though the interferon products are generally safe to use, they can be associated with potentially harmful adverse reactions. we recommend that every newly starting patient should have a baseline complete blood count, liver function tests, and thyroid-stimulating hormone (tsh) test. the liver function tests and blood count studies should be repeated in week, month, and every months thereafter; the tsh should be repeated every to months. glatiramer acetate. glatiramer acetate (ga) is a synthetic mixture of polypeptides produced by the random combinations of four amino acids that are frequent in mbp. after a preliminary study suggested efficacy, a phase iii randomized, double-blind, placebo-controlled, multicenter trial showed a % reduction in relapse rate. the fda has approved this medication for use in rrms. even though this disease-modifying therapy requires daily subcutaneous administration, the side effects are relatively minor compared to the interferons, and patients do not need regular laboratory monitoring (table - lesions, lesion volumes, and the percentage of new lesions that will evolve into t "black holes," although the mri effect may be less pronounced compared to the interferon products, and is not apparent until the agent has been used for at least months. [ ] [ ] [ ] the ebm calculations for ga using the "proportion relapse free" data show an rrr of %, arr of %, and an nnt of over years to increase the number of relapse free by one. combined azathioprine and interferon-b b. a small trial at nih showed significant reduction in the number of contrast-enhancing lesions when azathioprine in an average maintenance dose of mg/kg/day was added to interferon-b b in a study of six rrms patients followed for a median period of months. the addition of azathioprine may be considered in "treatment failure" cases, but this study was hampered by the small number of patients, no control subjects, and no blinding. intravenous immunoglobulin. monthly treatment with low-dose ( . to . g/kg) intravenous immunoglobulin (ivig) in rrms patients resulted in fewer and less severe relapses in addition to slowing the accumulation of disability in a single randomized trial. the outcome was similar to that of injectable interferons. this therapy is less accepted in the united states. more studies with larger number of patients and extended follow-up are needed to confirm these limited observations. recent studies have failed to demonstrate that ivig administration reverses long-standing deficits from ms and on. [ ] [ ] [ ] ivig was also recently studied in acute on and failed to demonstrate benefit on any of the outcome measures. natalizumab. in late , natalizumab was approved for the treatment of rrms. natalizumab is a humanized a- integrin antibody that inhibits the migration of all leukocytes (except for neutrophils) to target organs. a phase study established that a -mg monthly dose reduced the number of gadolinium-enhancing lesions by % and the clinical relapse rate by over % compared to placebo. this study was followed by the affirm and sentinel phase iii studies. the affirm study enrolled over patients with rrms; none of them had been on other approved immunomodulators for longer than months. the annualized relapse rate at year was reduced from . in the placebo group to . in the treated group ( % relative reduction, p < . ). the proportion of relapse-free patients was % in the treated group, % in the placebo group. the number of enhancing lesions was reduced by %, and the number of new or newly enlarging t lesions was reduced by %. the proportion of patients without clinical and mri activity was % in the natalizumab group, and % in the placebo group. in the sentinel trial, the combination of intramuscular interferon-b a and natalizumab was studied against im interferon-b a and placebo in patients who had demonstrated an incomplete response (relapse suppression) to interferon therapy. the ebm calculations of the affirm data based on proportion with relapses suggests an rrr of %, an arr of %, and an nnt of over year to increase the proportion of relapse free by one. the senti-nel data shows an rrr of %, an arr of %, and an nnt of over year to increase the proportion relapse free. the original pilot trial data shows a rrr of % and an arr of %, with an nnt of over months to increase the proportion relapse free. based on these data, the fda granted expedited approval of natalizumab on november , . on february , , the medication was voluntarily withdrawn from the market by the sponsor (biogen-elan) after two cases of progressive multifocal leukoencephalopathy (pml) were reported in the sentinel study cohort. both patients were in the combined interferon and natalizumab arm. a third pml case was later identified from one of the phase iii inflammatory bowel trials of this agent. at the time of writing this manuscript, natalizumab is still off the market. the natalizumab story has received significant media attention. several consequences can be drawn from this failure. first, highly potent immunomodulators like natalizumab are best used by specialists in selected cases. a large number of prescriptions were written for natalizumab during its short months on the market, including prescriptions by general practitioners. widespread use of such medication in relatively stable cases of ms is not indicated. second, the combination of potent immunomodulators may result in unpredictable adverse outcomes. many ms experts anticipate that in the future ms therapies will need to be administered in combination to optimize therapeutic benefit. however, the exact effect of such combinations on the highly complex immune system is difficult if not impossible to predict. furthermore, our inability to treat ms more effectively does not stem from the fact that we can not provide powerful immunosuppression, as evidenced by the autologous bone marrow transplantation studies. ms is a complex disease with a prominent inflammatory component; however, increasing evidence suggests that the neurodegenerative component of this illness may be independent of the inflammatory component, and is just as important, if not more important, from the standpoint of long-term disability. third, in chronic diseases such as ms, a short -year trial, no matter how convincing the outcome may be, should not be considered sufficient to approve a medication, which will then be used in tens of thousands of patients on a "lifelong" basis. there clearly is a need for new and more effective medications for treating ms; however, clinical trials in chronic conditions are very difficult to sustain. to overcome this, many ms trials use primary mri outcome measures, since inflammation and new lesion formation-related mri markers respond more immediately to treatment; however, these markers do not correlate well with long term disability, as discussed earlier. summary of recommendations for the treatment of rrms patients. when making decisions about starting an ms patients on immunomodulators, several factors must be considered. one must realize that even though there are medications available for relapsing forms of ms, all the currently available therapies are only partially effective, the most reliable data is about short-term relapse rate reduction, and a relapse rate reduction does not necessarily translate into reduction of future disabilities. natural history data clearly suggest that a subset of ms patients will do very well without treatment (see discussion about the olmsted county cohort later); this information can be very useful when deciding about treatment in patients with a -or -year disease history and minimal disability (edss . ). in this patient group, a careful wait and see approach with appropriate monitoring is acceptable. counseling of newly diagnosed ms patients is of crucial importance, and it should usually include family members. most patients have easy access to an abundance of frequently misleading information on the internet, or from relatives and friends with ms. it is important to realize that every case is different; however, through the rational use of natural history data, clinical and mri features of the specific case, and the clear understanding of the available clinical trial data, the clinician should be able to provide customized and relevant advice to patients and families. considering that the treatments are only partially effective, the wishes of an educated patient constitute an important part in the decision-making process. ultimately, the treatment decisions should remain individualized between the patients and their treating physicians, and the physician's role as an information clearinghouse and educator cannot be overemphasized in this process. the three interferon products and ga represent the most commonly used ms immunomodulators in the united states; therefore, it is important to draw some practical conclusions about these agents. by now, several class i studies demonstrate that these agents are effective in reducing the relapse rate in rrms over a -to -year period; the reduction is roughly % with the high-dose interferons and ga. the above-mentioned nnt data are also very useful for the clinician and the well-informed patient when making treatment decisions. there is evidence for a dose-response relationship among the interferon products, mostly from the evidence and incomin studies. the double dose im interferon-b a study did not show a dose-response relationship; this may be related to the fact that the increased dose was given with the same frequency as the standard dose. the injectable immunomodulators have incomplete evidence for efficacy in disability-based outcome measures. many of the long-term extension studies suffer from several drawbacks, including open label unblinded design, significant dropout rate, and lack of control subjects; this is especially true for the ga extension data. the currently available few head-to-head comparison studies are also hampered with methodological issues; new comparative studies are under way. overall, these agents remain partially effective in relapsing forms of ms; their long-term effects on reducing the clinically most important feature of ms-disability-still remains unclear. altering the course of secondary progressive ms. within years of onset, almost % of rrms patients will enter the secondary progressive phase of the disease. treatment approaches aimed to affect the natural course of disease are available for these patients. interferons. interferon-b b may have a beneficial effect on the overall outcome of spms and may also alter mr lesions, , but this question remains incompletely answered. in the placebo-controlled european study of inteferon-b b in spms, the time to worsening was extended for treated patients. treated patients were less likely to be wheelchair-bound and had fewer hospitalizations. another analysis of this study confirmed the benefits, though the dropout rate in this study was relatively high. the patients who responded best to interferon therapy were those who experienced relapses during their disease course. mri monitoring suggested that the benefit on t lesion activity was seen early and persisted into the second half of the second year of treatment. t lesion load increased in placebo-but not interferon-treated patients in the first years of treatment. contrasting with these results, in another trial involving patients with spms, both high dose ( mg) and lower dose ( mg) interferon-b a failed to change the primary outcome of time to disability worsening. positive effects were seen on relapse rate and reduction of mri activity, but the effect on disability did not replicate the european interferon-b b report. a combined analysis of the american and european trials concluded that continued relapse activity and more rapid progression over the preceding year (by > on the edss scale) are the best predictors of response. ivig in secondary progressive ms. a recent european trial reported that ivig did not have a significant impact on clinical and disability related outcome measures. ivig did reduce the accumulation of brain atrophy in spms, but did not reduce the incidence of blood-brain barrier abnormalities. there was no statistically significant change on magnetization transfer mri measurements; however, a trend for conservation of normal-appearing brain tissue was found. overall recommendations for spms. in general, as the evidence that interferons alter long-term disability is limited and controversial, we generally do not newly start spms patients on interferon products. in a subset of patients still having disabling relapses, interferon therapy may be offered to specifically reduce relapse rate. the data by confavreux and associates, however, suggest that the edss in populations of spms patients continues to progress independent of relapses once a "fixed" baseline level of moderate disability has been reached. therefore, while interferons may reduce the relapse rate in spms, the rate of progression of disability may not be reduced by these treatments. more usually, spms patients are already on an injectable immunomodulator, and the question of whether it is worth continuing the therapy may come up, especially in patients who have a hard time tolerating these medications and feel that the side effects of the medications have a clear negative impact on their overall health. in these cases, we usually allow the patients to stop their medications. just like in the rrms cases, however, patient education about spms trials and realistic expectations about the treatment is a crucial element in the decision-making process. understanding the patient's needs and fears and clarifying potential misconceptions constitute a very important role of the treating neurologist. in those patients who continue their interferon therapy, we must continue to follow them for toxicity and disease activity. please also see the following discussion under mitoxantrone for recommendations on the potential use of that specific agent in spms. mitoxantrone. mitoxantrone (novantrone) is an anthracenedione chemotherapeutic agent licensed . . .for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e. patients whose neurologic status is significantly abnormal between relapses). mitoxantrone is not indicated in treatment of patients with primary progressive multiple sclerosis. significant benefits were observed in a group of spms patients as in a european phase iii study of mitoxantrone. it has also been used in combination with methylprednisolone. several clinical and functional outcome measures were reported to stabilize or improve with every -month administration of this intravenous medication. secondary mri outcome measures, including enhancing lesion formation and overall t lesion load, were also better in the treated patients. the greatest concern regarding this medication is its cardiac toxicity: the cumulative lifetime maximum dose was established at mg/m . mitoxantrone can induce a seemingly dose-dependent cardiomyopathy, leading to potentially fatal congestive heart failure. we generally avoid exceeding a total lifetime dose of mg/m ( doses of mg/m ). patients receiving mitoxantrone should also be monitored every months with echocardiograms or muga (multiple gated acquisition) scans to determine the ejection fraction. reduction in the ejection fraction should prompt discontinuation of this therapy. besides the cardiac side effects, mitoxantrone may cause menstrual irregularities or overall ablation of the menstrual cycle, which may be permanent. in a review of the literature, ghalie estimated the risk of mitoxantrone therapyrelated acute leukemia in ms patients at . % to . %; in an international registry of ms patients taking mitoxantrone, the risk of leukemia seems somewhat higher. this therapy has been approved by the fda for treatment of spms, but no peer-reviewed full report of the mims study had been published until years after the initial report in an abstracts form. the study showed a treatment effect in rrms and spms patients with "recent rapid worsening." the study had a high dropout rate and a small sample size. most patients ( %) had relapses in the preceding years, suggesting this cohort mostly includes worsening rrms or prms patients, in whom a positive treatment effect is expected; however, it does not mean that for classic spms patients who no longer have relapses the study outcome is applicable, and it is especially not applicable to ppms cases. the primary outcome measure was a composite score comprised of five clinical measures: change in edss at years; change in ambulation index at years; change in the baseline standardized neurological status at years; number of relapses requiring corticosteroid treatment; and time to first relapse. seventy-seven percent completed months of follow-up. at months, benefit was reported in all five components of the composite measure for both active treatment arms, with the overall greatest benefit noted between placebo and the group receiving mitoxantrone at a dose of mg/m . the magnitude of the effect on edss was rather modest (mean edss change for high-dose mitoxantrone, - . [sd . ] versus þ . [sd . ] in the placebo group). the mri results of the mims trial were published in and are frankly disappointing. in a subset of patients (out of in the trial overall), the mg/m dose failed to reach a significant difference from placebo as measured by the primary mri outcome (total number of scans with gadoliniumenhancing lesions). the mg/m dose reduced the number of t -weighted lesions at month (p ¼ . ) and showed a trend at month (p ¼ . ). the number of active mr lesions showed a trend toward reduction in the mg/m group only at month (p ¼ . ). overall, the limited evidence to date supports the conclusion that mitoxantrone reduces relapse frequency and mri evidence for blood-brain barrier disruption in patients with very active ms. the benefit for patients with relapse-independent progression is uncertain at best. from the mims results, one would need to treat patients with secondary progressive multiple sclerosis for years to prevent one person from worsening by . edss point. this modest benefit must be carefully examined in light of the significant risk for toxicity. therapy of ppms. unfortunately, for classical ppms cases that present with insidious progression of usually myelopathy symptoms, none of the currently available treatments offer any clear benefit. the promise trial, in which over ppms patients were treated with ga, was terminated early owing to lack of effectiveness. the results of this trial have not yet been published. a small study with intramuscular interferon-b a was also negative. currently a large trial is under way with rituximab in csf ocb-positive ppms patients. until we clearly understand the pathophysiology of slow progression in ms, it is unlikely that we will find a treatment that has an important impact on this form of ms. symptomatic treatment modalities, including physical and occupational therapy, are very important, yet frequently overlooked in this patient population. other immunomodulator therapies. cyclophosphamide is an alkylating agent that has indiscriminate cytotoxic effects on rapidly dividing cells, including lymphocytes, making it a potent immunosuppressant. several studies have claimed a beneficial effect in both relapsing and progressive patients. because one of the major studies included acth, iv methylprednisolone is sometimes given with the cyclophosphamide. other trials have not found a favorable effect. because of the inconsistent results, high potential for serious side effects, and adverse reactions, including hemorrhagic cystitis and malignancy, cyclophosphamide is not widely used. some centers, however, use cyclophosphamide in patients with aggressive disease in whom more conventional treatments have failed. azathioprine, a purine analog antimetabolite, has marginal efficacy in the treatment of ms. a meta-analysis of all blinded, placebo-controlled studies confirmed a slight benefit of slowed progression and less frequent relapses. the toxicity of azathioprine and its slow onset of action have prevented its widespread use. besides the liver toxicity and hematological effects, the induction of malignancies has been a concern. one retrospective study did not find an increased incidence of cancer in ms patients treated with azathioprine, but this remains a potential risk. methotrexate is a folate antagonist that is effective in rheumatoid arthritis. weekly low-dose oral methotrexate was found to delay upper extremity dysfunction in spms patients, although it had no effect on the more traditional measures of disability, including the expanded disability status scale (edss). the use of cyclosporine in the treatment of ms has been evaluated in three clinical trials, none of which have demonstrated a convincing benefit. in addition, side effects such as hypertension and elevation of creatinine were common. numerous additional therapies have been tested, and many others are undergoing evaluation. the antiherpesvirus drug acyclovir has been shown to reduce relapse frequency in a small prospective trial. total lymphoid irradiation was found to slow the chronic progression of ms, but because this approach precludes the later initiation of immunosuppressant drugs and may be associated with a higher mortality rate, it is not widely used. cladribine is a nucleoside derivative that was found to decrease relapse rate and slow the progression in patients with spms in an initial investigation. the drug is better tolerated than other parenteral immunosuppressants, although bone marrow suppression is a risk. in a more extensive clinical trial, cladribine therapy did not change disability scores, but significant reduction in enhancing lesions and overall t lesion burden was observed with higher dose treatment. a study of a small number of patients treated with autologous stem cell transplantation suggested possible clinical stabilization or minor improvement over a -month period of follow-up in both secondary and primary progressive ms. the induction chemotherapy (beam regimen) resulted in one fatality in this trial; similar incidences are known in patients undergoing this procedure. the small number of patients and the different methods used (some patients received cd þ selected graft) makes the interpretation of this data very difficult. trials with higher number of patients under standardized circumstances are needed to verify the validity of these observations. symptomatic treatment of existing disabilities spasticity. spasticity is common even in patients with only minimal weakness (video , spastic gait). it is usually prudent to begin treatment of mild spasticity with a stretching program. a randomized controlled crossover trial of physical therapy ( -week blocks of therapy twice a week, for minutes per session) showed significant benefit on several outcome measures related to improved mobility. no apparent differences were observed between home-based or hospital-based therapy. the addition of an evening dose of benzodiazepine may help relieve extensor spasms and clonus that may interfere with sleep. as spasticity worsens, it becomes necessary to use baclofen. doses should be escalated slowly to prevent the occurrence of overt side effects, and up to mg/day may be required. although baclofen is well tolerated in most patients, limiting side effects such as sedation and increased muscle weakness may occur, and rarely a paradoxical increase in spasticity is noted. liver enzyme elevation and nonconvulsive status epilepticus presenting as encephalopathy have also been reported in association with baclofen. abrupt withdrawal of baclofen may result in hallucinations or seizures, making it necessary to taper doses. despite symptomatic improvement, antispasticity measures may not increase function or independence. in paraplegic patients with severe spasticity and intolerance to the required oral dose, intrathecal baclofen delivered by a subcutaneously implanted pump allows a much smaller dose and is often effective in alleviating intractable spasticity and may lessen urinary urgency. tizanidine seems to be as effective as baclofen, although it may be associated with more fatigue. dantrolene has been used for spasticity, although the therapeutic window is small. fatigue. for treating fatigue, medications are only partially effective. amantadine at mg twice a day is the standard initial treatment, although pemoline . mg daily is also superior to placebo. a recent, small pilot study by the mayo group suggested that high-dose aspirin ( mg/day) may sometimes be effective in the treatment of ms-related fatigue. this finding needs to be confirmed by a second, larger trial, however. the stimulating effects of the selective serotonin reuptake inhibitors may also be somewhat effective in combating ms-related fatigue. modafinil, a medication approved for the treatment of narcolepsy, has also been used with good success. often, however, patients need to limit activities and schedule rest periods. paroxysmal symptoms of ms. paroxysmal symptoms are highly responsive to medical treatment. a small dose of carbamazepine is often very effective. if not tolerated, several alternative medications may be tried, including phenytoin, acetazolamide, baclofen, and gabapentin. in addition, misoprostol has been claimed to be effective in ms-related trigeminal neuralgia. after about month of treatment, a periodic attempt at tapering off these medications is a reasonable approach because these symptoms usually remit. seizures in ms are treated no differently than in non-ms conditions. heat sensitivity. heat sensitivity may require avoidance of precipitating activities, but this depends on the nature of symptoms and the situation in which they occur. if the precipitating activity cannot be avoided, a cooling jacket may be an option. a potassium channel blocker, -aminopyridine, improves temperature sensitivity in some patients but occasionally causes seizures or disturbing paresthesias. action tremor. action tremor is a common disabling symptom (video , tremor with ataxia). unfortunately, it is often only marginally amenable to medical therapy. clonazepam may offer some relief, but tolerance frequently develops, necessitating increasing doses. isoniazid and carbamazepine have also been found marginally beneficial. one clinical trial showed ondansetron to reduce tremor-related disability. anecdotal reports suggest that gabapentin may be partially effective. improvements in stereotactic neurosurgery have made thalamotomy a legitimate option in those whose disability is mainly due to tremor and not ataxia. cognitive and memory problems. cognitive problems can also be seen in ms patients. these symptoms are generally not very severe; however, in some patients these may be one of their subjectively most bothersome complaints. it is important to make sure that such complaints are not depression related, as mood disorders are otherwise rather common in ms, and may explain the subjective cognitive impairment. while it is not fda approved for the treatment of ms related cognitive dysfunction, in a placebo controlled, randomized, -week long study of donepezil in patients, significant improvement was found on the selective reminding test (srt). this improvement was independent of ms subtype, gender, age, reading ability, and baseline srt results. the patients did not improve on other cognitive scales, but they were twice as likely to report cognitive improvement. dysesthetic pain. dysesthetic pains are difficult to control but sometimes respond to tricyclic antidepressants, carbamazepine, or baclofen. gabapentin, tramadol, and duloxetine may also be effective. standard analgesics are not often useful in ms-associated pain, and narcotics should be avoided in the treatment of chronic pain. emotional incontinence may be amenable to a low dose of a tricyclic antidepressant (video , dysarthria). symptoms of bladder dysfunction. symptoms of a hyper-reflexic bladder (urgency, frequency, and urge incontinence) are often manageable with anticholinergics such as oxybutynin, propantheline, or imipramine. a flaccid bladder can sometimes be aided by bethanechol, although intermittent self-catheterization is more often needed. symptoms that suggest urinary retention (a feeling of incomplete emptying, frequency, hesitancy, or a need to apply pressure to the lower abdomen to urinate) should prompt evaluation with urinalysis and a post-void residual urine measurement. residuals in excess of ml are abnormal; and if they are above ml, consideration should be given to urological consultation for more thorough investigation and to blood chemistries to determine urea and creatinine levels. detrusor-sphincter dyssynergia, diagnosed by cystometrography, is treated with anticholinergics, sometimes with the addition of an a- blocking agent (terazosin) or intermittent catheterization. it is important to reassess bladder function periodically, and residual urine volumes should be monitored if there are any persistent changes in function or symptoms. intermittent catheterization should be considered when post-void residuals reach ml. a chronic indwelling urinary catheter should be avoided if reasonably possible. it is usually not necessary to use antibiotics prophylactically in the prevention of urinary tract infections. urinary calculi may be prevented by acidification of the urine with cranberry juice. bowel dysfunction in ms. constipation can usually be managed with bulk laxatives and stool softeners. more severe cases may require osmotic agents, bowel stimulants, anal stimulation, suppositories, or enemas. bedridden patients may develop fecal impaction unresponsive to these measures and require manual disimpaction. fecal incontinence can be minimized by adherence to a schedule for bowel movements. fiber supplementation may be of some benefit even in these cases. sexual dysfunction in ms. the clinician should determine the precise nature of any sexual dysfunction in patients with ms. physical difficulty from spasticity may be alleviated by premedication with baclofen, and a fast-acting anticholinergic such as oxybutynin may calm urinary urgency. sexual dysfunction should not be automatically attributed to ms. it may be necessary to investigate hormonal levels and to obtain urological or gynecological consultation. manual lubrication with gel is a ready solution to vaginal dryness. erectile dysfunction responds very well to sildenafil. less frequently, vacuum devices, intracavernous injections of papaverine (or combinations of papaverine, prostaglandins, and epinephrine; triple agent), or penile implant are also used in the treatment of erectile dysfunction. thalamotomy or thalamic stimulation may provide some short-term clinical benefit to patients disabled by appendicular cerebellar tremor and ataxia. the benefits on disability and quality of life are much less clear, however, and the early benefits may wain within to years. , further studies are needed to clarify how best to select patients for these ablative and stimulation treatment interventions. general recommendations for ms patients. it is advisable for ms patients to attain good health habits, including proper diet and fitness. smoking, excess alcohol intake, and obesity should be avoided. exercise can help maximize function by increasing and maintaining joint mobility, strength, and stamina; may promote improved sleep hygiene; and may reduce the severity of fatigue. physical and occupational therapy can play an important role in regaining independence. canes, walkers, and wheelchairs or scooters may be needed to maintain safe mobility. hand controls can be installed in automobiles for patients with lower extremity dysfunction. in debilitated, immobilized patients, periodic shifts in posture to change weight-bearing regions and air or water mattresses prevent bedsores. passive range of motion exercises prevent contractures. when ventilatory dysfunction occurs, it should be evaluated and activity schedules should be appropriately modified. special considerations during pregnancy. before initiation of any drug in a woman of reproductive age, the potential for teratogenicity must be discussed. in general, immunomodulator therapy should be avoided if one is planning a pregnancy. the treatment of acute exacerbations is unchanged during pregnancy, although one might have a higher threshold for treatment. both corticosteroids and plasma exchange are relatively safe during pregnancy. none of the drugs used to alter the disease course, however, should be used during pregnancy. interferon-b drugs should be stopped to months before planning pregnancy. interferons are associated with an approximately % likelihood of abortions. this is close to eight times higher than the usually quoted approximately % spontaneous abortion rate in women. interferon-b use is also associated with lower birth weight. the cytotoxic immunosuppressants have teratogenic effects. the effects of many of the other drugs are unknown. it is best if these drugs are stopped several months before a planned pregnancy. prognosis and future perspectives. because most information on the prognosis of ms is reported in terms of the edss, it is important to have some understanding of this scale. the edss is a -point scale, with each increase representing worsening symptoms of function. the score is derived from severity scores in each of six systems as well as ambulation and work ability. a score of means no signs or symptoms; to represent mild disability with no or minimal impairment of ambulation; . to . refer to moderate disability and impairment of gait; the need for a cane to walk one-half block ( m) receives a score of ; an edss of refers to the need for a wheelchair and effective upper extremity function; an edss of refers to death related to ms. ms has a highly variable outcome, ranging from asymptomatic to fulminant with death ensuing in a matter of months. autopsy series have estimated that unsuspected ms may occur in as many as . % of the population. even when symptomatic, ms may cause only nuisance symptoms. benign ms, when defined as unrestricted ambulation or edss of or less years after onset, accounts for about one third of cases. however, many of these patients acquire more disability later. when considering all patients with ms, weinshenker found that years after onset, % had edss worse than , % had reached edss of or more, % were at edss , and % had died. the percentage of patients with initially rrms who develop spms increases steadily with disease duration. at years, % to % have continual deterioration; after years, approximately % have slow progression. in the most recent study published about the olmsted county ms prevalence cohort consisting of patients, the mean change in edss over years was point, and only % of patients had a change larger than . points. eighty-three percent of the patients with mild symptoms (edss < . ) were still ambulatory without cane years later. among the patients with an edss of to , % were using a cane; in the to edds range, % were wheelchair bound. strong predictors for the outcome were not identified in this study. population-based studies with complete ascertainment can effectively remove the bias of a referral practice, which is inherently biased towards the more active and more serious cases. these studies also provide some much needed balance to the "heavily skewed for recent disease activity" clinical trial experience. from the most recent extensions to the olmsted county ms cohort studies conducted by the mayo group, several conclusions can be drawn. the number of relapses in the first year of the disease do not predict long term outcome. the time to disability is not influenced by ongoing relapses once patients achieve an apparently permanent degree of moderate disability (edss . ). overall, % patients who are still classified as rrms into their second decade of disease continue to do well for to years with limited permanent disability. patients doing extremely well (edss . ) after years of ms generally do well in the next decade. however, very rarely patients doing well even for to decades may develop severe late disability. we advise that neurologists share these findings with patients who are in periods of prolonged remission during the discussions about the merits of beginning disease-modifying agents. natural history studies have identified several prognostic indicators that predict outcome to a limited extent. factors associated with a better prognosis (slower accumulation of disability, longer time before chronic progression) include young age at onset, female gender, rr course (as opposed to ppms), initial symptoms of sensory impairment or on, first manifestations affecting only one cns region, high degree of recovery from initial bout, longer interval between first and second relapses, low number of relapses in the first years, and less disability at years after onset (both edss and number of systems affected-sensory, motor, sphincter, brain stem, vision, cerebral). despite the indolent nature, a pp course is the worst prognostic factor, with the median time to reach edss of only years, compared with approximately years in rr patients. men and patients with an older age at onset are more likely to have ppms. the survival of ms patients is only slightly below expected. seventy-six percent of patients are alive years after onset, which is % of that seen in age-and sexmatched control subjects. ms is rarely the direct cause of death. complications of ms such as pneumonia, pulmonary emboli, aspiration, urosepsis, and decubiti are responsible for % of deaths. most of the other deaths are from heart disease, cancer, cerebrovascular disease, and trauma. suicide is the only cause of death that is overrepresented among these cases. the suicide rate among ms patients may be as high as two to seven times that of non-ms persons. neuromyelitis optica (nmo) is an uncommon neurological illness characterized by the occurrence of optic neuritis and myelitis. the names devic's syndrome, devic's disease, and nmo are often used interchangeably, although the first name encompasses all patients who fit the preceding definition and the second and third should only be used to refer to those patients presumed to have a distinct disorder. the term opticospinal ms is often used in the far east to denote patients with exclusive or predominant involvement of optic nerves and spinal cord, encompassing most patients with devic's syndrome. devic's disease (nmo) may be a monophasic illness, or may show a relapsingremitting course. it is the first inflammatory demyelinating disease with a known serum marker, the nmo-igg antibody. pathogenesis and pathophysiology. devic's syndrome may occur with adem, autoimmune disorders (e.g., systemic lupus erythematosus), ms, and possibly viral infections. also, patients with devic's disease may have other coexisting autoimmune conditions. classically, acute spinal cord lesions demonstrate diffuse swelling that extend over several levels or involve nearly the entire cross section of the cord. acutely, there is destruction with dense macrophage infiltration involving white and gray matter, loss of myelin and axons, and lymphocytic cuffing of vessels. in chronic lesions, the cord is atrophic and necrotic, occasionally with cystic degeneration and gliosis. in the absence of perivascular cuffing, these extensive lesions resemble infarctions. the prominent spinal cord swelling in the confines of the restrictive pia presumably may raise intramedullary pressure, leading to the collapse of small parenchymal vessels, further propagating tissue injury. proliferation of vessels with thickened and hyalinized walls similar to that seen after infarction or other extensive injury may occur. less fulminant lesions may coexist and are much more typical of inflammatory demyelination. the optic nerve lesions often involve the chiasm. even though nmo is usually restricted to the optic nerves and spinal cord, one may see classic ms like lesions in up to % of cases, and hypothalamic lesions have also been described in approximately %. the newly discovered serum marker, nmo-igg has a sensitivity of % and specificity of %. the discovery of this novel immune marker also clarified that most if not all cases of "opticospinal ms" reported in the japanese literature are also cases of nmo. to the surprise of the ms research community, the antigen is neither myelin nor neuron related: it is the aquaporin- water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the bloodbrain barrier. nmo thus may represent the first example of a novel class of autoimmune channelopathies. epidemiology and risk factors. devic's syndrome occurs in patients of varied ages (range, to years). the mean age at onset of monophasic devic's syndrome is , whereas relapsing nmo (see later) tends to occur in an older age group (mean age at onset of ). monophasic devic's syndrome affects males and females equally, whereas relapsing nmo affects females predominantly (f:m, . : ). one third of patients have a preceding infection within a few weeks of neurological symptom onset. most commonly this is a nonspecific upper respiratory tract infection, flu, or gastroenteritis. the most common specific infections preceding the development of devic's syndrome are chickenpox and pulmonary tuberculosis. devic's syndrome has also followed vaccination for swine flu and mumps. only a few instances of a possible familial occurrence of devic's syndrome have been reported, and in one of these families, a unique mitochondrial mutation was found. devic's syndrome is said to be more common in japan and east asia, although even there it is uncommon (less than per , ). three cases have been described in the literature with familial occurrence of devic's disease in the far east. in a genetic study, hla-dpb * was more frequently associated with "opticospinal ms," whereas hla-dpb * is the most strongly associated allele with conventional ms in the japanese. symptoms of on and myelitis develop over hours to days and are often preceded or accompanied by headache, nausea, somnolence, fever, or myalgias. continued progression of symptoms over weeks or months occasionally occurs. most patients (greater than %) develop bilateral optic neuritis. bitemporal or junctional field deficits, indicating chiasm involvement, are sometimes present early in the course of the on. visual loss is often accompanied by periocular pain, and myelitis onset is sometimes heralded by localized back or radicular pain. lhermitte's sign is common. severe degrees of neurological deficits are usual, and the degree of recovery is variable. approximately % of nmo patients have a monophasic illness, % develop relapses usually limited to the optic nerves and spinal cord (relapsing nmo or opticospinal ms), and rarely patients have a fulminantly progressive course without relapses or a course typical of ms. according to a study conducted at the mayo clinic, patients with a monophasic course usually presented with rapidly sequential events (median, days) with only moderate recovery. patients showing characteristics of the relapsing form of devic's had a median interval of days between index events, followed within years by clusters of severe relapses isolated to the optic nerves and spinal cord. most relapsing patients developed severe disability in a stepwise manner. approximately one third died from respiratory failure. predictors of a relapsing course in nmo include longer inter-attack intervals (relative risk [rr]: . per month increase), older age at onset (rr ¼ . per year increase), female sex (rr ¼ . ), and less severe motor impairment with sentinel myelitis event (rr ¼ . per severity scale point increase). autoimmune disease history (rr ¼ . ), higher attack frequency in first years (rr ¼ . per attack), and better recovery following index myelitis (rr ¼ . per point) are associated with increased mortality rate. features of nmo distinct from "typical" ms included normal initial brain mri, more than cells/ml in csf with polymorphonuclear predominance, and lesions extending over three or more vertebral segments on spinal cord mri. relapsing nmo is often associated with autoimmune disorders, most commonly systemic lupus erythematosus. these patients also frequently have an elevated erythrocyte sedimentation rate and nonspecific elevation of autoantibodies, including antinuclear antibodies, anti-ds-dna, and antiphospholipid antibodies. tonic spasms and neuropathic lower extremity pain are common sequelae to the spinal cord damage. symptoms referable to brain stem lesions (nystagmus, ophthalmoparesis, and vertigo) can occur in these patients as well. differential diagnosis. the differential diagnoses for devic's syndrome includes ms, adem, pulmonary tuberculosis, and viral infection (especially in the immunocompromised patient). in patients with an apparent affected family member, consideration should be given to mitochondrial disease. relapsing nmo should raise the suspicion for associated autoimmune disorders. because devic's syndrome can occur in persons older than age , when an unrelated ischemic optic neuropathy could occur, and because isolated or recurrent myelopathy may precede the on, additional consideration must be given to spinal cord compression, spinal cord tumor, and spinal arteriovenous malformation (avm) or dural fistula. evaluation. imaging is needed to exclude structural lesions and provide information on the pathological process. optic nerve or chiasm enlargement, t -weighted signal changes, and enhancement may be seen on head mri during the acute phase. increased t -weighted signal in the medulla is not uncommon and usually represents extension of high cervical lesions. spine mri characteristically shows cord swelling, signal changes, and enhancement extending over at least three levels ( fig. - ) . this appearance may resemble a spinal cord tumor, prompting consideration for biopsy. on magnetization transfer (mt) mri, no significant difference was found on normal-appearing white matter of devic's patients and control subjects, whereas ms patients had a significantly lower mt ratio peak and histogram average. t hypointense lesions in the cord and linear lesions that cross over more than two segments are more suggestive of devic's disease. an occasional patient may need prone and supine myelography to exclude a spinal dural-based avm. laboratory investigations reveal an elevated erythrocyte sedimentation rate in one third, positive antinuclear antibodies in nearly one half, and occasionally other autoantibodies (e.g., thyroperoxidase antibodies). it is reasonable to exclude syphilis, lyme disease, and human immunodeficiency virus by laboratory testing. in a few patients with the far east variety of devic's disease, hyperprolactinemia was described predominantly with optic nerve involvement. a chest x-ray helps to exclude pulmonary tuberculosis and sarcoidosis. csf examination is an essential part of the evaluation for devic's syndrome, and repeated studies are sometimes necessary to ensure that there is no infection in that the csf findings are sometimes atypical for inflammatory demyelination. a marked pleocytosis is often present, sometimes exceeding cells. moreover, neutrophils are commonly seen in csf and may predominate, a situation virtually unknown in ms. the protein concentration is often very high and in % exceeds mg/dl. anti-mog antibodies are the predominant autoantibody detected in csf; anti-mbp or anti-s b antibodies are less frequently seen. despite the intense inflammatory response, ocbs are conspicuously absent in the majority, being present in fewer than % of patients. csf serology for the herpesvirus family (hsv types and , vzv, ebv, and cmv) is important, and polymerase chain reaction testing should be done in cases suggestive of viral infection (immunocompromised patients). management. patients with acute or subacute devic's syndrome may respond to corticosteroids (e.g., intravenous methylprednisolone). they may respond to plasma exchange even when intravenous methylprednisolone does not produce significant improvement. attempts at preventing relapses and the subsequent disability are often disappointing even with the use of immunosuppressive agents. the classic injectable immunomodulators used in ms are insufficient to reduce the relapse rate in relapsing nmo. most commonly, a combination of azathioprine and prednisone is used for secondary prevention. other agents including mycophenolate mofetil, ivig, and mitoxantrone have been described to be effective in some cases. a small study of rituximab, a humanized anti-cd antibody showed a siginifcant reduction in the relapse rate of patients, making of relapse free. a large multicenter study of rituximab in nmo is in the planning stages. supportive care is important in the management of nmo. these patients are prone to many complications and require measures to prevent deep venous thrombosis and pulmonary embolism, urinary tract infection, decubiti, and contractures. mechanical ventilation may be needed either temporarily or permanently. patients with monophasic devic's syndrome generally have simultaneous or rapid onset of the on and myelitis (interval usually less than month). although some have significant residual disability, many recover remarkably and have little or no permanent deficits. a history of previous vague neurological symptoms or definite demyelinating events is predictive of future relapses, either typical of ms or relapsing nmo. those patients destined for recurrent myelitis and on have a longer interval between the onsets of myelitis and on. the vast majority of patients with relapsing nmo have very aggressive disease with frequent and severe exacerbations and a poor prognosis. adem is a monophasic inflammatory demyelinating disorder that characteristically begins within weeks of an antigenic challenge such as infection or immunization. it occurs more often in the young and causes the rapid development of multifocal or focal neurological deficits. perivenous inflammation, edema, and demyelination are the pathological hallmarks of adem, although these lesions commonly enlarge and coalesce, forming lesions pathologically indistinguishable from ms. moreover, perivascular changes typical of adem are common in patients with ms. there is considerable overlap in the epidemiological, clinical, csf, imaging, and pathological features between adem and ms, often making it difficult to distinguish between the two with reasonable confidence when encountering patients with a single demyelinating event. pathogenesis and pathophysiology. adem closely resembles the experimental allergic encephalomyelitis animal model of ms (eae) both clinically and pathologically, and is most likely due to a transient autoimmune response toward myelin. the occurrence of adem after vaccination with the rabbit spinal cord preparation of rabies virus led to the discovery of eae. infections and non-cnscontaining vaccinations may induce adem by molecular mimicry or by activating autoreactive t-cell clones in a nonspecific manner. lymphocyte reactivity toward mbp has been identified in blood and csf from patients with adem, but its absence in others indicates a role for other antigens. increased peripheral blood g interferon-producing t cells have been described in adem. epidemiology and risk factors. adem can occur at any age but perhaps because of the higher frequency of immunization and exposure to new antigens; it is most common during childhood. unlike ms, both sexes are affected with equal frequency. no association has been noted with pregnancy. adem has been reported to follow a number of different immunizations, usually within weeks, including those for pertussis, diphtheria, measles, mumps, rubella, influenza (postvaccination adem), tetanus, and yellow fever. in addition, there are case reports of adem following hepatitis b vaccination. however, the only epidemiologically and pathologically proved association is with rabies vaccination, which also causes demyelinating peripheral neuropathies. the original pasteur rabies vaccine, prepared in rabbit spinal cord, was associated with an incidence of adem of approximately per to per , vaccinations and is no longer in use. a later vaccine, made in duck embryo, which contains little neural tissue, carries a risk for adem of per , vaccines. the use of human diploid cell lines, which contain no nervous system tissue, for the production of rabies vaccine has virtually eliminated the risk of adem. the association of bee stings with adem has also been reported. parainfectious adem usually follows onset of the infectious illness, often during the recovery phase, but because of the latency between pathogen exposure and illness it may precede clinical symptoms of infection or the two may occur simultaneously. the most commonly reported associated illness is a nonspecific upper respiratory tract infection. there have been a vast number of specific infections associated with adem, such as virus infections (including rubella, mumps, vzv, ebv, cmv, influenza, coxsackievirus, and hepatitis c) and infection with mycoplasma, borrelia burgdorferi, and leptospira. measles carries the highest risk for adem of any infection, occurring in per to per cases. although adem has been reported in association with measles immunization, the risk is far lower than the risk of acquiring measles and its neurological complications. clinical features and associated disor-ders. a prodrome of headache, low-grade fever, myalgias, and malaise often precedes the onset of adem by a few days. in a german study of cases, the most frequent clinical signs were motor deficit ( %), followed by sensory deficits, brain stem signs, and cerebellar signs. csf findings were variable; normal results were present in up to % of patients. oligoclonal bands were positive in over %. almost all patients improved during the acute phase of the disease. of the patients with the final diagnosis of adem, had minor or no symptoms, died, the rest had moderate symptoms. compared to ms patients, the adem patients were older, and more often had a preceding infection, clinical signs of brain stem involvement, a higher csf albumin fraction, and infratentorial lesions. neurological symptoms develop rapidly in the acute phase and are commonly associated with encephalopathy, stupor, coma, meningismus, and seizures. peak severity occurs within several days, and recovery may begin soon afterward. occasionally, adem may evolve over a few months and there may be a second clinical deterioration or subacute progression for a time. in these unusual cases, the distinction from ms is difficult. three recent large retrospective series and an accompanying editorial have highlighted that there remain no clinical or laboratory features that accurately allow one to predict which adult or pediatric adem patients will develop. [ ] [ ] [ ] [ ] differential diagnosis. one of the primary concerns after a single demyelinating episode is whether other bouts can be expected (e.g., ms). several features may tip the balance toward one or the other, but the proper diagnosis becomes apparent only with time. classically, adem is characterized by the multifocal involvement at onset whereas ms often presents with monosymptomatic deficits such as on. however, adem may cause unifocal symptoms and ms may present with multifocal cns involvement, especially in children. the monosymptomatic deficits caused by adem are more commonly severe, such as bilateral on and complete transverse myelitis. although ocbs occur transiently in about one third of adem cases, their persistence implies a diagnosis of ms. the subsequent disappearance of ocbs, when performed by consistent techniques, is evidence against ms. the mri appearance of these two disorders is often identical, but the presence of basal ganglia or cortical lesions, or large globular white matter lesions, is more frequent in adem. the fulminant development of adem is distinctive but not pathognomonic, because a rare form of ms known as marburg's ms is also rapid in onset and often deadly. the appearance of brain stem, periventricular, and multiple, large cerebral white matter lesions and the presence of ocbs may distinguish marburg's variant from adem. on rare occasions, inflammatory demyelinating lesions may reach a large size and resemble tumors (especially lymphoma) on mri, necessitating biopsy for clarification. there is usually one dominant lesion, but smaller separate lesions may be identifiable. these have been referred to as both adem and ms in the literature. the prognosis for recovery is often quite good, although approximately one third suffer subsequent attacks. some develop typical ms, whereas others have recurring tumor-like lesions. the term multiphasic adem has been used when patients have large recurrences in the same location, and relapsing adem refers to recurrences at different sites. the relationship of these entities with ms is unclear. balo's concentric sclerosis refers to the pathological finding of alternating bands of demyelination and remyelination. these patients typically have large lesions and subacute deficits similar to those described earlier. typical demyelinating lesions commonly coexist, and rarely cdms patients are noted to have similar-appearing lesions. the reason for this peculiar alternating pattern is unknown. schilder's myelinoclastic diffuse sclerosis is another rare condition that may be confused with adem or other demyelinating conditions. this progressive demyelinating disorder usually begins in childhood. the features are often atypical and include dementia, aphasia, homonymous hemianopia, seizures, psychosis, elevated intracranial pressure, and the absence of ocbs. the most characteristic finding is the presence of two large, roughly symmetrical lesions on mri, one in each hemisphere. the diagnosis is made by excluding the known inherited leukodystrophies, especially adrenoleukodystrophy. management. treatment with intravenous methylprednisolone seems to halt progression and allow recovery to begin sooner, just as with ms. plasma exchange can be tried in those with severe deficits and little response to corticosteroids. ivig has also been used successfully according to case reports in the literature. one fulminant case responded to hypothermia only. genetics of multiple sclerosis utility of mri in suspected ms the use of mitoxantrone (novantrone) for the treatment of multiple sclerosis disease modifying therapies in multiple sclerosis natural history of multiple sclerosis a randomized study of two interferon-beta treatments in relapsing-remitting multiple sclerosis cortical lesions and brain atrophy in ms the pathology of multiple sclerosis management of multiple sclerosis: current trials and future options competing interests in multiple sclerosis 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intracranial imaging findings: a large single-centre experience date: - - journal: clin radiol doi: . /j.crad. . . sha: doc_id: cord_uid: r km aim to describe the neuroradiological changes in patients with coronavirus disease (covid- ). materials and methods a retrospective review was undertaken of , patients who were confirmed positive for severe acute respiratory syndrome coronavirus (sars-cov- ) infection, and admitted to our institution between march and may , and who underwent neuroimaging. abnormal brain imaging was evaluated in detail and various imaging patterns on magnetic resonance imaging mri were identified. results of the , patients with covid- , ( . %) had neurological signs or symptoms warranting neuroimaging. the most common indications were delirium ( / , %), focal neurology ( / , %), and altered consciousness ( / , %). neuroimaging showed abnormalities in % of patients, with mri being abnormal in patients and computed tomography (ct) in patients. the most consistent neuroradiological finding was microhaemorrhage with a predilection for the splenium of the corpus callosum ( / , %) followed by acute or subacute infarct ( / , %), watershed white matter hyperintensities ( / , %), and susceptibility changes on susceptibility-weighted imaging (swi) in the superficial veins ( / , %), acute haemorrhagic necrotising encephalopathy ( / , %), large parenchymal haemorrhage ( / , %), subarachnoid haemorrhage ( / , %), hypoxic–ischaemic changes ( / , %), and acute disseminated encephalomyelitis (adem)-like changes ( / , %). conclusion various imaging patterns on mri were observed including acute haemorrhagic necrotising encephalopathy, white matter hyperintensities, hypoxic-ischaemic changes, adem-like changes, and stroke. microhaemorrhages were the most common findings. prolonged hypoxaemia, consumption coagulopathy, and endothelial disruption are the likely pathological drivers and reflect disease severity in this patient cohort. ☒ performed the analysis ☒ wrote the paper infection with the novel pathogen, severe acute respiratory syndrome coronavirus (sars-cov- ) has resulted in a global pandemic, which has claimed the lives of over , globally (as of july ). severe infection culminating in acute respiratory distress syndrome (ards) along with relatively high transmission rates, has led to the greatest global public health crisis in years. there is predominant respiratory involvement; however, multi-organ complications have been reported. cerebrovascular events and altered mental status have been described as the most common neurological presentations in covid- [ ] . recent studies have described abnormal brain imaging findings of microhaemorrhages, multifocal white matter hyperintense lesions with variable enhancement, infarcts, haemorrhagic lesions, acute haemorrhagic necrotising encephalopathy, inflammatory cns syndromes including acute disseminated encephalomyelitis (adem), and medial temporal lobe abnormalities [ ] [ ] [ ] . as one of the largest uk centres, the present study describes the intracranial imaging findings and likely pathogenesis of patients with covid- . this retrospective observational study was approved by the institution's review board and the need for ethical approval was waived. consecutive patients with covid- and neurological manifestations who underwent brain imaging between march to may were assessed for inclusion. all patients had a confirmed diagnosis of covid- based on detection of sars-cov- by reverse transcription polymerase chain reaction (rt-pcr) from sputum or nasopharyngeal swabs. they required hospitalisation with neurological signs or symptoms during inpatient admission, warranting brain imaging. patients with abnormal brain imaging studies j o u r n a l p r e -p r o o f were included (fig. ) . informed consent was obtained from patients or where appropriate, consent was provided by the next of kin. clinical, laboratory, and imaging data ct brain imaging was performed using a -section multidetector ct system (siemens, erlangen, germany). mri was performed using a . t system (siemens, erlangen, germany) with a -channel phased-array head coil. the following sequences of the whole-brain were obtained: t -weighted sagittal, axial t - (table ). the most common indications were delirium (n= ), focal neurology (n= ), and altered consciousness (n= ). brain mri was abnormal in patients and ct was abnormal in patients. results of abnormal ct studies are summarised in table . findings included subacute infarct, acute infarct, basal ganglia haemorrhage, and subarachnoid haemorrhage, with most patients presenting with focal neurology. the majority of patients presenting with altered consciousness and delirium were investigated by brain mri. for patients who had an abnormal mri brain study, the mean age was . (range - ) years, and the male-to-female ratio was approximately : . sixty percent were of white ethnicity and % were from an asian background. eighteen outcome was variable with seven patients discharged home, six undergoing rehabilitation, four patients died, and the remaining three patients continued to remain as inpatients for at least month. patient demographic and clinical information is summarised in table . a number of neuroradiological findings were identified in patients with abnormal mri brain studies (n= ). mri patterns and likely pathogenesis are described in detail in electronic supplementary material table s . findings included microhaemorrhages j o u r n a l p r e -p r o o f (n= ), watershed white matter hyperintensities (n= ), susceptibility changes on swi in superficial veins (n= ), acute infarct (n= ), subacute infarct (n= ), acute haemorrhagic necrotising encephalopathy (n= ), large parenchymal haemorrhage (n= ), subarachnoid haemorrhage (n= ), hypoxic-ischaemic changes (n= ), and adem-like changes (n= ). results for mri findings are summarised in table (fig. ) . similar lesions were also seen in the corpus callosum and cerebellar white matter. in addition, microhaemorrhages were noticed in the splenium of the corpus callosum and brainstem. the other watershed pattern was of scattered dwi high signal lesions in centrum semiovale with micro-and macro-haemorrhages (fig. ) . susceptibility changes on swi were seen in superficial veins in % of patients, in conjunction with microhaemorrhages, likely representing microthrombi (fig. f) . all of these patients had diabetes and two of these three patients also had hypertension as a predisposing risk factor. haemorrhage. there is emerging evidence that the underlying pathogenesis for these presentations is closely linked to a combination of prolonged hypoxaemia, consumption coagulopathy, and endothelial dysfunction [ , ] . the spike protein of sars-cov- has a strong affinity for angiotensin-converting enzyme (ace ) receptor, which allows it to enter host cells. this protein is expressed on alveolar epithelial cells, intestinal enterocytes, and arterial and venous endothelial cells [ ] . using electron microscopy, sars-cov- viral elements have been demonstrated within endothelial cells themselves, associated with profound inflammation and tissue oedema in covid- patients at autopsy [ ] . a recent j o u r n a l p r e -p r o o f neuropathological series of patients has shown that although the virus was detected at low levels in five patients, there was no evidence of encephalitis and the explanation for this could have been due to in situ virions or viral rna from blood [ ] . all the patients in this neuropathological series demonstrated acute hypoxicischaemic damage. hypoxic-ischaemic damage has been shown to cause leukoencephalopathy and white matter cytotoxic oedema in critically ill patients. leukoencephalopathic changes with or without cytotoxic oedema are seen in many other condition including posterior reversible encephalopathy syndrome (pres), sepsis, adem, hypotension, hypoxia, prolonged ventilator support, drug therapy, and toxic metabolic diseases [ , ] . sars-cov- infection initiates a pro-inflammatory cytokine storm led by tumour necrosis factor α (tnf-α), interleukin (il- ), and interleukin β (il- β) [ ] . this results in a downstream increase in vascular permeability, blood-brain and blood-csf barrier dysfunction, neuroinflammation and subsequent leukoencephalopathy, thought to be due to oligodendroglial cell death and consequent demyelination predominantly in the deep watershed regions [ ] . one patient, who had sustained a cardiac arrest, showed restricted diffusion in the basal ganglia bilaterally, in keeping with hypoxic-ischaemic changes. in this patient, the imaging appearances were likely secondary to hypoxia from cardiac arrest, which could have been a complication of covid- infection involving the myocardium. a neuropathological study has also demonstrated similar appearances in the brain after cardiac arrest in one covid- patient, thought to be secondary to hypoxia [ ] . microvascular disruption of the endothelium in brain tissue may be responsible for extravasation of red blood cells and extensive microhaemorrhages [ , ] . microhaemorrhages have been reported previously in a number of locations j o u r n a l p r e -p r o o f including lobar, subcortical, deep, corpus callosum, pontine, and cerebellar [ , ] . a few studies have reported the splenium of corpus callosum as a predominant location for microhaemorrhages, with or without oedema [ , ] . microhaemorrhages in the splenium of the corpus callosum have been reported previously in severe ards and high-altitude cerebral oedema, thought to be due to hypoxaemia [ ] . it is increasingly recognised that respiratory failure may be due to micro-emboli, and these may also affect the cerebral microcirculation resulting in microthrombosis and microvascular ischaemia. linear structures resembling vessels were observed with susceptibility artefacts on swi, which are probably microthrombi. this increases the risk of stroke or ischaemia amplifying the cytokine-induced injury to the brain [ ] . ischaemic stroke was a common pattern seen on both mri and ct. fifteen patients presented with large vessel stroke on ct and five patients on mri; most were severe, including bilateral mca infarct, as noted previously [ ] . acute stroke seems to be the most common neuroradiological presentation in a large cohort of covid- patients [ ] . similar findings with ischaemic changes and microhaemorrhages have also been published in isolated case reports [ ] . elevated d-dimer levels were observed in most of the present patients, probably due to a hypercoagulable environment. four patients presented with intracerebral bleeds on ct and mri; causes could be due to predisposing vascular risk factors (in % of the patient cohort) such as hypertension, anticoagulation treatment as prophylaxis from thromboembolism, and ecmo. adem-like presentation was seen in one patient, with evidence of haemorrhage, also reported in a previous study [ ] . although scattered white matter demyelinating lesions and perivenular tracking raises the possibility of a parainfectious adem-like process, the authors' impression of the overall phenotype suggested a primarily vascular insult, with secondary white matter injury. a detailed neuropathological examination of one patient has been reported recently [ ] , which concluded that vascular insult was the primary driver of the neurological sequelae. at the peak of the pandemic, although delirium and neuro-cognitive symptoms were neurological and neuropsychiatric complications of covid- in patients: a uk-wide surveillance study the emerging spectrum of covid- neurology: clinical, radiological and laboratory findings brain mri findings in severe covid- : a retrospective observational study covid- -associated diffuse leukoencephalopathy and microhemorrhages covid- related coagulopathy: a distinct entity? endothelial cell infection and endotheliitis in covid- tissue distribution of ace protein, the functional receptor for sars coronavirus. a first step in understanding sars pathogenesis neuropathological features of covid- differences of clinical manifestations according to the patterns of brain lesions in acute encephalopathy with reduced diffusion in the bilateral hemispheres pattern of brain injury in the acute setting of human septic shock covid- : consider cytokine storm syndromes and immunosuppression hypoxic-ischemic leukoencephalopathy in man microvascular injury and j o u r n a l p r e -p r o o f hypoxic damage: emerging neuropathological signatures in covid- neuropathology of covid- : a spectrum of vascular and acute disseminated encephalomyelitis (adem)-like pathology unusual microbleeds in brain mri of covid- patients the pattern of brain microhemorrhages after severe lung failure resembles the one seen in high-altitude cerebral edema covid- related neuroimaging findings: a signal of thromboembolic complications and a strong prognostic marker of poor patient outcome evolving neuroimaging findings during covid- covid- -associated acute hemorrhagic necrotizing encephalopathy: imaging features transient cortical blindness in covid- pneumonia; a pres-like syndrome: case report key: cord- -dmcfy ht authors: chelghoum, rayene; ikhlef, ameur; hameurlaine, amina; jacquir, sabir title: transfer learning using convolutional neural network architectures for brain tumor classification from mri images date: - - journal: artificial intelligence applications and innovations doi: . / - - - - _ sha: doc_id: cord_uid: dmcfy ht brain tumor classification is very important in medical applications to develop an effective treatment. in this paper, we use brain contrast-enhanced magnetic resonance images (ce-mri) benchmark dataset to classify three types of brain tumor (glioma, meningioma and pituitary). due to the small number of training dataset, our classification systems evaluate deep transfer learning for feature extraction using nine deep pre-trained convolutional neural networks (cnns) architectures. the objective of this study is to increase the classification accuracy, speed the training time and avoid the overfitting. in this work, we trained our architectures involved minimal pre-processing for three different epoch number in order to study its impact on classification performance and consuming time. in addition, the paper benefits acceptable results with small number of epoch in limited time. our interpretations confirm that transfer learning provides reliable results in the case of small dataset. the proposed system outperforms the state-of-the-art methods and achieve . % classification accuracy. brain tumor diagnosis is very important in order to develop an effective plan of treatment. there are more than types of brain and central nervous system (cns) tumors. neurologists classify manually the brain mr images using the world health organization (who) classification [ ] . the automation of the classification procedure, in particular brain mr images classification help radiologist in their diagnosis and reduce enormously their interventions. the first automatic classification methods are the machine learning ones. these methods take a long time because they need pre-processing and handcrafted features by experts. the classification accuracy depends on the extracted features which depend on the expert competences. despite the limitation of machine learning methods, some works [ ] achieved between % and % classification accuracy with their proposed method used tumor extracted features such as shape, rotation invariant texture, intensity characteristics and mr images for brain tumor classification. to avoid handcrafted features extraction, deep learning (dl) methods involving deep neural networks to classify images in self-learning without the need of handcrafted features extraction are used by benjio [ ] and litjens et al. [ ] . among several dl methods, cnns are one of the most useful that have been used to solve complex problems in various applications such as detection [ ] , localization [ ] , segmentation [ ] and classification [ ] . they have also yielded good results in medical image application [ ] [ ] [ ] . the first real-word application of cnns was realized by yann lecun in to recognize hand written digits [ ] . since , imagenet launched an important visual database project called imagenet large scale visual recognition challenge (ilsvrc) [ ] . this challenge runs an annual software contest where research teams evaluate their algorithms on the given dataset and achieved higher accuracy. moreover, cnns become more useful when krizhevsky et al. ( ) proposed their cnn architecture called alexnet [ ] . the later competition allowed creating and improving real deep cnns architectures that have achieved higher accuracy on several visual recognition tasks. in recent years, cnns have achieved good results in medical image applications due to the growth of available labelled training data, the increase of powerful graphics processing gpu, the rise of accuracy to solve complicated applications over time and the appearance of numerous techniques to learn features. according to the statistics that we made from google scholar, the number of publications using cnns in the field of medical image applications in general and brain tumor in particular is increase since . this trend can be observed in fig. . and fig. . today, several public brain mr images datasets for classification are available for researchers. this help medical scientists to develop more automated classification methods [ ] . however, the cnns training become more complicated and can lead to overfitting because of the samples size of medical datasets. also, applying deep pre-trained cnns based on transfer learning in medical imaging needs to adjust the hyper-parameters and learning parameters of the models in order to achieve a good result. training the networks with transfer learning is usually much faster and easier than training the networks with randomly initialized weights [ ] [ ] [ ] . in [ ] , authors used a small cnn architecture and achieved . % classification accuracy. a block-wise fine-tuning has been proposed, this one, based on transfer learning, reached a classification accuracy of . % [ ] . other approach proposed by [ ] used pre-trained googlenet and transfer learning to classify brain mr images and achieved . % of classification accuracy. in this paper, we present an automatic classification system designed for three types of brain tumor. we use the brain ce-mri dataset from figshare [ ] which consists of three kind of brain tumors (glioma, meningioma and pituitary tumor) in order to classify only abnormal brain mr images. based on this dataset, we adopted deep transfer learning for feature extraction from from brain mr images using nine deep cnns architectures: alexnet [ ] , googlenet [ ] , vgg [ ] , vgg [ ] , residual networks (resnet , resnet , resnet ) [ ] , residual networks and inception-v (resnet-inception-v ) [ ] , squeeze and excitation network (senet) [ ] . this system makes easier the interventions of radiologist, helps them to solve brain tumor classification problem and develop an effective treatment. we report the overall classification accuracy of the nine pre-trained architectures based on training time and epoch number. we explore the impact of epochs number to minimize the consuming time. we classify the extracted features for three different epochs. we achieve good results compared to related works. also, with smaller number of epochs, we achieve acceptable results in short time. the paper is structured as follows. the proposed method and different pre-trained cnns architectures are given in sect. . the experimental setting, the networks preparation and dataset are shown in sect. . the experimental results with a brief discussion are provided in sect. , the conclusion and an outlook for future work are given in sect. . in this work, we applied nine pre-trained deep networks including alexnet, googlenet, vgg , vgg , resnet , resnet , resnet , resnet-inception-v and senet for brain tumor classification problem using transfer learning. cnns architectures have been designed to learn spatial hierarchies of features by building multiple blocks: convolution layers with a set of filters, pooling layers, and fully connected layers (fcls). the real deep architectures created until through ilsvrc challenge. the classification error of ilsvrc challenge winners is decreased from . % in alexnet ( ) [ ] to . % in senet ( ) [ ] . also, the number of layers is increased from layers to layers. table summarizes the differences between those architectures regarding the classification error, the number of layers, the tasks, the execution environment and the training datasets. alexnet. alexnet [ ] architecture is deeper and much greater than lenet architecture [ ] . it consists of eight layers, five convolutional layers most of them are followed by max pooling and three fully connected layers. the output is the -way softmax that represents the classes. it is trained on two parallel gtx gpu gb which communicate only in certain layers. this scheme reduces the top- error rates. alexnet is improved with zfnet architecture [ ] which visualizes the alexnet activities within the layers to debug problems and obtain better results. it allows observing the evolution googlenet. googlenet architecture codenamed inception-v is the improved utilization of computing resources inside the network [ ] . the network with the inception architecture is faster than the network with non-inception architecture. the googlenet architecture including the inception module uses rectified linear activation function, average pooling layer and not fully connected layer and dropout after removing fully connected layer. inception-v is improved to inception-v by ioffe and szegedy [ ] who tried to solve the internal covariate shift. they achieved a top- error rate of . %. this result is outperformed to . % by szegedy et al. [ ] with their new inception architecture called inception-v . table shows a comparison between the three inceptions. vggnet. karen simonyan and andrew zisserman [ ] investigated the effect of the neural convolutional network depth on its accuracy in image recognition. they pushing depth to - weight layers of the developed vggnet using very small ( × ) convolution filters. the configurations that use and weight layers, called vgg and vgg perform the best. the classification error decreases with the increased depth and saturated when the depth reached layers. authors confirm the importance of depth in visual representations. resnet/ inception-v . resnet [ ] used residual learning to ease the training of the deeper networks and reduce the errors from increasing depth. this architecture proposed many structures including: -layers, -layers, -layers, -layers and layers structure, where the -layers structure is better than the other ones. it is less complex and deeper than vgg, and has similar performances to the inception-v network, this is why szegedy et al. [ ] combined the inception architecture with residual connections. they evaluated the three resnet-inception and the inception-v architectures: the inception-resnet-v has similar performances to inception-v while the resnet-inception-v performs more than resnet-inception-v . the inception-v is simpler and has more inception modules than inception-v but has similar performances to resnet-inception-v . senet. senet [ ] used squeeze and excitation (se) block which improved the representational power of a network by enabling it to perform dynamic channel-wise feature recalibration. it was applied directly in the residual network architecture such as se-inception-resnet-v , se-resnet- , se-resnet- , se-resnet- and can be applied to the other existing architectures. it has been performed on imagenet, coco, cifar- and cifar- datasets across multiple tasks. transfer learning use the gained knowledge that solve one problem and applied them to solve different related problems by using trained model to learn different set of data. the setting for transfer learning used in this work is explained in the following statements. the pre-trained cnns architectures: alexnet, googlenet, vgg , vgg , resnet- , resnet- , resnet- , resnet-inception-v and senet consist of classes, . million training images, tested on k test images and evaluated on k validation images. they are challenging the accuracy of human with the best given results. the networks take an image as an input and produce the object label in the image as an output as well as the probabilities of the object categories. in this research, we focus on slice by slice classification of brain tumor using ce-mri dataset into three types of tumors. first, we modified the last three layers of pre-trained networks in order to adapt them to our classification task. next, we replaced the fully connected layer in the original pre-trained networks by another fully connected layers, in which the output size represents the three kind of tumor. the transfer learning setting and modification are shown in fig. . finally, we used transfer learned and fine-tuned deep pre-trained cnns for experiments using mri data. the proposed classification model is implemented in matlab b on a computer with the specifications of gb ram and intel i . ghz cpu. in this section, we describe the dataset used in the experiments, the training parameters and classification accuracy prediction. figure represents the pre-processing of training dataset and the use of transfer learning networks for brain tumor classification. dataset and pre-processing. the public database used to train and test the networks is available in [ ] . it has already used in previous works like in [ , ] . the dataset is collected from nanfang hospital, guangzhou and general hospital, tianjin medical university, in china during - . it contains abnormal brain ce-mri from patients with three kinds of brain tumor: meningioma ( slices), glioma ( slices), and pituitary tumor ( slices). it is based on two dimensional gray images ( d slices). those data are organized in matlab data format (. mat file). the size of images is × pixels and the pixel size is mm x mm. in our work, we normalize the gray mri images in the dataset in intensity values and we convert them into rgb images by corresponding color map to rgb format using matlab function. we specify the slices as an array of data type where the value corresponds to the first color in the color map. rgb images are returned as an m × n × numeric array with values in the range of [ , ]. the value corresponds to red, green and blue colors. then, we resize them according to the used network: ( × ) in alexnet and senet, ( × ) in googlenet, vggnet and resnet, ( × ) in resnet-inception-v rgb images. the dataset pre-processing is shown on fig. . we divide the data into training and test datasets, where % ( slices) of the images are used for training and % ( slices) used for test. the splitting of data into train and test set is performed on a slice basis. training parameters. for transfer learning, we train the networks by stochastic gradient descent (sgd) with . momentum. we use a minibatch size of images and a learning rate of − . to speed up the learning in the new layers, we rise the weight learn rate factor and the bias learn rate factor to . even though, the transferred layers are still slower than the new layers. in order to perform the transfer learning, we train for , and epochs where an epoch is a full pass during the dataset training. the networks are validated every iterations during training. in this part we use the trained networks to classify the test images and calculate the overall classification accuracy. the classification accuracy is the ability to predict correctly and guess the value of predicted attribute for new data. it is defined as the ratio of sum of true positives (tp) and true negatives (tn) to the total number of trials: where tp and tn are outcomes produced when the model correctly classifies the positive class and the negative class, respectively. while fp and fn are outcomes produced when the model incorrectly classifies the positive class and the negative class, respectively. we evaluate the classification performance using the nine pre-trained architectures and summarize our results in the form of tables. in fact, the purpose of this study is to increase the classification accuracy, speed the training time and avoid the overfitting. this can be assessed through the classification accuracy and the training time of our pre-trained networks. the classification accuracy and the training time using different transfer learning architectures trained for different epochs are respectively shown in table and table . all our pre-trained networks excepting senet are reached up to % classification accuracy for three different epochs. despite the use of transfer learning, senet has an overfitting with epoch equal to and , but achieves an acceptable result with epoch equal to . another characteristic observed during experiments is the impact of epoch number on the classification accuracy. this effect can be seen in table and table . the training time is increasing gradually with incremental epochs number, which means that we can consume less time using less epoch. however, the classification accuracy is neither influenced by the epochs number, nor the deep architectures. as shown in table the table shows a classification of three sample instances. we find that all of the prerained architectures pertain to the class glioma and meningioma. all of them, excepting resnet-inception-v pertain to the class pituitary. this confirms that the deeper architectures do not result good with small datasets. table provides a broad comparison based on classification accuracy with the existing methods on the same ce-mri dataset. abiwinanda et al. [ ] achieved . % accuracy with their proposed cnn. swati et al. [ ] propose a block-wise fine-tuning method based on transfer learning and achieved . % accuracy. deepak and ameer [ ] used a pre-trained googlenet to extract features from brain mri images and achieved . % classification accuracy. our proposed method using the pre-trained vgg achieved . % classification accuracy. this paper presents a fully automatic system for three kind of brain tumor classification using ce-mri dataset from figshare. the proposed system applied the concept of deep transfer learning using nine pre-trained architectures for brain mri images classification trained for three epochs. our system outperforms the classification accuracy compared to related works. it shows a good performance with a small number of training samples and small epochs number, which allows to reduce consuming time. the architectures which have fewer layers perform more than the deeper architectures. in the future work, we will apply our system to classify medical images from different modalities such as x-rays, positron emission tomography (pet) and computed tomography (ct) for other body organ. also, we will address the effect of epochs number to the classification performances. optimal symmetric multimodal templates and concatenated random forests for supervised brain tumor segmentation (simplified) with antsr classification of brain tumor type and grade using mri texture and shape in a machine learning scheme learning deep architectures for ai. found a survey on deep learning in medical image analysis autonomous concrete crack detection using deep fully convolutional neural network a coarse-to-fine deep convolutional neural network framework for frame duplication detection and localization in forged videos testing a deep convolutional neural network for automated hippocampus segmentation in a longitudinal sample of healthy participants image-based text classification using d convolutional neural networks automatic detection of cerebral microbleeds from mr images via d convolutional neural networks state-space model with deep learning for functional dynamics estimation in resting-state fmri deep convolutional neural networks for multi-modality isointense infant brain image segmentation gradient-based learning applied to document recognition imagenet large scale visual recognition challenge imagenet classification with deep convolutional neural networks brain mri tumor segmentation with d intracranial structure deformation features brainmrnet: brain tumor detection using magnetic resonance images with a novel convolutional neural network model active deep neural network features selection for segmentation and recognition of brain tumors using mri images deep convolutional neural networks for brain image analysis on magnetic resonance imaging: a review brain tumor classification using convolutional neural network brain tumor classification for mr images using transfer learning and fine-tuning brain tumor classification using deep cnn features via transfer learning going deeper with convolutions very deep convolutional networks for large-scale image recognition deep residual learning for image recognition inception-v , inception-resnet and the impact of residual connections on learning squeeze-and-excitation networks handwritten digit recognition with a back-propagation network | advances in neural information processing systems visualizing and understanding convolutional networks batch normalization: accelerating deep network training by reducing internal covariate shift rethinking the inception architecture for computer vision enhanced performance of brain tumor classification via tumor region augmentation and partition retrieval of brain tumors by adaptive spatial pooling and fisher vector representation key: cord- -lpeeugdf authors: ates, omer faruk; taydas, onur; dheir, hamad title: thorax magnetic resonance imaging findings in patients with coronavirus disease (covid- ) date: - - journal: acad radiol doi: . /j.acra. . . sha: doc_id: cord_uid: lpeeugdf rationale and objectives: the aim of this study was to compare the findings found in thorax computed tomography (ct), which is increasingly used in the diagnosis of the important public health problem of coronavirus disease (covid- ), and the findings of magnetic resonance imaging (mri) as an important diagnostic alternative. materials and methods: thirty-two patients diagnosed with covid- who underwent thorax ct for covid pneumonia and mri for any reason within hours after ct were included in the study. the number of lobes affected, number of lobes containing ground-glass opacities and consolidation, number of nodules, distribution of lesions (central, peripheral or diffuse), lobes with centrilobular nodular pattern, and the presence of pleural effusion were recorded separately for both imaging methods. results: seventeen of the patients were female ( %) and were male ( %). the mean age of the patients was . (range, - ) years. a total of patients ( %) had signs of pneumonia on ct. the most common finding in ct was ground-glass opacities in patients ( . %), followed by consolidation in patients ( . %). both consolidation and ground-glass opacities were also observed in mri in all of these patients. on ct, nodules were detected in patients ( . %) on ct and patients ( . %) on mri. the sensitivity and specificity of mri in nodule detection were calculated as . % and %, respectively. conclusion: although thorax ct is widely used in the imaging of covid- infection, due to its advantages, mri can also be used as an alternative diagnostic tool. in , a new corona virus disease caused by the severe acute respiratory syndrome coronavirus (sars-cov- ) was reported in the wuhan province of china ( ) . the disease spread first in china and then over all the world and was declared as a pandemic by the world health organization (who) ( ) . the sars-cov- virus has been shown to enter the cell through angiotensin converting enzyme (ace- ) receptors in humans. therefore, the virus first causes interstitial damage in the lungs followed by parenchymal damage ( ) . although the most important clinical symptoms are fever and cough, other indications, such as fatigue, headache and shortness of breath can also be seen. however, diagnostic tests are needed because these symptoms are not disease-specific, and the disease can progress rapidly to severe pneumonia ( ) . although the real-time reverse transcription polymerase chain reaction (rt-pcr) test for viral nucleic acids in the diagnosis of covid- is the gold standard, computed tomography (ct) has become increasingly more important in the diagnosis ( ) . however, considering that it contains ionizing radiation, ct should be used as a problem-solving method rather than for screening purposes in patients who are found negative for rt-pcr but present with clinical symptoms ( ) . also, the recent consensus statement from the fleischner society lists the risk of radiation exposure to the patient as one of the costs that diminish the value of imaging tests ( ) . due to concerns about the effects of ionizing radiation, magnetic resonance imaging (mri) is emerging ct as the primary cross-sectional imaging method in evaluating many organs. today, low dose ct scanning protocols are being developed, however, considering covid- pneumonia and similar pandemics that affect a large number of human populations, dose-dependent and dose-independent effects of ct that may occur due to radiation exposure, poses a serious risk in terms of malignancy that may develop after years ( ) . although the low proton content and movement artifacts of the lung parenchyma make it difficult to evaluate the lung with mri, with recent advances in mri scanner technology such as t -weighted spin-echo propeller mri sequence ( ) , it is now possible to overcome many of these challenges. in addition, the low proton content of the lung is, in fact, an advantage in imaging pneumonia because pulmonary consolidation and ground-glass opacities occurring in pneumonia cause an increase in proton and signal intensity, which becomes more pronounced with the background of the adjacent normal signal ( ) . in addition, cranial mri is very useful for the evaluation of anosmia which is frequently seen in these patients ( ) . the purpose of this study is to describe the thoracic mri findings of covid- pneumonia with those of ct and to suggest mri as an attractive alternative imaging modality is specific cases for this retrospective study, approval was obtained from the ethical committee of our institution. of the , patients diagnosed with covid- pneumonia (rt-pcr at least once + clinically confirmed) in our institution between march , and april , who underwent thorax ct for covid pneumonia and mri for any reason within hours after ct were included in the study. since one patient did not complete the mri examination; thus, his images could not be evaluated, but they were added to the image quality evaluation. a total of patients were included in the study, with being female ( %) and being male ( %). the mean age of the patients was . (range, - ) years. all patients had complaints of dry cough and shortness of breath. the patient population has a wide range from patients with mild disease to those in need of intensive care units. however, none of the patients were intubated. both ct and mri scans were for clinical purposes. t propeller images were generally obtained during mri scans for the following reasons: pulmonary mra obtained for suspicion of pulmonary thromboembolism in some patients with increased d-dimer without renal failure but with limited renal function and patients with suspected cardiac involvement and therefore imaged with cardiac mri. mri was performed with a . -t system (signa voyager; ge healthcare, milwaukee, wi, usa) using a phased array body coil. t -weighted fast spin echo propeller axial images were obtained with respiratory triggering (triggered by the expiration phase of the respiratory cycle) at an echo train length of , matrix of x , fov of cm, band width of hz, tr of - ms, effective echo time of ∼ ms, and four excitations. slice thickness was mm, and interslice gap was mm. the imaging time was approximately minutes, but it was extended to minutes in patients with breathing problems. ct images were obtained with a -row multidetector ct scanner ( mm slice thickness, matrix of x , kv automatically modulated ma; aquilion , toshiba medical systems, japan) for patients and with a -row multidetector ct scanner ( mm slice thickness, matrix of x , kv automatically modulated ma, alexion, toshiba medical systems, japan) for patients. all scans were performed during inspiration and with the patients placed in the supine position. the mri and ct images of all patients were evaluated for opacity and unilateral or bilateral involvement. the number of lobes affected (n = - ), number of lobes containing ground-glass and consolidation, number of nodules, distribution of lesions (central, peripheral or diffuse), lobes with centrilobular nodular pattern, and the presence of pleural effusion were also recorded separately for both imaging methods. on ct and mri, a density/intensity increase in which vascular boundaries could be distinguished was accepted as ground-glass, and a density/intensity increase in vascular structures that could not be differentiated was considered as consolidation. the affected lung volume ratio was evaluated observationally. by definition, a lung nodule is a rounded or irregular opacity, which may be well or poorly defined, measuring ≤ cm in diameter. the ct and mri images were assessed for quality: , excellent no artifacts; , good (few artifacts); , moderate (of diagnostic value but impaired by artifacts); , poor (of no diagnostic value); and , not tolerated (examination could not be completed). the causes of impaired quality were attributed to ghosting, motion or patient movement artifacts, or a combination thereof. the evaluation of the images was independently undertaken by two radiologists (both are board-certified and have years of experience) with the pre-diagnosis of covid- -related pneumonia. two weeks were waited for evaluation of mri images after evaluation of ct images to prevent memory bias. if their initial opinions differed, a consensus was reached. medcalc (ver. , ostend, belgium) was used for statistical analysis. the descriptive statistics were given as median (minimummaximum) and mean ± standard deviation. categorical variables were stated as frequencies and percentages. the chi-square test was used for the comparison of categorical variables. the independent samples t-test was used for the comparison of continuous variables with normal distribution and the mann-whitney u and kruskal wallis tests for the data that did not conform to normal distribution in the kolmogorov-smirnov test. coherence between two observers with respect to pulmonary findings was assessed by cohen's kappa coefficient. a value of p < . was accepted as statistically significant. a total of patients ( %) had signs of pneumonia on ct. pneumonia findings were observed in the mri of these patients. the most common involvement pattern was bilateral and peripheral (table ) (figure ). almost perfect agreement was found between the two observers in terms of pulmonary findings (κ = . ). the most common finding in ct was ground-glass opacities in patients ( . %). ground-glass opacities were also observed in the mri of all of these patients. lesions were observed in one or two lobes most frequently in both ct and mri ( . %) (figures and ) . while a total of lesions were detected on ct, were detected on mri, but there was no statistically significant difference (p = . ) ( table ). the second most frequently observed finding in ct was consolidation in patients ( . %), which was also observed in the same patients on mri. lesions were detected in one or two lobes most frequently in both ct and mri ( %) ( table ). nodules were detected in patients ( . %) by ct and patients ( . %) by mri. taking ct as reference, the sensitivity of mri in nodule detection was calculated as . %, specificity %, positive predictive value %, and negative predictive value . %. while nodules were observed in ct, were observed in mri, and no significant difference was found between the two modalities (p = . ) (figures and ). in addition, on both ct and mri, three patients ( . %) had a centrilobular nodular pattern ( figure ) and eight ( %) had pleural effusion. the median image quality score was for the ct images and for the mri images (table ). however, there was no significant difference between the two imaging methods (p = . ). the most important result of our study is the nearly complete overlap of ct and mri findings. minor differences between ct and mri may have been influenced by the fact that ct scanning is obtained during the inspiratory phase of respiration and thoracic mri with respiratory navigator during expiratory phase. in this context, mri was shown to be a useful modality in terms of showing both parenchymal and extraparenchymal (pleural effusion and lymphadenopathy) findings. in a recent study involving patients by yang et al., ultrashort echo time mri was evaluated and compared to ct. in this study, similar to our study, a perfect match was found between mri findings and ct findings. however, the most important difference of this study from our study is that no patient with a nodule was included in the study ( ) . there are also two case reports in the literature regarding the mri findings of covid- . the first belonged to a -year-old male patient and both parenchymal consolidation and pleural effusion was demonstrated using mri ( ). the other case report described a -year-old male patient, who was shown to have parenchymal ground-glass densities and consolidations successfully revealed by mri ( ) . various findings can be seen in the lung parenchyma in covid- infection ( ) . the most common of these is the ground-glass appearance, defined as an increase in fogshaped density in which the walls of the vessels and bronchi are not wiped ( , ) . it develops due to mild interstitial thickening or air loss within the airways ( ) . in a meta-analysis performed by salehi et al. involving patients, ground-glass density was determined in % of patients and reported as the most common imaging finding ( ) . in a study conducted in italy, all patients were found to have ground-glass density ( ) . similarly, in our study, all patients had ground-glass opacities. it is also known that ground-glass density is the earliest radiological finding of the disease ( ) . this appearance is considered to be due to edema and hyaline membranes in the lung ( ) . ground-glass opacities can be seen alone or together with different findings, such as interlobular septal thickening and consolidation ( ) . consolidation is defined as the air in the alveoli being completely replaced with pathological fluid, cells or tissues, resulting in an increase in density, and it is usually multifocal, segmental, patchy and subpleural or peribroncovascular in patients with covid- infection ( ) . in our study, there was consolidation in . % of patients. pathophysiologically, these cases are thought to be associated with fibromixoid exudate in the alveoli ( ) . in addition, the presence of consolidation has been associated with the prognosis of the ailment and may be an indicator of a progressive disease ( ) . crazy paving, which is defined as thickened interlobular and intralobular septa and the background with ground-glass density, is important because it is a sign of a progressive disease, although it is not as common as consolidation and ground-glass in covid- infection ( ) . apart from these major findings, a reticular pattern, air bronchogram, and nodules can also be seen ( ) . lymphadenopathy and pleural effusion are rarely observed in covid- infection and tends to suggest a bacterial infection in rt-pcr positive patients ( ) . the use of thorax mri has been increasing in recent years. since there is no radiation risk, mri allows multiple examinations to be performed on the same patient, and it can provide additional information to ct during patient follow-up. in a study by leutner et al., in which immunocompromised patients with pneumonia were included, all ground-glass opacities and consolidations could be diagnosed with mri. moreover, the presence of early-stage necrotic pneumonia, which could not be shown by contrastenhanced ct in % of patients, was demonstrated by mri ( ) . in subsequent studies with a similar patient group, mri was found to be very useful diagnostic tool, especially in its use during follow-up ( , ) ; furthermore, mri was reported to be promising in detecting nodules in these patients ( ) . in our study, the sensitivity of mri in nodule detection was . %, and its specificity was %. in a recent study by syrjala et al. including patients with immunocompetent pneumonia, the effectiveness of mri in diagnosis was investigated, and it was reported that mri was superior to direct radiography in diagnosis and showed almost identical accuracy with ct ( ). one of the disadvantages of mri in pneumonia patients is imaging time and artifacts. in addition to longer scan times, mr is less readily available and more expensive than ct. in our routine practice, we use the propeller technique, which has been shown to obtain better quality and less artifact images, while taking the thorax image ( ) . the t fse propeller sequence used in our study lasted an average of minutes. shortness of breath, which can be seen in patients with covid- -related pneumonia, can cause an increase in both ct and mri in motion-related artifacts. at the same time, since this sequence is obtained with a respiratory navigator, the scanning time is prolonged in patients with irregular breathing. although it is more sensitive to motion artifacts due to the long scanning time, respiratory navigation may be an advantage, especially in the imaging of some lesions adjacent to the diaphragm. in breath-hold ct, since inferior slices are taken toward the end of the patient's breath, more intense motion artifacts occur, especially in the inferior slices in patients with shortness of breath. in the technique we use, even the lesions adjacent to the diaphragm can be easily viewed in patients who regularly breathe quickly, as it is not necessary for them to hold their breath. although ct was better in terms of overall image quality in our study, there was no significant difference between the ct and mri examinations. in addition, no artifact formation at the level of no diagnosis was observed in the mri of any patient. in addition, no artifact formation at level (poor image quality, of no diagnostic value) was observed in any patient on mri. there were some limitations of our study. the first was the small number of patients included in the study, and second was the retrospective nature of the research. more comprehensive and prospective studies can be planned for this subject. finally, since the mri examinations were performed without contrast, the effect of the contrast agent could not be evaluated. in conclusion, although thorax ct is widely used in the imaging of covid- infection, we consider that mri can be used as an alternative due to its various advantages. especially, mri is important to assess lung pathology over time as more is learned about covid and the long-term impact on lung health. t -weighted spin-echo propeller sequence, variations of which are readily-available sequence on most mri scanners, is a good option for clinical translation to other platforms, sites. a novel coronavirus from patients with pneumonia in china severe outcomes among patients with coronavirus disease (covid- )-united states evolution of the novel coronavirus from the ongoing wuhan outbreak and modeling of its spike protein for risk of human transmission radiological approaches to covid- pneumonia clinical features of patients 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immunocompromised patients magnetic resonance imaging of pulmonary infection in immunocompromised children: comparison with multidetector computed tomography chest magnetic resonance imaging for pneumonia diagnosis in outpatients with lower respiratory tract infection key: cord- -ltatgq e authors: kesserwani, hassan title: cerebral microbleeds - to treat or not to treat, that is the question: a case report with a note on its radiologic deconstruction and therapeutic nuances date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: ltatgq e with the ubiquity of susceptibility weighted imaging (swi), cerebral microbleeds (cmbs) are fast becoming a prevalent phenomenon. they are tightly associated with age, neurodegeneration and diverse vascular etiologies. cmbs have a unique radiological signature. their morphology, number and topology are quite informative. they also pose a therapeutic conundrum, as they are associated with the risk of cerebral hemorrhage. we present the case of an -year-old woman who has a vascular dementia, binswanger's syndrome, and coronary artery disease, who presented with more than five cmbs. we present this case in order to highlight the dilemma of anti-platelet therapy in this group of patients and we demonstrate the cardinal radiologic features of cmbs. we then segue into the pathologic correlates of cmbs and associated risk factors. we finally analyze the risk of anti-platelet therapy in the presence of cmbs, and we unfold the latest data on cmb number and anti-platelet therapy. cerebral microbleeds (cmbs) are an increasingly recognized diagnostic entity. they represent microhemorrhages in brain parenchyma. pathologically, these microbleeds are hemosiderin-laden macrophages. deep seated microbleeds, in the corona radiata and basal ganglia, are more commonly seen in hypertension. cortical lesions are commonly seen with amyloid angiography. parasagittal linear streaks are more typical of brain trauma and diffuse axonal injury [ ] . in the rotterdam study of close to patients, cmb prevalence increases with age, from . % in people aged to years to . % in people older than years. . % of all patients had at least one cmb [ ] . systolic blood pressure, hypertension, smoking, lacunar infarcts and white matter lesions were associated with cmbs in a deep or infra-tentorial region, whereas apo-lipoprotein e (apo e ) and diastolic blood pressure were related to cmbs in a lobar location [ ] . there is an elevated risk of both hemorrhagic, odds ratio . ( . - ) , and ischemic strokes, odds ratio of . ( . - . ) , in patients with recent ischemic stroke or transient ischemic attacks (tia) and cmbs [ ] . radiologically, cmbs appear magnified on susceptibility weighted images (swi) due to their paramagnetic properties and this is known as a blooming artifact. cmbs appear dark, hypo-intense, on all swi images. however, this finding can be due to either iron or calcium deposits. in order to differentiate, phase mapping is obtained [ ] . these are rapid acquisition images at no extra cost. if the magnetic resonance imaging (mri) scanner software is endowed with a left-handed reference frame such as siemens, the cmbs appear hyperintense on the phase map. if the mri scanner software is endowed with a right-handed reference frame, the cmbs will appear hypo-intense on phase maps. to orient oneself, we can look at the superior sagittal sinus or a venous tributary, and establish the "color" of the mri acquisition sequence on the phase map. in the left-handed reference frame, the sinus will appear bright. in the right-handed system such as a general electric scanner, the cmbs appear dark by noting the dark sagittal sinus or a venous tributary. the reverse situation is seen in the left-handed siemens scanner; here the cmbs and sagittal sinus appear bright. swi images and phase mapping are advanced imaging techniques that are sensitive to cerebral microbleeds. they utilize long echo sequences and gradient echo sequences (gre). these image acquisitions rely on the magnetic susceptibility of tissues, whether paramagnetic or diamagnetic. paramagnetism occurs when atoms have an odd number of electrons. hence, they have a net magnetic dipole moment, which aligns and reinforces an applied magnetic field. if the number of electrons is even, that is paired, then there are no dipoles to align. however, the applied magnetic field distorts the motion of electrons via the lorentz force. the induced magnetic dipoles anti-align with the applied magnetic field, and reduce the applied magnetic field. such a material is diamagnetic. the filtered phase images or phase map exploit the magnetic properties of tissues; paramagnetic (such as iron) and diamagnetic (such as calcium), which have opposite signal intensities in phase mapping [ ] . we present the case of an -year-old woman with binswanger's disease characterized by a vascular dementia, lower half parkinsonism and more than five cmbs. binswanger's disease is a subcortical vascular dementia characterized by loss of executive function: planning, insight and foresight, with relative preservation of memory. it is frequently accompanied by a gait disorder. she has the typical risk factors of binswanger's disease including chronic hypertension, coronary artery disease, hyperlipidemia and is a lifelong smoker. the question at hand states: is anti-platelet therapy safe in this patient with more than five micro-hemorrhages (cmbs) in the brain? the data to answer this question is evolving [ ] . in this article, we lay out the pathologic correlates of cmbs, gently outline the radiological nuances involved in analyzing cmbs and finally we display the latest data addressing the role of anti-platelet therapy. as cmbs are incidentally discovered on routine mri studies, whether to continue or discontinue anti-platelet or anticoagulant therapy, is an open question. the clinician has to individualize therapy, weigh the benefits of therapy and consider the pros and cons, until more definitive data becomes available. we report the case of a previously active and independent -year-old divorced female patient who over the course of two years, especially last year, has become increasingly forgetful and confused. she left the stove on at least twice and once boiled eggs without water, forgets relevant family conversations and repeats questions frequently. she was no longer able to balance her checkbook and has become increasingly distracted, "spacey" and "not together", as per her daughter's testimony. her daughter also noted that she cannot keep up with conversations when there are more than two people conversing. sometimes she cannot finish a sentence, has become increasingly argumentative and quit driving five years ago due to anxiety from a car accident. her hygiene has declined, sometimes forgets to bathe or fix her hair, forgets to do laundry, but when remembers may wash clean clothes. in the past, she worked at convenience stores and focused on inventory. the patient now presents emotional lability with excessive crying, with abandonment of social activities, such as reading the newspaper and watching sitcoms. her medications include atorvastatin mg, lisinopril mg, escitalopram mg, baby aspirin mg and mirtazapine mg daily. her past medical history is significant for at least a -year-history of hypertension, coronary artery disease and hyperlipidemia. there is no family history of dementia. she has smoked cigarettes, at least one pack a day, for years. on examination, her blood pressure (bp) is / and a pulse of beats per minute. her height is five foot and three inches with a weight of pounds and a body mass index (bmi) of . . precordial examination revealed no murmurs and carotid auscultation revealed no bruits. her gait was stooped and shuffling, with adequate arm swing. no retropulsion was noted. at most, she had a mild symmetric bradykinesia but without a rest, postural or kinetic tremor. no sequence motion of the hands was noted with rapid finger apposition. cognitively she appeared distracted and a little paranoid despite a mini-mental state score (mmse) of / , which usually indicates a mild dementia when the score goes below . visuo-motor skills were impaired with pantomime mimic. she has ideomotor apraxia with tool use, using the hand as the tool object. deftness with a coin, limb-kinetic praxis, was preserved. despite the presence of a grasp reflex and a snout reflex, a palmo-mental reflex was absent. but gegenhalten (paratonia) was noted in the arms, with compensatory increasing resistance with increasing velocity of flexion at the elbow. her cranial nerve examination was significant for a lively gag reflex. power was preserved in the arms and legs, with symmetry. her deep tendon reflexes were lively in the arms and legs, with a negative plantar extensor response bilaterally. of note, stereognosis and graphesthesia were preserved in the hands. due to her dementia presentation and clinical findings of lower half parkinsonism, an mri scan of the brain was obtained revealing severe subcortical white matter disease ( figure ). susceptibility weighted images (swi) and phase map images reveal cerebral micro-bleeds (mcbs), more than five lesions; note hypo-intensity of bleeds on both sequences implying a right-handed reference frame ( figure ). cmbs and betraying the right-handed reference frame of the mri system (red arrows). these images look similar but are different acquisition sequences; note difference in peri-ventricular white matter intensity between both sequences (yellow arrow). mri: magnetic resonance imaging; cmb: cerebral micro-bleeds; swi: susceptibility weighted images. a carotid duplex scan and a transcranial doppler ultrasound did not reveal any significant cervical carotid or intra-cranial artery stenosis respectively. she has stable coronary artery disease and more than five cmbs on susceptibility mri of the brain. hence one faces a therapeutic dilemma; with such extensive cerebral white matter disease and stable coronary artery disease, is anti-platelet therapy warranted in the presence of more than five cmbs? our solution was to continue the statin, atorvastatin mg and aspirin mg daily for the following reasons. we considered substituting cilostazol, an anti-platelet phosphodiesterase inhibitor for aspirin, as we do know that when cilostazol is compared with aspirin, the risk of cerebral and gastrointestinal hemorrhage is lower, with a . % relative risk reduction of ischemic strokes, but only in patients with prior ischemic strokes [ ] . however, there is no data for the effectiveness of cilostazol in stable coronary artery disease. we decided to continue low dose aspirin therapy in order to protect her coronary arteries. we continued statin therapy, atorvastatin mg daily, as this too has anti-thrombotic effects on both the coronary and cerebral circulation. she was encouraged to quit smoking. for her cognitive impairment, the patient was started on an acetylcholine-esterase inhibitor, donepezil mg daily. the risk of an ischemic or hemorrhagic stroke in patients with less than five or more than five cmbs, treated with antiplatelets, will be outlined in the discussion section. as outlined earlier, cmbs are radiologically small round or ovoid regions of signal loss seen on paramagnetic mri sequences. cmbs are due to hemosiderin-laden macrophages. cmbs are a direct result of extravasation of erythrocytes from diseased arterioles and capillaries damaged by hypertension, such as the small perforating arteries of the deep gray and white matter, in the basal ganglia and the lobar regions. in caucasians with intracerebral hemorrhage, cmbs in a lobar distribution are associated with cerebral amyloid angiopathy (caa). caa leads to progressive deposition of β-amyloid in small cortical and leptomeningeal arterial walls, increasing their fragility [ , ] . lipohyalinosis, also known as fibrinoid necrosis, occurs in small vessels in hypertensives, affecting deep perforating arteries, which branch off from large arteries in the basal ganglia, white matter, brain stem and cerebellum. the fibrinoid deposition in the tunica media of the blood vessel wall is due to blood-brain barrier disruption leading to destruction of smooth muscles and the extracellular matrix. this leads to the formation of micro-aneurysms and micro-hemorrhages. hyaline arteriolosclerosis is characterized by thickening of the arteriolar wall by collagen deposits around the basement membrane, leading to fragility and cmbs [ , ] . the pathologic and radiologic findings of cmbs are summarized below ( table ) . size of lesion < millimeters; round or ovoid microbleed -extravasation of erythrocytes hyperintensity on gre/swi in patients with cerebral amyloid angiopathy (caa), the prevalence of cmbs is %. the distribution of cmbs in caa is lobar, mirroring the histopathology of amyloid angiopathy in cortical vessels. this lobar pattern is also seen in alzheimer's disease. involvement of the leptomeningeal vessels explains the occurrence of superficial siderosis that is observed in both caa and alzheimer's disease [ ] . cmbs also occur more frequently in patients with vascular dementia displaying a more central distribution pattern, and may involve the thalamus, brainstem and cerebellum [ ] . in diffuse axonal injury, cmbs are typically located in the corpus callosum and at the gray-white matter junction, and tend to have a more radial configuration following the perivascular spaces compared with the more spherical cmbs occurring with neurodegeneration or hypertension [ ] . radiation vascular injury begins above a dose of grays (gy). it can acutely involve the small vessels, through fibrinoid necrosis and telangiectasis with vessel permeability and vasogenic edema. chronically, the larger vessels are affected with vessel wall thickening, thrombosis and fibrinoid necrosis. cmbs occur in at least % of patients who have undergone radiation treatment, in pediatric and adult patients. the rate of cmb formation increases significantly two years after radiation treatment and is associated with cognitive impairment [ ] [ ] [ ] . cavernous angiomas have a popcorn-like high signal intensity on t -weighted images and a hypo-intense hemosiderin ring on t -weighted images. small type iv cavernous angiomas may be indistinguishable from cmbs. cavernous angiomas can be classified into four types: type i -extra-lesional blood beyond cavernous angioma; type ii -mixture of subacute and chronic blood; type iii -area of hemosiderin with a small central core; and type iv -area of hemosiderin deposition without a central core. because of a lack of a central core, type iv lesions are only visible on swi images as hypo-intense spots, identical with cmbs [ ] , type iv lesions being the most similar to cmbs. swi hypo-intensity and t hyper-intensity have been deployed to detect micro-metastases. these signal characteristics are five times more common in melanoma metastases than in lung cancer metastases. three quarters of melanoma metastases have one or the other signal characteristic and a quarter have both findings. this combination of findings was sixteen times more common with melanoma metastases than with lung cancer metastases. melanin leads to t shortening and the propensity of melanomas bleeding, with methemoglobin accumulation, can lead to t shortening. the susceptibility effects on swi are due to the presence of metal ions: iron, copper, manganese, and zinc. of note, % of melanomas had no t shortening and were only detected with swi [ ] . there are strong associations of cmbs with age and hypertension, more likely deep in the brain. carrying the apo-lipoprotein e (apo e ) gene increases the risk of lobar cmbs most frequently in the parietal lobes [ ] . cmbs are strongly correlated with volume of white matter disease [ ] . the presence and number of cmbs also correlates with the congestive heart failure/left ventricular systolic dysfunction, hypertension, age ≥ years, diabetes mellitus, stroke or tia or thromboembolism, vascular disease (chads -vasc) scores, which is used to estimate ischemic stroke risk in patients with atrial fibrillation. in a study of japanese patients with atrial fibrillation and controls without atrial fibrillation, patients with atrial fibrillation had a significantly higher prevalence of cmbs. there is also evidence that lobar cmbs may be more common than deep cmbs in patients with atrial fibrillation [ ] . the various causes of cmbs with their topography and mechanisms are listed below ( table ) . knudsen et al. [ in the study by lau et al., in patients who were prescribed anti-platelet therapy, the five-year risk of recurrent ischemic stroke and hemorrhagic stroke both increased with the number of cmbs [ ] . high cmb burden, greater than or equal to five, was an independent risk factor for recurrent ischemic stroke, hemorrhage stroke, all cause mortality, and nonvascular death. patients with greater than or equal to five cmbs experienced a three-fold higher risk of recurrent ischemic stroke and a -fold increased risk of hemorrhagic stroke than those without cmbs. for the patients with less than five cmbs, the five-year absolute risk of ischemic stroke was much higher than the incidence of intracranial hemorrhage. for those with greater than or equal to five cmbs, the risk of fatal and disabling ischemic and hemorrhagic strokes was similar in the first year, but this calculus changed from the second to fifth year, where the risk of a hemorrhagic stroke was much higher, almost times higher [ ] . in summary, cmbs are associated with a higher risk of ischemic strokes than hemorrhagic strokes during the first year, regardless of the number of cmbs and treatment with anti-platelets is recommended, if indicated. for more than or equal to five cmbs, this issue is still contentious, as a head to head study is not available. however, withdrawal of anti-platelet therapy may be considered depending on the risk profile. these findings are summarized below ( table ) . findings suggest that anti-platelet use is safe when cmb number is below five, but questionable when cmb number exceeds five from year two to year five [ ] . our case highlights the dilemma the clinician faces in patients who carry more than five cmbs on an mri of the brain and who have co-existent co-morbid diseases, such as coronary artery disease. as we highlight in the discussion section, anti-platelet therapy in patients who harbor more than five cmbs can be associated with as high as a -fold increased risk of an intracranial bleed, especially in those patients who are receiving anti-platelet therapy for more than one year. we tackle this therapeutic conundrum by considering an alternative therapy with cilostazol, a phosphodiesterase inhibitor, which is less likely to lead to an intracranial bleed. however, this approach was deemed insoluble, as there is no evidence for the effectiveness of cilostazol for coronary artery disease. the literature of cmbs is extensive. in this article, we streamline a lot of the data and address the key points. in particular, we unravel the radiological signature of cmbs, its pathophysiologic correlates, outline the risk factors and common diseases associated with cmbs and at the end of the discussion we address the risk of ischemic and hemorrhagic strokes in patients with cmbs who are receiving anti-platelet therapy. human subjects: consent was obtained by all participants in this study. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. cerebral microbleeds: histopathological correlation of neuroimaging prevalence and risk factors of cerebral microbleeds: an update of the rotterdam scan study cerebral microbleeds and recurrent stroke risk: systematic review and meta-analysis of prospective ischemic stroke and transient ischemic attack cohorts cerebral microbleeds: imaging and clinical significance cerebral microbleeds: a guide to detection and interpretation antiplatelet treatment after transient ischemic attack and ischemic stroke in patients with cerebral microbleeds in large cohorts and an updated systematic review benefit of cilostazol in patients with high risk of bleeding: subanalysis of cilostazol stroke prevention study fibrinoid necrosis of small brain arteries and arterioles and miliary aneurysms as causes of hypertensive hemorrhage: a critical reappraisal stroke patients with cerebral microbleeds on mri scans have arteriolosclerosis as well as systemic atherosclerosis clinical diagnosis of cerebral amyloid angiopathy: validation of the boston criteria use of antithrombotic drugs and the presence of cerebral microbleeds: the rotterdam scan study the difference in location between traumatic cerebral microbleeds and microangiopathic microbleeds associated with stroke -tesla susceptibility-weighted imaging to assess the effects of radiotherapy on normal-appearing brain in patients with glioma radiation-induced microbleeds after cranial irradiation: evaluation by phase-sensitive magnetic resonance imaging with . tesla presence of cerebral microbleeds is associated with worse executive function in pediatric brain tumor survivors the natural history of familial cavernous malformations: results of an ongoing study improved detection of metastatic melanoma by t *-weighted imaging white matter lesion progression in ladis: frequency, clinical effects, and sample size calculations cerebral microbleeds and asymptomatic cerebral infarctions in patients with atrial fibrillation covid- is associated with an unusual pattern of brain microbleeds in critically ill patients (preprint) key: cord- -xn s authors: jlassi, amal; elbedoui, khaoula; barhoumi, walid; maktouf, chokri title: unsupervised method based on superpixel segmentation for corpus callosum parcellation in mri scans date: - - journal: the impact of digital technologies on public health in developed and developing countries doi: . / - - - - _ sha: doc_id: cord_uid: xn s in this paper, we introduce an unsupervised method for the parcellation of the corpus callosum (cc) from mri images. since there are no visible landmarks within the structure that explicit its parcels, non-geometric cc parcellation is a challenging task especially that almost of proposed methods are geometric or data-based. in fact, in order to subdivide the cc from brain sagittal mri scans, we adopt the probabilistic neural network as a clustering technique. then, we use a cluster validity measure based on the maximum entropy (vmep) to obtain the optimal number of classes. after that, we obtain the isolated cc that we parcel automatically using slic (simple linear iterative clustering) as superpixel segmentation technique. the obtained results on two challenging public datasets prove the performance of the proposed method against geometric methods from the state of the art. indeed, as best as we know, it is the first work that investigates the validation of a cc parcellation method on ground-truth datasets using many objective metrics. thanks to advances in magnetic resonance imaging, neuroscientists and clinicians can study in depth the corpus callosum (cc) and mainly the correlation between the cc's dimensions and some neurological diseases. the cc, which is the largest white matter structure and the biggest fiber tract connecting corresponding regions of the cerebral cortex in the two cerebral hemispheres, integrates motor, sensory, and cognitive functions of the brain [ ] . anatomically, more than half of the axons composing the cc are surrounded by myelin, which gives this structure its remarkable appearance in midsagittal t -weighted mri images. however, in many sagittal brain mri slices, the fornix appears in the neighborhood of the cc with a similar intensity ( fig. ) [ ] . the cc is usually divided into smaller regions such as rostrum, genu, body, and splenium. this subdivision of the cc is called parcellation and it is proving to be very useful for an effective analysis of the cc [ , ] . in fact, the cc shape may be the cause of many neurodegenerative diseases such as epilepsy, alzheimer, autism, depression and other types of psychosis [ ] . the cc analysis is also important for studying aging, gender differences and laterality [ ] . hence, various studies have evaluated shape or volume variation of the cc parcels. they revealed a correlation between cc's abnormalities and many diseases. for instance, [ ] shows that the rate of change in cc or one of its sub-regions is more closely associated with the progression of alzheimer's disease. moreover, the cc parceling can be an appropriate group biomarker for an objective evaluation of treatments aimed at slowing the progression of alzheimer [ ] . furthermore, several works have identified volume alterations of the cc and its sub-regions in subjects with autism spectrum disorders (asd). in this context, a study of the cc volume of pre-schoolers, with different sex and age, suffering from asd was made by applying the "freesurfer" automated parcellation software. this study demonstrated that the total volume of the cc and its sub-regions is correlated with autism severity [ ] . another study conducted on participants with parkinson disease (pd) and healthy control (hc) confirms that cc sub-regions abnormalities might be the cause of parkinson disease. indeed, participants with pd showed an increase in the anterior callosal segments compared to hc [ ] . generally, the cc parcellation into callosal regions allows for a precise differentiation of motor connectivity and the structural integrity of these tracts in the cc [ ] . thus, the cc parcellation should be so helpful to better understand inter-hemispherical callosal connectivity in patients or healthy subjects [ ] . in particular, mri takes advantage of the macroscopic geometrical arrangement of white matter bundles that it makes capable of generating good cc visualization from the sagittal plane. in any way, the parcellation of the cc stills an important task for radiologic assessment despite there are no real or visible borders to allow this subdivision. nevertheless, the visual inspection of cc structures in mri scans suffers from both inter-and intra-specialist variability. on the one hand, the manual cc segmentation methods require strongly visual effort, specialized training skill, and are time-consuming processes. on the other hand, several geometrical methods for the cc parcellation have been proposed such as witelson and hofer methods [ ] . however, these methods cannot be satisfactorily validated due to the lack of qualitative parameters and reference standards. although all these difficulties, the development of an automatic cc parcellation method is an inescapable need to ensure a reliable diagnosis. such parcellation is so independent from the operator skills and may be extended to other brain structures parcellation. thus, since there are no visible landmarks indicating where the cc should be subdivided, the development of a fully automatic cc parcellation method is highly challenging, even for specialists. to deal with this issue, we propose to automatically parcel the cc within mri images. by validating it, for the first time, on large and public datasets, the proposed method records promising results. in fact, the contribution of this work is twofold: -as best as we know, we adopt for the first time the superpixel segmentation algorithm called simple linear iterative clustering (slic) for the cc parcellation [ ] . despite its simplicity, slic has been demonstrated to be effective in various computer vision applications [ ] . -the subdivision process of the proposed method is fully automatic and it is the second study that proposed a non-geometric analysis for the cc parcels, to the best of our knowledge [ ] . although it is based only on the mri data of each analyzed subject, with no parameter adjusting, the proposed method proved quantitatively its superiority over state-of-the-art methods. the rest of this paper is organized as follows. in sect. , we briefly review existing methods for the cc parcellation. section presents the proposed method based on slic. experimental results are discussed in sect. . the last section concludes the paper and points some directions for future work. few cc parcellation methods were proposed. however, most of these methods have not surmounted all the challenges encountered. in fact, the cc parcellation is a challenging task given that a normal shape of the cc might not clearly highlight all parcels, what can increase the diagnosis complexity. in addition, many internal abnormalities might include bumps which are hard to detect. existing cc parcellation methods can be divided into two main classes: geometric methods and non-geometric ones. on the one hand, since there are no real or visible boundaries allowing the cc parcellation, several geometrical methods were presented to perform this task. among these methods, two particular ones are widely adopted. the first was proposed by witelson and it is based on postmortem connectivity analysis in primates and humans [ ] . this method divides the cc into five regions ranging from anterior dimension to the posterior dimension. the cc subdivision is done into an anterior third, the middle of the anterior and posterior midbody, a posterior third and the posterior one-fifth. the rostrum, genu, and rostral body presenting the regions of the anterior third illustrate the prefrontal, premotor, and supplementary motor cortical areas. however, the posterior midbody is crossed by the somaesthesic and posterior parietal fiber bundles. the sub-regions of the posterior third, containing the isthmus and splenium, are allocated to temporal, parietal, and occipital cortical regions. thus, this parcellation method, and as any geometric methods, neither reflects the real texture nor the internal organization of the cc. in addition, the cc parcellation is strongly dependent on the brain conservation process, since it is based on post-mortem data. differently, hofer proposed the only work based on tractography of dti (diffusion tensor imaging) by subdividing the cc into five regions from an average behavior observed via tractography in a specific population of subjects [ ] . as already proposed by witelson, the geometric baseline in the midsagittal section of the cc is defining the anterior and posterior points of the structure. the first region, which represents the first sixth, contains fibers projected in the prefrontal region. the remainder of the anterior half cc illustrates the second region containing the fibers that form the motor and motor areas of the cerebral cortex. in fact, these fibers form together the largest cc region and are placed in the back section of the structure. the third region presents the posterior half minus the posterior third. it contains fibers responsible for the primary motor cortex. however, this part of the parcellation scheme is in conflict with witelson's method. the fourth region forms third minus the posterior quarter, presenting the primary sensory fibers. the last and the fifth region represents the cc posterior quarter crossed by the parietal, temporal and visual fibers. figure shows a comparison between the geometric schemes proposed by witelson and hofer. we notice that geometric methods allow only to divide the cc into the same regions among all subjects without considering the human and individual brain features between different subjects. on the second hand, differently to geometric parcellation methods, rittner proposed a data-driven method based on the watershed technique [ ] . this method is composed of four steps. the first step consists in the weighting of the fractional anisotropy. the second step performs the selection of the brain midsagittal plane, followed by the third and the last step which are the cc segmentation using the watershed technique, and its parcellation with fixed markers. nevertheless, this method suffers from sensitivity to parameters selection. in order to overcome its limitations, cover extended the rittner method with some important changes [ ] . practically, the author replaced all steps except the first step in order to lead to a more robust data-driven method. indeed, the parcellation is improved by applying the kmeans algorithm after defining the cc centerline. when comparing this method to that of rittner, and although both are based on watershed, it is confirmed that this method had a better generalization ability using no fixed markers to execute the watershed transform. however, due to the lack of quantitative metrics and reference standards, these methods cannot be correctly validated. differently to existing methods, we propose a subdivision scheme that considers only the mri data [ ] . using the slic superpixel segmentation technique, the method is composed of two main steps: cc segmentation and cc parcellation. this comes from that the slic presents one of the most popular images over segmentations that is commonly used as supporting regions for primitives to reduce computations in various computer vision tasks. we adopt herein our previous method [ ] for the automatic cc segmentation of mri sagittal section. it includes three main steps: image preprocessing using the anisotropic diffusion filtering (adf), classification based on the unsupervised probabilistic neural network (pnn) classifier, and cc isolation using a spatial filtering (fig. ) . in fact, the first step aims to enhance the signal-to-noise ratio by eliminating unwanted parts in the background and smoothing the internal part of the region while preserving its borders. in fact, adf allows to unblock high-frequency noise while preserving the main edges of structures [ ] . then, the classification step permits to define the target classes using k-means, before classifying them by the pnn [ ] . thereafter, the vmep index, which is based on the maximum entropy principle as an evaluation method that is called the cluster validity, is applied in order to determine the optimal number of clusters. the optimal number of classes is obtained when the vmep validity index reaches its maximum value. this number is adopted for the pnn classification process to obtain the final cluster map. once the cc class is identified, the cc region will be isolated by a spatial-based filtering. finally, we defined the cc contour by applying a follow-up algorithm on the border pixels of the cc region that are characterized by a maximum of the spatial gradient [ ] . we propose a cc parcellation method based on slic, which is non-geometric and fully automatic superpixel segmentation technique. it works with no parameter adjusting and with no instantaneous training, leading to a more robust technique. thus, in order to segment the cc into a set of superpixels, which refer to groups of pixels that represent perceptually significant small defined regions, we adopt the slic technique. it is an arrangement of k-means for superpixel generation in order to be faster than existing methods, more memory efficient while improving significantly the segmentation accuracy. it allows two important directions [ ] . firstly, it reduces greatly the number of distance calculations by restricting the search space to a region corresponding to the superpixel size. therefore, a reduction in the complexity of being linear is achieved in the pixels' number n and superpixels' number k that is independent and user-defined. in our case, n and k are equal to and , respectively. secondly, a combination of color and spatial proximity is reached by a weighted distance measure that allows both controls over the size and compactness of the superpixels. thus, each slice of the input mri image is partitioned into different size regions. in fact, the initial grid size is defined as s ( ). from the geometric center, the center superpixel of each region is computed. this geometrical center of each region is recursively updated in each iteration. in order to regroup the pixel, both spatial and intensity distances are used. the spatial distance between the pixels i and j is defined as follows ( ): where the coordinate values of pixel i and j are represented by p and q. the eq. calculates the intensity distance. where n j and n i represent the normalized intensity of pixel j and i, respectively. equation defines the combined distance measure c d of spatial and intensity. where e denotes the compactness coefficient. in fact, larger value of e illustrates more compact segments, whereas lower value of e represents flexible boundaries. the compactness coefficient is fixed in the range of [ , ]. the superpixel computation of the proposed method is shown in fig. . for the evaluation of the proposed parcellation method, we are the only study that used brain mri scans from two public datasets. on the one hand, we used the open access series of imaging studies (oasis) dataset, which is freely available on www.oasis-brains.org. it is created by washington university alzheimer's disease research centre. this mri dataset included a longitudinal collection of subjects aged between and years, men and women, including individuals with very mild to moderate alzheimer's disease (ad). all images were acquired on the same scanner using the same sequences. each subject was scanned on two or more visits, separated by at least one year for a total of imaging sessions. each mr image within this dataset is composed of slices with a resolution of × ( × mm). in this work, we selected sagittal images that are qualified by a quality control according to severe artifacts. on the other hand, autism brain imaging data exchange (abide) is also investigated. in order to accelerate understanding of the neural bases of autism, the abide dataset has supplied functional and structural brain imaging data collected from laboratories around the world. this dataset is composed of two large-scale collections called abide-i and abide-ii. each collection was collected independently across more than international brain imaging laboratories. thus, we generate a total of sagittal images with a resolution of × . it is worthy noting that we have a challenging heterogeneous set of images of normal subjects and individuals with autism and alzheimer. for each subject, the proposed parcellation method gives an apparent variation in the positioning of the cc parcels. this is because this method is purely automatic and does not follow any atlas or any prior knowledge (fig. ) . the geometric methods of hofer and witelson do not present the variation of their proportion of cc parcels and consequently, the same behavior can be observed on the results of all the subjects. figure shows that the proposed cc parcellation method is more similar to the hofer parcellation than the rittne one. this can be explained by the fact that hofer subdivisions are based on the connections of the cortical fibers to find the cc parcels. the largest differences between the proposed parcellation and that of witelson are observed in the parcels and . in fact, according to our collaborator clinician expert, the cc shape and parcellation are well defined and the delineated cc area shows closely the five anatomical subdivisions of the cc, especially the critical ones: the rostrum and the splenium. the fornix is correctly removed from the cc area and the obtained cc parcellation shows a precise subdivision of cc into five regions within brain mri scans, without penetrating the irrelevant neighboring structures. note that, within the selected sample of mri brain scans, the cc is extracted and parcelled both on female (column and ) and male (column and ) subjects. in fact, we applied the proposed method on subjects from the abide dataset (column and ) as well as from the oasis dataset (column and ). in order to evaluate the performance of the proposed method, we used the following commonly used metrics: dice, accuracy, sensitivity, specificity and precision. -the dice coefficient ( ) is a statistical measure that is used for comparing the similarity of two sample sets. -the accuracy ( ) is defined as the rate of correctly classified items. -the sensitivity ( ) is the proportion of positive items correctly classified. -the specificity ( ) is the rate of negative items rightly identified. -the precision ( ) is the ratio of correctly predicted positive samples to the total predicted positive samples. tp refers to the true positive (region correctly parcelled as the concerned parcel), tn refers to the true negative (region correctly classified as background), fp refers to the false positive (region which is parcelled as the concerned parcel) and fn refers to the false negative (region which is incorrectly classified as background). we notice that we produce five parcels, and for each parcel we measure the five metrics. it is worthy noting that for the first time, a very useful ground-truth for cc segmentation and parcellation within the challenging widely used oasis and abide datasets is used. therefore, we are the only work that is compared to a such ground-truth. however, the rittner method is evaluated only on the agreement between the results achieved by different cc parcellation methods. in fact, a professional neurologist from pasteur institute of tunis and a junior doctor have been charged with manually preparing the cc regions and parcels from all images belonging to the oasis and the abide datasets. besides, we applied post-processing in order to exclusively extract the cc area and parcels. table shows the recorded results comparatively to the ground-truth. it is clear that the proposed method (pm) records the higher dice coefficient score (> . ) in the parcels , , and , and a sufficient dice coefficient score (> . ) in parcels and comparatively to the ground-truth. evenly, it reaches a higher accuracy, specificity and sensitivity scores with values > . . the decline of the proposed method performance according to the precision metric can be explained by the cause of the ground-truth which is manually drawing and the processing applied to do the evaluation in each parcel. furthermore, for the two datasets and for each cc parcel, the dice coefficient was computed pairwise for the methods of the state of the art ( table ) as it is used in the rittner work. therefore, the previous analyzes allow only verifying the similarity between the resulting cc parcels, or which present statistical differences between methods of the literature since this is a problem without a gold standard (table ) . hence, it is now possible to know the correct cc parcellation by producing ground-truth for both witelson and hofer methods. since the hofer and witelson cc parcellation methods are based on geometric cc parcellation, their results did not vary among different subjects throughout the experimented dataset. this explains this overlap measurement obtained which would have maximum value if any of the methods was the same. the most pertinent difference between these cc parcellation methods was related to the automatic and non-geometric behavior defined by our proposed parcellation. table presents different results between methods while recording interesting similarities in some cases. the proposed cc parcellation method demonstrates to be nearby to the hofer method, mainly on parcels , and , while the witelson method presents significant statistical difference on the parcels and . cc is the biggest fiber tract within the human brain that allows the communication between the two cerebral hemispheres. the cc form and sub-regions might cause some diseases. the cc parcellation from mri images can predict future cases of diseases or progress neurological patterns in the development of different diseases. this paper presented a fully automatic non-geometric cc parcellation based on the slic superpixel algorithm, with no parameter adjusting and instantaneous training. since there is no gold standard used to evaluate the existing methods, we produced for the first time a ground-truth led to evaluate quantitatively cc parcellation methods. extensive experiments and quantitative comparisons with relevant cc parcellation methods, proved the accuracy of the proposed method on two challenging standard datasets. indeed, the proposed method achieves higher performance values for each parcel. as future work, we aim to propose a super voxel method based on the slic algorithm, from not only mri scans but also from functional magnetic resonance imaging. topography of the human corpus callosum revisitedcomprehensive fiber tractography using diffusion tensor magnetic resonance imaging anatomical mri study of corpus callosum in unipolar depression the relationship of hand preference to anatomy of the corpus callosum in men accurate automated detection of autism related corpus callosum abnormalities corpus callosum surface area across the human adult life span: effect of age and gender callosal circularity as an early marker for alzheimer's disease corpus callosum shape and size changes in early alzheimer's disease: a longitudinal mri study using the oasis brain database the effect of age, sex and clinical features on the volume of corpus callosum in pre-schoolers with autism spectrum disorder: a case-control study white matter abnormalities in the corpus callosum with cognitive impairment in parkinson disease parcellation of motor cortex-associated regions in the human corpus callosum on the basis of human connectome project data white-matter microstructural properties of the corpus callosum: test-retest and repositioning effects in two parcellation schemes data-driven corpus callosum parcellation method through diffusion tensor imaging computational methods for corpus callosum segmentation on mri: a systematic literature review slic superpixels compared to state-of-the-art superpixel methods automatic dti-based parcellation of the corpus callosum through the watershed transform hand and sex differences in the isthmus and genu of the human corpus callosum: a postmortem morphological study unsupervised method based on probabilistic neural network for the segmentation of corpus callosum in mri scans multimodal registration of pet/mr brain images based on adaptive mutual information boundaries detection based on polygonal approximation by genetic algorithms key: cord- - gicgsj authors: mahammedi, abdelkader; saba, luca; vagal, achala; leali, michela; rossi, andrea; gaskill, mary; sengupta, soma; zhang, bin; carriero, alessandro; bachir, suha; crivelli, paola; paschè, alessio; premi, enrico; padovani, alessandro; gasparotti, roberto title: imaging of neurologic disease in hospitalized patients with covid- : an italian multicenter retrospective observational study date: - - journal: radiology doi: . /radiol. sha: doc_id: cord_uid: gicgsj of consecutive hospitalized patients with coronavirus disease , ( %) had acute neurologic symptoms necessitating neurologic imaging. all images were obtained as per standard of care protocols. mri scans of brain and spine were obtained with . -t scanners with standardized protocols. gadopen-tetate dimeglumine ( . mmol/kg gadobutrol [gadovist; bayer, berlin, germany]) was used for contrast materialenhanced studies. the neurologic imaging characteristics that were evaluated are listed in table . all scans were initially analyzed by the institution's own neuroradiologists. subsequently, all images were reviewed by three neuroradiologists in consensus (r.g., l.s., and a.c., with , , and years of neuroradiology experience, respectively). continuous variables are presented as means standard deviations and were compared between patients with altered mental status by using the student t test; categoric variables are presented as frequencies with percentages. all statistical analyses were performed by using software (stata, version ; statacorp, college station, tex). p , . was indicative of a statistically significant difference. a total of consecutive hospitalized patients with covid- were reviewed. of these patients, ( %) met the eligibility criteria (fig ) . of the patients, ( %) were examined with unenhanced brain ct, ( %) with head and neck ct angiography, and ( %) with brain mri. of the patients who underwent brain mri, ( %) underwent mri with and without intravenous contrast material, ( %) underwent head and neck mr angiography, and three underwent additional mri of the whole spine for evaluation of lower extremity weakness. table summarizes the demographic characteristics, medical history, and neurologic characteristics. the most common neurologic symptoms were altered mental status in of the patients ( %) and ischemic stroke in imaging of neurologic disease in hospitalized patients with covid- : an italian multicenter retrospective observational study e had acute ischemic infarcts and two had intracranial hemorrhage. seventy-one of the patients ( %) had no acute findings on brain ct scans; seven of the patients who underwent mri ( %) had acute abnormalities on brain mri scans. there was a statistically significant association between the prevalence of altered mental status and patient age (mean age, years vs years ; p = . ). the main neurologic imaging hallmark was acute ischemic infarcts, which were present in of the patients ( %) ( [ %] on ct scans and four [ %] on mri scans). of these infarcts, ( %) were large ( in the middle cerebral artery territory, two in the posterior cerebral artery territory, two in the anterior cerebral artery territory), ( %) were small, three ( %) were cardioembolic, and one ( %) had an hypoxic-ischemic encephalopathy pattern. six of the patients ( %) had intracranial hemorrhages, with subarachnoid hemorrhage being the most common (n = , %). additional neurologic imaging findings are shown in table . ( ) note.-numbers are numbers of patients (numerator/ denominator), with percentages in parentheses. flair = fluid-attenuated inversion recovery, iv = intravenous, ms = multiple sclerosis, pres = posterior reversible encephalopathy syndrome. * one patient with miller-fisher syndrome, a regional variant of guillain-barré syndrome, had both cranial nerve and cauda equina enhancement. a -year-old man presented with bilateral facial nerve palsy, ophthalmoplegia, areflexia, and polyradiculopathy. results of real-time reverse-transcriptase polymerase chain reaction assay of the cerebrospinal fluid were negative for severe acute respiratory syndrome coronavirus . † a -year-old man without history of seizures presented with first time convulsion (fig ) . real-time reverse transcriptase polymerase chain reaction assay of the cerebrospinal fluid was negative for severe acute respiratory syndrome coronavirus . ‡ one patient, a -year-old woman, presented with seizures and altered mental status. ( %). of the patients, ( %) had no known past medical history and ( %) had at least one of the following chronic disorders: coronary artery disease (n = , %), cerebrovascular disease (n = , %), hypertension (n = , %), and diabetes (n = , %). of the patients without known past medical history (age range, - years) ( %), our study demonstrated that the neurologic imaging features of hospitalized patients with covid- were variable, without a specific pattern but dominated by acute ischemic infarcts and intracranial hemorrhages. we also showed that the neurologic mri spectrum may include posterior reversible encephalopathy syndrome, hypoxicischemic encephalopathy, exacerbation of demyelinating disease, and nonspecific cortical pattern of t fluid-attenuated inversion-recovery hyperintense signal with associated restriction diffusion that may be caused by systemic toxemia, viremia, and/or hypoxic effects ( ) . currently, we have a poor mechanistic understanding of the neurologic symptoms in patients with covid- , whether these are arising from critical illness or from direct central nervous system invasion of severe acute respiratory syndrome coronavirus ( ). accumulating evidence suggests that a subgroup of patients with severe covid- might have a cytokine storm syndrome that could be a trigger for ischemic strokes, probably related to the prothrombotic effect of the inflammatory response ( , ) . our results showed a lower prevalence of central nervous system symptoms than the wuhan experience ( ) ( % vs %, respectively); however, the prevalence of ischemic strokes was higher in our study ( % vs %). furthermore, our findings also support the suggested potential for co-vid- -associated guillain-barré syndrome and variants ( ) . none of our patients showed abnormal parenchymal or leptomeningeal enhancement. in conclusion, neurologists and neuroradiologists should be familiar with the broad spectrum of neurologic imaging patterns associated with covid- . coronavirus disease (covid- ) situation report - ct imaging features of novel coronavirus ( -ncov) acute cerebrovascular disease following co-vid- : a single center covid- -associated acute hemorrhagic necrotizing encephalopathy: ct and mri features neurological complications of coronavirus disease (covid- ): encephalopathy neurologic features in severe sars-cov- infection a first case of meningitis/encephalitis associated with sars-coronavirus- neurologic manifestations of hospitalized patients with coronavirus disease nervous system involvement after infection with cov-id- and other coronaviruses covid- : consider cytokine storm syndromes and immunosuppression guillain-barré syndrome associated with sars-cov- infection: causality or coincidence? we thank all patients and their families involved in the study.author contributions: guarantors of integrity of entire study, a.m., r.g.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; key: cord- -zrvykzof authors: zuhorn, frédéric; omaimen, hassan; ruprecht, bertram; stellbrink, christoph; rauch, michael; rogalewski, andreas; klingebiel, randolf; schäbitz, wolf-rüdiger title: parainfectious encephalitis in covid- : “the claustrum sign” date: - - journal: j neurol doi: . /s - - -y sha: doc_id: cord_uid: zrvykzof nan included positive serum antibody indices for sars-cov- . on day , respiratory deterioration required endotracheal intubation and treatment of bacterial superinfection was started according to antibiogram. eight days later, the patient could be extubated and pcr tests were negative for sars-cov- . yet, the patient continued to show concentration difficulties and delirious behavior. subsequent mri (fig. a c) revealed signal alterations within the claustrum/external capsule region, showing reduced diffusion. cerebrospinal fluid (csf) analysis disclosed a mild lymphocytic pleocytosis with negative test results for common neurotropic viruses. tests in serum and csf were also negative for various antineuronal antibodies. the patient recovered and was discharged with only mild cognitive impairment. follow-up has been carried out four months later showing a normalization in cell count of csf and improvement of mri findings, although the claustrum lesions persisted. clinically, his neurological and cognitive status was normal. our case is characterized by evidence of parainfectious autoimmune encephalitis in the context of severe covid- pneumonia. clinically, the patient presented with various neuropsychiatric symptoms, which were reported before in other covid- patients with encephalopathy [ ] . neither sars-cov- itself nor antibodies against the virus were found positive in the csf, precluding direct viral cns infection. comprehensive laboratory tests ruled out antineuronal antibodies as well as common infectious causes of encephalitis, altogether supporting the diagnosis of parainfectious autoimmune encephalitis. in addition, the diagnostic criteria for possible autoimmune encephalitis as proposed by gaus et al. were met [ ] . while immunological markers remained unspecific and imaging findings of acute necrotizing encephalitis were absent in our patient, brain mri disclosed a unique pattern, a.k.a. the claustrum sign. previously, this sign has been coined in mri studies of autoimmune epilepsy, where an immune-inflammatory-mediated encephalopathy is suspected [ ] . the claustrum is known to play a crucial role in regulating consciousness [ ] correlating well to the randolf klingebiel and wolf-rüdiger schäbitz both authors contributed equally to this work. clinical findings of impaired levels of consciousness in the presented case. in autoimmune epilepsy, the claustrum signals normalized in the majority but not in all patients [ ] , suggesting a varying severity of claustrum damage. this is confirmed by reduced diffusion in the first mri scan of our patient, heralding irreversible tissue damage (as proven by the -month mri follow-up). at no point in time, there was evidence for other causes of diffusion reduction, i.e., hypoxemia or status epilepticus. comparable claustrum lesions have also been reported in the context of autoimmune encephalitis without epileptic or anoxic episodes, supporting inflammation as a decisive factor [ ] . a particular vulnerability of claustral neurons to hypoxic stress has been shown [ ] , without relating to the inflammatory pathogenesis of our mri findings. yet, astrocyte proliferations and microglia/macrophage infiltrations of the claustrum have been observed in non-herpetic encephalitis [ ] . to which extent other pathomechanisms, such as encephalitic hypermetabolism as known from the striatum [ ] . additionally, compromise the claustrum remains speculative. common mri findings in a recent study of covid- encephalopathy were cortical signal abnormalities on flair images ( %), accompanied by diffusion reduction, leptomeningeal enhancement and cortical blooming artifacts in some cases. these imaging findings, termed by the authors themselves as "rather unspecific", did not allow [ ] . mri findings in covid- encephalitis, especially when suggesting autoimmune encephalopathy may imply therapeutic interventions, such as immunosuppressive therapy. recently, progressive clinical improvement along with a reduction of inflammatory csf parameters has been observed in covid- encephalitis, following high-dose steroid treatment [ ] . in summary, a previously undescribed imaging pattern in parainfectious covid- encephalitis is presented that bears a strong resemblance to mri findings in autoimmune encephalitic syndromes, such as known from epileptic or encephalitis caused by antineuronal antibodies. this claustrum sign should be added to the still limited knowledge of encephalitic imaging patterns in covid- , as it most probably represents an autoimmune phenomenon that might progress from reversible signal changes to permanent tissue damage and thus may trigger appropriate as well as timely therapy. author contributions fz is lead author, analyzed and interpreted the collected data and literature, designed and wrote the manuscript. ho&ar participated in the design and coordination of the manuscript. br&cs helped in drafting the manuscript. mr&rk provided figures and data and revised the manuscript for important intellectual content. imaging (d-e), the flair-hyperintensities persist (d) whereas tissue diffusion has normalized (e). csf-cytology (f) showed a slightly elevated cell count ( /µl) with a lymphocytic predominance ( % lymphocytes, % monocytes). a meaningful plasmacytic transformation was not observed, the monocytes being only slightly activated neurologic features in severe sars-cov- infection a clinical approach to diagnosis of autoimmune encephalitis new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome what is the function of the claustrum? voltage-gated potassium channel antibody-associated encephalitis with claustrum lesions claustral neurons are vulnerable to ischemic insults in cardiac arrest encephalopathy neuropathological studies of patients with possible non-herpetic acute limbic encephalitis and so-called acute juvenile female non-herpetic encephalitis striatal hypermetabolism in limbic encephalitis brain mri findings in patients in the intensive care unit with covid- infection steroidresponsive encephalitis in covid- disease key: cord- -l omunq authors: schönegger, carmen maria; gietl, sarah; heinzle, bernhard; freudenschuss, kurt; walder, gernot title: smell and taste disorders in covid- patients: objective testing and magnetic resonance imaging in five cases date: - - journal: sn compr clin med doi: . /s - - - sha: doc_id: cord_uid: l omunq smell and taste disorders are acknowledged as characteristic symptoms for sars-cov- infection by now. these symptoms have been linked to a neuroinvasive course of disease. in this study, we investigated five consecutive covid- patients with a prolonged course of dysosmia and dysgeusia. those with objectifiable alteration in taste or smell were subjected to mri with contrast agent to investigate possible involvement of the central nervous system. we found dysosmia and dysgeusia to be mostly objectifiable, but no evidence for neuroinvasiveness could be detected by mri in the late stage of the disease. alterations in taste and smell could be objectified in most patients. nevertheless, no evidence for a neuroinvasive potential could be identified by mri, at least in the late stage of disease. we encourage medical professionals to conduct specialized examinations and mris in the acute stage of disease, which guarantees an optimum patient care. although a lot of effort has been made in order to investigate this novel coronavirus, our knowledge about many pathogenic aspects of covid- is still limited. clinical and experimental studies proved that several coronaviruses have neuroinvasive capacities, since they show the ability to spread from the respiratory tract to the central nervous system [ ] . hypothesis of neurotropism of sars-cov- is based on covid- patients with neurological manifestations. furthermore, neurological complications up to actual damage hint neurovirulence [ ] . actual case reports substantiate this assumption. covid- can cause meningitis with a fatal outcome, which was evidenced by the case of a -year-old man in japan, who succumbed to the disease [ ] . brain mri demonstrated hemorrhagic lesions that were consistent with acute necrotizing hemorrhagic encephalopathy [ ] . another manifestation of nervous system involvement is the appearance of alterations of taste and smell [ ] . anosmia and dysgeusia are by now acknowledged as significant symptoms in association with covid- by the american academy of otolaryngology-head and neck surgery (aao-hns) and other researches [ , ] . case series show a high frequency of chemosensitive disorders in patients, ranging between . and % [ , ] . according to vaira et al., the presence of olfactory and gustatory dysfunction may predict a milder course of disease. on the other hand, the neglect of such symptoms suggests a more severe course of disease [ ] . some patients reported isolated olfactory or taste disorders, but more complained about a combined dysfunction. even though a complete recovery could be noted in regard to most patients, evidence has been found about persisting alterations in chemosensory function for a prolonged period [ ] . at the shahid beheshti university of medical sciences in tehran/iran, possible olfactory bulb alterations were investigated by olfactory bulb magnetic resonance imaging. in spite of isolated sudden onset anosmia and positive sars-cov- polymerase chain reaction during the acute phase of the carmen maria schönegger and sarah gietl contributed equally to this work. this article is part of the topical collection on covid- disease, the mri demonstrated normal volume and signal intensity of olfactory bulb with no sign of nasal congestion [ ] . the study was conducted on five patients reporting impairment of taste and smell with confirmed sars-cov- infection in east tyrol. written informed consent was obtained from all participants. age ranged between and years, and all the participants were female. clinical data and history of symptoms were assessed anamnestically. olfactory and gustatory testing was conducted between and days after disease onset, which was defined as the commencement of symptoms. in case objective testing revealed alterations in taste or smell, patients were subjected to mri in a timely manner. a follow-up examination was conducted in three of the patients whose mri raised suspicion of alterations in the first run. olfactory and gustatory function assessment was carried out by means of burghart screening test with taste strips in accordance with the manufacturer's instructions [ , ] . in order to evaluate olfactory function, an identification test, called sniffin' sticks, was performed [ ] . twelve common odorants were consecutively presented to the patient close to both nostrils. out of four options the participant was requested to identify the presented smell. results were interpreted according to a scoring system considering patients age. a score above ten was determined as normal, between six and ten a hyposmia was diagnosed and a score below six was reported as anosmia. gustatory testing was performed by taste strips covering the four basic gustatory qualities sweet, salty, sour, and bitter [ ] . taste strips were applied on patient's tongue. for each stripe, the test person had to choose the corresponding odor from four answers. according to the count of correct answers, four categories of classification were established: normal (score ), mild hypogeusia (score ), moderate hypogeusia (score ), severe hypogeusia (score ), and ageusia (score ). a standard brain mri protocol was used involving axial t tse, axial flair, axial dwi (b and b ), dadc, axial t w ffe, and isotropic t w d ir tfe with a -mm slice thickness without contrast media and cet w d mprage, on a . t prodiva philips mri machine. the d t sequences with and without contrast were reconstructed in coronal, axial, and sagittal projection for the radiologic evaluation. a short-term follow-up examination days later was performed with the same axial flair and dwi/dadc. sequences were used as well as isotropic d t and d flair sequences (appendix). olfactory and gustatory testing was conducted between and days after onset of disease, which was defined as the commencement of symptoms. out of the five patients three showed a manifest anosmia, one result was rated as a hyposmia and one as normosmia. gustatory testing revealed two normal scores ( / ), one moderate hypogeusia ( / ), one severe hypogeusia ( / ), and one ageusia ( / ). detailed results are summarized in table . three weeks after the first olfactory and gustatory examination, a follow-up testing was conducted with the three patients who also had a second mri. this investigation revealed one persistent anosmia ( / ), one persistent hyposmia ( / ), and one patient's condition improved from anosmia to hyposmia ( / ). gustatory testing showed an enhancement in two patients ( / ; / ); one patient had the same score ( / ). detailed results are summarized in table . none of the patients showed any changes in the paranasal sinuses, not even small fluid collections or mucosal swelling. the cribriform plate was normal in all cases, and the olfactory nerve was normal in size and signal, without any side differences and there was no neuronal or perineural enhancement. the meninges showed no enhancement or thickening. the gyrus rectus was normal in size and signal intensity in all patients and showed no swelling. no signal changes in the medial temporal lobes or the thalami could be found and no hemorrhagic microbleeding in t * sequences were observed. even though ischemic events and leptomeningeal enhancement have already been reported, there were no signs for an acute or chronic ischemic event [ ] . in the first examination, one patient showed a symmetric, slightly hyperintense signal in the head of the caudate nucleus, parahippocampal gyrus, and the uncus, predominantly on the left side. in t , the area appeared thicker and swollen with a higher si, but all the other sequences including dwi were normal. also, si measurements were slightly elevated with values of compared to on average in primarily healthy individuals. in the follow-up examination, there was a slight drop to , but the additional high-resolution d flair and t images showed no anomalies, so probably this finding lies within the normal range. all the other patients had a normal brain mri (images , , and ). in contrast to galougahi et al., we evaluated symptom status in the late stage of covid- [ ] . the smell and taste disorders could mostly be objectified, although not in regard to all patients, which underlines the necessity of objective testing. compared to dell'era et al., who reported a median recovery time of days, our findings show that olfactory impairment is a long-lasting sequela of covid- [ ] . even after to days, patients still suffered from objectifiable smell and taste disorders. in order to rule out permanent damage, further surveillance is necessary. however, it should be notified that a loss of smell and taste is not pathognomonic for covid- , as it appears as well in the course of other respiratory infections. nevertheless, controlled studies indicate that anosmia is more common in covid- patients than in patients suffering from other viral infections or controls [ ] . in contrast to other infectious smell impairments, a loss of smell and taste in covid- seems to be rarely accompanied by a severely blocked nose [ ] . the first mri images showed slight alterations in one patient, which could be associated with a sars-cov- infection. however, the follow-up examination contradicted this assumption. image mri cor t the mri investigation in our patients taught us two things: first, at least in chronic stages of the illness, we did not gain any evidence of prolonged neuroinvasive association. up to now, mri investigations have focused on the acute stage of illness and are very rare. in our case, the organization was hindered by the concern that such investigations might be an incalculable risk for the staff involved. according to politi et al., conducting an mri examination in a patient suffering from persistent severe anosmia and dysgeusia, cortical hyperintensity in the right gyrus rectus could be detected days after symptom onset. consistent with our results, a complete resolution of the previously seen signal alterations could be observed in a follow-up imaging days after symptom onset [ ] . contrary to assumptions of other researchers, no evidence of a general neuroinvasiveness could be given, at least in the chronic stage of disease [ ] . more extensive studies in the acute stage of illness followed by long-term follow-ups are desirable. contrary to other evaluations, our study population is rather small which is a limiting factor to the informative value. as hygiene measures proved to be sufficient avoiding contagion, we encourage medical professionals to conduct specialized examinations and mris in the acute stage of disease, which guarantees an optimum patient care. authorship contribution sg and cms wrote the manuscript and were responsible for the organization. bh was responsible for magnetic resonance imaging, kf for the objective olfactory and gustatory testing. gw supervised and reviewed the manuscript. conflict of interest the authors declare that they have no conflict of interest. consent for publication written informed consent was obtained from all participants. ethics approval ethical approval was not necessary as the evaluation was performed in the course of patient care and clinical monitoring. human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? viruses neurological complications of coronavirus and covid- a first case of meningitis/ encephalitis associated with sars-coronavirus- covid- -associated acute hemorrhagic necrotizing encephalopathy: ct and mri features evidence of the covid- virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms covid- anosmia reporting tool, american academy of otolaryngology-head and neck surgery self-reported loss of smell and taste in sars-cov- patients: primary care data to guide future early detection strategies isolated sudden onset anosmia in covid- infection. a novel syndrome? olfactory and gustatory dysfunctions as a clinical presentation of mild-tomoderate forms of the coronavirus disease (covid- ): a multicenter european study olfactory and gustatory function impairment in covid- patients: italian objective multicenter-study objective evaluation of anosmia and ageusia in covid- patients: single-center experience on cases olfactory bulb magnetic resonance imaging in sarscov- -induced anosmia: the first report normative data for the "sniffin' sticks" including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than , subjects taste strips" -a rapid, lateralized, gustatory bedside identification test based on impregnated filter papers neurologic features in severe sars-cov- infection smell and taste disorders during covid- outbreak: cross-sectional study on patients the role of self-reported smell and taste disorders in suspected covid- predictive value of sudden olfactory loss in the diagnosis of covid- magnetic resonance imaging alteration of the brain in a patient with coronavirus disease (covid- ) and anosmia sars-cov- : olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -znnlyz y authors: lim, peter a.c. title: transverse myelitis date: - - journal: essentials of physical medicine and rehabilitation doi: . /b - - - - . - sha: doc_id: cord_uid: znnlyz y transverse myelitis (tm) is an inflammatory condition across the spinal cord, along one or more levels and in the absence of compression. idiopathic acute tm is rare and with improvements in diagnostic tools and longer follow-up, the etiology which may include post-infectious, multiple sclerosis, or neuromyelitis optica often becomes clearer. the patient may present acutely with weakness, sensory impairments, or bowel and bladder changes. a careful history, physical examination, and appropriate diagnostic studies including blood tests and an mri scan may help determine the diagnosis and etiology. following the acute management, which may include use of steroids, immunosuppressive drugs, and plasma exchange, a comprehensive medical rehabilitation program is important to optimize recovery from the resultant impairments and disabilities and manage associated complications. complications such as paralysis, autonomic dysfunction, neuropathic and musculoskeletal pain, spasticity, contractures, neurogenic bladder and bowels, skin breakdown, and psychological issues will benefit from the expertise of the physiatrist. rehabilitation will include functional restoration with therapy as well as compensation of residual impairment with mobility and various other assistive devices. to maximum weakness in idiopathic tm has been reported to range from hours to days, with a mean of days. subacute presentations, progressing over days to weeks and ascending, are associated with a good to fair prognosis. acute and catastrophic presentations with back pain have a poorer outcome. recovery is often related to the clinical presentation and may or may not be complete. in general, one third of patients with acute tm make a good recovery, another third have fair recovery, and the rest either fail to improve or die. , , in idiopathic tm treated with methylprednisolone using the medical research council (mrc) scale for muscle strength, . % were reported to have complete recovery or minimal residual deficit (mrc - ), % had partial recovery (mrc ), and . % had severe disability or absent recovery (mrc - ). factors associated with poor outcomes include severe initial symptoms with spinal shock, delayed presentation to the hospital after maximum deficits have already occurred, development of syringomyelia, and extensive mri lesions. , if no recovery has occurred by to months, complete recovery is less likely. , patients with tm may present in the ambulatory clinic, urgent care center, or hospital setting with complaints of weakness of the limbs, sensory impairments, pain, and difficulties with the bowel and bladder. weakness may affect only the lower limbs or all four limbs with varying severity. it may be complete, incomplete, or may present as one of the spinal cord syndromes. the clinical spinal level usually corresponds to the lesion, but lower limb findings do not preclude a lesion at the cervical level. sensory complaints may include hypersensitivity, numbness, tingling, coldness, burning, or as a circumferential constriction. pain is a common symptom in one third to one half of patients and may be central or localized, aching or radicular in character. bowel frequency or constipation may occur, and bladder symptoms include increased frequency, retention, and incontinence. , , the history, including past medical, family, and detailed social, may reveal symptoms of recent infection, immunocompromised or autoimmune condition, space-occupying lesion, demyelinating disease, travel, vaccination, trauma, sexual exposure, animal, insect or tick bites. whether vaccination triggers tm has been debated. there were only seven cases of tm and eight of acute disseminated encephalomyelitis (adem) in the primary vaccination exposure window of to days prior to onset, after million doses within a healthcare network. the incidences were both nonstatistically significant except adem with tdap (tetanus, diphtheria, and pertussis) vaccine at p = . (translating into . cases per million doses). a careful review may yield systemic symptoms, including the upper respiratory tract with cough and difficulty in breathing, chest pain, rashes, joint aches, muscle pain, vision changes, nausea, diarrhea, constipation, and problems with urinary function. particular attention should be paid to details pointing toward potentially treatable or reversible conditions responsive to antimicrobials or surgical decompression. there may be a history of invasive spinal intervention for pain management, and tm relating to the infected catheter tip of an intrathecal morphine pump for chronic pain has been reported. the physical examination should be broadly systemic as well as focused on neurological findings such as motor weakness, changes in sensation (pinprick, light touch, vibration, position sense, or temperature), tone, muscle stretch reflexes, coordination, and bowel and bladder functioning. changes affecting the brain, such as cognitive dysfunction and cranial nerve and visual abnormalities, are generally not seen with idiopathic tm. fever, tachycardia, and tachypnea may indicate an infectious etiology. infections, autoimmune, and other conditions that cause acute inflammation of the spinal cord may also manifest in the other body systems. respiratory, cardiovascular, gastrointestinal, and genitourinary tracts as well as the musculoskeletal and integumentary systems should be assessed accordingly. the findings will assist in determining the level of spinal involvement, guide diagnostic testing, and help rule out other diagnoses. the physiatrist is likely to encounter the patient as a consultation for rehabilitation assessment and management, or referral for a specific problem, such as spasticity or pain intervention. the functional limitations in a patient with tm usually depend on the level of spinal cord involvement and corresponding muscles affected. debilitation and deconditioning from associated illnesses and prolonged recumbency will also affect function secondarily. the functional capability review according to spinal level may be influenced by whether the cord injury is unilateral or bilateral and the degree of completeness. high cervical lesions result in tetraplegia with sensory impairment and also affect the phrenic nerve (c -c ) with diaphragmatic paralysis requiring mechanical ventilation. a patient with c innervation preserved may or may not have respiratory difficulties but will be dependent for most self-care activities. using appropriate technology and devices, whether customized or commercially available, the patient may be able to control the home environment, summon assistance, direct their care, and mobilize in an electric wheelchair with a chin control or a sip-and-puff interface. a patient with c level may be able to self-feed and perform personal grooming with equipment such as a universal cuff for the hand allowing attachment of tools (e.g., fork, spoon, or comb). the patient can independently use a powered wheelchair and propel a lightweight manual wheelchair with hand rim projections ("quad knobs") for limited distances over level ground. c innervation allows independence with upper extremity dressing, bathing with equipment, and functional propulsion of a manual wheelchair indoors. the patient with superior balance and motor control could theoretically perform independent or supervised transfers with a sliding board, and self-catheterize with appropriate assistive devices. driving a specially adapted automatic transmission vehicle with powered steering, hand-controlled accelerator and brake can be achieved with c -c preservation. a c level allows independence in all self-care activities with equipment, independent transfers with ability to push off using intact elbow extensor muscles, and the patient may be able to live alone. a patient with c and t innervation will have improved manual strength and dexterity for self-care, is independent with a manual wheelchair, and should be able to self-catheterize. preservation of upper thoracic innervation allows a greater degree of trunk control, increasing stability during use and propulsion of a manual wheelchair. it also adds to ease and independence with bladder and bowel self-management. with bracing of the hips, knees, and ankles (kafo or knee-ankle-foot orthoses), minimal ambulation can be attempted, although mainly for training and exercise purposes than truly functional. independent ambulation, even with bracing and bilateral axillary or forearm crutches, is usually not realistic unless the patient has preservation of some upper lumbar innervation. further preservation of lumbar and sacral innervation will increase ease of ambulation with better trunk and pelvic control. the patient with incomplete spinal injury is less predictable, and functional abilities will largely depend on the degree and nature of neurologic preservation. with increasingly greater resolutions and techniques such as t -weighted fast spin-echo and short-tau inversion recovery (stir) to enhance or suppress the appearance of fat and tissues of different densities, the best tool when tm is suspected is mri. mri not only allows visualization of the lesion but also rules out treatable causes, such as tumor, abscess, and other lesions causing compressive myelopathy. contrast material can be given to highlight lesions, and myelography may rarely be considered if mri is not available. mri scans show features that help differentiate tm from disorders such as multiple sclerosis (figs. . and . ). the lesion in tm tends to affect the central region of the cord and involve more than two thirds of the cord diameter, whereas in multiple sclerosis it is usually more peripheral and involves less than half of the cord diameter. tm is more often associated with high signal intensity on t -weighted images extending longitudinally over more segments. , the number of segments involved may be from or up to , and the entire cord or sometimes only the medulla may be affected. , , , the lesion in tm at times resembles a spinal cord tumor and biopsy may even be attempted during investigation. , , mri of the brain with contrast enhancement is often performed to help determine whether the mri findings point toward multiple sclerosis rather than "idiopathic" tm. in idiopathic partial tm, a study that does not show brain lesions translates to the likelihood of evolving multiple sclerosis at % to %. when brain lesions such as white matter plaques (especially periventricular) are seen, the chance for development of multiple sclerosis increases to % to %. asymmetric motor or sensory symptoms and absence of peripheral nervous system involvement at presentation suggest acute myelopathic multiple sclerosis, whereas symmetric symptoms and peripheral nervous system involvement suggest acute tm. , immunoglobulin g antibodies may be useful for determining neuromyelitis optica (devic's disease) as the etiology in patients with acute complete tm. longitudinally extensive tm spanning three or more vertebral segments is an important feature and detection of anti-aquaporin -specific antibodies (anti-aqp , aq p-ab, or nmo-igg) is useful to determine both increased risk for recurrence and conversion to neuromyelitis optica. , other tests include the usual blood counts and chemistry, tests for autoimmune conditions, such as antinuclear antibodies, anti-double-stranded dna antibodies, anti-sm antibodies, erythrocyte sedimentation rate, ss-a antibody for sjögren disease, immunoglobulin levels, and vdrl. vitamin b enteric cytopathic human orphan virus may be elevated. the polymerase chain reaction (pcr) technique is useful for amplifying minute quantities of dna or rna. it was used in a recent case report on acute myelitis caused by zika virus infection, which responded well to high-dose prednisolone. a lumbar puncture allows assessment of cerebrospinal fluid pressure, and samples for cell count, determination of protein and glucose concentrations, measurement of immunoglobulins, and protein electrophoresis. oligoclonal bands detected in cerebrospinal fluid are useful in making a diagnosis. in one report, they were present in three of five patients with multiple sclerosis-associated tm, but in none of four patients with parainfectious tm. nerve conduction studies (ncs), electromyography (emg), as well as somatosensory and motor evoked potentials may be useful for establishing diagnosis and monitoring progress. , urinary system evaluation including cystourethrography, cystoscopy, a baseline renal ultrasound, and urodynamic studies with or without video, have been recommended because of the very high rates of persistent long-term bladder dysfunction. , bowel evaluation may require radiography, computed tomography (ct), and mri scans with or without contrast, or colonoscopy to rule out obstruction. in , the tm consortium working group proposed the criteria in table . for the diagnosis of idiopathic acute tm. a comparison by de seze of the clinical findings, mri results, laboratory profiles, and outcomes of patients with acute myelopathy according to etiology is presented in although the physiatrist may manage stable long-standing tm on an outpatient basis, hospitalization may be necessary during the initial presentation to monitor vital signs, manage respiratory difficulties, bowel or bladder complications, and carry out diagnostic investigations. , abnormalities of vital signs such as tachypnea or tachycardia may suggest impaired oxygenation or blood flow to be managed urgently. the ability to provide antiviral or antibacterial agents and surgical intervention may also be critical when a specific cause has been identified. several anti-inflammatory drugs have been tried for tm without clear success. although there is insufficient evidence for corticosteroid efficacy, intravenous methylprednisolone is often used to prevent further damage to the spinal cord as a result of swelling. , , during the acute phase, it may lead to faster recovery and less disability, and is well tolerated. cyclophosphamide exerts an immunosuppressive and immunomodulatory effect through suppression of cell-mediated and humoral immunity (on the t cells and b cells). cyclophosphamide together with methylprednisolone may help in lupus-related tm. , however, there appears to be an absence of any beneficial effect of immunosuppressive drugs (cyclophosphamide, azathioprine, intravenous immune globulin) in patients with idiopathic acute tm. , plasma exchange to remove autoreactive antibodies and other toxic molecules from plasma may be effective with a good clinical response, especially within days of onset and when nonresponsive to highdose corticosteroids. , the monoclonal antibody rituximab can be effective in decreasing relapses in tm due to nmo. the management of any spinal cord injury will include rehabilitation, and the more severely affected cases of tm will require a comprehensive multidisciplinary rehabilitation program led by a physiatrist. physical and occupational therapists on the team can work with strengthening, endurance, balance, coordination, joint range of motion, reconditioning, mobility, and independence with activities of daily living. the goal is one of optimal functioning and independence in the activities of daily living and mobility for the patient. functional independence measure and the modified barthel index are among the more widely used outcome measures during the rehabilitation process. assessment for appropriate equipment, such as a wellfitting wheelchair and other assistive and walking devices, is needed. gait efficiency, stability, and overall mobility can be improved with bracing devices such as an ankle-foot orthosis or kafo. education of the patient and family about the disease, resultant impairments, potential complications, rehabilitation plans and prognosis is important. the psychological state of the patient should not be neglected, and there should be monitoring for depression and medications initiated if necessary. sexual functioning is often affected, and education and counseling, with or without intervention, may be appropriate early. discharge planning needs and issues potentially affecting the patient's community reintegration, including vocational and recreational, should be assessed. recovery to some extent is expected in tm, but it is important to minimize the effects of even temporary impairments and immobility. all muscles and joints should be kept as active as possible, and daily exercises to preserve range of motion of the joints will help prevent contractures and keep joints flexible. progressive resistive exercises and possibly functional electrical stimulation (fes), also known as neuromuscular electrical stimulation, help maintain strength and decrease muscle atrophy. exercises for inspiratory muscles should be included and use of an incentive spirometer as needed. rarely, glossopharyngeal breathing may need to be taught and electrical stimulation of the phrenic nerve diaphragm considered in the high cervical cord patient not showing recovery. spasticity (see chapter ) is a possible complication and regular stretching with use of antispasticity medications such as baclofen, diazepam, gabapentin, and tizanidine, can minimize and decrease development of joint contractures. if pain is present, appropriate medications, thermal (heat, cold), and electrical modalities including transcutaneous electrical stimulation may be helpful. antiepileptic drugs such as gabapentin, pregabalin, and carbamazepine, may be prescribed as they have good efficacy for neuropathic pain. amitriptyline may also be useful, although caution is advised with its strong anticholinergic effects. thorough checks of the skin on a daily basis can help avoid pressure sores and associated infections. insensate areas, particularly over bony prominences, should be relieved with special cushions and mattresses such as eggcrate foam and alternating pressure overlays, and pressurerelieving ankle-foot orthoses (prafo) may be helpful. the many varieties of hydrophilic and antimicrobial wound dressings currently available promote faster healing of skin breakdown. bladder (see chapter ) and bowel (see chapter ) functioning should be assessed, and a bedside ultrasound for post-void residual urine volume is a simple informative procedure, as is a rectal examination. a program may be needed to avert a neglected neurogenic bowel or bladder leading to stool impaction and hydroureter or hydronephrosis. an indwelling catheter can initially be used for bladder drainage but intermittent catheterization, independently or otherwise, should be instituted whenever possible. longterm follow-up of to years in pediatric patients with tm has shown that residual bladder dysfunction is common even with improvement of paraparesis and lack of urologic symptoms. in one study, % had persistent bladder dysfunction and % had persistent bowel dysfunction. , a bowel program includes adequate fluids, proper diet, activity, and scheduled bowel movements. upper motor neuron bowels may need a stool softener (e.g., docusate), osmotic laxative (lactulose), or stimulant laxative (senna or bisacodyl) for evacuation. digital stimulation of the rectum is often effective and needs to be taught. with areflexic lower motor neuron bowels, use of bulk laxatives like psyllium or methylcellulose to produce formed stools may help during digital manual evacuation. bowel evacuation is often done on a daily basis in the hospital, but frequency can be extended to every or days once an individual returns home. the patient requiring a wheelchair, walker, crutches, or cane will need training, including maneuvering over steps and curbs. if transfers and ambulation require assistance, the training should also include family members or assistants. for patients with tm at the cervical level especially, various types of equipment and orthoses can be provided to help with self-care activities. proper bathroom equipment and modifications, such as a tub bench, commode, handheld shower, raised toilet seat, and grab bars, may make the difference between dependence and independence. selection of appropriate assistive devices helps maximize function. some of this equipment can be fairly expensive; hence, timing of purchases must be carefully considered, as they may not be required soon after. despite a reasonable prognosis for eventual recovery, complacency is to be avoided as it may result in unnecessary secondary complications. renal ultrasound and urodynamic evaluations are relatively routine procedures to assess and monitor bladder dysfunction. electrodiagnosis including ncs and emg are useful for diagnosis and for monitoring recovery. intramuscular botulinum toxin injections are very effective in the management of spasticity and commonly performed by the physiatrist, as are the alternatives of alcohol or phenol nerve and motor point blocks for spastic limb muscles. an intrathecal baclofen pump may be effective in intractable cases and allows much smaller doses and concomitantly fewer side effects. many physiatrists are able to manage the settings and refilling of these pumps. intractable neuropathic pain may respond to an intrathecal morphine pump, which will also require management. the field of rehabilitation uses a plethora of devices and technology during the process of restoring or compensating for the impairments and disabilities resulting from conditions such as tm. some individuals receive fes systems to help maintain fitness and muscle bulk or improve and restore function. fes for the forearm and arm muscles is a routinely employed technique with many devices commercially available. exercise bicycles for the lower as well as upper limbs (e.g., ergys [therapeutic alliances, inc.], rt -s [restorative therapies, inc.]) have also long been used, although are not cheap and have a risk for osteoporotic fractures. from simple body weight-support suspension devices, stationary and mobile, allowing for safer ambulation training, to motorized treadmills allowing flexibility in intensity, velocity, and effort, multiple devices from various manufacturers are available. robotic wheelchairs are ubiquitous equipment, available as either manual, powered, or hybrid, with an almost infinite offering of choices for size, weight, purpose, and even color. control of the wheelchair can be achieved by hand, chin, or other head part, and by voice activation. other than locomotion, there are also wheelchairs available for standing purposes, whether for activities at an erect level, or for weight-bearing exercise. braces or orthotics have also undergone much development and come with different materials, rigidity or flexibility, weight, and functional goals including for support, pressure relief, positioning, or protection. powered exoskeleton systems are currently of interest with systems to assist standing and ambulation such as the rewalk . (rewalk robotics inc.), hybrid assistive limb or hal (cyberdyne inc.), rex (rex bionics), ekso gt (ekso bionics), and indego (parker hannifin corp). at this time, they are mainly for training and exercise, and limited by the individual's abilities, terrain, device battery, and need for safety supervision including skin breakdown, falls, and equipment failure. the next wave for independent mobility in patients with handicaps could well be that of self-driving or autonomous cars undergoing trials by the major automobile companies and various research laboratories. environmental control units or multiple devices within a smart home controlled using simple touch-pad, infrared or motion-sensitive, and voice-activated mechanisms including automatic doors, curtains, and various electronics such as the television and personal computer, are now commercially available, easy to control, and importantly becoming increasingly affordable. apps (applications) that allow easy communication, videophone interactions, and ready access to the internet are already built-in for many smart phones. intelligent voicecontrolled personal assistants include the apple siri, google assistant, amazon alexa, microsoft cortana, and samsung bixby. there is no specific curative surgical procedure for tm. however, lesions such as abscesses, herniated disks, spinal stenosis, and tumors may need surgery as soon as possible to relieve pressure and prevent further damage to the cord. timely management of compressive lesions may reverse or at least halt further neurologic injury to the cord. pressure sores may require sharp débridement on the unit to remove dead or infected tissue and other debris to accelerate healing. tendon transfers may be considered at a later stage to increase an individual's functioning. nerve transfer in patients with permanent upper limb deficits may be considered to restore or to improve ability to voluntarily activate a muscle. in one case report, a child with tm who underwent multiple fascicle transfers from median and ulnar nerves to the musculocutaneous nerve, spinal accessory to suprascapular nerve, and medial cord to axillary nerve, had excellent recovery of elbow flexion. potential complications from the spinal cord dysfunction of tm are numerous and may require medical or surgical intervention. they include orthostatic hypotension, impaired thermoregulation, autonomic dysreflexia, lung and urinary tract infections, ileus and constipation, electrolyte imbalances, skin breakdown, spasticity and contractures, musculoskeletal and neuropathic pain, injury (including fractures) to bones, muscles and joints due to sensory impairments, heterotopic ossification, osteoporosis, kidney stones, depression, and anxiety. there may be respiratory muscle weakness depending on the level of spinal cord involved, and when severe, mechanical ventilation assistance may be required. the risk of bronchopneumonia and sleep apnea is compounded by any sedating medications or respirationdepressing medications. spasticity and joint contractures are common complications with spinal cord injury and management may be straightforward or extremely difficult, requiring several interventions simultaneously. heterotopic ossification (see chapter ) may develop around a joint, especially the elbow, knee, and hip. gastrointestinal complications include gaseous distension, regurgitation, indigestion, and chronic constipation. urinary tract infections and urosepsis are also common with a neurogenic bladder, as both retained urine and bladder instrumentation increase infection risk. autonomic dysreflexia/hyperreflexia may occur, especially for lesions above t . pain is a very frequent complaint and may arise from musculoskeletal sources or be neuropathic in nature. pain management may include medications such as analgesics, nonsteroidal anti-inflammatory drugs, short courses of cyclooxygenase- inhibitors, various anticonvulsants, and tricyclic antidepressants. overuse syndromes often occur because muscles and joints are overstressed during functional compensation for weakness or even during the process of rehabilitation training. shoulder pain is a common phenomenon with causes including tendinitis, rotator cuff injury, impingement syndromes, contractures, and inflammatory or degenerative arthritis. steroid and local anesthetic injections in the joint may sometimes be needed, but topical anti-inflammatory drugs, heat, cold, and other modalities, with proper transfer techniques or specific adaptive equipment such as sliding board, are often helpful. a common complication is ischemic breakdown of the skin if pressure relief is not regularly performed. awareness and monitoring for deep venous thrombosis and pulmonary embolism should be routine. prolonged pressure on a peripheral nerve can also cause dysesthesias, pain, or weakness. there may be sexuality, reproduction, and fertility concerns, particularly in younger as well as sexually active patients. the concerns and possible solutions should be discussed, addressed, or referred to a specialist as appropriate. depression and anxiety are not uncommon and usually respond to supportive counseling, but may need antidepressants such as the selective serotonin reuptake inhibitor or the serotonin-norepinephrine reuptake inhibitor drugs. treatment complications may occur because of the medications and equipment required to manage the disease and its complications. strictures or tracheal irritation can result from tracheostomy tubes, lung infections are common in this population, and the ventilators may break down, resulting in an emergency situation. high-dose corticosteroids frequently used for treatment of inflammation in the spinal cord may result in peptic ulcer disease or gastrointestinal bleeding. thromboembolism prophylaxis and anticoagulant treatment in the event of this happening may result in serious bleeding complications. skin breakdown may result at contact and pressure areas with devices or dressings used. frequent catheterization results in increased risk for urinary tract infections and accidental creation of false passages in the urethra with development of strictures. if bowel programs are not well managed or carried out gently, there may be discomfort, pain, and anorectal injuries. transverse myelitis consortium working group. proposed diagnostic criteria and nosology of acute transverse myelitis transverse myelitis fact sheet transverse myelitis: retrospective analysis of cases, with differentiation of cases associated with multiple sclerosis and parainfectious events acute transverse myelitis: incidence and etiological considerations idiopathic acute transverse myelitis: application of the recent diagnostic criteria long-term follow-up of acute partial transverse myelitis acute myelopathies: clinical, laboratory and outcome profiles in cases analysis of prognostic factors associated with longitudinally extensive transverse myelitis the clinical course of idiopathic acute transverse myelitis in patients from rio de janeiro a retrospective cohort study of years follow-up evidence-based guideline: clinical evaluation and treatment of transverse myelitis: report of the therapeutics and technology assessment subcommittee of the american academy of neurology idiopathic transverse myelitis: an experience in a tertiary care setup the prognosis of acute and subacute transverse myelopathy based on early signs and symptoms acute demyelinating events following vaccines: a case-centered analysis transverse myelitis associated with acinetobacter baumanii intrathecal pump catheter-related infection acute transverse myelitis: mr characteristics magnetic resonance imaging findings in cases of myelitis: comparison between patients with and without multiple sclerosis idiopathic transverse myelitis mimicking an intramedullary spinal cord tumor sjögren's syndrome with acute transverse myelopathy as the initial manifestation transverse myelopathy in systemic lupus erythematosus: an analysis of cases and review of the literature idiopathic transverse myelitis and neuromyelitis optica: clinical profiles, pathophysiology and therapeutic choices transverse myelitis. comparison of spinal cord presentations of multiple sclerosis discriminatory features of acute transverse myelitis: a retrospective analysis of patients distinct features between longitudinally extensive transverse myelitis presenting with and without anti-aquaporin antibodies acute myelitis due to zika virus infection clinical and evoked potential changes in acute transverse myelitis following methyl prednisolone residual bladder dysfunction to years after acute transverse myelitis transverse myelitis in children: long-term urological outcomes involvement of the entire spinal cord and medulla oblongata in acute catastrophic-onset transverse myelitis in sle neuromuscular electrical stimulation for muscle weakness in adults with advanced disease point: should phrenic nerve stimulation be the treatment of choice for spinal cord injury? effective management of intractable neuropathic pain using an intrathecal morphine pump in a patient with acute transverse myelitis effects of locomotor training after incomplete spinal cord injury: a systematic review robot-assisted gait training (lokomat) improves walking function and activity in people with spinal cord injury: a systematic review powered exoskeletons for walking assistance in persons with central nervous system injuries: a narrative review nerve transfers for restoration of upper extremity motor function in a child with upper extremity deficits due to transverse myelitis: case report key: cord- -i bfuvq authors: macdonald-laurs, emma; koirala, archana; britton, philip n.; rawlinson, william; hiew, chee chung; mcrae, jocelynne; dale, russell c.; jones, cheryl; macartney, kristine; mcmullan, brendan; pillai, sekhar title: csf neopterin, a useful biomarker in children presenting with influenza associated encephalopathy? date: - - journal: eur j paediatr neurol doi: . /j.ejpn. . . sha: doc_id: cord_uid: i bfuvq purpose: neurological complications of influenza cause significant disease in children. central nervous system inflammation, the presumed mechanism of influenza-associated encephalopathy, is difficult to detect. characteristics of children presenting with severe neurological complications of influenza, and potential biomarkers of influenza-associated encephalopathy are described. methods: a multi-center, retrospective case-series of children with influenza and neurological complications during was performed. enrolled cases met criteria for influenza-associated encephalopathy or had status epilepticus. functional outcome at discharge was compared between groups using the modified rankin scale (mrs). results: there were children with influenza studied of whom / had encephalopathy and / had status epilepticus. only one child had a documented influenza immunization. the biomarker csf neopterin was tested in / children with encephalopathy and was elevated in / . mri was performed in all children with encephalopathy and was abnormal in ( %). treatment of children with encephalopathy was with corticosteroids or intravenous immunoglobulin in / ( %). in all cases oseltamivir use was low ( %) while admission to the intensive care unit was frequent ( / , %). clinical outcome at discharge was moderate to severe disability (mrs score > ) in the majority of children with encephalopathy ( / , %), including one child who died. children with status epilepticus recovered to near-baseline function in all cases. conclusion: raised csf neopterin was present in most cases of encephalopathy, and along with diffusion restriction on mri, is a useful diagnostic biomarker. lack of seasonal influenza vaccination represents a missed opportunity to prevent illness in children, including severe neurological disease. severe neurological complications from seasonal influenza, including influenza-associated encephalopathy/encephalitis (iae), cause considerable morbidity and mortality in healthy children, and those with pre-existing neurological disease. e recent estimates indicate the annual incidence of iae in australia is . per , , in children under years, with around % of hospitalized influenza cases associated with iae. other populations show similar or higher incidence, with japan's annual incidence of iae recorded as e / , , . , neurological complications attributed to influenza range from a mildly altered mental state, vertigo and brief febrile seizures to life threatening complications such as status epilepticus, meningitis, stroke, and demyelinating disease. antiviral agents, predominantly neuraminidase inhibitors, and immunomodulatory treatments (corticosteroids, intravenous immunoglobulin), are used to treat patients with influenza-associated neurological disease but there is limited evidence on their efficacy. while it is thought that more extensive changes on mri correlate with disease severity there are no other available biomarkers that predict outcome. the australian influenza season typically occurs between july and october. the season saw the highest levels of influenza reported since the pandemic year. the authors of this report noted an apparent increase in iae and other severe neurological complications during . here, we describe the clinical presentation, laboratory testing, neuroimaging, treatment and short-term outcome of these cases. in addition, we observed elevated cerebrospinal fluid (csf) neopterin e a marker of central nervous system (cns) inflammation e amongst children with iae that has not previously described. we compared the frequency of iae during the influenza season with previously published incidence estimates. materials and methods we identified children aged e years, with evidence of influenza and associated severe neurological disease including status epilepticus or moderate to severe encephalopathy, admitted to two paediatric hospitals which comprise the sydney children's hospital network, the largest paediatric network in australia. cases were ascertained between april st and october st, . at the children's hospital at westmead, cases were identified from those recruited under pre-existing surveillance studies: the australian childhood encephalitis study (ace), and the influenza complications network (flucan) surveillance study. , at sydney children's hospital, children were identified from neurology consultation databases. children were included if they required hospital admission and consultation from a paediatric neurologist for a neurological complication or worsening of a pre-existing neurological condition due to proven influenza. all children included either presented with status epilepticus (for min or longer) or reached level diagnostic certainty on the brighton encephalopathy score. children were excluded if: influenza was not confirmed, neurological symptoms were mild, hospital admission was not required, and when an alternative diagnosis could better explain the presentation. data were retrospectively collected from electronic medical records. we collected demographic data, presenting clinical characteristics, intensive care unit (icu) admission, and length of stay, laboratory results including csf testing, and influenza testing. csf analysis included cell count, protein, glucose, microscopy, lactate, oligoclonal bands, neopterin and influenza pcr. an elevated csf neopterin result was defined as > nmol/l. electroencephalogram reports and brain magnetic resonance imaging (mri) (t weighted, flair and diffusion weighted imaging) were assessed by a neurologist (s.p.) and neuroradiologist (c.c.h.). the neuroradiologist was blinded to diagnosis during review of the mri. influenza was most commonly acutely diagnosed through the detection of influenza rna in respiratory samples. both hospitals used multiplex pcr assays (seegene, south korea) which detected up to respiratory viruses. the assay has targets for both influenza a and b and was performed daily with a turnaround time of e days. at sydney children's hospital, the assay also had targets for subtypes of influenza a: h strains and the pandemic strain h n / . when influenza serology was requested to diagnose a recent influenza illness, this was performed using a complement fixation assay (virion, germany). treatment given including oseltamivir, empiric aciclovir, or rd generation cephalosporins, ivig, corticosteroids, and e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y ( ) e plasmapheresis were recorded. time from admission to commencement of oseltamivir was recorded. each case was assigned a modified rankin scale (mrs) based on the examination at presentation and discharge from hospital. the mrs ranges from (no symptoms) to (death). a poor outcome was an mrs score of > which indicates at least moderate disability requiring assistance. the relation between categorical variables was investigated using the two tailed fisher exact test. the mannewhitney u test was used to determine the relation between continuous variables. ethics approval was granted by the sydney children's hospitals network ethics committee (lnr/ /schn/ ). twenty two children were included in this case series; % ( / ) were female. the median age at presentation was five years (range: . e years). eight children ( %) had preexisting epilepsy and/or developmental delay. one child had an immunodeficiency (hypogammaglobulinemia) and receives monthly ivig. this child, who presented with status epilepticus, was the only child recorded as having received the seasonal influenza vaccination. eleven children ( %) met level brighton criteria for encephalitis and were designated as influenza associated encephalopathy/encephalitis (iae). two children with iae had previous episodes of acute disseminated encephalomyelitis (adem) with complete clinical and radiological recovery ( table cases & ). one child had mosaic tetrasomy x, while another had epilepsy and developmental delay. the remaining children in our series had status epilepticus. in contrast to the children with iae, over half of this group (n ¼ ) had preexisting neurological disease including two children with refractory genetic epilepsies (dravet syndrome and cdkl ). the majority of children had a fever ( %) and two-thirds had respiratory symptoms. half presented with neurological symptoms within two days of onset of their influenza illness. sixteen children ( %) presented with an altered level of consciousness. seizures occurred in children ( %) at any stage of illness and status epilepticus was frequent (n ¼ , %). other neurological findings at presentation were weakness (n ¼ , %), pyramidal signs (n ¼ , %), movement disorder (n ¼ , %) and ataxia (n ¼ , %). hallucinations, meningism, cranial neuropathy and pupillary changes were infrequent (< %). the majority of children (n ¼ , %) had influenza a. of those sub-typed (n ¼ ) half were h ( ) and half were h . four children had other respiratory pathogens co-identified on npa (rhinovirus, coronavirus, mycoplasma pneumoniae). enterovirus was detected in the npa of one child but was absent in csf. one blood culture was positive for staphylococcus epidermidis, and this was assessed to be a contaminant. lumbar puncture was performed in children where it was considered clinically indicated ( table ) . of those who did not have a lumbar puncture performed most were children who presented with status epilepticus alone, usually with known pre-existing epilepsy. one case, with acute necrotising encephalopathy (ane), who was deemed to be too unwell to undergo a second lumbar puncture for measurement of neopterin. where sampled, csf showed pleocytosis and elevated protein in only a third (each n ¼ ). influenza pcr on csf was positive in of children tested, in an immunocompetent previously well year old. the csf neopterin was elevated in of children tested; in seven children it was considerably elevated ranging from to nmol/l (normal < nmol/l), one had a borderline result ( nmol/l). csf neopterin was measured in one child presenting with status epilepticus and was . nmol/l (borderline result). while most children with iae had a raised csf neopterin ( / , %), only three had csf pleocytosis ( , , cells/mm ) and two had an elevated csf protein ( . g/l and . g/l). oligoclonal bands were measured on serum and/or csf in / children with iae and were not present in any. some children with iae had anti-neuronal antibodies testing performed on serum and/or csf, usually nmda and vgkc (table ). these were negative apart from two cases with mildly elevated anti-thyroid antibodies. other routine laboratory data were normal or only mildly abnormal in most children (table ) . mri brain was performed in children and showed new abnormalities in eight ( %), all with iae. the common acute mri abnormalities were the presence of t -flair hyperintensities, diffusion restriction (each, n ¼ ), and gadolinium enhancement (n ¼ ). the spectrum of radiological features are shown in fig. aei . diverse clinico-radiological syndromes were diagnosed including: ane (n ¼ ), acute encephalopathy with biphasic seizures (aesd) (n ¼ ), posterior reversible encephalopathy (pres) (n ¼ ), hemiconvulsion hemiplegia syndrome (hhs) (n ¼ ), and cerebellitis. genetic testing of ran-binding protein (ranbp ) was performed in the child with ane (table case ) and the child who died from an ane-like illness ( table , case ). both were negative. one child who met criteria for iae was subsequently found to have a mutation in the polymerase gamma (polg) gene (table , case ). fourteen ( %) children were admitted to the icu and nine ( %) required mechanical ventilation. thirteen ( %) children received oseltamivir. median time to commencement of oseltamivir from presentation was day (mean . days, iqr e days), but > days in five cases. two icu ventilated children were commenced on oseltamivir nine days after admission. in contrast, nineteen ( %) children were treated with a rd generation cephalosporin, while ( %) received aciclovir. nineteen ( %) received anticonvulsants and ( %) continued these on discharge. first-line e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y ( ) e immunomodulatory treatment (corticosteroids and/or ivig, plasmapheresis) was given to nine children with iae (corticosteroids (n ¼ ), ivig (n ¼ ) and plasmapheresis (n ¼ )) but none of those with status epilepticus alone. the median length of icu and hospital stay was four days (range e ) and days (range e days) respectively. children with iae were more likely to have both longer hospital (mean . days vs . days; p ¼ . ) and picu admissions (mean . days vs days; p ¼ . ) compared to children with status epilepticus. one child with iae died following an ane-like illness, although mri findings were atypical (table , case ). her post-mortem was inconclusive: showing generalised cerebral oedema and some features of acute hemorrhagic leucoencephalitis. ten out of children with iae had an mrs score of (normal) at baseline. at discharge from hospital / ( %) of children with iae had a higher in mrs score (mrs > ; moderate disability) compared to those with status epilepticus. the change in mean mrs was significant between the two groups: children with iae had a change in mrs of . points while those in the status epilepticus group had a mean increase of mrs of . points (p-value: . ). nearly all children ( / , %) with mri diffusion restriction had a poor outcome. the child with mri diffusion restriction and a good outcome had posterior reversible encephalopathy syndrome (pres). among the children with iae and a considerably elevated neopterin, four had an mrs > while three had mild deficits (mrs , and ). there was a mean increase in the mrs of . points the seven children with highly elevated csf neopterin ( e nmol/l). in this case series we observed two groups of children who presented with severe influenza related neurological disease. one group of children fulfilled criteria for iae, while the other group, most often with pre-existing neurological disease, presented with status epilepticus but otherwise did not fulfill criteria for iae. amongst cases of iae, elevated csf neopterin appeared to correlate with the presence of diffusion restriction on mri brain and adverse outcome. use of oseltamivir was infrequent among all cases, although use of antibiotics occurred in the majority. only one child had documented influenza vaccine, even amongst those with pre-existing neurological co-morbidity, despite the fact that this is recommended in australia. influenza associated neurological complications are thought to occur due to an inflammatory or immunemediated response to influenza infection rather than direct viral invasion. , among those with iae we observed, similar to previous authors , , that csf pleocytosis and detection of influenza in the csf occurred in a minority (n ¼ ; %, and n ¼ / ; %). , , , however csf neopterin, a biomarker of inflammation, was elevated in most children with iae (n ¼ , %). neopterin, a catabolic product of guanosine triphosphate (gtp), is synthesized by human macrophages upon stimulation from interferon gamma and can be measured in urine, serum and csf. while serum neopterin levels are useful in the diagnosis and monitoring of systemic infectious or inflammatory diseases, such as hiv, csf neopterin, reflecting intrathecal production by microglial cells, more accurately detects cns inflammatory diseases (infectious or immune mediated). , a recent review assessing biomarkers of csf inflammation found, among clinically available tests, that csf neopterin performed better than the presence of oligoclonal bands or csf pleocytosis in detection of cns inflammation. there is limited data regarding prognostically significant biomarkers in iae. pro-inflammatory cytokines may impair the blood brain barrier and induce apoptosis of neurons. elevated cytokines such as interleukin- (il- ) and tumour necrosis factor alpha have been demonstrated in children with iae and correlates with poorer outcome. , , testing csf il- outside the research setting is currently unavailable. clasmatodendrosis, abnormal morphological changes in astrocytes, occurring presumably due to the effect of proinflammatory cytokines, has recently been suggested to be a pathological feature of iae on autopsy. clasmatodendrosis was found in the cerebral white matter, thalamus, corpus callosum, cerebellum, thalamus and hippocampus of children with iae and may correlate mri changes commonly seen. previous authors have associated abnormalities on mri brain with poorer outcome. in our cohort mri brain abnormalities were diverse and common, particularly diffusion restriction in the subcortical white matter. diffusion restriction correlated with a poor outcome, apart from in the child who had pres, and was associated with an elevated csf neopterin in most cases. further studies of iae are required to evaluate whether significant elevations of csf neopterin, particularly in combination with diffusion restriction and other mri changes, could predict short and long-term outcome. oseltamivir, a neuramidase inhibitor which prevents release of influenza virus from infected cells has been shown to reduce influenza symptoms in otherwise healthy children by h ( % ci e h,p ¼ . ). only % ( children) were treated with oseltamivir and there was a significant delay in commencement in cases (> days in hospital). in contrast, empirical rd generation cephalosporin ( %) and aciclovir use ( %) was more frequent. this may be related to the perception among practitioners that antiinfluenza therapy has little benefit. we suggest in accordance with local guidelines, that children with encephalitis should be empirically treated with oseltamivir during the influenza season (may to october). the evidence for use of immunotherapy (ivig, corticosteroids) in iae, is limited , however, in our case series, most children with iae were treated with first-line immunotherapy with uncertain benefit. no serious side effects were reported. in , the burden of influenza in australia (particularly the eastern states) was the highest seen since the pandemic. based on iae incidence estimates published by britton et al. from the e influenza seasons in australia and the population coverage of our hospitals, we calculated that we would expect . ( . e . ) cases of iae in children (< years) per year. the iae case frequency observed in our cohort was twice the expected point estimate based on these previous incidence estimates but within the % confidence interval, and so contribute to validating the estimates from britton et al. the short-term outcome of our cohort, particularly those with iae, was alarming with % having a poor outcome. while there was a significant rate of icu admission among the group of children with status epilepticus ( %) this was not as high as children with iae ( %) and, most often, non-iae children did not experience a significant change in their mrs. this supports previous observations that survivors of iae during the h n pandemic, and in more recent nonpandemic influenza seasons in australia, experienced significant ongoing disability. , we have previously shown in a large retrospective encephalitis cohort study that icu admission, mri diffusion restriction and status epilepticus and were risk factors for a long-term abnormal outcome. these risk factors were common ( %, %, %) in children with iae from our cohort. the medium and long-term outcome in our cohort should be assessed including formal neuropsychological testing. further research is required to understand and modulate the cns inflammatory cascade present in iae in order to modulate long term neurodisability. the overall influenza immunisation rate during in australia was low at %, however a recently observed rate of vaccine receipt among children was even lower at . %. four age-specific quadrivalent influenza vaccines containing two strains of influenza a (h n [michigan] and h n [hong kong]) and two strains of influenza b (brisbane and phuket) were available in . children older than six months were eligible to be vaccinated and the vaccine was provided free to children with neurological disease. in our cohort just one child had a documented influenza vaccination, although a third of children were eligible for free immunisation and the remainder could have received an immunisation at the cost of around $ e aud. we emphasise that the severe syndromes and adverse outcomes observed here should be considered preventable. following high rates of influenza related morbidity in (including these cases), new south wales and other australian states have introduced universal funded seasonal influenza immunisation to all children aged months to years. our series has limitations. we describe children with severe influenza-associated neurological complications but did not include children with mild neurological complications. children with pre-existing epilepsy may not have always been tested for influenza and may be under-represented. the collection of clinical data was retrospective, and some electronic data were incomplete. seasonal influenza immunisation status was not always clearly recorded, although we reviewed the australian immunisation register to verify vaccination status where possible. influenza sub-typing from npa samples and csf influenza pcr testing was not routinely performed. in the se group, csf studies, including csf neopterin were performed infrequently and mri brain infrequently requested. due to this we were unable to use this group as a direct control for the finding of elevated csf neopterin the iae group. serial csf neopterin to assess treatment and clinical progress were not performed. this is the first series to demonstrate that elevation of csf neopterin, a marker of cns inflammation, occurs commonly in children with iae. csf neopterin may be a useful diagnostic marker for iae while its role as a prognostic marker e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y ( ) e requires further evaluation. mri diffusion restriction was associated with a poor outcome in iae. short-term outcomes of children with neurological complications of influenza, especially within the iae group, were alarming, with nearly two-thirds of children having a poor outcome despite receipt of icu support, anticonvulsants, first-line immunotherapy and, in some, anti-viral treatment. given the severity of influenza associated neurological complications, we recommend a "treat and test" approach to the use of oseltamivir in children presenting with acute encephalopathy/encephalitis during the influenza season. finally, seasonal influenza vaccination should be universally provided to children and those at risk of severe influenza, with better education and awareness to increase uptake in the paediatric population. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. neurological manifestations of influenza infection in children and adults: results of a national british surveillance study the spectrum and burden of influenza-associated neurological disease in children: combined encephalitis and influenza sentinel site surveillance from australia neuroinfluenza: evaluation of 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marker of active central nervous system inflammation recovery of motor function after stroke atagi) atagoi. the australian immunisation handbook australian government department of health acute encephalopathy and encephalitis caused by influenza virus infection evidence for influenza virus cns invasion along the olfactory route in an immunocompromised infant neurological and muscular manifestations associated with influenza b infection in children influenza virus and cns manifestations central nervous system manifestations in pediatric patients with influenza a h n infection during the pandemic neopterin in the diagnosis and monitoring of infectious diseases csf fluid neopterin: an informative biomarker of cns immune activity in hiv- infection utility of csf cytokine/chemokines as markers of active intrathecal inflammation: comparison of demyelinating, anti-nmdar and enteroviral encephalitis h n encephalitis with malignant edema and review of neurologic complications from influenza influenza-associated neurological complications clasmatodendrosis is associated with dendritic spines and does not represent autophagic astrocyte death in influenzaassociated encephalopathy prevention and treatment of influenza oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments immunomodulatory therapies in neurologic critical care intravenous immunoglobulin for the treatment of childhood encephalitis national survey of pandemic influenza a (h n ) -associated encephalopathy in japanese children influenza-associated encephalitis/encephalopathy identified by the australian childhood encephalitis study e infectious and autoantibody-associated encephalitis: clinical features and long-term outcome influenza season in australia. a summary from the national influenza surveillance committee influenza epidemiology, vaccine coverage and vaccine effectiveness in children admitted to sentinel australian hospitals in : results from the paeds-flucan collaboration influenza vaccine effectiveness against pediatric deaths seasonal influenza vaccination the authors have stated that they had no interests, which might be perceived as posing a conflict or bias. this manuscript has been contributed to, seen, and approved by all the authors. all the authors fulfill the authorship credit requirements. no honorarium grant or other form of payment was received for the preparation of this manuscript. supplementary data to this article can be found online at https://doi.org/ . /j.ejpn. . . . r e f e r e n c e s key: cord- -sxd t tz authors: nan title: poster presentations date: - - journal: dev med child neurol doi: . /dmcn. sha: doc_id: cord_uid: sxd t tz nan what are the perspectives and understanding of healthcare professionals including occupational therapists on treatment and care of babies with infantile spasms and early-onset epilepsy? a qualitative design dm middleton university of roehampton-online, birmingham, uk objective: to explore the perspectives and understanding of allied healthcare professionals (occupational therapists, physiotherapists, speech & language therapists) that work with children and epilepsy in order to guide and advocate for this population group. methods: a qualitative study design using interpretive thematic analysis with the data from participants in semi-structured interviews. results: the professionals had worked across acute and community settings and had previous experiences of working with children with epilepsy with some awareness of these needs. there were themes that emerged: ( ) housing and social needs, ( ) epilepsy, psycho-social and mental health needs, ( ) therapy approaches, ( ) training for allied healthcare professionals, and ( ) adolescents, young girls, women and epilepsy. conclusions: there are gaps in service provision for certain areas and will be shared within the presentation. epilepsy requires additional considerations for safety that other conditions may not require. it is crucial in the interests of public health for children and families with epilepsy to be able to advocate for resources and their specific needs. poster no. time to onset of cannabidiol (cbd) treatment effect and resolution of adverse events in patients with dravet syndrome: pooled analysis of two randomised controlled trials solution) at mg/kg/day (cbd ; gwpcare ) or mg/ kg/day (cbd ; both trials) or placebo for weeks. cbd treatment started at . mg/kg/day and reached mg/kg/day on day and mg/kg/day on day . percent reduction in cumulative convulsive seizure frequency for each treatment day (including previous treatment days) and timing of adverse events (aes) were assessed. results: overall, patients were randomised to cbd and to placebo. cbd led to significantly greater percent reductions in convulsive seizure frequency than placebo in gwpcare (cbd % vs placebo %, p= . ) and gwpcare (cbd %, cbd % vs placebo %, p= . and p= . ). in the pooled data, treatment differences in seizure reduction emerged during titration and were maintained throughout the study, with nominal significance (p< . ) achieved by day for cbd and day for cbd . onset of the first reported ae occurred during titration in % of patients with aes. aes resolved within weeks of onset in % of patients and by the end of the study in %. increases in alt/ast (> upper limit of normal) occurred in ( %) patients for cbd , ( %) for cbd , and ( %) for placebo; all were on concomitant valproate. all elevations resolved, either spontaneously while continuing cbd, after discontinuing cbd, or after reducing cbd, valproate, and/or clobazam dose. conclusions: cbd treatment effect (seizure reductions and aes) may occur early, during titration. the majority of aes resolved during the study. poster no. low dose fenfluramine hydrochloride oral solution provides long-term, clinically meaningful (≥ %) reduction in seizure frequency in dravet syndrome: interim analysis of a long-term openlabel extension study objective: to characterize long-term safety and durability of effect for adjunctive fenfluramine (ffa) in treating dravet syndrome (ds). methods: patients ( - y) with ds entered a long-term openlabel extension (ole) ( ) after completing one of two phase studies: study ( wks; placebo or ffa . or . mg/kg/d [max, mg/d] or study ( wks; placebo or ffa . mg/kg/d [max, mg/d]) . stiripentol was excluded in study but mandatory in study . in , patients received ffa . mg/kg/d for month ; dosing was titrated to effect thereafter. effectiveness and tolerability were assessed at months , , and , then at -month intervals. results: at interim analysis ( -mar- ) , / patients continued into ole; % completed months of ffa (mean dose, . mg/d; median duration, d [range, - d] ). during the entire ole, median percentage change in monthly convulsive seizure frequency (mcsf) for ffa vs pretreatment phase study baseline was - . % (p< . ); clinically meaningful (≥ %) and profound (≥ %) mcsf reduction from baseline were % and %. at month , median and mean longest interval between convulsive seizures were and days (range, - d); % of caregivers and % of investigators rated patients 'much improved/very much improved'. the most common adverse events included appetite decrease, pyrexia, nasopharyngitis, and diarrhea. no valvular heart disease or pulmonary hypertension was observed in any patient. conclusions: treatment with ffa resulted in robust, sustained reductions in mcsf and was generally well tolerated. no valvular heart disease or pulmonary arterial hypertension was observed in any patient at any time. ffa may be an important, novel antiepileptic drug for long-term ds treatment. poster no. zx (low dose fenfluramine hydrochloride oral solution) provides long-term, clinically meaningful reduction of convulsive seizure frequency in young (< years old) dravet syndrome participants: analysis from a long-term open-label study results: a total of of ( . %) participants who enrolled in the ole were < years old upon entry into the phase studies. the median baseline monthly convulsive seizure frequency (mcsf) before double-blind treatment was . seizures/month (range, . - . ) in this patient subgroup (< y). at the time of the ole interim analysis, the median decrease in mcsf in the < years subgroup over the entire observation period compared to baseline was - % (p< . ) compared with - % in the overall study population ( - y). the most frequently reported adverse events included pyrexia, upper respiratory tract infections, decreased appetite, and diarrhea. no valvular heart disease or pulmonary arterial hypertension was observed. conclusions: treatment with zx provided sustained, clinically meaningful reduction in mcsf in ds participants < years old. importantly, effective control of seizures in this young age group might be expected to mitigate the negative neurodevelopmental outcomes reported to be associated with treatment-refractory seizures. the improving provision of epilepsy care for children in england and wales methods: all relevant health boards and trusts (hb/t) were invited to register to participate and identify a hb/t lead. a snapshot survey was completed via a bespoke online platform by the hb/t lead describing local provision as of april . data was analysed by the rcpch including regional and national aggregates and longitudinal comparison to previous , reports. results: hb/t with a paediatric epilepsy service across england and wales registered to participate and submitted data. . % ( / ) of hb/t employed a consultant paediatrician with expertise in epilepsy; . % ( / ) had some epilepsy specialist nurse (esn) provision; . % ( / ) had a defined epilepsy clinic seeing patients at secondary level. . % ( / ) of hb/t had agreed referral pathways to tertiary paediatric neurology services. satellite paediatric neurology clinics were hosted in . % ( / ) of hb/t. conclusions: there are improvements in the overall numbers of epilepsy nurse specialists, paediatricians with expertise and specific clinics for children and young people with epilepsies. the findings led to comprehensive recommendations to hb/ t and commissioners, informed updates to the epilepsy best practice tariff and themes within the nhs long term plan. poster no. diagnosing and managing seizures on picu: an explanatory sequential mixed methods approach tonic clonic seizures. awake and sleep eeg showed temporal focal slowing. she was labelled as non lesional focal epilepsy after a normal mri scan and was discharged on keppra. she had multiple admissions with cluster of brief seizures at the age of , , , , , and months associated sometimes with febrile illness with poor response to intravenous aed's. she was diagnosed with autism at months. nd child: months old younger sibling had seizure onset at months. seizures were tonic in nature, brief, multiple and in clusters over a period of to days. eeg's showed non-specific slowing during seizures. array cgh revealed chromosome p . microdeletion. keppra was commenced and increased but recurrent cluster of seizures at the age of , and months required admission with poor response to iv aed's. family history revealed that half-sister (biological father's daughter who had epilepsy and global developmental delay) was diagnosed with pcdh epilepsy. gene tests were requested on both siblings and both were heterozygous for pcdh mutation. she had delayed social and communication skills from years with a diagnosis of autism at months. rd child: year old half sibling (father's th child from rd relationship) has tested positive for pcdh . her development is normal and so far there have been no seizures. conclusions: pcdh epilepsy is increasingly recognised as one of the early onset infantile encephalopathies. gene testing is likely to yield a diagnosis with a family history or with a typical phenotype. poster no. seizure, developmental and cognitive outcomes in children post hemispherotomy tt tay , dr reed , vj josan , sr rust , jt tan university of manchester, manchester, uk; neuropsychology team, paediatric psychosocial service, royal manchester children's hospital, manchester, uk; neurosurgery, salford royal nhs foundation, manchester, uk; paediatric neuropsychology, royal manchester children's hospital, manchester, uk; paediatric neurology, royal manchester children's hospital, manchester, uk introduction: patients with focal refractory epilepsy secondary to structural hemispheric changes have been shown in retrospective studies to have significantly improved seizure outcomes following hemispheric disconnection. the aim of this study was to report the seizure and cognitive outcomes in our cohort and investigate prognostic factors for seizure outcomes. methods: this was a single-centre retrospective study on children and adolescents who had hemispherotomy for refractory epilepsy in the royal manchester children's hospital between and . results: twenty-two patients were included with median (range) age of seizure onset and of surgery of ( - ) and ( - ) months respectively. median (range) time from seizure onset to surgery was . ( - ) months. the most common aetiologies were antenatal/perinatal middle cerebral artery infarct (n= ) and malformations of cortical development (n= ). at year after surgery and at last follow-up (median [range] [ - ] months), % ( / ) and % ( / ) achieved complete seizure freedom. the number of anti-epileptic medications decreased for ( %) at last follow-up. lateralisation of ictal and interictal eeg (p= . , p= . ), aetiology (p= . ), age of first seizure (p= . ) were not associated with seizure recurrence. five who had formal neuropsychological testing using the wechsler intelligence scale for children (wisc) showed improvement in cognitive abilities across all subsets post-surgery. ten children showed reduction in median vineland adaptive behaviour score, from to . , indicating a failure to progress rather than regression of skills. nine ( %) had newly reported behavioural or psychiatric issues including sleeping problems, challenging behaviours, autistic spectrum disorder. sixteen ( %) were reported by parents/carers to show improved verbal abilities postoperatively while the rest had unchanged verbal abilities. conclusions: we present a cohort of children with early onset seizures who had hemispherotomy at a relatively early age. our cohort showed good seizure outcomes and cognitive improvements. there were no prognostic factors for seizure outcome identified in this small group. the mri phenotype of atp a -related disease contrast, all ahc patients with mri abnormalities ( %) had a hypoplastic corpus callosum. the only patient with normal mri was the patient carrying mutation p.g r, associated with a mild clinical phenotype. of the patients with clinical ataxia (n= ), ( %) had cerebellar atrophy on mri; patients with cerebellar atrophy were not ataxic. two ( %) of the patients with severe intellectual disability had cerebral atrophy. conclusions: atp a mutations have subtle radiological findings, clustering around callosal dysmorphisms, as well as pontine and cerebellar abnormalities that seem to form distinctive mri phenotypes for ahc and capos. study of larger cohorts is required to more accurately define mutation-specific phenotypes and allow for quantitative analysis. poster no. long-term safety and efficacy of adjunctive perampanel in paediatric patients (aged to < y) with partial-onset seizures (pos) or primary generalised tonic-clonic seizures (pgtcs) in study r flamini , a patten , ly ngo pediatric and adolescent neurodevelopmental associates, atlanta, ga, usa; eisai ltd., hatfield, hertfordshire, uk; eisai inc., woodcliff lake, nj, usa objective: study (nct ) was a multicentre, openlabel, single-arm study of perampanel oral suspension ( . mg/ ml) in paediatric patients (aged to < y) with pos (with/ without secondarily generalised seizures [sgs] ) or pgtcs. here, we report long-term ( y) safety and efficacy data of adjunctive perampanel in paediatric patients from study . methods: this analysis included cumulative data from all enrolled patients in the core study ( wks of treatment) and extension phase a ( wks of treatment). assessments included monitoring of treatment-emergent adverse events (teaes), median percent change in seizure frequency per days from baseline, and % responder and seizure-freedom rates. results: of patients enrolled in the core study (pos, n= ; sgs, n= ; pgtcs, n= ), patients entered extension a. of these, patients discontinued extension a; most common primary reasons for discontinuation were adverse events ( . %) and inadequate therapeutic effect ( . %). for all patients, mean (standard deviation [sd] ) time since diagnosis was . ( . ) years and mean (sd) duration of exposure was . ( . ) weeks. during baseline, . % of patients received two concomitant anti-seizure medications. teaes were reported in ( . %) patients; somnolence was the most commonly reported ( . %). median percent reductions in pos, sgs and pgtcs frequencies at weeks - were . %, . % and . %, respectively; these were maintained at weeks - and were . %, . % and . %, respectively. seizure-freedom rates for pos, sgs and pgtcs at weeks - were . %, . % and . %, respectively. conclusions: long-term ( y) adjunctive perampanel is generally safe, well tolerated and efficacious in paediatric patients aged to < with pos (with/without sgs) or pgtcs. poster no. long-term adjunctive perampanel and healthrelated quality of life (hrqol) in paediatric patients (aged to < y) with partial-onset seizures (pos) or primary generalised tonicclonic seizures (pgtcs): study ea portillo , a patten , g meier , m malhotra , ly ngo paediatric neurology unit, department of paediatrics, hospital universitario virgen del roc ıo, sevilla, spain; eisai ltd., hatfield, hertfordshire, uk; eisai inc., woodcliff lake, nj, usa objective: study (nct ) was a multicentre, openlabel study of adjunctive perampanel oral suspension in paediatric patients (aged to < y) with pos (with/without secondarily generalised seizures [sgs] ) or pgtcs. we report long-term ( y) hrqol data using the euroqol dimensions-youth (eq- d-y) scale from study . methods: this analysis included cumulative data from all enrolled patients in the core study and extension phase a ( and wks of treatment, respectively). eq- d-y was assessed at baseline, week and week , and included five domains (mobility, self-care, doing usual activities, pain/discomfort, feeling worried/sad/unhappy). the eq- d-y visual analogue scale (vas) was also assessed; increases in vas correspond with improvements. data are for observed cases. results: all enrolled patients were included in the eq- d-y analyses. the proportion of patients reporting 'a lot of problems' was similar during baseline vs week : mobility, / ( . %) vs / ( . ); self-care, / ( . %) vs / ( . %); doing usual activities, / ( . %) vs / ( . %); pain/discomfort, / ( . %) vs / ( . %); feeling worried/sad/unhappy, / ( . %) vs / ( . %). outcomes were also similar for 'no problems' during baseline vs week : mobility, / ( . %) vs / ( . %); self-care, / ( . %) vs / ( . %); doing usual activities, / ( . %) vs / ( . %); pain/discomfort, / ( . %) vs / ( . %); feeling worried/sad/unhappy, / ( . %) vs / ( . %). mean (standard deviation) change in eq- d-y vas from baseline at week was . ( . ). conclusions: long-term adjunctive perampanel treatment (up to y) does not negatively affect hrqol (based on all eq- d-y domains) in patients aged to < years with pos (with/without sgs) or pgtcs. poster no. efficacy and safety of adjunctive perampanel for partial-onset seizures (pos) in adult, adolescent and paediatric populations (studies , , , ) . in study , patients received perampanel ≤ mg/day (without enzyme-inducing anti-seizure medications [eiasms] ) or ≤ mg/day (with eiasms) ( -week treatment period). efficacy assessments included median percent change in seizure frequency/ days from baseline, % responder rate and seizure-free rate. safety assessments included the incidence of treatment-emergent adverse events (teaes). results: the median percent reduction in seizure frequency/ days was greater with perampanel at ( . %), ( . %) and mg/day ( . %) vs placebo ( . %; p< . ) in adolescent/adult patients and was . % in paediatric patients. the % responder rate during the maintenance period was greater with perampanel at ( . %), ( . %) and mg/ day ( . %) vs placebo ( . %; p< . ) in adolescent/adult patients and was . % in paediatric patients. seizure-freedom rates were greater with perampanel at ( . %), ( . %) and mg/day ( . %) vs placebo ( . %; p< . ) in adolescent/ adult patients and was . % in paediatric patients. teaes occurred in . %- . % of adolescent/adult patients with perampanel - mg/day (vs . % in placebo patients), and in . % of paediatric patients. teaes observed in pediatric patients were similar to those reported in adolescents and adults. conclusions: these studies suggest perampanel is efficacious and generally safe in paediatric, adolescent and adult patients with pos (with/without sgs). methods: patients who completed either of the rcts could enter this ole trial (gwpcare /nct ). patients received gw pharmaceuticals' plant-derived highly purified cbd medicine ( mg/ml oral solution). the primary endpoint was safety. the secondary efficacy endpoints were median percentage change from baseline in drop and total seizure frequency. results: overall, % ( / ) of eligible patients with lgs entered the ole. median follow-up was weeks ( d to wks); patients ( %) withdrew. mean age: years; % ≥ years; % male. baseline median seizure frequency/ days: drop seizures; total seizures. during the extended follow-up, the incidence of adverse events (ae) was %; serious aes %; aes leading to discontinuation %. most common aes (≥ %): diarrhoea, convulsion, pyrexia, somnolence, vomiting, upper respiratory tract infection, and decreased appetite. aes of alanine aminotransferase increased occurred in % of patients. there were deaths; none deemed treatment-related by the investigator(s). median percentage reductions in seizure frequency ( -wk windows over wks) was - % for drop seizures and - % for total seizures. conclusions: long-term treatment with add-on cbd in patients with lgs produced sustained seizure reductions, with no new safety concerns. poster no. management of status epilepticus in children with dravet syndrome jaa holland, u rajalingam paediatrics, hinchingbrooke hospital, huntingdon, uk objective: status epilepticus is reported to be the second greatest cause of mortality in children with dravet syndrome. we aimed to review the evidence on convulsive status management in children with dravet syndrome to guide local practice. methods: literature review. results: pubmed search using search terms 'dravet' or 'scn a' and 'status epilepticus' returned results, of which were relevant. only one of these articles presented specific data on reported effectiveness of medications used in acute seizure management; this was based upon retrospective questionnaire data and defined status epilepticus as seizures lasting minutes or longer. here, the most efficacious agents reported to terminate such seizures within minutes were intravenous barbiturates ( of patients) and benzodiazepines ( of patients). rectal benzodiazepines, chloral hydrate and intravenous phenytoin or lidocaine were reported as less effective. the remaining articles presented expert and consensus opinion, all advising early administration (some at seizure onset) of buccal or intravenous benzodiazepines. provision of rescue medication for home use, with individualised plans, is recommended. one author advocated giving three doses of benzodiazepines sequentially. an article summarising a consensus panel described sodium valproate as a preferred second line option where benzodiazepines are ineffective, but there was no overall agreement on other possible medications. several articles advised caution in using phenytoin in acute seizure management. one source discusses possible harm from high dose barbiturates. conclusions: status epilepticus management for children with dravet syndrome should feature early, rapidly acting benzodiazepine administration. for second line treatment, phenytoin and barbiturates are commonly used in 'standard' status epilepticus management protocols, but there are potentially concerns around their use in this patient group. these concerns, however, appear largely theoretical. in the absence of evidence favouring a specific management protocol, individualised care plans should be designed with involvement of patients and their carers. poster no. zx (low dose fenfluramine hydrochloride oral solution) significantly reduces frequency of generalized tonic-clonic seizures in dravet syndrome: pooled analysis from two phase clinical trials jh cross , a gil-nagel , b gunning , d battaglia , k riney , g farfel , , a mistry , , b galer , , g morrison , , a gammaitoni , , k pagano , great ormond street hospital, london, uk; servicio de neurologia, hospital ruber internacional, madrid, spain; stichting epilepsie instellingen, zwolle, the netherlands; gemelli hospital, rome, italy; mater children's hospital, brisbane, qld, australia; zogenix, inc and int, emeryville, ca, usa; zogenix, inc and int, maidenhead, uk objective: zx (low dose fenfluramine hcl oral solution) significantly reduced the frequency of convulsive seizures in patients with dravet syndrome (ds) in two phase clinical trials. we conducted a pooled analysis of these trials to analyze the effect of zx on the frequency of tonic-clonic seizures (tcs), recently identified as a major risk factor for sudden unexpected death in epilepsy. methods: the frequency of generalized tcs and focal-to-bilateral tcs in patients with ds enrolled in one of two phase clinical trials of zx added to current antiepileptic drug regimens were analyzed. results: patients ( % male, mean age y) were enrolled and randomized to placebo (n= ), or zx . (n= ), . (n= ), or . (n= ) mg/kg/day. the median baseline monthly frequency of generalized tcs ranged from . to . /month in the four dose groups, and decreased during treatment by %, %, and % in the zx . , . , and . mg/kg/day groups, respectively, and by % in the placebo group. focal-to-bilateral tcs were experienced by fewer patients and had a median baseline frequency of . to . / month. during treatment, median percentage reductions in focal-to-bilateral tc frequency were %, %, and % in the zx . , . , and . mg/kg/day groups, respectively, and % in the placebo group. most common adverse events included decreased appetite, diarrhea, and fatigue. no valvular heart disease or pulmonary arterial hypertension was seen in any participant at any time. conclusions: zx substantially reduced the frequency of tcs. zx may be an important, effective new treatment option for ds patients. objective: mutations affecting tbc d have been associated with an expanding spectrum of phenotypes including developmental delay, hearing impairment, doors syndrome and a range of epilepsies. a number of different movement disorders, including ataxia, spasticity and episodic paroxysmal dystonia have also been described. here we report two unrelated patients with biallelic tbc d variants, in whom exerciseinduced dystonia was a major disease feature. methods: both patients were diagnosed through whole-exome sequencing. clinical information was obtained by a review of the medical notes, clinical correspondence and available video footage. results: both patients were found to have compound heterozygous mutations in tbc d , associated with an episodic dystonic/dyskinetic movement disorder reliably triggered by exertion. in the case of patient , exertion of specific body parts induced specific localised symptoms: for example, singing would precipitate orolingual dyskinesia. both girls experienced truncal dystoniaspecifically, lateral flexion of the trunkbrought on by prolonged walking. both girls also had epilepsy; of note, the exercise-induced movements and postures were captured on eeg and had no ictal correlate. conclusions: although tbc d mutations are an established genetic cause of epilepsy, our study further confirms that not all paroxysmal events in people with tbc d mutations are epileptic in nature. tbc d should be included in the genetic differential diagnosis of patients with complex neurological syndromes associated with paroxysmal exercise-induced dyskinesia. objectives: heterozygous de novo rhobtb mutations have recently been reported in developmental and epileptic encephalopathy, but the associated movement phenotypes are not fully delineated. in order to better define the expanding phenotype and movement disorder in rhobtb -related disease, we report a series of unrelated patients presenting with complex movement disorders as well as epilepsy and developmental impairment. methods: cases were identified both in the uk (through the neurogenetic services at great ormond street hospital and the national hospital for neurology and neurosurgery, london), and from international collaborating centres. data were collected retrospectively by the patients' clinicians, using a standardised proforma. results: nine individuals were identified, aged from to years. / had epilepsy. of these, / had achieved seizure freedom at their last review. the commonest seizure types were focal onset with impaired awareness and/or focal to bilateral tonic-clonic seizures. / also had a paroxysmal movement disorder, which included hemiplegic or asymmetrical episodic weakness in / , generalised dyskinesia in / , episodic focal dystonia in / and episodic ataxia in / . all individuals affected by a movement disorder had at least two different types of episodes. movement disorders improved significantly after treatment with carbamazepine in three children. cognitive ability varied from average to severe intellectual disability and in all but one case, developmental delay predated the onset of epilepsy. conclusions: rhobtb mutations cause a complex neurological phenotype associated with both epileptic and non-epileptic paroxysms. paroxysmal events occurring in people with known rhobtb mutation should therefore not be assumed always to be epileptic in nature. our study confirms that a wide variety of movement disorders are reported, including some which fall within the spectrum of alternating hemiplegia of childhood (ahc). rhobtb should thus be considered as a potential gene for ahc, other complex movement disorder phenotypes and epilepsy-dyskinesia syndromes. poster no. evaluating seizure recognition and the use of electroencephalography in the paediatric intensive care unit objective: in the paediatric intensive care unit (picu), seizures are challenging to detect given patient complexity, comorbidity and sedation. this has led to both over-and under-treatment of seizures. there is growing literature on the use of continuous electroencephalography in picu, considered gold standard but not universally available, but little on standard electroencephalography (eeg). this study aims to investigate the indications for eeg requests, their efficacy and the use of antiepileptic drugs (aed) in picu, hypothesising a difficulty in clinically differentiating between epileptic and non-epileptic events and suboptimal use of aeds. methods: this retrospective study examined eeg reports over years at a tertiary picu. data was collected on participant characteristics, eeg indications and findings and aed use. results: eeg reports from participants were included. median age was months (iqr mo- y mo). indications for eeg (often multiple per eeg) included suspected clinical seizures ( %), suspected subclinical seizures ( %), prognostication ( %) and suspected encephalopathy ( %). % of participants with suspected seizures were sedated and % of all participants were encephalopathic. clinical episodes suspected to be seizures were captured in / eegs. only % of these were eeg-confirmed seizures. captured movements shown not to be seizures are qualitatively described. % of patients with suspected seizures had electrographic seizures with no clinical correlate. most confirmed seizures were in participants without pre-existing epilepsy. antiepileptic(s) were changed prior to / captured events. seizures were present in % of these cases, while % had neither clinical nor electrographic seizure activity. / participants with confirmed clinical seizures had aeds changed. conclusion: it is challenging for clinicians to differentiate between seizure and non-seizure movements in picu. moreover, there are issues of over-medication and low event-capture rate with eeg. we propose a multidisciplinary education strategy and investment in ceeg to address these issues. introduction: glucose transporter deficiency syndrome (glut -ds) is a rare neurometabolic disorder causing impaired glucose transport into the brain. in the majority of patients, it is caused by an autosomal dominant heterozygous mutation in the scl a gene. ketone bodies generated by a ketogenic diet (kd) provide the brain with an alternative energy source and is gold standard therapy. we report our experience for our cohort of patients at royal manchester children's hospital. methods: retrospective case note review of patients with glut -ds at royal manchester children's hospital from to . results: patients - male, female. age range to years. average age at diagnosis was years months (range mo- y). there was a history of seizures in of patients with average seizure onset of years months. seizures types were absences ( / ), generalised tonic-clonic ( / ), myoclonic ( / ), myoclonic astatic ( / ), tonic ( / ) and focal to bilateral tonic-clonic ( / ). ketogenic diet was used in all patients for a range of months to years months. no significant adverse effects occurred that required discontinuation. six patients complying with kd are seizure free and not taking antiepileptic drugs (aeds). one of these patients had occasional tonic-clonic seizures with illness and loss of ketosis but has been seizure free for > months. five patients are non-compliant with kdtwo have good seizure control with aeds, potentially limiting motivation, and two (siblings) have a parent with glut -ds and learning difficulties. learning difficulties were reported in patients. other symptoms included ataxia ( / ), dysarthria ( / ), tremor ( / ) and dystonia ( / ). one patient presented with episodic hemiplegia. conclusions: patients with glut -ds are a heterogeneous group leading to challenges in diagnosis, management and prognosis. ketogenic diet has been effective in managing this cohort but compliance was a limiting factor. objective: to conduct a survey regarding the management of relapse in children epilepsy in following weaning off aeds. methods: we conducted an online survey in the east of england (eoe) via the eastern paediatric epilepsy network (epen) regarding the management of relapse in children epilepsy after weaning aeds. epen is a network of paediatricians and nurse specialist with eoe who manage lead in management children with epilepsy within all the dgh's in the region. the questions in the survey asked about various aspects of management of patients after relapse, including the choice of anti-epileptic medication restarted, if started, any further investigations undertaken, and finally, the length of aed treatment before a second attempt at weaning might be considered. results: we received responses from paediatricians in dgh's across eoe. there was a large degree of variation in the responses to all of the questions in the survey. the frequency and semiology of seizures on relapse seemed to play a key role in decision making, as did the thoughts and views of the family and patient themselves. it was interesting to note there was a variation in response to whether any further investigations would be undertaken and if these were deemed necessary. most clinicians responded that they would continue aeds for another years before attempting weaning again. conclusions: there is variability in the management of epilepsy relapse in the eoe and we suspect that this may also be the case nationally. to investigate this further, we would envisage extending the survey nationally, via open ukwhich is an organisation that links the various regional paediatric epilepsy networks across uk. this would enable establishing a standardized guideline for management of epilepsy relapse in the future. objective: de novo dominant mutations in dhdds were recently identified as a cause of developmental and epileptic encephalopathy. dhdds encodes dehydrodolichyl diphosphate synthase, which is essential for dolichol monophosphate synthesis and protein glycosylation. we report two half-siblings with a new pathogenic, maternally inherited dhdds missense variant, c. g>a(p.arg gln), identified through whole-exome sequencing. method: case note and literature review. results: sibling , aged years, presented at months with global developmental delay, hypotonia and frequent absences with eyelid myoclonia. from age , she developed atonic drop attacks, myoclonic seizures, tremor, ataxia and facial dyskinesia. dyskinesia and mobility deteriorated from age and she is now largely non-ambulant. severe learning disability with possible cognitive deterioration and insatiable appetite are also features. sibling , aged years, developed blank spells associated with eyelid flickering at months and atonic drop attacks aged . development delay is present, but progress is greater than her sibling. dyskinesia, tremor, ataxia and deterioration in mobility are features. neither is dysmorphic. eegs on both showed bursts of irregular generalised spike wave associated with head nods and eyelid flutter. photosensitivity was not shown but both were treated with anti-epileptic medication. mri scans are normal. clobazam and zonisamide improved seizure control in both. mother has mild learning difficulties, tremor and dyspraxia. she had generalised tonic clonic seizures, from age to years, well controlled with lamotrigine. compared to the six known cases in the literature, our report confirms atonic seizures and dyskinesia as important features of this disorder, in addition to common characteristics of myoclonic component to seizures, hypotonia and tremor. learning disability is of variable severity. conclusions: this is the first report of familial inheritance of dhdds related developmental and epileptic encephalopathy and describes variable severity of the phenotype within family members. the features described are consistent with those previously observed. objectives: to evaluate whether the duration of treatment has an effect on the relapse rate in children with cae attending a paediatric neurology centre in cyprus, and whether the eeg can be used as a prognostic tool. methods: electronic patient database review of patients with cae, who have discontinued treatment attending the paediatric neurology clinic between years - . results: fourteen patients with cae, off treatment were identified ( male). age at presentation ranged from to years (median . y). all patients underwent an eeg to confirm diagnosis and those who presented with seizures other than absences were excluded. twelve patients were treated with valproic acid (depakine) and with ethosuximide (zarontin). in , absences resolved on first line monotherapy, whilst were refractory requiring combination therapy. positive family history was present in (non-identical twins), attention deficit in , and learning difficulties in patient. all initial eegs were consistent with cae, patients also underwent an eeg post seizure control to confirm resolution. mean time to seizure cessation was . months, mean duration of treatment . years; patients discontinued treatment after year of seizure freedom. prior to withdrawing treatment all patients had an eeg (normal , mildly abnormal with brief generalised discharges , photosensitivity , brief electrographic absence ). relapse occurred in patients who required re-instigation of treatment. mild abnormalities on eeg prior to coming off treatment did not correlate with a higher relapse rate. there was no difference in relapse rate in patients on treatment for , or more years. patients were followed up for a mean of . years. conclusions: treating patients with cae for less than years does not affect relapse rate provided patients are seizure free, also confirmed by eeg normalisation, which may be used as an additional predictor. background: mutations in unc , encoding part of the unc -unc -nalcn channel complex, causes autosomal-recessive severe infantile encephalopathy, this is a rare case of profound global developmental delay with psychomotor retardation. only individuals have been reported to date. unc deficiency is characterized by hypotonia, strabismus, oral motor dysfunction, postnatal growth deficiency, and developmental delay. the majority of individuals do not learn to walk. all individuals lack expressive language. additional features can include nystagmus, extremity hypertonia, a highpitched cry, repetitive and self-stimulatory behaviours, constipation, clubfeet, joint contractures, and scoliosis. there is no loss of skills suggestive of neurodegeneration. case presentation: -year-old, with a recent confirmed diagnosis of unc gene mutation and microcephaly. she had profound global developmental delay, learning disability, bilateral squint with cortical blindness, seizure disorder, sleep apnoea, head drops, movement disorders, feeding difficulty, scoliosis and constipation. term baby with normal anti-natal history. induction of labour for iugr. good apgar, at birth but developed respiratory distress with cardiac problems. birth weight g. neurologically: floppy with reduced muscle tone and microcephaly. had a short neonatal admission and discharged with cardiac, endocrine, neonatal and neurodevelopmental delay follow-up. she had no spoken words and communicated by crying. she was only able to sit transiently and never walked. she was wheelchair bound with gmfcs, macs, cfcs and edacs level each, needing full -hour support from patents and carers. ddd study confirmed unc gene mutation, her cousin was also noted to have same gene mutation via exome sequencing and with similar clinical picture. conclusion: early diagnosis is key for genetic counselling for further children and ensuring global support as reported individuals span ages from birth to year. the diagnosis is established in a pro-band with developmental delay and hypotonia by identification of bi-allelic pathogenic variants in unc on molecular genetic testing. poster no. cognition and disease burden in scn a positive dravet syndromea -year follow-up study development, disease burden and sleep profile of patients with dravet syndrome. methods: this is a follow-up to a study previously involving ds patients with detailed developmental and clinical information available. participants completed a structured postal questionnaire on epilepsy severity and disease burden, the adaptive behavioural assessment system (abas- ), the sleep disturbances scale for children, pediatric quality of life inventory (pedsql) and the strength and difficulties questionnaire. results: / from the original cohort were contactable and ( %) of carers completed the outcome measures. the developmental quotient at follow-up was significantly lower compared to the earlier study (p= . ), and % of affected individuals had a severe or profound learning disability. we observed the steepest decline in cognitive functioning in those that were youngest (age - y) at original study onset (p= . ). poorer developmental quotients correlated with early onset of initial developmental concerns (rs= . ; p= . ), later mobility problems (rs= . ; p= . ), higher levels of behaviour problems (rs= . ; p= . ) and worse pedsql scores (rs= . ; p= . ). carers health and wellbeing was negatively affected in % of cases and in %, at least one of the two carers quit their job due to their child's illness. sleep problems as measured by total sleep scale score were reported in % of patients, whilst % had at least one abnormal sleep scale category. only % of individuals with abnormal sleep scores received treatment. rs=spearman rho correlation coefficient. conclusions: this study highlights the ongoing cognitive decline in ds, particularly affecting younger patients, alongside often untreated sleep problems and a significant disease burden on primary carers. with new therapeutic opportunities on the horizon, early interventions appear crucial to avert the observed severe cognitive decline. poster no. forced normalisation as a factor in behaviour deterioration on the ketogenic diet e hassan , vj whiteley , , hj tan department of neurology, royal manchester children's hospital, manchester, uk; therapy and dietetics, royal manchester children's hospital, manchester, uk; school of health and society, university of salford, salford, uk introduction: there have been a number of reports that demonstrate a correlation between improved seizure management and deterioration of behaviour with psychosis in adults and children. forced normalisation is a concept where there is deterioration in behaviour when better seizure control is achieved with antiepileptic drugs (aeds) or epilepsy surgery. the ketogenic diet (kd) is a treatment option for children with refractory epilepsy with approximately to % showing at least % reduction of seizures and % of those patients reaching seizure freedom months after treatment. although forced normalisation has been discussed in literature following aeds and neurosurgical interventions, it has not been reported following the use of kd. cases: of the children that have commenced on kd over the last years at royal manchester children's hospital, . % responded to the diet (at least % improvement in seizures) and . % were non-compliant. we present patients under the care of the kd service, whose behaviour deteriorated on kd when seizure reduction was > %. the behaviour changes described by parents included poor sleep, unsettled, agitation, head-banging and shouting. five out of the six patients stopped kd treatment, with subsequent improvement in behaviour. conclusions: there are reports that patients on the ketogenic diet with seizure freedom show improvement in their behaviour, unlike our small cohort whose behaviour deteriorated. forced normalisation has been explored in paediatric patients as a cause for behaviour deterioration following surgical and medical management for intractable seizures. the associated factors of deteriorating behaviour have not yet been explored in depth with the ketogenic diet. objective: we wanted to determine how lacosamide was being used in children locally, and what their outcomes were at a year. methods: we undertook a registered, retrospective, clinical audit using hospital electronic records. we ascertained every patient aged < years who had been dispensed lacosamide january -january . the electronic health records were reviewed, and data collected using a standard proforma, including: patient demographics, age of seizure onset, seizure type, ecg and mri findings, baseline seizure frequency, seizure frequency , , and months on lacosamide, maximum dose prescribed (mg/kg/day), and adverse effects at , , and months. results: / ( %) patients were male, the median age was years (range mo to y), with a mean age of onset of years (range mo to y). / ( %) had epileptiform activity on eeg and / ( %) had an abnormal mri. / ( %) had focal seizures. / ( %) had a minimum of one seizure a week. / ( %) had previously tried or more antiepileptic drugs (aeds), and / ( %) had drug resistant epilepsy prior to starting lacosamide (already failed previous aeds). all patients had lacosamide alongside another aed. the mean daily dose of lacosamide was . mg/kg/day (range . - . ). at months, / ( %) of patients reported a > % reduction in seizure frequency. / ( %) remained on lacosamide year after starting, and / ( %) experienced an adverse side effect. conclusions: in this local audit, lacosamide was mostly prescribed for drug resistant epilepsies and was used in polytherapy. a third of patients saw a significant reduction in seizure frequency on lacosamide, although some were also started on other treatments during this period. most patients remained on lacosamide after months, and about in experienced one or more adverse side effect. cacna a is a large gene which encodes for the alpha subunit of a neuronal ion channel and it is expressed widely throughout the central nervous system (cns). pathogenic variants in this gene have been associated with many phenotypes. most commonly episodic ataxia type (ea ) and spinocerebellar ataxia type (sca ). rarer phenotypes include, familial hemiplegic migraine, paroxysmal tonic upgaze, epilepsy, and intellectual disability with autism. here we present the case of an month old girl who presented with new onset paroxysmal abnormal eye movements during an intercurrent illness. the referring clinicians felt these episodes may be epileptic. however, an electroencephalogram (eeg) captured these movements which were non-epileptic downbeat nystagmus. all other initial investigations including cerebrospinal fluid glucose and neurotransmitters were normal as was her neuroimaging. over the next year her nystagmus became constant. she had otherwise normal development. at months her gait was noted to be abnormally unsteady and broad based (even accounting for age). the nystagmus and ataxia changed in severity from day to day, she could have to more severe days followed by to better days, they never completely resolved. she had no family history of abnormal eye movements or ataxia. subsequent genetic testing revealed a cacna a c. g>a p(glu lys) missense variant described only twice previously in ea , both with very different phenotypes to our patient. neither of her parents carried the same genetic variant. this case is the first reported case of this cacna a variant presenting as downbeat nystagmus followed by ataxia. both her age of presentation and her initial presenting features are very different to the typical phenotypes associated with this gene. it broadens the phenotype of cacna a, and also broadens the differential diagnoses associated with abnormal eye movements in infancy. the importance of following up as yet undiagnosed patients who may go on to develop new and revealing symptoms is highlighted. objective: to undertake a questionnaire-based survey retrospectively exploring parents'/carers' recall of, and views on, the safety and risk advice given at the time of their child's epilepsy diagnosis. methods: questionnaires were distributed throughout scotland via scottish paediatric epilepsy network (spen). parents'/ carers' of to -year-old children were asked to complete the questionnaire prior to their seizure clinic appointment. results: questionnaires were suitable for inclusion. seizure burden was evenly distributed: % < seizure/month, % > seizure/month, % > seizure/week and % had absences only. respondents could recall post-diagnosis information being provided on: water safety ( %), taking medication regularly ( %), sports/activities ( %), seizures in sleep ( %), first aid ( %), prolonged seizures ( %) and/or sudep ( %). there was no statistically significant difference in the duration of epilepsy diagnosis between those who could recall information being given (m= . y, sd . ) and those who could not (m= . y, sd . ; t test p= . ). the majority of information was given via clinic discussions ( %). % received written information, % directed to websites and/or independent search ( %). most information was 'just right' ( % water safety, % on taking aed regularly, % on sports/activities, % on seizures in sleep, % on first-aid for seizures). approximately % of respondents want more information on seizures in sleep, water safety and sports/activities. % of respondents felt worried following information about seizures in sleep, % about prolonged seizures and % regarding sudep. conclusions: a substantial proportion of parents'/carers' do not recall receiving safety information on epilepsy despite this being standard practice through spen. this appears to be unrelated to the duration of their child's epilepsy. repeated timely reinforcement may be of benefit. a high proportion of parents'/carers' felt concerned following information provided on nocturnal seizures, prolonged seizures and sudep. this should be recognised with support in place for further discussions. poster no. seizure outcome in responsive vagus nerve stimulation therapy in children and young people v rasiah, n barnes, s carter, k das, r robinson, z tahir, s varadkar great ormond street hospital for children nhs foundation trust and ucl gosh institute of child health, london, uk aim: vagus nerve stimulation (vns) therapy is an established treatment for pharmacoresistant epilepsy. newer responsive-vns (rvns) systems use ictal-tachycardia detection as a biomarker of seizure onset and automatically deliver additional stimulation on detection to abort the seizure. we reviewed the seizure outcomes in children and young people (cyp) implanted with rvns at great ormond street between to . methods: data were collected prospectively on patients who had an aspiresr â rvns inserted during time period of to . reduction in seizure frequency and severity, wean of medications and treatment complications or side-effects were assessed at time-points of year, months, years and years post-implantation. results: cyp (mean age . y) had rvns inserted. at year, % ( / ) had a positive response graded as > % reduction in seizure frequency or severity (i.e., duration), % ( ) had benefit though < % benefit, and % ( ) of cyp were non-responders. this increased at months to % ( / ) of children showing response > %, a further % showed response % and only % ( / ) non-responders. response was over-all sustained, with response lessening in only children between months and years. reduction of medication burden was achieved in % ( / ) (not attempted in all cyp). no patients achieved seizure freedom. replacement of vns from an older model to rvns showed further benefit. complications were infrequent: % ( / ). device removal for infection was required in one child of small body size; successful replacement was possible within the year. conclusions: vns is a useful treatment option for cyp with pharmacoresistant epilepsy. seizure outcomes with rvns in cyp are better than with standard vns. response is sustained. benefit may not be seen by year; therapy should be continued until at least months. in our patients who responded later than -year, further optimisations of duty cycle and current were made. replacement of older vns. devices with rvns led to additional benefit. these findings are consistent with reported outcomes from adult series, though seizure freedom is not seen in cyp. in our centre, cyp who seemed to benefit most were those whose epilepsy was of structural aetiology and those with focal seizures, although our numbers were not large enough to assess the significance of this. poster no. atp a mutation in twins presenting with apnoeic episodes, suspected seizures and possible dystonic events objective: we report the case of monochorionic diamniotic twins presenting at the age of months with infantile seizures and apnoeic episodes. the eiee gene panel revealed a mutation in the gene atp a , supporting the clinical diagnosis of alternating hemiplegia of childhood (ahc). methods: case report. results: twin r presented with staring episodes, eye deviation and tonic posturing of limbs. episodes occurring mainly in clusters, affecting either side and requiring rescue medications for termination. profound apnoeic episodes needing resuscitation were also noted. twin s presented few weeks later with a very similar presentation. developmentally making satisfactory progress with twin r showing only very mild delay. the array cgh from twin r was normal. several investigations were performed including two normal standard eegs, a normal sleep eeg, a normal ecg, an echo showing a small pfo and an mri scan demonstrating a left sided mesial temporal lobe sclerosis. similar mri findings were reported in twin s. investigations such as urine organic acids and amino acids, plasma amino acids, carnitine, acylcarnitine, transferrin glycoforms, mucopolysaccharidosis screen, ammonia and lactate were all normal. pyridoxine was tried with no improvement, levetiracetam was added and afterwards changed to carbamazepine. sodium valproate was commenced eventually after an episode of prolonged clinical seizure. the eiee gene panel revealed a de novo atp a mutation in both twins. flunarizine was commenced following this result. a video telemetry managed to capture both epileptic and non-epileptic episodes in twin r. the epileptic episode was characterised solely as apnoeic episode due to a left temporal seizure activity spreading onto the opposite hemisphere which is concordant with the imaging finding of left mesial temporal sclerosis. conclusions: knowledge of the atp a mutation allowed clinical correlation of a diagnosis of ahc, matching the wide clinical spectrum of ahc including paroxysmal dystonia and epilepsy. poster no. epilepsy in a child development centre population pc kenyon, njv cordeiro, gl duffy rainbow house child development centre, irvine, ayrshire, uk objective: to assess all the cases in a child development centre (cdc) population with epilepsy, to enable characterisation of the caseload. methods: all case notes of children with an epilepsy diagnosis coded on the cdc database were retrospectively reviewed for demographic, investigation and treatment data. results: children were identified. % were diagnosed before a year of age, and over half before their third birthday. % of patients had an eeg, and of these, % had an abnormal eeg. % had genetic testing performed, and of these, % had a genetic cause of their epilepsy identified. % had an mri scan, and of these, % had a structural cause for their epilepsy identified. % had global developmental delay, and % had a diagnosis of learning disability. one third have a diagnosis of cerebral palsy, % have autism spectrum disorder, and % have a hemiplegia. % are seizure free, the majority of whom have their epilepsy controlled with one medication. % had adherence concerns identified. conclusions: compared to a general paediatric epilepsy clinic, this group of children were diagnosed earlier in life, had higher rates of genetic or structural causes identified, and were less likely to be seizure free. results: case . a -year-old with autism spectrum disorder (asd) developed hand waving in front of her face in bright light from years. multiple myoclonic seizures occurred with screen use and her family live in complete darkness. eeg demonstrated photosensitivity, generalised spike-slow wave after hand waving and - . hz spike-wave with myoclonia. clonazepam has been commenced. case . a -year-old with learning difficulties and a family history of generalised seizures presented aged years with forehead rubbing leading to loss of part of her eyebrow. eeg showed photosensitivity and the generalised spike-wave of absences and eyelid myoclonia (em). sodium valproate was used but replaced with lamotrigine due to weight gain. case . a -year-old with a family history of generalised seizures presented aged years with hand waving in front of her face, requiring her nursery to provide a dimly-lit setting. eeg demonstrated generalised polyspikewave, -hz spike-wave and myoclonia with photic stimulation. lamotrigine was ineffective and replaced with sodium valproate. case . an -year-old with likely asd developed hand waving in front of her face in bright light aged years, triggering generalised tonic convulsions (gtc). she had a non-induced gtc in dappled sunlight. there was on-going anxiety and thoughts of self-harm. eeg showed photosensitivity and bursts of spikes-polyspikes. lamotrigine was ineffective; seizures stopped with sodium valproate. conclusions: the self-induced seizures of sunflower syndrome are difficult to treat and are associated with physical, psychological and social impairments. sodium valproate is the most effective medication which may be problematic in this predominantly female patient group. what are the information needs of parents whose child is diagnosed with glutaric aciduria type to help preserve neuro-developmental outcome? objectives: to assess the information needs and support of parents at the time of diagnosis of ga in their child, and how to support them in preventing metabolic decompensation and preserving neuro-developmental function. methods: a focus group with five parents was conducted using a topic guide to direct the discussion, which was recorded and fully transcribed. data were analysed using thematic analysis. two researchers were involved in initial coding of data and key analytic decisions. results: two main themes were identified. 'understanding the condition' explored parent's needs to understand the scientific complexity of ga and to be aware of the 'worst case scenario' associated with loss of metabolic control, and brain injury. parents reported clinicians did not give then enough information on the ga , and were forced to use other information sources, sometimes seeking out scientific papers. information on managing crises was insufficient, with parents not understanding what the doctor meant about commencing the emergency regime when their child was 'sick'. parents reported living in terror of their child experiencing metabolic decompensation and permanent brain injury. 'managing the condition' explained how parents coordinated and controlled the involvement of other carers and outlined parents' need to be active partners in medical management to feel in control. parents wanted to know the results of regular biochemical tests for reassurance, but found they were not easily accessible. parents could not leave their child in the care of another adult because they did not have sufficient knowledgeable about ga or were known to 'cheat' by offering the child food they should not have. the transition into school was a particular challenge. conclusions: the study highlights the importance of addressing parents' initial and ongoing informational needs so they can fulfil their role and protect their child from metabolic decompensation and permanent brain injury. poster no. normal transferrin isoelectric focusing in a child with cog related congenital disorder of glycosylation objectives: congenital disorders of glycosylation (cdg) are a large group of rare multisystem diseases caused by defective linkage of oligosaccharides to newly synthesised proteins or lipids. several cdg subtypes are the result of mutations in subunits of the conserved oligomeric golgi (cog) complex. this includes cog -cdg, an autosomal recessive disorder caused by pathogenic variants in the cog gene. in the two cases previously reported transferrin isoforms were abnormal, consistent with defective n-glycosylation. methods: we describe a -year-old female born to non-consanguineous parents. she presented with severe global developmental delay, dysmorphic features, postnatal progressive microcephaly, complex epilepsy, rhizomelia, spastic quadriplegia, and feeding problems from early infancy. results: mri brain showed global cerebral atrophy, predominantly supratentorial, with relative cerebellar sparing. trio exome sequencing and analysis identified compound heterozygous cog variants in the proband, a maternally inherited pathogenic splice site variant c. + g>a and a paternally inherited likely pathogenic splice site variant c. + g>a. messenger rna analysis showed that the c. + g>a variant caused aberrant splicing, with skipping of exon and the introduction of a premature stop codon in exon , likely to result in nonsense mediated decay. analysis of transferrin isoforms was normal (by both isoelectric focussing and mass spectrometry). since cog -cdg also affects o-glycosylation apolipoprotein ciii (apociii) isoelectric focussing was undertaken, however this too was normal. conclusions: transferrin and apociii isoelectric focusing are screening tests for n-and o-glycosylation defects. however, both have their limitations and some cases of cdg have normal transferrin or apociii glycoforms escaping those screening tests. this is the first case of a patient with cog -cdg with normal biochemical markers to be described. this case also demonstrates the diagnostic power of next generation sequencing for rare metabolic disorders, where the biochemical screening may be inconclusive. poster no. developmental delay in a young infant with nonclassical combined malonic and methyl malonic aciduria (cmamma) caused by homozygous missense mutation in acsf gene kd dayasiri , eg goh , sk kodagali , jb baruteau , ga anand oxford university hospitals nhs foundation trust, oxford, uk; great ormond street hospital, london, uk introduction: acylcoa synthetase family member (acsf ) activates malonylcoa and methymalonylcoa into their respective thioesters. acsf deficiency causes non-classical cmamma, a rare inborn error of metabolism characterised by presence of methyl malonic acid in higher concentrations than malonic acid in urine. the reversal is seen with classic cmamma caused by malonylcoa decarboxylase deficiency (mcd). case report: -and-a-half-month old male infant second born to consanguineous south asian parents presented with severe failure to thrive and recurrent vomiting. his older sibling who had failure to thrive and neuro-developmental delay died at months without a genetic diagnosis. initial blood tests revealed metabolic acidosis, pancytopenia and coagulopathy. neuroimaging was unremarkable. subsequent evaluation revealed normal levels of methionine, homocysteine and red cell folate. significant methylmalonic aciduria with mild malonic aciduria without evidence of other abnormal metabolites (propionyl-coa metabolites: hydroxypropionate, and methylcitrate or tiglylglycine) in urine suggested the diagnosis of non-classic cmamma, confirmed by homozygous missense variants in acsf gene revealed by trio-exome sequencing. neurodevelopmental assessment at months revealed global developmental delay with general hypotonia; gross motor ( - mo); fine motor ( - mo); speech ( - mo) and social (under mo), and without any regression. carnitine was supplemented to avoid secondary depletion caused by the excretion of mma. parents were advised to avoid prolonged fasting and to provide emergency regimen (powdered carbohydrate drink mix) in the event of acute deterioration. conclusions: this report describes an unusual paediatric presentation of non-classic cmamma. urine organic acids allows identification of increased ma and mma excretion and highly suggestive of the diagnosis, thus avoiding additional investigations determination of urinary mma/ma ratio can help differentiating between classical and non-classical forms. methods: we conducted retrospective case note analysis of the five paediatric cases with confirmed diagnosis of the late onset pompe disease, referred to the highly specialised metabolic service. results: three of five patients (current age - y) presented with delayed motor milestones in early childhood (mean age: . y). one patient initially presented with episodes of thigh pain and high ck. in addition, when years he re-presented with recurrent abdominal pain with high ck. the remaining one presented with muscle pain upon exercise with high ck. all apart from one had muscle weakness affecting limb girdle muscles and axial muscles. the remaining one presented with proximal muscle weakness by the age of years. all patients remained ambulant, one developed scoliosis and two were on non-invasive ventilation. cardiac involvement as ventricular dysfunction requiring targeted treatment was observed in one. pathology showed vacuolated deposits in three patients and non-specific myopathic changes in one. four are on enzyme replacement therapy (ert) and tolerated well. conclusions: late onset pompe disease is a multisystem disease and should be considered in cases of isolated respiratory problems, lower back pain, rigid spine, and myopathy or exercise intolerance with elevated serum ck if these symptoms cannot be attributed to another disorder. poster no. delay in diagnosis and misdiagnosis of ataxiatelangiectasia: a systematic review pubmed, scopus). the cochrane library was also searched. the search protocol is available. the inclusion criteria were: all dates, all languages, all ages, human participants and clinical relevance. the exclusion criteria were: no reference to ataxia-telangiectasia within the article, not an original article, animal studies, article not clinically relevant. results: search returned articles; titles and abstracts were reviewed after removing duplicates. full text review includes articles of which case series and case reports were identified ( , exclusions; , articles not found or not accessible). mean age of first sign or symptom of a-t in cases reviewed to date was . months (range - d to mo). the mean age of diagnosis in cases in which it has been reported was . months (range - d to mo). there was a mean time of . months from presentation to clinician, to diagnosis of a-t (range - to mo, median mo) in the cases in which this was reported. / ( . %) cases had a documented alternative diagnosis prior to the diagnosis of a-t. / ( %) of these children were incorrectly diagnosed with cerebral palsy and / ( %) with hyper-igm syndrome. the mean delay from incorrect diagnosis to a diagnosis of a-t was months with the longest delay months. conclusions: this study is the first comprehensive systematic review of scientific literature on ataxia-telangiectasia. we aim to describe the natural history of the condition and, along with results from the natural history of a-t (n-hat) study, systematically define, where possible, the conditions presentation, course, and prognosis. ( %) people with a-t presented with gait ataxia or disturbance, and / ( . %) with truncal ataxia. the most common presenting feature in cases without ataxia were developmental delay, or regression, and choreoathetoid movements. the second most common neurological presenting sign was dysarthria in / ( . %) cases, and at least of these had no associated ataxia. dystonia was a presenting sign in / ( . %) cases, including / ( . %) with no associated ataxia. / ( . %) initially presented with no neurological signs or symptoms. conclusions: this study is the first comprehensive systematic review of scientific literature on ataxia-telangiectasia. these results show that . % of people with a diagnosis of a-t presented initially with at least one neurological sign or symptoms. this completed review will lead into the natural history of a-t (n-hat) study, a longitudinal, retrospective and cross-sectional study. the role of serum oxysterol in the diagnosis of niemann pick c m alcheikh, g connolly, n cluskey, s osullivan royal hospitals belfast health and social care trust, belfast, uk introduction: neimann pick c is a neurovisceral disease that is caused by cellular cholesterol trafficking disruption. historically, the diagnosis of niemann pick c was made using filipin staining and skin fibroblast cultures. recently genetic testing of npc an npc genes are available. mutations of either gene also affect cellular trafficking of cholesterol and detecting oxidative cholesterol metabolities can also be diagnostic of nieman pick c. serum oxysterol can be used as a first line test with subsequent genetic confirmation and has a positive predictive value of > %. methods: we present a case of an -year-old boy who was referred to genetics initially with absence of up gaze, severe restricted downward gaze, developmental delay, regression of skills and frequent falls. in the last year his parents and school observed progressive deterioration of his symptoms with gelastic cataplexy, markedly decreased tone, increasing difficulty with memory loss and slurred speech. these symptoms are strongly suggestive of niemann pick c disease and oxysterols were requested which showed elevated oxysterol level of . ng/ml (normal range . - ). he was started on miglustat. genetics confirmed the diagnosis. results: overall the child's parents report that since commencing the miglustat he is more confident and they have recently seen him hop and skip which they haven't seen in quite a while. conclusions: oxysterol is suitable biomarker for neimann pick c disease and can be used as first line with the genetic confirmation of gene npc and npc at later stage. as modifying treatment with miglustat is available it is important to attempt diagnosing the condition as early as possible and oxysterol level can be used as screening test for neimann pick c when clinically suspected. introduction: biotinidase deficiency is a rare autosomal recessive inborn error of biotin metabolism. biotinidase catalyses biocytin to biotin, a deficiency of which can present with neurological symptoms including hypotonia, seizures, feeding difficulties, lethargy, optic atrophy, and sensorineural deafness. case: a -week-old female presented with a -week history of seizures and developmental delay. examination revealed generalised and axial hypotonia and delayed smile. she continued to have seizures despite initial treatments including levetiracetam and carbamazepine. mri brain was normal and initial interictal eeg on day post admission revealed no significant abnormalities. ambulatory eeg on day showed a focal onset epileptic seizure with sharp and slow wave activity originating predominantly from the left occipito-parietal region. normal investigations included paired plasma and csf glucose, lactate and culture, csf neurotransmitters, microarray and epilepsy gene panel. on day post admission her biotinidase result was reported showing no activity. biotin was commenced at mg once daily and her seizures abruptly stopped. she was discharged home on day and weaned off levetiracetam and carbamazepine. her development was normal at -month follow-up. genetic testing was declined by the family. discussion: biotinidase deficiency can present from the neonatal period up to years of age with a mean age of . months. in recent years our understanding of pathogenic changes in the biotinidase gene has increased through sequencing for novel mutation. this has important implications for families and consideration should be given to offering affected families genetic counselling. treatment is available with oral biotin that rapidly improves symptoms, with seizures usually resolving within days and other symptoms showing improvement within weeks. objective: we present a previously well -year-old boy with a known m. t>c mutation experiencing weeks of vomiting, lethargy and exercise intolerance. method: he was mildly dehydrated, fully consciousness but tachycardic and hypotensive. his ph was . with be - . , hco . and lactate of . . electrolytes, fbc and inflammatory markers were normal. he was admitted to picu for fluid management and sodium bicarbonate. tachycardia persisted during the first hours though he remained stable. he had a good urine output, was on non-invasive monitoring and an echocardiogram was normal. his gas lactate ranged from . to . . the following day he deteriorated with kussmaul respirations, tachypnoea, increased tachycardia and hypotension. venous blood revealed a ph . , pco . hco . be - and lactate . . he became unresponsive with refractory hypotension and multiorgan failure. arterial blood showed a ph . , pco . and a lactate > with indeterminable be or hco . for over hours he had a blood lactate level of > . rhabdomyolysis and acute kidney injury occurred with a ck of > requiring haemofiltration. encephalopathy, with multiple white matter microhaemorrhages on mri brain, and acute liver failure, with thrombocytopenia and coagulopathy, ensued. multiple inotropes were required. the prognosis was very guarded. off sedation he was unresponsive, apnoeic and areflexic however an eeg showed an alpha rhythm which prompted on-going heroic efforts. he required prolonged haemofiltration, ventilation and inotropes with days intensive care. results: the patient made an astounding recovery. he required month of neurorehabilitation and returned to his cognitive baseline, achieving a grades at gcse months later. liver and renal dysfunction resolved. conclusions: this case demonstrates that mitochondrial metabolic crises in melas can be severe and result in profound acid-base derangements. our patient was expected to not survive but uniquely did so without significant neurodisability. neuronal ceroid lipofuscinosis in children from central africa gl fisher, n shah, p watts, ja te water naude noah's ark children's hospital, university hospital wales, cardiff, uk objective: the effective and rapid diagnosis of neuronal ceroid lipofuscinoses (ncls) has become more relevant with the advent of disease-modifying treatments. some ncls have a more stereotyped clinical presentation: we describe two cases in a non-consanguinous family, originally from the democratic republic of the congo, with variant ncl. methods: retrospective case series. results: the index case was initially diagnosed with a focal epilepsy: on review this child had myoclonic seizures in the context of a slow developmental decline, with mild spasticity. ophthalmology was not diagnostically helpful, and a putative diagnosis of ncl was suggested by lymphocyte inclusions. neither enzyme nor dna analysis was available at that stage, although dna was retained. a brother presented with nystagmus and visual inattention in : examination showed myoclonic jerks with a bull's eye maculopathy and an abnormal peripheral retinal vascular leak. mri imaging showed some element of cerebellar atrophy, which on review was also the case with his brother's scans. some lymphocytes ( %) contained fingerprint bodies, suggestive of variant ncl. this was confirmed by dna sequencing which was consistent with a diagnosis of mfsd /cln -related ncl. the identical dna alteration was also found in the index case. conclusions: ncl is not described in children from central africa: the presentation, investigations and laboratory findings and evolution are consistent with that for other children with variant ncl. obesity screening of patients affected by duchenne muscular dystrophy (dmd) in a tertiary paediatric neuromuscular centre and the effectiveness of metformin use in weight control in those with confirmed insulin resistance m neocleous , s spinty , r madhu , p dharmaraj , c degoede , k cooke , c greaves alder hey hospital, liverpool, uk; royal preston hospital, preston, uk objective: to assess whether patients affected by duchenne muscular dystrophy (dmd) who are currently followed up in alder hey hospital, uk are receiving obesity screening when clinically appropriate. to assess whether metformin use in those who are insulin-resistant, has been effective in controlling weight. methods: using the neurology department records, a list of patients with dmd currently under our services and those transitioned to adult services in the last years, was generated. the patient record system, meditech, was used to collect patients' demographics, latest weight/height value and bmi. for patients classified as overweight/obese, completion of obesity screening was assessed as well as initiation of appropriate treatment (metformin). for patients on metformin, the following parameters were collected: weight pre and post-steroids, age of start of excessive weight gain, confounding variables and medications, weight/height/bmi at initiation of metformin and at -monthly intervals, side-effects, cessation of medication and reasoning. results: sixteen out of patients were found to be above the th weight centile. in patients, weight was at or more centiles above height. using the non-dmd standardised bmi classification, patients were identified as being overweight/ obese. patients received obesity screening; were found to be insulin resistant. of those were started on metformin. patients overall were started on metformin. of those exhibited overall weight loss. patients were found to have gained weight and patient showed weight increase up to months post-metformin initiation with subsequent weight loss. conclusions: there is a need for a validated and agreed bmi classification in dmd. screening for insulin resistance in this patient group should be considered for implementation as standard practice, especially if patient is classified as overweight/obese. a larger-scale study would be required to assess the effectiveness of metformin in this patient population. objective: niemann-pick disease (npd) is an autosomal recessive metabolic disorder with a prevalence of . to . / worldwide, marked by varying degrees of lipid storage and foam cell infiltration in tissues, associated with hepatosplenomegaly, pulmonary insufficiency or central nervous system involvement. npd type a and b are allelic disorders caused by mutations in the sphingomyelin phosphodiesterase- gene, smpd ( p . - . ), characterized by a primary deficiency of acid sphingomyelinase activity, resulting in an accumulation of sphingomyelin. in contrast to npd-a, npd-b is the milder, lateronset form, with no neurological involvement. in this paper, we report on three paediatric cases with npd-b who present an atypical phenotype marked by neurological involvement. methods: the three patients were diagnosed at the age of with hepatosplenomegaly. the first is a girl who presented psychomotor regression at the age of and epileptic seizures at the age of . she died at the age of . the second is an years old girl who presented growth retardation, kyphosis and neurodevelopment regression since the age of . the third is a years old boy with a mild phenotype marked by developmental delay and an aggressive behaviour. splenectomy was performed at the age of . results: genetic testing was performed, and all patients presented mutations of the smpd gene, confirming the diagnosis of niemann-pick type b. the c. t>g(p.trp gly) mutation was common in all cases. in addition, heterozygous mutations c. delt(p.ser alafs* ) and del c. _ del were found in the first and second case, respectively. conclusions: all cases present a complex phenotype, marked by psychomotor regression which is atypical for npd type b. the severity of the disease seems to be correlated to the genetic mutation-the most severe phenotype was associated with c. delt. further work is necessary to more clearly delineate genotype-phenotype relationship in npd. objective: acute encephalitis syndrome (aes) is a group of symptoms and signs, which help diagnose encephalitis. since there is no definite treatment for most, role of fluids seems crucial. therefore, the objective of our study was to describe the association of low admission weight and weight loss in the hospital (as clinical marker of dehydration) with outcome of patients of acute encephalitis syndrome. to describe the association between changes in weight and blood lactate levels (at admission and discharge as indicators of hydration and acid base status) and outcome in children with acute encephalitis syndrome. methods: all children aged month to years with fever and altered sensorium and/or new onset seizures from september to september attending kanti children's hospital, kathmandu, nepal were recruited. weight-for-age (wfa) using z score and serum lactate were assessed at admission and discharge. total fluid input and output was monitored daily. results: of the patients, % had low admission wfa or lost weight-after-admission (lwaa) (group a) and % no low wfa or didn't lwaa (group b). there was times risk of death and times risk of bad outcome (death or sequelae) in group a compared to b. bad outcome was significantly associated with less admission wfa, more fluid deficit, and trend for higher admission serum lactate. death was significantly more in those with low wfa, more lwaa, longer illness, more % dextrose and . normal saline, higher sodium and higher urea at admission. methods: we conducted a prospective cross-sectional study recruiting children aged between month to years attending kanti children's hospital, kathmandu, nepal with altered sensorium and two of the following: fever, seizure, focal neurological deficit, csf pleocytosis, electroencephalogram and computer tomography suggestive of encephalitis, over year. in these patients, ve was if csf cell count was < cells/ mm (lymphocyte predominance) and absence of non-viral pathogens in the csf or blood. bm was csf cell count > cells/mm (polymorph predominance) and csf protein > . g/l and csf/plasma glucose < %, and/or positive gram stain and/or bacterial culture. je was ve with ≥ units of anti je-igm in the csf and/or serum. all cns infections were defined as, suspected cases by treating clinician with or without fever with lp showing csf cells > /mm . results: out of , bm was found in %, je % and other causes in %. although who definition of aes was not significantly associated with all cns infections (p= . ), it was significantly associated with ve (p< . , sensitivity %, specificity %, ppv %, npv %) and bm (p< . , sensitivity %, specificity %, ppv %, npv %). conclusion: we validate who aes definition of bm and ve as a significantly useful screening tool for children with these diseases specially in resource poor settings, endemic areas and where confirmatory tests were not easily available. objective: the aim of this case series is to raise awareness of this autosomal recessive encephalopathic syndrome that presents after birth in the multi-ethnic population in england. although aicardi goutieres syndrome (ags) is rare, its importance lies in the fact that that its presentation may be mistaken for other neurological conditions associated with congenital infections. results: all of the patients were seen in our paediatric outpatient neurology clinic. the age of presentation ranged from the neonatal period to the first weeks of life. all patients were of pakistani origin and were from consanguineous marriages. they all had an uneventful antenatal period with normal birth weight and head circumference. the initial presentation seems to be of poor feeding and irritability. further observations include truncal hypotonia, limb spasticity intermittent dystonic posturing coinciding with the onset of poor head growth and chilblains. of our patients had abnormal movements with diffuse slow wave electroencephalogram activity. nystagmus with visual inattention and poor visual acuity were a typical finding in all of them by the age of months. the ct scans showed cerebral calcification in all of them and mri suggested brain atrophy. the most striking abnormality was a raised level of csf interferon-alpha (infa) in an absence of other infection or metabolic disorder. csf inf a is a reliable diagnostic marker and can thus be used to differentiate patients with ags from other conditions. three of our patients had the same gene mutation, rnaseh c. conclusions: ags is a rare disorder, however in patients from consanguineous marriages that depicts microcephaly, poor tone and global developmental delay, diagnosis of ags should be considered. as ags is a progressive neurological condition, early support and prognosis can be provided for affected families. t thomas , ht yeo , sv barron , paediatric neurology, kk hospital, kampong java, singapore; university of newcastle, newcastle, uk objective: we report the association of mild encephalopathy with a reversible splenial lesion (mers) with a primary dengue virus infection. this case implies the existence of a wider spectrum of neurological involvement in dengue virus infections. case description: a -year-old girl presented with acute confusion, dysarthria and bilateral limb weakness following a -day history of fever. symptoms resolved after hours; neurological examination was completely normal. she later experienced a second episode of slurred speech, dysphasia and right arm weakness which lasted an hour. a contiguous lesion involving the genu, body and splenium of the corpus callosum and bilateral posterior periventricular white matter was evident on the mri brain scan, with restricted diffusion and t -hyperintensity. cerebrospinal fluid analysis showed no inflammation and polymerase chain reaction assay for respiratory viruses was negative. her clinical and radiological features were consistent with mild encephalopathy with a reversible splenial lesion (mers). on day of admission, she developed a generalised maculopapular rash with leukopenia (white blood cell count . /l) and thrombocytopenia (platelets /l). serology (igm/igg) for dengue virus was negative and a positive dengue ns antigen was thus indicative of a primary dengue virus infection. she was given fluid rehydration and advised bedrest. at discharge (day admission) she was well with no sequelae. conclusions: mers is a mild form of virus associated encephalopathy (vae), which are a spectrum of clinico-radiological syndromes associated with common childhood viral infections. the clinical and neurological symptoms in our patient occurred early in the course of illness (typical to vae) as opposed to after or late in the illness as is typical for postinfectious encephalopathy syndromes associated with dengue virus infections (e.g., acute disseminated encephalomyelitis). shouldering the burden of sepsis norfolk and norwich university hospital nhs trust, norwich, uk; sheffield children's hospital, sheffield, uk aim: we report a case of a -year-old boy who presented with right brachial plexus neuritis secondary to meningococcal group b sepsis. brachial plexus neuritis or neuralgic amyotrophy (also known as parsonage -turner syndrome) is a rare disorder affecting the brachial plexus. it can be caused by various infectious agents and is characterized by acute onset of intense pain in the shoulder and arm followed by weakness, sensory loss and atrophy. methods: a -year-old boy, previously fit and well presented to the emergency department with an acute onset of excruciating pain in his right shoulder, radiating down his arm and hand with associated paresthesia. few hours later, he developed an evolving non-blanching purpuric rash to the chest, back, shoulder and right arm. he gradually developed weakness in the right arm and sensory loss over the ulnar aspect of the right hand. he then began to complain of headache, photophobia with subsequent vomiting. he was treated for meningococcal sepsis with intravenous ceftriaxone and received three fluid boluses for hypotensive shock with vitamin k correction for his associated coagulopathy. he received analgesia for right shoulder pain. results: blood cultures and blood pcr confirmed neisseria meningitidis group b type, nt subtype. mri of the shoulder showed inflammation consistent with brachial plexus neuritis with motor impairment affecting the right side c to t myotomes and sensory impairment involving the right c dermatome. the patient was treated with oral prednisone and gabapentin whilst receiving neurorehabilitation from physiotherapy and occupational therapy. he made a very pleasing recovery after few months and currently has no motor or sensory deficit of his right shoulder and arm. conclusion: brachial plexus neuritis should be considered in the differential when a child presents with sudden onset pain and weakness of the shoulder and arm. in review of literature, brachial plexus neuritis associated with meningococcal infection has not been described previously. to the best of our knowledge, this is the first reported case of its kind. introduction: previous cohort studies on paediatric multiple sclerosis (ms) have reported very low frequencies for a primary progressive ms course (ppms) ranging from to %. an age-dependent increase in the rate of primary-progressive courses has been well described in the adult ms population. objectives and methods: we describe five patients presenting prior to the age of years and fulfilling the mcdonald criteria for ppms. patients were identified from the national hospital for neurology and neurosurgery (nhnn) and the uk childhood inflammatory demyelination (uk-cid) network. results: patients presented at a median age of years (range: - y), with at least -year history of progressive deterioration of their balance (n= ) or progressive worsening of lower limb function (n= ). over time, all patients developed lower limb spasticity, three patients developed cognitive difficulties, three had visual problems, three had bladder involvement. median edss at years was (range: to ). cerebrospinal fluid (csf) oligoclonal bands were detected in all patients tested. dissemination in space on first mri was seen in all patients with peri-ventricular (n= ), cortical juxtacoritcal (n= ), infratentorial and spinal cord (n= ) lesions. all patients showed new lesions on repeat mri imaging. contrast enhancement was present in out of ( %) during the disease course. three patients had genetic investigations to exclude other mimics. a trial of iv methylprednisolone was unsuccessful in patients. all patients were on symptomatic treatment for spasticity and pain, including oral/intra-thecal baclofen, gabapentin and sativex. conclusions: given the rarity of primary progressive course in paediatric ms, presentation with progressive neurological symptoms and signs in young people should prompt evaluation for genetic causes. nevertheless, our five patients presented with clinical, mri and immunological features consistent with a diagnosis of primary progressive multiple sclerosis. objective: clinical course in nmdar-antibody encephalitis is variable and difficult to predict. we aimed to identify clinical features in the presenting disease episode associated with worse functional outcome and/or relapsing disease course. methods: systematic review of the literature was conducted to identify published cases with individually reported data. clinical and treatment characteristics at first episode, outcome at ≥ months, and monophasic vs. relapsing disease course were recorded. results: cases were identified from articles ( % female; % ≤ years old at onset). % received immunotherapy at first episode: corticosteroids in %, ivig in % and therapeutic apheresis in %. second-line immunotherapies were used in % at first episode, most frequently rituximab ( %), cyclophosphamide ( . %), or both ( . %); emerging second-line treatments (intravenous/intrathecal methotrexate, subcutaneous/intravenous bortezomib, intravenous tocilizumab) were used in . %. life-threatening adverse events or death related to immunotherapy occurred in . %. in a univariate analysis of cases with ≥ months follow-up data, poor final outcome (defined as modified rankin scale [mrs] score - ) occurred in % and was associated with very young or elderly age at onset, movement disorder, decreased consciousness, autonomic dysfunction, mechanical ventilation, higher mrs score in the acute phase, longer hospital stay, extreme delta brush on eeg, abnormal mri, csf pleocytosis and elevated csf protein (all p< . ). a subset of cases followed up for ≥ months were analysed to identify associations with relapsing course, which occurred in %. in univariate analysis, factors protective against relapse were < days delay in first-line immune therapy, therapeutic apheresis, ivig, rituximab and other second-line treatments at first episode (all p< . ). conclusions: worse functional outcome of nmdar-antibody encephalitis is associated with very young or elderly age at onset and worse disease severity in the acute phase. relapsing disease course is associated with delayed or insufficient early immunotherapy. objective: we describe three children with familial hemophagocytic lymphohistiocytosis (fhlh), who presented with an atypical chronic demyelinating illness. an initial working diagnosis of 'clippers' (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) was made in two cases. methods: retrospective case series. results: case : an -year-old girl presented with diplopia and squint with evolving ataxia. mri showed multiple enhancing white matter lesions in the pons, medulla and cerebellum raising the possibility of 'clippers'. her symptoms and neuroimaging responded only partially to treatment with ivig and steroids. genetic testing revealed a compound heterozygote mutation in the rab a gene consistent with griscelli syndrome type with fhlh. case : a -year-old boy had nocturnal headaches with a squint evolving over time. mri showed demyelination and swelling predominantly in the cerebellum. significant radiological resolution with steroids was followed by recurrence of demyelination on weaning steroids. a brain biopsy lesion was consistent with 'clippers'. genetic testing revealed a heterozygote variant in the stxbp consistent with fhlh v. case : a -year-old girl had a -month of intermittent fevers, deranged lfts and recurrent bilateral optic neuritis responsive to steroids/ivig. mri brain showed multiple areas of demyelination largely in the subcortical white matter. oligoclonal bands were positive in the csf. she developed a pleural effusion, high ferritin, deranged coagulation, lymphadenopathy and a rash found to be a cutaneous t-cell lymphoma. genetic testing revealed a homozygous mutation in the unc gene consistent with fhlh . all three children are awaiting stem cell transplantation. conclusions: fhlh can present with an isolated atypical demyelinating illness or with neuroimaging suggestive of 'clippers'. there may be no signs of systemic inflammation. we propose that all children with atypical recurrent cns inflammation and presentations consistent with 'clip-pers' undergo genetic panel testing for fhlh and natural killer cell functional testing. objective: the most common paediatric presentation of mog-ab disease is with acute disseminated encephalomyelitis (adem), or optic neuritis (on). with increasing recognition of the association of mog-abs with seizures in children, we present a case series of affected children. methods: retrospective anonymised case note review of affected children presenting between - , from uk paediatric neurology centres. patients were followed up for median of years (range . - ). results: cases ( female) of mog-ab-positive epilepsy patients were identified; median age at first presentation was (range - y). the most common preceding mog-ab disease was multiphasic adem (mdem ; adem ; adem-on ; adem and transverse myelitis ; nmosd ; on ). median time to recurrent seizure onset was months (range - ). focal epilepsy/seizures were most common ( / ). eeg abnormalities were found in / patients, all demonstrated slowing/encephalopathy which was generalised or focal; epileptiform discharges were reported in patients. brain mri was abnormal in all patients ( with multifocal hazy/ poorly marginated lesions involving grey and white matter; leukodystrophy-like pattern, cortical encephalitis and reported with subtle changes in brainstem). patients received immunotherapy, all required at least anti-epileptic drug (aed) and children continue to have on-going breakthrough seizures. median mrs (modified rankin scale) at last follow-up was (range - ), indicating no significant disabilities despite symptoms in clinical examination, age appropriate behaviour and development. conclusions: focal epilepsy is more common and more likely to follow an mdem presentation in children with mog-abs. with the relapsing nature of mog-ab disease there is a high risk of long-term cognitive impairment. further preclinical studies are urgently required to determine whether this epilepsy is due to ongoing inflammation or as a result of the mri changes commonly seen. this will help inform future management decisions regarding immunotherapy. poster no. maternal mid-gestation cytokine dysregulation in mothers of children with autism spectrum disorder autism spectrum disorder (asd) is a developmental disorder characterised by a spectrum of deficits in social interactions/ communication combined with stereotypical, repetitive behaviours. recent evidence suggests maternal immune activation (mia) during pregnancy may predispose offspring to asd. the aim of this study was to examine the mid-gestation cytokine profile in mothers of children with a subsequent asd diagnosis. maternal-child dyads were recruited to a prospective population-based pregnancy study; the scope study, new zealand. children with confirmed diagnosis of asd at years were enrolled in the nested cohort, along with matched neurotypical controls. cytokine concentrations (pg/ ml; mean [sem]) were examined in maternal serum samples taken at and weeks gestation using mesoscale discovery proinflammatory, cytokine and chemokine assays. of mothers recruited to the scope-nz study, children completed follow-up and had reported asd at years. these were analysed alongside neurotypical matched controls. downregulation of il- a occurred at weeks gestation in cases when compared to controls (mean [sem]). -way anova revealed a relationship between il- a concentration and weeks' gestation f( , )= . ; p= . , and also il- a concentration and asd status f , )= . ; p= . . posthoc uncorrected fisher's lsd revealed a significant difference between cases (- . [ . ] ) and controls (- . [ . ]) at weeks gestation p= . . ifnc is also downregulated at weeks gestation in cases when compared to controls. -way anova revealed a relationship between ifny concentration and weeks gestation f( , ) = . ; p= . . posthoc uncorrected fisher's lsd revealed a significant difference between cases ( . [ . ] ) and controls ( . [ . ]) at weeks gestation p= . . we have shown altered cytokine expression at weeks gestation in mothers of children who progress to develop asd. this adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment. objective: acute disseminated encephalomyelitis (adem) is an immune mediated inflammatory cns disorder, predominantly affecting white matter, with a wide differential ( ). here we describe a rare mimic of adem that is essential to consider in order to avoid a catastrophic outcome. case history: a -year old girl presented with a day history of confusion, dysarthria, ataxia and left-sided squint, preceded by weeks of general malaise and headache. examination confirmed encephalopathy and a left third cranial nerve palsy. mri brain was suggestive of adem and mri spine was normal. a recommended work up for adem was performed. rapid resolution of her symptoms occurred following intravenous methylprednisolone for days. years later she presented with acute left lower limb ischaemia and underwent emergency embolectomy of a popliteal arterial obstruction, with myxomatous material identified. preoperative echocardiogram confirmed a large atrial mass which was surgically removed. pathology confirmed an atrial myxoma (am). retrospective review of her initial mri images concluded that embolic phenomena from the am was the most likely explanation of her first presentation. conclusions: am is a very rare primary cardiac tumour and left sided am can embolise to the cerebrovascular system. early identification of am is important as, untreated, it can cause multiple embolic events and sudden cardiac death. % of adults with am present with neurological symptoms and this can mimic multiple sclerosis. am presenting with acute neurological symptoms masquerading as adem in paediatrics has not been previously reported. careful follow up is essential as late neurological complications (including cerebral arterial aneurysms) are recognised. this case highlights that adem is a diagnosis of exclusion and that mimics for acute focal neurology with encephalopathy and t hyperintensities on mri require careful consideration, including embolic phenomena. clinical examination alone does not exclude am and consideration of echocardiography is recommended. we describe an year old boy with a rare demyelinating disorder: balo's concentric sclerosis. a routine optician review raised concerns about papilloedema in an asymptomatic child. a ct brain identified a well-demarcated high-density lesion in the left posterior frontal lobe with surrounding oedema. mri brain with contrast identified the lesion had central rim enhancement and slight diffusion restriction. alternating layers of high and low signal intensity gave it an 'onion bulb' appearance. the differential included balo's concentric sclerosis, a single demyelinating lesion, or a tumour. routine blood tests were unremarkable. csf oligoclonal bands were normal as were other csf indices. markers of immunology, including ana, anca, anti-mog, anticardiolipin, and aquaporin antibodies were all negative, with normal complement levels. esr was mildly elevated when taken during an episode of acute tonsillitis. imaging months later demonstrated an increase in the size of the lesion. a biopsy revealed inflammatory demyelinating pathology mediated by a perivascular and parenchymal t-and b-lymphocyte infiltrate and macrophage activity with associated demyelination lacking a perivenular distribution. there was no evidence of neoplasia, vasculitis, granulomas, or viral infection (including negative pcr testing). no treatment with corticosteroids was given, and the child remained asymptomatic. imaging, at months from presentation, revealed the lesion had substantially reduced in size. there was still a rim of enhancement. as with all single demyelinating lesions, it is difficult to predict the clinical course. we opted to adopt a 'wait and see policy' and offer surveillance imaging and clinical review. balo's concentric sclerosis is a rare demyelinating disease, characterized by concentric lamella of alternating demyelinated and partially myelinated tissues. mri shows one or more concentrically mulitlayered ring-like lesions, usually in the cerebral white matter. most case reports describe cases predominantly in young adults, with few reports of cases in children. objective: cognitive and acquired neurodevelopmental deficits have been reported in children with opsoclonus-myoclonus syndrome (oms) and are associated with more severe and relapsing disease course. however, there is a paucity of data regarding cognitive dysfunction in children with stable neurological disease. we report on serial cognitive assessments of children with oms demonstrating evolving cognitive dysfunction with milder disease course. methods: retrospective analysis of clinical features at presentation, investigations, treatments, clinical course including relapses and neuropsychological testing. results: four children (m:f : ) diagnosed with oms between and months were followed up for to years. neuroblastoma was identified in one child. oms severity scores ranged between to / at presentation. patients underwent immunotherapy in accordance with european oms protocol. all patients were in remission by months (range - mo), with treatment maintained for year. one child remained relapse free whilst other children had one clinical relapse which was immunotherapy responsive again. in all cases, progressive cognitive dysfunction was reported despite being in remission and stable off treatment for months (range of - mo; oms score / and one / ). sequential neuropsychological testing scores showed mean declines in fsiq of ( - ) , viq of ( - ) and piq of (- to ) between time of oms remission/stable disease and longer term follow-up time point ( - y). conclusions: our cases demonstrate progressive cognitive dysfunction occurring in children with oms who have a milder disease and long after completion of treatment. children continued to develop but with a widening gap in comparison with peers. damage to cerebellar-cortical circuits at onset of the disease that becomes more apparent with time or indeed persistent ongoing low grade inflammation may explain this deterioration. the past decade has seen increasing cases of acute flaccid paralysis (afp) associated with enterovirus d (evd ) infection. it presents in clusters approximately every years. we report three cases of afp due to evd that presented in november-december . cases: two patients developed afp following a viral upper respiratory tract infection and one developed lower limb hypotonia and weakness during an inpatient admission with refractory epilepsy. two required admission to the paediatric intensive care unit for respiratory compromise and required tracheostomy ventilation. mri showed acute flaccid myelitis (afm) consistent with evd in / cases, consisting of central cord t hyperintensity in the cervical region over multiple segments with subsequent enhancement of the thalamus and cauda equina on follow-up imaging in one patient; and ventral surface enhancement of the conus and cauda equina in another. mri in the third patient was normal. electromyography and nerve conduction studies were normal in two patients but revealed a severe generalised motor axonal poly-neuronopathy in the third. two patients received intravenous immunoglobulin, corticosteroids or plasma exchange therapy and showed slow motor improvement in a distal to proximal pattern. the one patient without mri changes had received long-term oral corticosteroids but received no additional treatment and returned to baseline neurological function within weeks. discussion: our cases demonstrate the range and clinical course of peripheral neurological presentations secondary to evd infection. we highlight the importance of sending repeat samples from multiple sites when the diagnosis is suspected, given that initial samples tested negative, and of sending samples to a national surveillance laboratory for confirmatory testing. ongoing national and multinational surveillance studies will hopefully continue to advance our understanding and treatment of this disease. poster no. nmda receptor encephalitis a potential complication of biologic therapy for juvenile idiopathic arthritis? n abbassi , t rossor , r close , a skippen , k armon , p bale , g ambegaonkar paediatric neurology, addenbrookes hospital, cambridge, uk; paediatric rheumatology, addenbrookes hospital, cambridge, uk a -year-old girl presented with headaches, confusion and agitation, followed by seizures. she had presented at months with polyarticular arthritis and was managed over subsequent years on methotrexate alone ( y) with added etanercept (anti-tnf alpha, y), tocilizumab (anti il- , y) and abatacept (cd / t-cell modifier, y prior to presentation). flares of disease following a period of control necessitated the changes in monoclonal antibody therapy. at this presentation she was managed on methotrexate, abatacept and mg prednisolone for polyarticular rheumatoid factor negative juvenile idiopathic arthritis (jia). at presentation the patient was agitated, non-verbal and had one generalised seizure. examination demonstrated acute confusion, with increased tone, brisk reflexes and bilateral clonus in her lower limbs. iv ceftriaxone, acyclovir and clarithromycin were commenced. full blood count, liver function tests and inflammatory markers were unremarkable. infective serology was non-contributory. csf was unreactive with normal protein and jc virus pcr negative. mri brain days after presentation showed increased t and flair signal intensity in the white matter of the right parietal lobe, in-keeping with an inflammatory process. eeg showed diffuse slowing with delta brush. she commenced iv methylprednisolone, followed by prednisolone. she continued to deteriorate and underwent plasmapheresis for treatment of presumed nmda receptor encephalitis, subsequently confirmed by anti-nmda receptor antibodies in serum and csf. she was commenced on rituximab (b-cell depletion, anti-cd ), and continued to undergo plasmapheresis over the course of weeks. she gradually improved and was discharged home after a -week inpatient stay. several adult and two paediatric cases of nmda receptor encephalitis are reported in patients on biologic therapy for autoimmune disease. autoimmune diseases are more common in those already affected by one autoimmune condition. it is unclear what contribution an autoimmune history or immunomodulation made on the development of this condition. introduction: the incidence of acute flaccid myelitis (afm) associated with enterovirus infection occurring in biennial clusters since has been reported in the us (bmj , ; :k ) and recently in europe. previously, cases with transverse myelitis (tm) with anterior-horn cell or peripheral nerve involvement have been collectively termed tm-plus (neurology ; ;s -s ). we aimed to identify cases of tm-plus from a retrospective cohort of children to identify potential cases of 'undiagnosed' afm, and to evaluate the clinical and radiological features alongside long-term outcome. methods: consecutive cases of children (< y of age) who presented to a large paediatric neurosciences centre from to fulfilling the transverse myelitis consortium working group criteria modified for the paediatric population (neurology ; : - ) were retrospectively evaluated for additional features of anterior horn-cell involvement (fulfilling criteria for afm (current treat options neurol ( ) : )) or peripheral nervous involvement; and were collectively evaluated with the contemporary tm-plus cohort ( ) ( ) ( ) . results: cases of tm were identified, of which were excluded from further analysis; ms (n= ), adem (n= ). cases of tm-plus were identified, before and after, all associated with a viral prodrome. flaccidity (n= ) and asymmetry (n= ) was noted at presentation, with corresponding nerve conduction studies revealing a motor axonopathy with sensory sparing (n= ) and anterior horn cell involvement confirmed in cases. all cases with anterior horn cell involvement had poor outcomes while both cases with good outcomes had peripheral involvement and normal mri brains. conclusions: tm-plus was detected in our cohort from to with biennial clusters noted in and . the clinical presentation, investigations and long-term outcomes appear consistent in both groups. acute necrotising encephalopathy is more severe when associated with influenza background and objective: acute necrotising encephalopathy (ane) is a rare but potentially life-threatening condition associated with viral infections. a familial and recurrent form (ane ) has been identified by mutations in the nuclear pore ran binding protein (ranbp ). we report the morbidity and mortality when associated with influenza infection. methods: we performed a review of paediatric ane cases from to evaluating the clinical, biochemical, microbiological and neuroimaging appearances as well as outcomes. results: the cohort comprised children ( boys), age ranging from months to years months (< y n= ), of which had a confirmed genetic diagnosis and were ranbp negative. there were episodes of encephalopathy, with recurrences in cases ( ane ). of these episodes had infectious aetiology identified: coronavirus n= , parainfluenza n= , adenovirus n= , h influenzae n= , influenza (h n n= , h n n= ). clinical features of fever and encephalopathy were consistent ( %), and seizures and sixth nerve palsies prominent ( % each). csf revealed absent pleocytosis, normal-elevated protein and negative virology. symmetric involvement of the thalami bilaterally was present in all cases, and all ane cases were associated with haemorrhage and external capsule/claustrum involvement ( % specific and sensitive). the outcome following influenza infection was striking, death n= , vegetative n= , limb motor and movement disorder n= . of these cases had previous episodes of encephalopathy with noninfluenza infection and did have recovery, albeit with moderate to severe disability. all cases were never immunised against influenza infection and suffered grave outcomes. conclusions: influenza infection in ane has the poorest outcome therefore vaccination should be a mandatory consideration for the known cases of ane. introduction: acute flaccid paralysis (afp) is characterized by a rapid onset of limb weakness. we describe six cases of afp in children aged months to years of age who presented to a tertiary paediatric neurology service in the east of england over a -year period from november -november . retrospective analysis of the six cases was performed, reviewing their clinical course and management, as well as their radiological, electrophysiology and laboratory results. results: case , a -month-old boy, presented in november with a viral urti requiring escalation of care to picu due to a significant respiratory compromise. only on subsequent recovery was the child found to have a unilateral upper limb flaccid paralysis. this child was positive for enterovirus serotype d . cases and in our series presented in with acute weakness of the lower limbs with an mri brain and spine showing enhancement of the lumbar spinal roots. both have made a good recovery. enterovirus was not detected in either case. the final three children in our series presented in autumn with weakness of a unilateral upper limb following a viral urti, with all three being positive for enterovirus. unfortunately, they have shown minimal recovery of motor function of the affected upper limb. one child, a year-old girl, showed a more severe clinical course involving a prolonged period of intensive care and a tracheostomy for long-term ventilation. she has undergone neurorehabilitation and an upper right arm nerve transfer. conclusions: in our case series, four patients presented with an acute viral urti associated with an upper extremity weakness, and subsequently all four were positive for enterovirus. clusters of acute limb weakness in paediatric patients have been linked to outbreaks of non-polio enteroviruses, termed acute flaccid myelitis (afm). objective: to present an interesting case of recurrent anti-mog demyelinating disease and provoke discussion regarding possible immunomodulatory therapy. methods: a year old girl presented, initially at years of age, with headache and vomiting. she was initially treated as atypical tuberculosis meningitis based on csf cell counts, but later developed a th nerve palsy and was diagnosed with optic neuritis. anti-mog antibodies were positive and they were commenced on iv methylprednisolone. she clinically improved and was discharged on weaning oral prednisolone, antibodies were negative following treatment. results: a few months later she had her first relapse, with an acute decline in visual acuity. an mri showed new lesions in her optic chiasm and both optic nerves with associated bilaterally reduced visual evoked potentials. she was again treated with iv methylprednisolone, with rapid improvement, followed by a switch to weaning oral prednisolone. anti-mog antibodies were negative following treatment. she was symptom free for years until her second relapse, when she presented with facial palsy, swallowing difficulties and slurred speech. mri showed brainstem and periventricular white matter demyelination, with positive anti-mog antibodies. she was again treated with iv methylprednisolone, followed by oral prednisolone, but was maintained on low dose prednisolone as her anti-mog antibodies remained weakly positive despite being symptom free. these were stopped at patient request due to low mood and abdominal pain in february , with no recurrence of symptoms as yet. repeat mog antibodies have been sent and are awaited. conclusions: this case shows an interesting relapsing/remitting pattern of anti-mog demyelinating disease, which appears to be very steroid responsive, however on her second relapse her anti-mog antibodies remained weakly positive despite steroid therapy. discussion is welcomed on whether prophylactic immune modulation therapy should be considered with this child, such as azathioprine, mycophenolate mofetil or rituximab. objective: to highlight the utility of early mr imaging in children presenting with acute severe encephalopathy and to consider whether there might be a subgroup of children with myelin oligodendrocyte glycoprotein antibody (mog-ab)associated demyelination who might be candidates for early intense immunomodulation. methods: we report two cases with mog-ab-associated acute demyelination who relapsed with new neurological symptoms after initial steroid therapy had been discontinued. results: two toddlers were initially admitted to intensive care with acute encephalopathy and acute symptomatic seizures. both had an initial ct head during picu admission; one was reported normal; the other was suggestive of diffuse cerebral oedema. both children improved with supportive care only and were discharged home within a week. both children presented again over the following to weeks with new neurological symptoms but without encephalopathy. mr imaging demonstrated demyelination and they were treated with steroids. both children relapsed as steroids were being weaned and/or stopped. repeat mr imaging at this stage demonstrated new enhancing lesions. it was subsequently found that both children were mog-ab positive. conclusions: reliance on cranial ct imaging in the context of a young child with acute encephalopathy and seizures can be misleading. prediction of the severity of mog-ab-associated demyelinating syndrome at onset is challenging. mr imaging in the acute phase with early follow up imaging may identify this subgroup. case: hb is a year old boy who presented with sudden onset diplopia and painful ophthalmoplegia, following a day history of frontal headache. on examination, he had a left vith nerve palsy, partial left iiird nerve palsy and normal right eye movements. the remainder of his neurological and general systems examination was normal. his initial ct head scan and pre-contrast mri of the brain were normal. he was discharged from the local hospital following normal blood tests and imaging. clinical course: nine days later, his symptoms worsened including severe vomiting, worsening frontal headache and photophobia. he was treated for a possible underlying infective cause with ceftriaxone and acyclovir. given the broad underlying differential diagnoses, hb had extensive infectious and immunological blood workup which was unremarkable. a repeat mri brain scan with contrast revealed a lesion in the left cavernous sinus, possibly of vascular origin. differentials included cerebrovascular venous sinus thrombosis, tumour and inflammatory causes such as tb, sarcoid and zoonoses. hb continued to be conservatively managed and completed his course of ceftriaxone and acyclovir. repeat mri imaging months later showed some resolution of the lesion and a diagnosis of tolosa-hunt syndrome was provisionally made. hb's symptoms continued to improve and further repeat mri scan months later showed ongoing resolution of the lesion. discussion: according to the ichd- beta classification of tolosa-hunt syndrome, hb fulfilled the diagnostic criteria given his presentation of unilateral headache, granulomatous inflammation of the cavernous sinus on mri, palsies of ipsilateral iiird, ivth and vith cranial nerves. steroid use has been reported to be beneficial although more evidence is required in the paediatric population, refractory cases may respond to azathioprine and methotrexate. objective: we present a case of internuclear ophthalmoplegia unresponsive to steroid treatment which clinically improved with folinic acid supplementation. method: a retrospective chart review. results: our patient presented with acute internuclear ophthalmoplegia, ataxia and bilateral ptosis. she had a background of hypoplasia of the corpus callosum and optic atrophy with visual impairment, learning difficulties and asd. mri brain demonstrated symmetrical high signal intensity in the region of the medial longitudinal fasciculus and periaqueductal grey matter. she was investigated to exclude an inflammatory cause and was treated with high dose steroids. follow up mri did not show any improvement post steroids and there was no clinical improvement. subsequent csf investigations showed a low level of -methyltetrahydrofolate of nmol/l (normal range - nmol/l). she was commenced on folinic acid mg once daily and her symptoms improved. on follow up her eye movements had significantly improved as had her ptosis. follow up mri brain showed partial resolution of the areas of abnormal signal in the periaqueductal grey matter. conclusion: internuclear ophthalmoplegia is a sign usually associated with an inflammatory or demyelinating cause. our case did not respond to steroid treatment but has associated low levels of -methyl tetrahydrofolate and has responded to treatment with folinic acid. this is sometimes associated with underlying mitochondrial disorders but muscle biopsy in this case did not show any evidence of mitochondrial disease. mri brain has shown partial resolution of the abnormal signal in the periaqueductal grey matter. introduction: paediatric intracranial aneurysms are rare. the pattern of disease is different to that in adults and there is far less literature available. i provide a case as an example of the presentation and progress of a child with a dissecting vertebrobasilar artery aneurysm. presentation: -year-old boy presented to his local hospital with sudden-onset headache, photophobia and vomiting. bloods and observations were normaldischarged. symptoms recurred more severely the following day. managed as meningitis. lumbar punctures were 'bloody' and considered failed. mri brain days post-admission demonstrated a vertebrobasilar aneurysm. transferred to the regional neurosurgical centre. transfer to neurosurgical/neurovascular centre: cerebral angiography revealed dissecting vertebrobasilar aneurysm ( mm). fusiform component extending beyond aici/ pica origins. wide-necked saccular component. procedure and progress: loaded with aspirin and clopidogrel. underwent endovascular procedure the following daycoil embolization, flow-diverting stent to the aneurysm. ongoing low dose dual anti-platelet therapy. made an excellent recovery with no neurological deficits. further imaging -x-ray cervical spine for possible arcuate foramen or atlantoaxial instability, normal. ultrasound liver/spleen, normal. discharged home days post-transfer. patient background: past medical historyunder the gp for months of headaches. traumasignificant fall from bicycle years before with forced lateral flexion of the neck. posited that this may have been a contributing factor in aneurysm development. no significant family history. lifestylean active boy, enjoys weightlifting and motocross. weightlifting also posited as a contributing factor. conclusions: i provide a case which i hope will raise awareness of paediatric intracranial aneurysms and stimulate discussion concerning their management and aetiology. poster no. cavernoma in children: cddft experience of two cases d jayachandran, s chandraiah darlington memorial hospital, cddft, darlington, uk aim: to report two cases of congenital cavernoma diagnosed in children presenting with neurological symptoms. cases: case : -year-old female presented with multiple left facial focal seizures in the form of twitches with full awareness. there was no family history of epilepsy. a typical event was captured lasting seconds during the awake eeg and was reported as focal seizure arising from right hemisphere. an mri brain scan showed popcorn balls lesions within the frontal/fronto parietal lobes, one on each side (right>left) with evidence of bleeding. she remains seizure free on carbamazepine. ccm gene results are awaited and neurosurgeon opinion was not for intervention and for local follow up. case : -year-old male had presented with confusion at years of age. he also had transient loss of vision, vomiting, headaches with a few minutes unresponsive episode during admission. with a diagnosis of migraine, he had an mri brain scan as op that showed multiple cavernous haemangiomas in the cerebrum and cerebellum with the largest demonstrating a fluid level in the left parieto-occipital region. family history revealed that father had seizures secondary to brain cavernomas. he was positive for krit (ccm ) mutation. neurosurgeons advised active monitoring and he presented again at years with focal onset seizures with impaired awareness. eeg was normal but mri showed a new cavernoma in the left temporal horn with bleeding. he remains well on carbamazepine with a plan for yearly mri scans. conclusions: congenital cavernomas of brain can be sporadic or familial, can be multiple and in any location including brain stem and can result in physical disability secondary to bleeding. in the majority of cases bleeding is spontaneous and diagnosed on mri scans after a neurological event. objective: foxp -related intellectual disability syndrome is characterised by developmental delay, variable physical features and autism. diagnosis has increased with better access to broad genetic testing. we present a case report of a child with foxp mutation whose presentation was notable for significant cerebral venous ectasia. case: child s presented aged year with gross motor delay (not sitting or weightbearing) along with relative macrocephaly ( st- th centile), strabismus and prominent superficial forehead veins. intracranial imaging was arranged in which ct angiogram raised a possibility of an arteriovenous fistula. subsequent catheter angiography excluded this but demonstrated extensive tortuous cerebral venous ectasia. the venous ectasia was not felt to explain her developmental difficulties. initial genetic testing including microarray and pik ca and pten analysis was normal. s made some developmental progress but remained globally delayed compared with her peers. reanalysis of her dna against a panel of genes associated with intellectual disability identified a de novo heterozygous pathogenic variant in the foxp gene, c. c>t, p.(arg ter) (east anglian medical genetics service). discussion: foxp acts as a transcription factor and is likely to be involved in the development of many different tissue types. a wide range of genetic aberrations affecting foxp , including point mutations and large structural anomalies, lead to overlapping clinical phenotypes. this patient demonstrates many relevant clinical features including developmental delay with autistic traits, relative macrocephaly with a prominent forehead, strabismus and early gross motor developmental delay. however, descriptions of associated neurovascular anomalies in foxp syndrome are scarce, with a single case report recording a venous angioma and none of cerebral venous ectasia to our knowledge. foxp follow up studies and whole exome or genome sequencing may help determine whether there is an additional genetic cause for this child's cerebral venous ectasia or whether it is foxp related. objective: a rcpch guideline was published to increase awareness of stroke in children and standardize best practice. the need for urgent (within h) ct angiography in children presenting with suspected stroke and criteria for thrombolysis were set out. we aimed to review the acute management and investigation of pais in children ( mo to y) since the introduction of the guideline with an emphasis on identifying candidates for thrombolysis. methods: retrospective notes review in a single regional neurology centre over a -month timeframe. results: eighteen cases were identified ( f: m) with two mortalities. age range months- years (mean . y). / presented in peripheral hospitals and / in the regional centre. no cases had pednihss score documented on presentation. / had dedicated vascular imaging (cta/ mra) on initial imaging. / presented with a hemiparesis, / with seizures, / dysphasia, / headache, / ataxia. / cases had a stroke post cardiac surgery, / idiopathic stroke, / post varicella angiitis, / arterial dissection, / cardiomyopathy and / embolic stroke as a complication of central line insertion. / presented with an acute hemiparesis with a clear time of onset. no cases received thrombolysis. / was imaged within hour of presentation. / had vascular imaging (mra or cta) on presentation. / cases was discussed acutely with paediatric neurology; this case was not suitable for thrombolysis due to cardiomyopathy. in retrospect the other / cases were suitable candidates for thrombolysis. conclusions: the results highlight the continued need for enhanced awareness of paediatric stroke as a medical emergency. most acute strokes will present to peripheral hospitals. therefore, there is a need for regional multidisciplinary integrated pathways amongst emergency department physicians, paediatricians and radiologists to ensure prompt vascular neuroimaging and discussion with a paediatric neurologist about the possibility of thrombolysis in suspected pais. poster no. 'a nudge, a fall and a weakness'a common but missed cause of paediatric stroke r shyam , r bahri , , a kumar , v jain department of paediatric neurology, santokba durlabhji hospital and medical research institute, jaipur, india; norwich medical school, university of east anglia, norwich, uk objective: this study retrospectively analysed paediatric strokes with further evaluations and outcomes of strokes related to minor injury, to isolate characteristic features and outcomes in these patients. methods: paediatric patients ( mo to y age), presenting with acute stroke between january to january were retrospectively recruited from a tertiary care hospital in north india. from this cohort, strokes following minor injury were analysed for clinical profile, investigations and outcomes (measured by international paediatric stroke study scoring system, ipss). results: of the total cases, ( . %) were post-minor injury (m: f . : ; mean age . ae . mo). of the remaining (n= ; mean age ae . y) most common aetiologies were moya-moya disease (n= , %) and transient unilateral arteriopathy (n= , %). the post-minor injury group revealed a median time of minutes from trauma to stroke onset. more than / rd ( %; n= ) had transient episodic hemi-dystonia on the hemi-paretic side after a median of days of symptoms onset. % ( / ) of children where results were available had anaemia. ct head in all (n= ) showed calcification of the lenticulo-striate vessels. subsequent brain mri (n= ) confirmed ct findings of basal ganglia ischaemia. mr angiogram and thrombophilia screen (n= ) done in the first few patients were normal and hence not pursued subsequently. follow ups of / ( - mo; median= mo) showed good recovery in the majority ( %; n= / ). the median ipss score for these children was . . conclusions: trivial injury leading to basal ganglia stroke was the most common cause of paediatric stroke, occurring exclusively in less than year-olds. ct head was diagnostic (calcification in lenticulo-striate blood vessels and ischemia) with no further information revealed from vascular imaging or thrombophilia work-up. children were commonly anaemic, a potential causative association. often transient episodic hemidystonia of the hemiparetic side after a few days was witnessed. neurological outcomes in most children with this entity is good. introduction: rcpch launched guidance on paediatric stroke in march . we present a series of paediatric patients who presented with stroke following this publication. we audited this group of patients against the key standards of the rcpch guidance. methods: we retrospectively analysed cases between april and april . we identified cases from a neurology database and audited acute management using rcpch guidance as standard. results: we identified children with stroke in the last years. ages ranged from months to years with a mean age of years at presentation. children had haemorrhagic stroke and had ischaemic stroke. the majority involved the anterior cerebral circulation ( / ). underlying aetiology was identified in patients, of whom had haemorrhagic stroke. of the patients died. only out of patients had brain imaging within an hour of presentation. only one patient was eligible for thrombolysis, however due to contraindication she underwent thrombectomy. discussion: stroke pathways are well developed in adult services. due to the rarity of stroke in childhood and challenges with recognising symptoms, treatment is often delayed. symptoms in children need a high index of suspicion. the findings of this audit support the development of an all wales paediatric stroke pathway. we aim to facilitate activation of the stroke pathway when children present with the fast symptoms. we also hope to increase awareness of stroke in childhood. withdrawn. objective: stroke is a common childhood neurological disorder, affecting at least children in the uk each year. the majority of children have residual sequelae across a wide domain of functions, with significant personal and societal consequences. recent rcpch guidelines have proposed criteria for hyperacute treatments; this would require rapid recognition of the potential diagnosis by clinicians. here we describe the acute care pathway of a group of children with confirmed arterial ischaemic stroke (ais). methods: parents of children aged > days and < years referred to gosh (ais) ( - ) were approached and sent a questionnaire exploring their experience of navigating through the healthcare system on initial presentation. responses were tabulated where possible and reported as frequencies; qualitive results were thematically coded and categorised for analysis. results: / eligible parents responded. and the gp were the first port of call for the majority (n= for each). ten parents stated they had 'no idea' what initial symptoms might represent. when directly asked if they had suspected a stroke, nearly / stated 'no'. f.a.s.t features (f: face a: arm s: speech t: time) were noted in a third of patients and only patients were given a diagnosis of stroke at first presentation. on initial discharge, a correct diagnosis of stroke was provided to patients. notably, the need for improved education of paediatric stroke, for healthcare providers was raised by nearly % of parents surveyed. conclusions: the study demonstrates the need for further education to be delivered in pre-hospital, primary and secondary healthcare settings for recognising acute stroke in children. this will be an essential step in the delivery of hyperacute treatments. background: hereditary spastic paraparesis refers to a heterogeneous group of inherited neurodegenerative disorders characterized by progressive lower limb spasticity and weakness. there is marked genetic heterogeneity in hsp with all modes of inheritance described for the different loci and causative genes implicated up to now. we present a case of a child with a complex diagnosis of hsp with a homozygous missense mutation in nt c underlying hereditary spastic paraplegia spg . case presentation: this child had initially been diagnosed as having bilateral cerebral palsy with diplegic pattern and gmfcs ii. he had gross motor and speech and language delay. there was a family history of consanguinity. mri scans had initially been described as showing evidence of periventricular leukomalacia and he had been referred for consideration of sdr. following tertiary assessment there were clinical concerns that the overall diagnosis may need to be reexplored. review of his mri scans demonstrated similarities to a case series of hsp with a rarer form of hsp (spg ). he subsequently tested positive for spg nt c . a second case with similar clinical findings has now been identified in our region. mri scan findings will be presented. summary: spg is a rare but important cause of a cerebral palsy phenotype and testing for nt c should be considered in the differential diagnosis and investigation of patients presenting with cp. recommendations on patient suitability for sdr has focused on children functioning at gmfcs level ii or iii. sdr has been considered for gmfcs levels iv and v however the decision to progress can be challenging. the goals in these children are significantly different with the focus being around comfort and pain relief rather than mobility. we describe the case of a boy with a mixed pattern movement disorder involving limbs which had initially been managed with oral medications baclofen, trihexiphenidyl and intramuscular botulinum toxin. due to the child having a vp shunt the family didn't wish to consider itb pump. despite optimisation of oral medications and intramuscular botulinum toxin spasticity was a significant issue adversely impacting on quality of life. escalation of baclofen was unsuccessful due to loss of head control and duration of action of botulinum toxin injections appeared to be limited to to weeks before tone increased again. this resulted in significant difficulties with moving and handling. in view of this the option of selective dorsal rhizotomy was explored. the goal was to improve ease of personal care and sleep. post-operative outcomes greatly exceeded the family expectations. along with a reduction in tone in the lower limbs they were delighted to report several unexpected improvements. these included: improved functional ability with the left upper limb which facilitated switch access; improved truncal control making moving and handling easier; a reduction in extension posturing which had been particularly problematic pre-operatively; significant improvement in sleep; improved mood. this resulted in the local team exploring eye gaze technology with him. these functional benefits have significantly improved the quality of life for not only the patient but his family. further research into the benefit of sdr in this group of patients should encompass care and comfort outcomes, sleep assessment and measurement of pain. introduction: clonidine has become increasingly repurposed for the management of childhood dystonia. one potential advantage of clonidine is the availability of patches for transdermal delivery. we aimed to review the use of transdermal clonidine patches in our institution. methods: a retrospective notes review of children and young people (cayp) with dystonia issued transdermal clonidine patches as identified from pharmacy records. results: a total of cayp were identified, median age at initiation of clonidine of years months (range mo to y and mo). prior to initiation of patches / cayp were already receiving clonidine, including acutely receiving iv clonidine infusions. one child with difficult iv access experiencing an acute deterioration of dystonia was lost to follow up following transfer to local services. the commonest indications for transdermal clonidine were concerns about 'on/off' effect of enteral doses (n= ) and concerns about enteral absorption (n= ). transdermal clonidine was discontinued by / cayp ( as patches wouldn't adhere, receiving patches as a temporary bridge from iv to enteral clonidine and due to severe local cutaneous reaction). one additional clonidine naive child experienced significant hypotension with a . µg/kg/hour transdermal dose but tolerated a reduced dose of . µg/kg/hour. follow up for the remaining / children ranged from months to . years (median y). the median transdermal dose was . µg/kg/hour (range . - . µg/kg/h). additional enteral clonidine was used by / cayp. efficacy of transdermal clonidine was difficult to determine, but / cayp retrospectively scored on the clinical global improvement-scale, suggesting significant improvement. conclusions: in cayp receiving enteral clonidine switching to transdermal clonidine patches appears to be well tolerated, with . % of cayp continuing with longer term use. further prospective work is required to determine the efficacy and safety profile of transdermal clonidine. objective: to review the indications for and outcomes following itb for children and young people (cayp) at our centre. methods: patients were identified undergoing itb pump insertion from to . had reports available. a retrospective note review was performed, with data extracted using a standardised data collection proforma. results: median age at itb pump insertion was (range to ). hypertonia was described as dystonia, spasticity and/or dyskinesia. median length of follow up was years (range: mo to y). choice of outcome measure was dependent upon the goals identified for surgery. care provider child health index living with disability (cpchild) data was available for cayp at baseline and cayp at year. cpchild improved from a median score of . to . at year (p= . , wilcoxon signed rank test). burke-fahn-marsden dystonia rating scale (bfmdrs) data was available for cayp at baseline (median: . for motor, for disability), cayp at year (median . for motor, median for disability), all with a clinical picture of dystonia. gross motor function measure (gmfm) was available for cayp at baseline (median= ), cayp at year (median ) and cayp beyond year (median= . ). gmfm and bfmdrs were not statistically significant. pain was measured with paediatric pain profile, available for cayp at baseline, cayp in year and cayp beyond year. median of most troublesome pain improved from at baseline to in year. conclusions: for a heterogeneous cohort of cayp with motor disorders, itb appeared to improve ease of care and comfort, indicated by change in cpchild. multiple measures are required to fully capture benefits seen in this cohort, which should be focused on their individual needs for intervention. objective: to evaluate neurosurgical interventions and outcomes in the management of hemidystonia. methods: the pubmed database was searched including terms 'hemidystonia', hemi-dystonia', 'unilateral dystonia', 'dystonia and (pallidotomy or thalamotomy)', 'dystonia and (dbs or 'deep brain stimulation')' and 'dystonia and (itb or 'intrathecal baclofen')', up to may . papers were included if written in english and presenting outcome data for human participants undergoing a neurosurgical intervention for management of hemidystonia. reference lists of included papers were also reviewed. individualised patient data was extracted. to facilitate comparison across patients with and without validated dystonia scale scores individual patient outcomes were categorised on a -point scale ranging from 'worsened compared to baseline' to 'very marked improvement'. results: we identified reports meeting inclusion criteria, describing unique patients ( < y of age). ablative methods ( / cases) most commonly targeted the thalamus, and dbs ( / cases) the gpi. in recent years dbs is reported far more commonly then ablative surgery. reported follow up ranged from months to years. one patient underwent itb but no further individual data was available. out of the cases had individual outcome data. objective measures were available in dbs and ablation cases, most commonly the bfmdrs. reported outcomes in dbs patients were / worsening compared to baseline, / no change, / slight improvement, / moderate improvement, / marked improvement and / very marked improvement. for the ablative cases / worsened, / no change, / slight improvement, / moderate improvement, / marked improvement and very marked improvement. complications were reported in dbs cases ( shielded battery syndrome, one infection) and ablative cases ( depression and transient hemiplegia). conclusions: available evidence for the neurosurgical treatment of hemidystonia is of low quality, but suggests generally positive results, with few complications reported. introduction: acute flaccid myelitis (afm) is a recently characterised condition causing multiple muscle paralysis and life-changing disability in children. no medical treatment is effective. however, recovery of denervated muscle function is possible via nerve transfer surgery. such treatment is complex, specific to the individual and should be carried out by specialist teams. objective: to describe the clinical features, management and outcomes of nerve transfer surgery following the afm outbreak. methods: retrospective analysis of patients with afm treated with nerve transfer surgery in . surgical criteria: persistent motor deficits (paralysis) months post onset with neurophysiologic signs of denervation and donor nerve availability. results: eight patients (m=f, aged - months; mean ) were referred between march and july . at initial onset/ infection: / had involvement of all four limbs and trunk and / had involvement of the phrenic nerve. mean date of initial assessment within specialist centre was . months post onset (range - ). at this time had upper limb paralysis ( right, left) and had bilateral lower limb paralysis. following consultation, declined surgical intervention and are awaiting surgery. / patients have proceeded to surgery: / cases presented with three-or-more nerve root involvement. nerve-transfers have been performed (median per patient). no surgical complications were encountered. early clinical functional outcomes from this cohort following surgery are currently being collated and evaluated and will be presented in full at conference. conclusion: this study supports international experience that nerve transfer surgery can improve functional outcomes in afm. the delivery of care in the nhs requires coordination and referral to specialist centres. experiences with this cohort will inform decision making and improve patient outcomes and family expectations during the next outbreak of afm. poster no. a catastrophic case of acute flaccid myelitis t chakrabarty , c lundy , g doherty , d bhattacharya , p moriarty , d peake royal belfast hospital for sick children, belfast, uk; royal victoria hospital, belfast, uk objective: acute flaccid myelitis (afm) is a rare but serious neurological condition characterised by acute onset of flaccid weakness in one or more limbs with distinct abnormalities of the spinal cord grey matter on magnetic resonance imaging (mri) and without any features suggesting an upper motor neuron disorder. in recent years, there has been a global increase in the incidence of afm associated in some cases with a non-polio enterovirus, ev-d . the long-term prognosis in most cases remain poor. we present a severe case of afm in a -year-old boy with catastrophic consequences. method: retrospective review of clinical course, neuroimaging, treatment and neurorehabilitation. results: a -year-old boy presented with clinical encephalitis. he deteriorated over hours and developed an encephalopathy, multiple cranial nerve deficits, and complete flaccid paresis requiring picu support. csf weeks apart showed a resolving lymphocytic pleocytosis with increased protein ( . to . g/dl). serial mri brain and spinal cord showed extensive signal abnormality involving thalamus, dorsal pons, medulla, cervical cord, conus along with cauda equina. nerve conduction studies were consistent with a severe acute motor axonal neuropathy. eeg showed a posterior dominant encephalopathy. infective (including edv- ), metabolic, immunological (aqp and mog abs) and genetic (ranbp ) tests were negative. immunomodulation therapies (methylprednisolone, ivig, and plasma exchange) resulted in no clinical improvement. resolution of signal changes in the thalami, brainstem and spinal cord along with mild generalised cerebral atrophy was noted in repeat mri after months. months following presentation he remains fully ventilated with no significant motor improvement despite intensive rehabilitation including use of passive range of movement devices and functional electrical stimulation. conclusion: this is one of the most severe cases of afm, representing the wider spectrum of afm involving encephalopathy, dominant bulbar signs and quadriparesis. mirror movement disorder (mmd) is a rare movement disorder with a prevalence of less than in a million in which involuntary symmetrical movement is observed in the limb contralateral to the voluntary limb movement. we report children with an mmd. case : a -year-old girl following an uneventful pregnancy and normal delivery, born to nonconsanguineous parents presented with difficulties with fine motor activities like writing. parents noticed from age of eight that her left hand would make similar movements to her right hand in activities like writing, combing etc. maternal grandfather has mmd. case : a -year-old girl following an eventful pregnancy and normal delivery to non-consanguineous parents presented with an mmd at age of years first noticed whilst writing and this continues affect her activities of daily living. there is no family history of mmd. both children are neurodevelopmentally normal and have normal mri brain and spine. mmd have been described congenitally due to prenatal insult before weeks gestation, kallman syndrome and klippel-feil syndrome or as an acquired due to hemiplegic stroke and parkinson's disease in adults. pathogenesis is thought to be due to lesions in supplementary motor area, corpus callosum or cervical lesions. mutations in dcc and rad gene are present in % of the cases. the multimodal mri and neurophysiological studies have revealed that the motor system is completely disorganised with abnormal crossing at brain stem level and abnormal communication between both brain hemispheres in these children. there is a positive family history in some cases. the upper limbs are commonly involved. diagnosis is usually clinical and treatment is symptomatic with support at school and limiting repeated complex and sustained movements involving both hands. poster no. acute spinal cord infarction in children: a review of the presentation, aetiological investigations and outcomes in children m shehata, ar hart, cd rittey, e davies department of paediatric neurology, sheffield children's hospital nhs foundation trust, sheffield, uk aims: acute spinal cord infarction is poorly understood in the paediatric population. we reviewed cases presenting to a single paediatric neurology centre in uk between and to explore common themes of presentation, aetiology and outcome. material and methods: cases of spinal cord infarction presenting to a single centre were identified from our spinal database and medical records were reviewed to determine clinical presentation, aetiological investigations, management and outcomes. results: six children/young people were identified, male, female, age range to years. participants presented with symptoms after seemingly trivial movements or trauma, including: being kicked in the back whilst playing football, bending forwards to tie hair up, getting up to walk in the garden, and performing a crab gymnastic movement. had no obvious precipitants. initial presentation was neck or back pain in all patients, progressing to bilateral lower limbs weakness, sensory deficit, lost reflexes, and urinary/bowel involvement. mri imaging failed to reveal the diagnosis when performed early in participant. the level of lesions for each participant were: t - ; t - ; t -t ; c -t ; c -t ; and isolated to the conus. aetiological investigations, including thrombophilia screens, failed to reveal a cause in any participant. initially received steroids because the differential diagnosis included an inflammatory disorder. patients received aspirin, / gained motor improvement but none returned to normal. all had residual bladder problems, had bowel sequelae. conclusions: spinal cord infarction may be related to minor trauma or movements. the association with a chiari malformation is previously described in adults. outcome is poor. although motor improvement can be seen, children do not return to normal functionally. aetiological investigations and treatments vary within a single centre. national recommendations are required to standardise practice. cost of care for long-term ventilation patients r belderbos, v kumar, l alkhalidi east lancashire nhs trust, lancashire, uk background: advances in neonatal and paediatric intensive care have increased the survival of children with life threatening or life limiting conditions. there has been a significant rise in children on long-term home invasive ventilation. high profile cases have been in the media recently with debate on whether such interventions should be implemented focussing on ethics but without evidence of cost benefit analysis. children on long-term invasive ventilation are a high cost group with complex and varying underlying medical conditions requiring input from multiple teams, including hour carers, medical and multidisciplinary team input as well as recurrent hospital and picu admissions. in addition, the cost of equipment and drugs makes this a costly intervention. in any limited healthcare system rationing decisions have to be made: drug and other therapies are subject to health economic analyses. this study aims to assess cost per annum for ltv and a cost benefit analysis. objective: identify patients on ltv including comorbidities. assess cost of ltv to quantify cost-benefit analysis. measure outcomes: death/admissions/recovery. methods: review of patients requiring home long-term invasive ventilation july -july . analysis of costs: clinic visits, hospital admissions, costs of equipment; cost of medication. outcomes and quality of life: mortality, admissions and length of stay; decannulation, ability to communicate and mobility analysis; ability of parents to work. results: patients: died (aged , and y), decannulated, ongoing ltv (aged mo, and y), night package £ pa, accessories £ pa, replaceables/service £ , average cost home ltv around £ pa. conclusions: ltv ventilation is an expensive treatment: its use should be analysed on a cost benefit analysis in a similar way to other available treatments. objective: to assess the feasibility of recruiting to a study, performing and interpreting aeeg in preterm infants, and to assess family and staff members' views. methods: a prospective feasibility study. preterm neonates between and weeks postmenstrual age were recruited for continuous aeeg monitoring using adhesive electrodes whilst receiving nicu care. we studied optimal methods of attaching leads, impedance data, number of electrode changes, and preliminary aeeg findings. staff and parents were asked for feedback on the process and their involvement. results: we recruited . % of eligible babies. nuprep and sorbaderm were the most effective combination for skin preparation. the aeeg recording was good quality if staff were engaged and knew when electrodes needed to be changed. four of the seven ( . %) babies showed seizure activity on aeeg, none of which were diagnosed clinically. babies with seizures were born earlier, had lower birthweights, and had more complications than babies without seizures. feedback showed parents and staff were positive, although staff reported caring for the baby was harder. . % of parents and . % of staff would 'definitely' recommend the study to parents with a premature baby. conclusions: the use of continuous aeeg in preterm neonates in feasible, with similar recruitment rates to other studies in the department, and a positive experience for parents and staff. a high rate of electrical seizures was detected. background: the 'magnetic resonance imaging (mri) to enhance the diagnosis of fetal developmental brain abnormalities in utero' (meridian) study showed improved diagnostic accuracy and confidence for detecting fetal neurological abnormalities compared to ultrasound. the additional information provided by in utero mri altered prognosis in % of women. the meridian study did not report whether the neuro-developmental prognoses given to women varied between clinicians or were accurate. objectives: to assess the variation in prognosis given to pregnant women by clinicians in feto-maternal units for different fetal brain abnormalities. methods: we contacted one clinician at each of the meridian feto-maternal units and asked what percentage chance of normal neuro-developmental outcome they would give pregnant women for fetal neurological abnormalities: isolated ventriculomegaly to mm; unilateral hypoplasia of the cerebellar hemisphere, isolated hypoplasia of the cerebellar vermis, isolated cisterna magna, and isolated blake's pouch cyst. respondents were asked to give a percentage chance of normal outcome, although some used free text to answer. results: responses were received from senior obstetricians in feto-maternal units. there was general agreement for isolated mild ventriculomegaly with respondents replying that to % would have normal developmental outcome. wider variation was seen for posterior fossa abnormalities, with the suggested chance of normal outcome for one condition ranging from to %. conclusion: estimating long-term neuro-developmental outcome based on antenatally detected neurological abnormalities is challenging due to limited high-quality data. our data highlights there is high variation in outcomes offered by different clinicians for the same abnormality. further work is needed to determine what advice is given by obstetricians on the potential developmental outcomes of a wide range of fetal brain abnormalities in current practice, how well these agree with published evidence, and whether the involvement of paediatricians with experience in neuro-developmental disorders improves prognostication. background: in-utero mri (iumri) detects fetal brain abnormalities more accurately than ultrasonography (uss) and provides additional clinical information in around half of pregnancies. there is little published data on whether postnatal neuroimaging beyond months of age changes the diagnostic accuracy of iumri nor its ability to predict developmental outcome. methods: families enrolled in the meridian study whose child survived to years of age were invited to have a case note review and assessment of developmental outcome with either the bayley scales of infant and toddler development, the ages and stages questionnaire or both. a paediatric neuroradiologist, blinded to the iumri results, reviewed the postnatal neuroimaging if the clinical report differed from iumri findings. diagnostic accuracy was recalculated. a paediatric neurologist and neonatologist categorised participants' development as normal, at risk, or abnormal, and the ability of iumri and uss to predict developmental outcome were assessed. results: participants had case note review, of whom ( . %) had mri after months of age. the diagnostic accuracy of iumri remained higher than uss (absolute differ-ence= %, % ci % to %, p< . ). developmental outcome data was analysed in participants: ( %) were normal, of whom ( %) had a normal or favourable prognosis on uss and ( %) on iumr (difference in speci-ficity= %, % ci % to %, p= . ). no statistically significant difference was seen in infants with abnormal outcome (difference in sensitivity= %, % ci - % to %, p= . ). conclusions: iumri remains the optimal tool to identify fetal brain abnormalities. it is less accurate at predicting developmental outcome, although iumri is better at identifying children with normal outcome than uss. further work is needed to determine how the prognostic abilities of iumri can be improved. poster no. introducing hypothermia or not decision algorithm (honda) guideline in the assessment of neonates following hypoxic insult at birth in a district general hospital a sproule, j courtney, m mcgowan ulster hospital, belfast, uk introduction: hypoxic-ischaemic encephalopathy (hie) accounts for up to % of cases of cerebral palsy. hie can be caused by multiple events and occurs in / births. hypoxic insult at the time of birth can result in an encephalopathic state characterised by: need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. the toby study demonstrated that induction of moderate hypothermia within hours of birth for hours duration in infants who had perinatal asphyxia resulted in improved neurologic outcomes in survivors. therapeutic hypothermia is the only proven neuroprotective treatment for hie. an assessment tool was required as there was no standard proforma for neurological assessment for babies with a low cord ph (< . ) in our district general hospital (dgh). this was to ensure that all infants who met the toby criteria received the appropriate treatment within the recommended timeframe. methods: the honda assessment tool was developed for use in the tertiary neonatal intensive care unit. this assessment tool was adapted to use in a dgh as a guideline. the honda included the criteria from the toby study with a user-friendly flow chart. a comprehensive neurological examination is outlined with text and images to ensure reliable and repeatable findings by different clinicians over time. results: the honda tool ensured a standard algorithm was used to assess those infants who had a hypoxic insult at birth. it has standardised record keeping and repeated neurological examination of at-risk infants. conclusions: the honda is a comprehensive and userfriendly algorithm to ensure those infants who meet requirement for therapeutic hypothermia are being appropriately identified and treated. poster no. foetal exposure to misoprostol and mobius syndrome s tilib-shamoun, a siddiqui, v ramesh king's college hospital, london, uk background: mobius syndrome is a rare condition comprising a collection of specific congenital anomalies, usually congenital lower motor neuron th and th cranial nerve palsies. hydrocephalus, cerebellar hypoplasia, orofacial and limbs deformities have been reported in some. the literature links mobius syndrome to early foetal exposure to misoprostol, a synthetic prostaglandin e analogue widely used for medical termination of pregnancy. for abortions it is used by itself or with the anti-progestogen mifepristone; the combination is % effective during the first trimester of pregnancy. the mechanism by which misoprostol disrupts brainstem development resulting in hypoplasia or absence of central brain nuclei is not elucidated as yet. suggested mechanisms include selective vulnerability to hypo-perfusion and ischaemic injury of the foetal brain stem due to direct disruption of the foetal vasculature or to global foetal hypoxia because of uterine contractions and placental ischaemia. clinical case: we report a case of an infant with known exposure to misoprostol from failed medical termination of pregnancy (top) at weeks gestation, who presented with an abnormally increased head circumference, multiple lower motor neuron cranial nerve palsies ( , and th cranial nerves). his mri scan showed hydrocephalus due to cerebral aqueduct stenosis, inferior vermian hypoplasia and loss of bulk of the right facial collculus of the pons. conclusions: it is vitally important to counsel expectant mothers following exposure to misoprostol and failed top of possible congenital anomalies if the woman elects to continue with the pregnancy. poster no. neurological examination in unwell neonates: health care professionals' perspectives a fadilah, ar hart department of paediatric neurology, sheffield children's hospital, sheffield, uk objective: to explore health care professionals' opinions of neurological examination in unwell neonates. methods: a questionnaire designed to assess views on examining unwell neonates neurologically was distributed to all uk neonatal and paediatric neurology units. questions included likert scales, with scores ranging from to . scores of to were taken to be positive, to negative or equivocal. answers were compared between consultants and other staff members using chi-squared testing, with p< . assumed statistically significant. results: responses were received, although not every question was answered. / ( . %) responders were based in general paediatrics, / ( . %) in tertiary neonatal units, and / ( . %) in paediatric neurology. / ( . %) were consultants. / ( . %) performed a neurological examination in all unwell neonates, / ( . %) in most. . % of consultants felt confident performing a neurological examination, compared to . % of other health care professionals (p< . ). consultants were also more confident at interpreting the results and using them to formulate management and prognosis (all p< . ). / ( . %) did not find a high-quality neurological examination documented routinely in medical notes of half or more unwell neonates. / ( . %) reported using the classical neurology examination adapted for neonates, ( . %) used the hammersmith neonatal neurological examination or an adapted version. the most difficult aspects were fundus and cranial nerve examination. the most frequently cited challenges were: effect of medication; difficulties in interpretation; equipment and lines; experience; time limitations; and risks of handling unwell neonates. / ( . %) wanted a new standardised neurological examination for unwell neonates; ( . %) did not. conclusions: non-consultant grade health care professionals feel less confident performing a neurological examination in unwell neonates. all responders highlighted a number of challenges to performing and interpreting the results. around three-quarters of responders want a new, standardised neurological examination for unwell neonates, which could address these challenges. use of re-standardised griffiths scales of child development ( rd edition) in a healthy cohort at to months of age objective: the griffiths scales of child development (gscd) is an established tool for the developmental assessment of children from birth to years. in , the gscd underwent significant revisions, and was re-standardised using contemporary cohorts. to date, no studies have reported on its use in healthy children post-marketing. our aim is to examine the use of the gscd-iii in a healthy population of infants aged to months and to provide the first published data on the use of the revised griffiths-iii. methods: in a prospective observational study of healthy, fullterm infants, participants were recruited into a randomized controlled trial of infant massage. griffiths iii assessments were performed by aricd-trained practitioners across subscales and a general development quotient (gd) at to months. results: children were considered in the analysis, male: female ratio / . mean (sd) birth weight was . ( . ) kg and mean birth gestational age was . weeks (sd . ). mean (sd) age at assessment was . ( . ) months, with ( . %) children being assessed according to / rounded norms, and ( . %) to / norms. no difference was found in either arm of the study in any subscale. scores were considerably greater than average (dq - ) in all subscales but particularly subscales b, d and gd. mean (sd) developmental quotients (dq) in a= . ( . ); b= . ( . ); c= . ( . ); d= . ( . ); e= . ( . ) and in gd= . ( . ). using the published cutoffs, we found that . % (n= ) of our cohort scored 'above average' or greater in gd. conclusions: we have provided the first data on the use of griffiths-iii in a healthy cohort. scores were higher than expected across all sub-scales. this may be due to the characteristics of our cohort but raises concern that griffiths-iii may overestimate ability in young infants. objective: metabolic investigations are important in the investigation of children with disordered development. the aim of this audit was to determine if paediatric metabolic investigations were ordered as per current best practice evidence at tallaght university hospital, dublin, republic of ireland. methods: we used recommendations from seven publications to guide this audit and identified indications for performing metabolic investigations. we reviewed metabolic investigations sent on paediatric patients at tallaght university hospital from january to december . we identified the clinical indication for investigating patients by reviewing dictated clinic letters available on the hospital intranet and confirmed investigation results by reviewing scanned copies available on the hospital intranet. we compared the indications for metabolic investigations with published expert guidelines. results: metabolic investigations were performed on patients from january to december . six patients had inconclusive results and were referred to the metabolic team at temple street children's university hospital dublin for further assessment. there have been no metabolic diagnoses made to date as per tallaght university hospital dictated letters. of the patients, had a diagnosis of autism spectrum disorder (asd). of those with asd, had a confirmed or suspected intellectual disability. patients ( %) met best practice recommendations for metabolic investigations. of the patients who did not fulfil recommendations, ( %) were for children with asd. conclusions: we identified two areas that could improve patient care by optimising diagnostic yield and improving resource utilisation at the hospital. first, we recommend clinicians send targeted investigations and avoid blanket investigations for children with disordered development, including asd. second, we recommend clinicians include relevant clinical details on request forms to improve diagnostic yield. finally, we question the value of metabolic investigations for intellectual disability in the absence of other clinical risk factors or comorbidities and suggest this requires further study. the early developmental course of babies with sturge-weber syndrome n thapa , t fosi , , v siyani , j sloneem , h richardson , s aylett , university college london medical school, london, uk; ucl great ormond street institute of child health, london, uk; neurodisability, great ormond street hospital, london, uk background: sturge-weber syndrome (sws) is a rare neurocutaneous condition which arises from a mutation in g protein subunit alpha q. the hallmark is leptomeningeal angiomas often associated with a facial port-wine birthmark. seizures, stroke-like episodes and hemiplegia are common clinical presentations. objective: to describe clinical features of infants with sws under years and their developmental trajectory in relation to seizure onset. methods: a retrospective case note review was conducted on children aged below years with sws under clinical review at our centre. the medical history and standardised developmental test results (language, cognition, motor and visuospatial skills) contained in patients' assessment reports were analysed. results: common clinical features of children with sws aged under years were: seizures in patients ( %), hemiplegia in patients ( . %) and glaucoma in patients ( . %). their developmental trajectory was a decrease in the mean percentiles (for language, cognition and motor skills) and mean developmental quotients (for visuospatial skills) over the first months. infants with unilateral brain involvement had significantly higher cognitive percentiles than those with bilateral brain involvement (p< . ), but both groups showed the aforementioned pattern. children with epilepsy had worse language (p= . ) and cognitive outcomes (p= . ) than children without seizure onset. there was seizure onset in the first year in infants ( . %). in these patients, earlier seizure onset was associated with a higher language percentile (p= . ) at age months or at the time of seizure onset. conclusions: following treatment of early seizures in sws language recovery appears to occur over time relative to cognition. the functional plasticity of language might account for these observations. it is proposed that seizure prevention and optimal seizure control in the crucial first year of life will benefit cognitive and language development in patients with sws. objective: rett syndrome (rtt) is a rare neurodevelopmental disorder primarily affecting females, characterized by loss of speech, stereotypies, abnormal hand movements, motor and cognitive impairment. diagnosing rtt before regression occurs remains a challenge and there is an increasing interest in early diagnosis, due to the ongoing gene therapy clinical trial in rtt. methods: retrospective case notes review. the patient was born at term after induction of labour for reduced movements, with meconium-stained liquor, but was well. poor crying and suck noted at birth with gradual deterioration of feeding, with frequent chest infections, necessitating peg-feeding at months. peripheral/axial muscle weakness and hypotonia were noted at this time. mri brain showed mild underopercularisation of sylvian-fissures; thin corpus-callosum. mrs, mri spine, echocardiogram, and eeg were normal. vitamin b deficiency was found, treated with hydroxycobalamin. sleep study showed hypoventilation with frequent apnoeas and low respiratory rate, leading nocturne bipap. emg was myopathic. muscle biopsy showed marginal loss of complex-i activity in the respiratory-chain-enzymes analysis. results: videofluoroscopy showed delayed swallow and disorganised pharyngeal stage leading to peg feeding. over the following months, no regression noted but only minimal motor progression seen; she was interactive and smiled. at months, regression in her motor abilities was notedshe stopped fixing, following and smiling with progressive microcephaly and hand writhing movements. eeg showed epileptic encephalopathy with tonic/myoclonic jerks. whole-exomesequencing showed a de-novo pathogenic mutation in the mecp gene (nm_ . :c. _ del,p.[leu fs] ) and the diagnosis of rtt was confirmed. after months, she restarted smiling and fixing/following and making motor progress but continues to have seizures. conclusions: this case illustrates early-onset features in atypical rtt with central breathing abnormalities, bulbar insufficiency, generalized hypotonia before regression. evidence of mitochondrial dysfunction is in keeping with recent reports suggesting neuronal redox imbalance in rtt as one of the disease pathogenic contributors. objective: neurodegeneration with brain iron accumulation (nbia) comprises a group of rare genetic disorders characterized by progressive extrapyramidal and other neurological symptoms due to focal iron accumulation in the basal ganglia. b-propeller protein-associated neurodegeneration (bpan) is the most recently identified subtype of nbia caused by heterozygous variants in wdr at xp . . we report a new subtype of bpan caused by a de novo wdr variant in a -year-old girl. methods: case report on a new subtype of b-propeller proteinassociated neurodegeneration (bpan) caused by a de novo wdr deletion in a -year-old girl and review of the literature. results: we report a year old girl with bpan due to a large ( bp) de novo chrx:g. , , _ , , del (hg ) deletion in wdr , presenting with early-onset global developmental delay, hypotonia, seizures, and speech apraxia. the patient presented at the age of months with hypotonia and motor developmental delay, following a normal birth history, and at months developed complex partial seizures and later on steroid-responsive electrical status epilepticus of slow-wave sleep (eses). she has made minimal developmental progress and has remained profoundly globally developmentally delayed and cognitively impaired, and has still not achieved independent ambulation. conclusion: we have described the clinical, neurophysiological and neuro-imaging findings in a -year-old girl, the unique combination of which may assist in the diagnosis of further similar cases. bpan is an exceedingly rare, severe and debilitating disorder with a broad spectrum of clinical heterogeneity and variable age at presentation with early-onset symptoms. early detection and diagnosis are very important in order to offer proper genetic counselling to affected families and provide symptomatic treatment to patients. next-generation broad-spectrum genetic analyses will enable early detection of bpan in the paediatric age group in order for patients to be diagnosed prior to reaching adulthood. introduction: how to measure the effectiveness of an early intervention program in low resource setting. can assessments lead to interventions? and with improvements leads to new interventions, can new assessment lead to new interventions? can this system be measured for its effectiveness and improved based on feedbacks and results? an attempt to set up child development centres in low resource countries using software, apps and e-learning. method: years of data in early interventions was analysed in lucknow, india. in phase , children with non-progressive neurological problems were given best available local interventions. only % compliances and improvement were seen. based on the feedback algorithms were written to create individual profile of children based on their skills (uk curriculum of excellence), disability score, information processing preference, educational and behaviour problems. based on the score each child generates an individualised profile and an intervention plan delivered by app for parents (p-bac-drv) and app (t-bac-drv) at child development centres. the assessment is repeated every months and new individualised profile is generated with new set of intervention. in total more than interventions are developed, and the algorithm helps in deciding which main areas to target at one time. result: the current system in low resource settings have either no service or results are close to % prevent disability in non-progressive neurological problems. our system has shown to prevent disability in about % of children. supported by government start up initiative the program has won in top data innovations in india. conclusion: use of technology to provide training, exams and support professionals in the low resources areas is the solution to provide effective services. pattern recognition is the key delivered by software and auto audits has been placed to measure and improve the system. introduction: medical advances in the treatment of cns tumours has enhanced survival but also impacted on levels of residual morbidity and participation. service provision has not increased alongside the improvement in survival, with many patients not being able to return to their previous level of activity and participation following their oncology treatment. nice cancer services for children and young people state: 'children and young people who have had a central nervous system malignancy should receive a specialist neuro-rehabilitation care package'. robbie's rehab, a charity funded physiotherapy service embedded within the southampton children's hospital therapy service, launched june , provides supplementary physiotherapy for children diagnosed with brain and spinal tumours under the care of southampton children's hospital. objective: to accurately identify and quantify the need for this service. method: prospective data was collated and reviewed june -may . results: year : patients; year : patients. new episodes of physiotherapy (average . per month), direct clinical contacts. reasons for accessing the service: need for enhanced intensity of rehabilitation on discharge (n= ), enhanced inpatient rehabilitation (n= ), bridge the gap whilst awaiting community services (n= ), change in symptoms (n= ), pre-op assessment (n= ), support for palliative care planning (n= ), support for complex social and emotional needs (n= ), disease progression (n= ), higher level rehabilitation not fulfilling community criteria (n= ), facilitate access to local exercise facilities (n= ), within oncology clinic for assessment/one-off treatment (n= ), post-op assessment (n= ), individualised goal orientated participation (n= ). patients had an estimated weeks reduction in acute bed days. conclusions: robbie's rehab referrals are for a variety of multifactorial reasons with rereferral often needed within their pathway. it has enabled earlier discharge, improved transition to community services and opportunities for therapy access previously not available. results: our proband presented at weeks with marked stridor and bulbar weakness after a normal pregnancy. he subsequently developed respiratory failure requiring nocturnal bipap and was found to have a type i laryngeal cleft. initially he met developmental milestones but at months developed features of axial weakness with further regression at months with limb weakness and loss of deep tendon reflexes. emg confirmed denervation in genioglossus, as well as proximal and distal limb muscles without evidence of neuropathy. genetics for smn gene and smard were negative. inherited peripheral neuropathy gene panel testing identified a heterozygous missense variant c. t>c, p.(cys arg) in exon . the variant is predicted to alter a highly conserved amino acid, has not been reported before and has not been identified in control databases. in silico prediction tools supports the pathogenicity of the variant. mutagenesis of the equivalent amino acid in mice produces impaired motor control and denervation. conclusions: the gars gene encodes an ubiquitously expressed glycyl trna synthetase which has an integral role in protein synthesis in all eukaryotic cells. missense gars mutations can lead to distal hereditary motor neuropathy as well as a sensorimotor neuropathy phenotype (cmt d) typically with adolescent or early adulthood onset. objective: to discuss sma, which is one of the differentials in a hypotonic child and bring to light the diagnosis is not always cerebral palsy (cp). method: descriptive case report. results: case : -month-old girl admitted to icu with severe pneumonia. case : -month-old boy, both admitted to the intensive care unit with severe pneumonia. case : -month-old girl, presented to outpatient with progressive 'floppy' limb weakness and swallowing and breathing difficulties. case : attended opd with worsening respiratory distress, difficulty feeding, difficulty managing secretions. all had perinatal histories of uncomplicated deliveries but subsequent early respiratory distress and oxygen requirement for the first few days of life. all had been 'floppy' since birth, with severe gross motor delay, feeding difficulties, poor weight gain and recurrent chest infections. cases , and had been diagnosed with cp despite having normal neuroimaging. examination of all children was similar and consistent with clinical diagnosis of sma. findings included an alert, interactive child; frog-legged posture; -limb hypotonia and weakness with legs more affected than arms; absent deep tendon reflexes; bell-shaped chest; and tongue fasciculation. genetic testing for all confirmed homozygous deletion of exon of the smn gene. in all the cases creatinine kinase levels were normal, ruling out myopathy. conclusions: the incidence of sma is / livebirths. it can be diagnosed clinically from pathognomic features when genetic testing is unavailable and should be considered in any hypotonic child, irrespective of perinatal history. a wide clinical spectrum that ranges from early death to near-normal adult life exists. families must be counselled regarding implications of this genetic diagnosis. correct early diagnosis and multidisciplinary intervention can vastly improve outcomes. poster no. syros studylong-term reduction in rate of respiratory function decline in patients with duchenne muscular dystrophy (dmd) treated with idebenone l servais , c lawrence , oh mayer , cm mcdonald , u schara , t voit , e mercuri , gm buyse respiratory function decline in dmd is caused by the underlying weakness and degeneration of the respiratory muscles leading to impaired inspiratory and expiratory effort and associated complications. idebenone reduced the rate of respiratory function decline over weeks in the phase iii delos trial. syros is a long-term study in former delos patients who transitioned to idebenone under expanded access programs following a variable untreated period. here, we aimed to characterize the long-term effects of idebenone on respiratory function. patients were managed according to routine clinical practice. respiratory function was assessed by calculating the annualized decline in forced vital capacity (fvc) and peak expiratory flow (pef), expressed as percent predicted (%p). comparisons were made between treated and untreated periods and to matched external controls. data on bronchopulmonary adverse events (baes) and hospitalizations were collected. data from / former delos patients were available. at delos baseline, mean (sd) age and fvc%p were . ( . ) years and . % ( . %); all patients were glucocorticoid non-users and . % were non-ambulatory. patients were treated for an average (min-max) of . ( . - . ) years compared to an average untreated period of . ( . - . ) years. the annual rate of fvc%p decline was almost halved ( . % vs . %) when comparing these periods. for the external comparisons, declines remained lower across all treatment years (up to y) compared to the matched group of untreated patients. comparable results were seen for pef%p. the risk of baes was reduced by % during longterm idebenone treatment versus untreated periods, leading to fewer hospitalizations due to respiratory causes ( . vs . events per year). long-term treatment with idebenone results in a consistent and sustained reduction in the rate of respiratory function decline for up to years. two placebo-controlled trials of -week duration (phase ii delphi, phase iii delos) showed that idebenone consistently reduced respiratory function decline rate in patients with advanced dmd. long-term data from the delphi-extension (delphi-e) study and syros (delos patients who transitioned to idebenone under an expanded access program) are now presented. the aim was to assess the consistency of the long-term effect of idebenone on respiratory function across both placebo-controlled trials and their respective long-term data collections. delphi-e and syros patients with abnormal (< %) forced vital capacity (as percent predicted, fvc%p) were treated with idebenone for an average of . and . years respectively. annualized fvc%p decline rates were compared to untreated patients from syros or matched external controls (matched for baseline fvc%p) from the cinrg duchenne natural history study (cinrg-dnhs). mean (sd) baseline age was . ( . ) and . ( . ) years in delphi (n= ) and delos (n= ), respectively, and fvc%p was . % ( . %) and . % ( . %). for the first -year period, where data were available for both studies, the average annual decline rate was comparable in treated patients ( . % and . % in delphi-e and syros) and lower than in untreated syros patients and external controls ( . % untreated and . % in cinrg-dnhs). during years to , the annual decline rate was consistently lower than for matched controls. treatment with idebenone resulted in a sustained reduction in the rate of decline in respiratory function across both placebo-controlled week studies and across both long-term data collections, with follow-up time of up to years. the consistency observed across independent datasets adds to the robustness of the treatment effect of idebenone and its potential to modify the course of respiratory function decline in dmd. poster no. a rare mutation in dync h causing a mixed clinical phenotype of spinal muscular atrophy with lower extremity predominance and hereditary spastic paraplegia: a case series in a family el goh , , s jayawant , g anand objective: to describe the identification of a rare mutation in the dync h gene as a cause of a mixed clinical phenotype of spinal muscular atrophy with lower extremity predominance (sma-led) and hereditary spastic paraplegia (hsp). methods: case series of three family members (father and two sons) across two generations. results: there was a history of early childhood-onset, progressive lower limb muscle weakness and atrophy. no relevant family history of neuromuscular disorders was reported on both the paternal and maternal sides of the family. examination revealed markedly diminished tone and power in the lower limbs, with wasting and a positive crossed adductor reflex. there were no abnormalities detected in the upper limbs and sensation was preserved throughout. neurophysiological testing showed moderate to severe chronic denervation of the lower limb muscles with sparing of the peripheral sensory nerves. hsp panel was negative but charcot-marie-tooth (cmt) panel demonstrated a heterozygous sequence change in the dync h gene: c. a>t p.(glu val), which was present in all affected family members. discussion and conclusions: mutations in the dynein gene are typically associated with sma-led or cmt. a mixed sma-led and hsp phenotype has previously been shown to be caused by mutations in bicd . bicd encodes a golgin, which is a component of dynein-based transport, and plays a key role in mrna transport during oogenesis and embryogenesis. we present the first case series of a mixed clinical phenotype of sma-led and hsp occurring due to a mutation in dync h . this was the first observation of the c. a>t p.(glu val) variant at our laboratory and was not listed in the genome aggregation database, suggesting an extremely rare variant. opening the lid on unilateral ptosis in paediatric nf e hassan , e witter , z mughal , l robinson , d weisburg , sa roberts , e hupton , j eelloo , e burkitt wright , , s garg , l lewis , dg evans , , sm stivaros , , , g vassallo , , introduction: neurofibromatosis type (nf ) is a genetic disorder with a birth incidence of in - individuals and prevalence of around in worldwide. ptosis is a welldocumented feature in this condition and is known to be associated with plexiform neurofibromas or in the noonan phenotype, with bilateral ptosis. unilateral ptosis in the absence of a plexiform neurofibroma is not a common feature in nf . we describe a number of patients with nf who demonstrated unilateral ptosis. methods: a retrospective cohort study was carried out using the patient database within the nf service based in st mary's hospital, manchester, uk. children and young adults aged to years with nf were identified via the patient database and patients with a presentation of ptosis were identified. results: six children with unilateral ptosis were identified, four females and two males (ages - , mean= . y). five had unilateral ptosis affecting the right and one the left, with no differences observed between sporadic or familial disease. five patients had complex disease; however, none had any other associated complication to account for the unilateral ptosis apart from nf . they did not meet the diagnostic criteria for noonan syndrome, and none had plexiform neurofibromas in the orbital or peri orbital area. discussion: it is unclear why there is an increased incidence of unilateral ptosis in our cohort of nf patients, in the absence of plexiform neurofibromas and noonan's syndrome. ptosis in nf has been associated with a noonan syndrome phenotype in nf patients. the general hypotonia and myopathy observed in these patients could also factor into the causes for ptosis. further research is necessary to investigate the aetiology of increased unilateral ptosis in nf patients. objective: sma is a severe neuromuscular disorder characterised by progressive muscle atrophy and weakness. scoliosis is a highly prevalent complication and surgery is almost invariably required in 'sitters'. data on secondary outcomes are limited, and this study investigates post-surgical respiratory (fvc%) and motor function, weight gain, pain and satisfaction. methods: we retrospectively reviewed the notes of patients who never walked or lost ambulation (sma type ii/iii) who successfully underwent scoliosis surgery at great ormond street hospital: spinal fusion ( ), magnetic ( ) or traditional ( ) growth rods. we performed phone interviews and run a focus group for families on pre and post-surgical satisfaction. results: median follow-up before and after surgery was . ( . - . ) and . ( . - . ) years respectively. mean annual rate of fvc% decline improved post-surgery in sma ii: - . versus - . (p< . ), with similar trajectories in sma iii. mean annual rate of hammersmith functional motor scale's scores decline did not change significantly (- . vs - . , p< . ), while the revised upper limb module's scores showed a less progressive deterioration (- . vs - . , p= . ). a negative deviation from previous weight curve after surgery was observed in / requiring food supplements ( ); one/ with significant weight loss (> % of total weight) needed gastrostomy. pain was frequently documented, especially hip pain ( / ) requiring painkillers ( ), intra-articular steroids ( ) and surgery ( ). nine/ families participating in the phone interview reported major improvements in posture, physical appearance, self-image; all rated the procedure as very successful. however, / did not report significant improvements in quality of life due to reduced mobility and increased unmet care needs. five families attended the focus group reporting on both positive and negative aspects of their experiences. conclusions: this study provides relevant data and suggestions to improve the current multidisciplinary approach of scoliosis surgery in children with sma. poster no. sunfish part : -month safety and exploratory outcomes of risdiplam (rg ) treatment in patients with type or spinal muscular atrophy (sma) objective: spinal muscular atrophy (sma) is a severe, progressive neuromuscular disease caused by reduced levels of survival of motor neuron (smn) protein due to deletions and/or mutations of the smn gene. while smn produces fulllength smn protein, a second gene, smn , produces only low levels of functional smn protein. risdiplam (rg / ro ) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates smn pre-mrna splicing to increase smn protein levels. sunfish (nct ) is an ongoing, multicentre, double-blind, placebo-controlled study (randomised : , risdiplam:placebo) in patients aged - years, with type or sma. methods: sunfish part (n= ) is a dose-finding study assessing the safety, tolerability and pk/pd of risdiplam; pivotal part (n= ) assesses the safety and efficacy of the risdiplam dose level that was selected based on results from part . sunfish part included patients of broad age ranges and clinical characteristics (functional level, scoliosis and contractures). an interim analysis of part (data cut-off, july ) showed a sustained, > -fold increase in median smn protein versus baseline after year of treatment. adverse events were mostly mild, resolved despite ongoing treatment and reflective of the underlying disease. despite not being designed to detect efficacy, risdiplam improved motor function measures over months versus natural history. results: safety, tolerability and pk/pd will be reported from all patients in part who have received treatment with risdiplam for a minimum of months. updated part exploratory efficacy data, including motor outcome measures, will also be presented. the clinical benefit of risdiplam is being assessed in part , which is ongoing worldwide. objective: ryr encodes the skeletal muscle ryanodine receptor, an intracellular calcium-release channel that is crucial to excitation-contraction coupling in muscle. gene variants can cause heterogeneous myopathies, including dominantly inherited central core disease. both autosomal dominant (ad) and autosomal recessive (ar) pattern of inheritance have been reported. methods: retrospective case notes review. results: sibling : female, presented during the first year of life with motor developmental delay. at years of age she is able to sit unsupported and crawl but not stand or walk. she has facial weakness, but no feeding difficulties or ophthlamplegia. she has axial and proximal weakness with antigravity power in neck flexors and hip flexors (mrc / ) and sub-gravity power in hip abductors/extensors and knee flexors/extensors (mrc / ). there are severe hip, knee and ankle fixed contractures. power and joint range is normal in upper limbs. muscle biopsy showed type- fibre predominance and core-like structures. sibling : female, presented at birth with feeding difficulties. at months of age she is fully nasogastric fed. there is no facial weakness or ophthlamplegia. she has good head control with active head lift in prone, and antigravity power in hips, knees and ankles. she has mild hip and knee contractures and shoulder girdle weakness. both siblings have been confirmed to be heterozygous for a ryr pathogenic frameshift variant (c. _ dupca p.(met fs)) inherited from father and a likely pathogenic missense variant (c. g>c p.(lys asn)) inherited from mother. both parents are asymptomatic. conclusions: the clinical and pathological features of ad ryr -related myopathy are well recognized but much less is known about ryr -related disorders secondary to an ar pattern of inheritance. we report two siblings with ar ryr related myopathy with similar genotypes but different phenotypic features demonstrating intra-familial variability and expanding current knowledge on this disorder. results: our probands were the second and third children of consanguineous irish parents who were fourth cousins. antenatally, reduced fetal movements and amniotic fluid was noted with both probands. at birth, both had arthrogryposis and the second sibling required prolonged intubation at birth. both had significant developmental delay; a more severe phenotype in the younger. on examination, both had myopathic facies, inability to bury eyelashes, full eye movements, high arches palates, drooling, a weak cry, micrognathia but a preserved suck. they both had long thin fingers, with thumbs held adducted and dimpling of elbows and hands. peripheral reflexes were absent but there were good anti-gravity movements of the lower limbs. both were noted to have pectus excavatum and progressive scoliosis. muscle biopsies showed dystrophic features of fibrosis, hypertrophy and atrophy of fibres and variation in fibre size with increased fibrous connective tissue. occasional central cords and multiple mini cords were also seen in the second proband. whole exome sequencing identified the compound heterozygote mutation (ttn c. delc in combination with ttn c c>tp. (ser leu) and ttn c. g >a p. (asp asn)). conclusions: mutations in the titin gene (ttn) have been implicated in several skeletal and or cardiac phenotypes to date. each individual variant of the compound heterozygote has not been reported as pathogenic mutations and have been detected in the general population at . % frequency. however, the presence of the triple count may certainly account for the severe phenotype of our probands. poster no. gene-replacement therapy (grt) in spinal muscular atrophy type (sma ): long-term follow-up from the onasemnogene abeparvovec phase / a clinical trial objective: sma is a rapidly progressing neurologic disease caused by biallelic survival motor neuron gene (smn ) deletion/mutation. the smn grt onasemnogene abeparvovec (formerly avxs- ; approved in us) treats the genetic root cause of sma and is designed for immediate, sustained smn protein expression. in a phase / a trial (start [cl- ]; nct ), sma patients received a one-time onasemnogene abeparvovec infusion at low dose (cohort , n= ) or high dose (cohort , n= ), and demonstrated improved outcomes versus natural history. no patients in start received nusinersen during the -month follow-up after dosing. sma patients in start could rollover into a long-term follow-up study (study lt- ; nct ). primary objective: long-term safety. methods: sma patients have annual visits ( y), then phone contact (additional y). patient record transfers are requested. safety assessments include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. efficacy assessments include developmental milestone evaluation to determine maintenance of the highest achieved milestone in the parent study. results: as of march , patients (cohort , n= ; cohort , n= ) had enrolled in study lt- and had a baseline visit. for patients in cohort , the mean (range) age and time since dosing were . ( . - . ) years and . ( . - . ) years, respectively. all patients in cohort ( / ) were alive. no developmental milestones achieved in start were lost, and new milestones have been achieved, supporting the durability of onasemnogene abeparvovec. updated data will be presented. conclusions: one-time onasemnogene abeparvovec administration at the high dose continues to provide prolonged and durable efficacy with milestone development in lt- . poster no. micu -myopathy: a mitochondrial disorder that mimics a congenital muscular dystrophyreport of siblings with variable phenotypes m fernandez, m sa, v gowda evelina london children's hospital, london, uk objective: micu encodes a selective calcium-channel subunit within mitochondrial inner membrane whose function is essential for buffering cytosolic ca + transients and activating atp production. mutations in micu have been reported in different families with muscle weakness, fatigability and developmental delay, with normal lactate despite being a mitochondrial disorder and persistently elevated creatine kinase (ck) usually in the range of congenital muscular dystrophies (cmd). the phenotypic spectrum is highly variable and keeps expandingother features include progressive extrapyramidal signs, learning disabilities, nystagmus and cataracts. we report the clinical features of siblings from a consanguineous family with the homozygous c. - g>c splicing mutation in micu . methods: retrospective case notes review. results: sibling : boy, older sibling, presented aged years. he had short stature which was investigated when found to have ck of iu/l. he complained of occasional cramps. muscle biopsy showed mild dystrophic changes with reduced alpha-dystroglycan that indicated a possible congenital disorder of glycosylation. his mri brain was normal. he was diagnosed with autism. sibling : girl, diagnosed antenatally with cerebellar hypoplasia, confirmed postnatally as inferior-vermis hypoplasia. presented at years with occasional cramps, mild tightness of tendo-achilles, and ck of iu/ l. her height and weight were on nd centile. muscle mri showed a small area of high signal in the left adductor magnus related to a group of normal vascular structures. neurophysiology studies were normal. no other systemic involvement was seen in either of them. next generation sequencing revealed the micu mutation described. conclusions: our work expands the phenotypical spectrum of micu deficiency and highlights the variability in patients within the same family. targeted analysis of the micu gene in patients with high ck levels resembling a cmd picture may be warranted, even in the absence of prominent muscle features. the role of dystrophin brain isoforms on early motor development and motor outcomes in young children with duchenne muscular dystrophy half of patients have central nervous system (cns) manifestations. two dystrophin isoforms, dp and dp , play an important role in cns function. those lacking dp have a more severe cns phenotype, most marked in those lacking dp and dp . our objective is to determine whether lack of dp and dp also has an adverse impact on early motor development. methods: the northstar ambulatory assessment (nsaa) is a scale of motor function. clinical information for dmd participants was classified by dmd mutation location and effects on isoform expression as follows: dp +_dp + (dp absent, dp /dp present), dp -_dp + (dp /dp absent, dp present) and dp -_dp -(dp /dp /dp absentall isoforms affected). results: amongst to year olds, median total nsaa scores were lower in the dp -_dp + (p= . ) and dp -_dp -groups (p= . ) than the dp +_dp + group, most markedly in the dp -_dp -group. for example, for -year olds, median total nsaa scores were (dp +_dp +), (dp -_dp +) and (dp -_dp -). amongst to year olds, a lower percentage of participants achieved a full score of (normal, achieves goal without assistance) for the nsaa sub-items in the dp -_dp + (p< . ) and dp -_dp -(p< . ) groups than in the dp +_dp + group, most markedly in the dp -_dp -group. for example, amongst -year-olds, percentage of visits for which a full score was recorded for jump were as follows: % (dp +_dp +), % (dp -_dp +) and % (dp -_dp -). conclusions: in addition to the known cns phenotype, young dmd patients lacking dp also exhibit lower median total nsaa scores and greater early motor delay, most markedly seen in those lacking both dp and dp (lacking all dystrophin brain isoforms). this has important implications for patient prognostication and clinical trial design. background: most commonly known as a rare subtype of guillain-barr e, miller fisher syndrome (mfs) has evolved since it was first described in . the syndrome is characterised by a triad of ophthalmoplegia, ataxia and areflexia but clinical variations do occur. it occurs more often in men than woman (ratio : ) with the average age of onset . years. mfs is associated with positive anti gq b antibodies, which is concentrated in cranial nerves iii, iv and viexplaining the link with ophthalmoplegia. clinical case: we present an unusual case of a -year-old boy with background of macrocephaly and pre-existing developmental delay with a previous mri which showed mild signal change in periventricular white matter bilaterally. he was admitted with a subacute history of proximal muscle weakness and fatiguability. he had no obvious focal neurological signs apart from intermittent lid hopping and ptosis. differential diagnosis included myasthenia, demyelinating disorders or an underlying pre-existing luecodystrophy. anti gq b antibodies were checked along with extensive metabolic investigations, lumbar puncture, muscle biopsy, anti-cholinesterase and antimusk antibodies along with repeat mri. all investigations were negative including mri which showed no significant change from previous. the only findings were strongly positive anti gq b antibodies. in the interim, the patient was started on trial with pyridostigmine with significant clinical improvement. conclusion: atypical variants of mfs should be a differential in children with subtle eye signs without ophthalmoplegia. lid hopping and fatiguability should raise the suspicion of mfs and anti gq b antibodies should be tested. pyridostigmine has been reported to be effective in mfs. potential utility of muscle mri in congenital myasthenia syndrome secondary to agrn mutation found on whole exome sequencing (wes) congenital myasthenia syndromes (cms) are caused by genetic defects affecting neuromuscular transmission, resulting in muscle weakness and fatigability. agrin, an extracellular matrix molecule released by the nerve is essential at the neuromuscular junction. the large coding gene agrn, has a number of exons and with increasing variants found on wes, it is time consuming and complex to undertake functional studies to define pathogencitiy. previous reports of agrn mutations have a phenotype with prominent distal leg weakness and changes in the soleus on mri. we describe a differing presentation and striking changes on mri, especially in the posterior compartment of the thigh. a -year-old presented with deterioration in his gait and difficulty climbing the stairs. he was born at term, via a normal vaginal delivery. his parents were consanguineous, and he had three well siblings. he was reported to walk by years. on examination he had a waddling gait and was unable to run or hop. he had proximal weakness with a positive gowers sign, together with weak eye closure. muscle biopsy showed non-specific myopathic features, however an mri of the lower leg found widespread fatty muscle atrophy of the thigh and calf with relative preservation of the adductor longus, rectus femoris and semitendonosis. wes revealed an agrn mutation (c. _ del) and a homozygous mutation in the nebulin gene (not felt to be clinically relevant). single fibre emg confirmed electrodecrement on repetitive nerve stimulation. the patient has been commenced on treatment with salbutamol. our patient had very distinctive changes on mri and nonspecific muscle biopsy changes. muscle mri changes prompted further genetic testing when symptoms fitted a clinical diagnosis of a congenital myasthenic syndrome. with increasing variants found of unknown significance in these patients, collation of mri imaging to try and elucidate patterns of changes will be important. mcardle disease (glycogen storage disease type v) is an autosomal recessive condition caused by pathogenic mutations in both copies of the muscle glycogen phosphorylase (pygm) gene encoding the muscle-specific isoform of glycogen phosphorylase, 'myophosphorylase' exclusively affecting skeletal muscle. it is the commonest form of glycogenosis. mcardle disease shows significant clinical variability, with symptoms ranging from mild discomfort during exercise to marked muscle weakness and rhabdomyolysis with myoglobinuria. the second wind phenomenon is unique to mcardle disease and consists of improved exercise tolerance with a decrease in heart rate after a rest. despite the majority of patients recalling symptoms during the first years of life, mcardle is infrequently diagnosed in children, % of patients being diagnosed after years of age according to a recent review. here we report two patients diagnosed with mcardle disease at the age of and years respectively. case one presented with fatigue and inability to increase pace of walking from the age of . hills lead to earlier fatigue. she was able to participate in gymnastics and dancing. presentation was with fluctuating ck levels ( to ). she had no second wind phenomenon or myoglobinuria. case two presented at years with a history from months of reduced exercise tolerance and myalgia after low intensity physical activity with no evidence of myoglobinuria or second wind. on formal assessment there was no evidence of muscle weakness or functional impairment. ck was persistently raised ranging from to . in the light of symptoms and ck levels a rhabdomyolysis panel was requested in both cases leading to diagnosis. objectives: to explore characteristics of anxiety experienced by young males with duchenne muscular dystrophy (dmd) using: . qualitative analysis of focus group discussions with dmd boys and their parents. . parent-report scales of anxiety/emotional problems. methods: eight boys aged to years with dmd and dmd parents participated in separate child and parent focus groups. perspectives on anxiety were elicited using semi-structured discussions, and framework analysis was applied to identify themes. scores on five parent-report scales were determined and scales were compared for content and sensitivity. results: from group discussions, six characteristics of anxiety were recurrently reported: catastrophic conclusions; rigidly held anxieties; extreme distress; unexpected/unfamiliar; social anxieties; physical changes and needs. many features echo the anxiety phenotype in autism spectrum disorder (asd). four further themes described relevant contextual factors: individual, family, social and environmental responses. from parent-report scales, younger dmd boys ( - y; n= ) had significantly higher total, general and social anxiety scores compared to population means on at least two scales (p< . ; p< . ; p< . ). the older dmd group ( - y; n= ) trended towards higher scores in total, general and separation anxiety (p= . ; p= . ; p= . ) compared to population norms. different scales varied in their diagnostic sensitivity and item content, which may influence their utility in dmd. conclusions: anxiety can be a pervasive and impactful issue in dmd. it appears to have some shared traits with anxiety in asd and may be influenced by situational factors, such as living with a disabling, life-limiting condition. screening with standard anxiety scales may not accurately capture the full spectrum of the phenotype in dmd, therefore further evaluation to determine optimal screening instruments in dmd is warranted. however, multi-modal assessments tailored to dmd are key to identifying those in need of support to optimise the mental well-being of young people with dmd. objective: as part of the clinical psychology service in paediatric neurology we developed a tic management group to support young people and their parents to develop positive coping in relation to their tics. the group combined psychoeducational, emotional regulation and habit reversal therapy (hrt) components. this evaluation aimed to establish the effectiveness of these groups in reducing tics and associated distress. method: twenty-eight children, aged to years and their parents attended one of seven tic management groups facilitated between february and november . these children had been referred to the clinical psychology for support with tics. each group consisted of weekly, -hour sessions with a review session weeks later. a parent group was held in parallel. both the young persons and parent groups were facilitated by the clinical psychology team. homework tasks were provided to support hrt skill practice and consolidation of learning of the group content between sessions. the following pre and post group measures were completed by the young people and their parents: the paediatric index of emotional distress, the yale global tic severity scale, the parent tic questionnaire and session rating scales. measures were collated and descriptive data reviewed. results: % of children found the group was helpful in the management of tics. % of children were 'less bothered by their tics'. % of children felt more confident in controlling their tics. parents reported a greater understanding of tics and a reduction in the severity of their child's tics. conclusions: results indicate the tic management group is effective in building young peoples' understanding of tics, confidence in tic management whilst providing peer support. the findings also indicate that parents found the groups informative and valued the opportunity to share experiences with others. background: patients with epilepsy often have deficits in cognitive, physical, psychological and social functioning, and treatment should aim to alleviate these deficits. epilepsy surgery is considered for medication refractory epilepsy with aims to improve patient quality of life. a recent study highlighted the importance of a multidisciplinary workup prior to epileptic surgery, including a neuropsychiatric assessment. part of this assessment should identify patient expectations of epilepsy surgery, so that these can be addressed peri-operatively. at king's college hospital (kch), london, these assessments are routinely performed by the paediatric liaison service as part of the children's epilepsy surgery service (cess). aim: to analyse retrospective data of pre-operative patient and carer expectations between october -september at kch. methods: a record of patient and carer expectations is routinely recorded as part of kch cess neuropsychiatric assessments. the responses were compiled and analysed using qualitative content analysis. results: a preliminary survey of cases with an average age of (range - ) identified responses that were grouped into broader classifications (cognitive, seizure experience, social process, school experience, mental state and general improvements). simple analysis showed carers most often expected surgery to reduce the need for medications ( %), ablate seizures ( %), increase school performance ( %), independence ( %) and overall quality of life ( %). this compared to child responses, where the most common expectations were a reduction in lifestyle restrictions ( %), a cure for epilepsy ( %), decrease in medications ( %) and increased independence ( %). conclusion: consideration of both child and carer expectations during pre-epilepsy surgery neuropsychiatric assessments is important in order for services to manage each individual's expectations. unmanaged unrealistic expectations may lead to a negative psychological outcome for either child or carer. expectations should be weighed up against an individual's clinical profile. poster no. neural correlates of conversion hemianaesthesia in an adolescent: a novel fmri case study m ray, a zaman, t alam leeds teaching hospital nhs trust, leeds, uk aim: to highlight the novel functional magnetic resonance imaging (fmri) findings in an adolescent with rare conversion hemianaesthesia. methods: we hereby report a right-handed y old boy who presented with inability to perceive sensations on the right half of body without any motor weakness causing him to have frequent injuries on his right leg as well as burns on his right hand without realizing. when he wore a jacket, he felt warm on one side of the body more than the other. his birth and developmental history were non-contributory. neurological examination was unremarkable except for right hemisensory disturbance. the mri of brain and spine, peripheral nerve conduction studies and somatosensory evoked potentials did not show any evidence of dysfunction were normal. he underwent fmri on a t philips achieva. the paradigm consisted of stimulating both the right and left hands and feet with three dissimilar stimuli (cold, brushing, pin-prick-pain) . the order of the stimuli was pseudorandomised and after each stimuli delivery, feedback was obtained. results: both the hand and foot sensory motor cortices were successfully stimulated. irrespective of which hand was being stimulated, there was left hemisphere sensory motor cortex dominance (with the brushing and cold stimuli), however selfreport from the participant confirmed detection of stimuli on the left-side only. there was more sensory-motor activation when the stimuli were delivered to the right hand. pain stimuli successfully activated parts of the 'pain matrix', furthermore enhanced attention effects (frontal pole activations) were observed with right-sided stimulation (supports lack of stimuli detection ability). the pain stimuli were more effective on the hands than foot, reflected by increasing activation and also self-report from the participant. conclusions: the fmri findings are unique and support the evidence of neuroplasticity and the current study paves the way for future studies investigating conversion hemianaesthesia. poster no. chronic paroxysmal hemicrania presenting as facial pain in a child with autism and bipolar disorder: diagnostic challenges case presentation: a boy diagnosed with disintegrative psychosis aged , revised to autism with bipolar disorder, had been on carbamazepine with risperidone for poor mood control. withdrawal of risperidone produced tardive oromotor diskinesia responsive to clonidine. aged , when mood improved on aripiprazole, carbamazepine was withdrawn. he then presented with episodes of distress preceded by withdrawal, unilateral but not side-locked facial flushing, with additional flushing of neck, back and wrists. behaviours included hitting wrists off walls, chewing of hard objects and requesting pressure to his head. episodes occurred - times/ day, lasting - minutes. he showed rhinorrhea and tearing, attributed to crying, during events. the attacks self-terminated. results: mri and electroencephalogram were normal. failed pharmacological trials included paracetamol, amitriptyline, gabapentin and oxcarbazepine. diclofenac provided mild pain relief and morphine reduced the incidence of attacks. reintroduction of carbamazepine resulted in improvement at mg/kg/day but did not eliminate pain. sequencing of scn a was normal. a plan to wean morphine alongside a trial of indometacin, initially at mg twice-daily was successful at mg twice-daily. episodes ceased, including all autonomic features. exacerbation at weeks occurred in context of an intercurrent illness and was managed with an additional dose of indometacin. conclusions: cph is underreported in the paediatric age group. in our case, the patient's inability to describe events, and an additional psychiatric diagnosis added complexity. the possibility of pain as a cause for early psychotic breakdown in a developmentally vulnerable child cannot be excluded. criteria emphasising side-locked headache and autonomic features, and not recognising associated symptoms elsewhere may also delay recognition in children. objectives: piih can be a challenging condition to diagnose and manage with risks of misdiagnosis, permanent sight loss and frequent comorbidities. we aimed to review our practice to identify areas of uncertainty to help formulate important questions to address within a clinical guideline. methods: a single centre retrospective case notes review of all cases referred to neurology with suspected piih (papilloedema confirmed by a consultant ophthalmologist in all cases) during an -month period. results: ( f: m) cases were identified. age range to years. mean years. / had a bmi > th centile. one case was referred to an obesity service. / had a comorbid headache disorder and / had anxiety/depression. all cases had neuroimaging ( mri, ct) with / having dedicated venography. in / cases lumbar punctures (lp) were conducted under general anaesthesia (ga). in / cases lp was not done; due to presence of a chiari malformation and due to procedural failure related to body habitus. intracranial pressure (icp) monitoring was done in one of these four cases. all children were treated with acetazolamide as first line therapy. frusemide, zonisamide and topiramate were also used in single cases. / children had repeat lps due to failure of resolution of symptoms. / cases had sight threatening piih with permanent visual loss in one case. / cases were discussed with neurosurgery. one child with evolving visual failure had an emergency ventriculo-peritoneal shunt. conclusions: important questions raised were: should all obese children with piih have access to a specialised obesity service? should all children have dedicated venographic imaging? how reliable is measuring csf opening pressure under ga? where lp is not possible should icp monitoring always be done? should repeat lps be done for persistent symptoms? should csf diversion surgery be restricted to cases of sight threatening piih only? objective: to describe a case of revesz syndrome due to a de novo missense variant in tinf . case report: a male infant was born at weeks gestation by emergency lscs due to maternal hypertension and reduced amniotic fluid. from week's gestation, reduced fetal growth was identified. the proband was born by at weeks. birth weight was . kg ( . th- nd centile) and occipitofrontal circumference (ofc) was . cm ( nd- th centile). he spent days in the scbu. he developed thrombocytopenia (nadir: /l), which resolved pre-discharge. periventricular calcifications on cranial ultrasound prompted torch screen and ophthalmology review. a right pre-retinal haemorrhage with overlying organised vitreous haemorrhage was identified, which remained stable on subsequent reviews. aged weeks, he was smiling, fixing and following with good head control. aged months, he developed new wobbly eye movements and was no longer fixing or following. bilateral retinal detachments were identified. ct and subsequent mri showed diffuse calcification within the thalami, posterior limb of the internal capsule, deep white matter, cerebellar atrophy and thin corpus callosum. findings on examination included ofc of . th centile, rotatory nystagmus and central hypotonia. whole-exome sequencing identified a pathogenic de novo variant in tinf (c. g>a, p.arg his). he subsequently developed thrombocytopenia and anaemia and is transfusion dependent. discussion: trf interacting nuclear factor- (tinf ), protein regulates telomerase and prevents telomere shortening. revesz syndrome is a severe form of dyskeratosis congentia, with multi-system involvement and early onset in-utero. revesz syndrome is characterised by intrauterine growth retardation (iugr), microcephaly, cerebellar hypoplasia, bilateral exudative retinopathy, intracranial calcifications and progressive bone marrow failure. revesz syndrome is distinguished from hoyeraal-hreidarsson syndrome by the presence of retinopathy. telomere disorders should be considered in infants with a background of iugr, thrombocytopenia, retinopathy and intra-cranial calcifications with a negative torch screen, as early features mimic congenital infection. objective: currently the most commonly reported neurological complication of sca is overt stroke. reversible cerebral vasoconstriction syndrome may be more frequent in patients with sickle cell anaemia than reported at present. the scarcity of prevalence studies however makes it difficult to improve diagnostic accuracy in these patients. methods: a -year-old ghanaian female was rushed to the paediatric emergency room with first episode of sudden severe global headaches initially started hours prior to arrival. the headache was so excruciating that she described it as her heart was beating in her head. there was associated neck pain, back pain, dizziness, and vomiting. there was no fever or dark urine. she was first diagnosed with sickle cell anaemia (genotype ss) at years of age after she was treated for dactilitis. she had since then been in her usual state of health with no history of blood transfusions or surgeries or admissions. she was compliant with her medications (folic acid mg daily). a physical examination and all investigations were also normal. on day six of admission patient had a generalized tonic clonic seizure with some degree of left sided weakness after having her bath. this was aborted with intravenous diazepam and a magnetic resonance imaging (mri) of the brain was requested. the mri of the brain revealed diffuse narrowing of the cerebral arteries with no areas of bleeding or oedema. reversible cerebral vasoconstriction syndrome was therefore suspected. results: the headache rapidly improved after starting nimodipine and repeat angiography at months showed no vasoconstriction, confirming the diagnosis. on follow up she is doing well academically with no neurological deficits. conclusions: the true incidence of rcvs in patients with sickle cell is uncertain, thus sensitizing medical practitioners is important. introduction: status dystonicus (sd) is a life-threatening disorder of generalised, painful dystonic movements and muscular spasm in patients with severe neurodisability. while rare, it may be complicated by rhabdomyolysis, multi-organ dysfunction, and death. infection, pain, gord, and medication failure are common triggers, but in approximately one-third of cases, sd is idiopathic. mordekar et al. ( ) identified a series of patients in whom sd occurred secondary to gi dysfunction. assisted feeding (e.g., via gastrostomy), and aberrant bowel peristalsis may trigger the onset of sd. this was a retrospective analysis which aimed to estimate an incidence rate for feed-induced sd (fisd). methods: patients presenting to sheffield children's hospital over a -year period with sd were identified. episodes were studied to assess for the nature of the onset of sd and as to the likelihood that the trigger was feed related. incidence of fisd as a proportion of total sd was calculated and or calculation performed to explore relative risk of sd between individual trigger factors. results: twenty-four individual episodes of sd were identified. ( %) arose from non-feed-related sources (nfisd), and were felt to be fisd ( %). additional patients were entered into a feed-induced dystonia (fid) group, whom showed clinical evidence of dystonia in relation to gi sources, but not sd. with the exception of infection, the relative risk of sd secondary to gi dysfunction was significantly higher than pain/gord and medication failure combined (or . ( % ci . - . ) and . ( % ci . - . ) respectively). conclusion: gi dysfunction coupled with severe neurodisability could serve as a trigger in a number of previously idiopathic sd cases through disruption of the neuro-enteric axis. however, overlap between triggers for fisd and nfisd, and significant variation between groups is evident, in addition to a lack of statistical study power. large, prospective studies are needed in the future to corroborate with these findings. poster no. dystonia can twist the patient, physician and the scans: hypermanganesemia, a rare cause of dystonia in children r kumar, s ali liaqat national hospital, karachi, pakistan introduction: manganese (mn) is a chemical element with symbol mn and atomic number . mn in the environment can cause toxicity with dystonia and other movement disorders. waterborne mn has a greater bioavailability than dietary manganese. according to results from a study, higher levels of exposure to mn in drinking water are associated with increased intellectual impairment and reduced intelligence quotients in school-age children. we have recently reported a suspected autosomal recessively inherited syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia in cases without environmental mn exposure. the rarity of the disease can become a challenge for the physicians to recognize this as a cause of dystonia in children. it also has a characteristic finding on mri with t hyperintensity in basal ganglia rather than on t . case report: we present a case of a -year-old girl with dystonia who was previously healthy. she has been suffering from this for the last months and currently one of her years old sister started showing similar symptoms. physical examination revealed marked dystonia (score of on baryalbright dystonia scale) and polycythemia (haematocrit ). magnetic resonance imaging (mri) brain showed basal ganglia hyperintensity on t weighted images. hypermanganesemia was suspected and samples send for serum level which came out to be high. water samples were tested, which came out to be normal. chelation was done and the dystonia improved. conclusions: dystonia in children should be thoroughly investigated and rare, treatable causes should not be ignored. objectives: sodium valproate is used primarily for the treatment of epilepsy in children. it is a well-established teratogen, with in babies at risk of developmental disorders and in babies at risk of birth defects. this risk has been known since the s and yet it is estimated that since then children in the uk have been left with disabilities as a result. in , the medicines and healthcare products regulatory agency released guidance for its use, which included a risk acknowledgement form. patient safety alerts were issued in asking all organisations to identify females taking this medication. we aimed to identify all girls taking sodium valproate in the south eastern trust under paediatrics requiring annual risk assessment; patients under the additional care of a neurologist; patients receiving an annual review. methods: patients were identified through paediatric epilepsy nurse records and data collected through the electronic care record and medical notes from august to december . results: % (n= ) of girls with epilepsy currently taking sodium valproate, % under the age of years, % profound learning difficulties/disability and considered to be at low risk of pregnancy, % (n= ) potentially currently at risk, % were under the additional care of a neurologist, % reviewed in the past year. conclusions: sodium valproate must not be considered first line treatment in girls with epilepsy and > % of girls in our trust are not receiving it. of those receiving it, the majority are felt to be low risk due to young age and/or profound disability. we identified two patients at risk and steps were taken to ameliorate this. we have demonstrated good awareness; however lifelong education of families is crucial to reducing the burden of fetal valproate syndrome. rett syndrome (rtt) is neurodevelopmental disorder affecting approximately in - live female births, most commonly associated with mutations in the mecp gene. hand stereotypies and gait disturbance, as well as spasticity and dystonia, have been noted in rtt since the first descriptions of the syndrome. objective: this review aimed to explore the prevalence of reported movement disorders in rtt. data sources and extraction: pubmed and embase databases for papers describing features of movement disorders in rett syndrome. papers were selected for inclusion to be reviewed if they included description of case report, cohort or case-series of patients with rtt which included a description of clinical features of their movement disorder. selected papers were divided into epochs: (i) pre- , (ii) to , and (iii) onwards. results: studies ( in the first epoch, in the second epoch and in the third epoch) reported on movement disorders including stereotypies in rtt patients. hand stereotypies were almost universal in reported cases, diminishing but not disappearing over time. gait disturbance and ataxia/tremor were also very common (> % cases). elements of hypertonia were also common, increasing with age. in earlier descriptions spasticity was commonly described, with more frequent reference to dystonia/rigidity in more recent reports. myoclonus and choreoathetosis are uncommonly reported in rtt. conclusions: movement disorders beyond hand stereotypies are common in rtt, most notably tremor. hypertonia is a common feature seen in rtt, increasing in prevalence with age, and with an apparent change in nomenclature over time, (i.e., early epoch spasticity, late epoch dystonia). dystonia was specifically reported in / cases. further work is required to explore the relative contribution of dystonia and rigidity to hypertonia in rtt, as well as the impact of these impairments when present. introduction: headache is the common complaint in children, and the source of it, a great deal of worry for general practitioners and parents. one of the commonest causes of headache in paediatrics is migraine. methods: a prospective study was conducted to evaluate the demographic data, clinical spectrum and grading the child with migraine by using the paediatrics migraine disability assessment (ped-midas) questionnaire and to start prophylactic treatment for those with the higher grades in the department of paediatrics in tertiary care hospital. all children with migraine from age to years were included while all other types of headache cases were excluded. results: total children with migraine were studied. approximately % children complained of bilateral frontotemporal headache in which . % presented with throbbing type. other associated features were photophobia, phonophobia, nausea and vomiting. % had skipped meal, followed by altered sleep and exam stress as aggravating factors. . % required medication for headache relief. headache duration and frequency was approx. days and days/month. . % cases were diagnosed migraine without aura and . % cases were diagnosed as migraine with aura. loss of full school days due to headache was approx. days for period of months. based on ped-midas score, % of children with migraine had grade i disability while . % and . % cases had grade ii and grade iii disability respectively. correlation of ped-midas score with frequency and severity were significant (p< . ) while with duration of headache was insignificant (p< . ). conclusions: all patients with higher ped-midas grade are warranted prophylactic treatment. both ped-midas scores and grading can be successfully used for assessing the migraine disability and its easier, less time consuming, bedside diagnostic tool, can be used widely in routine clinical evaluation and management. objective: to review the cases referred to this uk-wide study of children with possible variant creutzfeldt-jakob disease (vcjd) and report the differential diagnosis in children presenting age years or older. methods: children meeting the case definition for progressive intellectual and neurological deterioration (pind) were identified via the british paediatric surveillance unit. details were obtained by standard questionnaire. results: between april and august , children had been notified to the study. were found not to meet the pind case definition. had an underlying diagnosis to explain their deterioration, with over different disorders including vcjd cases (the last identified in ). there were children who presented to clinicians when aged years or over, including all the vcjd cases. of the other disorders in this age group the commonest were: mitochondrial cytopathy , adrenoleukodystrophy , lafora body disease , huntington's disease , neuronal-ceroid lipofuscinoses , niemann-pick type c , metachromatic leukodystrophy , sspe , wilson's disease . when reviewed in there was no underlying diagnosis in pind cases; of them had diedonly underwent autopsy. the recent identification of the first patient with vcjd who was mv heterozygous at prnp codon reinforces the need for continued vcjd surveillance, particularly as a study of archived appendix samples from uk hospitals published in indicated that approximately in of the uk population is carrying abnormal prion protein in the gastrointestinal tract. in the absence of a validated vcjd screening test the pind study remains the only means of performing systematic surveillance of the neurodegenerative diseases that make up the differential diagnosis of vcjd. objective: transient lesions in the splenium of corpus callosum (scc) are rare findings in mri brain in paediatrics. in literature, it has been described as reversible splenial lesions syndrome (resles) and mild encephalitis/encephalopathy with reversible splenial lesions (mers). the condition has diverse aetiology and widely variable neurological presentation but the prognosis is usually favourable. we present two cases of resles with predominantly expressive dysphasia but varying causal associations. method: retrospective review of resles case series exploring clinical course, investigations, neuroimaging, treatment and recovery. result: case : a year-old-girl presented with confusion, fever and low oxygen saturation. she had alagille syndrome and partially corrected tetralogy of fallot. her neurological manifestations were expressive dysphasia, dysarthria and difficulties with spatial awareness. interestingly she was able to use occasional words that were abusive in nature. mri showed prominent focus of abnormal signal and restricted diffusion in scc. her blood culture grew staphylococcus aureus and echo revealed infected shunt. treatment involved shunt replacement and prolonged iv antibiotics. repeat mri showed resolution of splenial lesions. she continued to improve neurologically. case : a year-old-girl presented with paroxysmal episodes of head turning, head drop and staring for a few seconds. she refused to feed. she showed emotional lability with expressive dysphasia but preservation of expletives. neurologically she was intact. mri brain showed high signal with restricted diffusion in scc. her blood and csf investigations including mog, aquaporin, nmdar, lyme antibodies were negative except asot was . her eeg was normal. she received a course of ivig and azithromycin. her repeat mri showed resolution of the lesion in splenium. she made complete recovery over next few months. conclusion: splenial lesions are rare but clinically significant but not 'non-specific'. expressive dysphasia is a prominent symptom. awareness of resles/mers will avoid unnecessary investigations and assist in the prognostication. background: the evidence-base on managing paediatric-headaches is sparse resulting in wide variation in practice with nice guidelines commencing over years of age. this study aims to evaluate outpatient management of paediatric headaches. objective: to investigate paediatric headache referrals to a tertiary hospital over a -year period, exploring patient demographics, headache type, role of neuroimaging, management and outcome. methods: this prospective study reviewed headache referrals for the year - . the data was collected following weekly emails to relevant clinicians. the patient demographics, headache classification, imaging, management and outcome were collated on a proforma from the electronic patient-records. results: there were patients. the median age of patients at first outpatient appointment was years (range - y); . % were female. incidence of headaches increased with age. female preponderance of headaches existed in all age groups and was most substantial post-puberty with a . : female-to-male ratio in patients aged to years. migraine was the most common diagnosis, affecting . % of patients. % of referred patients underwent a brain mri scan, all of whom had a normal neurological examination. no mri scans found pathology contributing to headache presentation. % of patients were discharged from neurology clinic after first or second neurology appointment. non-pharmacological management was the most common intervention and consisted of: headache diary, lifestyle advice, education, relaxation techniques. the most common medications prescribed bar simple analgesia were sumatriptan ( %), propranolol ( %) and pizotifen ( %). conclusions: a multidisciplinary and biopsychosocial approach to managing paediatric headaches, consisting of non-pharmacological and pharmacological methods resulted in a positive outcome, with majority discharged from tertiary care after first appointment. prescription of sumatriptan and propranolol first line for acute and prophylactic management respectively, was in accordance with current clinical recommendations. the role of mri scanning for paediatric headaches requires further exploration and perhaps more stringent guidelines. objective: the head-up tilt test (hutt) is the gold standard autonomic function test for identifying disorders of blood pressure (bp) and heart rate (hr) regulation, specifically with excessive falls in bp and or hr, as well as excessive postural tachycardia (pt). the minute active standing test (ast) is quicker and easier to apply, e.g., in an outpatient clinic, and may be more sensitive in demonstrating pt. we aimed to compare the yield of these abnormalities when using ast vs hutt. methods: this was a retrospective, clinical notes review, and registered clinical audit of unselected consecutive children and young people undergoing hutt immediately preceded by an ast. results: data was available on children and young people, ( %) female, aged to years (median ). / ( %) with complete data sets for the first minutes of hutt and the ast had abnormally large drops in bp and or hr on hutt. only / positive on hutt was also positive on ast. however, an additional / ( %) were positive on ast but not on hutt, giving / ( %) positive in total. / ( %) with hr data sets for minute hutt and ast had abnormally large rises in hr on hutt. only / positive on hutt were also positive on ast. however, an additional / ( %) were positive on ast but not on hutt, giving / ( %) positive in total. while hutt yielded more cases with significant falls in bp and or hr than ast ( % vs %), combining the tests gave the highest yield ( %). while ast yielded more cases with significant rises in hr than hutt ( % vs %), combining the tests gave the highest yield ( %). conclusions: we recommend routinely undertaking a minute ast prior to the minute °hutt, in children and young people. objective: the aim of our work is to describe the respiratory function trajectories and their correlation with motor function in a cohort of spinal muscular atrophy type and non-ambulant sma paediatric patients. methods: this is a retrospective -year study in patients recruited in the ismac natural history study (uk, italy, us). the following respiratory data were collected: lung function data (forced vital capacity absolute (fvc) and fvc% predicted, non-invasive ventilation (niv) requirement. recumbent or ulnar length were used as surrogate for height in fvc%pred. calculation. comorbidities affecting lung function such as aspiration were collected. anthropometrics and motor function scores as hammersmith functional motor scale (hfms), revised performance of upper limb (rulm) were noted. we excluded patients in interventional clinical trials and nusinersen therapy. results: data were available for patients: sma , sma . mean age at first visit was . (ae . ) and . (ae ) years for sma and . / ( %) sma and / of significant lesions. a review of practice of asking routine or non-urgent mri requests should be considered in view of an unlikely significant result. retrospective review of brain magnetic resonance imaging referrals in children less than years (r[ ] ) is an ultrarare disease characterised by drug-refractory epilepsy, cognitive impairment and behavioural problems. non-pharmacological treatments should be considered alongside antiepileptic drugs (aeds) early after diagnosis to benefit prompt seizure control and preserve cognitive function. we aimed to understand the use and experience of ketogenic diet therapy (kdt) in r( ) by patients families carers (pfcs) and healthcare professionals (hcps), assessing its efficacy and safety, and contrasting nhs kdt service provision with patient demand. methods: literature searches were conducted on use of kdt in r( ) and similar complex epilepsies. two surveys were developed to gather demographic, diagnostic and clinical care information. surveys were qualitative and descriptive with patient and expert collaborators assessing content accuracy and readability. responses were discussed at a patient and expert workshop. results: the number of responses ( pfcs, hcps) was considered significant given the ultra-rare status of r( ). % of pfcs had tried kdt. seizure activity, behaviour and cognitive outcomes were ranked equally important by hcps and pfcs. significant improvement in seizure activity, cognition and alertness were reported; side-effects were typically mild but with one report of increased seizure frequency. the high rate of comorbidities, older age at presentation, behavioural problems and cognitive impairment can make implementing kdt in r( ) challenging. pfcs report quality of life would be most improved with reduced aed side-effects; hcps report they would consider reducing or withdrawing aeds where kdt is successful. conclusions: kdt may not be suitable for every r( ) patient, but there is a strong consensus that it should be considered as an early intervention. in the uk, nhs kdt services are predominantly available for paediatric patients, with very limited adult access. a detailed health economic analysis illustrating reduced acute care costs and improved quality of life may encourage more widespread kdt implementation. objectives: whole exome sequencing (wes) with a -week result turnaround time has become available on the nhs for children in an intensive care setting. we aimed to determine the diagnostic utility and impact on clinical care of wes in a regional paediatric neurology centre. methods: retrospective case notes review. results: six cases ( m, f) were identified. three patients were dependent on long-term respiratory support. a pathogenic mutation was detected on wes in / cases ( %). one case required 'reverse phenotyping' with an abnormal transferrin glycoform electrophoresis confirming that two heterozygote variants of the rtf gene were consistent with a congenital disorder of glycosylation (cdg). no other variants of unknown significance were found. three children presented with neonatal onset epileptic encephalopathy (two cases had scn a, one case wwox), one child with intractable epilepsy from months of age (rft mutation associated with cdg) and one child with hypotonia and ventilator dependence after a respiratory infection at months of age (ighmbp mutation associated with spinal muscular atrophy with respiratory distress). wes found no pathogenic mutation in a -year-old with intracranial calcification, microcephaly, epileptic encephalopathy and severe developmental regression. in / cases other single genes/panels had been sent prior to initiation of wes with multiple single genes/panels sent in / cases. in / cases wes detected the gene thought most likely based on clinical phenotyping on the request form. conclusions: wes has a high diagnostic yield in this cohort of patients. reaching a prompt diagnosis facilitated withdrawal of care in one case (ighmbp ) and helped to exclude an epilepsy surgery hypothesis in four cases as well as guide prognosis in all cases. wes should be considered as a cost-effective alternative when multiple single genes and/or genetic panels are being sent off in parallel due to clinical urgency. objective: the care provided in the time surrounding the death of a child shapes long-term memories and has potential to impact on the grieving process. there are no specific guidelines for picu staff in relation to what good care looks like at this time. we sought insight into practice across the uk to build an evidence base, improve care provided and share good practice. conclusions: from the survey feedback, we found this was an area that all units believe can be improved. in relation to acps, we hope this will be more widely introduced. we know that % of patients admitted to picu are life limited. these difficult conversations with family help guide management, understand wishes, and formal documentation ensures all staff are aware. several units with higher uptake of hospice/home care found early conversations with families beneficial. units with a dedicated palliative nurse stated this allowed more time with families. we believe this should become a standard of care. staff training is limited in most units. for something so difficult and frequently encountered, it is vital we equip staff better. prioritising children with epilepsy in the first seizure clinic cp white, s brown, ka hapgood, s tuohy children's epilepsy service, morriston hospital, swansea, uk objective: rising demand for limited first seizure clinic appointments was leading to increasing waiting times and the feeling that children with epilepsy were waiting too long for their first assessment. concern was also expressed that families were not receiving our first seizure leaflet or given instructions about capturing any further episodes either on video or by making a written record when initially seen. methods: from april all families were sent a letter acknowledging the referral and asking them to contact the specialist epilepsy nurse if they had any concerns prior to the appointment. later modifications included a seizure information leaflet and a seizure record document. we have analysed the results of the first year of using this system. patients were identified from the clinic database and further information was obtained by reviewing clinic letters. results: our initial concern that the specialist nurse would be inundated with phone calls from worried parents were not realised as only % ( / ) of parents contacted the service before their appointment. these were invariably parents whose children had had a second episode ( / ). had had further generalised tonic clonic seizures. children had eegs performed before their first appointment. this included all the children given a diagnosis of epilepsy. % of these children ( / ) were given a diagnosis of epilepsy made compared to . % of other referrals (p< . ). although a higher percentage of families who were reminded about videoing any further episodes did so the difference between the two groups was not statistically significant. unfortunately, overall waiting times were not affected. conclusions: a simple change to the way in which the service is delivered has led to earlier identification of those children with epilepsy. we are looking at other ways of improving the accuracy and timeliness of the appointments. introduction: paediatric idiopathic intracranial hypertension (iih) is an uncommon disorder and presentation is varied with children presenting to paediatricians, paediatric neurologist, and ophthalmologists. there are many areas of diagnosis and management where evidence is limited. a national adult evidence and consensus-based guideline was published in . no national paediatric guideline exists to aid the further investigations and management of the cases. the iih meeting at the bpna conference in and january set the scene for collaborative work on this topic. aim: to develop a national paediatric iih guideline based on the available literature such as modified dandy criteria, friedman classification and icdh- classification and consensus amongst various members of bpna chan group, members of rcpch, ophthalmology, neurosurgery and radiology, and patients. methods: a core children's headache iih guideline development group was established and has met at four national special interest group meetings between november and september . topics discussed include incidence of papillioedmea, csf dynamics in iih, bpnsu iih data, ophthalmology good practice, regional iih pathways in uk and setting up of the delphi process. the paediatric iih study day in september with invited patient/parent representatives highlighted the impact on families with the disorder with need for better communication about the disorder, clear guidelines and sharing of good practice amongst clinicians. an email list of bpna chan group, rcpch members, ophthalmologists interested in the guideline was created. results: a set of statements were drafted for delphi consensus work. these are currently being reviewed by the core guideline development group prior to being circulated to the wider working group. conclusions: goal setting for the next process with the delphi process to work with the core committee and a wider working group will be presented at the bpna conference . objective: nhs england's marginal rate emergency threshold (mret) and readmission fund funded the chameleon project (twitter account: @chameleonproje ), to improve children's end of life care. this funded a lead disability paediatrician with expertise in paediatric palliative care ( h/wk), a children's palliative care nurse ( d/wk) a network administrator ( d/wk), and additional hours for paediatricians in the critical care, oncology, and neonatal units, and in each of the local district general hospitals (total h/wk). methods: tools were developed to aid identification of children in the last year of life and to support anticipatory care planning. the team attended ward rounds and provided teaching sessions, advice and support. children who died an expected death in the months of the project were ascertained from the child death review teams. non-elective admissions, bed days, and costs were tabulated. we also evaluated the documentation of care plans and post bereavement family feedback questionnaires. results: children died an expected death. the same number died during the previous months. the median number of non-elective admissions reduced from to per child, specialist ward bed days reduced from to ( % reduction). for children admitted to picu in the last months of life, the total picu bed days reduced from to ( % reduction), the median length of stay reduced from days to days, and the maximum length of stay reduced from days to days. the percentage of children who died an expected death who had documented anticipatory care plans rose from % to %. conclusions: the network of clinicians with expertise in paediatric palliative care working together across a region improved anticipatory care planning and reduced admissions and bed days for children in their last year of life: better care with reduced costs. child a, a boy with speech and language delay, presented at years of age with self-resolving episodes of floppiness, ataxia, and disorientation. there was associated muscle weakness and drooling. these unusual episodes occurred to times per week and were often triggered by excitement, especially physical and emotional overstimulation. they lasted from a few minutes to an hour, with no residual deficit. episodes could also be triggered by having late meals (fasting episodes). investigations including an mri/mra brain, eeg, sleepdeprived eeg and video telemetry did not reveal any significant abnormalities. metabolic and endocrine tests were normal. as his presenting symptoms were consistent with episodic ataxia, possibly a periodic paralysis spectrum, a trial of acetazolamide was given, which showed some improvement in the number and severity of the episodes. at years of age, genetic sequencing results revealed child a has a recessive kb deletion within the long arm of chromosome , band q . . this is a homozygous intragenic deletion within the tango gene. tango is a 'transport and golgi organization ' homolog. the function of tango is unknown; however, in previous studies, depletion in drosophila s tissue culture cells was observed to cause fusion of the golgi with the er. a recent study of individuals with tango , illustrated that child a has a clinical phenotype which is consistent with those previously reported in the literature. although seizures are present in % of individuals with tango , child a has not had any seizures to date. although no effective treatments for this rare condition are known, early diagnosis is important so that individuals and their families are aware of the potential encephalomyopathic crises and arrhythmias which occur. further research in elucidating the structure and function of the tango protein may lead to effective therapies in the future. objective: hie affects around . / live births. prognostication relies on clinical progress, neurophysiology, neurological examination, and magnetic resonance imaging (mri). there is limited information on the relationships between mrs brain results and visual appearances of the brain on mri and clinical features. this work studied the use of mrs in this cohort. methods: mrs is used routinely in all neonates with hie in our unit, so approval for this service evaluation was obtained from our clinical governance department. we identified neonates with hie between jan and march who had mri and mrs in the first days of life. medical notes were reviewed, and mri results categorised as normal or abnormal. mrs results and clinical features were compared between mri groups using parametric or non-parametric testing. correlation and regression analyses studied relationships between clinical features and mrs results. p-values of < . were assumed to be significant. results: participants were identified, were excluded because they did not meet our inclusion criteria. data from a total number of neonates were analysed using r studio. babies with abnormal mri scans had significantly lower birth weight (p= . ), gestational age (p= . ), and higher scores in the sarnat staging scale (p= . ). the analysis of the mrs data also revealed that these babies had lower levels of n-acetylaspartate (naa) in their parieto-occipital region (p= . ), as well as higher levels of lactate and lactate to choline both in the parietooccipital region (p= . and p= . respectively). finally, these significant mrs variables were significantly correlated with time to normalisation of lactate in single linear regression. background: more children and young people are surviving with an acquired central nervous system injury (traumatic or non-traumatic). the first nhs england (nhse) specialist specification for paediatric neurorehabilitation services was written in . evidence for benefits of early neurorehabilitaion after adult stroke are compellingevidence for early neurorehabilitation in cyp is emerging. methods: service information was collected from all england and wales pnr units in . results: / units contributed. activity is increasing ( ( / ); ( / ); ( / ). / ( %) are major trauma units ( %) have dedicated coordinators. several units cannot offer daily therapy. most units discharge cyp home. conclusions: considerable neurorehabilitation in-patient activity is taking place but there remains an absence of secure funding, adequate staff, dedicated beds, key members of the mdt, protected time for pro-active patient specific discharge planning. neurorehabilitation is an integral part of the neuroscience clinical pathway and our children deserve a fully resourced service as described in the service specification. tuberculosis/sarcoidosis ( ). out of the sub-categories, the group of refractory seizures/status epilepticus were most likely to have repeated imaging with either ct or mri within years ( %), followed by the group of ventriculo-peritoneal shunt blockage ( %), space occupying lesion ( %) then head injury ( %). out of patients with refractory seizures/ status epilepticus, were already known to have epilepsy. also, most repeated imaging included a subsequent head mri. conclusions: most common indications for ct head were head injury and shunt blockage (as this was a neurosurgical centre). the groups most likely to have repeated imaging were refractory seizures/status epilepticus and shunt blockage. with children presenting with known epileptic seizures in the emergency department, it is important to consider clinical data and seek to devolve decision to image. poster no. isolated radial nerve palsy, a rare presentation of congenital wrist drop c duggan, n mcsweeney cork university hospital, cork, ireland isolated congenital radial nerve palsies are a rare phenomenon and typically spontaneously recover within months. the true incidence is not known, but in a recent study . % of infants presenting to a brachial plexus injury clinic had an isolated congenital radial nerve palsy. patient a is a -week-old male who presented at birth with a left sided wrist drop following a non-traumatic elective caesarean section at + / . his birthweight was . kg ( st centile). movement of the wrist and digits were impaired to absent with preservation of function at the shoulder and elbow. there was a nodule noted in the left upper limb, anatomically superficial to the radial nerve. it was a normal pregnancy with no antenatal or postnatal issues. he attended physiotherapy and occupational therapy who provided a splint. on examination at weeks, there was weakness of the extensors of the left wrist. the rd, th and th digits remained fully flexed at rest and could be extended passively but not actively. extension of the thumb and index finger had recovered at -week review. function at the shoulder and elbow joints were preserved with normal flexion of the wrist and digits. a scar was noted superficial to the radial nerve at the same location as the lesion described at birth. the remaining systemic and neurological examinations were normal with typical development and appropriate growth. the working diagnosis at present is an isolated radial nerve palsy likely caused by in-utero compression. the nodule and scar noted above are consistent with lesions described in a previous case series. these were hypothesised to be areas of fat necrosis secondary to compression; resulting in the palsy. patient a's lack of further neurology such as a generalised brachial plexus palsy makes a birth injury less likely. further investigations and follow-up are awaited. background: valproate is an effective antiepileptic medication. if a woman becomes pregnant while taking valproate, her baby is at risk of congenital malformations ( in ) and developmental disorders ( in ). furthermore, it is associated with an increased risk of autism spectrum disorder and adhd. in , the nhs/hse recommended new restrictions on the use of valproate, including a national pregnancy prevention program (prevent) and avoidance in prescribing to female patients of childbearing potential unless other treatments are ineffective or not tolerated. objective: to review the use of valproate in a well-defined population of at risk females with moderate to profound intellectual disability (id). identify the patients at risk and imbed the guideline into our practice. methods: a retrospective chart review was carried out of all girls aged between and years, attending the daughters of charity disability service (doc) in dublin, ireland. data such as diagnosis, valproate use, degree of id/gross motor function classification system (gmfcs), documentation of menarche and discussion regarding risk of valproate use were recorded. results: in total females aged between and years where identified as currently using valproate out of charts reviewed ( %). of the patients identified, / had moderate id (gmfcs iii) and / had severe to profound id (gmfcs iv-v). / had menarche documented. / had the risk of valproate discussed. conclusions: in our cohort, a significant number of girls remain on valproate. % complied with new guidelines regarding discussions around the risks of valproate; highlighting the % of patients in need of counselling. an annual risk acknowledgement form was placed in their charts to prompt discussion next visit. in children with intellectual disability, conversations regarding contraception are difficult but essential. if valproate is used, then the risks must be fully understood by parents and carers. evaluation of the management of children up to age of years with cerebral palsy in southend university hospital large district university general hospital against nice guidelines (nice guidelines ng ). methods: clinic notes of all registered children with cerebral palsy (cp) up to years of age as of june were included in the study. this was because there was no early data on children above years age. results: patients were age to years and patients age to years. were male and females. had hemiplegic, quadriplegic, diplegic and dystonic cp. only ( %) had gmfcs levels recorded. ( %) were < weeks, ( %) were to weeks and ( %) were term. mri head findings: white matter changes including pvlin ( %), ( %) hie changes, ( %) basal ganglia changes, ( %) congenital brain malformation, ( %) infarction. migrated to area with no mri report. all the children received multidisciplinary team (mdt) input including physiotherapy. comorbidities werechildren on medications for gastro-esophageal reflux - (with peginsertions). for epilepsy - , for dystonia/spasticity - , for constipation - , for poor salivary control - . behavioral issues noted in and was on adhd medications. had botulinum toxin injections and had selective dorsal rhizotomy for spasticity. documented discussion of diagnosis with family was in ( %) patients and none in patients ( %). only % patients had vitamin d levels checked. conclusions: management was in line with nice guidelines. they all had mdt input. there is a need to improve documentation of -evidence of discussion with parents, gmfcs level by age ½ years plus, hip surveillance from age years for gmfcs level iii to v and annual vitamin d levels especially for gmfcs level iii to v, peg fed and children on multiple anti-epileptic medications. poster no. intracranial hypertension in children: an updated systematic review l di genova , n desai , s esposito , p prabhakar pediatric clinic, department of surgical and biomedical sciences, universit a degli studi di perugia, perugia, italy; department of paediatric neurology, great ormond street hospital nhs foundation trust, london, uk; neurosciences, great ormond street hospital nhs foundation trust, london, uk objective: our goal is to provide an overview on paediatric intracranial hypertension. methods: given that the last update of the diagnostic criteria of idiopathic intracranial hypertension was published in , a thorough medline search of all english articles was conducted between and . results: intracranial hypertension may be primary, with a paediatric annual incidence ranging between . and . per children or arise from a secondary cause. misdiagnosis or delayed intervention can lead to poor quality of life and morbidity. in , this condition was reconsidered, due to new accepted values for opening pressure and advances in neuroimaging; the importance to develop effective therapeutic strategies in order to prevent blindness was thus highlighted. to date, the main strategies described involved both medical and surgical approaches; nevertheless, there have been no paediatric intervention studies. disease monitoring plays a key role in the definition of the best timing and modality of treatment. recently, a risk stratification has been proposed with the aim to facilitate an adequate evaluation and proper care of children with intracranial hypertension: visual monitoring could represent an objective tool to manage these patients. in recent years, important evidence for the efficacy of acetazolamide emerged in the idiopathic intracranial hypertension treatment trial. surgical treatment is the modality of choice in children with worsening vision impairment, intractable headaches despite maximal medical management or in case of intolerance to medical therapy. conclusions: there are poor evidences about paediatric intracranial hypertension's outcomes. unfortunately, children's quality of life is heavily influenced by pain and permanent vision loss. standardized therapeutic strategies remains uncertain, highlighting the need for longitudinal studies to identify the best treatment in childhood. in order to alleviate symptoms and prevent permanent chronic sequelae, careful clinical evaluation and ophthalmological monitoring could be a useful guide to better manage this medical condition. objective: cerebral sinovenous thrombosis in childhood is a life-threatening neurological entity with uncertain epidemiology, potentially complicated by secondary intracranial hypertension. in the literature, there is a lack of evidence supporting the main strategies to approach both these medical conditions. our objective is to highlight the value of a prompt diagnosis aiming to define a tailored management approach based on children monitoring. methods: we review the main findings regarding cerebral sinovenous thrombosis and intracranial hypertension in children through illustration of a case with otogenic sinus thrombosis and secondary intracranial hypertension. results: a -year-old boy developed a local venous sinus thrombosis because of the spreading of a primary infective process from his middle ear into the sigmoid sinus complex, facilitated by anaemia and dehydration. the venous outflow disturbances led to secondary intracranial hypertension. the management aimed to treat cerebral thrombosis with anticoagulants and intracranial hypertension through medical and surgical strategies. the insertion of the lumbar-peritoneal shunt was necessary when medical approached failed and visual function deterioration was evident. careful clinical evaluation and ophthalmological monitoring helped us in the tailoring of the best treatment with the aim to alleviate symptoms and prevent sequelae of increased intracranial pressure. in the literature, no paediatric intervention studies regarding the main strategies to reduce intracranial pressure have been published. moreover, there is a lack of evidence supporting the safety of anticoagulation therapy, reducing the possibilities to safely manage cerebral thrombosis in childhood. conclusions: in children, a multidisciplinary approach is essential to manage both cerebral thrombosis and intracranial hypertension and ensure an optimal follow-up, aiming to prevent visual and therapy-related complications, possible relapses and their early diagnosis. from our perspective, monitoring our patient with clinical manifestations and visual status helped us to plan the best timing and modality of treatment and intervention. yearly rate of progression of fvc% predicted (available in n= ) was . % in sma and . % in sma . in sma , fvc% predicted declined steeply from to years of age, followed by a levelling. conversely, in sma patients fvc% predicted declined slower but steadily from years of age. / ( %) sma and / ( %) required non-invasive ventilation due to respiratory infections or hypoventilation conclusions: the results of this ongoing collaborative work suggests that in sma and lung function declines from age and respectively. lung and motor function correlate well in both sma and . this data will help the assessment of the long-term efficacy of new treatments for sma this review aims to study the appropriateness of mri brain referrals following implementation of local changes to improve compliance to the nice cg standard. methods: following an earlier survey (es; / / - / / ) of mri brain referrals for headaches in children over years, key recommendations included adding pop-ups in the neuroimaging request system (ice) of nice cg and headsmart clinical guideline v as well as verbal consent obtained from senior paediatrician before request was made. following these implementations, requests for mri brain were analysed during / / - / / in the same district general hospital. referral was deemed compliant if the nice guideline cg standard were met. results: children were referred for mri brain scan (mean / month vs /month in es). ( %) referrals were compliant (vs % compliance in es). ( %) referrals were 'urgent' (vs % urgent es) and ( %) 'routine' or non-urgent (vs % routine es). ( %) of urgent referrals (vs % es) and ( %) of routine referrals (vs % es) were compliant mri brain guidelines for neuroimaging in less than years exist (headsmart clinical guideline v and nice epilepsy qs ) but are limited. this study aimed to assess current practice of mri brain referrals in children under years. methods: retrospective review of mri brain referrals in children under years performed between mri brain scans were done (m:f . : ) ( %) referrals under headsmart and ( %) of these were urgent requests; significant brain abnormality was seen in ( %) in urgent and ( . %) in nonurgent cases. ( %) referrals under epilepsy qs and ( %) were urgent requests; significant brain abnormality in ( %) in urgent and ( %) in non-urgent cases. ( %) were miscellaneous requests and ( %) were urgent; significant brain abnormality in ( %) in urgent and ( %) in non-urgent cases. overall mri brain showed significant abnormality in urgent requests ( %) compared to non-urgent requests ( %) poster no. investigating factors that influence unplanned admissions and a&e attendances in those with pre-existing neurological conditions in childhood s dowsell , k kananaviciute , r parslow , am childs university of leeds, leeds, uk; paediatric neurology, leeds general infirmary, leeds, uk objective: previous papers have shown increasing demands and costs to the nhs in relation to the inpatient care of children with neurological conditions. unplanned admissions may reflect a lack of effective care and have been shown to correlate with high outpatient clinic did not attend (dna) rates . the aim of this study was to determine factors underlying unplanned admissions and accident & emergency (a&e) attendances in a cohort of patients under the care of the leeds regional paediatric neurology service over a -year period. methods: all children < years who had paediatric neurology outpatient appointments in were identified using hospital databases. clinical and demographic data was extracted from electronic case notes. those without a definitive neurological diagnosis or who had moved to adult services during the study period were excluded. the cohort was cross referenced to a&e databases and admission records from to . poisson regression was used to identify any correlation between specific predetermined factors to assess their influence on a&e attendance and admission rates. results: a cohort of patients was established and had a total of unplanned admissions during the study period. patients had a&e attendances with a total of attendances. higher dna rates, younger age and certain diagnostic categories correlated with increased rates of unplanned admissions. the role of emergency care plans in preventing admission was unclear as only / patients with epilepsy had care plans in place. conclusions: this study confirms the association between increased rates of a&e attendances and unplanned admissions in children with specific neurological disorders and high dna rates. this is relevant for service planning as it highlights the need to target scarce resources towards 'higher' risk patients with more complex diagnoses where more integrated care and support may prevent or reduce unplanned hospital attendances.poster no. audit comparing great ormond street hospital headache clinic diagnoses and management of patients aged to years to nice clinical guidelines a ward , , p prabhakar neurology, great ormond street hospital, london, uk; university of glasgow, glasgow, uk introduction: between / / and / / the gosh headache clinic saw new patients aged to years. the nice clinical guideline (cg ) on the diagnosis and management of headaches in over s covers tension-type headache, migraine, cluster headache and medication overuse headache. this audit aims to compare gosh diagnosis and management to those of the cg . methods: using the patient list from the headache clinic data was gathered by accessing outgoing clinic letters via epic. raw data was collected on; age, gender, description of headache (pain location, quality, intensity, duration and frequency) and associated symptoms, triggers, previous imaging, previous and current treatments. the management data collected include: diagnosis and treatments offered, as well as whether gosh offered lifestyle advice, psychology, occipital nerve block or riboflavin. this data was then compared to cg . results: ( . %) of diagnoses made by gosh matched the cg diagnosis. ( . %) diagnoses differed, with of these due to discrepancy between chronic/episodic and/or presence of aura and due to the vague diagnoses of migraine-type, new daily persistent, migrainous etc. fitting the cg definition of chronic migraine. all but one patient was managed in line with the guidelines. . % of patients had brain imaging prior to attending the clinic, with . % of these reporting positive findings. discussion: despite patients' diagnosis differing between gosh and cg , all but one patient was managed in line with the guidelines. this is likely due to nice recommended management being the same for any type of migraine. improvements could be made in documentation of frequency and duration of headache and aura, as well as more routinely offered lifestyle advice, psychology and riboflavin recorded in outgoing clinic letters. objective: to review the purpose of ct head requests from emergency department of a busy tertiary hospital as part of quality improvement. due to increasing evidence of ct scan radiation predisposing to leukaemia and brain tumours, it is best to keep ct scans to the minimum if clinically indicated. this project reviewed the indications for ct head and also looked at patients who had repeated ct or mri head scans within years. methods: data was collected retrospectively looking at a snapshot period of months between september-november . patients were < years of age and they had a ct head from emergency department at king's college hospital, london. trauma patients were excluded. data was collated with aid of the neuro ct department 'cris' system. results: out of patients, reasons for ct included: head injury ( ), ventriculo-peritoneal shunt blockage ( ), refractory seizures/status epilepticus ( ), space occupying lesion ( ), orbital cellulitis ( ), intracranial haemorrhage ( ) objectives: mutations in kif a are associated with a wide range of neurological disorders, ranging from hereditary spastic paraparesis (hsp) to sensory neuropathies to a severe infantile neurodegenerative disorder. collectively, they are extremely uncommon but likely to be under-recognised. we aim to report the spectrum of kif a-related disorders from a single tertiary neurology centre, with a view to improving understanding and awareness of these rare conditions. methods: affected individuals known to great ormond street hospital were identified through liaison with consultants involved in the care of children and young people with movement disorders. clinical information was collected through a retrospective review of case notes. results: twelve individuals in families were identified. all had heterozygous kif a mutations including three previously unreported variants. severity ranged from a fatal neonatalonset disorder with contractures, absence of visual development, and agenesis of the corpus callosum on mri to hsp with preservation of ambulation into the second or third decade of life and entirely normal mri. upper motor neuron signs were found in / children and a primarily sensory neuropathy was present in / children assessed. / children also had extrapyramidal signs (dystonia). some degree of learning difficulties and/or disorders of mood or behaviour were present in all children. optic atrophy, mr brain white matter changes and epilepsy were also common, especially in those children who were more severely affected overall. conclusions: kif a related disorders are so diverse that it is arguably misleading to consider them as a single disease entity. features common to the majority of affected patients include upper motor neuron involvement, and neuropathy (even in the absence of an obvious sensory deficit), with high risk of other neurological and neurobehavioural comorbidities. objective: ataxia with oculomotor apraxia type (aoa ) is a slowly progressive, autosomal recessive disease characterised by the triad of ataxia, oculomotor apraxia, and sensorimotor neuropathy that results from mutations in the gene encoding senataxin (setx), a dna/rna repair protein essential for genomic stability. we investigated a -year old male with a history of unsteady gate for genetic and molecular changes associated with aoa . in this report we describe a case of aoa with two clear pathogenic setx mutations, one of which is novel, as well as two further setx changes likely to be in cis polymorphisms that have previously been reported as pathogenic. methods: two independent lymphoblastoid cell lines obtained from the patient were used for western blotting of senataxin and protein markers of other autosomal recessive cerebellar ataxias. the setx gene was sequenced to identify possible disease-causing mutations. results: western blotting showed reduced levels of senataxin. serum afp level was elevated at lg/l (normal . - . lg/l). genetic sequencing revealed two clear pathogenic setx mutations. one of these was a novel mutation, c. delg; p.(cys phefster ), a deletion causing a reading frameshift resulting in truncation and loss of expression of senataxin protein from this allele. the other, c. c>t; p.(pro leu) was a missense mutation within the helicase domain which has previously only been reported in the homozygous state in a japanese aoa patient. two further sequence changes, c. a>g; p.(asn asp) and c. c>a; p.(gln lys), were also identified in our patient. conclusions: the reduced senataxin expression and elevated afp levels support a diagnosis of aoa in our patient. genetic analysis found a novel pathogenic mutation and documented the first case of another pathogenic mutation in the helicase domain outside of japan. the case contributes to the growing diversity of setx mutations known to be responsible for aoa . key: cord- -r l hdrk authors: gao, min; huang, siying; pan, xuequn; liao, xuan; yang, ru; liu, jun title: machine learning-based radiomics predicting tumor grades and expression of multiple pathologic biomarkers in gliomas date: - - journal: front oncol doi: . /fonc. . sha: doc_id: cord_uid: r l hdrk background: the grading and pathologic biomarkers of glioma has important guiding significance for the individual treatment. in clinical, it is often necessary to obtain tumor samples through invasive operation for pathological diagnosis. the present study aimed to use conventional machine learning algorithms to predict the tumor grades and pathologic biomarkers on magnetic resonance imaging (mri) data. methods: the present study retrospectively collected a dataset of glioma patients, who had pathological reports and underwent mri scans between october and march . the radiomic features were extracted from enhanced mri images, and three frequently-used machine-learning models of lc, support vector machine (svm), and random forests (rf) were built for four predictive tasks: ( ) glioma grades, ( ) ki expression level, ( ) gfap expression level, and ( ) s expression level in gliomas. each sub dataset was split into training and testing sets at a ratio of : . the training sets were used for training and tuning models. the testing sets were used for evaluating models. according to the area under curve (auc) and accuracy, the best classifier was chosen for each task. results: the rf algorithm was found to be stable and consistently performed better than logistic regression and svm for all the tasks. the rf classifier on glioma grades achieved a predictive performance (auc: . , accuracy: . ). the rf classifier also achieved a predictive performance on the ki expression (auc: . , accuracy: . ). the auc and accuracy score for the gfap classifier were . and . . the auc and accuracy score for s expression levels are . and . . conclusion: the machine-learning based radiomics approach can provide a non-invasive method for the prediction of glioma grades and expression levels of multiple pathologic biomarkers, preoperatively, with favorable predictive accuracy and stability. gliomas are the most common brain tumors and are often classified as world health organization (who) grades i-iv, depending on the different tumor cells, and the degree of abnormality ( , ) . as a tumor's grade increases, gliomas process more aggressively ( ) . treatment options and responses differ from glioma grades ( ) . pathological findings are the premise of rational treatment. usually, glioma grades are confirmed by pathological examination during surgery or biopsy ( ) . then, a following immunohistochemistry (ihc) test determines the molecular biomarkers of tumor tissues at the microscopic level. these pathologic biomarkers, typical proteins, are useful indicators for diagnosis, prognosis, or treatment response ( ) . however, obtaining such information for gliomas requires invasive approaches. the surgical decision making could be difficult and time-consuming for many patients. those patients who are not eligible for a surgery or seek nonsurgical treatment may have limited treatment options without pathological guidance. therefore, presurgical glioma grades and the expression of biomarkers are valued and preferred with non-invasive approaches. at present, the medical imaging can differentiate the tumor phenotype and intra-tumor heterogeneity ( ) . conventional magnetic resonance imaging (mri) is routinely used in the diagnosis and management of glioma patients. t -weighted contrast-enhanced mri (t c) is the current standard for initial brain tumor imaging ( ) . radiomics can generate image features with high dimensional data from the intensity histogram, geometry and texture analyses on the entire tumor volume ( ) . with the emergence of artificial intelligence (ai) technologies, advanced informatics tools have become accessible to facilitate machine learning (ml) based radiomics applications using image features as the data source ( ) . radiomics is gaining ground in oncology and have the potential to accurately classify or predict tumor characteristics. radiomics approaches have been applied for the predictions of glioma grades or differential diagnoses ( , ) . several studies have reached a prediction accuracy of above % using popular ml models. the commonly and frequently used ml algorithms in radiomics include logistic regression (lr), random forests (rf), support vector machine (svm), and etc. each ml method has their own advantages in the classification. for example, lr fits the variables coefficients and predicts a logit transformation of the probability of being one class or the other. svm separates the classes by finding an optimal hyperplane. rf uses bootstrap aggregating to decision trees and improves classification performance. when compared to tumor grading, to make predictions at a molecular level is more challenging. kickingereder et al. reported the association between established mri features and cancer gene variations (egfr amplification and cdkn a loss), but failed to build a sufficient ml model to predict the molecular characteristics ( ) . in clinic, pathologic biomarkers are more frequently tested for than genetic testing. idh is one important glioma biomarker and idh mutation along with p/ q is a part of the molecular diagnosis in the updated who classification ( ) . ki , s , and gfap are also the common protein targets for gliomas. idh , ki , and gfap were once considered as the golden triad of glioma ihc ( ) ki is highly correlated to proliferation that may indicate the tumor grades and prognosis ( ) ( ) ( ) . s has been implicated in the regulation of cellular activities, such as metabolism, motility, and proliferation. under the pathological conditions of tumor and inflammation, the concentration of the s protein increases to the micromole level, which stimulates microglia and astrocytes, and increases the expression of pro-inflammatory cytokines ( ) ( ) ( ) ( ) ( ) . gfap is the most widely used markers of astrocytes ( ) . under the condition of injury (trauma or disease), the expression of gfap in astrocytes rapidly increases ( ) . gfap is often used to reveal the astrocytic lineage of glial cells and glial tumor cells, and plays a more significant role in tumor pathology, when compared to the differential diagnosis of astrocytoma. ki , s , or gfap may not be a reliable diagnostic biomarker for gliomas, because their roles in gliomas are still under investigations, while controversies have been observed in experiments ( ) . however, there is no doubt that these proteins can provide some insights into the tumor intramicroenvironment. so far, it is not surprising to know that most radiomics studies favor the prediction of the idh expression for molecular diagnosis ( , ) , with a few reports on ki ( ) . in order to expand predictive effects of radiomics, the investigators aimed to assess the prediction feasibility of glioma grades and the pathologic biomarkers of ki , s , and gfap in gliomas. the investigators believed that the combination of multiple biomarkers can increase the predictive power, and the information obtained can help in understanding the underlying pathologic process in gliomas. the investigators designed the present retrospective study and extracted hundreds of radiomic features from the t c images of glioma patients. three machine-learning-based models (lr, svm, and rf) were built to perform the tasks: ( ) classify the glioma grades, and ( ) predict the expression levels of ki , s , and gfap. this study demonstrated that multiple pathologic biomarkers in gliomas can be estimated to the certainty levels of clinical using common ml models on conventional mri data and pathological records. the investigators retrospectively collected a data set of glioma patients, who had pathological reports and mri scans performed between october and march , from the second xiangya hospital of central south university. the patients who met the following criteria were included: (i) a histopathological diagnosis of primary glioma based on the who classification, (ii) the availability of ihc profiles of biomarkers (s , gfap, and ki ), (iii) preoperative mri data of post-contrast axial t -weighted (t c), and (iv) age > years old. patients were excluded due to the following: (i) secondary gliomas or postoperative recurrence of gliomas, (ii) obvious artifacts in mri. ethics approval was obtained for the present study from the ethics committee of the second xiangya hospital, central south university. patient demographics (age and gender), and histopathologic diagnosis and ihc results were obtained from a surgical pathology report. on these reports, the diagnosis included a specific glioma type by cells (e.g., astrocytoma and oligodendrogliomas) and a given who grade (i-iv). the ihc results were presented in the list of glioma biomarkers (e.g., s , gfap, or ki ) and their own expression profile in tumor cells. it is noteworthy that the list was not standard and varied upon the request or availability of the biomarkers at that time. for example, few patients received an idh test before , but after , the who classification standard was published, and idh tests became common. so, a patient might have a different set of tested biomarkers, and the number of cases can differ for each biomarker. their ihc results depended on the scoring system used. the expression levels were usually evaluated by the staining intensity of positive cells, and points were assigned to describe these positive cells by count (e.g., points as negative (−), point as positive (+), points as medium positive, and points as high positive), percentage (e.g., points as none, point less than %, points approximately - %, and points above %), or the appearance of a clear brown color (e.g., point for light yellow). in the study, the glioma grades were classified as low-grade (who i-ii, benign) and high-grade (who iii-iv, malignant), and expression levels of biomarkers were divided into two categories: a low expression scored less than points and a high expression scored points or above. magnetic resonance imaging scans were acquired from different scanners over time. the picture archiving and communication system (pacs) exported the selected dicom images to a local computer using the radiant dicom viewer (medixant, pl). in order to reduce the influence of different scanning parameters, post-processing and image registration were applied using the advanced normalization tools (ants . , pa). then, the dicom images were loaded into itk-snap for segmentation and standardization ( ) . two neuroradiologists ( years of experience) drew the region of interest (roi) around the tumor boundary on the t c images. the neuroradiologists were blinded to the patient identification and diagnosis. after a joint effort, disagreements with the boundary were solved. the roi segmentations were resampled to match the dimensions of the original images, and both images were saved in.narrd as the input for feature extraction. the pyradiomics extractor was customized to calculate and extract the features ( ). all built-in filters [wavelet, laplacian of gaussian (log), square, square root, logarithm, and exponential] were enabled on five image feature classes [first order statistics, shape descriptors, and texture features on the gray-level co-occurrence matrix (glcm), gray-level run length matrix (glrlm), and gray-level size zone matrix (glszm)]. feature definitions and calculation algorithms were available in the pyradiomics documentation . the feature importance and the following predictive ml methods were implemented using python (version . . ) with machinelearning library scikit-learn (version . ) ( ) . all features were standardized through min-max scaling. features with all zero scores were removed. clinical data (age and gender) were added in constructing the final prediction models. the feature importance helped in understanding the importance of the features, since a large number radiomics features with high-dimensional data are difficult to interpret. three technique approaches were used to identify the important features. first, chi-squared (chi ) tests were applied in the scikit-learn selectkbest class to obtain a list of the top best features. second, the heatmap of correlated features was plotted to identify features highly correlated to predicting targets (glioma grade and biomarker expression) using the seaborn library. third, a rf classifier was initiated and the in-build feature importance was used to extract the top features. three frequently-used machine-learning based models of lr, svm, and rf were built for four predictive tasks: ( ) glioma grades, ( ) ki expression level, ( ) gfap expression level, and ( ) s expression level in gliomas. each sub dataset was divided into training and testing sets at a ratio of : (train_size = . , test_size = . ). principal component analysis (pca) was applied for high-dimension reduction that maps n-dimensional features to k-dimensional features (n > k), resulting in brand new orthogonal features. for the unbalanced data in different classes, the synthetic minority over-sampling technique (smote) algorithm was used to oversample the minority class ( ) . on training set, the grid search with crossvalidation was applied for hyper parameters tuning (rf and svm), and k fold validation was used for lr. the accuracy score was compared with the result from their base models (default settings in scikit-learn) for model selection. the testing set was used for final model evaluation. the performance of the models was evaluated according to accuracy, the area under curve (auc) of the receiver operating characteristic (roc), sensitivity, specificity, the positive prediction value (ppv), and the negative predictive value (npv). according to the auc and accuracy, the best classifier was chosen for each task. one way-anova or simple t-test was applied to test the differences among gender, age, glioma grade, and the expression levels of the biomarkers. descriptive statistics was used to summarize the important features through filters and feature classes. all significant levels were tested at . . a data set of preoperative mri and surgical pathologic reports of glioma patients were collected. a total of patients were excluded for not meeting the inclusion criteria. among these patients, patients were under years old, seven patients had quality issues on their mri data, and four patients did not have an assigned who classification level in their records. the age of the enrolled patients ranged within - years old (mean age: . ± . years old), and consisted of males (age: . ± . years old), and females (age: . ± . years old). the clinical characteristics of patients and the distribution of the selected biomarkers across glioma grades are presented in table . the expression of gfap, ki , and s was reported as follows: patients had gfap results with four negatives ( point), positives ( point), and medium ( points), or high positives ( points); patients underwent ki tests, including negatives or low positives (≤ % in tumor cells), and strong positives (> %); patients underwent s tests, which included eight negatives ( points), positives ( point), and medium positives ( points). there was a significant age difference among male and female patients, as determined by one-way anova [f ( , ) = . , p < . ]. furthermore, there were significant differences in age, gender and tumor volume among glioma grades (who i-iv). moreover, there were significant differences in glioma grade, tumor size, age and gender for the ki expression. however, there were no significant differences in age, gender and glioma grade for s and gfap expression. the t-test and one-way anova results are shown in table . the investigators obtained the list of the top important features based on the scores obtained from the chi-squared stats between each non-negative feature and the glioma grade, and s , gfap, and ki expression levels. the features and their scores are shown in table . the scores ranged within . - . . the mean score of the top important features was . , with a standard deviation of . . the frequent top features within the image type were exponential ( ), wavelet ( ) , square ( ), square root ( ), original ( ), gradian ( ), and ihp- d ( ). for the feature classes, the frequent top features were divided as follows: glszm ( ) , glcm ( ), glrlm ( ), gldm ( ), first order ( ), and ngtdm ( ) . the heatmaps of the correlated features for glioma grade and the biomarkers of ki , gfap, and s are presented in figure . the rf model built-in feature importance is presented in figure . the performance of the predictive models is presented in table . the rf models performed slightly better, when compared to the other models. the comparisons with accuracy and the results are presented below. figure shows the auc_roc for the rf classifier in sub test sets. the sub data set was randomly split into the training set of cases and the test set of cases. with a pca retention of . , the pca process reduced the dimensions frontiers in oncology | www.frontiersin.org a total of patients had s test results, which included low expression levels (< points) and high expression levels (≥ points). the class distribution was : . the training set and test set were split into and , respectively. after the smote oversampling, the resampled number increased to . with a pca retention of . , the pca process reduced the dimensions to components, and these were used for the final prediction model for the s expression. after grid search with cross validation (cv = ) or k fold validation (n_splits = ), the selected classifier included: ( ) lr (penalty = "l , " c = . ), ( ) svm (c = , kernel = "rbf, " and gamma = "auto"), and ( ) rf (min_samples_leaf = ,min_samples_split = , and n_estimators = ). among these classifiers, the rf classifier achieved the best prediction performance on the s expression, based on the measurements (auc: . , accuracy: . , averageweighted sensitivity: . specificity: . , and f score: . ). it is noteworthy that the average-weight computes f for each class, and returns the average while considering the proportion for each class in the dataset. for s low expression levels: accuracy ( . ), sensitivity ( . ), specificity ( . ), and f ( . ). for high expression levels: none of the four high expression cases was correctly predicted. a total of patients had a gfap test. among these patients, there were low expression levels and high expression levels. the class distribution ratio was : . the training set and test set were split into and , respectively. after the smote oversampling, the number of samples increased to . with a pca retention of . , the pca process reduced the dimensions to components, and those that remained were used for the final prediction model for the gfap expression. after grid search with cross validation (cv = ) or k fold validation (n_splits = ), the selected classifier included: ( ) lr (penalty = "l , " c = . ), ( ) svm (c = , kernel = "rbf, " and gamma = "auto"), and ( ) rf (min_samples_leaf = ,min_samples_split = , and n_estimators = ). among these three classifiers, the rf classifier achieved the best predictive performance on the gfap expression measured, as follows: auc ( . ), accuracy ( . ), average-weighted sensitivity ( . ), specificity ( . ), and f score ( . ). the machine-learning based radiomics approach was applied to predict glioma grades and the expression levels of pathologic biomarkers ki , gfap, and s in low or high. the overall performance of the ml models was satisfactory. the rf algorithm was found to be stable and consistently performed better than lr and svm. feature importance varies on predictive tasks, glioma grade or specific protein expression. the most frequent important feature classes were textual and first order statistics. we selected lr, svm, and rf as classifiers mainly for their popularity. lr, svm, and rf classifiers can work on non-text data set less than k. whether the data is linearly divisible or not, the linearly separable models (lr, svm), and the non-linear separable model (rf) are helpful to view the effect and avoid the impact due to poor data. lr shows a higher auc, in gfap's prediction model, but performs worst in s 's prediction. comparing the overall results from three biomarker prediction models, the combination of pca reduction and rf classification consistently performed best. it suggests a common ml pipeline that may be helpful in standardizing the prediction process of multiple protein expressions. also more recently, researchers have demonstrated achievements of deep learning (dl) in the image segmentation and glioma grades prediction ( ) ( ) ( ) ( ) ( ) ( ) . convolutional neural networks (cnns) started outperforming other methods on several high-profile image analysis projects. dl has advantages in computation, as high-performance graphics processing unit (gpu) supports fast computing and less time on modeling. like a kind of end-to-end learning, dl can automatically extract relevant functions from images, and tasks such as raw data processing and classification can be completed automatically. however, dl is complex and requires thousands of images to start with, otherwise due to a relatively small collection of images like ours, overfitting is more likely. the classic ml methods met our needs and suited the data. rf models performed well for predicting glioma grades and pathologic biomarkers s , ki , and gfap. as it is known, the roles of these biomarkers can be complicated and controversial in laboratory experiments ( ) . in addition to the abilities of predicting tumor phenotypes, radiomics might offer a new approach to evaluate biomarkers, since their differentiation can be identified through the analysis of imaging features. the expression level of ki was significantly correlated with the tumor grade and tumor volume, as well as the patient age and gender. a study once reported that the high level of ki- expression was correlated to poor overall survival (os) and progression free survival (pfs) ( ) . the accurate prediction of high level ki is more meaningful than its low level expression to indicate poor prognosis for glioma patients. the gfap has been widely expressed in gliomas. merely four patients presented as gfap negative. the majority of the patients ( of , %) had gfap positive (+), and patients with low expression gfap ( %), combined with four that scored (−), were distributed all over the gliomas grades, including low grade ( , %), and high grade ( , %). the minority of the patients ( of , %) had gfap medium positive (++) or high positive (+++) distributed in low grade ( , . %) and high grade ( , . %). in the literature, a high gfap expression is likely to be found in low grade gliomas. the present result was confusing, that is, the high and low expression levels of gfap were more correlated to high grade gliomas. this result may echo that gfap is not a direct predictor of low grade gliomas ( , ) . on the classification report of the rf_gfap model, the accuracy score of predicting a gfap low expression was up to, while that of predicting high expression levels of gfap was much lower. the overall prediction performance might not be meaningful, since gfap was lowly expressed in % of patients, and the model could always answer % correctly. the same problem was found in the predictive model of s . it required the rethinking of these two models. there was a need to determine which expression class is more valued. and then, as one solution, the roc thresholds can tuned, increasing the sensitivity of the favored class. the interpretation of the predicted results is complex, but may be helpful to understand the molecular mechanisms it underlies. in addition, the investigators selected ce mri from several typical cases for demonstration, in which the different expression levels of biomarkers exhibited different imaging characteristics (figure ) . for the high expression of s case (figure a) , the tumor exhibited an obvious rosette enhancement, no enhancement of internal necrotic components, and a few edema zones around it, and was diagnosed as glioblastoma (who iv grade). in the image of the tumor with a low expression of s (figure b) , the tumor mass effect was obvious, but there was no obvious enhancement, and the surrounding edema was not obvious, which was diagnosed as astrocytoma (who ii grade). in this case, the positive correlation appeared as both the s and glioma grade moved in the same direction that was contrary to many observations. the study conducted by wang et al. has proven that s is expressed in most gliomas, and that this is an important inducer of ccl ( ) . ccl participates in the transport of tumor-associated macrophages (tam) in gliomas, which affects angiogenesis, invasion, local tumor recurrence and immunosuppression. this may explain the relationship between the degree of tumor enhancement and the expression of s in the present cases. there are some limitations in our study. first, we only used conventional mri sequences with a default set of tumor features extracted by pyradiomics. advanced mri sequences (e.g., dwi, dki, mrs, asl, et al.) can reflect the microstructure and metabolic information of tumors. in future study, we will further investigate the molecular phenotype of gliomas using a multimode magnetic resonance scheme. second, we only selected common pathologic biomarkers for gliomas from a wide range of biomarkers either current available or under investigation. we have to develop an evaluation plan for other glioma biomarkers and find candidates that can be benefit from radiomics applications. third, imbalance classes did not reflect the incidences of glioma in real world, where glioblastoma is the most common subtype, and grade i glioma is relatively rare in adults. we used the smote algorithm to balance data, oversampling the minority class, but the differences in data distribution cannot be ignored. in our experiments, before and after the use of smote, auc was only changed slightly. a larger dataset from multiple sites is expected to complement predictive effects, and the resulting classifiers can be more accurate and stable. fourth, after pca reducing feature dimensions, a new set of features was less remained but difficult to interpret. a combination of hierarchical clustering on pca may help us to select feature more efficiently. at the current stage, a real-world application is out of our scope, but further prospective assessment is warranted. based on the results we obtained as a reference, we will extend the study to identify the best classifier algorithm and the best set of features to simplify the classification tasks. the standardized computation methods would greatly enhance the reproducibility of radiomics studies, and it may also lead to standardized software solutions available in clinical practice. in conclusion, the machine-learning based radiomics application provided a non-invasive approach for the prediction of glioma grades and expression levels of multiple pathologic biomarkers, with favorable predictive accuracy and stability. the study also demonstrated the potential of radiomics for pathological assessment and individualized cancer treatment. the raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. the studies involving human participants were reviewed and approved by ethics committee of the second xiangya hospital of central south university. written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements. the who classification of tumours of the central nervous system glioblastoma and other malignant gliomas: a clinical review cbtrus statistical report: primary brain and central nervous system tumors diagnosed in the united states in - malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods limitations of stereotactic biopsy in the initial management of gliomas molecular pathology of tumors of the central nervous system how clinical imaging can assess cancer biology current clinical brain tumor imaging radiomics in glioblastoma: current status and challenges facing clinical implementation computational radiomics system to decode the radiographic phenotype multimodal mri features predict isocitrate dehydrogenase genotype in highgrade gliomas machine learningbased radiomics for molecular subtyping of gliomas radiogenomics of glioblastoma: machine learning-based classification of molecular characteristics by using multiparametric and multiregional mr imaging features the world health organization classification of tumors of the central nervous system: a summary ki and idh : perhaps the golden triad of glioma immunohistochemistry ki- is a valuable prognostic factor in gliomas: evidence from a systematic review and meta-analysis the use of the monoclonal antibody ki- in the identification of proliferating cells: application to surgical neuropathology diagnostic and prognostic role of ki immunostaining in human astrocytomas using four different antibodies s b promotes glioma growth through chemoattraction of myeloid-derived macrophages the heterodimeric complex of mrp- (s a ) and mrp- (s a ) biochemical characterization and subcellular localization in different cell lines anti-infective protective properties of s calgranulins biology of the s proteins-introduction glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease effects of traumatic brain injury on reactive astrogliosis and seizures in mouse models of alexander disease importance of gfap isoform−specific analyses in astrocytoma a radiomics nomogram may improve the prediction of idh genotype for astrocytoma before surgery radiomic features predict ki- expression level and survival in lower grade gliomas userguided d active contour segmentation of anatomical structures: significantly improved efficiency and reliability scikit-learn: machine learning in python smote for high-dimensional class-imbalanced data deep multi-scale d convolutional neural network (cnn) for mri gliomas brain tumor classification automated glioma grading on conventional mri images using deep convolutional neural networks prediction of lower-grade glioma molecular subtypes using deep learning deep transfer learning and radiomics feature prediction of survival of patients with highgrade gliomas a novel fully automated mri-based deep-learning method for classification of idh mutation status in brain gliomas idhresidual convolutional neural network for the determination of status in low-and high-grade gliomas from mr imaging jl, mg, and sh: conception and design, and provision of study materials or patients. jl and ry: administrative support. mg, sh, xp, xl, and jl: collection and assembly of data. mg, sh, xp, and jl: data analysis and interpretation. all authors: writing and final approval of the manuscript. the authors express their appreciation to ying zeng for the acquisition, analysis, and interpretation of data for the work. key: cord- -fmq aa authors: gooding, k. m.; lienczewski, c.; papale, m.; koivuviita, n.; maziarz, m.; dutius andersson, a.-m.; sharma, k.; pontrelli, p.; garcia hernandez, a.; bailey, j.; tobin, k.; saunavaara, v.; zetterqvist, a.; shelley, d.; teh, i.; ball, c.; puppala, s.; ibberson, m.; karihaloo, a.; metsärinne, k.; banks, r.; gilmour, p. s.; mansfield, m.; gilchrist, m.; de zeeuw, d.; heerspink, h. j.; nuutila, p.; kretzler, m.; wellberry-smith, m.; gesualdo, l.; andress, d.; grenier, n.; shore, a. c.; gomez, m. f.; sourbron, s.; investigators, ibeat title: prognostic imaging biomarkers for diabetic kidney disease (ibeat): study protocol date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: fmq aa diabetic kidney disease (dkd) is traditionally classified based on albuminuria and reduced kidney function (estimated glomerular filtration rate (egfr)), but these have limitations as prognostic biomarkers due to the heterogeneity of dkd. novel prognostic markers are needed to improve stratification of patients based on risk of disease progression. the ibeat study, part of the beat-dkd consortium, aims to determine whether renal imaging biomarkers (magnetic resonance imaging (mri) and ultrasound (us)) provide insight into the pathogenesis and heterogeneity of dkd (primary aim), and whether they have potential as prognostic biomarkers in dkd progression (secondary aim). ibeat is a prospective multi-centre observational cohort study recruiting patients with type diabetes (t d) and egfr > ml/min/ . m . at baseline each participant will undergo quantitative renal mri and us imaging with central processing for mri images. blood sampling, urine collection and clinical examinations will be performed and medical history obtained at baseline, and these assessments will be repeated annually for years. biological samples will be stored in a central laboratory for later biomarker and validation studies. all data will be stored in a central data depository. data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers may improve the prediction of dkd progression rates. embedded within ibeat are ancillary substudies that will ( ) validate imaging biomarkers against renal histopathology; ( ) validate mri based renal blood flow against water-labelled positron-emission tomography (pet); ( ) develop machine-learning methods for automated processing of renal mri images; ( ) examine longitudinal changes in imaging biomarkers; ( ) examine whether the glycocalyx, microvascular function and structure are associated with imaging biomarkers and egfr decline; ( ) a pilot study to examine whether the findings in t d can be extrapolated to type diabetes. the ibeat study, the largest dkd imaging study to date, will provide invaluable insights into the progression and heterogeneity of dkd, and aims to contribute to a more personalized approach to the management of dkd in patients with type diabetes. diabetic kidney disease (dkd) is the leading cause of end stage renal disease ( , ) . it is currently estimated that approximately - % of people with diabetes will develop dkd ( ) , and this is expected to rise in the future. with the global increase in the prevalence of diabetes ( ), particularly type diabetes, dkd is reaching epidemic proportions, with health and quality of life implications (e.g. increased risk of cardiovascular mortality) for the individual ( ) . even with current approaches to management of diabetes and renin-angiotensin-aldosterone system blockade, there is still large residual risk in dkd ( ) . dkd is routinely classified clinically based on albuminuria and reduced kidney function (estimated glomerular filtration rate (egfr)). albuminuria is traditionally viewed as a hallmark of diabetes related kidney damage. however, there are limitations of using albuminuria to classify dkd, which include the need for multiple measurements to mitigate spurious results due to factors such as infection and physical activity. additionally, the heterogeneity of dkd is increasingly recognised, as reflected, for example, by the disparity in dkd progression (fast versus slow dkd progression) and by patients with declining kidney function but normoalbuminuria. for example, % of participants in the uk prospective diabetes study whose egfr declined below ml/min/ . m had normoalbuminuria ( ) . this heterogeneity in dkd highlights the need for novel biomarkers and a more personalized medicine-based approach to managing dkd. the fundamental aim of the biomarker enterprise to attack dkd (beat-dkd) consortium is to increase our understanding of the pathogenesis and heterogeneity of dkd, enabling the identification of novel biomarkers and treatment targets, to facilitate a more personalized medicinebased approach to managing dkd and increase the efficiency of clinical trials ( ) . cross-sectional imaging, in particular mri and us, is increasingly proposed as an alternative source of biomarkers to inform chronic kidney disease (ckd) management ( , ) . an important example is the qualification by the food and drug administration (fda) and the european medicines agency (ema) of total kidney volume (tkv) as a prognostic enrichment biomarker for autosomal dominant polycystic kidney disease (adpkd) -one of only a handful of clinical biomarkers approved by the fda so far ( , ) . in recent years the interest is increasingly moving towards advanced mri and us techniques that are sensitive to structural and functional tissue characteristics such as perfusion, oxygenation, blood flow, glomerular filtration, tubular flow, fibrosis, inflammation, metabolism and tissue composition. additional utility derives from the fact that these characteristics can be measured separately for left and right kidney, for cortex and medulla, or to map functional and structural heterogeneity within those areas. a number of preclinical and single-centre clinical studies have indicated a potential utility of mri and us biomarkers in dkd specifically. for instance, us-based measurements of kidney volume have suggested that kidney enlargement is associated with poorer outcomes in early and advanced dkd, despite the often better gfr of larger kidneys ( ) ( ) ( ) . a possible explanation is that hypertrophy indicates a sustained state of primary or secondary hyperfiltration and associated damage due to intraglomerular pressures. a mechanistic study suggested that the mri method bold (blood oxygenation level dependent mri) can highlight areas at risk of ischemic damage due to oxygen depletion after sustained hyperfiltration ( ) , and a recent clinical study has confirmed that the bold signal is predictive of ckd progression ( ) . some mri biomarkers derived from diffusionweighted mri are sensitive to renal fibrosis ( , ) and can identify microstructural changes after sustained hyperfiltration ( ) , though the clinical potential of mri measures of fibrosis and microstructure remains to be confirmed ( ) . kidney perfusion and glomerular filtration can be measured with mri. renal blood flow has been shown to correlate with egfr in dkd ( ) . other non-renal imaging biomarkers characterising general risk factors for diabetes and its associated complications may be relevant in this context as well and can easily be measured in the same mri scan session, such as liver and pancreatic fat fraction ( ) . the aim of ibeat is to evaluate the evidence for the utility of imaging biomarkers in dkd in a large cohort of heterogeneous type diabetes patients, in the early stages of dkd where there is high potential for effective interventions to slow the rate of dkd progression. the key hypotheses are that ( ) imaging-based biomarkers of dkd provide additional information on the pathogenesis and histological and clinical heterogeneity of dkd compared to biomarkers sourced from samples or physical exams, and ( ) that changes in imaging biomarkers precede increases in albuminuria and decline in kidney function as measured by egfr. as a result, we expect imaging biomarkers to improve the identification of dkd patients at risk of rapid decline in kidney function, either when used alone or combined with clinical data / biological fluid biomarkers. an additional aim of the ibeat study is to establish a biobank of biological samples (blood-and urine-based) from well-characterised patients for use within the beat-dkd programme and future dkd studies. this will facilitate biomarker discovery studies using novel blood-and urine-based biomarkers and may serve as the foundation for a comprehensive multi-scale phenotyping strategy linking data from blood, urine, tissue, microvascular assessments, imaging, physical measurements and medical histories. the specific study objectives are:  primary objective: to examine whether renal imaging biomarkers are associated with severity of dkd as defined using classical biomarkers of dkd, albuminuria and egfr, in individuals with type diabetes and egfr > ml/min/ . m .  secondary objective: to examine whether renal imaging biomarkers are associated with changes in renal function over time as measured by egfr over a -year period. ibeat (registered at clinicaltrials.gov under nct ) is a prospective observational study that will enrol participants, stratified into six subgroups based on three albumin-to-creatinine ratio (acr) and two egfr categories, with type diabetes (t d) and egfr greater than ml/min/ . m across five european centers. a schematic overview of the study assessments is presented in table . at baseline, each participant will undergo comprehensive renal imaging (mri and us), biological sample collection (blood and urine), physical measurements and their medical history will be collected. they will then be invited back annually for years, where all measurements except the imaging will be repeated. participants can then be followed remotely, through medical notes and/or questionnaires, for a further years. the organisation of ibeat is shown in figure . the study is led by the coordinating centre in leeds with a co-lead in exeter and a study manager in michigan, currently there are recruiting centers (university of leeds, university of exeter medical school, university of bari, university of bordeaux and university of turku), a central laboratory (lund university) and a central data repository (swiss institute of bioinformatics (sib)). all ethical and relevant local approvals are in place at each recruiting site. as a beat-dkd work package the study is supported by the beat-dkd consortium steering committee and an external scientific advisor. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint the ibeat study will recruit participants with a diagnosis of type diabetes, egfr greater than ml/min/ . m , aged between - years, who are able to give informed consent, and do not satisfy any of the exclusion criteria. the exclusion criteria are listed in table (see also supplement . ). ibeat will recruit across six strata defined by the a -a albuminuria range (normo-, micro-and macroalbuminuria) and the (g +g )-g egfr range. in line with the national kidney foundation guidelines ( ), albuminuria will be classified using two (or three) independent values of acrs measured within a -month period: one at the screening visit, one at the baseline study visit, and a third if the classification differs between the first two samples. we define normo-, micro-and macro-albuminuria as an acr of < . , . - , > mg/mmol for men, respectively, and as acr < . , . - , > mg/mmol for women, respectively. following the provision of written informed consent at the start of the screening visit, potential participants undergo a number of health assessments including, for example, medical history, random spot urine collection for assessment of acr and a blood sample for the assessment of egfr (unless these have been performed in the last months) to assess eligibility for the study. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint baseline study assessments participant preparation: fasting blood samples are taken in the morning following an overnight fast. medications may be withheld or altered on the day of study visit to ensure participant wellbeing (e.g. omitting morning insulin injection to maintain blood glucose levels) and integrity of the study. a point of care glucose measurement will be performed upon participant arrival and the visit will be cancelled if glucose levels are below . mmol/l or if the participant reports a symptomatic hypoglycaemic event on the morning of the visit. all other assessments are performed following a standardised meal. participants are required to be on stable diabetes and hypertension related treatment (though dose changes to current medications are allowed) for the months prior to study assessments. the study visit will include a checklist to record the adherence to instructions (supplement . ). mri biomarkers: primary mri biomarkers will be recorded (see supplement . for a full list), characterising general body composition (e.g. visceral fat volume, pancreatic and liver fat fraction), renal morphology (e.g. parenchymal volume, cortical thickness), renal tissue structure (e.g. mr relaxation times, apparent water diffusion coefficient), renal hemodynamics (e.g. cortical perfusion, renal artery blood flow), filtration (e.g. single-kidney gfr, filtration fraction). all mr scanning is performed at t on siemens, philips and general electric scanners. mri data are uploaded on a central xnat database hosted by sib and quality controlled within hrs by the central processing site in leeds. the mri protocol takes approximately hr and mins and involves the injection of a quarter dose of clinical macrocyclic mri contrast agent. the protocol was first developed on the reference siemens scanner in leeds using an iterative optimisation guided by the nist (national institute of standards and technology) phantom and healthy volunteers. the resulting final protocol was then characterised on each mri vendor using a repeatability study in healthy volunteers to determine within-site variability ( volunteers with scans each). the nist phantom is scanned at regular intervals in all sites to check for between-site calibration. full details of the mri acquisition protocol on the t siemens reference scanner in leeds can be found in supplement . . renal ultrasound: kidney size will be non-invasively determined from longitudinal and transversal images of each kidney. resistive index (ri), indicator of the resistance to flow within the kidney, will be determined from three measurements in each kidney (upper, mid and lower poles). the mean of the three measurements will represent ri for each respective kidney. a list of us biomarkers are provided in the supplement . and the standard operating procedures (sops) for us scanning are in supplement . . blood and urine sampling: fasting blood samples (~ mls designated for ibeat central requirement) will be collected from each participant for participant characterisation and biomarker analysis. glycated haemoglobin (hba c), full blood count and fasting glucose assessments will be performed locally (supplement . ). the remaining plasma and serum samples will be processed and stored following a standardised protocol (see supplemental . - . ). a first morning urine void and one additional morning void (same day) are collected by all participants. a small proportion of the first morning void is sent to the local laboratories for acr assessment. the remainder of the first morning and second void are then processed and stored following a standardised protocol (see supplemental . - . ). the standardised sample collection and processing protocol, informed by provalid and neptune trials ( , ) , was developed to maximise the utility of stored samples for future biomarker analysis (e.g. lipidomics, rna analysis, urinary vesicles and urinary sediment) within beat-dkd and to form a biobank for future dkd related studies. a separate check is performed to confirm that all samples are collected and processed according to protocol (supplement . ). . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint the central biochemical laboratory is located at the clinical research centre (crc) facility in malmö (university of lund). the central lab will prepare and distribute kits with sample collection and processing materials for each patient labelled and barcoded with the study id. each kit comprises of storage tubes per patient. the samples will be temporarily stored at each recruiting site, with regular shipments returning them to the biobank in malmö. samples will be stored under secure conditions and monitored with a dedicated electronic sample tracking system (laboratory information management systems). a small volume of blood and urine will be analysed in malmö for known clinical biomarkers (e.g. renal function (serum creatinine, cystatin c, potassium and albumin), lipid profile (total cholesterol and sub-fractions, triglycerides) and c-reactive protein) at the central laboratory, according to standardised methods, and the remainder will be stored for future analyses by beat-dkd investigators. the samples will also remain available for secondary research provided approval is granted by the ibeat steering committee. physical examination: the core physical examination assessments include blood pressures (sitting and standing blood pressures) and anthropometrics (height, weight, waist and hip circumference) assessments. see supplement . for details. medical history. a detailed medical history (including, for example, current medications, smoking history and presence of co-morbidities) is also collected. see supplements . and . for data fields that are captured. routine lab data: routine local laboratory data will be captured to aid in the interpretation of the results by tracking temporal changes at a finer time scale than the yearly follow-ups. only laboratory values available for clinical indication will be captured at this time. supplement . lists the data fields to be captured but missing data from the local chart is not deemed a protocol violation. the biological sampling protocol, medical history and physical examination will be repeated at , and years (± months) following study enrolment. for participants who are unable to attend the local research centre for an annual follow-up visit but are still willing to participate in the study an update on their medical history will be collected via direct communication with the participant and / or by accessing their available medical records. clinical images, associated data and metadata will be stored using the xnat platform (www.xnat.org) hosted on the dedicated beat-dkd server at sib. clinical study data will be managed using redcap (www.project-redcap.org), also installed on the dedicated beat-dkd server. all variables will be recorded on ibeat central clinical record folders (crf's -see supplements . - . ) and uploaded onto the central redcap instance. it is envisaged that the ibeat clinical study will be set up as a federated node enabling remote analysis of the data generated in the future, and integration of the ibeat data with other datasets collected in beat-dkd. sample size: the sample size calculation for a study such as this one would be complex and unlikely to be accurate. thus, we opted for a more pragmatic approach, and arrived at the sample size by considering the scientific and feasibility aspects of the study. specifically, in considering the sampling design, we were mainly concerned with whether it would allow us to answer the scientific questions we have and whether it would be feasible to carry out. we opted for a stratified sampling design, as we were interested in evaluating the association between imaging renal biomarkers and dkd in type diabetes patients in various stages of dkd, as measured by acr and egfr, widely used biomarkers of dkd. this ensures that we will have a reasonable sample size for all combinations of acr (a , a , a ) and egfr (g +g , g ), even those that are typically rare, specifically a and g , as well as a and g +g . in terms of feasibility, we considered the number of imaging facilities available to us and the estimated rate of recruitment in each for each strata of our sample. based on these considerations we arrived at a stratified sample of patients, groups of and two groups of . see table in supplement . for details. we will begin by describing our data, comparing the descriptive statistics of all covariates across the study centers, assessing the bivariate relationships between sets of related covariates. we will then perform a cross-sectional analysis using data collected at baseline, as well as a longitudinal analysis using the imaging data collected at baseline and blood and urine markers collected over the three years. given the large number of covariates in our study, we will use variable selection and regularization methods such as lasso ( ) and the elastic net regularization ( ) . the modelling will be done appropriately for a given setting, with linear models for the crosssectional analyses, and linear mixed effects models for the longitudinal analysis. the analyses will be performed separately in each strata and, whenever possible, accounting for the stratification in the modelling, as we expect there to be effect modification in the potential associations we will be estimating across the strata. we will adjust for multiple comparisons as needed. if we identify any renal imaging biomarkers as having promise as early markers of dkd progression, we will use them in risk prediction and evaluate their predictive accuracy, as measured by prediction error, receiver operating characteristics curve (roc) and the area under the roc (area under the curve, auc), using cross-validation. we plan to take a conservative approach in all of our analyses, meaning that we will be careful with the number of models we fit and statistical tests we perform, and will treat our analyses as exploratory and hypotheses generating, rather than hypothesis testing. building on the strengths and interests across the ibeat participating centres, six ancillary studies have been incorporated within the central ibeat study. participants taking part in the ancillary studies will be recruited from the central ibeat study at the relevant sites. ancillary study : to examine whether mri and us based imaging biomarkers correlate with histopathological markers of dkd and discriminate different renal lesions in this t d cohort. for this ancillary study, led by bari university, ibeat participants will undergo a renal tissue core biopsy (n= ). all biopsies will be digitalized and characterized by light microscopy (hematoxylin-eosin, periodic acid-schiff, silver methenamine, and masson's trichrome), immunofluorescence microscopy (with the use of antisera against igg, igm, iga, c , c , c q and fibrinogen) and electron microscopy. glomerular and vascular lesions, interstitial cell infiltrate, fibrosis and tubular atrophy will be quantified ( ) . samples will also be processed and stored for later biomarker discovery. the procedures for processing, storing and capturing meta-data regarding the renal biopsy tissue are described in more detail in supplement . . ancillary study : to examine whether mri-based measurements of renal blood flow correlate with h o-positron emission tomography (pet) renal perfusion measurements, validating the mri based measurements against the standard pet perfusion measurements. for this ancillary study, led by turku university, a direct comparison of mri and pet-based measurements of renal blood flow will be performed in a cohort of ibeat participants. renal perfusion will be assessed during hyperaemia with both systems. ancillary study : to develop machine-learning methods for automated or semi-automated processing of multiparametric renal mri. in its current form the generation of biomarkers from complex functional mri scans involves significant manual intervention as well as automated but slow iterative optimisation methods. in this study, led by leeds university, a subset of the ibeat data will be used as training data to develop an ideally automated approach for image processing, which will then be validated on the remaining test data against the manual results. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint ancillary study : to investigate the longitudinal changes in mri and us based biomarkers, compare them against changes in egfr and other known markers, and determine whether changes in imaging biomarkers precede dkd progression as assessed by egfr decline. for this study a cohort of patients will receive repeat mri and us after years, and changes in imaging biomarkers over that period will be correlated against changes in egfr and other assessments. ancillary study : to examine whether the glycocalyx, microvascular function and structure (retinal and skin) are ( ) altered in microalbuminuria; ( ) associated with dkd progression as assessed by egfr decline and ( ) are associated with novel mri and us imaging dkd biomarkers. for this study, led by university of exeter, ibeat participants will also undergo comprehensive microvascular assessments (including non-invasive estimation of sublingual endothelial glycocalyx integrity, retinal vascular oxygenation and skin maximum hyperaemia) at baseline and at years follow-up. ancillary study : a pilot study to examine whether the findings in t d can be extrapolated to type diabetes. in this ancillary study a cohort of patients with type diabetes will be assessed using the same procedures as the type cohort and observed findings / trends will be compared across the two populations. patient and public involvement and engagement is a significant component of the ibeat study. potential participants have played an important role in ibeat, reviewing the protocol to ensure the feasibility of the study design (core and ancillary studies) as well as contributing to the development of patient facing documents (e.g. patient information sheets), ensuring that they are clear and informative. participants within the ibeat study will play an integral role in the dissemination of the study results to the wider, non-expert population. within the beat-dkd consortium discussions with patient representatives, ranging from experienced patient advocates to ibeat participants, will help inform how research from the beat-dkd consortium is taken forward to implement a more precision medicine based approach in dkd into clinical practice; for example, validation and qualification of new biomarkers by regulatory agencies, optimising clinical study design and integration in the regulatory process of drug registration. indeed, this has already commenced with an ibeat participant, along with other patient representatives, attending the nd beat-dkd stakeholders' symposiums in april ( ) . quantitative and functional imaging of the kidney has been an active topic of research in the mri physics and radiology community for over two decades ( ) , but the last few years have seen an explosive growth in clinical interest. the first international meeting on functional renal mri was held in and attendance has been increasing steadily ever since ( ) ( ) ( ) . in , a pan-european network of researchers in renal mri (www.renalmri.org) was funded for years by the european cooperation in science and technology (www.cost.eu). in , nephrology dialysis transplantation published a special issue on renal mri with a clinical position statement supported by over authors including leading european nephrologists ( ) . in the same year, in the us, the national institute of diabetes and digestive and kidney diseases (niddk) at the national institutes of health (nih) conducted a workshop on renal imaging to review the state-of-the-art and plan potential future endeavours [ ] . also in , the uk renal imaging network (ukrin) received a -year partnership grant to create a national infrastructure for quantitative renal mri, and has advanced plans for a year cohort study in ckd patients (afirm study; principal investigator: nick selby, university of nottingham). ibeat builds on these developments and is the first study to respond to the clinical need for systematically collected evidence at a larger scale and across institutions, with well-validated methods linking up the imaging findings with other sources of data so the added value can be identified. in that sense, ibeat is inspired by the landmark study crisp (consortium for radiologic imaging studies of polycystic kidney disease) ( ) -the first multi-centre cohort study exploring a quantitative mri biomarker (tkv) in ckd and a foundation for the aforementioned fda qualification of tkv. like crisp, ibeat has built in a technical validation phase of the imaging biomarkers by including a repeatability study on all scanner types deployed in ibeat, and by calibrating betweenscanner differences through a travelling test object developed for this purpose by the national institute of standards and technology ( ) . also following the example of crisp, ibeat is committed to sharing the technical details of its imaging protocols and expertise in image processing and quality assurance -not only to facilitate the cost and setup of future studies but also to maximise alignment and future opportunities for pooling the data. an example is an ongoing collaboration with the dynamo consortium (https://www.duke-nus.edu.sg/about/achievements/awards/collaborativegrants) in setting up an imaging biomarker study aligned with ibeat. collectively, the integration of the ancillary studies into ibeat will provide valuable information on the pathogenesis of dkd and the clinical utility of these imaging biomarkers. crucially, they will explore the association of renal based imaging biomarkers against histopathological markers and different histological lesions of dkd, validating the imaging biomarkers and substantiating their clinical utility. mri renal based perfusion measurements will also be validated against h o-pet renal perfusion measurements. the potential automation of the mri image processing will streamline a labour intensive process, thereby increasing the clinical applicability of the assessments. the microvascular assessments, including the examination of glycocalyx integrity and endothelial function, will provide invaluable information on the pathogenesis and heterogeneity of dkd, and may well aid the identification of individuals with fast progressing dkd, for example, we hypothesise that individuals with type diabetes with early signs of perturbations to the glycocalyx will be at an increased risk of dkd progression. ibeat has greatly benefitted in its setup from study documents and standard operating procedures (sops) provided by other investigators, in particular the provalid ( ) and neptune ( ) studies. in turn, ibeat is committed to a "pay-it-forward" philosophy and will aim to share its study documentation and procedures widely for use by other investigators. ibeat collaborators are also committed to maximise the opportunities for data sharing in order to increase the lifetime value of their research data as assets for human health and to do so timely, responsibly, with as few restrictions as possible, in a way consistent with the law, regulation and recognised good practice. beyond data, ibeat will aim to form a powerful resource for future biomarker discovery sources by . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint collecting a rich collection of blood and urine samples in its central biobank. these will be made available for external investigators subject to formal application and approval by the ibeat steering committee. after a -year setup period the first study participant was recruited into ibeat in october . first results on technical validation of mri methods on the reference scanner are expected at the end of . the projected deadline for recruitment is september and first results on the primary objective (cross-sectional analysis of baseline data) are expected to be made public in . completion of follow-up data is expected in sept with results on the longitudinal analysis expected to be submitted for publication in . this project has received funding from the innovative medicines initiative joint undertaking under grant agreement no . this joint undertaking receives support from the european union's horizon research and innovation programme and efpia with jdrf. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint chronic kidney disease: global dimension and perspectives. the lancet diabetes and ckd in the united states population diabetic kidney disease: challenges, progress, and possibilities global prevalence of diabetes: estimates for the year and projections for albuminuria and renal function as predictors of cardiovascular events and mortality in a general population of patients with type diabetes: a nationwide observational study from the swedish national diabetes register the effect of raas blockade on the progression of diabetic nephropathy microvascular disease: what does the ukpds tell us about diabetic nephropathy biomarker enterprise to attack diabetic kidney disease magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the european cooperation in science and technology action parenchima functional magnetic resonance imaging of the kidneys: where do we stand? the perspective of the european cost action parenchima clinical review of pkd outcomes consortium biomarker qualification submissionle renal duplex sonographic evaluation of type diabetic patients persistent renal hypertrophy and faster decline of glomerular filtration rate precede the development of microalbuminuria in type diabetes large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease renal diffusion and bold mri in experimental diabetic nephropathy reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease new magnetic resonance imaging index for renal fibrosis assessment: a comparison between diffusion-weighted imaging and t mapping with histological validation magnetic resonance diffusion tensor imaging for evaluation of histopathological changes in a rat model of diabetic nephropathy use of diffusion tensor mri to identify early changes in diabetic nephropathy could mri be used to image kidney fibrosis? a review of recent advances and remaining barriers arterial spin labeling mri is able to detect early hemodynamic changes in diabetic nephropathy remission of human type diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for β cell recovery national kidney foundation. k/doqi clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification design of the nephrotic syndrome study network (neptune) to evaluate primary glomerular nephropathy by a multidisciplinary approach a prospective cohort study in patients with type diabetes mellitus for validation of biomarkers (provalid) -study design and baseline characteristics regression shrinkage and selection via the lasso regularization and variable selection via the elastic net pathologic classification of diabetic nephropathy highlights from the beat-dkd symposium on precision medicine in diabetic kidney disease radiologic imaging of the renal parenchyma structure and function st international meeting on renal mri d international meeting on renal mri volume progression in polycystic kidney disease quantitative magnetic resonance imaging phantoms: a review and the need for a system phantom key: cord- -vtf o ml authors: zhang, tianshu; hirsh, ellen; zandieh, shadi; rodricks, michael b. title: covid- -associated acute multi-infarct encephalopathy in an asymptomatic cadasil patient date: - - journal: neurocrit care doi: . /s - - - sha: doc_id: cord_uid: vtf o ml nan and myalgias which were mild, lasted days, and were self-limited. her sister did not seek any medical care. the patient fell ill days after her sister's return with similar symptoms of a headache and myalgias. after developing lethargy, dysphagia, and speech difficulties, she was brought to the emergency department. the physical examination revealed a patient in moderate acute distress. she was febrile with a temperature of . °f. her blood pressure was / with a heart rate of and a respiratory rate of . the room air oxygen saturation was %. neurologically, she was awake and alert and followed commands although sluggishly. she had difficulty with her speech with components of both dysarthria and expressive aphasia, difficulty handling her secretions, and dysphagia. there was no meningismus which could be elicited. her pupils were equal round and reactive, but she showed a right gaze preference and a mild left facial droop. she had mildly decreased but equal bilateral strength. the deep tendon reflexes were preserved. the remainder of the examination was only notable for diffuse rhonchi on auscultation of her lungs. initial laboratory studies showed a mild leukocytosis with lymphopenia. the chest x-ray demonstrated patchy consolidation in the right lower lung. a non-contrast computed tomography (ct) of the head showed no evidence of intracranial hemorrhage, but there were multifocal patchy areas of white matter hypoattenuation (fig. ) . a lumbar puncture was performed to clarify the diagnosis and to exclude central nervous system infection. cerebrospinal fluid (csf) analysis revealed normal cell counts, protein, and glucose. a polymerase chain reaction (pcr) panel for meningitis and encephalitis, including herpes simplex and , human herpes , cryptococcus, and varicella zoster virus, was entirely negative as were bacterial cultures. a lyme titer was negative. an electroencephalogram (eeg) did not show electrical evidence of seizures. the covid- pcr test of a nasal swab became available days after admission and detected the novel coronavirus (sars-cov- ) target nucleic acid. the covid- pcr test of csf was negative (cepheid genexpert system). to assess the white matter lesions found on head ct, a magnetic resonance imaging (mri) of the brain with and without contrast was obtained. the mri showed extensive patchy areas of abnormal signal involving bilateral frontoparietal white matter, anterior temporal lobes, basal ganglia, external capsules, and thalami. additionally, some of these foci demonstrated diffusion-weighted imaging (dwi) changes and corresponding apparent diffusion coefficient (adc) changes, with questionable minimal enhancement (fig. ). magnetic resonance angiography (mra) of the brain and neck was essentially normal. the patient was treated with hydroxychloroquine, ceftriaxone, and a -day course of intravenous immunoglobulins (ivig). steroids were not used as it was felt to be contraindicated given the acute covid- diagnosis and in keeping with the then current guidelines. the patient was also given aspirin for stroke prophylaxis. after days of ivig, the patient showed signs of improvement-she was better able to handle secretions, less dysarthric, afebrile and had no respiratory symptoms. because of her acute covid- diagnosis, it was difficult to get her placed in a rehabilitation facility. the patient's speech, strength, and ability to swallow continued to improve, and she was able to be discharged to home by hospital day . at an outpatient follow-up week after discharge, the patient was found to be almost at baseline-tolerating a regular diet, normal speech, symmetric face, normal motor and sensory examination, and able to ambulate independently albeit at a slow pace, with some easy fatigability. a follow-up brain mri (fig. ) was performed weeks after the initial mri study. it showed that the initial dwi and adc changes had largely disappeared. there was a hypodense area on t flair images without enhancement and with persistent t flair changes in a similar distribution as previous mri. the chronological changes from the initial dwi and adc images to the disappearance of these signals in the follow-up mri support that the patient had acute subcortical ischemic changes or necrotic changes. the patient continued to recover from her acute illness, and weeks post-discharge she resumed driving and returned to her previous work. an additional workup became available a month after the second mri including a negative myelin antibody and notch genetic testing. it revealed the presence of a pathogenic variant in the notch gene-a heterozygous missense mutation (sequencing test by athena diagnostics) which was consistent with a diagnosis of cadasil. it is important to consider other infectious etiologies with or without a diagnosis of covid- in a patient with fever, neurological deficits, and encephalopathy. an electroencephalogram (eeg) is indicated to exclude subclinical seizures and non-convulsive status epilepticus. the ct findings prompted a further workup for cerebral abscesses and septic emboli. it is difficult to perform an mri on a covid- -positive patient or a person under investigation (pui) due to the concern for contamination of equipment, the requisite patient transportation, and the risk of exposure to healthcare providers. given the clinical picture and the ct findings, it seemed rational to take the necessary steps to obtain such imaging. the brain mri showed multiple dwi lesions and corresponding adc sequence changes which were consistent with multiple acute infarcts possibly related to hypoxic-ischemic injury from systemic perturbations and resultant tissue hypoxia. the predominance of the extensive t flair signal changes in the cerebral white matter lesions is more suggestive of a demyelinating process. these lesions are extensive, bilateral, and predominantly subcortical, with additional involvement of the deep nuclei. these features are compatible with an acute inflammatory encephalopathy in the setting of a recent or ongoing systemic viral infection with acute neurological deficits. this case potentially represents atypical acute disseminated encephalomyelitis (adem) as the csf did not show any pleocytosis or increased protein levels [ ] , though absence of csf changes could be related to the timing of lumbar puncture. the initial presentation of multiple sclerosis is within the differential diagnosis, but given the lack of any prior neurological symptoms and the clinical picture described as well as the acute diagnosis of covid- it seems unlikely. myelin oligodendrocyte glycoprotein (mog) antibody-associated encephalitis is also a consideration; however, the patient had negative myelin antibody. in a patient with multiple infarcts, the differential diagnosis also includes a cardioembolic cause. in this case, it was initially suspected that these multiple infarcts could be from a combination of hypoxia and a hypercoagulable state from the acute covid- infection [ ] . the subcortical multiple infarcts this patient experienced along with the relatively symmetric white matter lesions seen on brain mri suggest a case of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil). the acute infection combined with a complete lack of family history of stroke, dementia or migraine, and the patient lacking of prior migraine with aura, stroke, cognitive impairment, or psychiatric illness is unusual but does not exclude a diagnosis of cadasil as de novo cases have been described. the clinical course of complete recovery in a few weeks is also atypical for a diagnosis of cadasil. our patient did undergo genetic testing which revealed the presence of a pathogenic variant in the notch gene consistent with cadasil. it is still not clear if the multiple subcortical infarctions seen on mris are from cadasil itself, or some combination of direct viral invasion, an immunological reaction, or a cytokine storm syndrome despite the findings of normal csf and a negative covid- pcr of the csf. the distribution of the ct and mri changes in our case is similar to a recent case report of acute hemorrhagic necrotizing encephalopathy in a covid- patient [ ] , which case, to our knowledge, was not tested for a pathological notch mutation. we present a unique case of acute multi-infarct encephalopathy in a covid- patient. the clinical features and ct and mri changes are consistent with acute subcortical multiple infarctions which could be related to or provoked by a viral infection. further genetic testing revealed this previously asymptomatic patient to have a pathogenic variant of the notch gene consistent with cadasil. even though it is known that there are vascular wall smooth muscle abnormalities related to cadasil gene mutations, it is not clear what triggers the multiple infarcts in these patients. the acute infection likely induced a milieu of inflammation, hypoxia, and coagulopathy in this covid- patient which triggered multiple infarcts. further investigation as to the precipitants of the hypoxic-ischemic process in cadasil patients is of interest. our described case is an atypical presentation of an acute covid- infection in a previously asymptomatic cadasil patient who presented with multiple infarcts and encephalopathy. it is illustrative of the difficulty in searching for a definite diagnosis and the requisite workup to explore the different treatable etiologies of this clinical picture. acute disseminated encephalomyelitis in patients: a retrospective, multicenter us study arterial and venous strokes in the setting of covid- covid- -associated acute hemorrhagic necrotizing encephalopathy: ct and mri features the submission of the manuscript was approved by the rwjuh somerset institutional review board. all authors participated in the clinical work. t. zhang and m.b. rodricks wrote the draft. none. the authors declare that they have no conflict of interest.ethical approval/informed consent irb approval was obtained for this study. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- - ah li authors: yang, shuyi; zhang, yunfei; shen, jie; dai, yongming; ling, yun; lu, hongzhou; zhang, rengyin; ding, xueting; qi, huali; shi, yuxin; zhang, zhiyong; shan, fei title: clinical potential of ute‐mri for assessing covid‐ : patient‐ and lesion‐based comparative analysis date: - - journal: j magn reson imaging doi: . /jmri. sha: doc_id: cord_uid: ah li background: chest computed tomography (ct) has shown tremendous clinical potential for screening, diagnosis, and surveillance of covid‐ . however, safety concerns are warranted due to repeated exposure of x‐rays over a short period of time. recent advances in mri suggested that ultrashort echo time mri (ute‐mri) was valuable for pulmonary applications. purpose: to evaluate the effectiveness of ute‐mri for assessing covid‐ . study type: prospective. population: in all, patients with covid‐ and with an average interval of . days between hospital admission and image examination. field strength/sequence: t; respiratory‐gated three‐dimensional radial ute pulse sequence. assessment: image quality score. patient‐ and lesion‐based interobserver and intermethod agreement for identifying the representative image findings of covid‐ . statistical tests: wilcoxon‐rank sum test, kendall's coefficient of concordance (kendall's w), intraclass coefficients (iccs), and weighted kappa statistics. results: there was no significant difference between the image quality of ct and ute‐mri (ct vs. ute‐mri: . ± . vs. . ± . , p = . ). moreover, both patient‐ and lesion‐based interobserver agreement of ct and ute‐mri for evaluating the image signs of covid‐ were determined as excellent (icc: . – . , p < . ; kendall's w: . – . , p < . .). in addition, the intermethod agreement of two image modalities for assessing the representative findings of covid‐ including affected lobes, total severity score, ground glass opacities (ggo), consolidation, ggo with consolidation, the number of crazy paving pattern, and linear opacities, as well as pseudocavity were all determined as substantial or excellent (kappa: . – . , p < . ; icc: . – . , p < . ). data conclusion: pulmonary mri with ute is valuable for assessing the representative image findings of covid‐ with a high concordance to ct. evidence level: technical efficacy stage: demand with limited manufacturing capacity of rt-pcr kits, especially in less-developed countries. ) false-negative rt-pcr results have been broadly reported. , given the aforementioned challenges, chest computed tomography (ct) has been strongly recommended and encouraged for screening for covid- . , ai et al suggested that chest ct has ultra-high sensitivity ( %) for diagnosing covid- . besides, excellent performance of chest ct has been reported for diagnosing cases with negative rt-pcr results. previous studies have reported the clinical and ct imaging features of covid- . , typical ct findings include ground glass opacities (ggo), ggo with consolidation, crazy paving pattern, or consolidation in a peripheral, posterior, and diffuse or lower lung zone. [ ] [ ] [ ] ct is helpful to guide clinical management and surveil the progression of covid- . because of the rapid progression of covid- , the interval between the initial confirmation and the transfer to an intensive care unit (icu) can be as short as a day. patients often receive more than one chest ct during their disease episode. , hence, there is a theoretical radiation risk to these often young patients. an image modality without ionizing radiation would be of great clinical significance for evaluating covid- . as an image modality without ionizing radiation, magnetic resonance imaging (mri) may be a potential alternative to ct for pulmonary application. being less susceptible to fast t * decay as well as respiratory motions, respiratorygated ultrashort echo time mri (ute-mri) has shown utility in pulmonary applications. [ ] [ ] [ ] ohno et al concluded that ute-mri could be applied for visualizing the ggo, consolidation, and so on, in high concordance with ct. we therefore hypothesized that ute-mri may serve as a valuable technique for noninvasively assessing covid- . based on the aforementioned points, this study aimed to evaluate the clinical potential of ute-mri for assessing covid- with ct as the reference according to both a lesion-based and patient-based comparative analysis. this prospective study was approved by the ethical committee of shanghai public health clinical center. written informed consent of each patient was obtained. from february to april , a total of patients were enrolled in this prospective study. the inclusion and exclusion criteria were as the follows: inclusion criteria: . patients confirmed as covid- according to the results of rt-pcr. exclusion criteria: . the absence of ute-mri examinations. . the time interval between ct and mri examinations was greater than days. the average time interval between the hospital admission and ct examination as well as hospital admission and mri examination was . days (median: days) and . days (median: days), respectively. ten patients were excluded because the intervals between the ct examination and ute-mri examination were larger than days. three patients were excluded because of the absence of ute-mri examination. ultimately, this prospective study included patients. ct acquisition: ct examinations were performed with a -section scanner (scenaria ct; hitachi medical, kashiwa, chiba prefecture, japan). the scanning parameters were listed as: tube voltage, kv; tube current - ma; pitch: . ; slice thickness: the entire thoracic cavity was excited with a nonselective hard pulse, followed by acquisition of a free induction decay (fid) signal instead of an echo (as in the case of most conventional clinical sequences), resulting in a center-out radial encoding trajectory. signal acquisition was initiated during the ramp-up stage of encoding gradient to further reduce the effective echo time as well as potential susceptibility artifact as a result of the air-tissue boundaries in the lung. the direction of the encoding gradient was incremented from one acquisition to another to cover the whole k-space in a "koosh ball" pattern. a total of , encoding directions was prescribed. in order to alleviate respiratory motion artifacts, the ute sequence was interleaved with a navigator sequence to track the diaphragm displacement in the superior-inferior direction. the acquisition module was enabled only within a certain predetermined displacement range, during which fids were collected each time. during reconstruction, the radial k-space data were first regridded onto cartesian the coordinate using a kaiser-bessel convolution kernel. all the qualitative and quantitative assessment of ct and ute-mri were carried out by three experienced radiologists (s.y.y., with more than years' experience of chest ct diagnosis and years' experience of pulmonary mri; f.s., with more than years' experience of chest ct diagnosis and years' experience of pulmonary mri; z.y.z., with more than years' experience of chest ct diagnosis and years' experience of pulmonary mri). all the ct and ute-mri images were randomized and independently analyzed by the above three radiologists without any information about the patients' clinical characteristics and results of other image techniques. image quality analysis. all ct and ute-mri images were independently scored by three radiologists with a -point scoring system. detailed scoring standards were: : unacceptable nondiagnostic image quality, : poor image quality, : acceptable image quality, : good image quality, and : excellent image quality. patient-based evaluation. patient-based quantitative imaging indexes including the number of affected lobes, the number of ggos, the number of consolidations, the number of ggos with consolidation, the number of crazy paving patterns, the number of linear opacities, total lung severity score (the sum of the severity score of each lobe; severity score of each lung lobe was based on the involvement) (score : none involvement [ %], score : minimal involvement [ - %], score : mild involvement [ - %], score : moderate involvement [ - %], or score : severe involvement [ - %]) were independently evaluated by three radiologists. lesion-based evaluation. three radiologists independently evaluated the presence of representative image signs and the shapiro-wilk test was performed to evaluate the data normality of the image quality score. the image quality of ute-mri and ct was compared with a wilcoxon-rank sum test, because both the image quality score of ct and ute-mri were not in normal distribution (p < . ). kendall's coefficient of concordance (kendall's w), intraclass coefficients (icc), and weighted kappa statistics were calculated for determining the interobserver and intermethod agreement. the interobserver and intermethod agreement were determined as excellent for kendall's w = . it should be noted that: ) all the statistical results concerning the interobserver agreement evaluation were calculated by the independent evaluation of three radiologists. ) intermethod comparison of image quality and patient-and lesion-based evaluation of intermethod agreement were based on the evaluation of the z.y.z., who is a nationwide recognized radiologist (with more than years' experience of chest ct diagnosis and years' experience of pulmonary mri). intermethod statistical analysis was according to the previously reported method. two-sided p values of less than . were regarded as statistically significant. all the statistical analyses in this study were conducted with spss . (chicago, il). a total of patients (men: , women: ; median age: , age range: - ) were finally included in this study for subsequent analysis. table summarizes the clinical characteristics of the included patients. as shown in table , chest ct examination showed that seven ( . %) patients had one affected lobe, five ( . %) patients had two affected lobes, four ( . %) patients had three affected lobes, five ( . %) patients had four affected lobes, and two ( . %) patients had five affected lobes. in terms of lesion distribution, bilateral involvement was present in ( . %) patients and multifocal involvement was presented in ( . %) patients. ggo with consolidation was identified in ( . %) patients, pure ggo and pure consolidation were respectively identified in eight ( . %) and six ( . %) patients. air bronchograms ( , . %) and crazy paving patterns (two, . %) were also observed within the lesion. other secondary image findings included linear opacities ( , . %), adjacent pleura thickening ( , . %), vessel expansion ( , . %), and pleural effusion (one, . %) also occurred. figures - demonstrate that representative radiological signs of covid- including ggo, consolidation, ggo with consolidation, air bronchogram, and pseudocavity could be visualized with ute-mri. table shows the interobserver iccs of the evaluation of the image quality score of ct and ute-mri, which were . (p < . ) and . (p < . ). as fig. shows, there was no significant difference between the image quality of two image modalities (ct: mean score: . median score: . ; ute-mri: mean score: . median score: . ; z statistics: . , p = . ). the results of interobserver agreement evaluation in table suggest that the interobserver iccs of the patientbased evaluation of covid- ranged between . - . (p < . ). as demonstrated in table , the overall detection rate of affected lobes, ggo, consolidation, ggo with consolidation, crazy pattern, as well as linear opacities were . %, . %, %, . %, %, and . %, respectively. moreover, intermethod iccs of two image modalities ranged from . - . (p < . ). the total severity score quantified by ct and ute-mri were . and . , respectively (icc = . , p < . ). kendall's w statistic was utilized for quantifying the interobserver agreement of the lesion-based evaluation of image signs, which is listed in table . table demonstrates that kendall's w was between . - . (p < . ). lesion-based intermethod agreement of ute-mri and ct for assessing representative pulmonary findings of covid- are shown in table and fig. . a total of lesions were included for the comparative analysis. the intermethod agreements for assessing the ggo, consolidation, ggo with consolidation, crazy paving pattern, pseudocavity, air bronchogram, axial location, and anteroposterior location were all statistically significant, with kappa values ranging from . - . (p < . ). notably, the intermethod agreement for evaluating the ggo, consolidation, ggo with consolidation, axial location, and anteroposterior location was determined as substantial or excellent (kappa: . - . , p < . ). as shown in fig. , the visual score differences between ute-mri and ct for assessing the different representative signs of covid- were small for most lesions. in detail, for assessing ggo, ggo with consolidation, consolidation, pseudocavity, crazy paving pattern, and air bronchogram, the proportion of lesions with a difference in visual score less than were . %, . %, . %, . %, . %, and . %, respectively, which indicated there was a high intermethod concordance. the results of this study suggest that there was not only high concordance between ute-mri and ct in assessing the representative image findings of covid- but also similar image quality for two image modalities, which implies that ute-mri could have potential in aiding the diagnosis and surveillance of covid- . the imaging findings of covid- by ct have been reported recently. , , typical image manifestations have been described as multifocal ggo, patchy consolidation, crazy-paving pattern, air bronchogram, and multiple lesions with bilateral involvement. our study suggests that the ggo with consolidation, ggo, and bilateral and multifocal involvement with periphery distribution were the most frequently occurring ct imaging signs. pathologically, the alveolar damage with alveolar and interstitial edema results in the appearance of ggo and crazy paving pattern. as the alveoli are progressively filled with alveolar fibrinous exudate with hyaline membranes and reactive pneumocytes, ggo evolves into the appearance of consolidation. chung et al indicated that % of patients had the image manifestations of ggo or consolidation. similarly, li and xia indicated that the two principal signs of covid- were ggo and consolidation. however, similar to some previous studies that reported that - % of confirmed covid- patients were with pleural effusion , , ; pleural effusion was less frequently observed in this study. it is known that the pulmonary application of mri has been severely limited by respiratory motion artifact, low proton density, and fast signal decay caused by short tissue t *. in this study, there was no significant difference in image quality for the two methods. the results presented above indicate that ute-mri was capable of providing image quality similar to ct when it was utilized for evaluating covid- , which was concordant with several previous studies. , , a pilot study carried out by delacoste et al showed that ute-mri had image quality similar to ct for quantifying lung nodule volumes. moreover, another study revealed that submillimeter resolution could be achieved with ute-mri for assessing cystic fibrosis, which suggested that ute-mri holds promise in serving as an alternative to unenhanced ct. the excellent performance of ute-mri for providing an image quality similar to ct was due to the following aspects. ) respiratory-gated mri is effective at greatly reducing respiratory artifacts. ) with the assistance of ultrashort echo time, ute-mri is capable of compromising the fast t * signal decay, which improved the signal-to-noise ratio of images. both the lesion-and patient-based comparative analysis showed that ute-mri has high concordance with ct for detecting typical pulmonary lesions, including ggo, consolidation, ggo with consolidation, axial location, anteroposterior location, the number of affected lobes, the number of crazy paving pattern, and the number of linear opacities. however, the lesion-based intermethod agreement for evaluating secondary signs such as air bronchogram, pseudocavity, and crazy paving pattern were between fair and moderate. the potential cause for this may be the lower image resolution of ute-mri as compared with ct. the above results are consistent with one previously reported study. ohno et al suggested that the intermethod agreement of ute-mri and ct for assessing the representative pulmonary findings such as ggo, consolidation, nodule, fibrosis, and so on, were all between substantial and excellent (kappa value: . - . ). ute-mri also displayed an image quality similar to low-dose ct. due to the high concordance with ct for visualizing the representative pulmonary findings and an image quality similar to ct, ute-mri is considered valuable for evaluating the radiological findings of patients with various pulmonary parenchyma diseases. given the short supply of rt-pcr kits, which was caused by the surge in confirmed covid- cases, especially in less-developed countries, and the high diagnostic sensitivity of image techniques, chest ct has been strongly encouraged for aiding prevention and control of covid- . however, biosafety concerns are warranted due to repeated exposure of x-rays over a short period of time in the hospital. one previous cohort study demonstrated that each patient with covid- underwent an average of four ct examinations within days. therefore, ute-mri may be a valuable technique for noninvasively evaluating covid- . first, because of the strict inclusion criteria and the singleinstitution study, the sample size of this study was relatively small, which may have potential risk for leading to bias. second, the ct image acquisition and ute-mri image acquisition were respectively performed at end-inspiration and end-expiration. moreover, there was a time interval between ct and mri (no more than days), which was established due to consideration of the clinical process. the above issues may affect the quantification of the intermethod agreement. with the continuous and rapid global spread of covid- , imaging examination has been widely accepted as a useful tool for aiding the control of covid- patients. this study suggests that ute-mri may act as a potential alternative to ct for noninvasively evaluating covid- . this study was funded by the novel coronavirus special research foundation of the shanghai municipal science and technology commission (no. ). coronavirus disease (covid- ) situation report - nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study correlation of chest ct and rt-pcr testing in coronavirus disease (covid- ) in china: a report of cases sensitivity of chest ct for covid- : comparison to rt-pcr clinical features of patients infected with novel coronavirus in wuhan china epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study chest ct manifestations of new coronavirus disease (covid- ): a pictorial review radiological findings from patients with covid- pneumonia in wuhan, china: a descriptive study performance of radiologists in differentiating covid- from viral pneumonia on chest ct ct imaging features of novel coronavirus ( -ncov) time course of lung changes on chest ct during recovery from novel coronavirus (covid- ) pneumonia pathological findings of covid- associated with acute respiratory distress syndrome coronavirus disease (covid- ): role of chest ct in diagnosis and management assessment of the radiation effects of cardiac ct angiography using protein and genetic biomarkers ultrashort echo time imaging of the lungs under high-frequency noninvasive ventilation: a new approach to lung imaging can texture analysis in ultrashort echo-time mri distinguish primary graft dysfunction from acute rejection in lung transplants? a multidimensional assessment in a mouse model iterative motioncompensation reconstruction ultra-short te (imoco ute) for highresolution free-breathing pulmonary mri pulmonary high-resolution ultrashort te mr imaging: comparison with thin-section standard-and low-dose computed tomography for the assessment of pulmonary parenchyma diseases differentiation between malignant and benign solitary pulmonary nodules: use of volume first-pass perfusion and combined with routine computed tomography chest ct findings in patients with corona virus disease and its relationship with clinical features coronavirus disease (covid- ): a perspective from china clinical and ct features of early-stage patients with covid- : a retrospective analysis of imported cases in shanghai high-resolution lung mri with ultrashort-te: . or tesla? mr volumetry of lung nodules: a pilot study lung morphology assessment of cystic fibrosis using mri with ultra-short echo time at submillimeter spatial resolution k-space water-fat decomposition with t * estimation and multifrequency fat spectrum modeling for ultrashort echo time imaging key: cord- -ymqnb a authors: kremer, stéphane; lersy, françois; de sèze, jérome; ferré, jean-christophe; maamar, adel; carsin-nicol, béatrice; collange, olivier; bonneville, fabrice; adam, gilles; martin-blondel, guillaume; rafiq, marie; geeraerts, thomas; delamarre, louis; grand, sylvie; krainik, alexandre; caillard, sophie; marc constans, jean; metanbou, serge; heintz, adrien; helms, julie; schenck, maleka; lefèbvre, nicolas; boutet, claire; fabre, xavier; forestier, géraud; de beaurepaire, isaure; bornet, grégoire; lacalm, audrey; oesterlé, hélène; bolognini, federico; messie, julien; hmeydia, ghazi; benzakoun, joseph; oppenheim, catherine; bapst, blanche; megdiche, imen; henri-feugeas, marie-cécile; khalil, antoine; gaudemer, augustin; jager, lavinia; nesser, patrick; talla mba, yannick; hemmert, céline; feuerstein, philippe; sebag, nathan; carré, sophie; alleg, manel; lecocq, claire; schmitt, emmanuelle; anxionnat, rené; zhu, françois; comby, pierre-olivier; ricolfi, frédéric; thouant, pierre; desal, hubert; boulouis, grégoire; berge, jérome; kazémi, apolline; pyatigorskaya, nadya; lecler, augustin; saleme, suzana; edjlali-goujon, myriam; kerleroux, basile; zorn, pierre-emmanuel; mathieu, muriel; baloglu, seyyid; ardellier, françois-daniel; willaume, thibault; brisset, jean christophe; boulay, clotilde; mutschler, véronique; hansmann, yves; mertes, paul-michel; schneider, francis; fafi-kremer, samira; ohana, mickael; meziani, ferhat; david, jean-stéphane; meyer, nicolas; anheim, mathieu; cotton, pr françois title: brain mri findings in severe covid- : a retrospective observational study date: - - journal: radiology doi: . /radiol. sha: doc_id: cord_uid: ymqnb a background: brain mri parenchymal signal abnormalities have been in association with sars-cov- . purpose: describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe covid- infection. methods: this was a retrospective study of patients evaluated from march th, to april th, at hospitals. inclusion criteria were: (i) positive nasopharyngeal or lower respiratory tract reverse transcriptase-polymerase chain reaction assays; (ii) severe covid infection defined as requirement for hospitalization and oxygen therapy; (iii) neurologic manifestations; (iv) abnormal brain mri. exclusion criteria were patients with missing or non-contributory data regarding brain mri or a brain mri showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. categorical data were compared using fisher exact test. quantitative data were compared using student’s t-test or wilcoxon test. a p-value lower than . was considered significant. results: thirty men ( %) and women ( %) met inclusion criteria, with a mean age of +/- years (range: - ). the most common neurologic manifestations were alteration of consciousness ( / , %), pathological wakefulness when the sedation was stopped ( / , %), confusion ( / , %), and agitation ( / , %). the most frequent mri findings were: signal abnormalities located in the medial temporal lobe in / ( %, % ci - %) patients, non-confluent multifocal white matter hyperintense lesions on flair and diffusion sequences, with variable enhancement, with associated hemorrhagic lesions in / patients ( %, % ci - %), and extensive and isolated white matter microhemorrhages in / patients ( %, % ci - %). a majority of patients ( / , %) had intracerebral hemorrhagic lesions with a more severe clinical presentation: higher admission rate in intensive care units, / patients, % versus / patients, %, p= . ; development of the acute respiratory distress syndrome in / patients, % versus / patients, %, p= . . only one patient was positive for sars-cov- rna in the cerebrospinal fluid. conclusion: patients with severe covid- and without ischemic infarcts had a wide range of neurologic manifestations that were be associated with abnormal brain mris. eight distinctive neuroradiological patterns were described. eight distinctive neuroradiologic patterns (excluding ischemic infarcts) were identified in patients with severe covid- infection with abnormal brain mris. in patients with covid- , the most frequent neuroimaging features were: involvement of the medial temporal lobe, non-confluent multifocal white matter hyperintense lesions on flair with variable enhancement and hemorrhagic lesions, and extensive and isolated white matter microhemorrhages. a majority of our patients presented intracerebral hemorrhagic lesions, which were associated with worse clinical status. . of patients, only one was positive for sars-cov- rna in the cerebrospinal fluid. describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe covid- infection. this was a retrospective study of patients evaluated from march th , to april th , at hospitals. inclusion criteria were: (i) positive nasopharyngeal or lower respiratory tract reverse transcriptase-polymerase chain reaction assays; (ii) severe covid infection defined as requirement for hospitalization and oxygen therapy; (iii) neurologic manifestations; (iv) abnormal brain mri. exclusion criteria were patients with missing or non-contributory data regarding brain mri or a brain mri showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. categorical data were compared using fisher exact test. quantitative data were compared using student's t-test or wilcoxon test. a p-value lower than . was considered significant. thirty men ( %) and women ( %) met inclusion criteria, with a mean age of +/- years (range: - ). the most common neurologic manifestations were alteration of consciousness ( / , %), pathological wakefulness when the sedation was stopped ( / , %), confusion ( / , %), and agitation ( / patients with severe covid- and without ischemic infarcts had a wide range of neurologic manifestations that were be associated with abnormal brain mris. eight distinctive neuroradiological patterns were described. i n p r e s s sars-cov- is the seventh member of the family of coronaviruses (covs) that infect humans ( ) and induces covid- disease. human covs (hcovs) have neuroinvasive capacities and may be neurovirulent by two main mechanisms ( ) ( ) ( ) : viral replication into glial or neuronal cells of the brain, or autoimmune reaction with a misdirected host immune response ( ) . thus, a few cases of acute encephalitis-like syndromes with hcovs were reported in the past two decades ( ) ( ) ( ) ( ) . concerning covid- , current data on central nervous system (cns) involvement is uncommon but growing ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , demonstrating the high frequency of neurological symptoms. however, the delineation of a large cohort of confirmed brain mri parenchymal signal abnormalities (excluding ischemic infarcts) related to covid- has never been performed, and the underlying pathophysiological mechanisms remain unknown. the purpose of this current study was to describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe covid- and report the clinico-biological profile of these patients. this retrospective observational national multicenter study was initiated by the french society of neuroradiology (sfnr) in collaboration with neurologists, intensivists, and infectious disease specialists, and brought together hospitals. the study was approved by the ethical committee of strasbourg university hospital (ce- - ) and was in accordance with the helsinki declaration and its later amendments. due to the emergency in the context of covid- pandemic responsible for acute respiratory and neurological manifestations pandemic, the requirement for patients' written informed consent was waived. consecutive patients with covid- infection and neurologic manifestations who underwent brain mri were included from march th, , to april th, , in french centers, including university hospitals and general hospitals. inclusion criteria were: (i) diagnosis of covid- based on possible exposure history or symptoms clinically compatible, validated with a detection of sars-cov- by reverse transcriptase-polymerase chain reaction (rt-pcr) assays on the nasopharyngeal, throat or lower respiratory tract swabs; (ii) severe covid- infection defined as requirement for hospitalization and oxygen therapy; (iii) neurologic manifestations; (iv) abnormal brain mri with acute/subacute abnormalities. exclusion criteria were: (i) patients with missing or non-contributory data (lack of sequences, numerous artifacts) regarding brain mri; (ii) a brain mri showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. clinical and laboratory data were extracted from the patients' electronic medical records in the hospital information system. only laboratory analysis within three days before the brain mri were considered. in the case of redundancy of the tests, the worst value has been kept. clinical and biological data were reviewed by two neurologists (j.d.s., and m.a. with and years of clinical expertise on neurology, respectively), and by one virologist (s.f-k). they participated to the elaboration of the study design, the interpretation of the data, and to manuscript editing. when available, all electroencephalogram (eeg) were reviewed by one expert neurologist (c.b.) and classified into five groups (normal, under sedation, nonspecific, encephalopathy or seizures). quantitative real-time rt-pcr tests for sars-cov- nucleic acid were performed on nasopharyngeal or lower respiratory tract swabs, and cerebrospinal fluid (csf). primer and probe sequences target two regions on the rdrp gene and are specific to sars-cov- . assay sensitivity is around copies/reaction (in house-method, institut pasteur, paris, france) ( ). imaging studies were conducted either on . -or -tesla mri. the multicenter nature of the study and the various clinical setups did not allow standardization of sequences. the most frequently sequences performed were d t weighted spin-echo mri with and without contrast enhancement, diffusion-weighted imaging (dwi), gradient-echo t or susceptibility-weighted imaging, and d or d flair after administration of gadolinium-based contrast agent. after anonymization, images were presented to readers with our ge picture archiving and communication system (general electric, milwaukee, wi, usa). after review of mri studies by three neuroradiologists (s.k., f.c., and f.l. with , , and years of experience in neuroradiology, respectively) who were blinded to all patient data, brain mri findings were divided by consensus into eight groups: (a) unilateral flair and/or diffusion hyperintensities located in medial temporal lobe; (b) flair and diffusion ovoid hyperintense lesion located in the central part of the splenium of the corpus callosum; (c) non-confluent multifocal white matter (wm) hyperintense lesions on flair and diffusion, with variable enhancement; (d) non-confluent multifocal wm hyperintense lesions on flair and diffusion, with variable enhancement, associated with hemorrhagic lesions; (e) acute necrotizing encephalopathy (ane) ( ) when symmetric thalamic lesions (edema, petechial hemorrhage, and necrosis), with variable involvement of the brainstem, internal capsule, putamen, cerebral and cerebellar wm; (f) extensive and isolated wm microhemorrhages; (g) extensive and confluent supratentorial wm flair hyperintensities; (h) flair hyperintense lesions involving both middle cerebellar peduncles. patients could have had more than one pattern. data were described using frequency and proportion (n, %) for categorical variables, using mean, median, interquartile range, and range for quantitative data. in a second step, patients with hemorrhagic lesions were gathered into a single group called « patients with hemorrhagic complications », to look for clinico-biological differences between the two populations. categorical data were compared using fisher exact test. quantitative data were compared using student's t-test or wilcoxon test. a p-value lower than . was considered significant. between march th, , and april th, , consecutive patients with covid- infection and neurologic manifestations, performed a brain mri in hospitals. among them, were excluded all patients with normal brain mri, ischemic infarcts, cerebral venous thrombosis or chronic lesions unrelated to the current event. a total of patients with covid- infection were finally included in this study (figure ). the average age of the patients was +/- years with men and women included (table ). the majority of our patients ( / , %) were admitted to intensive care units (icus) because of acute respiratory failure. the most frequent neurologic manifestations were alteration of consciousness ( / , %), pathological wakefulness after sedation ( / , %), confusion ( / , %), and agitation ( / , %). among the eeg performed, ( %) were considered as normal, ( %) were realized under sedation, ( %) showed nonspecific findings, ( %) were classified as encephalopathy, and ( %) case of seizures was also described. at the end of the study, the mortality rate was %. the blood counts of patients showed leukocytosis, lymphopenia, and anemia. patients had elevated serum levels of c-reactive protein, ferritin, alanine aminotransferase, aspartate aminotransferase, urea, creatinine, fibrinogen, and d-dimers (table ) . fifteen out of the patients ( %) studied for the presence of a lupus anticoagulant were positive. thirty-one patients underwent a lumbar puncture, and among them, / ( %) had increased markers of inflammation (high white blood cell count, and/or high proteinorachia, and/or elevated immunoglobulin g). one patient demonstrated the presence of sars-cov- on rt-pcr. high levels of interleukin- were found in out of patients (table ) . the results of mri findings are summarized in figure . among the patients included, / ( %) were associated with one neuroimaging pattern, / ( %) with two patterns, and / ( %) showed three patterns (figures - ). the most frequent neuroimaging findings were: signal abnormalities located in the medial temporal lobe in / ( %, %ic - %) patients (figure ), non-confluent multifocal wm hyperintense lesions on flair and diffusion, with variable enhancement, associated with hemorrhagic lesions in / ( %, %ic - %) patients (figure ), and in / ( %, %ic - %) patients extensive and isolated wm microhemorrhages were detected (figure ). the comparison between patients with and without intracerebral hemorrhagic lesions shows that the hemorrhagic complications were more frequently associated with icu admission ( / , % versus / , %, p= . ), with acute respiratory distress syndrome (ards) ( / , % versus / , %, p= . ) and with pathological wakefulness when sedative therapies were stopped ( / , % versus / , %, p= . ). the time between the onset of symptoms (most often respiratory) to brain mri was longer for patients with intracerebral hemorrhagic lesions (mean duration of days versus days, p< . ). leukocytosis (median of . x /l versus . x /l, p= . ), anemia (median of g/l versus g/l, p< . ), and renal dysfunction (urea's median of mmol/l versus mmol/l, p= . ) were more pronounced in the case of hemorrhagic lesions. among the eight groups of brain mri features classification, three main neuroradiological patterns appeared more frequently in patient with severe covid- : signal abnormalities located in the medial temporal lobe, non-confluent multifocal wm hyperintense lesions on flair and diffusion with variable enhancement, associated with hemorrhagic lesions, and extensive and isolated wm microhemorrhages. the presence of hemorrhage was frequent, and the detection is of clinical importance as it was associated with worse respiratory, neurological, and biological status. nevertheless, the underlying mechanism of brain abnormalities remains unsolved, and the direct implication of sars-cov- is not clear as only one patient was positive for sars-cov- rna in the csf. unilateral flair and/or diffusion hyperintensities located in medial temporal lobe were frequent and have been previously reported in one patient with covid- ( ) . the latter is frequently observed in case of infectious encephalitis (especially with some viruses like herpes simplex virus, human herpesvirus , or epstein-barr virus) or in association with autoimmune limbic encephalitis ( ) . non-confluent multifocal wm hyperintense lesions on flair and diffusion, with variable enhancement, which could be associated with hemorrhagic lesions, have rarely been reported in patients with covid- ( ) . the latter presentation is close to what can be observed on brain mris in case of an inflammatory demyelinating disease such as acute disseminated encephalomyelitis (adem) or acute hemorrhagic leukoencephalitis. however, these two latter diagnoses cannot only be retained on the radiological presentation without the typical csf analysis or clinical presentation ( , ) . several putative mechanisms underlying neurological consequences of covid- are evoked and among them immunological parainfectious processes ( ) . the immunologic assumption is also reinforced by a recent neuropathological study which described adem-like lesions in the subcortical wm in a patient with severe covid- ( ) . extensive and isolated wm microhemorrhages pattern was recently described in critically ill patients with covid- ( ) and in the neuropathology study above mentioned ( ) . a similar pattern was recently described in one case ( ) with disseminated intravascular coagulation. however, according to the criteria endorsed by the international society on thrombosis and haemostasis ( ) , when they were available, no case of disseminated intravascular coagulation was present in our cohort. its precise pathophysiology remains uncertain and will require further studies. radmanesh et al. ( ) evoking the assumptions of hypoxia or small vessel vasculitis. a small number of patients presented extensive and confluent supratentorial wm flair hyperintensities (figure ), as previously described by kandemirli et al. ( ) and radmanesh et al. ( ) . its precise pathophysiology remains unclear: viral encephalitis (not supported by csf analysis) or post-infectious demyelinating diseases, as previously mentioned, may be evoked. since most of our patients were admitted to icus for an ards, more general assumptions may be considered, such as delayed post-hypoxic leukoencephalopathy ( ) , metabolic or toxic encephalopathy, and posterior reversible encephalopathy syndrome (pres). this last hypothesis is in accordance with recently published nonhemorrhagic and hemorrhagic pres in patients with covid- ( ) . even if this national neuroimaging cohort remains unique, our study has several limitations, mainly due to his retrospective design. the main limitation is that certain laboratory data were missing for some patients, notably the immunological tests. moreover, patients' outcomes were not always known at the time of this communication. thus, the mortality rate is probably underestimated in our cohort. in conclusion, in this multi-institutional study, we report patients with covid- and abnormal brain mris (excluding ischemic infarcts). three main neuroradiological patterns could be distinguished, and the presence of hemorrhage was associated with worse clinical status. sars-cov- rna was detected in the csf only in one patient, and the underlying mechanisms of brain involvement remain unclear. imaging and neurological follow up has to be undertaken in order to evaluate the prognosis of these patients. n is the total number of patients with available data, and n the number of positive patients. i n p r e s s a novel coronavirus from patients with pneumonia in china neurologic alterations due to respiratory virus infections human coronaviruses: viral and cellular factors involved in neuroinvasiveness and neuropathogenesis human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? viruses coronavirus infections in the central nervous system and respiratory tract show distinct features in hospitalized children severe neurologic syndrome associated with middle east respiratory syndrome corona virus (mers-cov) neurological complications during treatment of middle east respiratory syndrome detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis covid- -associated acute hemorrhagic necrotizing encephalopathy: ct and mri features a first case of meningitis/encephalitis associated with sars-coronavirus- brain mri findings in patients in the intensive care unit with covid- infection covid- -associated diffuse leukoencephalopathy and microhemorrhages hemorrhagic posterior reversible encephalopathy syndrome as a manifestation of covid- infection neurologic manifestations of hospitalized patients with coronavirus disease imaging in neurological disease of hospitalized covid- patients: an italian multicenter retrospective observational study neurologic features in severe sars-cov- infection neurologic manifestations in hospitalized patients with covid- : the albacovid registry protocol: real-time rt-pcr assays for the detection of sars-cov- institut pasteur diagnosing autoimmune limbic encephalitis covid- -associated acute disseminated encephalomyelitis (adem) acute disseminated encephalomyelitis: updates on an inflammatory cns syndrome weston-hurst syndrome: a rare fulminant form of acute disseminated encephalomyelitis (adem) neurological implications of covid- infections neuropathology of covid- : a spectrum of vascular and acute disseminated encephalomyelitis (adem)-like pathology severe cerebral involvement in adultonset hemophagocytic lymphohistiocytosis towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation posterior reversible encephalopathy syndrome (pres) as a neurological association in severe covid- i n p r e s s key: cord- -i q authors: brix, gunnar; kolem, heinrich; nitz, wolfgang r.; bock, michael; huppertz, alexander; zech, cristoph j.; dietrich, olaf title: basics of magnetic resonance imaging and magnetic resonance spectroscopy date: journal: magnetic resonance tomography doi: . / - - - - _ sha: doc_id: cord_uid: i q in this chapter, the basic principles of magnetic resonance imaging (mri) and magnetic resonance spectroscopy (mrs) (sects. . , . , and . ), the technical components of the mri scanner (sect. . ), and the basics of contrast agents and the application thereof (sect. . ) are described. furthermore, flow phenomena and mr angiography (sect. . ) as well as diffusion and tensor imaging (sect. . ) are elucidated. in this chapter, the basic principles of magnetic resonance imaging (mri) and magnetic resonance spectroscopy (mrs) (sects. . , . , and . ), the technical components of the mri scanner (sect. . ), and the basics of contrast agents and the application thereof (sect. . ) are described. furthermore, flow phenomena and mr angiography (sect. . ) as well as diffusion and tensor imaging (sect. . ) are elucidated. the basic physical principles of the nuclear magnetic resonance (nmr in medical literature: magnetic resonance [mr] ) can be understood in depth and in detail based on quantum mechanics. in sect. . , however, another description is attempted that is almost physically exact and uses only a few simple arguments of quantum mechanics. in turn, the presentation will be more complex, but still can be understood with only basic knowledge in physics. for this reason, this synopsis should precede the detailed description in the following sections to guide the reader. mr examinations are possible if atomic nuclei of tissue of interest possess a nuclear magnetic moment µ. atomic nuclei with odd numbers of nucleons (here: protons, neutrons) do possess such magnetic moments. the nucleus of the hydrogen atom consisting of only one proton is the simplest atomic nucleus with an odd number of nucleons and thus has the biggest magnetic moment of all nuclei. its natural abundance of almost % and its ubiquitous occurrence and the high mobility of water protons in living matter are further prepositions for using low-sensitivity nmr method for imaging in human subjects. this low sensitivity compared with other imaging methods-e.g., positron emission tomography-cannot be emphasized enough. the sensitivity difference of this both methods is several orders of magnitude (~ - ). this fact has to be taken into account when magnetic resonance imaging is envisioned for specific probe imaging, nowadays known as molecular imaging. in spite of the abovementioned low sensitivity of mr, proton imaging is possible in humans because of the high magnetic moment, ~ % abundance, high concentra- tion, and high mobility of protons in tissue. the following consideration will be restricted to the hydrogen nuclei only. the basis of the magnetic resonance imaging is a simple resonance phenomenon. in a magnetic field, free environmental magnetic moments of a specimen are not oriented at all; however, in an external magnetic field the magnetic moments are no longer randomly oriented. the application of an external magnetic field b forces the magnetic moments µ to align along the magnetic field. due to basic physics principles, the orientation has two quantum states with respect to the external magnetic field: first the parallel, and second the antiparallel state, both of which have different magnetic energies em, and its energy difference being ∆em = γ · ħ · b , and γ, ħ being the gyromagnetic ratio and planck's constant, respectively. in thermal equilibrium, both states possess different occupation numbers, with the low-energy parallel state having higher probability of occupation than does the low-energy antiparallel state, resulting in a macroscopic and therefore measurable net magnetization parallel to the orientation of the external magnetic field. this thermal equilibrium state can be distorted by irradiation with alternating electromagnetic field having a radiation energy erf identically to the energy-splitting ∆em caused by the magnetic field, and the radiation energy being erf = ħ · ω , and ω being the resonance frequency of the spin system-the so-called larmor frequency. due to the resonant irradiation, the spin system takes up additional energy that can be dissipated only if the system is coupled to its microenvironment. this coupling strength is described by the so-called t relaxation time (also known as longitudinal or spin-lattice relaxation time). an equivalent for the coupling of the spins to each other is the t relaxation time (also known as transversal or spin-spin relaxation time). for tissues, typical t relaxation times for tissues are between and , ms and t relaxation times between and , ms. mr imaging utilizing pulsed nmr-this means the alternating electromagnetic field, the so-called radiofrequency (rf) field-is applied only for a short period of time (in general, pulses are some milliseconds). the short rf pulse excites the spin system via a transmitter coil. after irradiation of the nuclear spin system, a receiver coil can detect a damped time-dependent signal with a frequency of ω . this signal is called the free induction decay (fid) . the damping of the signal is ruled by the t relaxation times, and the period by the strength of the external magnetic field (constant magnetic moment assumed). in practical terms, not only does the t relaxation time influence the damping of the signal, but also the technically related inhomogeneity of the external magnetic field. the signal damping caused by the inhomogeneity is called t * relaxation time, and is in general much stronger than that caused by t relaxation times. only special pulse sequences (e.g., spin-echo sequences) can eliminate the influence of the inhomogeneity of the external magnetic field and thus allow the measurement of the t relaxation times specific to the substance/tissue. the influence of t relaxation times is mainly limited to the amplitude of the signal. preposition for the image reconstruction (sect. . ) is the exact information about the mr signal's origin. this spatial information can be generated by space-dependent magnetic fields additionally applied along the three space coordinates. these space-dependent magnetic fieldscalled magnetic field gradients-are small as compared with the main external field and are generated by special coils mounted in the bore of the magnet. due to these additional magnetic field gradients, the total magnetic field is slightly different in each volume element (voxel) and in turn, so is the resonance frequency of the spin system in each voxel. as a result, irradiation with a rf pulse of defined frequency ω′ excites only those nuclei in such voxels where the larmor frequency ω given by the field strength matches the resonance condition. suitable changes of the field gradients allow moving a volume element in space, fulfilling this condition. keeping in mind that the signal intensity of a volume element is given by the number of the spins in the volume element, the relaxation times of the tissue and the specific measurement parameters (e.g., pulse repetition time, echo time etc.), this signal intensity is assigned to the corresponding picture element (pixel). in this manner, the region of interest can be sampled by moving the volume element through space, and successively, an image with respect to pixels can be constructed. this method requires a long time to acquire images, assuming every experiment needs about s to measure a voxel and a pixel, respectively. thus, the measurement of an image × pixels will require more than , s to complete. nowadays, d-, d-, and/or phase encoding methods as well as half-fourier methods are applied, allowing data acquisition times of minutes or even less. special fast imaging techniques (e.g., flash, rare, epi sequences) allow further reduction of the acquisition time (cf. sect. . ) . in contrast to x-ray computed tomography, where the attenuation is governed purely by the electron density, as mentioned above, in mri the signal intensity is a complex function of the proton density and the t , t , and t * relaxation times. additionally, the signal intensity-and hence the image contrast-can be influenced by the measurement parameters (e.g., echo time, repetition time) set at the scanner. the knowledge of these interrelations of the different parameters influencing the signal intensity and hence the image contrast is mandatory in interpreting mr images correctly. the mr scanner is a complex system (sect. . ). its main components are the magnet, the rf system, and the gradient coils. the entire system is controlled and supervised by a computer. the development of mr imaging was only possible after the development of fourier trans-form nmr as well as fast computers calculating fast fourier transformations within minutes. the development of large-bore superconducting magnets of ≥ . - . t in the s accelerated the development and the application of mri in clinical practice. nowadays, -t scanners are in routine clinical use. scanners with ≥ t are installed and will further accelerate the development of mri and mrs. most of the magnets are made of solenoid coils. other magnet types, like scanners with helmholtz coils configuration, give better access to the patients; however, are installed mostly for special purposes, e.g., in an operation suite. mr scanners with conventional resistivity magnets and fields smaller than . t are rarely used, except in countries with short supplies of helium or other restrictions that may not allow installation of a superconducting system. the risk of side effects is assumed low if the magnetic fields are ≤ . t, except for the danger caused by ferromagnetic subjects accelerated into the magnet. nevertheless, at fields of . t and even ≥ t, the knowledge about side effects is rare, especially the long-term exposure due to high static magnetic fields, gradient fields, and rf fields to organisms. the problems concerning safety are extensively discussed in sect. . . in the early days of mri, the simplicity and wide range with which to manipulate contrasts in mri by changing the imaging parameters led to the conclusion that development of mr contrast agents is dispensable. however, experience taught that contrast media significantly improve mr diagnostics, not only in the central nervous system, but also in other diagnostic procedures. in contrary to x-ray contrast agents, where absorption is the dominating physical effect producing the contrast, mr contrast media are based on other principles. the paramagnetic and/or super-paramagnetic properties of the contrast media influence the relaxation times of tissue, or change contrast by obliterating the signal of protons and thus increase contrast. whereas in x-ray the contrast is proportional to the concentration of the contrast medium, in mr the dependency on the concentration is in general much stronger than linear -most often exponential. mr-contrast media are described in sect. . . the intrinsic sensitivity of nmr to motion was already observed early in the s. in mr imaging, motion, in particular flow, is often recognized as artifacts. however, these phenomena can be used to measure flow and/or represent the vascular system. two effects are used for these kinds of measurements, the time-of-flight phenomenon (or the wash-in/wash-out effect) or the spin-phase phenomenon. in time-of-flight measurements, moving spins are excited at one location (in the vessel), and detection of the spins is performed downstream at another known location (slice). the delay time between excitation and detection can be used to calculate the flow velocity. several modifications of the method exist (e.g., presaturation, bolus tracking), and are used depending on the setup of the measurement and sequences used. the spin-phase phenomenon can be used for angiographic imaging as well. the phase of the transverse magnetization of moving spins along a field gradient changes according to the larmor equation. these phase-shift effects are observed for flow in all directions. the phase changes are prone to different flow parameters (e.g., velocity, turbulences, acceleration, etc.) and on the pulse sequences used. the signal variations produced by the two effects can be used to produce images of the vascular structures. using phase-sensitive effects, magnitude subtraction is a common procedure: dephased and rephrased image are acquired sequentially and are subtracted. using time-offlight effects, mostly maximum-intensity projection is used to construct images of the vasculature. the angiographic techniques are described in detail sect. . . diffusion-weighted and -tensor imaging is a method applied first for clinical problems in brain, e.g. stroke, characterization of brain tumors, multiple sclerosis, etc. molecules in gases and fluids undergo microscopic random motions due to the thermal energy proportional to the temperature of the gas or fluid. if the molecules-in this context only water molecules are considered-are imbedded in a structure, for instance in tissues, the random walk motion may be restricted by the cellular tissue structure and hence reduce diffusion constants. if the structure of tissue has a preferred direction, diffusion will no longer isotropic; the diffusion will have higher components in the preferred direction of tissue. this kind of diffusion is called anisotropic diffusion. in mathematical terms, the anisotropic diffusion can be represented by a tensor. the so-called apparent diffusion coefficient can be measured, and the anisotropy of the diffusion can be determined and contains information about the structure of tissue. the basics of diffusion imaging are elucidated in sect. . . g. brix all nuclei with an odd number of protons and/or neutrons possess in their ground state a non-zero angular momentum or nuclear spin i, which results from the intrinsic angular momentums and the orbital angular momentums of the constituent protons and neutrons. as with any other angular momentum at the atomic and nuclear level, the angular momentum vector i is quantized. this quantization is described by the following fundamental postulates of quantum physics: • quantization of the magnitude: the magnitude (length) |i | of the angular momentum vector can only take the discrete values |i| = ħ i(i + ), with ħ being the planck's constant (ħ = . × - js) and i the spin quantum number, which is either integer or half-integer. • quantization of the direction: the component iz of the angular momentum vector i along the direction of an external magnetic field is quantized. for a given value of i, only the discrete values of iz= mħ are admitted, where m is the magnetic quantum number which is limited to the values -i, -i + , . . . , i - , i. in total, there are thus only i + orientations of the angular momentum vector i allowed. example: figure . . illustrates spin quantization in form of a vector diagram for a nucleus with the spin quantum number i = / . in this case, there are i + = · / + = orientations of the spin vector i with the magnitude (length) i(i+ ) |i| / · ( / + ) / ћ ћ ћ allowed. remark: the spin quantum number i is frequently referred to as "nuclear spin, " which means that the maximum (minimum) component of the vector i along the chosen axes is ħi (-ħi). the angular momentum i of an atomic nucleus is always related with a magnetic moment μ. this nuclear magnetism forms the basis of magnetic resonance. remark: an atomic nucleus can be imagined as a rotating, positively charged sphere ( fig. . . ). the rotation of the charge results in a circular electric current, inducing a magnetic dipolar field. both the direction and magnitude of the magnetic field are characterized by the magnetic moment μ. in the simple model considered, the vector μ is collinear with the mechanical angular momentum of the sphere. surprisingly, in quantum physics this simple relationship is even valid when the angular momentum is an inherent property of a particle (e.g., an electron or a nucleus) which is not associated with a mechanic rotation. as shown by a large number of experiments, there is a linear relationship between the nuclear magnetic moment and the nuclear spin μ = γ i. ( . . ) the proportionality constant γ is denoted as gyromagnetic ratio and is a characteristic property of a nuclide. whereas all nuclei with i ≠ can be used in principle for spectroscopic mr examinations, the nucleus of the hy- in the classical model, the rotation of a charged particle, described by its angular momentum i, results in an electric current, which induces a magnetic dipolar field. direction and magnitude of this field are described by the magnetic moment μ. the vector μ is directed collinear to the angular momentum i of the sphere (magnetomechanic parallelism) drogen atom, which has a spin quantum number of i = / , is almost exclusively used in mri due to two reasons: • it is the most abundant nucleus in biological systems. • it has the largest gyromagnetic ratio of all stable nuclei. in the absence of a magnetic field, all allowed orientations of the magnetic moment μ = γ i are energetically equal. this corresponds to the well-known fact that a bar magnet can be positioned arbitrarily within the field-free space; its potential energy is independent of its orientation. however, if the nucleus is located in a homogenous static magnetic field with the magnetic flux density b (magnitude, b = |b |) directed along the z-axis of a coordinate system, the nucleus has the additional potential energy splitting of the energy levels of a nucleus with the spin quantum number i = / in an external magnetic field with the flux density b . the energy difference between the four equidistant nuclear zeeman levels is Δe = ħω = γħb the b field represents the "real" magnetic field that interacts with the magnetic moments of the nuclei. the relation between the two magnetic field quantities is explained in sect. . . . . when considering an isolated magnetic moment within a static magnetic field, one will find that transitions between the different energy levels are prohibited due to the law of energy conservation. transitions can exclusively be induced by an additional time-dependent electromagnetic rf field that interacts with the magnetic moment, the effect is known as magnetic resonance (mr). in mr, transitions are induced by a magnetic rf field b (t) with the angular frequency ωrf, which is irradiated perpendicular to the direction of the static magnetic field b . such a time-dependent magnetic field, however, can only induce transitions fulfilling the selection rule ∆m = ± , i.e., transitions between neighboring energy levels. as a consequence, the energy erf = ħωrf of a photon of the rf field must be identical with the energy difference Δe = ħω = γħb between two neighbored energy levels, which yields the resonance condition ωrf = ω = γb . ( . . ) remarkably, planck's constant ħ does not occur in this fundamental equation of magnetic resonance. this indicates that the basic principles of magnetic resonance can-not only be described by quantum physics, but also by a classical approach, which is mediated by the intuitive semi-classical model described in the next section. in an external magnetic field, a cylindrical permanent magnet-characterized by a magnetic moment μ-experiences a mechanical torque that tends to align the permanent magnet parallel to the external magnetic field and thus minimize the potential energy of the system. however, in the case that the permanent magnet rotates around its longitudinal axis and thus possesses an angular momentum ("magnetic gyroscope"), it cannot align parallel to the external field due to the conservation of the angular momentum. in this situation, it experiences a torque perpendicular to both the direction of the magnetic field and the angular momentum, which results in a rotation (precession) of the magnet on a cone about the direction of the external b field (see fig. . . b). the frequency of this precession, the larmor frequency, corresponds to the resonance frequency ω given by eq. . . . magnetic field can be illustrated by a mechanic analog. when a child's spinning top is deflected so that its axis is not parallel to the top and the nucleus is that the nucleus possesses an intrinsic angular momentum i, whereas the angular momentum l of the top has to be initiated mechanically the direction of the gravitational field, it will continue rotating around its axis, but the axis itself will start rotating-the top precesses on a cone around the direction of the gravitational field ( fig. . . a). it should be mentioned, however, that the child's top and the nucleus differ with regard to the fact that the child's top has to be spun, whereas the nucleus possesses an intrinsic angular momentum. the quantization of direction of the nuclear magnetic moment μ can be integrated into this classical description by limiting the angle between the field axis and the precession cone to the discrete values which relate to the i + orientations of the angular momentum i permitted. for a spin- / nucleus, this results in a double-precession cone as shown in fig. . . . however, this semiclassical model is rendered questionable, because the classical concept of a continuous trajectory in space is hardly compatible with the quantization of physical quantities. for instance, what would the trajectory of the vector μ look like when transitions between the various precession cones, reflecting discrete energy levels, are induced by an rf field, such as for a spin- / nucleus, the transition from the lower to the upper precession cone (cf. fig. . . )? is it possible to assign to the vector μ a well-defined direction in space at any point in time, and would this direction change over time? if so, then this negates the postulate of discrete energy and angular momentum levels. this aporime can only be solved by a rigorous quantum mechanical treatment of the system. however, when considering only the mean values of physical quantities averaged over a large ensemble of nuclei-which can only be measured in a real mr experiment-it becomes obvious that the models and laws of classical physics are valid. in field-free space, the magnetic moments of nuclei in a macroscopic sample are randomly oriented due to their thermal motion and thus mutually compensate each other. in a homogeneous static magnetic field b , however, only i + discrete orientations of the magnetic moments with respect to the direction of the external field are permitted, the energy levels of which differ according eq. . . . in thermal equilibrium, the population of the i + levels (spin states) is described by the boltzmann statistic: the lower the energy em = -γħb m of a state with the magnetic moment μz = γħm in the zdirection, the greater is the occupation number. example: let us consider an ensemble of hydrogen nuclei in a static magnetic field of the flux density b = t. according to the boltzmann statistic, more nuclei will occupy the state of the lower energy (m = + / , µz parallel to b ) than the state of the higher energy (m = - / , µz antiparallel to b ) (fig. . . ). however, as compared with the thermal energy, the difference between the two energy levels is extremely small, so that the difference in the occupation numbers of the two levels is very small. at body temperature of °c, the difference in the occupation numbers with respect to the total number of spins is as low as . ! fig . . double-precession cone for a nucleus with the nuclear spin quantum number i = / . the two permitted spin states (precession cones) are characterized by the magnetic quantum numbers m = ± / origin of the nuclear magnetization. in thermal equilibrium, the distribution of an ensemble of spin- / nuclei on the two allowed precession cones is described by the boltzmann statistic. the occupation number of the state of the lower energy (m = + / , µz parallel to b ) is somewhat higher than that of the state of the higher energy (m = - / , µz antiparallel to b ) which leads to macroscopic (bulk) magnetization m although the difference in the occupation numbers is extremely small, it results in a measurable bulk magnetic moment along the direction of the b field due to the large number of nuclei in a macroscopic sample ("nuclear paramagnetism"). the macroscopic magnetization in thermal equilibrium is described by the magnetization vector m , which is defined as the vector sum of the nuclear magnetic moments per unit volume v. the magnitude of the equilibrium magnetization m is given by where n is the total number of nuclei in the sample, t the absolute temperature of the sample, and k boltzmann's constant (k = . · - j/k). the ratio ρ = n/v is called spin density. as both the body temperature and the spin density cannot be altered in living beings, the equilibrium magnetization m can only be increased according to eq. . . by increasing the magnetic flux density b . the equilibrium state of a spin system can be disturbed by a magnetic rf field b (t) with a frequency ωrf equal to the larmor frequency ω , which tilts the magnetization m. whereas a nuclear magnetic moment μ can only take i + discrete orientations relative to the static magnetic field b (quantization of direction), the macroscopic magnetization m can take any direction in space and change it steadily. the action of a magnetic rf field b (t), which rotates with the larmor frequency ω around the direction of the static b field, can be analyzed most effectively in a rotating frame, i.e., a coordinate system that rotates with the larmor frequency around the z-axis ( fig. . . ) . the change to a rotating frame with the axes (x′, y′, z) has two advantages: • as the x′-y′-plane of the rotating frame is synchronized with the rf field, the b vector remains stationary in this frame. in the following analysis, we will assume that the static b field points along the x′-axis ( fig. . . ). • as shown in sect. . . . , a nuclear magnetic moment μ precesses with the larmor frequency ω around the direction of the b field (see fig. . . ). of course, this holds equally for the sum of the nuclear magnetic moments, i.e., for the macroscopic magnetization m. therefore, an observer observing the precession of the magnetization m from the rotating frame will come to conclude that the position of the magnetization does not change. from his point of view, the magnetization behaves as if the b field is absent (larmor's theorem). summarizing both reflections, it can be concluded that the dynamics of the magnetization m in the rotating frame is determined only by the static b field. if it points toward the x′-axis, then the magnetization m will precess around the x′-axis ( fig. . . a). analogous to eq. . . , the frequency ω of this precession is given by ω = γb . ( . . ) when looking at this simple rotation of the magnetization m in the y′-z-plane of the rotating frame from a laboratory frame of reference (x, y, z), the movement is superimposed by a markedly faster rotation (b > b ) around the z-axis. thus, within the laboratory frame of reference, the tip of the vector m moves in a helical manner on the surface of a sphere around the b field; the length of the vector m remains constant ( fig. . . b ). if the magnetization m points toward the static field b before the rf field b (t) is switched on, the magnetization m is rotated from the equilibrium position under the influence of the rf field during the duration tpby the flip angle: ( . . ) if the duration tp of the rf field is chosen to rotate the magnetization in the rotating frame by °, then this radiofrequency field in a stationary and in a rotating frame of reference. in the stationary frame (x, y, z) the magnetic rf field b (t) rotates with the angular frequency ωrfin the x-yplane around the z-axis. if one observes this rotation from a rotating frame (x′, y′, z) , which rotates with the angular frequency ωrf around the z-axis, the vector is stationary. typically, the rotating frame is chosen in such a way that the b field points in the x′-direction pulse is denoted as ° or π/ pulse ( fig. . . a ). accordingly, the magnetization m is rotated by ° when the duration of the rf pulse is doubled at the same flux density b . this pulse, which inverts the magnetization from the positive to the negative z-direction, is called ° or π pulse ( fig. . . b). remark: precisely speaking, a short rf pulse with the carrier frequency ωrf will excite not only the nuclei that exactly fulfill the resonance condition ωrf = ω , but also nuclei whose resonance frequency slightly differs from ωrf. this is because the frequency spectrum of an rf pulse of finite duration consists of a continuous frequency band around the nominal frequency ωrf (fig. . . ). the width of the frequency distribution is inversely proportional to the duration tp of the pulse: the shorter the pulse, the broader the frequency spectrum is be distributed around ωrf. if the rf field is irradiated over a very long period (tp → ∞), the spectrum will be quasi-monochromatic. to simplify the following analysis, the magnetization m is separated into two components: the longitudinal magnetization mz, which is parallel to the direction of the static magnetic field b , and the transverse magnetization mxy, which is perpendicular to it ( fig. . . ). in the laboratory frame the transverse magnetization mxy precesses with the larmor frequency ω ; in the rotating frame it remains stationary. it is instructive to describe the effect of a °/ ° pulse on an ensemble of spin- / nuclei within the semiclassi-cal model described in sect. . . . . as can be shown, the magnetic rf field induces transitions between the two permitted spin states (precession cones) until the occupation numbers are either identical ( ° pulse) or inverted ( ° pulse). furthermore, irradiation of a ° pulse results in a phase synchronization of the nuclear magnetic moments of the sample, which yields a macroscopic transverse magnetization mxy, the magnitude of which is equal to that of the equilibrium magnetization m . figuratively speaking, this means that the precession of the transverse magnetization mxy can be described as a common (phase coherent) precession of a "spin package" (fig. . . ). up to this point, we have assumed that interactions of nuclear spins between one another and with their environment can be neglected. however, this assumption is not valid for real spin systems, as the magnetization returns to its equilibrium (mxy = , mz = m ) after rf excitation. this process is called relaxation. two different relaxation processes have to be distinguished: • the relaxation of the longitudinal magnetization mz characterized by the longitudinal or spin-lattice relaxation time t • the relaxation of the transverse magnetization mxy characterized by the transverse or spin-spin relaxation time t . fig . . resonance excitation. a in a rotating frame of reference, which rotates with the larmor frequency ω around the direction of the b field, the magnetization m precesses with the frequency ω around the stationary b field. b in the stationary frame this simple rotation is superimposed by the markedly faster rotation around the z-axis. therefore, the tip of the vector m moves in a helical manner on the surface of a sphere fig. . . ° and ° pulse. if one chooses the rotating frame so that the rf pulse is irradiated along the x′-axis, the magnetization m will be rotated (a) by a ° pulse along the y′-direction and (b) by a ° pulse to the negative z-direction . physical basics in real spin systems, every nucleus is surrounded by other intra- and intermolecular magnetic moments, which are in motion due to rotations, translations, and vibrations of molecules as well as exchange processes. these processes induce an additional fluctuating magnetic field blok(t) at the position of a given nucleus, which has to be added to the external field. as the movements and exchange processes are random, the fluctuating fields differ in time from nucleus to nucleus-in contrast to the coherent rf field blok(t) irradiated from the outside. as any other temporal process, the locally fluctuating magnetic fields blok(t) can be decomposed into its frequency components. remark: the decomposition of a function into harmonic (i.e., sinusoidal) basis functions is denoted as fourier analysis, the mathematical operation that gives the intensity (amplitude) of the harmonic basis functions as fourier transformation. if the given function is periodic with period t, it can be decomposed into a sum of sinus and/or cosine functions with the discrete frequencies ω, ω, ω . . . (ω = π/t ). in contrast, a nonperiodic function has a continuous spectrum of frequencies. the contribution of the different frequency components to the fluctuating local field blok(t) is described by the spectral density function j(ω). a general feature of this function is that the more rapidly the molecular motion is, the broader the frequency spectrum ( fig. . . ). rf pulse in the time and frequency domain. a rf pulse with carrier frequency ωrf and duration tp. b fourier transformation of the rf pulse. due to its finite duration, the frequency spectrum of the pulse is not monochromatic, but contains an entire frequency band, which is distributed around the nominal frequency ωrf phase synchronization by a ° pulse. the ° pulse leads to a synchronization of the phases of the magnetic moments μ of the nuclei in the sample (spin packet), which results in a macroscopic transverse magnetization mxy, the magnitude of which corresponds to that of the longitudinal magnetization before irradiation of the ° pulse. in the figure, only the part of the magnetic moments of the sample which are distributed in an anisotropic manner on the precession cone is shown fig. . . definition of the longitudinal and transverse magnetization. as the macroscopic magnetization m precesses in the stationary frame around the z-axis, it is beneficial to split it into two components: the rotating transverse magnetization mxy and the longitudinal magnetization mz in order to understand the effect of the fluctuating local magnetic fields blok(t) on a spin system, the components parallel and perpendicular to b have to be discussed separately. whereas the parallel component exclusively contributes to t relaxation, the perpendicular component influences both t and t relaxation: • the field component perpendicular to the b field induces-in analogy to the external rf field b (t) -transitions between the energy levels (precession cones) of an individual spin. the probability of these transitions depends on the intensity of the frequency component of the fluctuating fields that oscillates at the larmor frequency ω : the higher the spectral density j(ω ), the more transitions are induced. as fig. . . shows, j(ω ) assumes a maximum when the limiting frequency ωg of the spectral density function is comparable to the larmor frequency ω . the described relaxation process allows the excited spin system to emit and absorb photons of energy ħω until the boltzmann distribution of the energy levels is reached. the energy difference between the excited and the equilibrium state is dissipated to the surrounding medium or "lattice. " since the change in the occupational numbers of the spin states (precession cones) is related with a change in the macroscopic longitudinal magnetization mz, the described mechanism contributes to longitudinal relaxation. moreover, it contributes to t relaxation, as the locally induced transitions between the precession cones destroy the phase coherence between those spins which form, as a spin-package, the macroscopic transverse magnetization (cf. fig. . . ). • the component of the fluctuating field blok(t) oriented parallel to the z-axis locally modulates the static field b at the position of a nucleus and thereby changes the precession frequency ω of its nuclear magnetic moment μ. since the local fluctuations seen by the nuclei are spatially uncorrelated, the precessing magnetic moments within a sample lose their phase coherence, which causes the transverse magnetization to decay (see fig. . . ) . given the fact that the effect of the high-frequency components of the fluctuating field vanishes when averaged over time, only the quasistatic frequency components, the intensity of which is approximately given by j(ω = ), have a measurable effect on the transversal magnetization (see fig. . . ) . as no transitions between the energy levels (precession cones) are induced by the described relaxation mechanism, the longitudinal magnetization mz remains unchanged, which means that the mechanism solely contributes to transversal relaxation. the qualitative discussion of the relaxation mechanisms reveals that their effectiveness depends on two different factors, namely on the magnitude and the temporal characteristics of the field fluctuations. the dependence from the magnitude is utilized when using paramagnetic con-trast agents (see sect. . ), which possess unpaired electron spins and consequently a magnetic moment. when considering the fact that the magnetic moment of an electron amounts to times the magnetic moment of a proton, one can easily understand why even the slightest amounts of paramagnetic substances can lower the relaxation times considerably. for spin systems with a sufficiently high molecular mobility, relaxation processes can be described by exponential functions with the time constant t or t . the longitudinal magnetization increases exponentially toward its equilibrium value mz = m , the transverse magnetization decreases exponentially toward mxy = . figure . . shows the exponential relaxation of both magnetization components after excitation of the spin system by a ° pulse and gives a simple interpretation of the relaxation times t and t : • the longitudinal relaxation time t gives the time required for the longitudinal magnetization after a ° pulse to grow again to % of its equilibrium value m . • the transverse relaxation time t gives the time required for the transverse magnetization after a ° pulse do drop to % of its original magnitude. schematic representation of the density function j(ω) for three substances with a different thermal mobility of the constituting atoms or molecules. a if the atoms or molecules move very slowly (such as in solids), the intensity of high-frequency components is very low. b this is different in fluids. in this case, the atoms or molecules move very rapidly, so that the spectral density function contains high-frequency components to a significant degree. c at a given frequency ω the intensity j (ω ) will attain a maximum if the cut-off frequency ωg of the spectral density function approximately corresponds to the given frequency ω . at low frequencies, j (ω) is nearly independent on the frequency, so that the density of the quasi-static frequency components can be approximated by j (ω = ) dephasing of the transverse magnetization. the transverse magnetization mxy of the sample is split up into several magnetization components, which precess with slightly differing larmor frequencies around the direction of the b field. a immediately after the ° pulse, all magnetization components are aligned parallel. b-d afterward, the components dephase due to their different larmor frequencies, and thus the macroscopic transverse magnetization decays the process of transverse relaxation can be described intuitively on the macroscopic level. to this end, the transversal magnetization mxy is split into different magnetization components, or spin packets. whereas the spins of each spin packet precess with the same larmor frequency, the spins in different packets slightly differ in their lamor frequencies. right after excitation, all components of the magnetization point toward the same direction; shortly afterward, however, some parts precess more quickly than others around the direction of the b field. due to this fact, the components fan out (dephasing), and the resulting transverse magnetization decreases ( fig. . . ). in real mr experiments always macroscopic samples are examined, so that not only the fluctuating local magnetic fields, but also spatial field inhomogeneities of the external field b , introduced by technical imperfections, contribute to the transverse relaxation. as both effects superpose on one another, the resulting effective relaxation time t * is always shorter than the real, substancespecific transverse relaxation time t . relaxation times in solids and fluids differ markedly (fig. . . ) . whereas the longitudinal relaxation in solids can take hours or even days, in pure fluids it only takes some seconds. this difference is because the spectral density function j(ω ) at the larmor frequency is much larger in fluids than it is in solids, in which the low-frequency components dominate (see fig. . . ). for the same physical reason, the t relaxation time in solids usually only amounts to some microseconds, whereas in fluids it is only slightly shorter than the longitudinal relaxation time t . soft tissues range, based on their consistency, between solids and pure fluids: with regard to their relaxation be-havior, they can in general be treated as viscose fluids. table . . summarizes representative proton relaxation times for different biological tissues. due to the considerable differences in the tissue relaxation times, it is possible to acquire mr images with an excellent tissue contrast even when the proton densities of the tissues or organs only slightly differ from one another. when interpreting the relaxation times, two aspects have to be taken into account: • the relaxation time t of biological tissues strongly depends on the larmor frequency, whereas the relaxation time t is nearly independent of the frequency. when comparing t values, one therefore needs to consider the magnetic flux density b at which the t measurement was done. • relaxation processes often consist of multiple components, so that the description by a mono-exponential function is only a rough approximation. the relaxation times given in table . . therefore only represent weighted mean values of an entire spectrum of exponential functions, characterizing the relaxation behavior of protons in different cell and tissue compartments between which the water exchange is slow. however, at the timescale relevant for mri, relaxation processes of most tissues can be approximated rather well by a single exponential function. an exception is fat-containing tissue (such as subcutaneous fatty tissue or bone marrow), which demands at least two exponential functions to be considered for the parameterization of the relaxation processes observed. figure . . shows the general setup of an mr experiment; technical details will be presented in sect. . . the sample to be examined is located within a very homogeneous static magnetic field b , which is created either by a permanent magnet or by a (superconducting) coil. the rf field required for the excitation of the spin system is generated by a transmit coil connected to the rf transmit system. this rf coil is positioned in such a way that the radiofrequency field b (t) is irradiated perpendicular to the b field into the sample volume. remark: whereas atomic nuclei with a nuclear spin quantum number of i ≥ can interact with both the electric and the magnetic component of the electromagnetic rf field, spin- / nuclei are only affected by the magnetic component b (t) of the rf field. after excitation of the spin system by an rf pulse, the precessing transverse magnetization mxy in turn induces a weak alternating voltage in a receiver coil, which in general is identical to the transmit coil ( fig. . . a). the measured voltage is amplified, filtered, digitalized, and fed to the computer of the mr system. the measured mr signal s(t) has the form of a damped oscillation (fig. . . b ), which is denoted as the free induction decay (fid). the fid signal has the following characteristic features: • it oscillates with the larmor frequency ω of the stimulated nuclei. • it decays in time with the time constant t *. • its initial amplitude is proportional to the number n of the excited spins in the sample (n = ρv ∝ m v; cf. eq. . . ). if the sample contains nuclei of a certain type whose resonance frequency slightly differs due to intramolecular interactions (see sect. . . ), the mr signal induced in the receiver coil will consist of several interfering decay curves. however, such a curve is rather complicated to analyze and interpret. therefore, the detected curve is usually spit up into its frequency components (fourier analysis, see sect. . . . ) and presented as frequency spectrum. both types of description are merely different representations of the same data, which can be transformed into one another mathematically by a fourier transformation. example: figure . . b,c illustrates the relation between the description of the mr signal in the time or frequency domain by the example of a substance whose mr spectrum only shows one resonance line. principle setup of an mr experiment. the object to be measured is placed within a homogeneous static magnetic field b . excitation of the spin system is performed by an rf field b (t) irradiated perpendicularly to b by an rf coil. after excitation, the mr signal of the sample is detected by an rf coil and transferred via a receiver channel to the computer of the mr system. (for details, see sect. . ) for quantitative analysis of an mr spectrum, the following features are important: • the center of the resonance curve is at the larmor frequency ω . • the full width Δω at half maximum of the curve is related with the characteristic time constant t * of the fid by the relation Δω = /t * . • the area under the curve is approximately proportional to the number of excited nuclei in the sample. in an mr experiment, only the rf signal can be determined by measurement, which is induced by the rotating transverse magnetization mxy in the receiver coil (cf. sect. . . ). nevertheless, a large variety of mr experiments can be realized that differ in the way by which the spin system is excited and prepared by means of rf pulses before the signal is acquired. a defined sequence of rf pulses, which is usually repeated several times, is called a pulse sequence. in the following, three "classical" pulse sequences are described that are frequently used for mr experiments (imaging sequences are described in sect. . ): • the saturation recovery sequence • the inversion recovery sequence • the spin-echo sequence. the saturation recovery (sr) sequence consists of only a single ° pulse, which rotates the longitudinal magnetization mz into the x-y-plane. the fid signal is acquired immediately after the rf excitation of the spin system. after a delay time, the repetition time tr, the sequence is repeated. the sr sequence is described schematically by the pulse scheme ( °-aq-tr) (aq = signal acquisition period; fig. . . a ). if the repetition time tr is long compared to t , the magnetization m relaxes back to its equilibrium state (see fig. . . ) . in this case, the initial amplitude of the fid, even after repeated excitations, does only depend on the equilibrium magnetization m and does not show any t dependency. however, if the repetition time tr is shortened to a value that is comparable to t , the longitudinal magnetization mz will not fully relax after excitation, and the following ° pulse will rotate the reduced longitudinal magnetization mz(tr) = m [ -exp(-tr/t )] into the x-y-plane (fig. . . b, c) . under the assumption that the transverse magnetization after the repetition time tr has been decreased to zero (tr >> t *), the following expression is obtained for the initial amplitude ssr of the fid signal: which exclusively depends on the relaxation time t and the number n of the excited spins in the sample. free induction decay (fid) and frequency spectrum. a after excitation of the spin system by a ° pulse the magnetization mxy precesses with the larmor frequency ω around the direction of the b field and induces an electric voltage in the receiver coil. b the measured fid signal s(t) has the form of a damped oscillation, the frequency of which is given by the larmor frequency ω . the decay of the signal is defined by the time constant t *. c a fourier transformation of the fid signal gives the frequency spectrum of the mr signal. the resonance curve has its center at the larmor frequency ω ; its full width at half maximum (fwhm) is related with the characteristic time constant t * of the fid by the relation Δω = /t * in the inversion recovery (ir) method, the longitudinal magnetization is inverted by a ° pulse (inversion pulse), which is followed after an inversion time ti by a ° pulse (readout pulse). immediately after the ° pulse, which rotates the partially relaxed longitudinal magnetization mz(ti) into the x-y-plane, the fid signal is acquired (fig. . . ). the ir sequence is described by the pulse scheme ( °-ti - ° - aq). the initial amplitude sir of the fid signal is directly proportional to the longitudinal magnetization immediately before irradiation of the read-out pulse, just as is the case in the sr method. in contrast to saturation recovery sequence. a pulse scheme of the sr sequence (aq: signal acquisition). b the ° pulse rotates the actual longitudinal magnetization into the x-y-plane. during the repetition time tr, the longitudinal magnetization relaxes toward the equilibrium magnetization m . the speed of this process is described by the longitudinal relaxation time t . note that by the first ° pulse, the equilibrium magnetization m is rotated into the x-y-plane, whereas the subsequent ° pulses rotate the reduced longitudinal magnetization mz(tr) = m [ -exp(-tr /t )]. c temporal evolution of the transverse magnetization mxy in the rotating frame. d induced mr signal ssr(t) inversion recovery sequence. a pulse scheme of the ir sequence (aq: signal acquisition). b initially, the longitudinal magnetization is inverted by the ° pulse (inversion pulse), which is followed after an inversion time tiby a ° pulse (readout pulse), which rotates the existing longitudinal magnetization mz(ti) into the x-y-plane. after the ° pulse, the longitudinal magnetization relaxes toward the equilibrium magnetization m . c temporal evolution of the transverse magnetization mxy in the rotating frame. d induced mr signal sir(t) the sr sequence, however, the change in the longitudinal magnetization is twice as high and thus-in analogy to eq. . . -the following expression is obtained (compare figs. . . b and . . ) ssr ∝ n ( - e -t i /t ). ( . . ) the derivation of this relation is based on the assumption that the spin system is in its equilibrium state before it is excited by the inversion pulse. when repeating the ir sequence, one has therefore to make sure that the repetition time tr is markedly longer than the relaxation time t . remark: if the ir sequence is repeated several times with different inversion times ti, it is possible to sample the temporal course of the longitudinal magnetization step by step, since the initial amplitude of the fid signal is directly proportional to the longitudinal magnetization at time ti (see fig. . . ) . this procedure is applied frequently in order to determine the relaxation time t of a sample according to eq. . . . as explained in sect. . . . the temporal decay of the transverse magnetization mxy is caused by two effects: fluctuating local magnetic fields and spatial inhomogeneities of the magnetic field b . the transverse magnetization mxy therefore relaxes not with the substance-specific relaxation time t but rather with the effective time constant t * (t * < t ). when determining the relaxation time t , it is therefore important to compensate the effect of the field inhomogeneities. this can be done, as e. hahn has already shown in , by using the so-called spinecho (se) sequence. this sequence utilizes the fact that the dephasing of the transverse magnetization caused by b inhomogeneities is reversible since they do not vary in time, whereas the influence of the fluctuating local magnetic fields is irreversible. in order to understand the principle of the se sequence with the pulse scheme ( ° - τ - ° - τ - aq; see fig. . . a), we initially neglect the influence of the explanation of the spin-echo experiment in the rotating frame. for the sake of simplicity, the substance-specific transverse relaxation is not been considered in this figure. a the ° pulse rotates the longitudinal magnetization into the x′-y′plane. b,c in the course of time, the magnetization components, which form together the transverse magnetization mxy, dephase so that the transverse magnetization decays with the characteristic time constant t * (see fig. . . ). d,e irradiation of the ° pulse along the x′-axis mirrors the dephased magnetiza-tion vectors at the x′-axis. as neither the precession direction nor the precession velocity of the magnetization components are altered by the ° pulse, the components rephase and thus the transverse magnetization increases. the regeneration of the transverse magnetization is called a spin echo. f at the time te = τ, all magnetization components point into the same direction again. due to the rephrasing effect of the ° pulse, the amplitude mz(te = τ) of the spin echo is independent of the static inhomogeneities of the b field fluctuating local magnetic fields and solely consider the static magnetic field inhomogeneities. immediately after the ° pulse, all magnetization components composing the transverse magnetization mxy point along the y′-axis ( fig. . . a ). shortly afterward, some components precess faster, others more slowly around the direction of the b field, so that the initial phase coherence is lost (see fig. . . ) . when looking at this situation from a rotating frame, one observes a fanning out of the magnetization components around the y′-axis (fig. . . .b, c) . if a ° pulse is applied after a time delay τ along the x′-axis, the magnetization components will be mirrored with respect to this axis ( fig. . . d) . however, the ° pulse does not change the rotational direction of the magnetization components, but merely inverts the distribution of the components: the faster components now follow the slower ones ( fig. . . e). after the time t = τ, all magnetization components again point to the same direction, and the signal comes to a maximum ( fig. . . f ). the ° pulse thus induces a rephasing of the dephased transverse magnetization, which causes the mr signal to increase and to generate a spin echo (fig. . . ). after the spin-echo time te = τ  , the echo decays againas the original fid does-with the time constant t *. due to the rephasing effect of the ° pulse, the spinecho signal sse(te) is independent from the inhomogeneities of the static magnetic field: the loss of signal at the time t = te as compared to the initial signal sse( ) is determined exclusively via the substance-specific relaxation time t . if one irradiates a sequence of k ° pulses at the times τ, τ, τ, …, ( k- )τ, one can detect a spin echo in between the subsequent ° pulses (fig. . . ). the envelope of the echo signals sse( τk) (k = , , , …, k) decays exponentially with the relaxation time t . sse ∝ n e - τk/t . ( . . ) the major advantage of this multi echo sequence consists in the fact that the t decay can very effectively be detected by a single measurement ( fig. . . ). all the considerations so far have been based on the assumption that the external magnetic field b created by the rf coil is not altered by the electrons surrounding a nucleus. however, this is not the case as the electrons interact with the applied external magnetic field. in biological tissues in which atoms are covalently bound, two related effects need to be considered, the diamagnetism and the chemical shift. diamagnetism is a general feature of matter and is because electrons attempt to shield the interior of the sample against the external magnetic field. in electrodynamics, this effect is described by lenz's law. it states that the current induced in a circuit by the change of a magnetic field is directed in such a way that the secondary magnetic field induced by the electric current weakens the primary magnetic field ( fig. . . ). if a sample is positioned in an external magnetic field, a current is induced in the electron shell of the atoms and molecules, whose magnetic moment is directed against the external magnetic field, following lenz's law. however, in contrast to the electrons within a macroscopic circuit, the electrons in the electron shell are "frictionless, " which means that an induced electron current remains constant until the external magnetic field changes or until the sample is removed from the magnetic field. the sum of the induced magnetic moments of the electrons per volume is-similar to the nuclear magnetization m-denoted as electron magnetization me. for averaging, the volume has to be chosen in such a way that, on the one hand, a great number of atoms and molecules is contained, and, on the other hand, that it is small compared to the volume of the sample (for example, µm water contains about . · water molecules). the magnetization me thus represents a macroscopic quantity per definitionem. remark: due to practical reasons, distinction is made in electrodynamics between free and bound currents: free currents are experimentally controllable and are linked to macroscopic circuits, whereas bound currents are linked to atomic and molecular magnetic moments in matter. the field related to free currents is denoted as magnetic field h (unit: ampere/meter), the field created by the total current, i.e. by both the free and the bound current, as magnetic flux density b (unit: tesla). at every point in space, the vector quantities h, b, and me are related by the dimensionless proportionality constant χ is called the magnetic susceptibility. for diamagnetic substances, χ is, according to lenz's law, always negative and has a very small absolute value (e.g. water: χ = - . · - ). when putting a diamagnetic sample into an originally homogeneous magnetic field, a magnetization me is induced according to eq. . . , which itself creates a magnetic field that counters the primary field. therefore, the field distribution of the magnetic flux density b differs both inside and outside of the sample from the original field distribution. example: figure . . shows the field distribution of the magnetic flux density b inside and outside of a homogeneously magnetized sphere (χ = constant), which has been brought into an originally homogeneous field b . inside the sphere, the magnetic flux density b is given by b = ( + χ / ) b . it should be noted, however, that the homogeneously magnetized sphere represents an ideal case in which the b field is homogeneous on multi echo sequence. a pulse scheme (aq: signal acquisition). b decay of the echo amplitudes as a function of time. the signal decay is determined exclusively by the substance-specific transverse relaxation time t , whereas the decay and the regeneration of the fid are essentially determined by technically conditioned field inhomogeneities lenz's law. when a circuit is approached to a bar magnet with the magnetic flux density b, a current i is induced in the circuit. this current induces a magnetic dipolar field, which is directed in such a way that it weakens the primary magnetic field. magnitude and orientation of the dipolar field are described by the magnetic moment μ its inside, whereas in general, the b field is also inhomogeneous inside the object. the discussion provides three important aspects with respect to mr examinations of humans: • the distribution of the magnetic flux density b in the human body depends on the position, size, form, and magnetic susceptibility of all tissues and organs of the body. • at the interface between tissues with different magnetic susceptibilities, there are local field inhomogeneities. • the distortion of the external magnetic field caused by the body adds to the technical imperfections of the external field b . in mri, susceptibility-related inhomogeneities of the static magnetic field inside the body are obviously unavoidable and can result in image artifacts. in spectroscopic examinations, however, this problem can be reduced by acquiring only mr signals from small, morphologically homogeneous tissues regions. furthermore, one has the possibility to locally adjust the b field by means of external shim coils generating a weak additional magnetic field, so the homogeneity within the examined region fulfils the demands. when speaking of the homogeneity of the b field within a given region of the body, this relates to the average macroscopic field; on the microscopic scale, the magnetic field is always inhomogeneous. the larmor frequency of a nucleus is determined by the local magnetic field blok at the position of the nucleus, not by the macroscopic field b, which has been averaged over a small but microscopically large volume surrounding the nucleus. denoting the perturbation of the mean field b at the position of a nucleus caused by the surrounding electrons of the molecule by Δb, we get the relation blok = b + Δb. ( . . ) as experimental and theoretical investigations have shown, the small local field perturbation Δb is proportional to the macroscopic field Δb = -σb, ( . . ) which yields the following expression for the resonance frequency of the nucleus, considered the dimensionless "shielding constant" σ gives the relative resonance frequency shift that is independent of the magnitude of the magnetic field. this shift depends on the distribution of the electrons around the nucleus and thus has different values in different molecules. the magnitude of the additional field Δb at the position of a nucleus generally depends on the orientation of the molecule relative to the macroscopic field b. in molecules that rotate rapidly, such as in fluids and soft tissues, the chemical shift anisotropy vanishes, so the quantity σ in eq. . . could be defined as a direction-independent constant. this quantity describes the shielding effect of the electron shell averaged over all spatial directions. as the absolute value of the frequency shift cannot easily by measured, it is usually determined relative to the resonance frequency ωr of a reference substance. the difference (ω -ωr) of the resonance frequencies is expressed as dimensionless constant relative to the frequency ω = γb of the mr system in parts per million (ppm). the chemical shift δ provides information about how the atom with the nucleus under study is bonded in the molecule and thus makes mr spectroscopy a powerful tool for the determination of the structure of molecules as well as for the investigation of biochemical processes. for the h nucleus, which is surrounded by only one electron, the chemical shift is about ppm; for atoms with several electrons (e.g., c, f, and p) it can amount to several hundreds of ppm. to resolve these small differences in frequency it is necessary to use a strong and homogeneous static magnetic field (b ≥ . t, ∆b/b < . - . ppm depending on the nucleus). variation of the magnetic field by a diamagnetic sphere. distribution of the b field inside and outside a homogeneously magnetized sphere, which was positioned in an originally homogeneous magnetic field. it should be noted, however, that field variations caused by biological tissue are markedly weaker than illustrated here if the object to be imaged, such as the human body, is divided into small cuboidal volume elements (i.e., voxels), the task in mr imaging is to distinguish the signal contributions of the voxels to the detected summation signal from one another and to present them in form of sectional images (tomograms). this can be achieved by superimposing the homogeneous magnetic field b by an additional magnetic field with a well-defined dependence on the spatial position, so the larmor frequency of the mr signal becomes a function of space. in practice, image reconstruction is achieved almost exclusively by means of magnetic gradient fields. these are three additional magnetic fields b x , b y , and b z , whose field vectors point toward the z-direction and whose field strengths depend linearly on the spatial position x, y, or z, respectively ( fig. . . ). if the z-components of the three magnetic gradient fields are denoted by b x , b y , and b z , the fields can be expressed as where the proportionality constants g x , g y , and g z describe the magnitude or steepness of the orthogonal gradient fields. remark: the magnetic gradient fields are shortly denoted as x-, y-, or z-gradients. what is meant are magnetic fields b x , b y , and b z , the magnitude of which varies linearly along the x-, y-, or zaxis, respectively (see fig. . . ). in order to avoid image distortions, the magnitude of the gradients has to be chosen in such a way that the local field variations are markedly greater than the local inhomogeneities of the main magnetic field b ; typical values are between and mt/m. technically, the gradient fields b x , b y , and b z are produced by three coil systems (gradient coils), which can be operated independently from one another. example: assuming a patient diameter in the x-direction of x = cm, a magnetic flux density of the static field of b = t, and a gradient strength of g x = mt/m, the magnetic field b = b + g x x will increase within the patient (-x/ ≤ x ≤ + x/ ) linearly from . to . t. in mr imaging, the magnetic gradient fields are used in two different ways: • for selective excitation of the nuclear spins in a partial body region (e.g., a slice). • for position encoding within an excited partial body region (e.g., a slice). for image reconstruction, the homogeneous magnetic field b shown in a is superimposed by additional magnetic fields b x , b y , and b z , so-called gradient fields, the field vector of which points into the z-direction and the magnitude of which (length of the black arrows) depends linearly on the spatial coordinate x, y, and z, respectively. b and c show the field distributions in case the field b is superimposed by a gra-dient field b y and b z , respectively. the open arrows indicate the direction of the field variation, whereas the constants g y and g z represent the magnitude of the field variation per unit of length. if the z-components of the two magnetic gradient fields are given by b y and b z , then the gradient strengths are defined by g y = Δb y /Δy and g z = Δb z /Δz, respectively an mr signal can principally only be detected from the volume in which the nuclei have been excited before by an rf pulse. this fact is used in planar imaging methods, in order to reduce the primarily d reconstruction problem to a d one by selectively exciting only nuclei in a thin slice of the body. remark: depending on the type of the selectively excited partial body volume, one distinguishes between single-point, line, planar, and volume sampling strategies (fig. . . ). as the intensity of the detected mr signal is proportional to the number of nuclei within the excited volume, the different strategies markedly differ in the time required for the acquisition of qualitatively comparable mr images. due to the long measurement time, single-point and line scanning techniques have not been successful in clinical practice. in order to excite a distinct slice of the body selectively, the homogeneous static magnetic field b is superimposed with a gradient field (slice-selection gradient) that varies perpendicular to the slice, i.e., for an axial slice a gradient field in longitudinal direction of the body. due to this superposition, the larmor frequency ω of the nu-clei varies along the direction of the gradient. if we consider, for instance, a z-gradient with magnitude g z , the larmor frequency is given by (see fig. . . c): consequently, an object slice z ≤ z ≤ z is characterized by a narrow frequency interval γ(b + g z z ) ≤ ω ≤ γ(b + g z z ). if one irradiates an rf pulse, the frequency spectrum of which coincides with this frequency range, only the nuclei within the chosen slice will be excited ( fig. . . ) . for the definition of a body slice, this has two implications: • the width d = z -z of the slice can be varied by changing either the bandwidth of the rf pulse, i.e. the width of the frequency distribution, or the gradient strength g z . • the position of the slice can be altered by shifting the frequency spectrum of the rf pulse. the practical realization of the concept of slice-selective excitation requires not only the shape of the rf pulse but also the switching mode of the slice-selection gradient to be carefully optimized: the main magnetic field b is superimposed with a magnetic gradient field b z = g z z in z-direction (slice-selection gradient), so the larmor frequency ω(z) = γ(b + g z z) of the nuclei depends linearly from the spatial coordinate z. the slice z ≤ z ≤ z within the object is thus unambiguously described by the frequency interval ω(z ) ≤ ω(z) ≤ ω(z ). if one irradiates an rf pulse with a frequency spectrum that corresponds to this frequency interval, only the nuclei within the chosen slice will be excited • pulse modulation: as shown in fig. . . , the frequency spectrum of a rectangular rf pulse consists of several frequency bands with varying intensities. if such a pulse is used for the rf excitation, the profile of the excited slice is defined insufficiently. in order to obtain a uniform distribution of the transverse magnetization over the slice width, the shape of the selective rf pulse is modulated so that the frequency spectrum becomes as rectangular as possible ("sinc pulse, " see fig. . . a). • compensation gradients: if one imaginatively dissects an object slice into several thin subslices, then the magnetization components of all subslices will be deflected by the same angle from the z-direction when an optimized rf pulse is used for slice-selective excitation. however, the magnetization components will be dephased at the end of the excitation period tp, since the larmor frequencies of the distinct subslices differ from one another as the slice-selection gradient is switched on. this effect can be compensated by reversing the polarity of the gradient field for a well-defined period after rf excitation ( fig. . . b). after selective excitation of a partial body region, the mr signal from each voxel within this volume, e.g., a slice, needs to be spatially encoded. this can be achieved by two techniques: frequency and phase encoding of the mr signal. the principle of both encoding techniques will be explained in the following by the example of an axial slice parallel to the x-y-plane. for the sake of simplicity, relaxation effects are neglected in this connection. if the body to be imaged is placed in a homogenous magnetic field with the flux density b , the magnetization components of all voxels in the excited slice will precess with the same frequency around the direction of the b field. thus, the frequency spectrum consist of only a single resonance line at the larmor frequency ω = γ b -it does not contain any spatial information. however, if a magnetic gradient field, e.g., b x = g x x, is switched on during the acquisition phase of the mr signal ( fig. . . ), pulse modulation and gradient refocusing. a in order to obtain an approximately rectangular slice profile, one uses an rf pulse, the envelope of which is not rectangular but modulated in time. b if one dissects a thicker slice of the object into several thin subslices, an optimized rf pulse will deflect the magnetization of each subslice by the same angle from the z-direction, but the magnetization components are dephased after rf excitation, because the larmor frequencies in the subslices differ. if a ° pulse with duration tp is used for slice-selective excitation, then the dephasing effect can be compensated in good approximation by inverting the gradient field after excitation for the duration tp/ readout or frequency-encoding gradient. in frequency encoding, the main magnetic field b is superimposed with a gradient field (here b x + g x x) during the acquisition of the rf signal, so the precession frequency of the transverse magnetization in the selectively excited slice becomes a function of the coordinate x the larmor frequency is related to the position x (see fig. . . ) by the resonance condition or in other words, nuclei in parallel strips oriented perpendicular to the direction of the readout (or frequencyencoding) gradient will experience a different magnetic field and thus contribute with different larmor frequencies ω(x) to the detected mr signal of the excited slicethe spatial information is encoded in the resonance frequency. in order to determine the contribution of the distinct frequency components to the summation signal, a fourier transformation of the measured fid has to be performed (cf. sect. . . ). the intensity i(ω) of the resulting spectrum at the frequency ω is proportional to the number of nuclei precessing with this frequency, i.e., to the number of nuclei that are according to eq. . . at the position x = (ω - γb ) / γ g x . the frequency spectrum of the fid signal therefore gives the projection of the spin density distribution in the excited slice onto the direction of the readout gradient ( fig. . . ). remark: when explaining the concept of frequency encoding, we assumed that there is only one resonance line in the frequency spectrum of the excited body region in the absence of the readout gradient. if this assumption is not fulfilled, i.e., if the spectrum contains several resonance lines due to chemical shift effects described in sect. . . . , then these frequency shifts will be interpreted by the decoding procedure (i.e., the fourier analysis) of the fid signal as position information. consequently, the spin density projections of molecules with different chemical shifts are shifted in space against one another. in h imaging, the situation is rather easy, as only two dominant proton components contribute to the mr signal of the organism, the protons of the water molecules and those of the ch group of fatty acids. as the resonance frequencies of the two components differ by about . ppm (fig. . . ) , fat-and water-containing structures of the body are slightly shifted against one another in readout direction. this chemical-shift artifact becomes apparent predominantly at the interfaces between fat- and water-containing tissue. from a technical point of view, the fid signal s(t) can only be sampled and stored in discrete steps over a limited period of time taq. consequently, there is only a limited number n = taq /Δt of data points that can be used for fourier transformation. due to this reason, the spatial sampling interval Δx of the spin density projection is limited too. the following relations hold between the number n of data points, the maximum object size x, the spatial sampling interval Δx, the temporal principle of frequency encoding. if the fid signal from a slice is measured in the presence of a gradient field b x = g x x (see fig. . . ) , then nuclei in strips oriented perpendicular to the direction of the gradient contribute with different larmor frequencies ω(x) = γ(b = g x x) to the measured mr signal. the contribution i(ω) of the distinct frequency components to the summation signal can be calculated by a fourier transformation of the fid signal. as the intensity i(ω) of the resulting spectrum at the frequency ω is, on the one hand, proportional to the number of nuclei precessing with this frequency, and, on the other hand, the spatial information is encoded in the frequency, the fourier transformation yields the projection of the spin density distribution within the considered object slice on the direction of the readout gradient in vivo h spectrum of a human thigh at . t. the two resonance lines can be attributed to protons in water and in the ch groups of fatty acids sampling interval ∆t, and the gradient strength g x (sampling theorem): example: if the fid signal is sampled times at ∆t = µs in the presence of a magnetic gradient field of the strength g x = . mt/m, then the resolution along the x-axis is ∆x = . mm, and the maximum object size that can be imaged is x = nΔx = cm. with frequency encoding, the mr signal is sampled at discrete points in time tn = nΔt ( ≤ n ≤ n). according to eq. . . , the transverse magnetization at the position x precesses under the influence of the readout gradient until the time tn by the angle the spatial information is therefore encoded via the frequency ω(x) in the phase angles φn(x) ( ≤ n ≤ n). however, the same phase angles can be realized by increasing the gradient strength gn x = nΔg x in equidistant steps Δg x at a fixed switch-on time of the gradient. this equivalent approach is called phase encoding. the concept of phase encoding can easily be realized by applying a magnetic gradient field, e.g., b x = g x x, for a fixed time tx before the fid signal is detected (fig. . . ) . under the effect of this phase-encoding gradient, the magnetization at the position x precesses by the phase angle the parameter kn = γgn x tx = γnΔg x tx is named spatial frequency. after switching off the phase-encoding gradient, the magnetization components of the voxels in the slice precess again with the original, position-independent larmor frequency ω = γb around the direction of the b field-now, however, with position-dependent phase angles φn (x). this is to say, in phase-encoding, all magnetization components of the excited voxels contribute to the detected mr signal with the same frequency ω , but with differing phases φn (x). in order to calculate the projection of the spin density distribution in the slice onto the direction of the phase-encoding gradient, the chosen sequence is repeated n times with different spatial frequencies kn = n(γ Δg x tx) = nΔk ( ≤ n ≤ n) (fig. . . ). however, in contrast to frequency encoding, during phase encoding not the entire fid is sampled, but only the mr signal s(kn, t ) at a definitive time t . after n measurements (sequence cycles), the spin density projection can be calculated by a fourier transformation of the acquired data set s(Δk, t ), s( Δk, t ), s( Δk, t ), …, s(nΔk, t in practical mri, techniques of image reconstruction have prevailed that merely differ only in the way the aforementioned techniques of selective excitation and spatial encoding are combined. phase-encoding gradient. in phase encoding, a gradient field (here b x = g x x), the magnitude of which is increased in equidistant steps ∆g x at each sequence cycle, is switched on for a fixed time tx before the fid signal is acquired. this method, which p. lauterbur used in to generate the first mr image, is based on a technique of image reconstruction used in computed tomography. its basic idea is easy to understand: if projections of the spin density distribution of an object slice are available for various viewing angels Φn ( ≤ n ≤ n), the spin density distribution in the slice can be reconstructed by "smearing back" the (filtered) profiles over the image plane along their viewing directions (fig. . . ). this approach can be implemented easily by making use of the frequency-encoding technique by repeating the sequence shown in fig. . . several times while rotating step by step the direction of the readout gradient in the slice plane. in order to reconstruct a planar image of n × n picture elements (pixel), a minimum of n projections with n data points each is needed. the stepwise rotation of the readout gradient by the angle ΔΦ= °/n is performed electronically by a weighted superposition of two orthogonal gradient fields. the projection reconstruction method is easy to understand, but both mathematical description and data processing are rather complex. furthermore, it carries the disadvantage that magnetic field inhomogeneities and patient movements result in considerable image artifacts. due to these reasons, the fourier techniques described in the following sections are preferred for the reconstruction of mr images. principle of phase encoding (displayed in the rotating frame). as shown in fig. . . , a phase-encoding gradient g x is switched on for a fixed time tx before the fid signal is acquired (aq). a-d the sequence is repeated several times at equidistantly increasing gradient strengths. under the influence of the gradient field b x = g x x, the magnetization components of the different voxels in the slice precess with different larmor frequencies. if the gradient is switched off after the time tx, all components rotate again with the original, position-independent frequency ω = γb around the direction of the b field. however, magnetization components which precess more quickly during the operating time tx of the gradient field, will maintain their advance compared with the slower ones. this advance is described by the phase angle φ(x) = γg x xtx of the different magnetization components. the figure shows the dependence of the phase angle φ(x) on the gradient strength g x and the spatial coordinate x schematically for four different gradient strengths (g x = , ∆g x , ∆g x , and ∆g x ) and three adjacent voxels (with the magnetization vectors m , m , and m ). as shown in b, the magnetization m will rotate at the position x under the influence of the gradient field by the phase angle φ(x ) = ° and the magnetization m at the position x by the phase angle φ(x ) = ° comparison between frequency and phase encoding. with both encoding techniques, the transverse magnetizations of all voxels within the excited slice contribute to the detected mr signal; the spatial information is encoded in both cases by the different phase of the magnetization components, which was formed by the influence of a magnetic gradient field (here b x = g x x) up to the moment of signal detection. in order to calculate the projection of an object onto the direction of the gradient, the mr signal s has to be measured n times (e.g., n = or ), with the phase difference between the magnetization components of the different voxels varying in a well-defined way form measurement to measurement. the difference between the two encoding techniques merely consists in the technique with which the data set {s , s , . . . , sn} is acquired. a with frequency encoding, the mr signal is sampled at equidistant time steps ∆t in presence of a constant gradient field (in the figure ∆g x ). as the magnetization components of the voxels within the excited slice steadily dephase under the influence of the gradient field, there is a different phase difference between them at every point in time tn= n∆t ( ≤ n ≤ n), so the whole data set {s , s , . . . , sn} can be detected by a single application of the sequence. the figure shows the first three values of the signal. it should be noted that only the temporal change of the mr signal caused by the gradient field is shown here, whereas the rapid oscillation of the signal with the larmor frequency ω = γb as well as the t * decay of the signal is neglected. b with phase encoding, a phase-encoding gradient is switched on for a fixed duration tx before the fid signal is acquired. the magnitude of this gradient is increased at each sequence repetition by ∆g x . during the switch-on period of the gradient field, the magnetization components of the different voxels precess with different frequencies so that a phase difference is established between them which is proportional to the magnitude of the gradient applied (see fig. . . ) . after switching off the gradient, all components rotate again with the original, position-independent frequency ω = γb around the direction of the b field. in the chosen description, one therefore observes an mr signal sn that is constant over time. in order to acquire the entire data set {s , s , …, sn}, the sequence needs to be repeated n times with different gradient strengths g x = n∆g x . the figure shows the dependence of the mr signal from the gradient strength schematically for three different gradient strengths (g x = , ∆g x , ∆g x ). if the product of the gradient strength and the switch-on time of the gradient up to the time of signal detection is equal in both encoding techniques, the phase difference between the various magnetization components at the time of signal detection is also identical and thus the same mr signal is measured. the product of the two quantities is indicated in the figure by the dark areas in the planar version of fourier imaging, just as in projection reconstruction, the spins in a slice are selectively excited by an rf pulse in the first step. afterwards, however, spatial encoding of the spins in the slice is not done by a successive rotation of a readout gradient, but by a combination of frequency and phase encoding using two orthogonal gradient fields. if we consider an axial slice parallel to the x-y-plane, then these gradients are g x and g y (fig. . . ). the sequence is repeated n times for different values of the phase-encoding gradient gn x = nΔg x ( ≤ n ≤ n), with the mr signal being measured m times during each sequence cycle at the times tm = mΔt ( ≤ m ≤ m) in the presence of the readout gradient g y . thus, one obtains a measurement value for each combination (kn, tm) of the parameters kn = γnΔg x tx and tm = mΔt, i.e., a matrix of n × m data points. a d fourier transformation of this data set, the so-called hologram or kspace matrix (see fig. . . ), yields the mr image of the slice with a resolution of n × m pixels. in order to extend the d fourier method to a d one, the slice-selection gradient is replaced by a second phaseencoding gradient as shown in fig. . . . this means that the rf pulse excites all spins in the sensitive volume of the rf coil and that the spatial information is encoded exclusively by orthogonal gradients-by two phase-encoding gradients and one frequency-encoding gradient. the spatial resolution in the third dimension is defined by the strength of the related phase-encoding gradient and the number k of the phase-encoding steps. depending reconstruction by back projection. the figure shows three different projections of two objects in the field of view. if many projections are acquired at different viewing angles, an image can be reconstructed by (filtered) back projection of the profiles. for the measurement of the various projections, the frequency-encoding technique is used, with the readout gradient rotating step by step fig. . . typical pulse and gradient sequence in d fourier imaging. g z is the slice-selection gradient, g x the phase-encoding gradient, and g y the readout gradient on the choice of these parameters, the voxels have a cubic or cuboidal shape (isotropic or anisotropic resolution). in order to acquire a d k-space matrix with n × m × k independent measurement values, the imaging sequence needs to be repeated n × k times. a d fourier transformation of the acquired d k-space matrix yields the d image data set of the partial body region excited by the rf pulse. based on this image data set, multiplanar images in any orientation can be refor-matted, which offers-among others-the possibility to look at an organ or a body structure from various viewing directions. in addition to the described conventional fashion of filling the k-space in fourier imaging, there are a number of alternative strategies. • spiral acquisition. as will be described later, the epi sequence is commonly using an oscillating frequencyencoding gradient. if both, the phase encoding as well as the frequency-encoding gradient are oscillating with increasing gradient amplitudes, the acquired data points will be along a spiral trajectory through k-space. that is why such an acquisition is called spiral epi. • radial acquisition. if the direction of the frequencyencoding gradient is rotated as described in sect. . . . , the k-space trajectories will present a star. • blade, propeller, multivane. these hybrid techniques sample k-space data in blocks (so-called blades) each of which consists of some parallel k-space lines. in order to successively cover the entire k-space, the direction of the blades is rotated with a fixed radial increment. this sampling strategy offers some advantages. since each blade contains data points close to the center of the k-space, patient movements can, for example, be easily detected and corrected. to reconstruct mr images from alternative k-space trajectories by means of a conventional d or d fourier transformation, it is necessary to re-grid the sampled kspace data to a rectangular grid. data acquisition by d imaging techniques can be carried out very efficiently when considering the fact that the time required for slice-selective excitation, spatial encoding, and acquisition of the mr signal is much shorter than the time needed by the spin system to relax at least partially after rf excitation, before it can be excited once again. the long waiting periods can be used to excite-in a temporally shifted manner-adjacent slices and to detect the spatially encoded mr signal from these slices. thus, mr images from different parallel slices can be acquired simultaneously without prolongation of the total acquisition time (fig. . . ). example: let us consider that ms are needed for excitation, spatial encoding, and data acquisition per sequence cycle and that the sequence is repeated after tr = , ms. then mr data from adjacent slices can be acquired simultaneously without prolonging the measurement time. typical pulse and gradient sequence in d fourier imaging. g x and g y are the phase-encoding gradients and g z the readout gradient however, when using the multiple-slice technique, one has to consider that the distance between slices may not be too small, as the slice profile usually is not rectangular, but bell shaped. in order to avoid repeated excitation of spins in overlapping slice regions, the gap between adjacent slices should correspond approximately to the width of the slice itself. images from adjacent slices can be obtained in an interleaved manner by applying the sequence twice: in the first measurement, data are acquired from the odd slices and in the second from the even slices ( fig. . . ). principle of the multiple-slice technique. in most d imaging sequences, the time t required for slice-selective excitation, spatial encoding, and detection of the mr signal is markedly shorter than the repetition time tr. the long waiting periods can be used to subsequently excite spins in parallel slices and to detect the spatially encoded signals from these slices consideration of the slice profile by the multipleslice technique. the profile of a slice is generally not rectangular but rather bell shaped. the thickness (th) of the slice is therefore usually defined by the full-width at half-maximum. in order to prevent overlapping of adjacent slices in the multiple-slice technique, a sufficient gap (g) between the two adjacent slices has to be chosen (g ≥ th). often the distance (d = g + th) between the slices is indicated instead of the gap g. images from adjacent slices can be detected without overlap by using in a first step a sequence that acquires data from the even slices and in a second step a sequence that acquires data from the odd slices. in both measurements, the gap g should be identical with the slice thickness th (d = g + th = th) the main advantage of mr imaging, apart from the flexibility in slice orientation, is the excellent soft-tissue contrast in the reconstructed mr images. it is based on the different relaxation times t and t of the tissues, which depend on the complex interaction between the hydrogen nuclei and their surroundings. compared to that, differences in proton densities (pd) are only of minor relevance, at least when considering soft tissues. the term proton density in mr imaging designates only those hydrogen nuclei whose magnetization contributes to the detectable image signal. essentially, this refers to hydrogen nuclei in the ubiquitous water molecules and in the methylene groups of the mobile fatty acids (see sect. . . . and fig. . . ). hydrogen atoms, which are included in cellular membranes, proteins, or other relatively immobile macromolecular structures, usually do not contribute to the mr signal; their fid signal has already decayed to zero at the time of data acquisition (t << te) (brix ). another important contrast factor is the collective flow of the nuclei. the influence of flowing blood on the image signal will be discussed in sect. . separately, in the context of mr angiography. whereas the image contrast of a ct scan only depends on the electron density of the tissues considered (as well as on the tube voltage and beam filtering), the mr signal and thus the character of an mr image is determined by the intrinsic tissue parameter pd, t , and t as well as by the type of the sequence used and by the selected acquisition parameters. this variability offers the opportunity to enhance the image contrast between distinct tissues by cleverly selecting the type of sequence and the corresponding acquisition parameters, and thus to optimize the differentiation between these tissue structures. however, the subtle interplay of the many parameters bears the danger of misinterpretations. in order to prevent these, several mr images are always acquired in clinical routine, with different sequence parameters that are selected in such a way that the tissue contrast of the various images is determined mainly by a single tissue parameter; in this context, one uses the term t -, t -, or pd-weighted images. sometimes, one even goes one step further to calculate "pure" t , t , and pd parameter maps on the basis of several mr images that were acquired with different acquisition parameters. the advantage in doing this consists of the fact that the image contrast on the calculated parameter maps is usually more accentuated than in the weighted images. the calculated tissue parameters can furthermore be used to characterize various normal and pathological tissues. however, experience has shown that a characterization or typing of tissues by means of calculated mr tissue parameters is only possible with reservations (bottomley et al. ; higer and bielke ; pfannenstiel et al. ). this may be due not only to the insufficient measurement and analysis techniques used, but also to the fact that morphological information of the mr images as well as the clinical expertise of the radiologist have been left aside in many cases. these considerations indicate that each mr practitioners should be aware of the dependence of the image contrast on the selected type of imaging sequence as well as on the sequence and tissue parameters in order to fully benefit from the potential of mri and to avoid misinterpretations. the term imaging sequence designates the temporal sequence of rf pulses and magnetic gradient fields, which are used to determine the image contrast and for image reconstruction, respectively. the foregone section has made intuitive use of the term image contrast in order to describe the possibility to distinguish between adjacent tissue structures in an mr image. we will now define this term. if one describes the signal intensities of two adjacent tissues structures a and b with sa and sb, the image contrast between the two tissues can be expressed by the absolute value of the signal difference cab = |sa - sb| ( . . ) or by the normalized difference ( . . ) remark: the delineation of a tissue structure depends, of course, also on the signal-to-noise ratio (s/n) as tiny, weakly contrasted structures can be masked by image noise. some authors therefore proposed to use the contrast-to-noise ratio for evaluating the detectability of a detail. however, the explanatory power of this quantity can hardly be objectified since the contrast-detail detectability strongly depends on the signal detection in the human retina as well as on the signal processing in the central visual system of the observer. in the following, we will therefore use the absolute contrast defined in eq. . . . example: in order to analyze the influence of the tissue and acquisition parameters on the image contrast by an example, we will consider in the following the contrast between white and gray brain matter. representative tissues parameters, which have been measured for a patient collective at . t, are summarized table . . . in clinical routine, the spin-echo (se) sequence is still a frequently applied imaging sequence, due to two reasons: • it is rather insensitive to static field inhomogeneities and other inaccuracies of the mr system. • it allows for the acquisition of t -, t -, and pdweighted images by an appropriate choice of the acquisition parameters tr and te. of about t . usually, however, the sequence is repeated much earlier, so that the longitudinal magnetization will be reduced at the beginning of the next sequence cycle compared to the equilibrium magnetization by the t factor [ - exp(-tr / t )]. accordingly, the t contrast of an se image can be varied by the choice of the repetition time tr. in fig. . . a, the t factor is plotted for white and gray brain matter. as this example shows, the t contrast reaches a maximum if the repetition time tr is between the t relaxation times of the two tissues considered. if tr is markedly longer than the longer t time, then the t contrast vanishes. • t dependence: the influence of the t relaxation process on the signal intensity is described by the t factor exp (-te / t ) in the signal equation. for a given t time the signal loss is the bigger, the longer the echo time te becomes. in fig. . . b, the t factor is plotted for white and gray brain matter versus the echo time te. the contrast will reach a maximum when the echo time te ranges between the t relaxation times of the two tissues considered. for small te values (te << t ), the contrast approximates zero, as the signal intensities in this case are independent of t . and gray (gm) brain matter. as can be seen, the t contrast between the two tissues approaches for very long as well as for very short repetition times. the highest t contrast is obtained for tr ~ ms, i.e. for a repetition time in between the t times of the two tissues considered (see table . . ). b the same considerations hold for the t factor exp(-te /t ). the t contrast maximum is at te ~ ms influence of the acquisition parameters tr and te on the contrast behavior of an se image. the figure shows the interplay of the longitudinal and transversal relaxation for this sequence at the example of white (wm) and gray brain matter (gm) for a fixed repetition time of tr = . ms. in the left part, the temporal evolution of the longitudinal magnetization mz during the recovery period ( ≤ t ≤ tr) is depicted. at t = tr, the partially relaxed longitudinal magnetization is flipped into the x-y-plane by the ° excitation pulse. the t relaxation of the resulting transversal magnetization mxy is plotted in the right part as a function of the echo time te. as can be seen, there is a reversal behavior of the t and t contrast. for te = ms, the contrast is , so that the two types of brain matter cannot be differentiated in the relating se image in spite of differing tissue parameters (see fig. . . d). note that the detected mr signal is directly proportional to the transversal magnetization mxy in general, adjacent tissues differ in all three tissue parameters pd, t and t , so the different factors of the se signal equation, which can partially compensate one another, need to be considered altogether. this holds even more as the relaxation times are usually positively correlated, i.e., the tissues with longer t times usually also have longer t times. in order to illustrate this statement, fig. . . shows the course of the longitudinal and transverse magnetization for both white and gray brain matter for a repetition time of tr = , ms. as can be seen, the transverse magnetization of both substances-and therefore the signal intensities (sse ∝ mxy)-are identical at an echo time of te = ms, so the tissues cannot be distinguished on the related se image in spite of different tissue parameters. fig. . . shows the contrast between white and gray matter as a function of both the repetition and echo time. as expected, there are two regions with a high tissue contrast, which are separated by a low contrast region (cf. fig. inversion time ti as well as a on the repetition time tr. in order to optimize the t contrast, the inversion time ti is usually varied, whereas with the parameter td, respectively tris chosen as high as possible (td >> t ), to allow the recovery of a considerable longitudinal magnetization after rf excitation. the maximum range of values of the t factor is between - and + , thus being double the range of values of the se sequence. there are two types of ir sequences depending on signal interpretation: if only the absolute values of the signal are considered (magnitude reconstruction, irm), the range of values is limited de facto to the interval between and , as in the se sequence. if this mode of data representation is chosen, then the t factor will initially decrease to and then converges toward the equilibrium magnetization m . figure . . shows the dependence of the t factor from the inversion time ti for both possible modes of data representation for white and gray brain matter (tr = , ms). as this example reveals, the neglect of the sign of the t factors in the absolute value representation leads to a destructive t contrast behavior in the region between the zeros of both t functions considered. an ir sequence differentiating between parallel or antiparallel alignment of the longitudinal magnetization at the time of the excitation pulse is called phase sensitive. for evaluation of the tissue contrast, the pd and t dependence of the image signal sir needs to be included in the considerations, too. figure . . demonstrates this with an example. in this figure, the tissue contrast between white and gray brain matter is plotted as a function of the echo time te for ti= ms and tr = , ms. for the chosen ti value, there is a reversal behavior of the t and t contrast, as the relaxation times of the two tissues if the last-mentioned mode of data representation is used, there will be a destructive t contrast behavior in the region between the zeros of the two tissue curves. the t contrast maximum in the considered case is at ti~ ms, i.e., in between the t times of the two tissues considered (see table . . ) examined are positively correlated, i.e., the substance with the longer t time also has a longer t time. in order to fully grasp the complex interplay between the different tissue and acquisition parameters as a whole, the image contrast between white and gray brain matter is plotted in fig. the influence of the acquisition parameters te, ti, and td on the contrast of an ir image is summarized in table . . . in order to maximize the t contrast (t -weighted image), the ti time should be between the t times of the two tissues considered, and the echo time te should be chosen as short as possible. as even for the acquisition of t -weighted images, relatively long repetition times are needed (td >> t ), the ir sequence requires much more time than the se sequence. advantages occur mainly when the image signal of a given tissue structure shall be suppressed, e.g., the retrobulbar fatty tissue for the evaluation of the optic nerve. in this case, the acquisition parameter ti needs to be chosen so that the t factor of the tissue to be suppressed is approximately (fig. remark: an ir sequence with a very short ti time is called stir (short-tau inversion recovery) sequence. if the ti time is selected to suppress the signal from liquor, the sequence is called flair (fluid-attenuated inversion recovery). influence of the acquisition parameters ti and te on the contrast behavior of the ir sequence (absolute value representation). the figure shows the interplay of the longitudinal and transversal relaxation for this sequence at the example of white (wm) and gray brain matter (gm) for a fixed inversion time ti = ms and a fixed repetition time tr = , ms. the left part shows the temporal evolution of the longitudinal magnetization mz during the inversion phase ( ≤ t ≤ ti). at t = ti, the partially relaxed longitudinal magnetization is flipped into the x-y-plane by the ° excitation pulse. the t relaxation of the resulting transversal magnetization mxy is plotted in the right part as a function of the echo time te. in the case considered, there is a reversal behavior of the t and t contrast, so that the contrast between the two brain tissues rapidly reduces with prolonged echo time. note that the detected mr signal is directly proportional to the transversal magnetization mxy • in some cases, the imaging sequence is repeated several times (e.g., naq = or ), in order to improve the signal-to-noise ratio ( . this is especially valid for t -weighted se images, which have a relatively low s/n ratio due to the short repetition time. example: based on these considerations, the following representative acquisition times are obtained for se images: t = . min for a t -weighted image (tr = ms, nph = , naq = ) and t = . min for a t -weighted and/or a pd-weighted image (tr = , ms, nph = , naq = ). by using the multiple slice technique described in sect. . . , one can simultaneously acquire mr images from multiple parallel slices within the given acquisition times, but the overall acquisition time required for the acquisition of the images will not be reduced. in clinical practice, this basic limitation of conventional imaging sequences leads to the following problems: • depending on the clinical question, the time needed for a patient examination ranges between and min. • this demands high cooperation from the patient, as the patient will be asked to remain motionless during the examination in order to assure the comparability of differently weighted mr images. • critically ill patients may not be examined full scale or might not fit for examination at all. • the image quality is impaired by motion artifacts (such as heart beat, blood flow, breathing, or peristaltic movement). this problem is especially acute in patients with thorax and abdominal diseases, as mr images in general cannot be acquired completely during breath hold, as is the case in ct. • dynamic imaging studies are limited. to overcome these limitations, several methods aiming to shorten the acquisition examination times have been developed. they can be categorized into two groups, depending on whether the repetition time tr or the number of sequence cycles nph needed for phase encoding is reduced (see eq. . . ). the two strategies will be discussed in the following sections at the example of some selected imaging sequences. an almost complete overview of the clinically used fast imaging sequences will be provided in sect. . . . the long scan times of conventional imaging sequences are due to the fact that the ° excitation pulse rotates the entire longitudinal magnetization into the x-y-plane, so the pulse sequence can only be repeated when the longitudinal magnetization has been-at least partially-recovered by t relaxation processes. to acquire mr images with an acceptable s/n, the sequence repetition time tr has to be of the order of the t relaxation time. this basic problem in conventional imaging can be prevented, however, by using an rf pulse with a flip angle of α < ° to excite the spin system, so that only a part of the longitudinal magnetization mz will be rotated to the x-y-plane, nevertheless, one obtains a relatively large transverse magnetization. example: if, for instance, a flip angle of α = ° is used, then the longitudinal magnetization mz will be reduced by %, whereas the transverse magnetization mxy amounts to % of the maximum value (fig. . . ) . in order to discuss the principle of low-flip angle excitation, we will initially neglect the gradient fields needed for spatial encoding and consider the simple sequence shown in fig. . . a. it consists of a single rf pulse with a flip angle α< ° and a spoiler gradient, which destroys the remaining transverse magnetization after the acquisition of the fid. remark: as an alternative to spoiler gradients, the phase of the rf excitation pulse may be varied with every sequence cycle, in order to prevent the buildup of a steady state for the transverse magnetization (rf spoiling). if the considered sequence is repeated several times, then the spin system already reaches a dynamic equilibrium after a few sequence cycles. figure . . shows the transient behavior of the longitudinal magnetization in white the value of the steady-state longitudinal magnetization depends not only on the flip angle α of the excitation pulse, but also on the repetition time tr and the longitudinal relaxation time t . it will be smaller when α becomes bigger. for α = °, the longitudinal magnetization reaches the steady-state value m z ss = m [ -e -t r /t ] after the first excitation, as expected. however, the mr signal is not given by the longitudinal magnetization but by the transverse magnetization mxy at the time of data acquisition. by using eq. . . the amplitude s of the mr signal can be described by ( . . ) whereas the factor exp (-te/t *) describes the decay of the fid signal during the delay time te, the factor sinα gives the fraction of the steady state magnetization m z ss , which is rotated in the x-y-plane (see fig. . . b,c). to illustrate this relation, fig. . . shows the signal intensity s as a function of the ratio tr/t . from this plot, two important statements can be derived: • as compared with conventional ° excitation, lowflip angle excitation yields considerably higher signal values for short repetition times. • when using low-flip angle excitation, the signal is already independent of t for tr < t . the signal increase realized by low-flip angle excitation in combination with short repetition times is obtained, however, by omitting the ° pulse generating a spinecho, as the ° pulse not only inverts the phase of the transverse magnetization, but also the longitudinal magnetization (see fig. in contrast to the conventional imaging sequences, the nomenclature of the gre sequences is not unified, but is handled differently by different manufacturers. in the following, the fundamentals of gre imaging will be discussed in detail at the example of two representative sequences denoted by the acronyms flash and truefisp. the excitation of the spin system and position encoding are identical in both sequences; they differ only in that the transverse magnetization is destroyed after acquisition of the mr signal in the flash sequence (spoiled gre sequence), whereas it is maximized in the truefisp sequence (refocused gre sequence). this difference, however, leads to an entirely different contrast behavior. dephasing of the transversal magnetization caused by the slice selection and the readout gradient is compensated by two additional inverted gradients, so that a gradient-echo occurs. the figure shows the de- and rephasing process of two magnetization components (a,b), which are at different positions and therefore precess under the influence of the gradient-fields with different larmor frequencies. φx, φy, and φz are the corresponding phase angles however, this does not imply that for this angle the tissue contrast between two structures is at its maximum. in fig. . . the tissue contrast between white and gray brain matter is plotted for te << t *, i.e., exp(-te / t ) ≈ , as a function of the repetition time tr and the flip angle α. for low flip angles, two contrast regions can be distinguished: for short tr times, the t contrast dominates (t -weighted images), for longer tr times, the pd contrast (pd-weighted image). example: in order to illustrated the discussed contrast behavior, fig. the influence of the acquisition parameters on the contrast of a flash image is summarized in table . . . in , oppelt et al. introduced a gre sequence with the acronym fisp (fast imaging with steady precession), which considerably differs in its contrast from the flash sequence. this sequence was later renamed to truefisp (see below). the pulse and gradient scheme of this sequence is shown in fig. . . . instead of the spoiler gra- influence of the acquisition parameters tr and α on the t contrast of a flash image. for low excitation angles α, there will only be a considerable t contrast (here between white and gray brain matter) when short repetition times are selected. if the flip angle is increased, the t contrast maximum will shift to a higher tr value dient of the flash sequence, refocusing gradient pulses are introduced in slice-selection direction as well as in the direction of frequency and phase encoding, through which the transverse magnetization is not destroyed after the data acquisition of the mr signal, but rather rephased or refocused (fig. . . ). as practice has shown, the truefisp sequence is very susceptible to inhomogeneities of the static magnetic field, which are rendered visible as disturbing image artifacts. a more favorable behavior is achieved by omitting the gradient pulses (which have been shaded darkly in fig. . . ) . in this case, only the dephasing of the transverse magnetization caused by the slice selection and phase-encoding gradient is completely compensated. this realization is called fisp sequence. in the truefisp sequence, not only the longitudinal, but also the transversal magnetization reaches an equilibrium state after several sequence cycles. as both magnetization components are different from zero at the end two different contrast regions can be distinguished for low flip angles: for short tr times, the t contrast dominates (t -weighted image), for longer tr times, the pd contrast (pd-weighted image). if the flip angle is increased, then the t contrast curve will gradually approach the known contrast behavior of the se sequence (α = °). correspondingly, long repetition times need to be chosen in order to acquire pdweighted or t -weighted images of a sequence cycle, they will be mixed by the following rf pulse, i.e., a part of the longitudinal magnetization is flipped into the x-y-plane and a part of the transverse magnetization into the z-direction. consequently, both magnetization components dependent on t and on t . the t dependence increases proportional to the magnitude of the transverse magnetization remaining at the end of the sequence cycle (i.e., with decreasing tr/t ratio). vice versa, this means that the fisp signal for high tr values (tr>>t ) will approximate the flash signal. remark: the difference in the latter case merely consists in the fact, that in the flash sequence the transverse magnetization is rapidly destroyed by a spoiler gradient after the acquisition of the fid, whereas in the fisp sequence it decays with the time constant t . therefore, the flash sequence is more useful for the acquisition of t -weighted and pd-weighted images than is the fisp sequence. as the discussion has shown, the characteristic signal behavior of the fisp sequence manifests itself only for very short repetition times. for this special situation, the dependence of the signal intensity of the fisp sequence on the tissue parameters t , t , and pd can be described due to the complex gradient switching, the dephasing of the transversal magnetization caused by the three gradients is completely compensated after acquisition of the gradient-echo, so the transversal magnetization is restored before irradiation of the subsequent excitation pulse. the figure shows the de- and rephasing process for two magnetization components (a,b), which are at different positions and therefore precess with different larmor frequencies under the influence of the gradient fields. φx, φy, and φz are the corresponding phase angles. at the end of the sequence, both magnetization components are in phase again (φx = φy= φz = ), independent of their spatial position pulse and gradient scheme of the truefisp sequence. α flip angle of the excitation pulse, g z slice-selection gradient, g x phase-encoding gradient, g y readout gradient. instead of the spoiler gradient used in the flash sequence, there are refocusing gradient pulses in all three gradient directions, so that the transversal magnetization after acquisition of the gradient-echo is not destroyed but reconstructed (see fig. . . ) . in practice, the gradient pulses (marked darkly) here is frequently omitted in order to reduce the susceptibility of the sequence for artifacts leading to a fisp sequence approximately by the expression , ( . . ) which is independent of the repetition time tr. as this equation shows, the signal intensity of a fisp image for tr< ms), the t times differ strongly (see fig. . . ). the t times of the hf nuclei are generally higher than ms, whereas for hr nuclei they are less than µs due to the strong dephasing effect of neighboring spins. the different t times are mirrored in the h spectrum (fig. . . ) . as the width ∆ω of a resonance line is inversely proportional to the t time (see sect. . . ), the hf pool has a line width of a few hertz, whereas the spectral width of the hr nuclei is more than khz. it is crucial that the two h pools interact due to intermolecular processes (spin-spin interaction) and/or chemical exchange processes (wolff and balaban ). due to this reason, any change in the magnetization in one pool results in an alteration of magnetization of the other pool. this effect is called magnetization transfer (mt). to utilize this effect for mr imaging, the magnetization of the hrpool is saturated by frequency-selective preparation pulses (saturation transfer). due to the mt effect, this leads to a significant reduction of the mr signal of hf nuclei and thereby to a reduction of the image signal. in the simplest case, the frequency spectrum of the preparation pulse is defined by a rectangular function below and/or above the resonance frequency of the hf pool, as is shown in fig. . . . when doing this, the offset frequency has to be chosen big enough, so that local variations of the resonance frequencies of the hf nuclei due to inhomogeneities of the static magnetic field and differences in tissue susceptibilities do not lead to a direct effect on the hf magnetization. mt preparation pulses are often used in mr angiography to increase the blood-tissue contrast. this interesting application is based on the fact that the mt effect reduces the hf magnetization of stationary tissue, whereas the magnetization of the flowing blood is not affected. imaging in magnetic resonance is based on spin warp imaging but is commonly referred to as fourier imaging. the main underlying principle is the use of magnetic field gradients to prepare the slice-selective excitation and to phase and frequency encode the signal that is induced by the rotating transverse magnetization. the motivation of continued sequence development is fuelled by the aim to improve the tissue distinction and the shortening of measurement time. in recent years, a great number of sequences have been developed (see table . . ), each of which are utilized in routine clinical applications. the following paragraph provides a systematic overview of the sequence families. schematic depiction of a h spectrum of biological tissues. apart from the resonance line of h nuclei in free water ( hf), with a low spectral line width (< hz), there is a broad underground due to h nuclei in macromolecules with reduced mobility ( hr), the mr signal of which cannot be detected directly because of their short t times. note that the spectral widths are not depicted in true scale. the frequency spectrum of a mt preparation pulse is marked in gray a first sequence classification can be performed in assigning the type of sequence in either a spin-echo or a gradient-echo group. the main difference between se and gre is the influence of susceptibility gradients on image contrast. in general, in gre imaging susceptibility gradients lead to a faster decay of the signal, whereas in se imaging dephasing mechanisms that are fixed in location and consistent over time are refocused by the ° refocusing rf pulse. se image contrast depends on the tissue specific transversal relaxation time t , whereas gre image contrast is a function of the transversal relaxation time t *. some gre techniques utilize the excitation pulse also as a refocusing pulse, causing spin-echo components to contribute to the image contrast. within the se and the gre group, the contrast can be manipulated by preparing the longitudinal magnetization prior to starting the imaging sequence or prior to the measurement of a fourier line. in multi-echo imaging, the transverse magnetization is refocused and reutilized after the collection of a fourier line, omitting the necessity of a further excitation for the collection of another fourier line. this method is applicable within the se group as well as the gre group. again, a preparation of the magnetization is generating another sequence family. using only one excitation and multiple phase-encoded echoes to acquire all required k-space lines without a further excitation is called a single-shot technique. figure . . shows an overview scheme that provides one possible sequence-classification. within d gre with low-flip angle excitation and "spoiling" after data acquisition of a single fourier line and fourier interpolation in the direction of partition encoding combines the half-fourier method with a tse sequence to a degree at which only a single excitation pulse suffices to fill the raw-data matrix with following spin-echoes, one applies the so-called haste technique (half-fourier single-shot turbo spin-echo). the mix of spin-echoes with gradient-echoes or, more precisely the acquisition of gradient-echoes within an se envelope leads to the tgse (turbo gradient-echo sequence) sequence, also called grase (gradient and spin-echo). as expected, with the introduction of gradient-echoes within a multi-echo spin-echo sequence, the contrast behavior is also t * related. this sequence is also called a hybrid. similar to the se sequences, the gre sequences can be grouped into: • conventional gre sequences (e.g., flash, fisp, truefisp, dess, ciss, psif) • gre sequences with preparation of the magnetization (e.g., turboflash, mp-rage) • multi-echo gre sequences (e.g., medic, segmented epi) • multi-echo gre sequences with preparation of the magnetization (e.g., segmented dw-se-epi) • single-shot gre sequences (epi) • single-shot gre sequences with preparation of the magnetization (e.g., dw-se-epi) as indicated above, conventional gre sequences can be further divided into: • ssi group (steady-state incoherent), which only aims at a steady state in the longitudinal magnetization (e.g., flash, spgr, t -ffe) and • the ssc group (steady-state coherent), during which the steady state of the transversal magnetization equally contributes to the signal (e.g., fisp, truefisp, grass, fiesta, ffe, bffe). acronyms of the ssi group are flash (fast low-angle shot), spgr (spoiled gradient-recalled acquisition in the steady state), and t -ffe (t -fast field echo). in the ssc group there are truefisp (fast imaging with steady precession), grass (gradient-recalled acquisition in the steady state), and ffe (fast field echo). within the ssc group, there is a slow transition toward spin-echoes, as excitation pulses do not only excite, but also refocus various echo paths of a remaining or refocused transverse magnetization. the extreme form is psif (a backward-running fisp), also named ssfp (general electric) or t -ffe (philips). in these techniques, the excitation pulse of the following measurement operates as a refocusing pulse for the transverse magnetization of the previous excitation. the contrast is t weighted, as the effective echo time amounts to almost two repetition times. a combination of fisp echo and psif echo is called dess (double-echo steady state), and having the fisp and psif echo coincide in time will result in a ciss (constructive interference steady state) or a truefisp sequence. the same preparation of the magnetization utilized for se techniques can be applied to gre techniques. with a very rapid gre sequence (rage, or rapid acquired gradient-echoes), with the aim of measuring as fast as possible, the tr is set to a minimum and consequently so is te, and the excitation angle is set to an optimum (ernst angle) in order to generate as much signal as possible. to reestablish a t weighting, a saturation or inversion pulse is applied, but not prior each fourier line as in se imaging, but at the beginning of the whole measurement. those techniques are called turboflash, fspgr (fast spoiled gradient-recalled acquisition in the steady state), tfe (turbo field echo) or, placing the inversion within the partition loop of a d sequence, mp-rage (magnetization prepared rapid acquired gradientechoes). as is the case in fast se sequences, gre sequences also can make use of multi-echo acquisitions. medic (multiecho data image combination) uses multiple echoes for averaging, thus improving snr and t * contrast. the classical form of a single-shot gre technique, during which the raw data matrix is filled after a single excitation with several phase-encoded gradient-echoes, is called epi (echo planar imaging). simply collecting the free induction decay with multiple phase-encoded gradient-echoes is called fid-epi. placing the gradient-echoes beneath an se envelope is called se-epi. the most common magnetization prepared single shot gradient-echo technique is the diffusion-weighted spinecho echo planar imaging sequence (dw-se-epi). the idea of using multiple phase-encoded spin-echoes to fill the k-space more rapidly as compared with conventional imaging has surfaced as early as , with the acronym rare-rapid acquisition with relaxation enhancement ( fig. . . ). the number of applied echoes is directly proportional to the potential reduction in measurement time. the overall image contrast is dominated by the weighting of those fourier lines acquired in the center of k-space (effective echo time). the qualities of the early images were not close to the quality of conventional t -weighted se imaging. in the course of hard- and software developments, mulkern and melki "re-discovered" multi-echo se imaging during a search for a fast t -localizer, creating the acronym fse (fast spin-echo). siemens and philips use the acronym tse for turbo spin-echo. since the higher spatial frequencies, the "outer" k-space lines, are usually acquired using late echoes, early concern has been that small objects might be missed. fortu-nately, the time saving achieved with the use of multiple echoes has been utilized to improve the contrast by selecting longer repetition times and to improve the spatial resolution by increasing the matrix size. both measures have more than compensated the effect of an under-representation of high spatial frequencies within the k-space matrix. t -weighted tse has replaced conventional spinecho imaging in all clinical applications. the acquired phase-encoded echo train can also be used to create pdweighted and t -weighted images similar to conventional dual-echo spin-echo imaging. the use of phase-encoded echoes for the k-space of the pd-weighted image as well as the k-space of the t -weighted image is customary and this procedure is called shared echo. t -weighted tse imaging is also an option for some applications, although additional echoes will increase (unwanted) t -weighting. t -weighted tse imaging is rarely applied to the central nervous system as the use of additional echoes prolongs the time needed for a single slice and the number of necessary slices may not fit into the desired tr. for the genitourinary system (uterus, cervix, bladder, etc.) about three echoes are used to improve snr or to reduce measurement time. in areas where the amount of t -weighting is less of an issue, e.g. t weighted imaging of the cervical and the lumbar spine for degenerative disease, tse is usually used with an echo train length (etl) of five echoes. the same protocol is applied for enhanced and unenhanced studies of suspected vertebral metastases. t -weighted tse imaging for the abdomen is not an issue, since the restriction of the measurement time down to a breath hold period is suggesting t -weighted gre imaging. the remaining point of concern in comparing tse imaging with conventional se imaging is the reduced sensitivity to susceptibility artifacts. hemorrhagic lesions appear less suspicious on tse imaging as compared with conventional se imaging. the fourier transformation assumes a consistent signal contribution for all fourier lines. any violation of this assumption will lead to over- or under-representation of spatial frequencies, with a correlated image blurring. although tse violates this assumption in using multiple phase-encoded echoes to r structure of the tse sequence. excitation, refocusing, frequency, and phase encoding are done as in the conventional se sequence. the dephasing done for the purpose of spatial encoding is rephased prior to generating another spin-echo using a ° rf pulse followed by another phase-encoding step fill the k-space, where the signal amplitude of the echoes diminishes following t decay, there are several parameter that can be utilized to minimize the artifacts related to the t decay-related k-space asymmetry: • first, especially for t -weighted imaging, the signal amplitudes for the late and closely spaced echoes can be approximated as being constant. tse sequences are mainly used for the acquisition of t -weighted images. as lesions usually have a long t relaxation time, the signal loss caused by the t decay does not play a major role during data acquisition. • second, the matrix dimensions used in tse imaging are usually higher as compared with conventional se imaging. this will significantly minimize the risk of missing small objects. • third, in t -weighted tse imaging, the repetition time is increased considerably, which leads to a remarkable improvement in contrast, again reducing the potential risk of missing small objects due to k-space asymmetry. in a typical tse protocol, - echoes per excitation are used for imaging, implying a theoretical shortening of measurement time of the factor - . in practice, the shortening is about the factor - . longer repetition times are selected for improved pd and t weighting, and larger image matrices are used for improved spatial resolution, diminishing the potential shortening of the measurement time when using multiple phase-encoded echoes. as the mentioned influence on the space encod-ing is only present in the direction of the phase encoding, the effect can be demonstrated by exchanging of the frequency-and phase-encoding gradients. figure . . shows this in the example of the cauda equine. apart from use for high-resolution images, tse sequences are also applied in cardiology, as shown in fig. fast spin-echo imaging demonstrates two essential differences in imaging appearance as compared with conventional spin-echo imaging: fat appears bright, and there is a reduced sensitivity to hemorrhagic lesions. the bright appearance of fat is related to the j-coupling. the so-called j-coupling (see sect. . . ) of the carbon-bound protons provides a slow dephasing of transversal magnetization in conventional se imaging, in spite of the refocusing pulse. if the refocusing pulses follow shortly after image of the cauda equina, acquired with a tse sequence with a the phase-encoding direction from left to right, and b the phase-encoding direction from head to foot. the longitudinal structures of the relatively thin nerves will be better visible, if the frequency-encoding direction is perpendicular to the nerve fiber. the resolution in frequency-encoding direction is not influenced as much by the t decay as by the resolution in phase-encoding direction one another, as is the case in tse imaging, the j-coupling will be overcome; the dephasing will be suppressed. consequently, fat tissue appears brighter in the tse image than it does in a conventional image. if desired fat saturation or fat suppression (see sect. . . . ) can be utilized to suppress this appearance. the susceptibility-related artifact of hemorrhagic lesions in spin-echo imaging is due to diffusion in between excitation, refocusing, and data acquisition. reducing this diffusion time by rapidly succeeding refocusing pulses will also reduce the related artifacts, thus making tse imaging less sensitive for hemorrhagic lesions. the tse sequence, like the conventional se technique, can be used with an inversion pulse for preparation of the longitudinal magnetization. thus, it becomes possible to yield a suppression of the fat signal, based on the short relaxation time of fat (see fig. . . b). relaxation dependent fat suppression using an inversion pulse prior to the fast spin-echo train is routinely used to demonstrate bone infarctions and bone marrow abnormalities like bone marrow edema, e.g., in sickle cell anemia. this fat suppression scheme is also used in genitourinary applications, where the high signal intensity of fat may obscure contrast-enhanced tumor spread. since only the fat suppression is desired, the used inversion recovery technique is not phase sensitive, only the magnitude of the longitudinal magnetization is used. the acronym used in this case is tirm (turbo inversion recovery with magnitude consideration). the structure of a turbo inversion recovery (tir) sequence is presented in fig. . . . the reduction in measurement time due to the utilization of multiple phase-encoded spin-echoes permits the use of inversion times in the order of s, keeping the measurement time acceptable. an inversion time of . s will provide a relaxation dependent suppression of the cerebral spinal fluid (csf) signal ( fig. . . ). the utilization of a long inversion time is called fluid-attenuated inversion recovery, or flair. in combination with tse imaging (the structure of a d tse sequence is presented in fig. . . ), the technique is called turboflair or simply tirm. since csf has the longest t relaxation time, the longitudinal magnetization within all other tissues will be aligned parallel to the main magnetic field, and it is not necessary to have a phase sensitive ir method for this application. the attenuated csf signal allows a better differentiation of periventricular lesions and has demonstrated a superior sensitivity for focal white matter changes in the supratentorial brain, whereas posterior fossa located lesions can be missed. the turboflair method apparently allows the identification of hyperacute subarachnoid hemorrhage with mr, precluding the need for an additional ct. the time-consuming ir method has been used in the past for studying the development of white matter tracts in developmental pediatrics. this technique has been replaced using an inversion pulse prior to a spin-echo train of a tse sequence. the selected inversion time (~ ms) allows a better delineation of small differences in t relaxation times, e.g., for the documentation of the development of the pediatric brain. the improved tissue characterization between gray matter and white matter tracts allows, e.g., the demonstration of mesial temporal sclerosis and visualizing hippocampal atrophy. for this application a so-called phase-sensitive inversion recovery is required to differentiate nuclear magnetization aligned parallel to the magnetic field as compared with antiparallel alignment at the time of excitation. the according acronym is tir. the residual transverse magnetization after measuring a single fourier line, or, in case of multi-echo imaging, after measuring the "package" of fourier lines, is usually spoiled. a later-introduced concept refocuses the transverse magnetization at the end of the echo train and uses an rf pulse to "restore" the residual transverse magnetization back to the longitudinal direction. the method "improves" the recovery of the longitudinal magnetization for tissue with long relaxation times, allowing a further shortening of the repetition time without loss of contrast. the technique is called restore (siemens), fast recovery fast spin-echo frfse (ge) and drive (philips). it does not make a difference whether the magnetization is prepared after the measurement of a fourier line or at the very beginning of a new excitation cycle. for this reason it is justified to list restore as a turbo spin-echo scheme with preparation of the longitudinal magnetization. multi-echo spin-echo imaging has the potential to acquire t -and/or t -weighted spin-echo imaging of the beating heart within a breath hold. the only obstacle that needs to be addressed is the significant flow artifacts caused by the flowing blood. the introduction of dark-blood preparation scheme finally revolutionized cardiac mr imaging. with this preparation scheme, it is now possible to acquire t -and t -weighted images of the beating heart within a breath hold, without any flow artifacts. the magnetization of the whole imaging volume is inverted nonselectively, followed by a selective reinversion of the slice. this is done at end diastole, with the detection of the qrs complex. during the waiting period to follow, most of the reinverted blood will be washed out of the slice, being replaced by the inverted blood-and the spin-echo train acquired again toward end diastole will show "black" blood. a double inversion pulse will even allow not only the black-blood preparation, but also the suppression of fat signal, which will be helpful in characterizing fatty infiltration of the myocardium in arrhythmogenic right ventricular dysplasia (ard). single shot, per definition, refers to a single excitation pulse and the use of multiple phase-encoded echoes to fill the required fourier lines. the original rare has been published as a single-shot spin-echo technique. other acronyms found in the literature are ss fse for single-shot fast spin-echo (ge) or ss tse of single-shot turbo spin-echo (philips). the combination with a half-fourier technique allows a further reduction in measurement time and has been named haste: half-fourier acquired single-shot turbo spin-echo. as elaborated on earlier, the first and the last data point of a fourier line are characterized by the transverse magnetization of adjacent voxel pointing into opposite direction. the same situation is found for the first and last fourier line within k-space, considering the transverse magnetization within adjacent voxel aligned in the direction of phase encoding. k-space is symmetrical. although this hermitian symmetry is ideal and reality is slightly different, it has been claimed, that the deviation from the ideal situation are only of coarse nature and that a few (e.g., eight) fourier lines measured beyond the center of k-space should be sufficient to correct for this insufficiency. as an example for a * matrix, a single-shot spin-echo technique using the half fourier approach would use / + = phase-encoded echoes to fill the k-space. the measurement time using this acquisition method is about a second per slice. the high numbers of echoes suggest that this technique is only useful for t -weighted imaging and the blurring effect due to signal variation in k-space as a result of t decay will be prohibitive for high resolution studies. nevertheless, it is an alternative, even in the brain, for a fast t -weighted study for patients who are not able or willing to cooperate. since it is the perfect technique to visualize fluid-filled cavities, haste is used, e.g., for mrcp (magnetic resonance cholangiopancreatography). a typical result of this sequence is shown in fig. . . . progress in hardware development and the correlated improvement in image quality, together with the pioneering research within this field have recently led to an impressive increase in haste utilization for obstetric imaging. although sonography remains the imaging technique of choice for prenatal assessment, the complementary role of mr imaging is getting more and more important in the early evaluation of brain development of the unborn child or even in the early detection of complications within the fetal circulatory system. the search for shorter measurement times for faster imaging led to the group of gradient-echoes (gre) in . an mr signal can be detected immediately after the excitation pulse. that signal is the free induction decay (fid). in addition to the spin-spin interaction causing the t relaxation, other dephasing mechanism will contribute to the image contrast, dephasing mechanisms that are based on differences in precessional frequencies due to magnetic field variations across a voxel. the main sources of local magnetic field variations are differences in tis-sue-specific susceptibility values. since these dephasing mechanisms are fixed in location and are constant over time, they are refocused using a ° rf refocusing pulse in se imaging. omitting this pulse will lead to a contribution of these dephasing mechanisms to the image contrast. the observed tissue specific relaxation parameter is then called t * rather than t . with t ´ being both machine and sample dependent. although the missing ° rf refocusing pulse will cause a rapid dephasing of the transverse magnetization and with that a rapidly dephasing mr signal, the echo time can be reduced as well and so can the repetition time. the shorter echo time will allow, in most cases, a detection of a signal despite the rapid dephasing of the transverse magnetization. since the echo is now formed by using a bipolar gradient pulse in the direction of frequency encoding, these techniques are called gre. with shorter repetition times an extension of phase encoding for the direction of slice or slab selection can be considered, and d imaging becomes feasible. the short excitation pulses used in common gre imaging will result in a less perfect slice profile as compared with the slice profile achieved with a - ° combination of longer rf pulses as typically utilized in se imaging. as a result, there will be significant contributions of the low angle-excited outer regions of a slice, explaining the basic difference in contrast between a gre image as compared with an se image, even if a ° excitation angle is utilized. similar to the spin-echo sequence acquisition scheme, there is residual transverse magnetization left at the end of the acquisition of one fourier line-and similar to the spoiling of the transverse magnetization at the end of the measurement in se imaging, the same process can be applied to gre imaging as well. spoiling can be done with a gradient pulse, distributing the transverse magnetization evenly, so that the next excitation pulse will not generate a stimulated echo. or the phases of the excitation pulses can be randomized in order to avoid the buildup of a steady state for the transverse magnetization (rf spoiling). spoiled gradient-echo imaging has been introduced as fast low angle shot (flash), t -weighted fast field echo (t -ffe), or spoiled gradient recalled acquisition in the steady state (spgr). flash imaging allows multislice imaging in measurement times short enough to allow breath hold acquisitions. since the contrast mainly depends on the t relaxation time, flash images are usually called t weighted. in clinical routine, flash sequences have been introduced for diagnosing cartilage lesions (fig. . . ), for abdominal breath-hold t weighted imaging (fig. . . ), and in dynamic contrast enhanced studies. as has been discussed in sect. . . . , not only the amplitude of the signal can be controlled, but also the basic contrast behavior can be influenced. for instance, when using an extremely small excitation angle and moderate repetition times, one can minimize the influence of the t relaxation time (see fig. . . ) . thus, one can obtain the alternative to spoiling the residual transverse magnetization after the end of the fourier line acquisition is to rephase what has been dephased for spatial encoding. this was introduced as fast imaging with steady precession (fisp) (oppelt et al. ), later to be called true-fisp. the original implementation and publication of fisp uses a gradient refocusing in phase encoding as well as in frequency-encoding direction and slice-select direction. as this sequence was susceptible to artifacts at the time, the implemented and released fisp sequence, still used today, is only refocused in the direction of phase encoding, and no refocusing in readout and slice-selection direction. such a sequence has been called roast (resonant offset acquired steady state [haacke et al. ] ). for the fisp sequence, the phase encoding is reversed after the acquisition of the fourier line, undoing the dephasing that was applied for spatial encoding. this approach will lead to a steady state not only for the longitudinal magnetization, but also for the transverse magnetization-for tissue with long t relaxation times. differences in fisp contrast as compared with flash applications will only be visible for short repetition times; large excitation angles and will only enhance signal within tissue with long t relaxation times. general electric introduced this technique as gradient-recalled acquisition in the steady state (grass). philips is using the fast field echo (ffe). if one rephases at the end of the measurement of a fourier line, all parts of the transverse magnetization that have been dephased for spatial encoding and if one compensates in advance for the dephasing to be expected while the slice selection gradient is switched on, one obtains the truefisp sequence ( fig. . . ). this technique combines the advantages of the fisp sequence and the psif sequence, with further echo paths contributing to the overall signal. a clinical application of this sequence is shown in fig. . . . this original approach of refocusing all transverse magnetization at the end of the mea- structure of the truefisp sequence. the sequence seems to be "balanced" due to a symmetry in time. all components of the transverse magnetization are refocused at the end of the measurement, leading to a steady state surement of one fourier line will not only cause a steady state for the transverse magnetization, but also the next excitation pulse will also operate as a refocusing pulse. the excitation pulse will not only convert longitudinal magnetization to transverse magnetization, but will also generate a spin-echo. the sequence seems to be symmetric, balanced. the challenge is to get all the generated echoes to have one phase, otherwise the echoes will destructively interfere, causing band-like artifacts. the po-sitions of these bands also depend on the starting phase of the rf pulse. adding another acquisition with a phase shifted rf will lead to a technique called constructive interference steady state technique, (ciss), or phasecycled fast imaging-employing steady-state acquisition (pc-fiesta, the acronym used by ge). since ciss contains spin-echo components, the technique is even useful in regions with significant susceptibility gradients, e.g., nerve imaging at the base of the skull. since this technique is a fast technique with hyperintense appearance of fluid filled cavities, it is primarily applied to study abnormalities of the internal auditory canal. the originally published fisp is the truefisp, where all the dephasing is reversed and even the slice selection gradient is preparing the dephasing to be expected during the first half of the next excitation pulse. the truefisp technique is a fast gradient-echo sequence with spin-echo contributions leading to hyperintense appearance of all tissues with long t relaxation times. the technique is primarily used se signal. such a sequence is called double echo steady state (dess, fig. . . ) . the dess sequence is routinely used in orthopedic imaging (fig. . . ) . it links the advantages of the fisp sequence with the additional signal enhancement of the psif sequence for tissues with long t (e.g., edema and joint effusion). in fast cardiac imaging, for cine snapshots of the beating heart. general electric is using the acronym fiesta for the same technique. philips is using bffe (balanced fast field echo) as the acronym for his technique. the previously mentioned spin-echo component of a balanced technique can be isolated and can be used to generate an image. the psif sequence shown in fig. . . appears to be violating the causality at first: a fisp sequence running backward. the signal inducing transverse magnetization is produced with the first excitation at the end of the first cycle, refocused with the second excitation at the end of the second cycle, and inducing a signal at the beginning of the third cycle. the effective echo time therefore amounts to almost two repetition times. the resulting images consequently show a remarkable t weighting. (note that in this case, it is a spin-echo and not a gradient-echo.) the psif sequence is insensitive to susceptibility gradients. in contrast to ciss, the psif is very sensitive to flow and motion, thus it is not applied for iac imaging but rather used as an adjunct to demonstrate abnormal csf flow pattern. general electric is calling this technique simply steady state free precession (sffp), while philips is using the acronym t -ffe. imaging of the cochlea (fig. . . ) is no longer performed with psif but rather with ciss, due to the intrinsic flow insensitivity of the latter. when combining a fisp image with a psif image, one obtains an image with a t * weighting via the gre signal and a t weighting via the in theory, all the magnetization preparation schemes previously applied for the se group can also be applied for the gre sequences. however, it has to be kept in mind that gre sequences are usually using shorter te and shorter tr than se imaging does, and therefore some preparation schemes should be slightly altered. as, for an example, the fat saturation scheme: the time necessary for a spectral saturation pulse followed by a gradient spoiler will add up to the slice-loop time for an otherwise short tr gre sequence. a feasible modification is to skip the fat saturation for a few slices-this is referred to as "quick fat sat. " although a slice-dependent recovery of the fat signal is observed, the compromise is in general acceptable, since the fat signal stays low and more slices can be measured per tr. the quality of a spectral saturation pulse depends on the overall homogeneity within the imaging volume. in addition, the spectral fat saturating rf pulse is very close to the water resonance, causing a loss in overall snr. for a nonselective excitation, it is theoretically possible to also simply excite either fat or water using the tissue specific larmor frequency. in practice, such an approach is very prone to artifacts due to imperfect field homogeneity within the volume of interest. better results in water excitation or fat excitation have been achieved with binomial pulses ( - , - - , or - - - ). the mechanism of e.g., a - - rf pulse is described as follows, leading finally to a ° rf excitation pulse for just water. after an initial . ° rf pulse, there will be a waiting period, allowing the magnetization within fat to fall behind the magnetization of water. at the point of opposite position of the magnetizations, a ° excitation angle will than move the magnetization within water to a . ° position with respect to the longitudinal direction, whereas the magnetization within fat will be flipped back to the . ° position. after the previously mentioned waiting period, another . ° excitation pulse will accomplish the ° excitation for water, while the magnetization of fat will be restored to the longitudinal position, not contributing to the mr signal. another advantage of these binomial pulses is that they can be either executed using nonselective rf pulses or selective rf pulses. in the latter case, they are called spatial spectral frequency or simply composite pulses. inversion pulse prior to the measurement to improve t contrast short tr, short te gre imaging, utilizing the ernst angle leads to pd-weighted images rather than t -weighted images. in se imaging, the t contrast is improved by placing an inversion pulse prior to the acquisition of the fourier line. this approach is not feasible in gre imaging, since the inversion time would be much larger than the commonly used repetition times. in fast gre imaging, an inversion pulse is used prior to the whole imaging sequence (fig. . . ) . that concept has been introduced as turboflash (snapshotflash (haase et al. ) , fast spgr (fspgr) or turbo field echo (tfe)). the minor drawback is that the longitudinal magnetization, and consequently the generated transverse magnetization, will change throughout the measurement. the resulting violation of k-space symmetry will cause an under-or over-representation of some spatial frequencies producing a slight image blurring, typical for turboflash imaging. when using this method, one has to consider the following three facts: the longitudinal component of the macroscopic magnetization will recover after the inversion pulse with the t relaxation time. this relaxation process also takes place during data acquisition. the various measured fourier lines will have different t weightings. the image contrast is dominated by the t weighting of the fourier line measured at the center of k-space. the recovery of the longitudinal magnetization is influenced by the excitation angles of the rapid gre data after an inversion pulse and an inversion time, the small-angle excitation is repeated several times until the raw data matrix is filled acquisition. in order to minimize this influence and to obtain a maximum effect of the preparation-pulse on the image contrast, the rapid gre acquisition needs to be executed with small excitation angles. every fourier line is measured with a different phase encoding gradient and contains the spatial information of the object in direction of phase encoding. the k-space symmetry is significantly violated due to the change in signal contribution for each spatial frequency measured as a consequence of t relaxation during sampling. as a result, the images appear to be blurred, with imprecise edges and coarse signal oscillations parallel to the edges. with the introduction of short tr gradient-echo acquisition schemes, d imaging became feasible. the application of an inversion pulse prior to a d acquisition scheme is not very promising, since the preparation of the longitudinal magnetization would vastly diminish during the relatively long measurement time and the significant number of low angle excitation pulses. a feasible alternative is to repeat the preparation of the longitudinal magnetization in either the partition-encoding loop, or the phase-encoding loop. although the timesavings would be larger for placing the inversion pulse prior to the longer phase encoding loop, fortunately at the time it was only possible to place the inversion pulse prior to the partition-encoding loop. fortunately, because the previously described turboflash-artifact based on the overand under-representation of k-space lines is now omitted. the phase-encoding gradient is prepared; the inversion pulse is set followed by a rapid execution of the partitionencoding loop, during which the amount of longitudinal magnetization will change according to the course of the t relaxation (recovery influenced by the low-angle excitation pulses). after this, the next phase-encoding line is prepared, the inversion pulse set, and again the whole partition loop executed. the amount of signal within each partition is identical for all phase-encoding steps and the k-space is again symmetric, resulting in artifact-free images. this technique has been introduced as magnetization prepared rapid acquired gradient-echoes (mp-rage, mulger and brookeman ) (fig. . . ). figure . . shows as a typical application of the mp-rage sequence showing the medial-sagittal t -weighted slice out of of an examination covering the entire skull in less than min. the sequence had some promise to replace the conventional t -weighted spin-echo imaging of the brain, since it allows the gapless coverage of the whole brain in less than min. but, it is a gradient-echo sequence. susceptibility gradients especially at the base of the skull will cause geometric distorted representation of the anatomy or even signal voids. another disturbing effect is the appearance of contrast enhancement in active lesions. due to the commonly "squishy" content of lesions, the appear- phase-encoding gradient activated during readout period. such a technique would be called fid-epi, since signal sampling is done during free induction decay. another variant is placing the gradient-echoes under an se envelope (fig. . . ). in this case the central k-space contains a t contrast, in opposition to the t * contrast of the fid-epi version. the se-epi sequence shows a lower sensitivity for susceptibility gradients. fig. . . shows a se-epi with an alternative approach to phase encoding. in this example, phase encoding is done using gradient "blips" during the ramping time of the frequency-encoding gradient. such a technique is called blipped epi. after an excitation pulse, multiple gres are generated using an oscillating frequency-encoding gradient. in this example the phase encoding is achieved with a low-amplitude, constant phase-encoding gradient throughout the measurement rf fig. . . se-epi sequence. after an excitation and refocusing-pulse, multiple gres are generated using an oscillating frequency-encoding gradient. the phase encoding is achieved in this sequence using small gradient pulses (blips) during ramping of the frequency-encoding gradient ance is usually iso- to hypointense in t -weighted imaging. mp-rage allows better control over t weighting, potentially causing the lesion to be more hypointense as compared with se imaging. in conjunction with contrast uptake, lesions will show up hyperintense on t -weighted se imaging. they may or may not show up hyperintense on mp-rage imaging. the appearance has been reported to be inconsistent, likely to be due to the better t weighting (a hypointense lesion may show up isointense after contrast uptake). the rapid acquisition of a gradient-echo or steady state sequence following an inversion is sometimes referred to as single-shot technique. this is not quite correct since as many low angle excitation pulses are applied as fourier lines are needed to fill the k-space. but the singleshot nomenclature allows a differentiation compared to the segmented, or multi-phase, imaging of the beating heart. similar to the stir approach used in fat signalsuppressed imaging, the inversion pulse prior to a singleshot technique enables the nulling of signal for a specific tissue (depending on the t relaxation time). the turboflash technique is used to study the firstpass of a contrast bolus through the cardiac chamber, showing a delayed enhancement in perfusion restricted ischemic myocardium. the inversion time is adjusted, so that normal myocardium will give no signal. in the early phase normal myocardium will be perfused with the t -shortening contrast agent, whereas the perfusion restricted ischemic myocardium will remain hypointense. the same method of tissue signal nulling can be applied to the truefisp. this technique has been used to demonstrate the late enhancement of infarcted myocardium. an advantage for the truefisp versus turboflash is that the additional signal contributions due to refocusing and balancing (spin-echo components), allowing a higher bandwidth acquisition correlated with a shorter te, a shorter tr, and therefore a shorter measurement time (~ ms). in addition, the truefisp has a significant lower sensitivity to flow and motion artifacts as compared to the turboflash, leading to (almost) artifact-free images. both methods are currently evaluated regarding their value in characterizing myocardial viability. the single-shot gradient-echo imaging is echo planar imaging (epi). similar to tse imaging, epi makes use of several phase-encoded echoes to fill the raw data matrix (fig. . . ). there are multiple ways to acquire the data. a single excitation can be utilized, followed by multiple phase-encoded gradient-echoes with a small, constant addressing a different way of k-space sampling, both, the frequency-encoding" gradient and the "phase-encoding" gradient may oscillate, causing a spiral trajectory through k-space. such a method is known as spiral epi. the quotation marks are used to indicate that the magnetic field gradients do no longer have the apparent meaning of frequency and phase encoding. the high sensitivity of epi to local field inhomogeneities is utilized in (brain) perfusion imaging and for monitoring the oxygen level to identify cortical activation in bold (blood oxygenation level-dependent) imaging. in spite of many limitations, the epi sequences have attained high clinical potential in functional imaging and in perfusion studies. the preparation of the longitudinal magnetization is not only possible with the previously described multi-shot techniques, but also with the single-shot version. single shot, per definition, means one excitation pulse and multiple phase-encoded gradient-echoes for sampling of all fourier lines. the primary preparation scheme for singleshot gradient-echo imaging is diffusion weighting. any magnetic field gradient in the presence of a transverse magnetization will cause the larmor frequency to be a function of location. sometimes this effect is desired, as in any phase encoding, and sometimes it is a byproduct of another desired functionality, e.g. the frequency encoding. to rephase or refocus the dephased transverse magnetization, a magnetic field gradient of opposite polarity can be used prior to the frequency-encoding gradient. but, this will only work if the transverse magnetization does not change the position in the meantime, as is the case for diffusion. if the transverse magnetization changed positions, then the phase history will be different as compared with stationary tissue at that new location, and the rephasing will be insufficient. insufficient rephasing will result in a reduced signal. the signal drop is characterized by with b being a system or method specific parameter, and d being the diffusion coefficient for the tissue. the method specific parameter b is a function of the gradient amplitude g used, the duration δ for each amplitude and the temporal distance ∆ between the two gradient amplitudes. ∆ is also called the diffusion time. a typical value for b = , s/mm . a sequence illustration is given in fig. . . . the result of the application of such a technique to a patient with an acute infarction is shown in fig. . . . diffusion-weighted imaging allows an evaluation of the extent of cerebral ischemia in a period where possible interventions could limit or prevent further brain injury. the diffusion anisotropy potentially measured with this method allows the mapping of neuronal connectivity and offers an exciting perspective to brain research. the turbo gradient spin-echo sequence (tgse), also called gradient and spin-echo (grase) is a combination of multiple gradient-echoes that are acquired within multiple se envelopes of a tse sequence, as shown in fig. . . . this method holds several advantages in comparison to the "simple" tse sequence: the use of several phase-encoded gradient-echoes has the potential of further shortening measurement time. figure . . shows a transversal t -weighted head image with a matrix size of , , which has been measured with a tgse sequence in . min. another advantage is the fact that with the use of several gradient-echoes per spin-echo envelope, the gap between the refocusing pulses widens. therefore, the j-coupling remains intact. fat appears darker, and the contrast approaches the contrast of conventional se sequences. further, the enhanced sensitivity toward the susceptibility gradients that has been introduced with the gradient-echoes allows for a better depiction of blooddecay products, similar to conventional se-imaging. clinical mr systems come in various types and shapes; however, the fundamental components of a clinical mr tomograph are essentially the same. these are: • the magnet: the magnet creates a static and homogeneous magnetic field b , which is needed to establish a longitudinal magnetization. • the gradients: the gradient coils generate additional linearly ascending magnetic fields that can be switched on and off. the gradient fields allow assigning a spatial location to the received mr signals (spatial encoding). for an image acquisition three independent gradient systems in x-, y-, and z-direction are required. • the radio frequency (rf) system: to rotate the longitudinal magnetization from its equilibrium orientation along b into the transverse plane, an oscillating magnetic field b is required. this rf field is generated by a transmitter and coupled into the patient via an antenna, the rf coil. radio frequency coils are also used to receive the weak induced mr signals from the patient, which are then amplified and digitized. • the computer system: measurement setup and image post-processing are performed by (distributed) computers that are controlled by a host computer. at this host computer, new measurements are planned and started and the reconstructed images are stored and analyzed. a schematic of the components of a clinical mr system is shown in fig. . . ; more detailed descriptions can be found in the works of oppelt ( ) , vlaardingerbroek et al. ( ), and chen and hoult ( ) . in the upper part, a cross-section through a superconducting magnet can be seen, with field-generating magnet windings embedded in a cryostatic tank. closer to the patient, the gradient coil and the whole-body rf coil are located outside the cryostat. the magnet is surrounded by an electrically conducting cabin (faraday cage) which is needed to optimally detect the weak mr signals, without rf background from other rf sources (e.g., radio transmitters). in the lower part, the computing architecture and the hardware control cabinets are shown. a hardware computer controls the gradient amplifier, the rf transmitter, and the receiver. the received and digitized mr signals are passed on to an image-reconstruction computer, which finally transfers the reconstructed image data sets to the host computer for display and storage. to generate the main magnetic field three different types of magnets can be utilized: permanent magnets, resistive magnets, and superconducting magnets (oppelt ; vlaardingerbroek ; chen ) . the choice of an individual magnet type is determined by the requirements on the magnetic field. important characteristics are the field strength b , spatial field homogeneity, temporal field stability, patient accessibility, as well as construction and servicing costs. as outlined in sect. . a high magnetic induction is desirable as the mr signal s is approximately proportional to b ², and the signal-to-noise ratio (snr) increases approximately linearly with b . it is thus expected that with increasing field strength the measurement time can be substantially decreased. the field strength is limited however for the following reasons: • for tissues in typical magnetic fields of . t and higher, the longitudinal relaxation time t increases with field strength. if the same pulse sequence with identical measurement parameters (tr, te, etc.) would be used at low field and high field, the t contrast would be less pronounced in the high-field image, since image contrast typically depends on the ratio of tr over t . to achieve a similar t contrast with a conventional se or gre pulse sequence, tr (and thus the total measurement time) needs to be increased. • the resonance frequency ω increases linearly with field strength according to ω = γ b . at higher frequencies the wavelength of the rf waves are of the order of or even smaller than the dimensions of the objects to be imaged. under these circumstances, standing waves can be created in the human body, which manifests in areas of higher rf fields (hot spots) and neighboring areas of reduced rf intensity. these unwanted rf inhomogeneities are difficult to control, as they are dependent on the geometry and the electric properties of the imaged object. • the power that is deposited in the tissue during rf excitation rises quadratically with ω (and thus with b ). to ensure patient safety at all times during the imaging procedure the specific absorption rate (sar), i.e., the amount of rf power deposited per kilogram of body weight, is monitored and limited by the mr system. with increasing field strength, the rf power generated by a pulse sequence increases, and thus the flip angle needs to be lowered to stay within the guidelines of sar monitoring. since most pulse sequences require certain flip angles (e.g., a - ° pulse pair for an se), the rf pulses need to be lengthened at higher field strength to reduce the rf power per pulse. additionally, the time-averaged power can be lowered by increasing the tr. • at field strengths above t, only superconducting magnets are used for whole-body imaging systems. these magnets become very heavy and expensive. a typical . -t mr magnet weighs about t, whereas a -t magnet already has a weight of about t. shielding of the stray fields, which is, e.g., necessary to avoid ( ) that is filled with liquid helium. the cryotank also houses the primary magnet coils ( ) together with the shielding coils ( ) that create the magnetic field. the cryotank is embedded in a vacuum tank ( ). in a separate tubular structure in the magnet bore, the gradient coil ( ) and the rf body coil ( ) are mounted. an mr measurement is initiated by the user from the host computer. the timing of the sequence is monitored by the hardware computer, which controls (among others) the rf transmitter, rf receiver, and the gradient system. during the measurement, the rf pulses generated by the transmitter are applied (typically) via the integrated body coil, whereas signal reception is done with multiple receive coils. the digitized mr signals are reconstructed at the image-reconstruction computer, which finally sends the image data to the host for further post-processing and storage interference with cardiac pacemakers, becomes increasingly difficult. • the absolute differences in resonance frequency between chemical substances increase with field strength. this effect is beneficial for high-resolution spectroscopy, as high field strengths allow separating the individual resonance lines. during imaging, however, a substantially increased chemical shift artifact (i.e., a geometric shift of the fatty tissues versus the water-containing tissues) is seen, which can only be compensated using higher readout bandwidths. • differences in magnetic susceptibility between neighboring tissues create a static field gradient at the tissue boundaries. the strength of these unwanted intrinsic field gradients scales with b . therefore, increasingly higher imaging gradients are required at higher field strength to encode the imaging signal without geometric distortion; however, gradient strengths are technically limited. on the other hand, in neurofunctional mri (fmri) the increased sensitivity at higher field strengths is utilized to visualize those brain areas where local susceptibility differences in the blood are modulated during task performance. in the clinical environment, magnetic field strengths between . and t are common. low-field mr systems (b < t) are often used for orthopedic or interventional mri, where the access to the patient during the imaging procedure is important. high field strengths between t and t are used for all other diagnostic imaging applications. recently, whole body mr systems with field strengths up to . t have been realized (robitaille et al. ) . with these systems, in particular neurofunctional studies, high-resolution imaging and spectroscopy as well as non-proton imaging (e.g., for molecular imaging) are planned, since these applications are expected to profit most from the high static magnetic field. in the following, the three different types of magnet are described that are used to create the static magnetic field. permanent mri magnets are typically constructed of the magnetic material ndbfe. permanent magnet materials are characterized by the hysteresis curve, which describes the non-linear response of the material to an external magnetic field. if an external field is slowly increased, the magnetization of the material will also increase until all magnetic domains in the material are aligned-at this point the magnet is saturated, and no further amplification of the external field is possible. if the external field is then switched off a constant, non-vanishing magnetic field remains in the material because some of the domains remain aligned. permanent magnets offer very high remanence field strength. permanent magnets require nearly no maintenance because they provide the magnetic field directly without any electrical components. permanent magnets often use a design with two poles, which are either above or below (fig. . . ) or at the sides of the imaging volume. within this volume the magnetic field lines should be as parallel as possible (high field homogeneity), which is achieved by shaping of the pole shoes. due to their construction, the magnetic field is typically orthogonal to the patient axis, whereas high-field superconductors use solenoid magnets with a parallel field orientation. magnetic field lines are always closed; therefore, an iron yoke is used in permanent magnets to guide the magnetic flux between the pole shoes. with increasing field strength permanent magnets become very heavy ( t and more), and the high price of the material ndbfe becomes a limiting factor. additionally, to achieve high temporal field stability the material requires a constant room temperature, which should not vary by more than k. for these reasons, permanent magnets are typically used only for field strengths below . t. if an electrical current is flowing through a conductor, a magnetic field is created perpendicular to the flow direc- tion that is proportional to the current amplitude. unfortunately, in conventional conductors (e.g., copper wire) the electric resistance converts most of the electric energy into unwanted thermal energy and not into a magnetic field. therefore, a permanent current supply is required to maintain the magnetic field and to compensate for the ohmic losses in the wire. additionally, to dissipate the thermal energy resistive magnets need permanent water cooling as their power consumption reaches several kw. resistive magnets use iron yokes to amplify and guide the magnetic field created by the electric currents. the iron yoke is surrounded by the current-bearing wires so that the field lines stay within the iron. in the simplest form, the closed iron yoke has a gap at the imaging location and the magnet takes the form of a c-arc, which can also be rotated by ° to provide a good access for the patient (fig. . . ). other magnet designs use two or four iron posts that connect the pole shoes. the magnetic field of a resistive magnet is typically not as homogeneous as that of a superconducting magnet of the same size. to achieve high field homogeneity within the imaging field-of-view, the diameter of the pole shoes should not be less than . times the desired diameter of the imaging volume (dfov), and the pole separation should be more than . dfov. at a typical pole separation of cm, the imaging volume would thus have a diameter of cm, and the pole shoe diameter amounts to cm. resistive magnets are susceptible to field variations caused by instabilities of the electric power supply. to minimize this effect the magnetic field of the magnet can be stabilized using an independent method to measure the field strength (e.g., electron spin resonance). the difference between actual and desired field strength is then used to regulate the current in the magnet in a closed feedback loop. to create magnetic fields of more than . t with a bore size of cm or more, today, typically superconducting magnets are utilized (fig. . . ) . in principle, these magnets operate in a similar fashion as resistive magnets without iron yoke-superconducting magnets also generate their magnetic field by wire loops that carry a current. instead of copper wire, superconductors use special metallic alloys such as niobium-titanium (nbti). the alloys completely lose their electric resistance below a certain transition temperature that is characteristic for the material; this effect is called superconductivity. the transition temperature itself is a function of the magnetic field, so that lower temperatures are required when a current is flowing through the wire. unfortunately, an upper limit for the current density in the wire exists, which is also a function of the temperature and the magnetic field. to maintain the required low temperatures cooling with liquid helium is typically necessary (t < - °c). the imaging volume of the mr system is typically kept at room temperature (t = °c), whereas the surrounding superconducting wires require temperatures near the absolute zero (- . °c). to maintain this enormous temperature gradient, the field-generating superconducting coils are encased in an isolating tank, the cryostat. the cryostat is a non-magnetic steel structure that contains radiation shields to prevent heat diffusion, heat conduction, and heat transport. if this isolation is not working properly and the wire is locally warming up over the transition temperature, then this section of the wire will become normally conducting, and the energy stored in the current will be dissipated as heat. the heat will then be transported to adjacent sections of the wire, which will also lose their superconductivity. this very rapid process is called a quench. when the magnet wire is heating up the liquid helium will evaporate, and the cryo- fig. . . iron-frame electromagnet . -t mr system (upright tm mri, fonar) with a horizontal magnetic field. this special construction of the mr systems allows for imaging in both upright and lying positions. this flexibility is especially advantageous for mr imaging of the musculoskeletal system . technical components stat is exposed to an enormous pressure. to prevent the cryostat from exploding, a so-called quench tube is connected to superconducting magnets with helium cooling, which safely guides the cold helium vapor out of the magnet room. recently also ceramic superconducting materials on the basis of niobium-tin (nb sn) alloys have been used to make superconducting wires. the brittle nb sn alloys show a higher transition temperature (- °c) and thus do not necessarily require liquid helium cooling. if the cryostat is equipped with a good thermal vacuum isolation, a conventional cooling system (e.g., gifford-mc-mahon cooler) can be used to maintain the temperature. this technology has been realized both in a dual-magnet system (general electric sp, b = . t) and a low-field open mr system (toshiba opart, b = . t). because a helium-filled cryostat requires more space than does a system without helium, these magnets can be installed in smaller areas than can comparable magnets with helium. in the recent years, several mr magnets have been equipped with helium liquefiers to regain the evaporated helium gas in the magnet. once filled with helium these so-called zero boil-off magnets can operate in principle without any additional helium filling. magnets without helium liquefiers require replenishment of the helium at intervals between several months and - years, depending on the quality of the cryostat and the usage of the mr system. the most widespread form of a superconducting magnet is the solenoid, where the windings of the superconducting wire form loops around the horizontal bore of the cylindrical magnet. at a typical inner bore diameter of cm for clinical mri systems, solenoid magnets can create very homogeneous magnetic fields with varia-tions of only a few parts per million (ppm). because the relatively bulky magnet structure limits access to the patient, shorter magnets of . m length with wider diameters of cm have been designed (siemens magnetom espree, b = . t) (fig. . . ). in these magnets, obese patients can be imaged more conveniently, claustrophobic patients feel more at ease and some mr-guided percutaneous interventions might become feasible. another variant of the solenoid is a dual magnet mr system consisting of two collinear short solenoid magnets (general electric sp, b = . t) - here the imaging area is located in between the two magnets and even intra-operative mr imaging is possible. recently, also two-pole systems with a magnet design similar to low-field resistive magnets have become, which offer a good patient access in combination with higher field strengths ( fig. . . ) . outside a superconducting magnet, the field strength his falling off with the inverse third power of the distance ( /r ³) so that the stray fields can extend far outside the mr room. magnetic fields in commonly accessible areas must not exceed . mt, because higher fields can affect pace makers and other active electric devices (fig. . . ) . for this reason, two shielding technologies have been utilized to reduce the magnetic fringe fields. with passive shielding ferromagnetic materials such as steel are mounted near the magnet. this shielding technique confines the field lines to the interior of the shielding material, and the stray fields are reduced. unfortunately, the amount of shielding material rapidly increases with increasing magnetic field, and between t and t of steel are required to shield a -t magnet (schmitt et al. ) . with active shielding a second set of wire loops is integrated in the cryostat of the magnet. the shielding fig. . . conventional . -t superconducting mr magnet (magnetom symphony, siemens) with a magnet length of cm and a free open-inner bore diameter of cm. the system is equipped with an in-room monitor (left), which allows controlling the mr system from within the rf cabin coils create a magnetic field in the opposite direction of the imaging field so that the stray field falls off more rapidly. the shielding coils have a larger diameter than do the field-generating primary coils. thus, the desired magnetic field within the magnet can be maintained by increasing the current in both coil systems. additionally, the shielding coils and the primary coils repel each other (lorentz forces), which requires a magnet design with more stable coil formers. the attractive forces acting on paramagnetic or ferromagnetic objects near such an actively shielded magnet are significantly higher than near an unshielded magnet; device compatibility and safety should thus always be specified with regard to the investigated magnet type. and an open-bore diameter of cm. the additional cm in bore diameter over conventional mr system with solenoid magnets and the shorter magnet length offer a better access to the patient, so that, e.g., percutaneous interventions can be performed in this magnet structure to localize the mr signals emitted by the imaging object, a linearly increasing magnetic field, the gradient g, is superimposed on the static magnetic field b . the gradient fields are created by gradient coils that are located between the magnet and the imaging volume (schmitt et al. ). for each spatial direction (x, y, and z) a separate gradient coil is required, and angulated gradient fields are realized by linear superposition of the physical gradient fields. in a cylindrical bore superconducting magnet, the gradient coils are mounted on a cylindrical structure, which is often made of epoxy resin. this gradient tube reduces the available space in the cryostat from typically cm, without gradient coils, to cm, with gradient coils. the functional principle of a gradient system is best illustrated by a setup of two coaxial wire loops with a radius a that are separated by a distance d (fig. . . ). if the two coils both carry the same current, however, in counterpropagating directions, their respective magnetic fields cancel at the iso-center of the setup. at distances not too far from iso-center the magnetic field will increase linearly, which is exactly the desired behavior of a gradient field. to achieve this linear gradient field the condition d = a must be met (maxwell coil pair) (jin ) . in commercially available gradient system, much more complicated wiring paths are utilized, which are optimized using the so-called target field approach (turner ). this often results in wire patterns that, when plotted on a sheet of paper, resemble fingerprints (fingerprint design). nevertheless, a common feature of all gradient systems is the absence of current at the cen-tral plane, which allows separating the gradient coils, e.g., for c-arc-type magnets. the quality of the gradient system is characterized by several parameters: the maximum gradient strength gmax, the slew rate smax, the homogeneity, the duty cycle, the type of shielding, and gradient pulse stability and precision. today, clinical mr systems have maximum gradient strengths of up to gmax = mt/m at bore diameters of cm. even higher gradient strengths of mt/m and more can be realized when so-called gradient inserts with smaller diameters are used (e.g., for head imaging). the maximum gradient strength is limited by the capabilities of the power supply of the gradient system-modern gradient systems use power supplies that can deliver voltages up to , v and currents up to a. another limiting factor for gmax is gradient heating: with increasing current through the gradient coil, the windings heat up to levels at which the gradient could be destroyed. therefore, to remove the heat from the gradient tube, pipes are integrated in the gradient coils for water-cooling. the maximum slew rate smax is the ratio of gmax over the shortest time required to switch on the gradient (rise time). when the current in the gradient coil is increased during gradient switching, according to lenz's law the coil will produce a current, which opposes the change. thus, it counteracts the switching process, and the rise time cannot be made infinitely short. during mr imaging, however, it is desirable to have very short rise times (i.e., high slew rates), as these times only prolong the imaging process. clinical mri systems have slew rates between mt/m/ms and mt/m/ms. if the gradient coil is connected to a capacitance via a fast switch, very short rise times can be achieved, as the inductance of the gradient coil and the capacitance form a resonance circuit. such a resonant gradient system has the disadvantage that the characteristic frequency of the resonance circuit determines the possible rise times. additionally, gradients can only be switched on after the capacitances have been charged. resonant gradient systems have nevertheless been successfully applied to epi studies, in which the sinusoidal gradient waveforms are beneficial, and multistage resonant systems have been utilized to approximate the trapezoidal gradient waveforms (harvey ) . when the gradient is switched on, the maximal rate of field change is observed at the ends of the gradient coil (i.e., fovmax/ ): db/dt = smax fovmax/ . a changing magnetic field induces currents in electrically conducting structures in its vicinity-outside the gradient coil this structure is given by the cryostat, and on the inside the patient can act as a conductor. to avoid these parasitic currents (eddy currents) in the cryostat, which in turn create magnetic fields counteracting the gradients, often a second outer gradient structure is integrated in the gradient tube. the inner and outer gradient coils are designed so that their combined gradient field vanishes everywhere outside the gradient coil, whereas the desired gradient amplitudes are realized on the inside. this technique is called active shielding, and is conceptionally similar to the active shielding of superconducting magnets (mansfield and chapman ; harvey ) . gradient-induced currents in the human body pose a more severe problem, as these currents can potentially lead to painful peripheral nerve stimulation or, at higher amplitudes, to cardiac stimulation (mansfield and harvey ; schaefer ; liu et al. ) . these physiologic effects are not only dependent on the amplitude, but also on the frequency of field change. for clinical mr systems, different theoretical models have been established to determine the threshold for peripheral nerve stimulation. to make the best use of the available gradient system some fast pulse sequences (e.g., for contrast-enhanced mra or epi) operate very close to these threshold values. as individuals are more or less susceptible to peripheral nerve stimulation, for some patients the individual threshold might be exceeded, and they experience a tickling sensation during fast mr imaging. this physiologic effect currently prohibits the use of stronger gradient systems. since the field change is lower at shorter distances from iso-center, peripheral nerve stimulation can be avoided if shorter gradient systems are used. unfortunately, a shorter gradient system only covers a limited fov, and the anatomical coverage is compromised. to overcome this limitation a combined gradient system with a shorter, more powerful inner coil and a longer, less intense outer coil has been proposed (twin gradients) (harvey ). such a system can be used, e.g., to rapidly image the beat-ing heart with the small coil, or to acquire image data from the surrounding anatomy at lower frame rates. when the gradient system is mounted in the mr magnet, strong mechanical forces act on the gradient tube, which are proportional to the gradient current. these forces are generated by the interaction of the gradient field with the static magnetic field and thus increase with b . the permanent gradient switching creates time-varying forces that lead to acoustic noise. several techniques have been proposed to reduce noise generation, which in some cases can exceed dangerous sound pressure levels of db. the wire paths in the coil can be designed in such a way that the forces are locally balanced, the gradient tube can be mechanically stabilized, the gradients can be integrated in a vacuum chamber to prevent sound propagation in air, or the gradient system can be mounted externally to reduce acoustic coupling to the cryostat (pianissimo gradient, toshiba). another possibility to reduce acoustic noise is to limit the slew rates in the pulse sequences to lower values than technically possible; in some pulse sequences (e.g., spin-echo sequences), this does not significantly affect the pulse sequence performance, but severely increase patient comfort. shimming is a procedure to make the static magnetic field in the mr system as homogeneous as possible. inhomogeneities of the magnetic field that are caused during the manufacturing of the magnet structure can be compensated with small magnetic plates (passive shim). after a localized measurement of the initial magnetic field, the position of the plates is calculated, and the plates are placed in the magnet. this procedure is repeated until the desired homogeneity of the field is achieved (e.g., . ppm in a sphere of radius cm). during mr imaging, objects are present in the static magnetic field that distort the homogeneous static field. field distortion is caused by susceptibility differences at the tissue interfaces and is thus specific for each patient. to at least locally compensate these field distortions, adjustable magnetic fields are required (active shim). if the field distortion is linear in space, then the gradient coils can be used for compensation. for higher-order field variations, additional shim coils are required. typically, shim coils up to fifth order are present in an mr system. higher-order shimming is particularly important for mr spectroscopy, where the field homogeneity directly affects the spectral line width. to optimize the shim currents, an interactive measurement process (the shim) is started after the patient is positioned in the magnet. during active shimming the field homogeneity is measured (e.g., using localized mr spectroscopy or a field mapping technique), and the currents are then adjusted to improve the field homogeneity (webb and macovski ). the radiofrequency (rf) system of an mr scanner is used to both create the transverse magnetization via resonant excitation and to acquire the mr signals (oppelt ; vlaardingerbroek et al. ; chen and hoult ). the rf system consists of a transmit chain and a receive chain. in the following, the details of the rf system are described. the mr signals, which are acquired by the rf coils of the mr system, are typically very low. to optimally detect these low signals, any other electromagnetic signals (e.g., radio waves) must be suppressed. therefore, the mr system is placed in a radiofrequency cabin (also called a faraday cage), which dampens rf signals at the resonance frequency by typically db and more. in low-field mr tomographs, the rf screening is sometimes realized as a wire mesh that is integrated in the mr system. this has the advantage that rf-emitting equipment such as television screens can be placed very close to the mr unit. at larger magnet dimensions, these local screens are often not suitable. here, the whole mr room is designed as an rf cabin, and the screening material is integrated into the walls, doors, and windows. for screening often copper sheets are used, which are glued to the wall panels, or the cabin consists completely of steel plates. to be able to transmit signals to and receive signals from the rf cabin, openings are integrated in the cabin. in general, one distinguishes between so-called filter plates, which contain electronic filters and open waveguides. waveguides are realized as open tubes with a certain length-to-diameter ratio, which is dependent on the wavelength of the rf frequency. waveguides are used to deliver anesthesia gases to the rf cabin and to guide the quench tube out of the shielded room. at the beginning of the transmit chain the rf transmitter is found, which consists of a synthesizer with highfrequency stability and an rf power amplifier. the lowpower synthesizer oscillates at the larmor frequency. its output signal is modulated by a digitally controlled pulse shaper to form the rf pulse, which is then amplified by the power amplifier. for typical clinical mr systems, the transmitter needs to provide peak power output at the larmor frequency of kw and more. besides high peak power, the rf transmitter should also allow for a high time-averaged power output, as several pulse sequences such as fast spin-echo sequences require rf pulses at short repetition times. the rf power is then transferred into the rf cabin via a shielded cable, and is delivered to the transmit rf coil. to guarantee a safe operation of the transmitter and to limit the rf power to values below the regulatory constraints for the specific absorption rates (sar), directional couplers are integrated in the transmission line. these couplers measure the rf power sent to the rf coil as well as the reflected power. high power reflection is an indicator of a malfunctioning of the connected coil, which could endanger the patient. if the reflected power exceeds a given threshold (e.g., % of the forward power), then the rf amplifier could be damaged by the reflected rf power and the transmitter is switched off. to couple the rf power of the rf transmitter to the human body an rf antenna is required, the so-called rf coil. before mr imaging starts, the coil is tuned to the resonance frequency of the mr system (rf tuning). simultaneously, the properties of the connecting circuitry are dynamically changed to match the resistance of the coil with the imaging object (loaded coil) to the resistance of the transmit cable (rf matching). once the coil is tuned and matched, the transmitter is adjusted. during this procedure, the mr system determines the transmitter voltage required to create a certain flip angle. for a given reference rf pulse shape sref (t), the transmitter voltage uref is varied until the desired flip angle αref (e.g., °) is realized. during the subsequent imaging experiments, use is made of the fact that the flip angle is linearly proportional to the (known) integral over the rf pulse shape, so that the required voltages can be computed from the reference values by linear scaling. radiofrequency coils are categorized into transmit (tx) coils, receive (rx) coils, and transmit/receive (txrx) coils. tx coils are only used to expose the imaging object to an rf b field during rf excitation, whereas rx coils detect the weak echo signal emitted from the human body-only if a coil performs both tasks, is it called a txrx coil. a typical example of a txrx coil is the body coil integrated into most superconducting mr systems; however, in some modern mr systems, it is used as a tx coil only due to its suboptimal receive characteristics. rx-only rf coils are the typical local coils found in mr systems that possess a (global) body coil, and local txrx coils are used in all other mr systems without a body coil (ultra-high field, dedicated interventional systems, openconfiguration low field). during signal reception, the oscillating magnetization in the human body induces a voltage in the rf coil. for an optimal detection of this weak signal, the rf coil should be placed as close to the imaging volume as possible. for this reason, optimized imaging coils exist for nearly any part of the human body. the largest coil of an mr system is typically the body coil (if present), which is often integrated in the magnet cover. to image the head or the knee, smaller volume resonators are used, where the imaging volume is in the interior of the rf coil ( fig. . . ). flexible coils exist, that can be wrapped around the imaging volume (e.g., the shoulder). small circular surface coils are used to image structures close to the body surface (e.g., eyes). unfortunately, the sensitivity of these coils is rapidly decreasing with distance from the coil center, so that they are not suitable for imaging experiments, where a larger volume needs to be covered. during rf transmission, rx coils need to be deactivated, because a tuned and matched rx coil would ideally absorb the transmitted rf power, and a significant amount of the rf energy would be deposited in the coil. to avoid any electronic damages, the coil is actively de-tuned during rf transmission; this is often accomplished by fast electronic switches (e.g., pin diodes), which connect a dedicated detuning circuitry. to combine the high sensitivity of small surface coils with the volume coverage of a large volume resonator, the concept of the so-called phased-array coils has been introduced (roemer et al. ) . a phased-array coil consists of several small coil elements, which are directly connected to individual receiver channels of the mr system. the separate reconstruction of the coil elements is technically demanding, because a full set of receiver electronics (amplifiers, analog-to-digital converters) as well as an individual image reconstruction are required for each coil element. the signals of the individual coil elements are finally combined using a sum-of-squares algorithm, which yields a noise-optimal signal combination. under certain conditions when snr can be sacrificed, also a suboptimal image reconstruction can be achieved by a direct combination of the coil element signals, which reduces the number of receive channels and shortens the image reconstruction time. to be able to manually adjust snr versus reconstruction overhead, special electronic mixing circuits have been introduced which allow combining, e.g., three coil elements into a primary, a secondary, and a tertiary signal (total imaging matrix tim, siemens). in a phased-array coil, the coil elements are positioned in such a way that an induced voltage in one element does not couple to the adjacent element-this can be achieved by an overlapping arrangement of the coil elements (geometric decoupling). phased-array coils with up to elements have been realized; however, typically the number of elements ranges between and . today, mri systems with independent receiver channels are available, at which up to coil elements can be positioned simultaneously. the individual coil elements can be selected manually or automatically to achieve the highest possible snr for a given imaging location. phased-array coils are not only required to achieve a high snr. the individual coil elements can also be used to partially encode the spatial location in the image; this procedure is called parallel imaging. the simplest version of parallel imaging uses two adjacent coil elements with non-overlapping sensitivities. if one wants to image the full fov covered by both coils only fov/ needs to be encoded, since each coil element is sensitive over this distance only. if the phase-encoding direction is chosen in this direction, the phase fov can be reduced by a factor of , which in turn halves the total acquisition time. in practice, the sensitivity profiles of the coil elements overlap and more sophisticated techniques such as smash sodickson and manning ) or sense (dumooulin et al. ) are required to reconstruct the image. nevertheless, in parallel imaging the intrinsic spatial encoding present in the different locations of the imaging coils is exploited to reduce the number of phase encoding steps. various receive coils on the patient table of a clinical . -t mr system (magnetom avanto, siemens) with receive channels and the possibility to connect a total of coil elements. the head coil with coil elements is combined with a neck coil ( elements), and the remaining parts of the anatomy are imaged with multiple flexible anterior phased-array coils ( × elements) and the corresponding posterior coils, which are integrated in the patient table. for smaller imaging volumes dedicated surface coils (flexible coil, open loop coil, small loop coil) can be used, which share a common amplifier interface because the phase encoding direction is different for different slice orientations, the optimal phased-array coil for parallel imaging offers coil elements with separated sensitivity profiles in all directions. for mr spectroscopy and non-proton imaging, rf coils with resonance frequencies for the respective nuclei are required. these non-proton coils can also incorporate a coil at the proton resonance frequency to acquire proton images without the need for patient repositioning. double-resonant coils are also important in situations when both frequencies are used at the same time as, e.g., in decoupling experiments. for interventional mri, dedicated tracking coils have been developed that are attached to the interventional devices (e.g., catheters or needles). the signal from these coils can be used for high-resolution imaging (e.g., of the vessel wall), but it is often only utilized to determine the position of the device (doumoulin et al. ) . in these tracking experiments, the signal of the coil is encoded in a single direction using a non-selective rf excitation, and the position of the coil in this direction is extracted after a one-dimensional fourier transform. the mr signal received by the imaging coil is a weak, analog, high-frequency electric signal. to perform an image reconstruction or a spectral analysis, this signal must be amplified, digitized, and demodulated. the signal amplification is typically performed very close to the imaging coil to avoid signal interference from other signal sources. if the rf coil is a txrx coil, then the signal passes a transmit-receive switch that separates the transmit from the receive path. the amplified analog signal still contains the high-frequency component of the larmor frequency. to remove this unwanted frequency component, the signal is sent to a demodulator, which receives the information about the current larmor frequency from the synthesizer of the transmitter. after demodulation, the mr signal contains only the low-frequency information imposed by the gradients. finally, the analog voltage is converted into a digital signal using an analog-to-digital converter (adc). over the recent years the conversion into a digital signal has increasingly been performed at an earlier stage in the receiver chain (e.g., before demodulation), and all subsequent steps were carried out in the digital domain. at the end of the receiver chain, the digital signal is then handed over to the image reconstruction computer. the computing system of an mr tomograph is typically realized by a system of distributed computers that are connected by a local high-speed network. the requirements for the computing system are manifold: for the user of the system it should provide an intuitive interface for measurement control, image processing, archiving, and printing. during sequence execution, the computers should control the hardware (i.e., gradients, rf, adcs, patient monitoring, etc.) in real time. additionally, the computing system must reconstruct and visualize the incoming mr data. since a single computer cannot perform all of these tasks at the same time, typically three computers are used in an mr system: the host computer for interaction with the user, the hardware control computer for real-time sequence control, and the image reconstruction computer for high-speed data reconstruction. the host computer provides the interface between the user and the mr system. through the mr user interface, the whole mr system can be controlled, mr measurements can be started, and the patient monitoring is visualized. at the host computer, the incoming images are sorted into an internal database for viewing, post-processing, and archiving. the internal database stores and sorts the images by patients, studies, and series. the database is often connected to the picture archiving and communication system (pacs) of the hospital, from where it retrieves the patient information to maintain a unique patient registry. a × mr image typically requires about kb of storage space, and for each patient investigation between and , images are acquired. on an average working day between and patients can be examined. the data of all of these patients need to be stored in the database so that a storage volume of about gb per day should be provided. with increasing matrix sizes and image acquisition rates, these numbers can easily be multiplied by factors of and more. the host computer is also used to transfer the acquired data to archiving media such as magneto-optical disks (mod), tapes, compact disks (cd), digital versatile disks (dvd), or external computer archives (typically, the pacs). data transfer is increasingly accomplished using the image standard dicom (digital imaging and communications in medicine), which regulates not only the image data format, but also the transfer protocols. it is due to this imaging standard that images can be exchanged between systems from different vendors and can be shared between different modalities. for post-processing, typically different software packages are integrated. in mr spectroscopy, software packages for spectral post-processing are available to calculate, e.g., peak integrals automatically. for mr diffusion measurements, the apparent diffusion coefficient can be mapped. with flow-evaluation software, the flow velocities and flow volumes can be assessed. to visualize threedimensional data sets often multi-planar reformatting tools or projection techniques such as the maximum intensity projection (mip) are used. all of these software packages retrieve the image data from the integrated image database, into which the calculated images are finally stored. dedicated computer monitors are connected to the host computer for image visualization, which fulfill the special requirements for diagnostic imaging equipment. in addition, these screens must not be susceptible to distortions due to the magnetic field; for this reason liquid crystal monitors based on the thin-film transistor (tft) technology are increasingly used. for interventional mr, shielded monitors for in-room image display have been designed, where the monitor is shielded against electromagnetic interference. these monitors can be used within the faraday cage of the mr system without interfering with the image acquisition. the control of the imaging hardware (i.e., the gradients in x, y, and z, the rf sub-system, the receiver, and the patient-monitoring system) requires a computer with a real-time operating system. compared with conventional operating systems where the instructions are processed in an order and at a time that are influenced by many factors, a real-time operating system ensures that operations are executed on an exactly defined time scale. this real-time execution is necessary to maintain, e.g., the phase coherence during spin-echo mri or to ensure that a given steady state is established during balanced ssfp imaging. during sequence execution, the different instructions for the hardware are typically sent by the control program to digital signal processors (dsp) that control the individual units. thus, new instructions can be prepared by the control program, whereas the actual execution is controlled close to the individual hardware. to ensure that enough hardware instructions are available, many time steps are computed in advance during sequence execution. for real-time pulse sequences, this advance calculation needs to be minimized to be able to interactively change sequence parameters such as the slice position (controlled by the rf frequency) or orientation (controlled by the gradient rotation matrix). in real-time sequences, the information about the current imaging parameters is thus retrieved not only once at the beginning of the scan, but continuously during the whole imaging experiment. the reconstruction of the data arriving at the adcs is performed by the image-reconstruction computer. to estimate the amount of data this computer needs to process the following estimate can be used: during high-speed data acquisition about raw data points (i.e., × bytes) arrive per imaging coil at time intervals of tr = ms, so that with rx coils a data rate of mb/s results. these incoming data need to be rearranged, corrected, fourier transformed, combined, and geometrically distorted before the final image is sent to the host computer. to perform this task today multiprocessor cpus are used to perform some of these tasks in parallel. in particular, the image reconstruction for multiple coils lends itself naturally to parallelization, since each of the coils is independent of the other. additionally, some manufacturers are including simple post-processing steps into the standard image reconstruction. since the reconstruction computer does not provide a direct user interface, these reconstruction steps need to be designed in such a way that no user interaction is necessary. this is the case for the calculation of activation maps in fmri, for mip calculations under standard views in mr angiography, or for the calculation of the arrival time of a contrast agent bolus in perfusion studies. at the end of the image reconstruction, the image data are transferred to the host computer via the internal computer network. special mr imaging techniques require additional mr components that are not necessarily available at any mr scanner. these components often monitor certain physiologic signals such as the electrical activity of the heart (electrocardiogram, ecg) or breathing motion (fig. . . ) . typically, the measured physiologic signals are not used to assess the health status of the patient but to synchronise the image acquisition with the organ motion, since heart and breathing motion can cause significant artifacts during abdominal imaging. synchronization of the image acquisition is performed either with prospective or retrospective gating. with prospective gating (or triggering), the imaging is started with the arrival of a certain physiologic signal (e.g., the r wave in the ecg). therefore, the physiologic signal is post-processed (e.g., thresholding and low-pass filtering) to create a trigger signal when the physiologic condition is present. with retrospective gating, the measurement is not interrupted, but data are acquired continuously, and for each measured data set, the physiologic state is stored with the data (e.g., the time duration after the last r wave). during image reconstruction, the measured data are sorted in such a way that images are formed from data with similar physiologic signals (e.g., diastolic measurements). the advantage of the retrospective over the prospective data acquisition is the continuous measurement without gaps that could lead to artifacts in steady state pulse sequences. the post-processing effort of retrospectively acquired data is higher because data need to be analyzed and sorted before image reconstruction. additionally, on average more data need to be acquired as compared to prospective triggering to ensure that for each physiologic condition at least one data set is present (over-sampling). to measure the ecg in the mr system mr-compatible electrodes made of silver-silver chloride (ag/agcl) are used. the measurement of the ecg in an mr system is difficult, because the switching of the gradients can induce voltages in the ecg cables that completely mask the ecg signal. this effect can be minimized, if short and loopless ecg cables are utilized. short ecg cables are additionally advantageous since long cables with a loose contact to the skin can be the cause for patient burns that are induced by the interaction with the rf field during rf excitation (kugel et al. ) . to reduce this potential danger to a minimum, ecg systems have been developed that amplify the ecg signal close to the electrodes, and which transmit the ecg signal to the mr system either via optical cables (felblinger et al. ) or as an rf signal at a frequency different from the larmor frequency. with this technology, ecg signals can be acquired even during echo planar imag-ing when gradients are permanently switched on and off (ives et al. ) . it should be noted that the ecg signal in the mr system significantly differs from the signal outside the magnet. the electrically conducting blood is flowing at different velocities in the cardiac cycle. within the magnetic field the blood flow induces velocity-dependent electric fields (hall effect) across the blood vessels, which in turn change the electric potentials measured at the ecg electrodes. typically, the t wave of the ecg is augmented, an effect that is more pronounced at higher field strengths (kangarlu and robitaille ) . for this reason, the ecg acquired in the mr system should not be regarded as of diagnostic quality. pulse oximeters measure the absorption of a red and an infrared light beam that is sent through perfused tissue (e.g., a finger). the absorption is proportional to the oxygen content, so that devices can determine the partial oxygen pressure (po ). additionally, the pulsation of the blood leads to a pulse-related variation of the transmitted light signal, which is used in the mr systems to derive a pulse-related trigger signal (shellock et al. ). since the pulse wave arrives at the periphery with a significant delay after the onset of systole, it is difficult to use the po signal for triggering in systolic mr imaging. pulse oximeters consist solely of non-magnetic and non-conduction optical elements, so that they are not susceptible to any interference with the gradient or rf activity. fig. . . whole-body imaging with array coils covering the patient from head to toe (exelart vantage tm , toshiba). since not all coils are in the imaging volume of the mr system at the same time, a lower number of receiver channels (here: ) are sufficient for signal reception . technical components to detect breathing motion, several mechanical devices such as breathing belts or cushions have been introduced. essentially, all these systems are air filled and change their internal pressure as a function of the breathing cycle when they are attached to the thorax of the patient. the pressure is continuously monitored and is used as an indicator for breathing status. as with the pulse oximeters, these systems are also free of any electrically conducting elements, so that no rf heating is expected. however, in clinical practice breathing triggering can pose a problem in long-lasting acquisitions since patients start to relax over time, and the initial breathing pattern is not reproduced. an alternative approach to the measurement of the breathing cycle is offered by the mr itself: if a single image line is excited in head-foot direction through the thorax (using, e.g., a ° and ° slice that intersect along the desired line), then the signal of this line has high contrast at the liver-lung interface. this diaphragm position can be detected automatically and can be used to extract the relative position in the breathing cycle. this technique is called a navigator echo (ehman and felmlee ) , since an additional echo for navigation needs to be inserted into the pulse sequence. similar approaches using lowresolution two-or three-dimensional imaging can be used to correct for patient motion in long-lasting image acquisitions such as fmri (welch et al. ) . here, the change in position is determined and used to realign the imaging slices (prospective motion correction). for neurofunctional studies, electroencephalogram (eeg) systems have been developed that can be operated in the mr tomography (muri et al. ) . compared with the ecg, the voltages induced during brain activity are about times smaller in eeg recording, which poses a significant detection problem (goldman et al. ; sijbersa et al. ) . blood pulsation, patient motion, as well as induced voltages during gradient and rf activity can cause spurious signals in the eeg leads, which obscure the true eeg signal. to remove the imaging-related artifacts, dynamic filtering can be used, which removes all signal contributions associated with the basic frequencies of the mr system. a large variety of mr systems with different magnet types, coil configurations, and gradient sets is currently available for diagnostic and interventional mr imaging. to choose from these systems, the desired imaging applications as well as economic factors need to be considered: a small hospital might with few mr patients might want to use a low-field permanent magnet system with low maintenance cost, whereas a university hospital with a diverse patient clientele and high patient throughput should better offer a high-field mr system with state-ofthe-art gradient systems. physiologic monitoring and triggering units. the three electrodes of the ecg system as well as the tube of the breathing sensor are connected with a transceiver that transmits both signals to the patient monitoring unit of the mr system. the optical pulse sensor is attached to the finger, and the signals are guided via optical fibers to the detection unit. for increased patient safety the ecg system must be used together with a holder system (not shown here), which provides additional distance between the ecg leads and the patient body . . muri rm, felblinger j, rosler km, jung b, hess cw, boesch c ( ) during the pioneer period of mr imaging, expectations were that the high inherent contrast in mr imaging makes the use of contrast agents superfluous. however, increasing use of the modality in the clinical setting has revealed that a number of diagnostic questions require the application of a contrast agent. similar to other imaging modalities, the use of contrast agents in mr imaging aims at increasing sensitivity and specificity and, thereby, the diagnostic accuracy. the main contrast parameters in mr imaging are proton density, relaxation times, and magnetic susceptibility (ability of a material or substance to become magnetized by an external magnetic field). mr imaging contrast agents focus upon relaxation time and susceptibility changes. most of them are either para- or superparamagnetic. the most efficient elements for use as mr imaging contrast agents are gadolinium (gd), manganese (mn), dysprosium (dy), and iron (fe). the magnetic field produced by an electron is much stronger than that produced by a proton. however, in most substances the electrons are paired, resulting in a weak net magnetic field. gd with its seven unpaired electrons possesses the highest ability to alter the relaxation time of adjacent protons (relaxivity). for mr contrast agents, differentiation between positive and negative agents has to be made. paramagnetic contrast agents gd and mn have a similar effect on t and t and are classified as positive agents. since the t of tissues is much higher than the t , the predominant effect of these contrast agents at low concentrations is that of t shortening. thus, tissues that take up gd- or mn-based agents become bright in t -weighted sequences. on the other hand, negative-contrast agents influence signal intensity by shortening t and t *. superparamagnetic agents belong to this group and produce local magnetic field inhomogeneities of the local magnetic field. t is reduced due to the diffusion of water through these field gradients. magnetite, fe o , is such a paramagnetic particle. coated with inert material (e.g., dextranes, starch), it can be used for oral or intravenous applications. in addition to the classification in positive or negative agents, mr contrast agents can be differentiated according to their target tissue. the targeting of an agent is determined by the pharmaceutical profile of the substance. in the clinical environment, we differentiate currently three classes of agents: • unspecific extracellular fluid space agents • blood-pool and intravascular agents • targeted and organ-specific agents unspecific extracellular fluid space agents. low-molecular-weight paramagnetic contrast agents distribute into the intravascular and extracellular fluid space (ecf) of the body. their contrast effect is caused by the central metal ion. all approved ecf agents contain a gd ion, which contains seven unpaired electrons. because gd itself is toxic, the ion is bound in highly stable complexes. the different complexes and the physicochemical properties of all clinically used agents are listed in table . . . the agents are not metabolized and are excreted in unchanged form via the kidneys. bound, they form low-molecular-weight, water-soluble contrast agents. gadopentetate dimeglumine (magnevist, bayer schering pharma, berlin, germany) and gadoterate meglumine (dotarem, laboratoires guerbet, aulnay-sous-bois, france) are ionic high-osmolality agents, whereas gadodiamide (omniscan, ge healthcare, buckinghamshire, uk) and gadoteriol (prohance, bracco imaging, milan, italy) are non-ionic low-osmolality agents. due to the low total amount of contrast agent usually applied in mr imaging, no difference in tolerance between both classes could be demonstrated (oudkerk et al. ; shellock ). an estimated % of ecf agents (as for example in gadopentetate dimeglumine, size da) is cleared from the vascular space into the extravascular compartment on the initial passage through the capillaries. two agents in the group of ecf agents have to be mentioned separately. gadopentate dimeglumine (mul-tihance, bracco imaging) is an agent with a weak protein binding (about %) in human plasma. the bound fraction of the agent has a higher relaxivity than does the unbound fraction. in sum, the relaxivity of gadopentate dimeglumine is % higher as compared with gadopentetate dimeglumine at . t/ °c in plasma. the effect of higher relaxivity is highest at low field strengths (table . . ). the concentration of the contrast agent is . mol/l. gadopentate dimeglumine was primarily developed as a liver-specific mr imaging agent, and is currently approved both in the indication detection of focal liver lesions and in mr angiography. most of the injected dose of gadopentate is excreted unchanged in urine within h, although a fraction corresponding to . - . % of the injected dose is eliminated through the bile and recovered in the feces (spinazzi et al. ). the second particular ecf agent, gadobutrol (gadovist, bayer schering pharma) is approved in a higher concentration ( m) than all other available mr imaging contrast agents. in addition, gadobutrol has a higher relaxivity than most extracellular . m contrast agents on the market (table . . ). the higher concentration has revealed to be particularly useful for mr perfusion studies and mr angiography (tombach et al. ). stay within the intravascular space with no or only slow physiologic extravasation. the agents can be used for firstpass imaging and delayed blood-pool phase imaging. the prolonged imaging window allows more favorable image resolution and signal-to-noise ratio. the absence of early extravasation also improves the contrast-to-noise ratio. the pharmacokinetic properties of blood-pool agents are expected to be well suited to mr angiography and coronary angiography, perfusion imaging, and permeability imaging (detection of ischemia and tumor grading). currently, three types of blood-pool agents are being developed: gd compounds with a strong but reversible affinity to human proteins such as albumin macromolecular-bound gd complexes ultra small or very small super-paramagnetic particles of iron oxide (uspio and vsop) there are important differences between the three groups regarding pharmacokinetics in the body, i.e., distribution and elimination. gd compounds with a strong but reversible affinity to human proteins such as albumin exhibit prolonged plasma elimination half-life and increased relaxivity. the elimination is done by glomerular filtration of its unbound fraction. given that there is equilibrium between the bound and unbound fraction in the presence of albumin, the excreted molecules are immediately substituted due to dissociation of agent from the agent-albumin complex. two agents with affinities to albumin were developed and tested in clinical trials: gadofosveset (vasovist®, bayer schering pharma) - % bound in human plasma (lauffer et al. ) and gadocoletic acid (b / , bracco imaging), with a protein binding of approximately % in humans (cavagna et al. ; la noce et al. ) . currently, gadofosveset is the only blood-pool agent approved (for mra in europe). all other contrast agents with blood-pool characteristics are in clinical or in earlier phase development. gadofosveset is a stable gd diethylenetriaminepentaacetic acid (gd-dtpa) chelate substituted with a diphenylcyclohexylphosphate group. the mean plasma concentration at , and h after the . ± . . ± . . ± . . ± . . ± . . ± . bolus injection of . mmol/kg body weight dose were %, respectively % and % of the concentration reached min after injection. the mean half-life of the distribution phase (t / α) was . ± . h. relative to the reported clearance values of the non-protein-bound mri contrast agents, the clearance values of gadofosveset are markedly slower. gadofosveset is provided in a concentration of . mol/l and a dose of . mmol/kg body weight is recommended for mra (perrault et al. ) . as a further benefit, gd compounds with a strong, but reversible affinity to human proteins provide a long-lasting blood-pool effect even when small amounts of the substance leak out of the vasculature. the blood-pool effect persists because albumin remains highly concentrated in plasma while it shows a two-to three-times lower concentration in the extravascular space. thus, even when vasovist® leaks from the vasculature, the receptor-induced magnetization enhancement (rime) effect within the vascular spaces ensures that the signal enhancement in the blood dominates the mri contrast. in rabbits, enhancement with gadofosveset persisted at relatively constant levels from two minutes to up to h, whereas the enhancement of ecf had virtually disappeared within min (lauffer et al. ). the second blood-pool agent with binding to human serum albumin, gadocoletic acid has been tested in coronary mra (paetsch et al. ) . compared with gadofosveset, the slightly higher percentage of bounded agent may result in a lower percentage of extravasation and a further decreased elimination period. macromolecular gd-based blood-pool agents are large molecules with sizes between and kda. they are eliminated rapidly by glomerular filtration. due to their large size, they do not extravasate into the interstitial space. the two agents used in clinical trials were gadomer (schering) and p (laboratoires guerbet, aulnay-sous-bois). gadomer contains multiple gd molecules ( gd atoms, mr , ). p is a monodisperse monogadolinated macromolecular compound with mr . kda, based on a gadoterate meglumine core (port et al. ) . four hydrophilic arms account for its intravascular properties. in a preclinical study, p allowed acquisition of high-quality mr angiograms. image quality was rated as superior for p in the postbolus phase images compared with ecf agents. the intravascular properties lead to an excellent signal in the vasculature with limited background enhancement (ruehm et al. ). the first clinical use of uspio was done in specific parenchymal organ imaging due to the incorporation of uspio/spio into cells of the reticuloendothelial system of the liver, bone marrow, spleen, or lymphatic tissue. these particles produce a strong augmentation of the local magnetic field. predominant shortening of t and t * produces a loss of signal intensity on mr images. the agents that have been developed as blood-pool agents provide different characteristics with a predominating t effect and a prolonged intravascular residence time due to the small size of the particles. nc (clariscan, ge healthcare) was the first uspio tested for mra (taylor et al. : weishaupt et al. . it is a strictly intravascular agent with an oxidized starch coating and has an approximate diameter of nm. the half-life is - min, and it has shown to reduce blood t to below ms (wagenseil ). another iron oxide particle mr contrast agent in the phase of clinical development is vsop-c (ferupharm, teltow, germany). it is classified as a vsop with a core diameter of nm and a total diameter of . nm. vsop-c is coated with citrate. the relaxivities in water at . t are (t ) . and (t ) . l/[mmol*s]. the plasma elimination half-life at . mmol fe/kg was . ± . minutes in rats and . ± . minutes in pigs, resulting in a t relaxation time of plasma of < ms for min in pigs (wagner et al. ) . qualitative evaluation of image quality, contrast, and delineation of vessels showed that the results obtained with vsop-c at doses of . and . mmol fe/ kg was similar to those of gadopentetate dimeglumine at . and . mmol gd/kg. vsop-c is suitable for firstpass mra and thus, in addition to its blood-pool characteristics, allows for selective visualization of the arteries without interfering venous signal (schorr et al. ). another uspio is sh u c (supravist, bayer schering pharma), an optimized formulation of carboxydextran-coated ferucarbotran (resovist; bayer schering pharma), which was formerly identified as sh u a, with respect to t -weighted mr imaging. sh u c has a mean core particle size of about - nm and a mean hydrodynamic diameter of about nm in an aqueous environment. relaxivity measurements yielded an r of s - (mmol/l) - and an r of s - (mmol/l) - at °c and mhz in water (reimer et al. ). the efficacy of mri contrast agents is not just determined by their pharmacokinetic properties (distribution and time dependence of their concentration in the area of interest), but also by their magnetic properties, described by their t and t relaxivities. for all commercially available mri contrast agents, relaxivities are published and listed in the respective package inserts. however, the most commonly used field strength for relaxation measurements ( . t) is different from the currently most frequently used field strength of clinical mri instruments ( - t). rohrer et al. evaluated in a well-conducted and standardized phantom measurement study the t and t relaxivities of all currently commercially available mr contrast agents in water and in blood plasma at . , . , , and . t, as well as in whole blood at . t (rohrer et al. ) . they quantified significant dependencies of relaxivities on the field strength and solvents (table . . ). protein binding leads to both increased field strength and solvent dependencies and hence to significantly altered t relaxivity values at higher magnetic field strengths. mr contrast agents are in clinical use since , and a wide experience is reported. severe or acute reactions after single intravenous injection of gd-based ecf agents are rare. in two large multiple-year surveys including, respectively, , and more than , examinations, an incidence of acute adverse reactions between . and . % were reported (li et al. : murphy et al. . the severity of these adverse reactions was classified as mild ( - %), moderate ( - %), and severe ( - %). typical nonallergic adverse reactions include nausea, headache, taste perversion, or vomiting, and typical reactions resembling allergy include hives, diffuse erythema, skin irritation, or respiratory symptoms. the incidence of severe anaphylactoid reaction is very low and was reported to be between . and . % in the literature (de ridder et al. ; li et al. : murphy et al. . the reported life-threatening reactions resembling allergy were severe chest tightness, respiratory distress, and periorbital edema. known risk factors for the development of adverse reactions are prior adverse reactions to iodinated contrast media, prior reactions to a gd-based contrast agent, asthma, and history of drug/food allergy. concerning liver-specific contrast media, a higher percentage of associated adverse reactions were reported for mangafodipir trisodium ( - %) and ferumoxides ( %) (runge ). the recently approved bolus-injectable agent ferucarbotran (resovist, bayer schering pharma) has proven a better tolerance profile during the clinical development compared to ferumoxides. even bolus injections caused no cardiovascular side effects, lumbar back pain, or clinically relevant laboratory changes (reimer and balzer ). for the two approved gdbased agents gadopentate dimeglumine and gadoxetic acid, far fewer patients have been examined to date. according to the results of the clinical trials conducted for the approval of both agents, they are comparable to gdbased ecf agents in terms of safety (bluemke et al. ; halavaara et al. ; huppertz et al. ). post-marketing surveillance of gadopentate dimeglumine reporting approximately , doses revealed an overall adverse event incidence of < . %, with serious adverse eventss reported for < . % of patients (kirchin et al. ). in the class of blood-pool agents, only gadofosveset (bayer schering pharma) has been approved recently in some european countries. the tolerance of the agent must be estimated based on the clinical trials. based on these data, gadofosveset is well tolerated, and the incidence and profile of undesired side effects is very similar to ecf agents (goyen et al. ; petersein et al. ; rapp et al. ) . magnetic resonance contrast agents, particularly the gd-based agents, are extremely safe (niendorf et al. ) and lack in the usually applied diagnostic dosage the nephrotoxicity associated with iodinated contrast media. nevertheless, health care personnel should be aware of the (extremely uncommon) potential for severe anaphylactoid reactions in association with the use of mr contrast media and be prepared should complications arise. nephrogenic systemic fibrosis (nsf) is a rare disease occurring in renal insufficiency that only has been described since . in , a first report about a potential relationship with intravenous administration of gdbased mr contrast medium gadodiamide was published (us food and drug administration ). nsf appears to occur in patients with kidney failure, along with high levels of acid in body fluids (a condition known as metabolic acidosis) that is common in patients with kidney failure. the disease is characterized by skin changes that mimic progressive systemic sclerosis with a predilection for peripheral extremity involvement that can extend to the torso. however, unlike scleroderma, nsf spares the face and lacks the serologic markers of scleroderma. nsf may also result in fibrosis, or scarring, of body organs. diagnosis of nsf is done by looking at a sample of skin under a microscope. the risk of nsf in patients with advanced renal insufficiency does not suggest being the same for all gdbased contrast agents, because distinct physicochemical properties affect their stabilities and thus the release of free gd ions (bundesinstitut für arzneimittel und medizinprodukte [federal institute for drugs and medical devices] ). some gd-based contrast media are more likely than are others to release free gd + through a process called transmetallation, with endogenous ions from the body (thomsen et al. ). these agents have the largest amount of excess chelate. gadodiamide and gadoversetamide differ from other gd-based contrast media because of an excess of chelate and is more likely to release free gd + as compared with other agents. cyclic molecules offer better protection and binding to gd + , compared with linear molecules (thomsen et al. ). the non-linear, non-ionic chelates gadodiamide and gadoversetamide seem to be associated with the highest risk of nsf (broome et al. ; sadowski et al. ) . the recommendations to prevent development of nsf are nonspecific (us food and drug administration ): • gd-containing contrast agents, especially at high doses, should be used only if clearly necessary in patients with advanced kidney failure (those currently na not applicable requiring dialysis or with a glomerular filtration rate (gfr) = ml/min or less). • it may be prudent to institute prompt dialysis in patients with advanced kidney dysfunction who receive a gd contrast mra. although there are no data to determine the utility of dialysis to prevent or treat nsf in patients with decreased kidney function. the use of contrast agents in neuroimaging is an accepted standard for the assessment of pathological processes, which utilizes the extravasation of contrast agents through a compromised blood-brain or blood-spinal cord barrier. compared with contrast-enhanced ct, mr imaging with gd-based contrast agents is far more sensitive and depicts even subtle disruptions of the blood-brain barrier that are caused by a variety of noxious agents as, for example neoplastic or inflammatory processes and ischemic stress. moreover, mr contrast agents are increasingly used to evaluate brain perfusion in clinical practice for a variety of applications, including tumor characterization, stroke, and dementia. the contrast-enhanced brain perfusion mr examination is based on a magnetic susceptibility contrast phenomenon that occurs owing to the t and t * relaxation effects of rapidly intravenous bolus-injected contrast agents. the contrast agents in current use are the standard ecf gd chelates (table . . ). these extracellular agents show no appreciable differences in their enhancement properties and biologic behavior (akeson et al. ; brugieres et al. ; grossman et al. ; oudkerk et al. ; valk et al. ; yuh et al. ) . they equilibrate rapidly between the intra- and extracellular spaces of soft tissues and enter central nervous system lesions only at sites of damaged blood-brain barrier. the standard dose for mr imaging of the central nervous system is . mmol/kg body weight; however, it has been shown that a higher dose of gd chelate-based contrast agents may help reveal more subtle disease states of the bloodbrain barrier regardless whether caused by tumors or by inflammatory lesions (bastianello et al. ; haustein et al. ; yuh et al. ) . this raises the question, in how far gd contrast agents with a higher concentration as for example gadobutrol or agents with a higher relaxivity as for example gadopentate dimeglumine help to increase the sensitivity and accuracy to detect lesions as compared to standard gd chelates. for gadobutrol, no comparative studies to standard gd chelates exist up to now; however, based on smaller cohorts it can be assumed that the higher amount of gd, which can be achieved by the higher gd concentration, is of value for lesion detection and characterization (vogl et al. ) . moreover, based on animal experiments the amount of gd in gliomas was higher after injection of gadobutrol in comparison to gadopentetate dimeglumine although identical doses of gd per kilogram body weight were injected for both contrast agents (le duc et al. ) . gadopentate dimeglumine proved significantly superior tumor enhancement of intraaxial enhancing primary and secondary brain tumors at a dosage of . mmol/kg body weight as compared with the same dosage of gadopentetate dimeglumine (knopp et al. ) . similar results were also obtained in comparison of gadopentate dimeglumine with other contrast agents as well as in special populations as for example in pediatric patients (colismo et al. (colismo et al. , (colismo et al. , . the increased contrast enhancement resulted also in an increased number of detected brain metastases. dynamic susceptibility-weighted (dsc) contrast agent-enhanced mr imaging is increasingly used for the assessment of cerebral perfusion in many different clinical settings, such as ischemic stroke (parsons et al. ) , neurovascular diseases (doerfler et al. ), brain tumors (essig et al. ) , and neurodegenerative disorders (bozzao et al. ) . unlike mr angiography, which depicts the blood flow within larger vessels, perfusion-weighted mr techniques are sensitive to perfusion on the level of the capillaries. the technique is based on the intravenous injection of a t *-relaxing contrast agent and subsequent bolus tracking using a fast susceptibility-weighted imaging sequence. after converting voxel signal into concentration values, parametric maps of regional cerebral blood volume (rcbv) and blood flow (rcbf) can be calculated by unfolding tissue concentration curves and the concentration curve of the feeding artery. the contrast agents used for dynamic susceptibility-weighted mr perfusion are usually standard gd chelates; however, the dosages of gd per kilogram of body weight as well as the value of higher concentrated agents have been widely discussed. during the first pass of the gd chelate, the high intravascular concentration of gd causes the t * effects, which can be measured by rapid imaging techniques. the length and the peak concentration of the bolus seem to have influence on the resulting measured signal with a highly concentrated small bolus of contrast agent being advantageous for mr brain perfusion imaging (essig et al. ; heiland et al. ) . in between the standard gd chelates, no notably different behavior of the available agents has been published up to now. the recommended dose for dsc perfusion mri is in the range of . - . mmol/kg body weight, with most authors preferring a value of . , because the volume of the bolus gets too high when higher dosages are applied (bruening et al. ) . therefore, the use of higher concentrated contrast agents or agents with higher relaxivity are also interesting for cerebral perfusion mri. again, studies were able to demonstrate the value of the m gabobutrol and gadopentate dimeglumine. tombach et al. ( ) showed that m gadobutrol resulted in a significantly improved quality of the perfusion examination in comparison to . m gadobutrol at the same dosage of . mmol/kg body weight. the results were explained by the sharper, more concentrated bolus, which could be achieved due to the smaller injection volume. essig et al. directly compared m gadobutrol and . m gadopentate dimeglumine at . t with a similar dosage of . mmol/ kg body weight and found no significant differences between the two agents (essig ) . the benefit of a double dose of . mmol was observed only as a trend; however, it was not considered to be of clinical relevance. similar results in a comparison between the two agents were recently obtained also on a -t system (thilmann et al. ) . for both agents sufficient high-quality perfusion examinations can be achieved with an acceptable injection volume, which is helpful for their clinical application in daily practice and can be considered superior to standard gd chelates (essig et al. ; thiman et al. ; tombach et al. ) . in a limited number of proof-of-concept studies, uspio were also used in neuroimaging (corot et al. ; manniger et al. ) . the long blood-circulating time and the progressive macrophage uptake in inflammatory tissues of uspios are two properties of major importance for pathologic tissue characterization. in the human carotid artery uspio, accumulation in activated macrophages induced a focal drop in signal intensity compared with unenhanced mri. the uspio signal alterations observed in ischemic areas of stroke patients is probably related to the visualization of inflammatory macrophage recruitment into human brain infarction, since animal experiments in such models demonstrated the internalization of uspio into the macrophages localized in these areas. in brain tumors, uspio particles that do not pass the ruptured bloodbrain barrier at early times post injection can be used to assess tumoral microvascular heterogeneity. twenty-four hours after injection, when the cellular phase of uspio takes place, the uspio tumoral contrast enhancement was higher in high-grade than in low-grade tumors. several experimental studies and a pilot multiple sclerosis clinical trial in patients have shown that uspio contrast agents can reveal the presence of inflammatory lesions related to multiple sclerosis. the enhancement with uspio does not completely overlap with the gd-chelate enhancement. during the last few years magnetic resonance angiography (mra) has been established as a non-invasive alternative to conventional x-ray angiography in the diagnosis of arteriosclerotic and other vascular diseases (meany et al. ; meany ) . with the exception of imaging intracerebral vessels (gibbs et al. ; ozsarlak et al. ), contrast-enhanced techniques have revealed superiority over non-contrast-enhanced techniques as the time-of-flight (tof-mra) or phase-contrast (pc mra) technique (sharafuddin et al. ) . the main advantages over unenhanced techniques are the possibilities to acquire larger volumes, allowing, e.g., demonstration of the carotid artery from its origin to the intracranial portion, shorter acquisition times, and reduced sensibility to flow artifacts. contrast-enhanced mr angiography can be performed during the first-pass of a contrast agent, preferably in breath-hold technique, after rapid bolus injection or during steady-state conditions after injection of vascular specific blood-pool agents. most experiences were reported for first-pass mra after injection of ecf contrast agents. the demands on the agent are a high influence on the signal intensity on blood after injection and the possibility of fast and compact bolus injection. the most commonly applied group of contrast agents are . molar ecf. in the last years, two novel ecf agents with innovative properties were used for mra. the first one, the . m contrast agent gadopentate dimeglumine offers a higher t relaxivity. in studies in which gadopentate dimeglumine is compared at equal dose with other gd-based mr contrast agents without relevant protein binding in plasma, gadopentate dimeglumine has consistently shown significantly better quantitative and qualitative performance (goyen and debatin ) . even at lower doses compared with gadopentetate dimeglumine injected at a dose of . mmol/kg body weight, the greater relaxivity of gadopentate dimeglumine provides higher intravascular signal and signal-to-noise ratio (pediconi et al. ) . thus, gadopentate dimeglumine can be considered to have a very favorable risk-benefit ratio for mra. the second one, gadobutrol is available in m concentration. in combination with a higher relaxivity compared to other ecf agents, the agent has revealed in quantitative evaluations a significant increase in signalto-noise and contrast-to-noise ratios in comparison to gadopentetate dimeglumine in pelvic mra and in whole body mra (goyen et al. (goyen et al. , . better delineation of arterial morphology was reported especially for small vessels, but no statistically significant difference in image quality could be seen. two different options for injection have been described: reduction of the injection rate by % compared to injection protocols using . m ecf (equimolar dosing) or reduction of the injection time by %. the equimolar dosing mainly exploits the higher relaxivity potential of gadobutrol. in this case, the injection duration is identical to a corresponding protocol using a . m contrast agent a similar bolus geometry, and contrast delivery in the roi is obtained (e.g., in a -kg-weighing patient ml of gadobutrol are injected at ml/s compared with ml of gadopentetate dimeglumine injected fig. . . whole-body mra of a healthy volunteer after bolus injection of gadofosveset ( . mmol/kg body weight). firstpass and steady-state acquisition acquired immediately (a) and min (b) after injection of the contrast agent. t -weighted d gradient recalled echo sequence (tr/te/α . / . / , spatial resolution . × × . mm). first-pass imaging depicts exclusively the arteries. steady-state imaging shows an enhancement of both arteries and veins. due to the higher concentration of the contrast agent during first-pass imaging the absolute level of enhancement is higher (a) at ml/s). hence, well-known protocols can be adopted with good results. the second option keeps the injection speed unchanged in comparison to the . m agent protocol, resulting in shortening of the initial bolus duration by a factor of two (fink et al. ). the philosophy is to use a very compact, high-relaxivity bolus and to fully exploit the potential of m gadobutrol. this approach is particularly recommended in conjunction with very fast acquisition techniques, e.g., time-resolved (often referred to as d) mra. although the effective bolus geometry in the respective roi is broadened, dependent on individual physiology and mainly influenced by the lung passage, this approach requires higher demands on precise bolus timing and is recommended to users with advanced mra experience and ultrafast imaging equipment. in addition, a further approach was reported by reducing the amount of contrast agent by a factor of two in abdominal mra (vosshenrich et al. ) . the injection speed was kept constant in comparison to a . m agent protocol, resulting in very short total bolus duration. vosshenrich et al. used an amount of . mmol/kg body weight. they compared the examinations qualitatively and quantitatively to exams acquired after injection of gadopentetate dimeglumine ( . mmol/kg), and concluded that for mra of the hepatic arteries and the portal veins, gadobutrol can be used at half the dosage as recommended for a standard . m contrast agent. the concept of contrast-enhanced mra based on ecf agents has some limitations. the primary problem is the rapid extravasation of the contrast agents limiting acquisition time and therefore spatial resolution as well as contrast-to-noise-ratio. to improve spatial resolution it is necessary to prolong imaging time. intravascular contrast agents are able to overcome the restrictions of spatial resolution. the longer acquisition period can be used to decrease voxel size, to repeat measurements, or to trigger acquisitions by ecg and/or respiratory gating. the second limitation of currently used mra is the quantification of artery stenoses, which still seems to be inferior to invasive catheter angiography. the cause is the inferior spatial resolution in mra using ecf agents, with which the increase of spatial resolution is limited by the acquisition time during first-pass (arterial phase). with intravascular contrast agents, a longer data acquisition during the distribution phase is possible. the spatial resolution can be increased on a similar level compared with catheter angiography and, therefore, the accuracy of stenosis quantification is significantly increased. optimally, a blood-pool agent permits a long acquisition window including first-pass mra as well as the possibility of separate imaging of arteries and veins by timing the injection and data acquisition. gadofosveset, the first mr blood-pool agent approved for clinical use, permits both a high-resolution approach with a long acquisition windows and first-pass contrast-enhanced mra (fig. . . ). the approval was based on the data of clinical trials in all different types of arterial vessels including high-flow vessels with large diameter (e.g., the pelvic arteries), low-flow vessels (e.g., foot arteries), and high-flow vessels with a small diameter (e.g., the renal arteries). ecf contrast agents are widely used in mr imaging of soft-tissue lesions. the enhancement in either inflammatory or neoplastic lesions makes their use inevitable for the detection and characterization of soft tissue lesions. relevant anatomical sites that in the daily clinical practice are subject to mr imaging are the female breast and the soft tissue related to the musculoskeletal system. for the female breast, mr imaging with extracellular contrast agents (mr mammography) is nowadays widely used for the detection and for the characterization of unclear breast tumors morris et al. ) . the histopathological basis of the different enhancement patterns in breast masses is not yet fully understood; however, it is well known that angiogenesis with the formation of new vessels, is an important aspect (knopp et al. ). the amount of angiogenesis and contrast agent extravasation is considered different for several benign and malignant lesions; however, the visible phenomenon of different enhancement is usually too small to be analyzed only visually. the discrete changes of contrast-agent enhancement are usually evaluated by using a semiquantitative evaluation with region-of-interest measurements at different time-points (kuhl et al. ) . the thereby achieved enhancement kinetics, as represented by the time-signal intensity curves, differ significantly for benign and malignant enhancing lesions, and are used as an aid in differential diagnosis. usually four to six measurements with an interval of - min are applied in the daily clinical practice (kuhl et al. ; pediconi et al. ) . a recently published study showed that the temporal resolution for the assessment of time-signal intensity curves is not as critical as the spatial resolution; therefore, the recommendations for the dynamic postcontrast mr imaging tend toward a -min interval with a high spatial resolution (e.g., full imaging matrix) (kuhl et al. ) . a more detailed evaluation of perfusion parameters needs, however, a very high temporal resolution in a range of - s. first results for the differentiation of unclear breast tumors in an investigational setting are very promising; however, due to the high temporal resolution only single slices can be measured, which is not feasible for daily practice (brix et al. ) . usually standard gd chelates at a dose of . mmol/ kg body weight are used for contrastenhanced mr mammography. first results indicate that the use of the high-relaxivity mr contrast agent gadopentate dimeglumine in the same dosage can achieve a superior detection and identification of malignant breast lesions at mr imaging as compared with gadopentetate dimeglumine. however, up to now gadopentate dimeglumine is not officially approved for this indication. there are also first approaches to perform mr mammography with blood-pool contrast agents. a major limitation of ecf is that they extravasate nonselectively from the vasculature into the interstitium of both normal and pathological tissues in the breast. it is hypothesized that the degree of microvascular endothelial disruption inherent to cancer vessels with the resulting extravasation of macromolecular contrast agents may predict tumor aggressiveness and tumor grade more accurately that with standard gd chelates (daldrup-link and brasch ; daldrup-link et al. ) . first results with uspio have shown an improved characterization of unclear breast tumors at the expense of tumor enhancement, which is important for tumor detection. an interesting approach is also the use of small molecular gd chelates, which bind reversibly to plasma proteins as for example gadofosveset. this might allow for a sensitivity and specificity due to the presence of small and large molecules (daldrup-link et al. ) . the assessment of microvascular changes in experimental breast tumors seem not to be reliably depicted with theses agents in contrast to the macromolecular albumin-gd-(dtpa) (daldrup-link et al. ; turetscheck et al. ) . however, clinical experience on breast tumors does not exist now. although potential diagnostic applications have been investigated with various sized albumin-gd-dtpa, this contrast agent is considered a poor candidate for development as a clinical drug due to slow and incomplete elimination and a potentially immunologic toxicity (daldrup-link and brasch ) . for soft-tissue or bone lesions in the musculoskeletal system, the application of extracellular gd-contrast agents has become a clinical standard for characterization, staging of the local extent, biopsy planning, and the therapy monitoring (verstraete and lang ). the basic principle of contrast-enhanced imaging is as described above the distribution of the gd chelates in the intravascular space, showing enhancement in tumors with dense vascularity and neoangiogenesis as well as distribution into the extracellular space. for these clinical standard applications, there seem to be no relevant differences in the diagnostic performance between the different extracellular gd chelates, similar to neuroimaging. the role of gd-enhanced mri for exact tissue characterization is still very limited. a differential diagnosis in between different sarcomas, nerve sheath tumors, or other mesenchymal tumors is not possible based on the contrast agent behavior up to know. the differentiation between benign and malignant tumors is also often very limited, even with tools like dynamic time-resolved contrast-enhanced mri (verstraete and lange ). nevertheless, surrogate parameters for angiogenesis like histological tumor-vessel density can be correlated with this method (van dijke et al. ) . one major limitation is the extravasation of standard gd chelates through the intact endothelium so that pathological extravasation in tumor vessels disrupted endothelium cannot be separated from the physiological distribution. therefore, the experimental studies mainly focus on contrast agents which show no or only minor physiological extravasation. different studies-mainly in the animal-experimental stage-were able to show that characterization in benign and malignant tumors, evaluation of angiogenesis, and even tumor grading is feasible with blood-pool contrast agents (daldrup et al. ; kobayashi et al. ; preda et al. a, b) . there have been promising results with albumin-gd-(dtpa); however, as mentioned above this agent is unlikely to be available for diagnostic use in humans (daldrup et al. ; daldrup-link and brasch ) . similar to breast tumors, uspio have also been utilized for the evaluation of perfusion and for the characterization of soft-tissue tumors in the past (bentzen et al. ). the basic group of contrast agents for hepatobiliary imaging is the group of ecf gd-based contrast agents. however, there are also tissue-specific contrast agents available, which allow for an increased detection and characterization of focal and diffuse liver disease. liver-specific contrast agents can be divided into two groups: on the one hand, there are iron-oxide particles (spio, or superparamagnetic particles of iron oxide), which are targeted to the reticuloendothelial system (res) to the so-called kupffer cells. these agents cause a signal decrease in t /t *-weighted sequences by inducing local inhomogeneities of the magnetic field. on the other hand, there is the group of hepatobiliary contrast agents, which are targeted directly to the hepatocyte and are excreted via the bile. these agents cause signal increase in t -weigthed sequences by shortening of the t relaxation time. in europe there are five different liver specific contrast agents available on the market (table . . ). the basic principle behind spio is the fact, that there are usually no kupffer cells in malignant liver tumors, in contrast to the normal liver parenchyma and to solid benign liver lesions. therefore, in the liver specific phase, which starts for ferucarbotran after about ten min and for ferumoxide after about min, high contrast is produced in between malignant liver lesions and normal liver parenchyma. due to the signal loss in normal liver parenchyma the malignant lesions are contrasted as hyperintense lesions in t *-weighted and t -weighted sequences against the dark liver parenchyma. the first spio on the market in europe has been ferumoxide (endorem®, guerbet, aulnay sous bois, france). since in most european countries and in asia the bolus-injectable ferucarbotran (resovist®, bayer schering pharma ag, berlin, germany) is available. with regard to the basic principle of imaging there is no difference between the two agents; however, direct comparative studies have not been performed so far. the most striking advantage of ferucarbotran is the better workflow due to the possibility to inject ferucarbotran as a bolus. bolus-applicability is possible for ferucarbotran due to the different particle sizes and the coating of the particles; this is also responsible for the fewer rate of side effects (especially fewer events of severe back pain), which are encountered with ferucarbotran. in earlier clinical trials the effects of spio particles were evaluated almost exclusively on t -weighted fse and t * -weighted gre sequences, whereas usually not much attention was paid to the t -effects. however, the effect of spio particles on proton relaxation is not confined to t and t * . they also influence t relaxivity with increased signal intensity on t -weighted gre sequences at low concentrations (chambon et al. ). this gave raise to the hope, that with the bolus-injectable ferucarbotran vascularity of focal liver lesions could be depicted; however, investigations have been shown, that the ferucarbotran-enhanced early dynamic examination with t -weighted sequences does not permit to evaluate lesion vascularity, since (with exception of the cotton-wool paddling of hemangioma) the expected enhancement pattern cannot be seen with reliability (zech et al. ) . with regard to the t /t * effects there might be differences between both agents, which could be related to the different average particle size of both agents (approximately nm for ferumoxide and nm for ferucarbotran). with help of spio-enhanced mr an accurate liver lesion detection can be achieved. there have been several studies comparing spio to ct during arterial portography (ctap), which has been considered as best practice and reference standard. these studies showed detection rates of more than % (ba-ssalamah et al. ; vogl et al. ) . in comparison to ctap this detection rate was comparable; moreover, spio-enhanced mr is more specific than ctap, in which false positive lesions are encountered frequently. the above cited references investigated spio-enhance mr in a mixed collective of patients; publications focusing on the cirrhotic liver showed, that in these patients the combination of spio and extracellular gd-contrast agents have to be considered as the gold-standard for lesion detection (ward et al. ) . with regard to lesion characterization spio particles can be of help for the differential diagnosis of focal liver lesions based on the cellular composition and function of the different lesions (or rather based on different kuppfer cell density and function). when the same mr sequence is acquired pre-contrast and after a definite time interval, then the signal loss in normal liver parenchyma and in different focal liver lesions can be quantitatively evaluated. this is helpful for the differentiation of benign and malignant lesions; when a threshold of % signal loss is chosen, than lesions with less signal loss are of a malignant nature with over % sensitivity and specificity (namkung and zech et al. ). however, the sequence must have the same parameters (including the same acceleration in case parallel imaging is used), since application of parallel imaging makes systematic changes in the spread of image-noise (zech et al. ). the second important group is the group of hepatobiliary contrast agents. the basic principle behind this group of contrast agents is the specific uptake directly into the hepatocyte. since the agents all shorten the t relaxation times, they cause a signal increase in normal liver parenchyma and in solid benign lesions, whereas in malignant lesions like metastases no specific uptake can be seen. these lesions contrast as hypointense lesions against the bright liver parenchyma. approved agents in europe are the manganese-based agent mangafodipir trisodium (teslascan®, ge healthcare), and the gd-based agents gadopentate dimeglumine and gadoxetic acid (primovist®, bayer schering pharma). mangafodipir has the drawback that it must not be administered as a bolus, but only as a short infusion; therefore, dynamic studies are not possible with mangafodipir. however, the liver specificity is high and the high uptake in normal liver parenchyma enables imaging of, e.g., metastases with high contrast to the surrounding liver parenchyma. gadopentate dimeglumine and gadoxetic acid are injectable as boluses. with both contrast agents, a valid early dynamic examination is feasible, allowing differentiation of lesions with regard to their hyper-or hypovascularity (huppertz et al. ; petersein et al. b ). due to the lower liver specificity of gadopentate dimeglumine, the imaging time-point of the liver-specific phase starts about min after injection; whereas gadoxetic acid allows for imaging at min after injection. this can be of value with regard to the workflow in the mr department. similar to the situation at spio agents, direct comparative studies between the agents have not been published yet; therefore, the following remarks again hold true for all hepatobiliary contrast agents. however, with regard to lesion characterization, only gadoxetic acid has the official approval to be used for this indication. all three hepatobiliary agents are approved for lesion detection. in comparison to spio agents, the potential advantage of hepatobilary agents is the fact that t -weighted sequences usually can be performed with less acquisition time, less artifacts, and substantial higher spatial resolution. this holds true especially for t -weighted d-gre sequences derived from mr angiography sequences as, for example, vibe, or volumetric interpolated breathhold examination (siemens medical solutions, erlangen, germany), or lava, for liver acquisition with volume acceleration (ge healthcare). in how far these high-resolution sequences with a slice thickness of usually below mm allow further increasing the detection of small (< cm) malignant lesions has to be investigated in the future. the present date for the hepatobiliary agents was acquired mostly with conventional d-gre sequences and a slice thickness between and mm; however even in this setting the detection of lesions < cm was improved in comparison to baseline mri and spiral ct (bartolozzi et al. ; gehl et al. ; huppertz et al. ; peterseing et al. b ). an earlier trial showed slight superiority of spio-enhanced mri versus hepatobiliary mri in detection of liver metastases; however, the potential advantaged of modern t -weighted d gre sequences were not available for this evaluation (del frate et al. ) . a recent evaluation showed comparable detection rates between these two contrast agent groups (kim et al. ) . for the diagnosis of solid benign liver lesions (as focal nodular hyperplasia [fnh] and hepatocellular adenoma), the basis is still the extracellular contrast agent behavior with flush-like, mostly homogenous arterial hypervascularization and fast, but only faint washout, being in portovenous and equilibrium phase mostly slightly hyperintense (and not hypointense in contrast to the strong washout in malignant lesions). contrast agents used for patients with suspected solid benign lesions must enable that this information can be acquired. therefore, spio agents or mangafodipir alone are not sufficient for this indication; however, especially spio can contribute to the diagnosis of these lesions in combination with extracellular contrast agents, which have to show the abovementioned enhancement pattern. with spio agents solid benign lesions typically show liver-specific uptake of the substance in the range of normal liver parenchyma, thereby allowing the differentiation from malignant lesions as for example hepatocellular carcinoma (hcc). with regard to the differential diagnosis between fnh and adenoma, results in a limited number of patients indicated that the quantification of iron uptake can be helpful for this issue, because in our cohort, adenoma showed stronger iron uptake in comparison to fnh, with only minimal overlap of the percentage sig-nal intensity loss (psil) measured in a t -weighted fse sequence with fat-sat (namkung and zech et al. ). with the hepatobiliary contrast agents gadopentate dimeglumine and gadoxetic acid, diagnosis of fnh and adenoma is also possible on the one hand based on the extracellular contrast phenomena, on the other based on the liver specific uptake of the agents into these lesions (grazioli et al. (grazioli et al. , huppertz et al. ) . there is also valid data indicating that the differentiation between fnh and adenoma is feasible with hepatobiliary contrast agents. therefore, with the bolus-injectable agents of this class a time- and presumably cost-effective diagnosis can be achieved (fig. . . ) . in patients with extrahepatic malignoma, confirmation or ruling out of liver metastasis is often crucial for the therapeutic management. moreover, the exact staging of metastatic disease of the liver is getting more and more important, since sophisticated, stage-adapted therapeutic regimens with different options from atypical liver resection over local ablative minimally invasive treatment (e.g., radiofrequency ablation) up to extended liver resection exist. therefore, contrast agents used for this indication have to provide an excellent detection rate for focal liver lesions; however, the characterization of these lesions is also important, especially the differential diagnosis of small cystic metastases and small benign cysts or atypical hemangioma. after injection of extracellular contrast agents, the vascularity can be differentiated in hypo-und hypervascular metastases. hypovascular metastases appear as hypointense lesions in the portovenous phase, whereas hypervascular metastases appear as hyperintense lesions in the arterial-dominant phase. in contrast to the enhancement pattern of benign lesions, the nodular "cotton-wool"-like paddling in hemangioma or the homogeneous enhancement of fnh or adenoma metastases typically show a heterogeneous, ring-like enhancement with strong washout in the portovenous and equilibrium phase, resulting in first hyper-, and then hypointense lesions. however, in very small lesions the morphology of vascularization between the different en- fig. . . mr images of a -year-old male patient with a formerly unclear liver lesion. the primary mr examination (upper row) with gadopentetate dimeglumine and ferucarbotran shows a lesion (arrow) with strong arterial enhancement in the gd-enhanced t -weighted d-gre sequence (a) (tr, . ms; te, . ms; flip angle °) and ongoing washout in portovenous and equilibrium phase (not shown). the t -weighted fse sequence with fat-saturation min after application of ferucarbotran (b) depicts the lesion as nearly liver isointense. the calculated percentage iron uptake compared to the pre-contrast t -weighted sequence was about %, showing the benignity of the lesion. based on these imaging features and the lobulated margins as well as the central scar, the diagnosis of a fnh was made. the follow-up study (lower row) was performed with gadoxetic acid after a single bolus injection. in the t -weighted d-gre sequence (same parameters as above) in the arterial phase (c), the same enhancement characteristics as the in prior study can be delineated. in the delayed t -weighted d-gre sequence (d), the presence of hepatocytes is proven due to the liver-specific enhancement. note the excellent delineation of the central scar in the delayed images. in contrast to the upper row, the followup study gave information about vascularity and tissue composition, with a single contrast agent injection only tities is getting more and more similar, so that the present or missing liver-specific uptake is an additional criterion for differentiation. several publications have shown that detection of metastasis is feasible with the highest accuracy with help of liver-specific contrast agents, regardless if spio or hepatobiliary. according to the literature for detection of liver metastases, all liver-specific agents can be used with a very high diagnostic reliability and superiority to merely extracellular mri or spiral ct (bartolozzi et al. ; ba-ssalamah et al. ; del frate et al. ; gehl et al. ; huppertz et al. ; kim et al. ; petersein et al. b; vogl et al. ) . a difficult situation is liver imaging in cirrhotic liver. it is known that extracellular agents are helpful for detection and characterization of hcc nodules, the sensitivity is with t -weighted d-gre sequences and % specificity (burrel et al. ) . moreover, for diagnosis a hcc according to the accepted guidelines, hypervascularity has to be demonstrated. therefore, a valid early dynamic phase is a mandatory part for imaging in the cirrhotic liver. because regenerative nodules, which can be found frequently in the cirrhotic liver, also can show hypervascularity differentiation between these nodules and hcc nodules, it is a crucial issue for the management of patients suffering from liver cirrhosis. this is the reason that liver-specific contrast agents play an important role for imaging of the cirrhotic liver. it has been demonstrated that hcc shows no relevant uptake of spio particles in contrast to benign regenerative nodules (bhartia et al. ; imai et al. ; ward et al. ; namkung and zech et al. ). since in the cirrhotic liver fibrotic areas are present frequently, spio alone are not sufficient to evaluate the cirrhotic liver. a reasonable approach for the diagnosis of hcc based on imaging alone is the correlation of hypervascularity and missing or at least decreased iron uptake (bhartia et al. ; ward et al. ) . however, there is also an indefinite area of overlapping phenomena between dysplastic nodules and well-differentiated hcc, which is the reason for false negative findings-meaning well-differentiated hcc with substantial iron uptake (imai et al. ) . with regard to lesion detection, the availability of high-resolution mr sequences gives advantages for gd-enhanced arterial-phase imaging alone (kwak et al. ) or in combination with spio as double contrast (ward et al. ) . imaging with hepatobiliary contrast agents is considered as inferior in comparison to spio agents in the cirrhotic liver, mainly due to substantial overlapping in the liver-specific uptake between well-differentiated hcc and regenerative nodules. the assessment of lymph node affections by extranodal tissue, i.e., lymph node metastasis, is currently based on morphologic parameters including, lymph node size, shape, irregular border, and signal intensity inhomogeneities (brown et al. ; zerhouni et al. ) . for all parameters, no clear cut-off values or cut-off characteristics can be defined. the definition of a cut-off value in individual studies is the result of finding a compromise between sensitivity and specificity (e.g., larger values around mm give a high specificity but low sensitivity, whereas the reverse of low specificity and high sensitivity is observed when smaller diameter < mm are defined). the use of unspecific gd-based extracellular contrast agents has not revealed to overcome this limitation. lymphotropic mr contrast agents were, therefore, developed to increase the diagnostic accuracy of positive lymph node involvement. currently, none of these agents is approved for clinical use, and the experience with different formulations is limited to clinical studies. the most frequently used agents are uspios. they are administered intravenously and, as a result of their small diameter and their electrical neutrality, pass the first lymphatic barriers, i.e., the liver and the spleen. in the lymphatic nodes, they are phagocytosed by local macrophages. in healthy lymphatic tissue, the local concentration of iron oxides is resulting in a significant decrease of t and t * relaxation, resulting in a marked decrease of signal in t - and t *-weighted sequences. in contrast, metastatic tissue replacing the lymphatic tissue shows no relevant uptake of uspio, and no relevant change in signal intensity can be observed. gradient-recalled echo t -weighted sequences are considered the most accurate to detect the signal loss in nonmetastatic nodes. the application of uspios offers not only the possibility to differentiate between tumorfree, reactive (koh et al. ) and tumor-positive lymph nodes, but enables to depict micrometastasis in case sequences when high spatial resolutions are used (harisinghani et al. ) . one representative of the group of lymph node-specific uspio, ferumoxtran- (sinerem ® guerbet, paris, france) is infused after dilution. the recommended dose is . mg fe/kg body weight. the optimal time-point for postcontrast imaging is - h after application. during their clinical development, uspios have shown to be effective in staging lymph nodes of patients with various primary malignancies (deserno et al. ; jager et al. ; michel et al. ; nguyen et al. ) . the usual way for diagnosis is to perform an initial precontrast scan and to compare the images with postcontrast images acquired - h after infusion of uspios for signal changes between both time-points. the type, onset, and intensity of adverse events after application of ferumoxtran- was evaluated in phase iii studies and seems to be similar to those related to infusion of ferumoxides (anzai et al. ) . in patients with esophageal or gastric cancer, uspios revealed a sensitivity of % and specificity between . and . % (diagnostic accuracy between . and . %) for diagnosis of metastatic nodes (nishimura et al. ; tatsumi et al. ) . in patients with carcinomas of the upper aerodigestive tract, application of ferumoxtran- has shown to increase the sensitivity from to % while maintaining a specificity of . %, compared with precontrast imaging (curvo-semedo et al. ). in patients with rectum cancer, uspios have shown wellpredictable signal characteristics in normal and reactive lymph nodes, and were able to differentiate the latter from malignant lymph nodes (koh et al. ) . dissimilarly, keller et al. studied females with uterine carcinoma and were able to show high specificity, but a low sensitivity for metastatic lymph nodes; mainly micro-metastases around mm diameter were missed. a possible way to further improve the diagnostic accuracy for detection of small positive lymph nodes could be the use of -t high magnetic field strength scanner resulting in a lower spatial resolution (heesakkers et al. ) . different results were published concerning the necessity of both pre-and postcontrast images. whereas the majority of clinical publications using uspio for lymph node imaging used both pre-and postcontrast images and stets et al. ( ) were able to statistically prove the advantage of pre- and postcontrast studies, harisinghani et al. ( ) were showed that on ferumoxtran- -enhanced mr lymphangiography, contrast-enhanced images alone may be sufficient for lymph node characterization. however, a certain level of interpretation experience seems to be required before contrast-enhanced images can be used alone. both uspios (rogers et al. ) and spios (maza et al. ) can alternatively be administered with subcutaneous or submucosal injection. this application route is able to identify sentinel lymph nodes and lymphatic drainage patterns (fig. . . ) . additionally, high diagnostic accuracy of interstitial mr lymphography using blood-pool gd-based agents has been described (herborn et al. (herborn et al. , .using different macromolecular agents or gd-based agents with high protein binding in animal models, herborn et al. were able to show that the differentiation of tumor-bearing lymph nodes from reactive inflammatory and normal nodes based on a contrast uptake pattern assessed qualitatively as well as quantitatively is possible. in difference to the intravenous administration, subcutaneous injection gives the possibility to acquire the mr images as early as some min after application. the use of gd-based non-lymphotropic blood-pool agents induced a relatively short and inhomogeneous lymph node enhancement (misselwitz et al. ) . with the aim to become more specific, a new generation of lymphotropic t contrast agents was developed and tested in animal models after subcutaneous injection. these perfluorinated gd chelates were able to visualize fine lymphatic vasculature, even the thoracic duct in animal models (staatz et al. ). bowel mr contrast agents are generally classified as either positive (bright lumen) or negative (dark lumen) agents. in addition to enteral contrast agents especially approved for mr imaging, several existing pharmaceutical agents, such as methyl cellulose, mannitol, and polyethylene glycol preparations, licensed for other enteric application than mri, have also been exploited. fig. . . lymphatic drainage of a mucosal melanoma in the left nasal cavity to a lymph node located in the left submandibular region. mr images (upper row) and spect images (lower row). a concordant alignment of hot spots caused by the skin markers on the spect images with the vitamin e caps on the mr images (yellow arrows). b accurate sentinel lymph node localization (blue arrow) after subcutaneous injection of ferucarbotran (mg fe/kg body weight). t *-weighted d gradient-recalled echo sequence tr /te /a / / . homogeneous signal intensity decrease in the depicted lymph node (arrow) indicates normal lymphatic tissue and, thereby, metastatic involvement can be ruled out (maza et al. ) the specific demands for enteral contrast media include: for enteral and rectal application a special formulation of gadopentetate dimeglumine was developed (magnevist enteral, schering). the agent contains a total of g mannitol/l to prevent the absorption of the fluid simultaneously introduced in the gi tract, thus allowing homogeneous filling, distension, and constant gd concentration during the entire examination period. in the early development, an increase in diagnostic accuracy in examinations of the pancreas in the diagnostics of abdominal lymphoma and in pelvic mr imaging was shown (claussen et al. ). negative agents provide desirable contrast to those pathologic processes that are signal intense. they have been shown to improve the quality of images obtained by techniques such as mr cholangiopancreaticography (mrcp) and mr urography by eliminating unwanted signal from fluid-containing adjacent bowel loops, thus allowing better visualization of the pancreatic/biliary ducts and the urinary tract. an alternative to oral spios was described by using ordinary pineapple juice. it was demonstrated that pineapple juice decreased t signal intensity on a standard mrcp sequence to a similar degree than a commercially available negative contrast agent (ferumoxsil) (riordan et al. ) . oral spio preparations usually contain larger particles than injectable agents do. in europe, two spio preparations with the inn code ferumoxsil are approved for oral use: lumirem (laboratoires guerbet, france) with a particle size of nm, and (oral magnetic particles) abdoscan (ge healthcare) with a particle size of nm. they are coated with a non-biodegradable and insoluble matrix (siloxane for lumirem and polystyrene for abdoscan), and suspended in viscosity-increasing agents (usually based on ordinary food additives, such as starch and cellulose). these preparations can prevent the ingested iron from being absorbed, particles from aggregating, and improve homogeneous contrast distribution throughout the bowel. if spio particle aggregating occurs, magnetic susceptibility artifact may result, especially when high magnetic field strength and gradientecho pulse sequence are used (wang et al. ) . lumirem is composed of crystals of approximately nm; the hydrodynamic diameter is approximately nm (debatin and patak ) . the recommended concentration is . - . mmol fe/l. oral spio are administered over - min, with a volume of ml for contrast enhancement of the whole abdomen, and ml for imaging of the upper abdomen. oral spio suspensions are well tolerated by the patients (haldemann et al. ) ; the iron is not absorbed and the intestinal mucosal membrane is not irritated. combination of gd-enhanced t -weighted sequences and t -weighted sequences after oral contrast with spio has revealed highest accuracy in the evaluation of crohn's disease (maccioni et al. ) . furthermore, it has been shown that mri with negative superparamagnetic oral contrast is comparable to endoscopy in the assessment of ulcerative colitis. in difference to patients with crohn's disease, the double-contrast imaging does not provide more information than single oral contrast (de ridder et al. ) . in mrcp, negative oral contrast agents can be given before the examination to provide non-superimposed visualization of the bile and pancreatic ducts. there is no negative influence of the oral contrast agents on the diameter of the ducts (petersein et al. a). in cardiac mri, contrast agents are obligatory for the assessment of myocardial perfusion, for the evaluation of enhancement of cardiac masses, and for the evaluation of myocardial viability. in addition, contrast agents are frequently used when mr angiography of the coronary arteries is performed. myocardial perfusion imaging is a promising and rapidly increasing field in cardiac mr imaging. in comparison to radionuclide techniques, mr imaging has several advantages, including higher spatial resolution, no radiation exposure, and no attenuation problem related to anatomical limitations. the examination is performed after rapid intravenous administration (e.g., - ml/sec) of a contrast agent and evaluation of the first-pass transit of the agent through the myocardium. with the use of fast scan techniques, perfusion imaging can be performed as a multislice technique, with imaging of three to five slice levels per heartbeat, possibly allowing coverage of the entire ventricle. from a series of images, signal intensity-time curves are derived from regions of interest in the myocardial tissue for generation of parametric images. the majority of data are published using ecf agents. in clinical practice, most investigators are using fast t -weighted imaging and bolus injection of doses of . up to . mmol/kg body weight (edelman ) . for the evaluation, both quantitative and qualitative approaches can be used. in case of ecf agents, generally semiquantitative assessments are applied. to quantify myocardial perfusion a calculation was published by wilke et al. on the basis of first-pass data acquired after fast bolus injection of . mmol/kg body weight of ecf agents (wilke et al. ) . in practice, gd concentrations between . and . mmol/l result in a linear progression of the mr signal compared with the concentration of the agent itself. above this dose, the maximal relative increase in signal intensity begins to saturate (schwitter et al. ) . when the evaluation is performed by visual evaluation, a higher dose of . - . mmol/kg should be preferred to reach better myocardial enhancement and image quality. good correlation between the perfusion reserve with mr imaging and the coronary flow reserve with doppler ultrasonography could be proven. blood-pool agents have the potential to be applied for quantitative measurements also because their volume of distribution is limited to the intravascular space. a requirement for quantitative perfusion measurements is that the relation between the measured signal intensity on the mr images and the contrast agent concentration in the blood is known (brasch ) . there are two major differences between first-pass curves obtained from blood-pool agents and extracellular contrast agents. first, blood-pool contrast agents reach a lower tissue signal because their volume of distribution is limited to the intravascular space (wendland et al. ; wilke et al. ) . second, there is a better return to baseline for blood-pool contrast agents. the wash-in kinetics and the signal intensity in the myocardial tissue depend on the concentration of the contrast agent, the coronary flow rate, diffusion of the contrast agent into the interstitium, relative tissue volume fractions, bolus duration, and recirculation effects (burstein et al. ) . absolute quantification of myocardial perfusion has been performed in animal models using nc . a high absolute quantification correlation was found between mri and contrast-enhanced ultrasound (johansson et al. ) . delayed enhancement allows direct visualization of necrotic or scarred tissue and is an easy and robust method to assess myocardial viability. by measuring the transmural extent of late enhancement, a prognosis toward the degree of functional recovery of cardiac tissue may be possible. although several studies have been aimed at describing the mechanisms of late enhancement, these could not be fully explained up to now. the extent of late enhancement possibly depends on the time-point after injection as well as the time-point after myocardial infarction. relevant publications about delayed enhance-ment are reporting data after the administration of . m ecf agents in a dose range of . - . mmol/kg. ecf agents are probably more efficient in assessing the cellular integrity when they are distributed homogenously through damaged myocardium (wendland et al. ) , but homogenous distribution is not always the case, as in microvascular obstruction (kroft and de roos ) . differences exist between the distribution patterns of extracellular and blood-pool agents, and hypo-enhanced cores may be observed earlier using blood-pool agents (schwitter et al. ) . the sensitivity of blood-pool agents for myocardial infarction and, therefore, their potential value for the evaluation of myocardial viability, is unknown. a different strategy to determine myocardial viability is the use of necrosis-specific mr contrast agents. gadophrin- and - (schering) have shown to possess a marked and specific affinity for necrotic tissue components and showed persistent enhancement in necrotic tissue ( min to h in myocardial infarction). in preclinical studies, the agent has not proven superiority in estimation of infarcts compared with ecf agents, and the further development of the agent was, therefore, not continued (barkhausen et al. ) . to depict coronary arteries in mri, both unenhanced and contrast-enhanced techniques are used. a frequently performed contrast-enhanced examination strategy with acquisition of multiple d slaps in breath-hold depicting each coronary artery separately was primarily described by wielopolski et al. ( ) . for d coronary mr angiography, however, the contrast between blood and myocardium in relation to the inflow of unsaturated protons is reduced. thus, the use of an intravascular contrast agent may be particularly convenient due to the t relaxation time reduction in blood. the application of ecf agents has proven to be most effective for breath-hold acquisitions. however, the concentration of ecf agents declines rapidly as they extravasate into the interstitial space, thereby reducing the contrast between blood and myocardium. newly developed strategies use high-resolution free-breathing mr sequences for coronary mra. in this situation, ecf agents are less beneficial due to the relatively long acquisition time of these free breathing d sequences. this problem can be solved by the use of intravascular contrast agents. an additional benefit from application of a blood-pool agent is a longer acquisition window, which may be used to further increase both the signal-to-noise ratio and/or image resolution (nassenstein et al. ) . in an animal model use of the macromolecular gd-based agent p with a free-breathing technique allowed more distal visualization of the coronary arteries than did an ecf agent or non-enhanced mr images (dirksen et al. ). colosimo c, demaerel p, tortori-donati p et al ( ) comparison of gadopentate dimeglumine (gd-bopta) with gadopentetate dimeglumine (gd-dtpa) for enhanced mr imaging of brain and spine tumors in children. ( ) barkhausen j ( ) ( b) one of the strengths of mri is the ability to visualize soft tissues with different image contrasts. additionally, various two and three-dimensional mr imaging techniques for morphologic and functional examinations exist. among the functional techniques the visualization and measurement of blood flow is of particular interest, since nearly all physiologic processes rely on an adequate blood supply. as with many other mr imaging techniques, the sensitivity of mri to blood flow was first observed in artifacts visible near larger blood vessels. to suppress these artifacts new imaging methods have been investigated. in a further refinement of these techniques the artifact (here: the blood flow) has been made the primary source of the imaging technique; thus, in search for new methods of flow artifact suppression the blood flow itself became the contrast-generating element. the delineation of the vascular tree with mri, mr angiography (mra), is such a development: in t -weighted d gradient-echo data, it was observed that the blood vessel signal of the margin partitions was significantly higher than at the center of the image stack. furthermore, signal voids were seen in regions of turbulent flow, and in blood vessels with pulsating flow, ghost images of the vessel were visible in phase encoding direction. in the following, the underlying physical phenomena of these artifacts will be discussed, as they form the basis for time-of-flight mra, phase-contrast mra, and mr flow measurements. since the pioneering work of prince ( ) , many mr angiographies are acquired using contrast-enhanced acquisition techniques. in contrast-enhanced mra, the signal difference between the bright blood vessel and the dark surrounding tissue is induced by a reduction of the blood's t relaxation time. again, this technique has evolved from an unwanted vascular signal artifact in spin-echo images acquired after contrast agent injection into a major mr application. with the development of new contrast agents with a longer half-life in the vascular system, the so-called intravascular contrast agents, contrast-enhanced mra has been developed even further. in this section, techniques for mra with either intravascular or extracellular contrast agents will be presented. the visualization of the blood vessels with mri relies particularly on the specific properties of blood. blood consists nearly entirely of liquids, so that blood has a very high spin density and thus yields a strong mr signal. the t time of blood is long compared to that of other tissues (e.g., ms at . t) (gomori et al. ) , and it depends on its oxygenation state. long t values are a disadvantage in t -weighted acquisition strategies as the signal decreases with increasing t . this disadvantage can be converted into an advantage if the blood signal needs to be suppressed (black-blood angiography) for visualization of the vessel walls. furthermore, using an inversion (or saturation) recovery technique, the prepared magnetization can be tracked for a longer time, as the preparation persists much longer than in other tissues; this is the basis of arterial spin labeling techniques. typical t values are of the order of - ms (at . t). this t value is long enough to provide a high signal in the blood vessels using dedicated t -weighted image acquisition strategies. with conventional t weighted spin-echo techniques, mr angiographies are difficult to acquire since the motion of the blood needs to be compensated; nevertheless, t -weighted mra pulse sequences for imaging of the peripheral vasculature have been reported (miyazaki et al. ) . another approach is the use of balanced ssfp pulse sequences, where the contrast is dependent on the ratio of t /t -these fast pulse sequences have found a widespread use in the visualization of the cardiac system. in addition to the relaxation times, blood velocity is an important parameter. in healthy arterial vessels velocity values between cm/s (e.g., in the aortic arch) and cm/s (e.g., in the intracranial vessels) are common, whereas much lower values are found in the venous vasculature. high blood flow velocities lead to a pronounced inflow of fresh, unsaturated magnetization into an imaging slice, which increases the signal in the blood vesselsthis is the well-known time-of-flight contrast. furthermore, the velocity in the arterial system is not constant but changes as a function of time in the cardiac cycle. this pulsatility can be exploited to separate arterial from venous vessels, if image data are acquired with cardiac synchronization. all of the presented mra techniques rely on these properties of the blood; some exploit only one of them, whereas others use a combination of them to increase the vascular contrast even further. in any mr pulse sequence, the magnetization in a measurement slice is exposed to a series of radio frequency (rf) pulses. if the magnetization does not move out of the measurement slice (e.g., in static tissue) it approaches a so-called steady state which, for a spoiled gradient-echo pulse sequence, depends on the flip angle, the repetition time tr, and the relaxation times t and t . the steady state magnetization is smaller than the magnetization at the beginning of the experiment-it is partially saturated. fresh, unsaturated blood flowing into the imaging slice is carrying the full magnetization and thus generates a significantly higher mr signal (fig. . . ); this is known as time-of-flight (tof) contrast (anderson and lee ; potchen et al. ) . a major disadvantage of tof mra is the sensitivity to blood signal saturation: the longer the inflowing blood remains in the measurement slice, the more its signal is saturated. in situations where the blood vessel is oriented over a long distance parallel to the imaging slice (or d slab), the inflowing magnetization is progressively saturated. thus, blood appears bright near the entry site but is seen less intense with increasing distance from this position. to maintain the tof contrast over the whole imaging volume tof mra should therefore be performed as a d acquisition with thin slices or, if a d acquisition technique is preferred, in the arterial vasculature where high-flow velocities result in fewer saturation pulses for the arterial blood. the inflow effect can be maximized if the measurement slice is oriented perpendicular to the blood vessel. this is often possible for the straight arterial vessels (e.g., the carotids in the head), but can be difficult for extended vascular territories with tortuous vessels. in d acquisitions of larger vessel structures, the saturation effect can be partially compensated, if the flip angle is increased from the entry side of the slab to the exit side (fig. . . ) . thus, the saturation effect is less pronounced during entry, and the magnetization is still visible when it enters smaller vessels that are far away from the entry side. often, an rf pulse with a linearly increasing flip angle is utilized (tilted optimized non-saturating excitation, or tone [nagele et al. ] ). for an optimal vessel contrast the blood flow velocity, the repetition time, the mean flip angle, and the slope of the rf pulse profile are important parameters. in d tof mra, a very strong tof contrast can be achieved, if the slice thickness d is chosen such that the magnetization flowing with a velocity v is completely replaced during one tr interval, i.e. d ≤ tr · v. at a typi- fig. . . transient longitudinal magnetization, which is subjected to a series of excitation pulses ( °) at a repetition time of ms after entering the readout slice at t = during tof mra. the longer the blood spins remain in the slice the more they are saturated, and a differentiation between blood and surrounding tissue becomes difficult fig. . . d tof mra data set of the intracranial vasculature in lateral (top) and axial (bottom) maximum intensity projection. to minimize saturation, a tone rf pulse was used for excitation, and the signal from static brain tissue was additionally suppressed using magnetization transfer pulses cal tr of ms and a blood flow velocity of cm/s, the slice thickness should thus not be larger than mm. with these small slice thicknesses, the data acquisition in larger vascular territories such as the legs is very timeconsuming, and patient movements cannot be excluded during the several minutes of scan time. patient movements lead to artificial vessels shifts between the imaging slices, which are particularly observed in orthogonal data reformats-these artifacts can mimic pathologies such as stenoses and thus significantly reduce the diagnostic quality of the data sets (fig. . . ) . d tof mra is advantageous over sequential d tof mra because an isotropic spatial resolution in all directions can be achieved. to reduce the saturation effects in d tof mra not only one thick, but also several thinner d slabs are acquired consecutively. thus, the saturation effects are smaller for the individual slabs and a stronger tof contrast is seen. unfortunately, the flip angle in fast d acquisitions is not constant over the slab, but is declining towards its margins. this inhomogeneous excitation results in a higher signal for the stationary tissue at the slab margin, providing an inhomogeneous signal background in lateral views of the data. combined with a higher tof contrast at the entry side compared with the exit side, spatially varying signal intensity is seen in lateral views of the whole data set (venetian blind artifact). to reduce this artifact, overlapping d slabs are acquired (multiple overlapping thin slab acquisition, or motsa [parker et al. ] ), and the marginal slices of each slab are removed; however, this results in an increased total scan time. to increase the contrast between the blood vessels and the surrounding tissue in tof mra, often magnetization transfer pulses are included in the pulse sequences (edelman et al. ). using off-resonant rf pulses, the magnetization transfer contrast (mtc) selectively saturates those tissues where macromolecules are present. for brain tissue, these additional rf pulses can reduce the signal from background tissue by % and more, which increases the conspicuity especially of the smaller blood vessels. the use of magnetization transfer pulses however increases the minimally achievable tr and, thus, the total acquisition time. additionally, through the integration of the mtc pulses more rf power is applied to the patient, so that the regulatory power limits for the specific absorption rate (sar) might be exceeded, an effect that is more pronounced at higher field strengths. nevertheless, mtc is often included in intracranial tof mra protocols where longer trs can be an advantage, as long trs additionally reduce the saturation effect. the flow velocity in arteries is typically not constant but varies over the cardiac cycle. thus, the tof contrast is a function of time, so that for image acquisition times that are longer than one cardiac cycle, a signal variation during k-space sampling is present. this periodic signal variation results in phantom images of the blood vessels in phase encoding direction after image reconstruction: the so-called pulsation artifacts or ghost images (haacke and patrick ; wood and henkelman ) . to avoid pulsation artifacts, the image acquisition can be synchronized with the cardiac cycle using ecg triggering, which typically prolongs the total acquisition time, as only part of the measurement time is used for data acquisition. another option to reduce pulsation artifacts is to saturate the inflowing blood in a slice upstream of the imaging slice. therefore, a slice-selective rf excitation is applied in a (typically parallel) saturation slice, so that the magnetization of the inflowing blood is significantly reduced. spatial presaturation avoids pulsation artifacts; however, the interior of the blood vessel now has a negative contrast, and the positive tof contrast is gone. another important ingredient of a tof mra pulse sequence is flow compensation (cf. paragraphs on flow measurements, below): the movement of the spins causes an additional velocity-dependent phase shift that is seen in tof mra data sets without flow compensation as a displacement. if multiple velocities are present as in turbulent flow, the different phases can cause signal cancellation (intra-voxel dephasing) that manifests, e.g., as a signal void behind a stenosis (saloner et al. ) . with special compensation gradients the velocity-depen- tof mra data sets of the arterial vasculature in the neck. due to swallowing, the blood vessel can move from one acquisition to the next, and the edges appear with discontinuities in the lateral views of the maximum intensity projection dent phase shifts can be reduced; however, this typically prolongs the echo time te. tof mra is susceptible to several artifacts and is strongly dependent on a sufficient inflow velocity of unsaturated blood. therefore, d tof mra techniques are typically only used in the head, where the arterial flow velocities are high and enough time is available for imaging. for abdominal studies, tof techniques are of minor interest, because long measurement times are not possible due to respiratory motion. in conventional tof mra, the difference in longitudinal magnetization between the saturated stationary tissue and the unsaturated inflowing blood is exploited to create a positive contrast between blood and tissue. with arterial spin-labeling techniques, a similar approach is taken to the visualization of the inflowing blood; however, here only a certain fraction of the inflowing blood is tagged (or labeled) and subsequently visualized, whereas in tof mra all inflowing material is detected (detre et al. ) . spin-labeling pulse sequences consist typically of a labeling section, during which an rf pulse is applied to the spins upstream of the imaging slice (fig. . . ) . for labeling often adiabatic inversion pulses are used, which are less susceptible to motion during the inversion and that allow inverting the magnetization even in rf coils with a limited transmit homogeneity (e.g., a transmit/receive head coil). after an (often variable) inflow delay time ti, during which the labeled blood is flowing into the vascular target structure, the signal in the imaging slice is acquired. for signal reception different image-acquisition strategies can be employed such as segmented spoiled gradient-echo (flash), fast spin-echo (rare, haste), or even echo planar imaging (epi). note: this image data set contains both the signal from the labeled blood and the static background tissue. in a second acquisition, the entire pulse sequence is repeated without labeling of the blood, and a second image data set is acquired. to selectively visualize only the labeled blood the two data sets are subtracted; since the signal intensity of the blood differs in both acquisitions, a non-vanishing blood signal is seen, whereas the signal contribution from static tissue cancels. if the phase of the second image data set is shifted by ° compared to the first, labeled data set, the images can be added (the minus sign is provided by the phase), and the technique is called signal targeting with alternating radiofrequencies (star) (edelman et al. ) . in clinical mri systems, arterial spin labeling (asl) is typically implemented with the described labeling pulses, which are applied only once per data readout; this approach is also termed pulsed arterial spin labeling (pasl). another method for asl uses a small transmit coil for the labeling pulse, which continuously applies an rf pulse to the arterial vessel, and thus achieves a much higher degree of inversion. unfortunately, these continuous asl techniques often cannot be used in a clinical mr system due to the regulatory constraints for the maximum rf power applied to the patient (sar limits). asl techniques are typically applied to study perfusion in the brain and other organs, where the inflow delay is chosen long enough for the labeled blood to have reached the capillary bed (golay et al. ). unfortunately, the labeling in the blood does not persist for much longer than one t time (i.e., - s at . t), and the signal differences are generally very small ( - % of the total signal), which makes perfusion measurement asl a time-consuming procedure. another application to asl is the time-resolved visualization of blood flow, e.g., in intracranial malformations (essig et al. ) , where saturation effects limit the diagnostic quality of conventional d tof mras. here, dynamic asl data sets are acquired at a series of inflow delays to visualize the transit of the labeled bolus through the nidus of the malformation, and, more importantly, the arrival of the blood in the draining venous vessels, concept of arterial spin labeling: magnetization is prepared (e.g., using a slice-selective inversion pulse) in a section of the artery (red). after an inflow delay of several hundred milliseconds, the magnetization has reached the imaging slice (green), and an image is acquired. the procedure is repeated without preparation, and the two data sets are subtracted to remove the signal background from static tissue that cannot be seen on the tof data sets (fig. . . ) . in addition to a morphologic representation of these blood vessels, transit-time measurement of the blood becomes feasible, which could be used as an indicator, e.g., for an increase in vascular resistance after a radiation therapy. mr angiographies can also be acquired using the special contrast properties of blood. in balanced steady state free precession pulse sequences (bssfp, truefisp, fiesta), an image contrast is created that depends on the ratio of the relaxation times t and t (oppelt et al. ) . for blood, this ratio is high, and thus the interior of the blood vessels are shown with higher signal intensity than the surrounding tissue. unfortunately, other liquid-filled spaces such as the ventricles also appear with a bright signal, so that conventional mra post-processing strategies such as the maximum intensity projection cannot be used to visualize the vascular tree (fig. . . ) . despite their short repetition times and balanced gradient schemes, these pulse sequences are susceptible to flow artifacts caused by intra-voxel dephasing, which can be compensated using flow-compensation gradients (storey et al. ; bieri and scheffler ) . another problem with balanced steady state pulse sequences is the susceptibility to off-resonance artifacts: since both transverse and longitudinal magnetizations contribute to the mr signal, perfect phase coherence must be main-tained within one tr to establish the desired contrast. in off-resonant regions, this phase coherence is perturbed, and a contrast variation is seen in the form of dark bands. the banding artifacts can be reduced using a repetition time that is shorter than the inverse of the off-resonance frequency, i.e., for a -hz off-resonance, the tr should be shorter than ms. off-resonance frequencies scale with field strength, so that banding artifacts become an increasing problem at higher field strengths. nevertheless, fast balanced ssfp pulse sequences are increasingly used in mra studies of the heart and the neighboring vessels in combination with ecg triggering to visualize the vascular anatomy and to assess. in conventional spin-echo images, one often observes that the interior of the blood vessels is darker than the surrounding tissue. this so-called black-blood contrast is caused by an incomplete signal refocusing of the ° pulse. compared with tof mra with gradient-echo sequences, where the inflow of blood causes signal amplification, spin-echo sequences attenuate the signal from flowing blood because spins leave the imaging slice between the ° excitation pulse and the ° refocusing pulse, and thus do not contribute to the mr signal. therefore, blood signal attenuation can be increased with a longer spacing between the two rf pulses, i.e., with longer echo times te. to further suppress signals from slowly flowing blood near the vessel walls, often addi- fig. . . tof mra (top) and timeresolved dynamic mra with arterial spin labeling (bottom) of an intracranial arteriovenous malformation. in the tof mra, the nidus of the malformation is clearly seen, but the draining vein can hardly be identified because the inflowing blood is already completely saturated when it arrives in this part of the avm. in the three asl images acquired , , and ms after signal preparation, the filling of the nidus and the drainage through the vein is clearly visible tional strong gradients are introduced in the black-blood pulse sequences, which cause an increased intra-voxel dephasing and thus suppress the signal (lin et al. ) . a different technique for blood signal suppression makes use of an inversion recovery blood signal preparation (edelman et al. ): similar to arterial spin labeling a non-selective ° inversion pulse is applied; however, the signal in the imaging slice is reinverted by a subsequent slice-selective inversion pulse. with this preparation ,the magnetization of the blood (and of all other tissues) outside the imaging slice is selectively inverted. after a delay-time that is chosen to achieve a zero crossing of the longitudinal magnetization of the inverted blood, an image is acquired. if the blood has been completely exchanged during the delay, then the signal of the labeled blood is nulled and only the static tissue is visible. this technique is often used in combination with cardiac triggering to visualize, e.g., the myocardium (fig. . . ) . in cardiac black-blood applications, both techniques are combined, which is possible, because data are acquired during diastole when the heart is nearly at rest, whereas the signal preparation is applied during systole. in this image blood is seen with high signal intensity; however, the surrounding tissue also appears with a strong mr signal. in the ascending aorta, signal voids are seen which are caused by turbulent flow, and banding artifacts are visible in the subcuta-neous fat. nevertheless, balanced ssfp sequences provide good angiographic overview images in very short acquisition times, without the need for contrast agent injection. in the contrastenhanced data acquisition, a better background suppression is possible, and the projection image of the d data set clearly delineates the aorta and the adjacent vessels fig. . . ecg-triggered dark blood image of the heart acquired with a single-shot fast spin-echo technique (haste). the blood signal both in the heart and in the cross-section of the descending aorta is completely suppressed the tof contrast relies on the increase in signal amplitude due to the inflow of unsaturated magnetization. in addition to elevated signal amplitude, the spin movement can also create a change in the phase of the mr signal. if a gradient is turned on and blood moves along the gradient direction (here: the x-direction), the phase ϕ(t) of the mr signal is given by: ( . . ) here, the motion x(t) of the magnetization is expressed as a taylor series, and only the constant term (i.e., the initial position x ) and the linear term (i.e., the velocity v ) are considered. the two integrals m and m solely depend on the gradient timing and are called the zeroth and first moment of g(t). the next higher order term is proportional to the acceleration of the spins; however, the proportionality constant m only becomes large if long time scales are considered; thus, the estimation of the spin phase from the zeroth and first moments is justified for gradient-echo sequences with short echo times. if the gradient timing is modified such that the first moment is zero, the gradients are called flow compensated. flow compensation is important ingredient in many mr pulse sequences: if a range of velocities is present in a single voxel, then the mr signal amplitude is attenuated due to the incoherent addition of the signals. with flow compensation, the individual signals all have the same phase, and the signals of the different velocities add up coherently. flow compensation is especially important in regions of high velocity gradients as, e.g., turbulent jets or in highly angulated vessels. in general, both m and m will be non-vanishing, and the phase of the signal will become proportional to the local spin velocity. unfortunately, many other factors such as off-resonance, field inhomogeneity, or chemical shift also affect the spin phase, so that a direct velocity measurement is not possible with a single mr experiment alone. to create an mr image that is dependent on the local velocity, a minimum of two image acquisitions are required. in the first, velocity-sensitized acquisition a gradient timing is used with a carefully selected, nonvanishing first gradient moment (the zeroth moment is defining the spatial encoding, i.e., the k-space trajectory). in a second, flow-compensated acquisition, a gradient timing is chosen that cancels m . if the two phase images are directly subtracted, the result is a phase difference image that is linearly dependent on the spin velocity: this is the basis of an mr flow measurement (bryant et al. ) . since phase data are only unambiguous in the angular range of ± °, so is the velocity information in an mr flow measurement. to avoid artifacts due to multiple rotations of the spin phase (so-called wrap around artifacts), the first moment needs to be chosen such that the maximum velocity in the image creates a phase shift of °. in general, this velocity is set via the so-called velocity encoding, or venc, parameter in the pulse sequence. higher venc values require weaker encoding gradients, which can be realized in shorter echo times. despite an inadequate choice of the venc value, mr flow measurements are susceptible to phase noise, which is present in regions of low signal amplitude. if the snr is or less, the phase in the image is nearly uniformly distributed between - ° and + °; under these conditions a meaningful flow measurement is not possible. unfortunately, phase noise is also often present near blood vessels (e.g., in the air-filled spaces of the lung, close to the pulmonary vessels). here, the measurement of velocity values requires a very careful placement of the regions of interest (rois) to avoid systematic errors from included noise pixels. in a conventional flow measurement, velocity encoding is typically performed in slice-selection direction only, because the orthogonal placement of the flow measurement slice induces a high tof signal in the cross-section of the vessel lumen. additionally, a parallel orientation of the velocity encoding direction with the image plane makes the image acquisition susceptible to systematic errors due to displacement, as, e.g., the readout gradient are used for both spatial encoding and velocity measurement simultaneously. flow measurements in arterial vessels are often performed with cardiac synchronization to account for the pulsatility of the blood flow. cardiac synchronization can be performed by prospective ecg triggering or retrospective ecg gating. with prospective triggering, data acquisition is started by a trigger signal, which is generated by the ecg electronics during the qrs complex of the ecg (fig. . . ) . after data have been acquired for a certain number of cardiac phases, the measurement sequence is stopped until a new cardiac trigger signal is detected. in retrospective gating, image data are continuously acquired, and the time between the last trigger and the current data set is stored. later, data are resorted into predefined time intervals (bins) in the cardiac cycle, and the images are reconstructed. prospective triggering is less time-consuming during image reconstruction and is very precise in the delineation of the cardiac activity; however, a temporal gap at the end of the cardiac cycle is required and thus flow measurements at late diastole are difficult. prospective gating uses continuous image acquisition, and the magnetization steady state is always maintained. unfortunately, more data need to be acquired than with prospective triggering to ensure a sufficient coverage of the cardiac cycle, and a temporal blurring due to the interpolation is seen in the velocity data. when the complex image data of the two acquisitions are subtracted instead of the phases, and the magnitude of the difference is displayed, a so-called phase-contrast mra image is created (dumoulin ) . this pc mra image is not only dependent on the velocity of the spins, but also on the signal amplitude in both acquisitions; thus, every pc mra data set always has an overlaid tof contrast (fig. . . ). an advantage of pc mra is the fact that signal background of the surrounding stationary tissue is almost completely suppressed, and vessels can be traced further into the vascular periphery than with tof mra, with comparable measurement parameters. in pc mra, often not only the velocity in one spatial direction is encoded, but in all three directions. since separate velocity-encoded acquisitions have to be performed for each direction, the measurement time of a pc mra is two- to fourfold longer than that of a tof mra. a careful selection of the venc value is especially important in pc mra. if, e.g., the maximum velocity in the imaging slice is twice the venc value, a phase shift of ° (or °, which cannot be distinguished) is created. under these conditions, the velocity-encoded and the velocity-compensated acquisition have the same phase, and no pc mra signal would be observable. as blood does not flow with a constant velocity and velocity values can be reduced by pathologies (aneurysms) or increased (stenoses), the optimum choice of venc value is often difficult. because pc mra is more time-consuming, is susceptible to artifacts, and suffers from the same signal saturation as tof mra, it is rarely used in clinical routine. with tof and pc mra techniques, the blood motion is used to create a signal difference between the vessel lumen and the surrounding tissue, whereas contrastenhanced mra utilizes the reduction of the longitudinal relaxation time t after administration of a contrast agent. when a contrast agent is injected, the t of blood is shortened from t blood = . s (for b = . t) to less than ms during the first bolus passage (first pass). the relaxation rate r (i.e., / t ) is a function of the local contrast agent concentration: ( . . ) the proportionality constant between contrast agent concentration c and the change in relaxation rate is called the relaxivity r . the relaxivity is different for each contrast agent - typical values range from to mmol - s - . in general, high relaxivities are desirable because lower contrast-agent concentrations are needed to achieve the same change in image contrast. to enhance the signal in the contrast agent bolus and to suppress the signal background from static tissue, heavily t -weighted spoiled gradient-echo sequences (flash) with very short repetition times (tr < ms) and high flip angles (α = °- °) are used (fig. . . ) . the use of short trs is advantageous because very short acquisition times of only a few seconds can be achieved even for the acquisition of a complete d data set. these short acquisition times are needed, because the contrast agent is progressively diluted during the passage, which reduces the vessel-to-background contrast. short acquisition times are also favorable because mra data sets can thus be acquired in a single breath hold; for this reason, contrast-enhanced mra techniques are especially suited for abdominal applications (prince ; sodickson and manning ) . to ensure isotropic visualization of the vascular territories, typically d techniques are used for data acquisition. conventional d techniques have measurement times of several minutes, so that even with short repetition times larger parts of the k-space data are acquired after the contrast agent concentration has fallen to levels where only a weak signal enhancement is observable. for this reason, the measurement times are reduced using partial k-space sampling, parallel imaging, and view sharing between subsequent d data sets (sodickson and manning ; wilson et al. ; goyen ) . in general, contrast agents can be categorized into extracellular agents that can leave the blood stream and intravascular agents that are specifically designed to remain in the vascular system. historically, the first approved mr contrast agent was gd-dtpa (gadopentate dimeglumine, magnevist, schering, germany), an extracellular agent, which has the paramagnetic gd + ion as the central atom in an open-chain ionic complex (chelate). over the years, several similar extracellular agents such as gd-bt-do a (gadovist, schering), gd-dota (dotarem, guerbet, france), gd-bma (omniscan, ge healthcare), gd-hp-do a (prohance, bracco imaging, italy), and gd-bopta (multihance, bracco, italy) have been approved for clinical use, which only slightly differ in the stability of the gd chelates, pharmacokinetic properties, and safety profiles. in general, the most recently approved contrast agents have higher relaxivities and thus allow acquiring mra data sets with higher contrast at the same dose or with similar contrast at lower dose. only recently, the first intravascular contrast agent gadofosveset trisodium (vasovist, schering) has been approved for clinical use in europe (goyen ). this fig. . . phase-contrast images encoding flow in head-foot (top) and left-right (center) direction, and phase contrast mra image (bottom). in the flow images, a velocity-sensitive and a velocity-compensated data set are subtracted, whereas the pc mra image is generated by complex subtraction of the respective signal amplitudes. note, that the pc mra image has nearly no background signal from static tissue molecule has a diphenylcyclohexyl group, which is covalently bound to a gd complex, which creates a reversible, non-covalent binding of the molecule to serum albumin that significantly prolongs the half-life of the agent in blood to about h. after injection of the agent, at first a more rapid decline of concentration is observed, because the fraction of the contrast agent bound to albumin is dependent on the contrast agent concentration; thus, a steady-state concentration is established after the unbound fraction is renally excreted. both extracellular and intravascular agents can be imaged during the first pass of the contrast agent, when a high vessel-to-background contrast is present, whereas intravascular contrast agents additionally allow angiographic imaging during the subsequent steady state. the t shortening is dependent on the contrast agent concentration, which is getting smaller already a few seconds after infusion of the contrast agent, as the contrast agent bolus in the blood is increasingly diluted and, for the extracellular agents, the contrast agent is extravasculized. therefore, contrast-enhanced mra techniques usually use pulse sequences with very short acquisition times (ta < s). the short passage time of the contrast agent bolus of a few seconds requires that imaging be precisely synchronized with the contrast agent infusion. the transit time of the bolus from the point of injection (usually a vein in the arm) through to the vascular target structure (e.g., the renal arteries) varies significantly with the heart rate and cardiac output and can be difficult to predict. therefore, various synchronization and acquisition tech-niques have been proposed for a reliable mra data acquisition: an automatic technique to start the d mra data acquisition (smartprep™, general electric) uses a fast pulse sequence before the d mra, which continuously acquires the signal in the vascular target region . after administration of the contrast agent, this signal exceeds a certain signal threshold, and the d mra acquisition is automatically started. if the signal threshold is selected too low, image noise can mimic a bolus arrival and the measurement is triggered too early, whereas a too high value of the threshold can lead to an omission of the data acquisition. with the test bolus technique, a small bolus of a few milliliters of the contrast agent is infused, and the passage of the bolus is imaged near the target vessel with a fast time-resolved d mr measurement (earls et al. ) . the trigger delay td for the subsequent d measurement is then calculated from the transit time of the bolus tt and the acquisition time of the d mra ta as: td = tt - necho × ta. here, necho denotes the fraction of ta before the center of k-space is acquired (fig. . . ). as in the automatic start of the sequence, fluoroscopic previews (carebolus™, siemens medical solutions) image the contrast bolus during its passage; however, here fast d sequences are used with real-time image reconstruction and display riederer et al. ; wilman et al. ) . once the bolus has reached the target region, the operator of the mr scanner manually switches to the predefined d mra pulse sequence, which is then executed with minimal time delay. fig. . . signal intensity as a function of t -contrast in a spoiled gradient-echo pulse sequence (flash). at high flip angles and short repetition times the signal from tissue (t > ms at . t) is nearly completely saturated, whereas a high intraluminal signal is seen due to the high concentrations of the contrast agent • multiphase mra time-resolved mra has been increasingly used to completely avoid manual or automated synchronization. multiphasic acquisitions consecutively acquire d mra data sets during the bolus passage so that the optimal vessel contrast is obtained in at least one of the data sets. various methods of measurement acceleration are combined to ensure adequate temporal resolution; these include parallel imaging, asymmetric k-space readout, and temporal data interpolation (korosec et al. ; fink et al. ). nevertheless, timeresolved mra data sets are usually of a lower spatial resolution than are optimally acquired mra data with bolus synchronization (fig. . . ). artifacts arise, if the d mra data acquisition is not perfectly synchronized with the bolus passage. the appearance of these artifacts depends on the relative timing of the k-space acquisition and the concentration-time curve of the contrast agent. if the bolus arrives too late in the target vessel, then the center of the k-space has already been sampled and large structures, such as the interior of the blood vessel, appear dark, whereas fine structures, such as vessel margins, have a high signal if the bolus arrives during sampling of the k-space periphery. if the data acquisition is started too late, then the bolus has already reached the target vessel and the contrast has partly disappeared -thus, the signal is significantly reduced compared with an optimally synchronized data acquisition (maki et al. ; wilman et al. ; svensson et al. ) . another disadvantage of suboptimal bolus timing is the fact that the bolus may have passed from the arterial to the venous system in some vascular regions (e.g., the extremities) so that both veins and arteries are seen in the images. this venous contamination makes the interpretation of the image data difficult in cases where arterial and venous vessels are parallel to each other. the variation in contrast agent concentration over time also results in a reduction in the achievable image resolution (fain et al. ) . the spatial resolution of an mr image sampled with cartesian data acquisition is always uniquely defined by the measured number of k-space lines. with increasing number of k-space lines (i.e., larger k-space coverage), finer image details are encoded in the image. this so-called nyquist scanning theorem only applies if the signal intensity is constant during data acquisition. even with perfect synchronization with the contrast agent bolus, the contrast agent concentration is only optimal during acquisition of the central k-space lines. later on, the concentration is reduced and the peripheral k-space regions are acquired with significantly reduced signal intensity (fig. . . ). this different weighting of the k-space regions results in a reduction in spatial resolution (blurring), which is mathematically described by the point-spread function, psf. the psf is the image of a point object - for linear imaging systems, it is used to describe the imperfections of the image acquisition system. the psf depends on the acquisition time, the contrast agent dynamics, and the measurement parameters of the pulse sequence. the deviation from an ideal psf is particularly visible in those spatial directions that are acquired with the lowest sampling velocity. in conventional d acquisition, this is either the phase encoding direction or the partition encoding direction. to eliminate this asymmetry and to fig. . . test bolus measurement in the heart (blue) and the aorta (red) of a patient. for an optimal visualization of the aortic arch, a time delay of s is required between contrast agent injection and the acquisition of the central k-space lines evenly distribute the blurring in both spatial directions, elliptical scanning of the phase and partition encoding steps has been proposed (bampton et al. ; , where the encoding steps are acquired along an elliptical path, starting from the center of the k-space. using the signal-time curve of a test bolus, the signal variation during data acquisition can be avoided. therefore, an injection scheme is calculated for the signal-time curve using linear system theory, where the injection rate is modulated such that there is a constant contrast agent concentration (i.e., an ideal psf) in the target region throughout the data acquisition. this technique requires a programmable contrast-agent injector and additional computations, and the constant concentration can only be achieved in a limited target volume. another option for reducing the intensity changes is to induce a blood flow stasis for a brief period after contrast agent inflow. this can be achieved in the peripheral blood vessels, without endangering the patient using an inflatable cuff, which temporarily blocks the blood flow during data acquisition; this technique has been used successfully applied to contrast-enhanced mra studies of the hand (zhang et al. ) and the legs (zhang et al. ; vogt et al. ) . in addition to reducing t , an mr contrast agent always also reduces t (and t *). the reduction in t * can lead to a significant signal reduction in the mra image at high contrast agent concentrations; often the venous vessel through which the bolus is infused are seen dark in the mra data sets (albert et al. ) . to avoid these ar-tifacts, the contrast agent concentration or the echo time te can be reduced. besides reducing t *, the contrast agent also causes a concentration-dependent resonance frequency shift. radial or spiral k-space data acquisitions especially susceptible to these frequency shifts that cause blurring artifacts, which can be compensated using dedicated off-resonance correction algorithms. contrast-enhanced mra studies are also susceptible to artifacts known from tof mra. in particular, pulsation artifacts are visible in contrast-enhanced measurements (al-kwifi et al. ) . intra-voxel dephasing is observed, although the effect is much lower due to the shorter tes used here. to keep the acquisition time short, generally flow compensation is not integrated into contrast-enhanced mra pulse sequences, because the additional gradients significantly prolong the measurement time. contrast-enhanced mra offers substantial advantages over tof or pc mra, because the saturation effects seen in tof mra are almost completely avoided. thus, extended vascular structures for example in the abdomen or the extremities can be visualized with a few slices oriented parallel to the vessel. the short acquisition times of contrast-enhanced mra allow breath-held acquisitions (ta < s), which significantly reduces motion artifacts . the dynamic information of multiphase d mra contains information about vascular anatomy, flow direction (e.g., in aortal aneurysms), tissue perfusion (e.g., in the kidney), and vascular anomalies, which might not be visible on a single mra data set. using intravascular agents, the contrast agent concentration in the blood is maintained over time spans of minutes to hours. in general, the same pulse sequences can be applied for mra with intravascular contrast agents as with the extracellular contrast agents, as they share the same contrast mechanism; however, as the concentration of intravascular contrast agent in blood attains an equilibrium state after a few re-circulations (typically - s), mra data sets can also be acquired over longer acquisition times. this prolonged acquisition window can be used to increase the image resolution, because an ideal psf can be achieved and, thus, no blurring should be present (van bemmel et al. a; grist et al. ) . because data acquisition does not have to be synchronized with the contrast agent bolus, data acquisition can be started once the contrast agent concentration has reached equilibrium. the contrast agent injection does not need to be performed with a contrast agent pump, but can be infused manually via a venous access port even prior to the mr examination. with intravascular contrast agents, the acquisition time ta is not limited by the transit time of the bolus, and data sets can be acquired over much longer acquisition periods. with longer acquisition times, special trigger and gating techniques (ecg triggering, respiratory gating, navigator echoes [ahlstrom et al. ] ) to suppress motion artifacts are required. if image data are acquired in the equilibrium phase, venous overlay is a fundamental problem in mra with intravascular contrast agents (fig. . . ). venous contamination particularly makes those images hard to interpret that are calculated through a projection technique such as the maximum intensity projection (mip), because here, the depth information is lost. a separation of arterial and venous vessels is possible with the help of dedicated post-processing software. therefore, a region in an arterial vessel is identified and a region-growing algorithm is used to find all connected regions. unfortu-nately, when arteries and veins are in close proximity the algorithm may artifactually connect arterial to venous vessels. with equilibrium-phase mra, data sets of intravascular contrast agents, these artifacts are easier to avoid than in first-pass studies because of the higher spatial resolution. nevertheless, for direct arteriovenous connections or shunts, a manual correction of the segmentation is always required (van bemmel et al. b; svensson et al. ) . the use of intravascular contrast agent is not limited to the equilibrium phase, but can be combined with a first-pass study during the initial contrast agent injection to obtain both the dynamics of the contrast agent passage as well as the vascular morphology (grist et al. ) . additionally, the dynamic information can be utilized to separate arteries from veins in the high-resolution equilibrium-phase d mra data sets (bock et al. ) . although the long half-life of the intravascular contrast agent is advantageous for intraluminal studies, it can become a problem if a dynamic study has to be repeated. with extracellular contrast agents, this is possible within a few minutes, whereas up to several hours have to be waited after a study with an intravascular contrast agent. in practice, intravascular contrast agents are still advantageous for mra, as they allow combining high spatial resolution in the equilibrium phase with dynamic information during first passage. additionally, these contrast agents can be used to quantify perfusion (prasad et al. ) or to delineate vessels during mr-guided intravascular procedures (wacker et al. ; martin et al. ). various techniques for mr angiography and mr flow measurements exist that make use of the different physical properties of blood: flow, pulsation, or signal variation following administration of contrast agent. tof mra is often used in anatomical regions where a high inflow is fig. . . surface rendering (left) and mip (right) visualization of an abdominal mra with an intravascular contrast agent. the three-dimensional character of the data set is better captured with the surface display, whereas the finer details are better visualized on the mip. the presence of venous signal is making the interpretation of the data more difficult; however, a significantly higher spatial resolution can be achieved with intravascular contrast agents present, and long measurement times can be tolerated. phase-contrast flow measurements provide a quantitative assessment of blood flow when combined with cardiac triggering. contrast-enhanced studies are favorable in abdominal regions and the periphery, where saturation effects are a limiting factor for tof mra. intravascular contrast agents further extend the capabilities of contrastenhanced mra because high-resolution data sets can be acquired over an extended time. diffusion in the context of diffusion-weighted mri or diffusion tensor imaging (dti) refers to the stochastic thermal motion of molecules or atoms in fluids and gases, a phenomenon also known as brownian motion. this motion depends on the size, the temperature, and in particular on the microscopic environment of the examined molecules. diffusion measurements can therefore be used to derive information about the microstructure of tissue. in mri, stochastic molecular motion can be observed as signal attenuation. this was first recognized in the nmr spin-echo experiment by e.l. hahn in (hahn , long before the invention of actual magnetic resonance imaging. a number of more sophisticated experiments were described in following years that allowed the quantitative measurement of the diffusion coefficient (carr and purcell ; torrey ; woessner ) . of particular importance is the pulsed-gradient spin-echo (pgse) technique proposed by stejskal and tanner in (stejskal and tanner ) that is described in detail in sect. . . . . diffusion as an imaging-contrast mechanism was first incorporated in mri pulse sequences in (taylor and bushell ; merboldt et al. ) and applied in vivo in (lebihan et al. ). its great potential for clinical mri became evident in around , when diffusionweighted images were recognized to be extremely valuable for the early detection of stroke (moseley et al. a,b; chien et al. chien et al. , . areas of focal cerebral ischemia appear hyperintense in diffusion-weighted images only minutes after the onset of symptoms (see also chap. , sect. . ) . having thus been pushed into publicity, diffusion-weighted imaging was evaluated in many other applications such as the characterization of brain tumors (tien et al. ; sugahara et al. ; okamoto et al. ) and of multiple sclerosis lesions (cercignani et al. ; filippi and inglese ) , but none of these reached the clinical significance of stroke diagnosis. mainly due to limitations of image quality, there are considerably fewer publications about diffusion-weighted imaging outside the central nervous system. examples of these are studies with the purpose of differentiating osteoporotic and malignant vertebral compression fractures (baur et al. (baur et al. , herneth et al. ) or benign and malignant lesions of the liver (moteki et al. ; taouli et al. ) and the kidneys (cova et al. ) . molecular diffusion is a three-dimensional process and is-depending on the tissue microstructure-in general anisotropic, i.e., the extent of molecular motion depends on spatial orientation. a physical quantity called the diffusion tensor is required to fully describe anisotropic diffusion. mri techniques to measure the diffusion tensor have been introduced in the s (basser et al. ; pierpaoli et al. ) and gained considerably more popularity when tracking algorithms were proposed for three-dimensional reconstruction of white matter fiber tracts (mori et al. ; conturo et al. ) . today, diffusion tensor imaging is a valuable research tool with applications, e.g., in neurodevelopment snook et al. ) , neuropsychiatry (taber et al. , sullivan and pfefferbaum , or aging (moseley , sullivan and pfefferbaum , sullivan et al. ). all molecules in fluids or gases perform microscopic random motions. this motion is called molecular diffusion or brownian motion after robert brown ( brown ( - , who observed a minute motion of plant pollens floating in water in (brown ) . these pollens were constantly hit by fast-moving water molecules, resulting in a visible irregular motion of the much larger particles. due to brownian motion, a tracer such as a droplet of ink given into water will diffuse into its surroundings, resulting in spatially and temporally varying tracer concentrations, until the ink is diluted homogeneously in the water. however, brownian molecular motion does not require concentration gradients, but occurs also in fluids consisting of only a single kind of molecule. the molecules of any arbitrary droplet of water within a larger water reservoir will stochastically disperse into their surroundings; this process is called diffusion or, to emphasize that the observed molecules do not diffuse into an external medium, self-diffusion. it should be noted that diffusion always refers to a stochastic and not directed motion and is strictly to be distinguished from any kind of directional flow of a liquid. the molecules in fluids or gases perform random motions due to their thermal kinetic energy, ekin, which is proportional to the temperature, t: ekin = - kt (k = . × - j/k is the boltzmann constant). this energy corresponds to a mean velocity m e v kin = for a molecule of mass m; in the case of water at room temperature (t = k), the mean velocity is about m/s. due to frequent collisions with other particles, however, mol-strictly speaking, we calculate the square root of the mean value of squared velocity, i.e., mean (ν�) , which is slightly different (by a factor of π / ≈ . , i.e., by . %) from the actual mean value of the velocity due to the asymmetry of the maxwell distribution. ecules do not move linearly in a certain direction but follow a random course that can be visualized in a randomwalk simulation as shown in fig. . . a. this figure also demonstrates that, macroscopically, the mean displacement or diffusion distance, s, after a time t is much more interesting than is the linear velocity of the molecule. the mean diffusion distance of a particle is proportional to the square root of the diffusion time t and is described by the diffusion coefficient d: . this relation is shown in fig. . . b for a water molecule with a diffusion coefficient of d = . × - mm /s at a temperature of °c. since diffusion is a stochastic process, the diffusion distance after the time t is not the same for all molecules but is described by a gaussian probability distribution as illustrated in fig. . . . as shown in this illustration, after a diffusion time t most molecules are still found at or close to their original position; the diffusion distance s, corresponds to the standard deviation of the shown distributions. typical diffusion distances for free water molecules at room temperature are about µm after a diffusion time of ms and µm after s. in contrast to free diffusion in pure water ( fig. . . a) , the water molecules in tissue cannot move freely, but are hindered by the cellular tissue structure, in particular by cell membranes, cell organelles, and large macromolecules as shown schematically in fig. . . b. due to additional collisions with these obstacles, the mean diffusion distance of water molecules in tissue is reduced compared to that of free water, and a decreased effective diffusion coefficient is found in tissue called the apparent diffusion coefficient (adc). obviously, the adc depends on the number and size of obstacles and therefore on the cell types that compose the tissue. hence, diffusion properties can be used to distinguish different types of tissue. examples of diffusion coefficients in different tissues and in fluids at different temperatures are summarized in table . . . not only does the number and size of organelles influence diffusion, but also the geometrical arrangement of the cell membranes. in particular, the diffusion of water molecules can reflect an anisotropic arrangement of cells as indicated in fig. . . c. since cell membranes are barriers for diffusing molecules, water diffuses more freely along the long axis of the cell than perpendicular to it (beaulieu ) . hence, the adc measured in the direction parallel to the cellular orientation will be greater than that measured in an orthogonal direction. this property, the dependence of a quantity on its orientation in space, is called anisotropy. it has proven useful to illustrate the diffusion properties by spheres for isotropic diffusion and by three-dimensional ellipsoids for anisotropic diffusion as shown in fig. . . d-f. these shapes visualize the probability density function of diffusion distances in space. isotropic diffusion can be completely described by its (apparent) diffusion coefficient, d, which corresponds to the radius of the sphere (fig. . . d,e) . more quantities are required for a complete description of anisotropic diffusion, e.g., three angles that define the orientation of the ellipsoid in space, and the length of the three principal axes describing the magnitude of the diffusion coefficients. in physics or mathematics, a quantity that corresponds to such a three-dimensional ellipsoid is called a tensor. the physical object called tensor can also be explained by comparing it to more commonly known objects such as scalars and vectors. a scalar is a quantity that can be measured or described as a single number; typical examples are the temperature, the mass, or the density of an object. in imaging, the image intensity, e.g., in a t -weighted image, is a scalar: a single number is required for each pixel to describe the intensity. as demonstrated in the last example, scalars can be spatially dependent and be visualized as intensity maps; another example is a temperature map of an object that describes the temperature as scalar quantity for each spatial position of an object. other physical quantities cannot be described by a single number, such as the velocity or acceleration of a particle in space or the flow of a liquid. these quantities are vectors and require both a direction in space and a magnitude to be fully described. a vector is typically visualized as an arrow. for example, in the case of velocity, the direction of the arrow describes the direction of motion and the length of the arrow represents the magnitude of the vector, e.g., as measured in meters/second. such an arrow can be mathematically described by three independent numbers: either by its length and two angles defining its orientation or by three coordinates (x-, y-, and z-component of the vector). these coordinates are often presented as a column or row vector, e.g., v = (vx vy vz). vectors as well as scalars can depend on the spatial position; a flowing liquid can be described by a velocity vector at each position. a full data set consisting of a vector (i.e., an arrow) at each point in space is called a vector field. some quantities such as the molecular diffusion cannot be fully described as scalars or vectors; they are tensors. as mentioned above, the diffusion properties can be depicted by a three-dimensional ellipsoid and therefore require six independent numbers to define the direction and length of all axes. these six values are visualized in fig. . . as the three lengths of the axes defining the shape of the ellipsoid and the three angles describing its orientation. however, instead of using angles, tensors can equally well be described by six coordinates arranged in a symmetric × -matrix in analogy to the three coordinates of a vector. these coordinates are called dxx, dyy, dzz, dxy, dxz, and dyz and form the matrix representation this matrix is called symmetric because the elements are mirrored at the diagonal. of these matrix elements, only the diagonal elements, dxx, dyy, dzz, can be measured directly in mri and correspond to the diffusion in the x-, y-, and z-directions; the off-diagonal elements must be determined indirectly from further measurements as described in sect. . . . in the case of isotropic diffusion, i.e., if the ellipsoid is a sphere, then this matrix has a very simple form, because a single diffusion coefficient suffices to describe the diffusion. this diffusion coefficient is found on the diagonal of the matrix, and all off-diagonal elements are zero: the diffusion tensor has some properties that are important to understand in order to measure and interpret diffusion imaging data. the mean diffusivity, i.e., the diffu-sion coefficient averaged over all spatial orientations, can be derived from the trace of the diffusion tensor, i.e., the sum of its diagonal elements: . an mri measurement of the mean adc is therefore also called trace imaging. to analyze the non-isotropic properties of the diffusion tensor, a process called diagonalization of the tensor is used. the meaning of tensor diagonalization can be visualized as finding the three axes (i.e., their length and orientation) that define the ellipsoid in fig. . . . mathematically, the tensor matrix is transformed into a form where all off-diagonal elements are zero: since six parameters are still required to fully describe the tensor, in addition to the three diagonal elements, three vectors, v , v , v , are determined which are called eigenvectors. the eigenvectors, which are always orthogonal and have unit length, define the orientation of the ellipsoid and are shown as thick grey arrows in fig. . . d. the ratios of the diffusion eigenvalues describe the isotropy or anisotropy of diffusion. in the case of isotropic diffusion, all eigenvalues are the same, d = d = d , and diffusion is represented by a sphere; see fig. . . a. if the largest eigenvalue is much greater than the two other eigenvalues, d >> d ≈ d , then the tensor is represented by a cigar-like shape as in fig. . . b. in this case, diffusion in one direction is much less hindered than in the other directions and is sometimes called linear diffusion; this is typically found in white matter fiber tracts, where the motion of water molecules is restricted by the cell membranes and the glial cells perpendicular to the fiber tract orientation. the orientation of the fiber tracts is described by the eigenvector v belonging to the large eigenvalue, d . if two large eigenvalues are much greater than the third one, d ≈ d >> d , then the diffusion tensor is represented by a pancake-like shape; see fig. . . c . this tensor corresponds to preferred diffusion within a twodimensional plane, which can occur in layered structures and is referred to as planar diffusion. in order to describe the diffusion anisotropy quantitatively, several anisotropy indices have been introduced to reduce the diffusion tensor to a single number, i.e., a scalar, measuring the anisotropy. most frequently used is fig. . . tensor visualized as three-dimensional ellipsoid: six independent numbers are required to define a tensor, three lengths (eigenvalues), d , d , d , corresponding to the length of the principal axes of the ellipsoid (shown three-dimensionally in a and in two-dimensional sections b), and three angles, α, β, γ, describing the spatial orientation of the axes (c,d) . the eigenvectors of the tensor are shown as thick gray arrows in d the fractional anisotropy (fa), defined as where d = - (d + d + d ) is the mean diffusivity. the fractional anisotropy ranges from (isotropic diffusion) to (maximum anisotropy) and can be interpreted as the fraction of the magnitude of the tensor that can be ascribed to anisotropic diffusion . a similar index is the relative anisotropy (ra), defined as the relative anisotropy is the magnitude of the anisotropic part of the tensor divided by its isotropic part and ranges from (isotropy) to . ≈ (maximum anisotropy). in order to scale the maximum value of the ra to as well, a normalized (or scaled) definition with an additional factor of is sometimes used (and often called ra as well): less frequently used indices of anisotropy are the volume ratio (vr), all these anisotropy indices can be used to describe the diffusion anisotropy (kingsley and monahan ) , but fractional anisotropy may be considered the preferred index that is currently most frequently used. some typical values of these indices are compared in table . . ; fa, ra, nra, and vf start with for isotropic diffusion and increase with increasing anisotropy. the volume ratio is in the case of isotropic diffusion and decreases with increasing anisotropy. to introduce diffusion weighting in mri pulse sequences, today almost exclusively a technique proposed by stejskal and tanner in (stejskal and tanner ) is used. the basic idea is to insert additional gradients (usually referred to as diffusion gradients) into the pulse sequence in order to measure the stochastic molecular motion as signal attenuation. originally, these were two identical gradients on both sides of the refocusing ° rf pulse of a spin-echo sequence: the so-called pulsed-gradient spin echo (pgse) technique. however, to simplify the explanation, we will replace this scheme with two gradients with opposite signs that do not require a ° pulse in between, as shown in fig. . . . the contrast mechanism is the same for both gradient schemes. as illustrated in fig. . . , the diffusion gradients superpose a linear magnetic field gradient over the static field, b . since the larmor frequency of the spins is proportional to the magnetic field strength, spins at different positions now precess with different larmor frequencies and, thus, become dephased. if the spins are stationary (no diffusion, i.e., diffusion coefficient d = ) and remain at their position, the second diffusion gradient with opposite sign exactly compensates the effect of the first one and rephases the spins. hence, without diffusion, the signal after the application of the pair of diffusion gradients is the same as before (neglecting relaxation effects). in the case of diffusing spins, the second diffusion gradient cannot completely compensate the effect of the first one since spins have moved between the first and second gradient. the additional phase the spins gained during the first diffusion gradient is not reverted during the second one. consequently, rephasing is incomplete after the second diffusion gradient, resulting in diffusion-dependent signal attenuation. as can be deduced from this explanation, the signal attenuation is larger if the diffusivity, i.e., the mobility of the spins, is larger. quantitatively, the signal attenuation depends exponentially on the diffusion coefficient, dg, in the direction defined by the diffusion gradient gd: where s is the original (unattenuated) signal and s(dg, b) is the attenuated diffusion-weighted signal. the b-value, b, is the diffusion weighting that plays a similar role for diffusion-weighted imaging as the echo time for t weighted imaging: the diffusion contrast, i.e., the signal difference between two tissues with different adcs, is low at small b-values and can be maximized by choosing the optimal b-value as discussed below. the b-value is expressed in units of s/mm and depends on the timing and the amplitude, gd, of the diffusion gradients: as illustrated in fig. . . , δ is the duration of each diffusion gradient, and ∆ is the interval between the onsets of the gradients; γ is the gyromagnetic ratio of the diffusing spins. a typical b-value used for diffusion-weighted imaging of the brain is , s/mm²; for other applications b-values range between s/mm (dark blood liver imaging) and about , s/mm (imaging of the diffusion q-space [assaf et al. ; wedeen et al. ] ). to obtain b-values of about , s/mm , diffusion gradients are required to be much longer (e.g., δ = ms) and have larger amplitudes (e.g., gd = mt/m) than normal imaging gradients applied in mri; hence, diffusion-weighted imaging can be demanding for the gradient amplifiers and is often acoustically noisy. the formula for the b-value given above is valid only for a pair of stejskal-tanner diffusion gradients. the diffusion weighting of arbitrary time-dependent diffusion gradient shapes, gd(t), applied between t = and t = t, can be calculated according to (stejskal and tanner ) by applying diffusion gradients, diffusion-weighted images can be acquired in which the signal intensity depends on the adc, e.g., structures with large adc such as liquids appear hypointense. to quantify the adc at least two diffusion-weighted measurements with different diffusion weightings (i.e., different b-values) are required as shown in fig. . . . by determining the signal intensity at the lower b-value, s(b ), and the higher b-value, s(b ), the adc can be calculated as this can be done either for the mean signal intensities in a region of interest or pixel by pixel in order to calculate an adc map as in fig. . . . the adc can also be calculated from more than two b-values by fitting an exponential to the measured signal intensities or by linear regression analysis applied to the logarithm of signal intensities. it should be noted that diffusion-weighted images generally exhibit a mixture of different contrasts. many diffusion-weighted pulse sequences require relatively long echo times between and ms because of the long duration of the diffusion preparation. thus, diffusion-weighted images are often also t -weighted, and it can be difficult to differentiate image contrast due to diffusion and t effects. this is a typical problem in diffusion-weighted mri of the brain and known as t shinethrough effect (burdette et al. ) . a further consequence of the long minimum echo times due to the diffusion preparation is the relatively low signal-to-noise ratio of diffusion-weighted images. the combined effects of diffusion weighting, which particularly decreases the signal of fluids, and of t weighting, which predominantly reduces the signal of other (non-fluid) tissue, results in globally low signal intensity on diffusion-weighted images. therefore, signal-increasing techniques such as increasing the voxel volume or (magnitude) averaging are often required for diffusion-weighted mri. in addition, adc calculation can be corrected for the decreasing signal-to-noise ratio at higher b-values (dietrich et al. a) . the range of b-values chosen for a diffusion-weighted mri experiment should depend on the typical diffusion coefficients that are measured and on the signalto-noise ratio of the diffusion-weighted image data. as a rule of thumb, the signal attenuation should be at least in the case of diffusing spins, rephasing is incomplete since spins have moved between the first and second gradient; thus, diffusion-dependent signal attenuation is observed (red arrow) fig. . . acquisition of two images with different diffusion weightings (b-values b and b ) in order to calculate an adc map. note the large signal attenuation in csf at the higher b-value, b , and the correspondingly high diffusion coefficient in the adc map . diffusion-weighted imaging and diffusion tensor imaging about %, i.e., the product of diffusion coefficient and the b-value range, bmax-bmin, should be approximately (xing et al. ) . this corresponds to a b-value difference of about , - , s/mm in brain tissue with adcs between . × - and . × - mm /s. however, the choice of the largest b-value is frequently limited by signal-to-noise considerations, and thus, the maximum diffusion weighting is often reduced in order to maintain sufficient signal-to-noise ratio. a second point to consider is the choice of the lowest b-value. although a b-value of is often chosen, a slightly higher value of, for example, s/mm can be advantageous in order to suppress the influence of perfusion effects (lebihan et al. ; van rijswijk et al. ) . historically, the first mri pulse sequences with inserted diffusion gradients were stimulated-echo (taylor and bushell ; merboldt et al. ) and spin-echo sequences (lebihan et al. ); a schematic spin-echo pulse sequence with diffusion gradients is shown in fig. . . . in this diagram, diffusion gradients are added for all three spatial directions (readout, phase, and slice direction); however, they are usually switched on in only one or two of the three directions at a time. since spins are refocused by a ° pulse, both diffusion gradients have the same polarity. the main disadvantages of the diffusion-weighted spin-echo sequence are that it requires long acquisition times of many minutes per data set and is extremely sensitive to motion. examples of images acquired with a diffusion-weighted spin-echo sequence are shown in fig. . . a ,b. the volunteers were asked to avoid any movements, but no head fixation was applied; severe motion artifacts degrade the images. these artifacts are caused by inconsistent phase information of the complex-valued raw data; stimulated-echo, and spin-echo sequences are particularly sensitive to these effects because the diffusion preparation must be repeated for each raw data line and different states of motion will occur during these diffusion preparations. more details about the motion sensitivity of diffusion-weighted sequences and about approaches to reduce these artifacts are described in the following section. with techniques such as cardiac gating and navigator-echo correction, image quality of diffusion-weighted spin-echo sequences can be dramatically improved (fig. . . c,d) . today, the most commonly used pulse sequence for diffusion-weighted mri (particularly of the brain) is the single-shot echo planar imaging (epi) sequence with spin-echo excitation. the diffusion preparation of this sequence is the same as in the conventional spin-echo sequence of fig. . . , but instead of acquiring a single echo after each excitation, the full k-space can be read. the advantages of the diffusion-weighted epi sequence are a very short acquisition time of less than ms per slice and its insensitivity to motion. however, the image resolution is typically limited to × matrices and echo planar imaging is very sensitive to susceptibility variations as demonstrated in fig. . . a ,b-different susceptibilities of soft tissue, bone, and air, cause severe image distortion and signal cancellation close to interfaces between soft tissue and air or bone. these effects can be reduced with new imaging methods known as parallel imaging or parallel acquisition techniques (see sect. . ) . the underlying idea is to use several receiver coil elements with spatially different coil sensitivity profiles to acquire multiple data sets with reduced k-space sampling density in the phase-encode direction. these data sets are used to calculate a single image corresponding to a fully sampled k-space during post-processing. reducing the number of phase-encode steps shortens the epi echo train, decreases the minimum echo time as well as the total acquisition time, and increases the effective receiver bandwidth in the phase-encode direction. as a result, susceptibility-induced distortions are reduced as shown in fig. . . c,d. alternatively, the accelerated ac- diffusion-weighted imaging of the brain is almost exclusively performed with single-shot epi sequences (with or without parallel imaging). other organs or body areas, however, are less suited for echo-planar single-shot acquisitions because of much more severe susceptibility effects that often result in images of non-diagnostic quality. depending on the slice orientation and receiver coil system, these distortions can be reduced either with parallel imaging as described above or with segmented (i.e., multi-shot) epi sequences that assemble the raw data from multiple shorter echo trains (holder et al. ; ries et al. ; einarsdottir et al. ) . a disadvantage of this approach is the increased motion sensitivity since several excitations (and diffusion preparations) are required for a single data set, resulting in potentially inconsistent phase information; segmented epi sequences are therefore often combined with additional motion correction techniques. several other pulse sequences have been proposed for diffusion-weighted imaging. diffusion gradients can be added to single-shot fast spin-echo sequences with echo trains of multiple spin-echoes (see also sect. . ) such as haste or rare sequences (norris et al. ) . however, the additionally inserted diffusion gradients cause an irregular timing of the originally equidistant refocusing rf pulses. in combination with motion-dependent phase shifts, this violates the cpmg condition, which requires a certain phase relation between excitation and refocusing pulses. thus, in order to avoid artifacts, various modifications to diffusion-weighted fast spin-echo sequences have been suggested such as additional gradients (norris et al. ) , a split acquisition of echoes of even and odd parity (schick ) , or modified rf pulse trains (alsop ) . these modified diffusion-weighted singleshot fast spin-echo sequences are fast and insensitive to motion; disadvantages are a relatively low signal-to-noise ratio, and a certain image blurring that is characteristic for all single-shot fast spin-echo techniques. they have been applied in the brain (alsop ; lovblad et al. ) , the spine (tsuchiya et al. , clark and werring ) , and in several non-neuro applications such as imaging of musculoskeletal (dietrich et al. ) or breast (kinoshita et al. ) tumors. in contrast to echo-planar fig. . . diffusion-weighted spin-echo acquisitions (b = s/mm²) of two healthy and cooperative volunteers. a,b uncorrected images acquired without cardiac gating. c,d images after navigator echo correction acquired with cardiac gating fig. . . images acquired with a diffusion-weighted epi sequence. a,b conventional epi sequence exhibiting severe distortions (arrows). c,d epi sequence with parallel imaging (acceleration factor ) showing reduced susceptibility artifacts. (for better visualization of artifacts, only images without diffusion weighting (b = ) are shown) imaging, these techniques are insensitive to susceptibility variations and, thus, particularly suited for applications outside the brain. another, however only infrequently used alternative to echo-planar sequences are fast gradient-echo techniques (flash, mp-rage) with diffusion preparation (lee and price ; thomas et al. ) . a special sequence type that has successfully been employed for diffusion-weighted imaging is based on steady-state free-precession (ssfp) sequences (see also sect. . ). pulse sequences known as ce-fast or psif sequences (the acronym psif refers to a reverted fast imaging with steady precession, i.e., fisp, sequence) have been adopted to diffusion-weighted imaging by inserting a single diffusion gradient (lebihan ; merboldt et al. ) . however, in contrast to all previously described sequences, the diffusion weighting of this technique cannot be easily determined quantitatively. the observed signal attenuation does not only depend on the diffusion coefficient and the diffusion weighting, but also on the relaxation times, t and t , and the flip angle (buxton ) . since these quantities are usually not exactly known, the adc cannot be determined. instead, these sequences have been used to acquire diffusion-weighted images that are evaluated based only on visible image contrast. a general advantage of diffusion-weighted psif sequences is the relatively short acquisition time due to short repetition times of about ms. thus, they exhibit only low motion sensitivity. the most important application of this sequence type is the differential diagnosis of osteoporotic and malignant vertebral compression fractures (baur et al. (baur et al. , . other applications include diffusion-weighted imaging of the brain (miller and pauly ) and the cartilage (miller et al. ). as mentioned above, an unwanted side effect arising in virtually all diffusion-weighted pulse sequences is extreme motion sensitivity (trouard et al. ; norris ) . by introducing diffusion gradients, the pulse sequence is made sensitive to molecular motion in the micrometer range, but it also becomes susceptible to very small macroscopic motions of the imaged object since the diffusion gradients do not distinguish between stochastic molecular motion and macroscopic bulk motion. hence, even very small and involuntary movements of the patient, e.g., caused by cardiac motion, cerebrospinal fluid pulsation, breathing, swallowing, or peristalsis, can lead to severe image degradation due to gross motion artifacts. typical appearances of these artifacts are signal voids and ghosting in phase-encode direction. several techniques and pulse-sequence modifications have been proposed to reduce the motion sensitivity of diffusion-weighted mri. on the one hand, any kind of motion should be minimized. depending on the body region being imaged, this can be achieved by improved fixation of the patient to the scanner, by imaging during breath hold, or by applying cardiac gating. effects of motion can also be reduced by decreasing the acquisition time of a pulse sequence, i.e., by using fast acquisition techniques. this is particularly effective if singleshot sequences such as echo planar imaging techniques are applied. most motion artifacts in diffusion-weighted imaging arise from inconsistent phase information in the complex-valued raw data set. this is caused by different states of motion in the repeated diffusion preparations of the acquisition. in single-shot sequences, only a single diffusion preparation is applied, and thus inconsistent phase information is avoided. it should be noted, however, that even single-shot sequences might be affected by inconsistent phase information if complex data of several measurements is averaged. instead, only magnitude images should be averaged in diffusion-weighted mri in order to improve the signal-to-noise ratio. another approach to reduce motion artifacts is to correct for motion-related phase errors in the acquired raw data. this can be done using navigator echo-correction techniques (ordidge et al. ; anderson and gore ; dietrich et al. ) . the navigator echo is an additional echo without phase encoding acquired after each diffusion preparation. in the absence of motion, all navigator echoes should be identical. thus, by comparing the acquired navigator echoes, bulk motion can be detected, and degraded image echoes can be discarded or a phase correction can be applied. more advanced navigator-echo techniques acquire several navigator echoes in different spatial directions (butts et al. ) or use spiral navigator readouts (miller and pauly ) . certain pulse sequences are self-navigated, i.e., a subset of the acquired raw data can be used as navigator echo without the need for an extra navigator acquisition. examples are pulse sequences with radial or spiral k-space trajectories that acquire the origin of k-space in every readout (seifert et al. ; dietrich et al. b ). an improved self-navigation is possible with the propeller diffusion sequence, which repeatedly acquires a large area around the origin of k-space (pipe et al. ) . some image reconstruction techniques have been proposed that do not use the often-inconsistent phase information of raw data at all. in sequences with radial k-space trajectories, images can be reconstructed by filtered back projection of magnitude projection images (gmitro and alexander ) . another spin-echo-based approach known as line-scan diffusion imaging assembles the image from one-dimensional lines of magnitude data (gudbjartsson et al. ) . in addition to substantially reduced motion sensitivity, repetition times and thus image acquisition time can be considerably reduced since the one-dimensional lines are acquired independently of each other. on the other hand, the signal-to-noise ratio of line-scan sequences is substantially lower than that of conventional acquisition techniques and the spatial resolution of this approach is limited as well. a second unwanted side effect of diffusion-weighted sequences is eddy current effects caused by the extraordinarily long and strong diffusion gradients. eddy currents are induced electric currents in coils that occur after switching magnetic fields on or off. these currents then create unwanted additional gradient fields resulting in shifted or distorted images and in incorrect diffusion weightings. whereas most mri gradient systems compensate very well for eddy current effects after the switching of short gradients typically used for imaging, the longer diffusion gradients are often not well compensated. hence, diffusion-weighted images are sometimes distorted depending on the diffusion weighting and the direction of the diffusion gradients, resulting in artifacts on adc maps such as enhanced edges. to avoid these artifacts, several techniques have been suggested. diffusion gradients can be shortened by using bipolar diffusion gradients (alexander et al. ) or by adding additional ° pulses during the diffusion preparation (reese et al. ) ; eddy currents can be partially compensated for by an additional long gradient before the ° excitation pulse (alexander et al. ) ; or diffusion-weighted images can be acquired twice with diffusion gradients of opposite polarity (bodammer et al. ) . other eddycurrent correction schemes are based on the acquisition of diffusion gradient-dependent field maps and data correction in k-space (horsfield ; papdakis et al. ) . in general, (automated) image registration as the first step of postprocessing is recommended to reduce influences from both patient motion and eddy-current effects. imaging with the stejskal-tanner diffusion preparation as described above in sect. . . . , is only sensitive for molecular diffusion parallel to the direction of the diffusion gradient. the diffusion preparation causes a dephasing of spins that move in the direction of the applied field gradient, i.e., between positions with different magnetic field strengths as illustrated in fig. . . . molecular motion perpendicular to this direction does not contribute to the signal attenuation. in general, the diffusion displacement of spins depends on the considered spatial direction; e.g., protons of water molecules in nerve fibers move more freely parallel to the fiber direction than they do in perpendicular directions. this dependence of the diffusion on spatial orientation can be measured by applying diffusion gradients in different spatial directions, e.g., separately in slice, readout, and phase direction as demonstrated in fig. . . . the resulting diffusion-weighted images show substantial signal differences in areas with strong anisotropic diffusion such as the corpus callosum. the signal intensity of the corpus callosum is decreased if diffusion gradients in the left-right direction (readout direction in the example) are applied, but increased for diffusion gradients in the head-foot (slice) direction or the anterior-posterior (phase-encode) direction. this finding is explained by the fact that water molecules diffuse more freely in the left-right direction (parallel to the nerve fibers) than they do in perpendicular directions, i.e., the effective diffusion coefficient is greater in the left-right direction than it is in other directions, and thus the signal attenuation is increased. this orientation dependence is visible in the adc maps as well: the adc in the left-right direction of the corpus callosum is increased compared to the adcs in perpendicular directions. other areas such as gray matter or the csf do not show significant differences depending on the diffusion gradient direction, indicating approximately isotropic diffusion. if the mean (or average) diffusivity of molecules in tissue is to be measured, then diffusion coefficients for all spatial directions must be averaged as shown in fig. . . d ; the corresponding adc map is given by the mean value of the three direction-dependent maps. since the direction-independent or mean adc of tissue is proportional to the trace of the diffusion tensor, this measurement is also referred to as diffusion trace imaging. the measurement of such a direction-independent diffusion-weighted image can be very important to avoid misinterpretation of hyperintense areas due to high anisotropy as tissue with generally reduced adc such as areas of focal ischemia. therefore, diffusion-weighted stroke mri is generally based on isotropically diffusionweighted images. if only a single direction-independent diffusionweighted image is required for diagnosis, it appears disadvantageous to perform three orthogonal diffusion measurements at the cost of three-times-increased acquisition duration. it should be noted that it is not possible to simply apply gradients in all three directions simultaneously for this purpose; this results in a single magnetic field gradient in diagonal direction, which is again only sensitive for diffusion parallel to this diagonal. however, the stejskal-tanner diffusion preparation can be extended by a more sophisticated series of gradient pulses in different directions to achieve an isotropic diffusion weighting within a single diffusion measurement (wong et al. ; mori and van zilj ; chun et al. ; cercignani and horsefield ) . isotropically diffusion-weighted images can thus be acquired by either a single or three orthogonal diffusion preparations. however, three measurements are not yet sufficient to determine the properties of diffusion anisotropy in all cases. for example, if a nerve fiber is oriented diagonally to all three coordinate axes, then the diffusion attenuation in this fiber will be the same for the three measurements and cannot be distinguished from isotropic diffusion. the measurement of the full diffusion tensor (cf. sect. . . . ) is required to cope with these more general cases. in spite of this limitation, some studies have used the ratio of the largest and the smallest of three perpendicular diffusion coefficients as an estimation of the anisotropy (holder et al. ) . however, this approach should be regarded as an inferior method in comparison to diffusion tensor evaluation and is generally not recommended. to determine the diffusion tensor, i.e., to fully measure anisotropic diffusion, more than three diffusionsensitized measurements with diffusion gradients in different spatial directions are required. however, only the diagonal elements of the tensor, i.e., dxx, dyy, dzz, can be measured directly; these elements are exactly the direction-dependent adcs determined in the example above. the other three (off-diagonal) tensor components dxy, dxz, dyz do not describe diffusion in a spatial direction but the correlation of diffusion in two different directions; they cannot be measured directly, but must be calculated as linear combinations of several measurements. the minimum number of measurements required to determine the full diffusion tensor can be deduced from the form of the diffusion tensor matrix: the tensor has six independent components dxx, dyy, dzz, dxy, dxz, dyz and, thus, at least six independent diffusion measurements are required. each of these measurements is based on images of at least two different b-values; in order to reduce the total number of measurements, usually a b-value of is chosen as a direction-independent reference. thus, this reference image has to be acquired only once instead of separately for each diffusion direction. a possible and frequently used choice of seven diffusion-weighted acquisitions that are sufficient to determine the diffusion tensor (basser and pierpaoli ) is shown in fig. . . . none of the six tensor components dxx, dyy, dzz, dxy, dxz, or dyz is measured directly by this gradient scheme; instead, all components must be calculated as linear combinations of the diffusion coefficients in these six directions. this calculation is based on the so-called b-matrix (basser and pierpaoli ), a symmetric × matrix describing the diffusion weighting for an arbitrary diffusion gradient fig. . . diffusion-weighted imaging in different spatial directions. a diffusion gradients in slice (s), readout (r), and phase (p) direction; the row vectors (s, r, p) denote the selected gradients. b corresponding diffusion-weighted images. c calculated adc maps corresponding to the diffusion directions in a and images in b. d averaged adc map; all adcs are in units of - mm /s. note the differing contrast in the diffusion-weighted images and adc maps depending on the diffusion gradient direction (e.g., in the corpus callosum) where gg denotes the dyadic product of these two vectors. this matrix is used to describe the signal attenuation due to the diffusion gradient as where bd denotes the matrix product of the b-matrix and the diffusion tensor matrix. the elements of the diffusion tensor dij can be determined by solving a system of linear equations, since the b-matrix and the signal attenuation are known. the result of this calculation is shown in fig. . . . the three calculated diagonal elements correspond to the direct adc measurements of fig. . . . the off-diagonal elements are generally much lower than the diagonal elements (note the differently scaled intensity maps) are and are close to zero in areas with predominantly isotropic diffusion (gray matter and csf). a simple protocol for diffusion tensor imaging consists of one reference measurement without diffusion weighting (b-value is ) and six diffusion-weighted measurements with different gradient directions. these gradient directions should be "as different as possible, " i.e., pointing isotropically in all spatial directions. a typical b-value for dti measurements of the brain is , s/mm . averaging of multiple acquisitions is frequently performed to increase the snr especially of the images with diffusion weighting. however, all these parameters (b-values, diffusion directions, number of averages) have been evaluated in a number of studies with the aim of optimizing the accuracy of diffusion tensor data. several studies investigated the optimum choice of the b-values both for conventional diffusion-weighted imaging and for diffusion tensor imaging. although the results of these studies vary to a certain extent, generally b-values in the range between about and s/ mm have been found to provide the highest accuracy of diffusion measurements in the brain (jones et al. ; armitage and bastin ; kingsley and monahan ) . the optimum number of averages depends on the b-values, which influence the signal attenuation and, thus, the signal-to-noise ratio of the diffusion-weighted images. in general, a higher number of averages are recommended for the acquisition with the high b-value than for the reference image with low b-value or without fig. . . diffusion tensor imaging a choice of diffusion gradients (s slice, r readout, p phase direction; the row vector denotes the selected gradients and their polarity) and b corresponding diffusionweighted images for the determination of the diffusion tensor. note the different contrast in the diffusion-weighted images depending on the diffusion gradient direction (e.g., in the corpus callosum) any diffusion weighting. as shown by jones et al. ( ) for their choice of b-values, the optimum ratio of the total number of acquisitions with high b-value and low bvalue is about . . the number of diffusion gradients and their directions has also been investigated in several studies. generally, the accuracy of diffusion tensor data, especially of the diffusion anisotropy and main diffusion direction, is improved when the number of different diffusion directions is increased (jones et al. ; papadakis et al. ; skare et al. ; jones ). if the number of different directions is fixed, then the accuracy of the measurements can be increased by choosing an optimized set of diffusion directions (skare et al. ; hasan et al. ) . no final consensus about the optimum number and choice of directions of diffusion gradients has yet been established, but protocols with or more diffusion directions are currently recommended by many research groups. the diffusion tensor contains complex information about the tissue microstructure that is best visualized as a threedimensional ellipsoid as discussed in sect. . . . . however, diffusion tensor data may be insufficient to describe tissue in certain geometrical situations. a well-known example is the crossing of white-matter fibers within a single voxel as illustrated in fig. . . . water diffusion in such voxels cannot be fully described by a single ellipsoid, i.e., by the diffusion tensor. to overcome this limitation, more complex measurement techniques such as high-angular resolution diffusion imaging (hardi) (frank ; tuch et al. ) and q-ball imaging (tuch ) have been proposed. all these techniques use a large number of different diffusion directions (e.g., between [frank ] and [tuch ]) distributed isotropically in space. diffusion data is measured with high-angular resolution in order to determine the spatial distribution of diffusion in more detail as indicated in fig. . . d . a further generalization of diffusion tensor measurements loosens the assumption of gaussian diffusion, which was illustrated in fig. . . . if diffusion is severely restricted, e.g., by cell membranes, no or very few molecules will move through this border; the probability distribution of diffusion distances will be limited to distances within the cell volume and will no longer be gaussian. the exact displacement probabilities in restricted diffusion can be measured with methods called q-space diffusion imaging (assaf et al. ) or diffusion spectrum imaging (wedeen et al. ) . both techniques require the acquisition of images with a large number of different b-values and, in the case of diffusion spectrum imaging, of different diffusion directions; e.g., the total number of diffusion measurements reported by wedeen et al. ( ) is . obviously, this large number of measurements severely limits the applicability of these new techniques in clinical studies; the studies should therefore be regarded as experimental work. another approach to overcome the limitations of models based purely on gaussian diffusion has been proposed by jensen et al. as diffusional kurtosis imaging (jensen et al. ) . diffusion data is acquired for several b-values over a large range between and , s/mm similarly to the way data is acquired in q-space imaging, but with a different mathematical model of the non-exponential decay. this method is related to several other studies that investigated diffusion properties in tissue at high b-values and found non-mono-exponential diffusion attenuation curves (inglis et al. ; clark et al. ) . this observation has frequently been attributed to the simultaneous measurement of water molecules in different environments such as the intracellular and the extracellular space; however, no final agreement on the interpretation of these data has been established (sehy et al. ) . diffusion tensor data calculated from the measurements shown in fig. . . ; all diffusion coefficients are in units of - mm /s. a the three diagonal elements dxx, dyy, and dzz, and b the off-diagonal elements dxy, dxz, and dyz of the tensor matrix. note the different intensity scales for diagonal and off-diagonal elements. some remaining eddy-current artifacts can be seen as enhanced edges in the maps of the off-diagonal elements diffusion tensor imaging results in a large amount of data-a full diffusion tensor, i.e., a symmetric × matrix, is determined for each pixel of the image dataset. due to this complex data structure, there is no simple way to visualize the complete diffusion tensor as a single intensity or color map. it would be straightforward to display the six independent elements of the tensor as separate maps as shown in fig. . . ; however, this would not be very helpful for the interpretation or quantitative evaluation of diffusion tensor data. instead, several techniques are used to reduce the diffusion tensor information to simpler datasets that can as easily be displayed and interpreted as other imaging data. most results of imaging examinations are presented as either signal intensity images or scalar parameter maps. these images and maps have the advantage that they can easily be manipulated, e.g., the contrast can be interactively adjusted, and they can be quantitatively evaluated by statistics over regions of interest. in order to obtain similar parameter maps of diffusion tensor data, a single scalar reflecting a certain tensor property must be calculated. the most important examples of such scalars are the mean diffusivity or trace of the diffusion tensor and the anisotropy of the tensor. the mean diffusivity of a diffusion tensor measurement, i.e., the diffusion coefficient averaged over all spatial directions, is displayed as parameter maps in fig. . . a ,b. the same data can be displayed either as an intensity-coded map (fig. . . a ) or as a color-coded map (fig. . . b ). both maps illustrate, e.g., the high diffusivity of csf and the typical adcs of about . × - mm /s in the white matter. many different scalar measures have been proposed to describe diffusion anisotropy, cf. sect. . . . . the two most important are the fractional anisotropy and the relative anisotropy shown in fig. . . c ,d. the maps are very similar; both show the high anisotropy of white matter as hyperintense areas in contrast to low anisotropy in gray matter or csf. these two scalars derived from the diffusion tensor are by far the most important quantities for the clinical evaluation of diffusion tensor data. the vast majority of clinical studies based on diffusion tensor imaging determine the mean diffusivity and the anisotropy in regions of interest in order, e.g., to statistically compare these data between certain patient groups or between patients and healthy controls. the mean diffusivity and the anisotropy contain certain important information about the diffusion tensor; if the diffusion tensor is visualized as ellipsoid, then the diffusivity reflects the volume of the ellipsoid and the anisotropy its deviation from a spherical shape. however, any information about the main diffusion direction, i.e., the orientation of the longest axis of the diffusion tensor ellipsoid, is missing. this direction corresponds to the microstructural orientation of tissue, e.g., the orientation of white-matter tracts, and is determined as the eigenvector of the largest eigenvalue of the tensor (c.f. sect. . . . ). there are two common methods to visualize the direction of this eigenvector: color coding and direct vector display. the direction can be color-coded using the redgreen-blue (rgb) color model. each direction in space is defined by a three-component vector v = (vx vy vz) . if this three-component vector is interpreted as an rgb color specification, vectors in x-direction, v = ( ), appear as red pixels, vectors in y-direction as green pixels, and vectors in z-direction as blue pixels. eigenvectors in other directions are displayed as (additive) mixtures of different colors, e.g., the vector v = ( ) as mixture of red and blue, yielding violet pixels. the resulting color map is finally scaled with the diffusion anisotropy, since the fig. . . the diffusion tensor cannot represent diffusion properties in voxels with crossing nerve fibers. voxels with a single predominant fiber direction (a,b) show diffusion tensor ellipsoids whose longest axes correspond to the fiber orientation. voxels with crossing fibers (c) result in a diffusion tensor ellipsoid with reduced anisotropy pointing in an averaged fiber direction. advanced methods such as high angular resolution diffusion imaging (d) can resolve different fiber orientations within a single voxel . diffusion-weighted imaging and diffusion tensor imaging main diffusion direction is of interest only in areas with high anisotropy. some examples of these color-coded vector maps are shown in fig. . . . the red color of the corpus callosum demonstrates that the nerve fibers are predominantly oriented in the left-right direction. white-matter areas in green and blue are oriented in the anterior-posterior direction and the head-foot direction, respectively. alternatively, the main diffusion direction can be directly displayed by a small line in each pixel; some authors refer to this technique as whisker plots. this visualization is on the one hand more intuitive than color coding, but on the other hand difficult to display for large areas because of the large number of pixels (and hence lines) of a complete image. an example is shown in fig. . . ; the magnified area shows again the corpus callosum, where the diffusion directions follow the anatomical orientation of the nerve fibers. a general problem and limitation of the visualization of the main diffusion direction is that it is based on the assumption of linear diffusion, i.e., the diffusion ellipsoid is supposed to have a cigar-like shape. this is usually true in white matter tracts, but may lead to deceptive graphical depictions at crossing fibers or if diffusion is described by a planar tensor. another disadvantage is that vector maps are difficult to compare or to evaluate statistically. it is also possible to visualize the full diffusion tensor using the diffusion ellipsoid introduced in sect. . . . . as in the vector plots, it is often difficult to visualize the entire amount of data belonging to a single image slice at once. therefore, this d tensor visualization is usually combined with tools to zoom into the illustration and fig. . . parameter maps displaying scalar quantities calculated from the diffusion tensor. direction-independent mean diffusivity shown as gray-scaled map (a) and as color-coded map (b); the diffusion coefficients are given in units of - mm /s. (c) fractional anisotropy and (d) relative anisotropy fig. . . color-coded visualization of main diffusion orientation in four different slices (a-d). the main diffusion direction (orientation of the longest axes of the diffusion ellipsoid) is shown in red, green, and blue for left-right, anterior-posterior, and head-foot orientation, respectively, as indicated in e. the green rim at the frontal brain is caused by remaining eddy-current and susceptibility artifacts to rotate the slice in order to view the tensors in specific areas of the brain, as demonstrated in fig. . . . the ellipsoids are additionally color-coded to emphasize the direction of their longest axis (the main diffusion direction); their brightness is scaled by the anisotropy. thus, the ellipsoid visualization combines features of the techniques described in the previous sections and, e.g., csf is displayed as large but relatively dark spheres (denoting a high diffusion coefficient and low anisotropy), while the tensors in fiber tracts appear as bright elongated ellipsoids corresponding to linear diffusion in a single predominant orientation. the exact depiction of the tensor information is not standardized but may look different depending on the tools used. an alternative visualization may substitute the ellipsoids by cuboids with equivalent dimensions as shown in fig. . . . the presented information is the same as before, but the computational cost required to display cuboids is substantially lower than with smooth ellipsoids. thus, interactive manipulation of the d datasets may be faster using the cuboid visualization. close inspection of the main diffusion directions in figs. . . or . . suggests that the shape of white matter tracts can be reconstructed by connecting several diffusion directions in an appropriate way. this process is illustrated in fig. . . , based on a magnification of fig. . . . by choosing a start point and following the main diffusion direction, trajectories can be constructed that visualize the fiber tracts of white matter. a typical example is shown in fig. . . , where a seed region was placed within the corpus callosum, and all fibers through this seed region were reconstructed. the color of the fi- bers reflects the local anisotropy in this case, but various other color schemes could be used instead. fiber tracking or diffusion tractography was developed in the late s (mori et al. ; conturo et al. ; mori and van zijl ; melhem et al. ) , and a multitude of different algorithms to reconstruct fibers have been proposed since then. most techniques include data interpolation to increase the spatial resolution, and all require certain criteria to decide when the tracking of a fiber should be stopped (e.g., at pixels with low anisotropy or at sudden changes of diffusion direction). fiber tracking is usually based either on a single-region approach, in which all fibers are tracked that go through a user-defined region of interest, or on a two-region approach where connecting fibers between two regions are reconstructed. fiber tracking depends on good image quality, with sufficient signal-to-noise ratio and without substantial distortion artifacts. increased noise can reduce the calculated anisotropy (jones and basser ) and, thus, the length of the reconstructed fibers. image distortions cause a mismatch of anatomical fiber orientation and the measured diffusion direction and thus can lead to erroneous tractography results. therefore, parallel imaging and eddy-current correction techniques can improve the results of white-matter tractography. it is generally assumed that isotropic spatial image resolution is preferable for fiber tracking applications. a typical protocol suggested by jones et al. acquires data of the whole brain in isotropic . × . × . mm resolution (jones et al. b) . fiber tracking is a valuable tool to visualize white matter structures of the brain. however, it is still very difficult to evaluate tractography results quantitatively, to assess the accuracy of reconstructed fibers, or to compare the results of different examinations. first approaches to these questions include the spatial normalization of ten- fig. . . three-dimensional visualization of the full diffusion tensor as colorcoded cuboids; the cuboids are colored as in fig. (jones et al. a ) and the determination and visualization of uncertainties of diffusion tensor results (jones ; jones and pierpaoli ) . fig. . . reconstruction of white matter tracts starting at a seed region in the corpus callosum. visualization was performed with the "dti task card" provided by the mgh/mit/hms athinoula a. martinos center for functional and structural biomedical imaging (ruopeng wang) risks and safety issues related to mr examinations with the rapid development of mr technology and the significant level of growth in the number of patients examined with this versatile imaging modality, the consideration of possible risks and health effects associated with the use of mr procedures is gaining increasingly in importance. as described in detail in the previous chapters, three types of fields are employed: • a high static magnetic field generating a macroscopic nuclear magnetization • rapidly alternating magnetic gradient fields for spatial encoding of the mr signal • radiofrequency (rf) electromagnetic fields for excitation and preparation of the spin system in the following, the biophysical interaction mechanisms and biological effects of these fields are summarized as well as exposure limits and precautions to be taken to minimize health hazards and risks to patients and volunteers undergoing mr procedures. in the recent past, a number of excellent reviews and books related to this topic have been published. for details and supplementary information, the reader is referred to these publications quoted in the following and to the bibliographies given therein. because no ionizing radiation is used in mri, it is generally deemed safer than diagnostic x-ray or nuclear medicine procedures in terms of health protection of patients. in this context, a fundamental difference between ionizing and non-ionizing radiation has to be noted: radiation exposure to ionizing radiation-at least at the relatively low doses occurring in medical imaging-results in stochastic effects, whereas biological effects of (electro)magnetic fields are deterministic. a stochastic process is one where the exposure determines the probability of the occurrence of an event but not the magnitude of the effect. in contrast, deterministic effects are those for which the magnitude is related to the level of exposure and a threshold may be defined (international commission on non-ionizing radiation protection [icnirp] ). as a consequence, the probability of detrimental effects caused by diagnostic x-ray and nuclear medicine examinations performed over many years accumulate, whereas physiological stress induced by mr procedures is related to the acute exposure levels of a particular examination and does, to the present knowledge, not accumulate over years. in the recent past, regulations concerning mr safety have been largely harmonized. there are two comprehensive reviews by international commissions that form the basis for both national safety standards and the implementation of monitor systems by the manufacturers of mr devices: with μ = . × - vs/m the magnetic permeability in vacuum. due to the covalent binding of atoms, electron shells in most molecules are completely filled and thus all electron spins are paired. nevertheless, these diamagnetic materials can be weakly magnetized in an external magnetic field. as described in sect. . . . , this universal effect is caused by changes in the orbital motion of electrons in an external magnetic field. the induced magnetization is very small and in a direction opposite to that of the applied field (χ < ). paramagnetic materials, on the other hand, contain molecules with single, unpaired electrons. the intrinsic magnetic moments related with these electrons tend-comparable to the much weaker nuclear magnetic moment (cf. sect. . . )-to align in an external magnetic field. this effect increases the magnetic field in paramagnetic materials ( < χ < , ). in ferromagnetic materials-such as iron, cobalt, or nickel-unpaired electron spins align spontaneously with each other in the absence of a magnetic field in a region called a domain. these materials are characterized by a large positive magnetic susceptibility (χ > , ). biomolecules are in general diamagnetic and contain at most some paramagnetic centers. in almost all human tissues, the concentration of paramagnetic components is so low that they are characterized by susceptibilities differing by no more than % from that of water (χ = - , · - ) (schenck (schenck , . as a consequence, there is virtually no effect of the human body on an applied magnetic field (b ≅ μ h ). there are several established physical mechanisms through which static magnetic fields can interact with biological tissues and organisms. the most relevant mechanisms are discussed in the following. even in a uniform magnetic field, molecules or structurally ordered molecule assemblies with either a field-induced (diamagnetic) or permanent (paramagnetic) magnetic moment mmol experience a mechanical torque that tends to align their magnetic moment parallel (or antiparallel) to the external magnetic field and thus to minimize the potential energy ( fig. . . a ). orientation effects, however, can only occur when molecules or molecule clusters have a nonspherical structure and/or when the magnetic properties are anisotropically distributed. moreover, the alignment must result in an appreciable reduction of the potential energy (emag ∝ - mmol b) of the molecules in the external field with respect to their thermal energy (etherm ∝ kt). at higher temperatures, as for example in the human body, the alignment of molecules with small magnetic moments is prevented by their thermal movement (brownian movement) . in a non-uniform magnetic field, as for example in the periphery of an mr system, paramagnetic and ferromagnetic materials, moreover, are attracted and thus can quickly become dangerous projectiles (fig. . . b) . magneto-hydromechanical interactions. static magnetic fields also exert forces (called lorentz forces) on moving electrolytes (ionic charge carriers) giving rise to induced electric fields and currents. for an electrolyte with charge q, the lorentz force, which acts perpendicular to the direction of the magnetic field, b, and the velocity, v, of the electrolyte is given by ( . . ) since electrolytes with a positive or negative charge moving, for example, through a cylindrical blood vessel orientated perpendicular to a magnetic field are accelerated into opposite directions, this mechanism gives rise to an electrical voltage across the vessel, which is commonly referred to as blood flow potential (fig. . . ). moreover, the induced transversal velocity component also interacts with the magnetic field according to eq. . . , which results in a lorentz force that is directed antiparallel to the longitudinal velocity component. at very high magnetic field strengths, this secondary effect can reduce the flow velocity and the flow profile of blood in large vessels (tenforde ) . theoretically modeling of magneto-hydromechanical interaction processes was performed by tenforde ( ) based on the navier-stokes equation describing the flow of an electrically conductive fluid in the presence of a magnetic field using the finite element technique. induced current densities in the region of the sinoatrial node are predicted to by greater than ma/m at field levels of more than t in an adult human. moreover, magneto-hydromechanical interactions were predicted to reduce the volume flow rate of blood in the human aorta by a maximum of . , . , and . % at field levels of , , and t, respectively. magnetic effects on chemical reactions. as shown by in vitro studies, several classes of organic chemical reactions can be influenced by static magnetic fields under fig. . . magneto-mechanical effects. a orientation of a molecule with a magnetic moment m in a uniform magnetic field. b attraction of a paramagnetic or ferromagnetic object in a non-uniform magnetic field. the direction of the acting forces f is indicated by arrows appropriate, non-physiological conditions (grissom ; world health organization [who] ). an established effect consists in the modification of the kinetics of chemical reactions with radicals as intermediate products, brought about by splitting and modification of electron spin states in the magnetic field. an example is the conversion of ethanolamine to acetaldehyde by the bacterial enzyme ethanolamine ammonia lyase. radical pair magnetic field effects are thus used as a tool for invitro studies of enzyme reactions (who ). for individual macromolecules, the extent of orientation in strong magnetic fields is very small. for example, measurements on dna in solution have been shown that a magnetic flux density of t is required to produce orientation of about % of the molecules (maret et al. ) . in contrast, there are several examples of molecular aggregates that can be oriented to a large extend by static magnetic fields, such as outer segments of retinal rod cells, muscle fibers, and filamentous virus particles (icnirp ; who ). an example of an intact cell that can be oriented magnetically is the erythrocyte. it has been shown that both resting and flowing sickled erythrocytes align in fields of more than . t with their long axis perpendicular to the magnetic flux lines (brody et al. ; murayama ) . highashi et al. ( ) reported that normal erythrocytes could be oriented with their disk planes parallel to the magnetic field direction. this effect was detectable even at t, and almost % of the cells were oriented when exposed to t. on the other hand, calculations performed by schenck ( ) yielded that all of these orientation effects observed in vitro are probably too small to affect the orientation of the equivalent structures in vivo. however, although biophysical models make it possible to roughly estimate the magnitude of static magnetic field effects, the reality is so complex that calculations can in principle not rule out physiological effects (hore ) . based on the evidence at present, there is no strong likelihood of major physiological consequences arising from radical-pair magnetic field effects on enzymatic reactions. reasons against are the efficacy of homeo-static buffering and the fact that the contrived conditions needed to observe a magnetic field response in the laboratory are unlikely to occur under physiological conditions (hore ) . there have been only a few studies on the effects of static magnetic fields at the cellular level. they reveal that exposure to static magnetic fields alone has no or extremely small effects on cell growth, cell cycle distribution, and the frequency of genetic damage, regardless of the magnetic flux density. however, in combination with other external factors such as ionizing radiation or some chemicals, there is evidence to suggest that a static magnetic field modifies their effects (miyakoshi ) . with regard to possible effects on reproduction and development, no adverse effects of static magnetic fields have been consistently demonstrated; few good studies however have been carried out, especially to fields in excess of t (icnirp ; saunders ; who ) . several studies indicate that implantation as well as prenatal and postnatal development of the embryo and fetus is not affected by exposure for varying periods during gestation to magnetic fields of flux densities between and . t (konermann and mönig ; murakami et al. ; okazaki et al. ; sikov et al. ). on the other hand, mevissen et al. ( ) reported that continuous exposure of rats to a -mt field slightly decreased the numbers of viable fetuses per litter. electric flow potentials generated across the aorta and other major arteries by the flow of blood in a static magnetic field can routinely seen in the ecg of animals and humans, exposed to fields in excess of mt. in humans, the largest potentials occur across the aorta after ventricular contraction and appear superimposed on the t-wave amplitude of the ecg. different animal studies demonstrated effects of static magnetic fields on blood flow, arterial pressure, and other parameters of the cardiovascular system, often at fields with flux densities much less than t (saunders ). the results of these studies, however, have to be interpreted with caution because it is difficult to reach any firm conclusion from cardiovascular responses observed in anaesthetized animals (saunders ; who ). on the other hand, two recent studies on humans exposed to a maximum flux density of t (chakeres et al. ; kangarlu et al. ) did not yield clinically relevant changes in the heart rate, respiratory positively and negatively charged electrolytes moving with a velocity v through a blood vessel oriented perpendicular to a magnetic field are accelerated into opposite directions and thus induce an electric voltage uh across the vessel (blood flow potential). cross-hatches indicate the direction of the magnetic field into the paper plane . risks and safety issues related to mr examinations rate, diastolic blood pressures, finger pulse oxygenation levels, and core body temperature the only physiologic parameter that was found to be altered significantly by high-field exposure was a change in measured systolic blood pressure. this is consistent with a hemodynamic compensatory mechanism to counteract the drag on blood flow exerted by magneto-hydrodynamic forces as described in sect. . . . (chakeres and de vocht ) . various behavioral studies yielded that the movement of laboratory rodents in static magnetic fields above t may be unpleasant, inducing aversive responses and conditioned avoidance (who ) . such effects are thought to be consistent with magneto-hydrodynamic effects on the endolymph of the vestibular apparatus (who ) . this is in line with reports that some volunteers and patients exposed in static magnetic fields with flux densities above . t experienced sensations of vertigo, nausea, and a metallic taste in the mouth (chakeres et al. ; kangarlu et al. ; schenck schenck , . moreover, some of them reported on magnetophosphenes occurring during rapid eye movement in a field of at least t, which may be attributable to weak electric fields induced by movements of the eye, resulting in an excitation of structures in the retina (reilly ; schenck ) . two recent studies evaluated neurobehavioral effects among subjects exposed to static magnetic fields of . and t, respectively, using a neurobehavioral test battery. performance in an eye-hand coordination test and a near-visual contrast sensitivity task slightly declined at . t (de vocht et al. ) , whereas a small negative effect on short-term memory was noted at t (chakeres et al. ) . taking also into account the results of other neurobehavioral studies, it can be concluded that there is at present no evidence of any clinically relevant modification in human cognitive function related to static magnetic field exposure (chakeres and de vocht ) . there are only a few epidemiological studies available that were specifically designed to study health effects of static magnetic fields. the majority of these have been focused on cancer risks. in , the international agency for research on cancer (iarc) ( ) reviewed epidemiological studies focused on cancer risks. generally, these studies have not pointed to higher risks, although the number of studies was small, the numbers of cancer cases were limited, and the information on individual exposure levels was poor. therefore, the available evidence from epidemiological studies is at present not sufficient to draw any conclusions about potential health effects of static magnetic field exposure (feychting ; who ) . some epidemiological studies have investigated reproductive outcome for workers involved in aluminum industry or in mri. kanal et al. ( ) , for example, evaluated , pregnancies of women working at clinical mr facilities. comparing these pregnancies with those occurring in employees at other jobs, they did not find significant increased risks for spontaneous abortions, delivery before weeks, reduced birth weight, and male gender of the offspring. however, no studies of high quality have been carried out of workers occupationally exposed to fields greater than t. although there are initial experiences concerning the examination of volunteers and patients in ultra-high mr systems with magnetic flux densities of up to t, most clinical mr procedures have been performed so far at static magnetic fields below t. as summarized in sect. . . . , the literature does not indicate any serious adverse health effects from the exposure of healthy human subjects up to a flux density of t (icnirp ). however, because movements in static magnetic fields above t can produce nausea and vertigo, both the iec standard and the icnirp recommendation (table . . ) regulate that mr examinations above this static magnetic flux density should be performed in the controlled operating mode under medical supervision. the recommended upper limit for the operating mode is t, due to the limited information concerning possible effects above this magnetic flux density. for mr examinations performed in the experimental operating mode, there is no upper limit for the magnetic flux density. in a safety document issued in , the us food and drug administration (fda) ( ) deemed mr devices significant risk only when a static magnetic field of more than t is used. according to faraday's law, a time-varying magnetic field b(t) induces an electric field e(t), which has two important characteristics: the field strength is proportional to the time rate of change of the magnetic flux density, db(t)/dt, and the field lines form closed loops around the direction of the magnetic field. time-varying magnetic fields are used in mriamong others-to spatially encode mr signals arising from the different volume elements within the human body. to this end, three independent gradient coils are used to produce magnetic fields directed parallel to the static magnetic field b = ( , , b ) with a field strength varying in a linear manner along the x-, y- and z-direction as shown in fig. . . . for the special case of a spatially uniform magnetic field directed in the z-direction, bz(t), the electric field strength along a circular (conductive) loop of radius r in the x-y-plane is given by ( . . ) this equation reveals that the electric field strength in the considered circular loop increases linearly with its radius as well as with the rate of change, db(t)/dt. this model gives, for example, the electric field induced by the magnetic gradient field b = ( , , g z · z) of the z-gradient coil. in contrast, the distribution of the electric fields induced by the time-varying magnetic gradient fields b = ( , , g x · x) and b = ( , , g y · y) is much more complex, since the magnetic flux density of these fields is not uniform over the x-y-plane. moreover, the generation of these gradient fields is inevitable connected - due to fundamental principles of electrodynamics - with the occurrence of magnetic fields directed in the x- and y-direction, i.e., b = (bx, , ) and b = ( , by, ), respectively. although these "maxwell terms" are of no relevance for the acquisition of mr images, they have to be considered carefully with respect to biological effects. the distribution of electric fields induced by timevarying magnetic fields directed parallel and perpendicular to the long axis of the human body is schematically shown in fig. . . . the precise spatial and temporal distribution of the electric fields in the human body, of course, strongly depends on both the technical characteristics of the gradient coils implemented at a specific mr system and the morphology of the body region exposed, and thus cannot be described by a simple mathematical expression. for worst-case estimations, however, it can be assumed that the electric field induced by a non-uniform magnetic field is equal or smaller than the electric field produced by a uniform magnetic field with field strength equal to the maximum magnetic flux density of the nonuniform field (schmitt et al. ) . for a uniform magnetic field, the electric field strength reaches, in general, a maximum when the magnetic field is orientated perpendicular to the coronal plane of the body (see fig. . . , right) since the extension of conductive loops is largest in this direction (reilly ) . in conductive media, such as biological tissues, the internally induced electric field e(t), results in circulating eddy currents, j(t). both quantities are related by the electric conductivity of the medium, σ, ( . . ) calculation of the current distribution in the human body is complicated due to widely differing conductivities of various tissue components. for rough estimations, however, the body can be treated as a homogeneous medium with an average conductivity of σ = . s/m (reilly ). according to eqs. . . and . . , for example, a current density of ma/m is induced at a radius of cm by a rate of change in the magnetic flux density of dbz/dt = t/s. fig. . . schematic representation of the electric field induced by time-varying magnetic fields b(t) that are directed parallel (left) and perpendicular (right) to the long axis of the human body. the electric field lines form closed loops around the direction of the magnetic field the magnetic flux density of gradient fields used in mri is about two orders of magnitude lower than that of the static magnetic field b . therefore, time-varying magnetic fields produced by gradient coils in mri can be neglected compared to the strong static magnetic field as far as interactions of magnetic fields with biological tissues and organisms are concerned (cf. sect. . . . ). in contrast, however, biophysical effects related to the electric fields and currents induced by the magnetic fields have to be considered carefully. in general, rise times of magnetic gradients in mri are longer than µs, resulting in time-varying electric fields and currents with frequencies below khz. in this frequency range, the conductivity of cell membranes is several orders of magnitude lower than that of the extra-and intracellular fluid (foster and schwan ) . as illustrated in fig. . . , this has two important consequences. first, the cell membrane tends to shield the interior of cells very effectively from current flow, which is thus restricted to the extracellular fluid. second, voltages are induced across the membrane of cells. when the electric voltages are above a tissue-specific threshold level, they can stimulate nerve and muscle cells (foster and schwan ) . theoretical models describing cardiac and peripheral nerve stimulation have been presented by various scientists (i.e., by irnich, mansfield, and reilly) . a detailed discussion of the underlying assumptions of the different models and the differences between them can be found, among others, in (schaefer et al. ; schmitt et al. ). the best approximation to experimental data is given by a hyperbolic strength-duration expression ( . . ) which relates the stimulation threshold, expressed as rate of change db/dt of the magnetic flux density, with the stimulus duration t, i.e., the ramp time of the magnetic gradient field (schaefer et al. ; schmitt et al. ). a hyperbolic model comparable to eq. . . was first established by g. weiss in for an electric current pulse and the corresponding electric charge. this "fundamental law of electrostimulation" has been confirmed meanwhile in numerous studies for neural and cardiac excitation as well as for defibrillation (schaefer et al. ) . as shown in fig. . . , the threshold for the strength of a stimulus decreases with its duration. the asymptotic stimulus strength, b • ∞, for an infinite duration is denoted as "rheobase"; the characteristic response time constant, τc , as "chronaxie". it should be mentioned that according to a model presented by irnich et al. stimulation depends on mean (rather than peak) db/dt changes and is thus independent on the special shape of the gradient pulse (schaefer et al. ) . in current safety regulations, however, exposure limits are unanimously expressed as maximum db/dt values. in accordance with the biophysical mechanisms described in the previous section, there is now a strong body of evidence suggesting that the transduction processes through which induced electric fields and currents can influence cellular properties involve interactions at the level of the cell membrane (icnirp ) . in addition to the stimulation of electrically excitable tissues, changes in membrane properties-such as ion-binding to membrane macromolecules, ion transport across the membrane, or ligand-receptor interactions-may trigger transmembrane signaling events. cardiac and peripheral nerve stimulation. experimental studies with magnetic stimulation of the heart have been carried out since about , with the introduction of improved gradient hardware for epi. experiments fig. . . in the frequency range below khz, the conductivity of cell membranes (σm) is several orders of magnitude lower than that of the extra- and intracellular fluid (σext and σint, respectively) so that the induced electric fields (and also the resulting electric currents) are mainly restricted to the extracellular fluid (eext > eint). as a result, electric voltages are generated across the membrane of cells that can stimulate nerve and muscle cells were not performed of course with humans, but rather with dogs. the data, which are listed and reviewed by reilly ( ) , reveal that magnetic stimulation is most effective, when it is delivered during the t wave of the cardiac cycle. moreover, excitation thresholds for the heart are substantially greater than that for nerve as long as the pulse duration is sufficiently less than the chronaxie time of the heart of about ms. therefore, the avoidance of peripheral sensations in a patient provides a conservative safety margin with respect to cardiac stimulation. bourland et al. ( ) determined a mean value of . ± . for the ratio of cardiac (the induction of ectopic beats) to muscle stimulation in dogs for a pulse duration of µs, which is quite close to the theoretical heart/nerve ratio of . estimated by reilly ( ) . various studies yielded that the cardiac threshold variability of healthy persons is surprisingly low, which is confirmed by experimental and clinical experience that pacing thresholds are rather uniform (schmitt et al. ). drugs and changes in electrolyte concentrations can lower thresholds, but not below about % of the normal value (schmitt et al. ). peripheral nerve stimulation has been investigated in various volunteer studies. a systematic evaluation of the available data was presented by schaefer et al. in . they recalculated published threshold levels-often reported for different gradient coils and shapes in different terms-to the maximum db/dt occurring during the maximum switch rate of the gradient coil at a radius of cm from the central axis of the mr system, i.e., at the border of the volume normally accessible to patients. in fig. . . , the recalculated threshold levels are plotted for the y- (anterior/posterior) and z-gradient coils (superior/inferior) as compared to model estimates by reilly. as expected, y-gradient coils have lower stimulation threshold for a given ramp time than x-gradient coils since the x-z cross-sections of the body are usually larger than are x-y cross-sections. by fitting the hyperbolic strength-duration relationship defined in eq. . . to mean peripheral nerve stimulation thresholds measured by bourland et al. ( ) in human subjects, schaefer et al. estimated the following values for the rheobase/chronaxie: . t/s/ . ms for the y-gradient and . t/s / . ms for the z-gradient. as shown in fig. . . , the db/dt intensity to induce a sensation that the subject described as uncomfortable or even painful was significantly above the sensation threshold. bourland et al. ( ) also analyzed their stimulation data in the form of cumulative frequency distributions, that gives for a db/dt level the number of subjects that had already reported on perceptible, uncomfortable, or even intolerable sensations. they found that the db/dt level needed for the lowest percentile for uncomfortable stimulation is approximately equal to the median threshold for perception. the lowest percentile for intolerable stimulation occurs at a db/dt level approximately % above the median perception threshold. time-varying magnetic fields can also result in the perception of magnetophosphenes due to the induction of electrical currents, presumably in the retina (cf. sect. . . . ). a unique feature of phosphenes, which are not considered to be hazardous to humans, is their low excitation threshold and sharply defined excitation frequency of about hz as compared to other forms of neural stimulation (reilly ) . in general, a combination of magnetic gradient fields from all three gradient coils is used in mri. in this case, the biological relevant time-varying magnetic field is approximately given by the vector sum of the magnetic field components. a detailed discussion of the effect of stimulus shape, number of stimuli, and other experimental set- fig. . . hyperbolic strength-duration expression that relates the stimulation threshold, expressed as rate of change db/dt of the magnetic flux density, with the stimulus duration t, i.e., the ramp time of the magnetic gradient field. the asymptotic stimulus strength, b • ∞, for an infinite duration is denoted as rheobase; the characteristic response time constant, τc , as chronaxie . risks and safety issues related to mr examinations tings on stimulation thresholds can be found in (reilly ; schmitt et al. ). a comprehensive review of the current scientific evidence on biological effects of low-frequency electromagnetic fields in the frequency range up to khz has been published by icnirp in . the majority of the reviewed studies focus on extremely low-frequency (elf) magnetic fields associated with the use of electricity at power frequencies of or hz. according to the icnrip review, cellular studies do not provide convincing evidence that low-frequency magnetic fields alter cell division, calcium homeostasis, and signaling pathways. furthermore, no consistent effects were found in animals and humans with respect to genotoxicity, reproduction, development, immune system function, as well as endocrine and hematological parameters. on the other hand, a number of laboratory and field studies on humans demonstrated an effect of low-frequency magnetic fields at higher exposure levels on the power spectrum of different eeg frequency bands and on sleep structure. in the light of cognitive and performance studies yielding a number of biological effects, further studies are necessary to clarify the significance of the observed effects for human health. over the last two decades, a large number of high quality epidemiological investigations of long-term disease endpoints such as cancer, cardiovascular and neurodegenerative disorders have been performed in relation to time-varying-mainly elf-magnetic fields. following the mentioned icnirp review ( ), the results can be summarized as follows. among all the outcomes evaluated, childhood leukemia in relation to postnatal exposures to or hz magnetic fields at flux densities above . µt is the one for which there is most evidence of an association. however, the results are difficult to interpret in the absence of evidence from cellular and animal studies. there is also evidence for an association of amyotrophic lateral sclerosis (als) with occupational emf exposure although confounding is a potential explanation. whether there are associations with breast cancer and cardiovascular disease remains unsolved. from a safety standpoint, the primary concern with regard to rapid switching of magnetic gradients is cardiac fibrillation, because it is a life-threatening condition. in contrast, peripheral nerve stimulation is of practical concern because uncomfortable or intolerable stimulations would interfere with the examination (e.g., patient movements) or would even result in a termination of the examination. in the current safety recommendations issued by iec ( ) and and icnrip ( ), maximum db/dt values for time-varying magnetic fields created by gradient coils is limited for patient and volunteer examinations performed in the normal and the controlled operating mode by the db/dt level of % and % of the mean perception threshold for peripheral nerve stimulation, respectively. to this end, mean perception threshold levels have to be determined by the manufacturers for any given type of gradient system by means of experimental studies on human volunteers. as an alternative, the following empirical hyperbolic strength-duration expression for the mean threshold for peripheral nerve stimulation (expressed as maximum change of the magnetic flux density in t/s) can be used: ( . . ) in this equation, teff is the effective stimulation duration (in milliseconds), i.e., the duration of the period of monotonic increasing or decreasing gradient. a mathematical definition for arbitrary gradient shapes can be found in the iec standard ( ). time-varying magnetic fields used for the excitation and preparation of the spin system in mri (b fields, cf. sect. . . ) have typically frequencies above mhz. in this rf range, the conductivity of cell membranes is comparable to that of the extra-and intracellular fluid, which means that no substantial voltages are induced across the membranes (foster and schwan ) . due to this reason, stimulation of nerve and muscle cells is no longer a matter of concern. instead, thermal effects due to tissue heating are of importance. energy dissipation of rf fields in tissues is described by the frequency-dependent conductivity σ(ω), which characterizes energy losses due to the induction and orientation of electrical dipoles as well as the drift of free charge carriers in the induced time-varying electric field (foster and schwan ) . the energy absorbed per unit of tissue mass and time, the so-called specific absorption rate (sar, in w/kg), is approximately given by where e is the induced electric field, j the corresponding current density, and ρ the tissue density (cf., . . . ). absorption of energy in the human body strongly depends on the size and orientation of the body with respect to the rf field as well as on the frequency and polarization of the field. theoretical and experimental considerations reveal that rf absorption in the body approaches a maximum when the wavelength of the field is in the order of the body size. unfortunately, the wavelength of the rf fields used in mri falls into this "resonance range. " in order to discuss the effect of various measurement parameters on rf absorption, let us consider a simple mr sequence with only one rf pulse-such as a d or d flash sequence. in this case, the time-averaged sar can approximately be described by the expression ( . . ) according to this equation, the time-averaged sar is proportional • to the square of the static magnetic field, b , which means that energy absorption is markedly higher at high-field as compared to low-field mr systems • to the square of the pulse angle, α, so that a sequence with a ° or even a ° pulse will result in a much higher sar value than a sequence with a low-angle excitation pulse • to the duty cycle, tp / tr, of the sequence, e.g., the ratio of the pulse duration tp and the repetition time tr of the pulse or sequence • to the number of slices, ns, subsequently excited within the repetition time of a d sequence (multi-slice technique, cf. sect. . . ; ns = for d sequences) in case of a more complex mri sequence with various rf pulses, e.g., a spin-echo or a turbo spin-echo sequence, the contribution of the different rf pulses to patient exposure has to be summed up. the most relevant quantity for the characterization of physiological effects related to rf exposure is the temperature rise in the various body tissues, which is not only dependent on the localized sar and the duration of exposure, but also on the thermal conductivity and microvascular blood flow (perfusion). in case of a partial-body rf exposure, the latter two factors lead to fast temperature equalization within the body (adair ) . based on the bioheat equation, it can be shown (brix et al. ) that for this particular exposure scenario the temperature response in the center of a homogenous tissue region, which is larger in each direction than the so-called thermal equilibration length, λ, is given by a convolution of the exposure-time course, sar(t), with a tissue-specific system function, exp (-t/τ), ( . . ) where τ is the thermal equilibration time, ta the constant temperature of arterial blood, and c the specific heat capacity of the tissue. for representative tissues, equilibration lengths and times are between . and mm and . and min, respectively (brix et al. ) . both parameters are inversely related to tissue perfusion and thus vary considerably. in case of a continuous rf exposure, the temperature rise even in poorly perfused tissues is less than . °c for each w/kg of power dissipated. using a simple model of power deposition in the head, athey ( ) showed that continuous rf exposure over h is unlikely to raise the temperature of the eye by more than . °c when the average sar to the head is less than . w/kg. more complex computations were performed by gandhi and chen ( ) for a high-resolution model of the human body using the finite-difference time domain in order to assess sar distributions in the body for different rf coils. their calculations indicate that the maximum sar averaged over g of tissue can be ten times greater than the whole-body average sar ("hot spots"). established biological effects of rf fields used for mr examinations are primarily caused by tissue heating. therefore, it is important to critically evaluate the numerous number of studies focused on temperature effects, from the cellular and tissue level to the whole-body level, in-cluding potential effects on vulnerable persons. in contrast, non-thermal (or athermal) effects are not well understood but seem-as far as this can be assessed at moment-to have no relevance with respect to the assessment of adverse effects associated with mr examinations. non-thermal effects are those which can only be explained in terms of mechanisms other than increased random molecular motion (i.e., heating) or which occur at sar levels so low that a thermal mechanism seems unlikely (icnirp ) . as summarized in a review by lepock ( ) , relative short exposures of mammalian cells to temperatures in excess of - °c result in a variety of effects, such as inhibition of cell growth, cytotoxic changes, alteration of signal transduction pathways, and an increased sensitivity to other stresses such as ionizing radiation and chemical agents. this suggests that damage is not localized to a single target, but that multiple heat-labile targets are damaged. extensive protein denaturation has been observed at temperatures of - °c for moderate periods. the most sensitive animal responses to heat loads are thermoregulatory adjustments, such as reduced metabolic heat production, vasodilatation, and increased heart rate. the corresponding sar thresholds are between about . and w/kg (icnirp ) . the observed cardiovascular changes reflect normal thermoregulatory responses that facilitate the conduction of heat to the body surface in order to maintain normal body temperatures. direct quantitative extrapolation of the animal (including primate) data to humans, however, is difficult given the marked species differences in the basal metabolism and thermoregulatory ability (who ) . at levels of rf exposure that cause body temperature rises of °c or more, a large number of additional, in most cases reversible, physiological effects have been observed in animals, such as alterations in neural and neuromuscular functions, increased blood-brain barrier permeability, stress-associated changes in the immune system, and hematological changes (icnirp ; michaelson and swicord ; who ) . thermal sensitivities and thresholds for irreversible tissue damage from hyperthermia have been summarized by dewhirst et al. ( ) . the most sensitive organs to acute damage are the testes and brain as well as portions of the eye (lens opacities and corneal abnormalities). the sar threshold for irreversible effects even in the most sensitive tissues caused by rf exposure, however, is greater than w/kg under normal environmental conditions (icnirp ) . effects of heat on embryo and fetus have been thoroughly reviewed by edwards et al. ( ) . processes critical to embryonic development, such as cell proliferation, migration, differentiation, and apoptosis are adversely affected by elevated maternal temperatures. therefore, hyperthermia of animals during pregnancy can cause embryonic death, abortion, growth retardation, and developmental defects. especially the development of the central nervous system is susceptible to heat. however, most animal data indicate that implantation and the development of the embryo and fetus are unlikely to be affected by rf exposures that increase maternal body temperature by less than °c (who ). in humans, epidemiological studies suggest that an elevation of maternal body temperature by °c for at least h during fever can cause a range of developmental defects, but there is little information on temperature thresholds for shorter exposures (edwards et al. ) . humans possess comparatively effective heat loss mechanisms. in addition to a well-developed ability to sweat, the dynamic range of blood flow rates in the skin is much higher than it is in other species. studies focused on rf-induced heating of patients during mr procedures have been summarized and evaluated in a review by shellock ( ) . they indicate that exposure of resting humans for - min to rf fields producing a whole-body sar of up to w/kg results in a body temperature increase between . and . °c (who ) . of special interest is an extensive mr study reported by shellock et al. ( ) . in this study, thermal and physiologic responses of healthy volunteers undergoing an mr examination over min at a whole-body averaged sar of . w/kg were investigated in a cool ( °c) and a warm ( °c) environment. in both cases, significant variations of various physiologic parameters were observed, such as an increase in the heart rate, systolic blood pressure, or skin temperature. however, all variations were in a range that can be physiologically tolerated by an individual with normal thermoregulatory function (shellock et al. ) . generally, these studies are supported by mathematical modeling of human thermoregulatory responses to mr exposure (adair ; adair and berglund , ) . it should be noted, however, that heat tolerance or thermoregulation may be compromised in some individuals undergoing an mr examination, such as the elderly, the very young and people with certain medical conditions (e.g., obesity, hypertension, impaired cardiovascular functions, diabetes, fever, etc.) and/or taking certain medications (e.g., beta-blockers, calcium channel blockers, sedatives, etc.) (donaldson et al. ; goldstein et al. ; icnirp ; shellock ) . some regions of the human body, in particular the brain, are particularly vulnerable to raised temperatures. mild-to-moderate hyperthermia (body temperature less than °c) induced thermal stress. for example, it affects cognitive performance (sharma and hoopes ) and can produce specific alterations in the cns that may have long-term physiological and neuropathological consequences (hancock and vasmatzidis ) . there have been a large number of epidemiological studies over several decades, particularly on cancer, cardiovascular disease, and cataract, in relation to occupational, residential, and mobile-phone rf exposure. as summarized in a review published by the icnirp standing committee on epidemiology (ahlbom et al. ) , results of these studies give no consistent or convincing evidence of a causal relation between rf exposure and adverse health effect. it has to be noted, however, that the studies considered not only have too many deficiencies to rule out an association but also focus on chronic exposures at relatively low levels-an exposure scenario that is not comparable to mr examinations of patients. as reviewed in the previous section, no adverse health effects are expected if the rf-induced increase in body core temperature does not exceed °c. in case of infants, pregnant women, or persons with cardiocirculatory im-pairment, it is desirable to limit body core temperature increases to . °c. as indicated in table . . , these values have been laid down in the current safety recommendations (iec, icnirp) to limit the body core temperature for the normal and controlled operating mode. additionally, local temperatures under exposure to the head, trunk, and extremities are limited for each of the two operating modes to the values given in table . . . however, temperature changes in the different parts of the body are difficult to control during an mr procedure in clinical routine. therefore, sar limits have been derived on the basis of experimental and theoretical studies, which should not be exceeded in order to limit the temperature rise to the values given in table . . . as only parts of the body-at least in the case of adult patients-are exposed simultaneously during an mr procedure, not only the whole-body sar but also partial-body short-term sar the sar limit over any -s period shall not exceed times the corresponding average sar limit a partial-volume sars given by iec; icnirp limits sar exposure to the head to w/kg b partial-body sars scale dynamically with the ratio r between the patient mass exposed and the total patient mass: normal operating mode, sar= ( - . r) w/kg; controlled operating mode, sar = ( - . r) w/kg c in cases where the eye is in the field of a small local coil used for rf transmission, care should be taken to ensure that the temperature rise is limited to °c sars for the head, the trunk, and the extremities have to be estimated by means of suitable patient models (e.g., brix et al. ) and limited to the values given in table . . for the normal and controlled operating mode. with respect to the application of the sar levels defined in table . . , the following points should be taken into account: • when a volume coil is used to excite a greater field-of view homogeneously, the partial-body and the wholebody sars have to be controlled: in the case of a local rf transmit coil (e.g., a surface coils), the local and the whole-body sar (iec ). • partial-body sars scale dynamically with the ratio r between the patient mass exposed and the total patient mass. for r → they converge against the corresponding whole-body values, for r → against the localized sar level of w/kg established by icnirp for occupational exposure of head and trunk (icnirp ). • the recommended sar limits do not relate to an individual mr sequence, but rather to running sar averages computed over each -min-period, which is assumed a typical thermal equilibration time of smaller masses of tissue. but even if mr examinations are performed within the established sar limits, severe burns can occur under unfavorable conditions at small focal skin-to-skin contact zones. the potential danger is illustrated in fig . . by the case of a patient who developed third-degree burns at the calves after conventional mr imaging. in this case, the contact between the calves resulted in the formation of a closed conducting loop and high current densities near the small contact zone. therefore, patients should always be positioned in such a way that focal skin-to-skin contacts are avoided (e.g., by foam pads) (knopp et al. ). to protect volunteers, patients, accompanying persons, and uninformed healthcare workers from possible hazards and accidents associated with the mr environment, it is indispensable to perform a proper control of access to the mr environment. the greatest potential hazard comes from metallic, in particular ferromagnetic materials (such as coins, pins, hair clips, pocketknives, scissors, nail clippers, etc.), that are accelerated in the inhomogeneous magnetic field (cf. sect. . . . ) in the periphery of an mr system and quickly become dangerous projectiles (missile effect). this risk can only be minimized by a strict and careful screening of all individuals entering the mr environment for metallic objects. every patient or volunteer should complete a detailed questionnaire prior to the mr examination to ensure that every item posing a potential safety issue is considered. an example of such a form can be found, for example, in shellock and crues ( ) , or can be downloaded from http://www.mrisafety.com. next, an oral interview should be conducted to verify the information of the form and to allow discussion of any question or concern that the patient may have before undergoing the mr procedure. an in-depth discussion of the various aspects of screening patients for mr procedures and individuals for the mr environment can be found in various publications by shellock (e.g., shellock ; shellock and crues ) and the webpage mentioned above. here only a condensed summary of the most important risks and contraindications can be given. all patients (and volunteers) undergoing mr procedures should-at the very least-be visually (e.g., by using a camera system) and/or acoustically (using an intercom system) monitored. moreover, physiologic monitoring is indicated whenever a patient requires observation of vital functions due to a health problem or whenever the patient is unable to communicate with the mr technologist regarding pain, respiratory problems, cardiac stress, or other difficulty that might arise during the examination (shellock ) . this holds especially in the case of sedated or anesthetized patients. for patient monitoring, special mr-compatible devices are available (shellock ) . pregnant patients undergoing mr examinations are exposed to the static magnetic field, time-varying gradient fields and rf fields. the few studies concerning the combined effects of these fields on pregnancy outcome in humans following mr examinations have not revealed any adverse effects, but are very limited due to the small numbers of patients involved and difficulties in the interpretation of the results (colletti ; icnirp ) . it fig. . . current-induced third-degree burns due to a small focal skin-to-skin contact between the calves during the mr examination. (from knopp et al. , with permission by springer-verlag) is thus advised that mr procedures may be performed in pregnant patients, in particular in the first trimester, only after critical risk/benefit analysis and with verbal and written informed consent of the mother or parents (colletti ) . the standard of care is that mr imaging may be used in pregnant woman, if other non-ionizing forms of diagnostic imaging (e.g., sonography) are inadequate or if the examination provides important information that would otherwise require exposure to ionizing radiation (e.g., fluoroscopy or ct) (colletti ; shellock and crues ) . in any case, however, exposure levels of the normal operating mode should not be exceeded and the duration of exposure should be reduced as far as possible (icnirp ) . mr examinations of patients with implants or metallic objects (such as bullets, pellets) are always associated with a serious risk, even if all procedures are performed within the established exposure limits summarized in the previous sections. this risk can only be minimized by a careful interview of the patient, evaluation of the patient's file and contacting the implanting clinician and/or the manufacturer for advice on mr safety and compatibility of the implant (medical devices agency ). in any case, mr procedures should be performed only after critical risk/benefit analysis. it should be noted that having undergone a previous mr procedure without incident does not guarantee a safe subsequent mr examination, since various factors (type of mr system, orientation of the patients, etc.) can substantially change the scenario (shellock and crues ) . in the case of passive implants-e.g., vascular clips and clamps, intravascular stents and filters, vascular access ports and catheters, heart valve prostheses, orthopedic prostheses, sheets and screws, intrauterine contraceptive devices, etc.-it has to be clarified if they are made of or contain ferromagnetic materials. as already mentioned, strong forces act on ferromagnetic objects in a static magnetic field. these forces (astm a) may result in a movement and dislodgment of ferromagnetic objects that could injure vessels, nerves or other critical tissue structures. comprehensive information on the mr compatibility (astm b) of more than , implants and other metallic objects is available in a reference manual published by shellock ( ) and online at http://www. mrisafety.com. mr examinations are deemed relatively safe for patients with implants or objects that have been shown to be non-ferromagnetic or weakly ferromagnetic (shellock and sawyer-glover ) . furthermore, patients with certain implants that have relatively strong ferromagnetic qualities may safely undergo mr procedures when the object is held in place by sufficient retentive forces, is not located near vital structures, and will not heat excessively (shellock and sawyer-glover ) . however, such examinations should be restricted to essential cases and should be performed at mr systems with a low magnetic field strength. examinations of patients with active implants or lifesupport systems are strictly contraindicated at conventional mr systems, if the patient implant card does not explicitly state their safety in the mr environment. in addition to the risks already mentioned above, there is the possibility that the function of the active implant is changed or perturbed, which may result in a health hazard for the patient. clinically important examples are cardiac pacemakers, implantable cardioverter defibrillators, infusion pumps, programmable hydrocephalus shunts, neurostimulators, and cochlear implants, etc. (medical devices agency ; shellock and sawyer-glover ) . the induction of electric currents by rf fields during imaging in implants made from conducting materials can result in excessive heating and thus may pose risks to patients. excessive heating is typically associated with implants that have elongated configurations and/or are electronically activated, as for example the leads of cardiac pacemakers or neurostimulation systems (shellock and crues ) . the same holds for electrically conductive objects (e.g., ecg leads, cables, wires, etc.), in particular when they form conductive loops in the bore of the mr system. to avoid severe burns, the instructions for proper operation of the equipment provided by the manufacturer of the implant or device have strictly to be followed. practical recommendations concerning this issue can be found in (shellock and sawyer-glover ) . in various reports, transient skin irritations, cutaneous swellings or heating sensations were described in relation to the presence of both permanent (cosmetic) and decorative tattoos. these findings seem to be associated with the use of iron oxide or other metal-based pigments that are prone to magnetic field-related interactions and/or rf-induced heating, in particular when the pigments are organized as loops or rings. according to a survey performed by tope and shellock ( ) , however, this side effect has an extremely low rate of occurrence in a population of subjects with tattoos and should not prevent patients-after informed consent-from undergoing a clinically indicated mr procedures (shellock and crues ) . as a precautionary measure, a cold compress may be applied to the tattoo site during the mr examination (tope and shellock ) . real-time position monitoring of invasive devices using magnetic resonance adaptive technique for highdefinition mr imaging of moving structures electrocardiogram acquisition during mr examinations for patient monitoring and sequence triggering acquiring simultaneous eeg and functional mri the modular (twin) gradient coil-high resolution, high contrast, diffusion weighted epi at . tesla resonant trapezoidal gradient generation for use in echo planar imaging monitoring the patient's eeg during echo planar mri biological effects and health implications in magnetic resonance imaging hazardous situation in the mr bore: induction in ecg leads causes fire on the induced electric field gradients in the human body for magnetic stimulation by gradient coils in mri active magnetic screening of coils for static and time-dependent magnetic field generated in nmr imaging limits to neural stimulation in echo planar imaging nmr probeheads for biophysical and biomedical experiments: theoretical principles and practical guidelines contrastenhanced mri of the central nervous system: comparison between gadodiamide injection and gd-dtpa evaluation of neck and body metastases to nodes with ferumoxtran -enhanced mr imaging: phase iii safety and efficacy study imaging of myocardial infarction: comparison of magnevist and gadophrin- in rabbits detection of colorectal liver metastases: a prospective multicenter trial comparing unenhanced mri, mndpdp-enhanced mri, and spiral ct detection of focal hepatic lesions: comparison of unenhanced and shu a-enhanced mr imaging versus biphasic helical ctap sensitivity of enhanced mr in multiple sclerosis: effects of contrast dose and magnetization transfer contrast evaluation of retroperitoneal and pelvic lymph node metastases with mri and mr lymphangiography intravascular contrast agent-enhanced mri measuring contrast clearance and tumor blood volume and the effects of vascular modifiers in an experimental tumor hepatocellular carcinoma in cirrhotic livers: double-contrast thin-section mr imaging with pathologic correlation of explanted tissue efficacy and safety of mr imaging with liver-specific contrast agent: us multicenter phase iii study diffusion and perfusion mr imaging in cases of alzheimer's disease: correlations with cortical atrophy and lesion load rationale and applications for macromolecular gd-based contrast agents microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic mr image series gadodiamide-associated nephrogenic systemic fibrosis: why radiologists should be concerned morphologic predictors of lymph node status in rectal cancer with use of high-spatial-resolution mr imaging with histopathologic comparison effects of three different doses of a bolus injection of gadodiamide: assessment of regional cerebral blood volume maps in a blinded reader study randomized double blind trial of the safety and efficacy of two gd complexes (gd-dtpa and gd-dota) public assessment reports increased risk of nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis and gd-containing mri contrast agents mri angiography is superior to helical ct for detection of hcc prior to liver transplantation: an explant correlation factors in myocardial "perfusion" imaging with ultrafast mri and gd-dtpa administration preclinical profile and clinical potential of gadocoletic acid trisodium salt (b / ), a new intravascular contrast medium for mri superparamagnetic iron oxides as positive mr contrast agents: in vitro and in vivo evidence oral contrast media for magnetic resonance tomography 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ssfp sequences separation of arteries and veins in d mr angiography using correlation analysis measurement of flow with nmr imaging using a gradient pulse and phase difference technique tissue specific perfusion imaging using arterial spin labeling phase contrast mr angiography techniques hepatic arterial-phase dynamic gadolinium-enhanced mr imaging: optimization with a test examination and a power injector fast selective black blood mr imaging improved time-offlight mr angiography of the brain with magnetization transfer contrast signal targeting with alternating radiofrequency (star) sequences: application to mr angiography cerebral arteriovenous malformations: improved nidus demarcation by means of dynamic tagging mr-angiography theoretical limits of spatial resolution in elliptical-centric contrast-enhanced d-mra time-resolved contrast-enhanced three-dimensional magnetic resonance angiography of the chest: combination of parallel imaging with view sharing (treat) perfusion imaging using arterial spin labeling nmr relaxation times of blood: dependence on field strength, oxidation state, and cell integrity steady-state and dynamic mr angiography with ms- : initial experience in humans reducing motion artifacts in two-dimensional fourier transform imaging time-resolved contrast-enhanced d mr angiography black blood angiography the effects of time varying intravascular signal intensity and kspace acquisition order on three-dimensional mr angiography image quality the effects of incomplete breath-holding on d mr image quality steady-state imaging for visualization of endovascular interventions non-contrast-enhanced mr angiography using d ecg-synchronized half-fourier fast spin-echo nonlinear excitation profiles for three-dimensional inflow mr angiography fisp-a new fast mri sequence mr angiography by multiple thin slab d acquisition first-pass renal perfusion imaging using ms- , an albumin-targeted mri contrast agent gadolinium-enhanced mr aortography body mr angiography with gadolinium contrast agents contrast-enhanced abdominal mr angiography: optimization of imaging delay time by automating the detection of contrast material arrival in the aorta sense: sensitivity encoding for fast mri mr flouroscopy: technical feasibility central intraluminal saturation stripe on mr angiograms of curved vessels: simulation, phantom, and clinical analysis simultaneous acquisition of spatial harmonics (smash): fast imaging with radiofrequency coil arrays flow artifacts in steady-state free precession cine imaging image artifacts due to a time-varying contrast medium concentration in d contrast-enhanced mra separation of arteries and veins using flow-induced phase effects in contrast-enhanced mra of the lower extremities venous compression at highspatial-resolution three-dimensional mr angiography of peripheral arteries use of a blood-pool contrast agent for mr-guided vascular procedures: feasibility of ultrasmall superparamagnetic iron oxide particles high-resolution magnetic resonance angiography of hands with timed arterial compression (tac-mra) improved centric phase encoding orders for three-dimensional magnetization-prepared mr angiography elliptical spiral phase encoding order: an optimal, field-of-viewdependent ordering scheme for breath-hold contrast-enhanced d mr angiography fluoroscopically triggered contrast-enhanced three-dimensional mr angiography with elliptical centric view order: application to the renal arteries quantitative evaluation of nonrepetitive phase-encoding orders for firstpass, d contrast-enhanced mr angiography parallel imaging in mr angiography mr image artifacts from periodic motion decreased venous contamination on d gadolinium-enhanced bolus chase peripheral mr angiography using thigh compression elimination of eddy current artifacts in diffusion-weighted echo planar images: the use of bipolar gradients phase insensitive preparation of singleshot rare: application to diffusion imaging in humans analysis and correction of motion artifacts in diffusion weighted imaging utilizing the diffusion-tonoise ratio to optimize magnetic resonance diffusion tensor acquisition strategies for improving measurements of diffusion anisotropy high b-value q-space analyzed diffusion-weighted mri: application to multiple sclerosis mr diffusion tensor spectroscopy and imaging microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor mri a simplified method to measure the diffusion tensor from seven mr images diffusion-weighted mr imaging of bone marrow: differentiation of benign versus pathologic compression fractures diffusion-weighted imaging of bone marrow: current status the basis of anisotropic water diffusion in the nervous system - a technical review eddy current correction in diffusion-weighted imaging using pairs of images acquired with opposite diffusion gradient polarity diffusionweighted mr imaging of the liver of hepatitis c patients on the particles contained in the pollen of plants; and on the general existence of active molecules in organic and inorganic bodies diffusion-weighted interleaved echo planar imaging with a pair of orthogonal navigator echoes the diffusion sensitivity of fast steady-state free precession imaging effects of diffusion on free precession in nuclear magnetic resonance experiments an optimized pulse sequence for isotropically weighted diffusion imaging pathologic damage in ms assessed by diffusion-weighted and magnetization transfer mri mr diffusion imaging of the human brain mr diffusion imaging of cerebral infarction in humans single-shot diffusion-weighted trace imaging on a clinical scanner diffusion tensor imaging in spinal cord: methods and applications - a review in vivo mapping of the fast and slow diffusion tensors in human brain tracking neuronal fiber pathways in the living human brain diffusion-weighted mri in the evaluation of renal lesions: preliminary results reducing motion artefacts in diffusion-weighted mri of the brain: efficacy of navigator echo correction and pulse triggering noise correction for the exact determination of apparent diffusion coefficients at low snr diffusion-weighted imaging of the spine using radial k-space trajectories a comparative evaluation of a rare-based single-shot pulse sequence for diffusionweighted mri of musculoskeletal soft-tissue tumors diffusion-weighted mri of soft tissue tumours overview of diffusion-weighted magnetic resonance studies in multiple sclerosis anisotropy in high angular resolution diffusion-weighted mri use of a projection reconstruction method to decrease motion sensitivity in diffusion-weighted mri line scan diffusion imaging spin-echoes comparison of gradient encoding schemes for diffusion-tensor mri diffusion-weighted mr imaging in normal human brains in various age groups vertebral metastases: assessment with apparent diffusion coefficient diffusion-weighted mr imaging of the normal human spinal cord in vivo mapping eddy current induced fields for the correction of diffusion-weighted echo planar images visualization of neural tissue water compartments using biexponential diffusion tensor mri diffusional kurtosis imaging: the quantification of non-gaussian water diffusion by means of magnetic resonance imaging determining and visualizing uncertainty in estimates of fiber orientation from diffusion tensor mri the effect of gradient sampling schemes on measures derived from diffusion tensor mri: a monte carlo study squashing peanuts and smashing pumpkins": how noise distorts diffusionweighted mr data confidence mapping in diffusion tensor magnetic resonance imaging tractography using a bootstrap approach optimal strategies for measuring diffusion in anisotropic systems by magnetic resonance imaging spatial normalization and averaging of diffusion tensor mri data sets isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable time selection of the optimum b factor for diffusion-weighted magnetic resonance imaging assessment of ischemic stroke contrast-to-noise ratios of diffusion anisotropy indices diffusion-weighted half-fourier singleshot turbo spin-echo imaging in breast tumors: differentiation of invasive ductal carcinoma from fibroadenoma intravoxel incoherent motion imaging using steady-state free precession mr imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders separation of diffusion and perfusion in intravoxel incoherent motion mr imaging diffusion imaging with the mp-rage sequence turbo spin-echo diffusionweighted mr of ischemic stroke diffusion tensor mr imaging of the brain and white matter tractography self-diffusion nmr imaging using stimulated echoes mri of "diffusion" in the human brain: new results using a modified ce-fast sequence nonlinear phase correction for navigated diffusion imaging steady-state diffusion-weighted imaging of in vivo knee cartilage self-diffusion in normal and heavy water in the range - ° diffusion weighting by the trace of the diffusion tensor within a single scan fiber tracking: principles and strategies - a technical review threedimensional tracking of axonal projections in the brain by magnetic resonance imaging diffusion tensor imaging and aging - a review early detection of regional cerebral ischemia in cats: comparison of diffusion- and t -weighted mri and spectroscopy diffusion-weighted mr imaging of acute stroke: correlation with t -weighted and magnetic susceptibility-enhanced mr imaging in cats diffusion-tensor imaging of cognitive performance evaluation of hepatic lesions and hepatic parenchyma using diffusion-weighted reordered turboflash magnetic resonance images diffusion tensor imaging of normal and injured developing human brain - a technical review implications of bulk motion for diffusion-weighted imaging experiments: effects, mechanisms, and solutions on the application of ultra-fast rare experiments diffusion-weighted echo planar mr imaging in differential diagnosis of brain tumors and tumor-like conditions correction of motional artifacts in diffusionweighted mr images using navigator echoes minimal gradient encoding for robust estimation of diffusion anisotropy ) k-space correction of eddy current-induced distortions in diffusion-weighted echo planar imaging diffusion tensor mr imaging of the human brain multishot diffusion-weighted fse using propeller mri reduction of eddy current-induced distortion in diffusion mri using a twice-refocused spin-echo diffusion tensor mri of the spinal cord diffusion-weighted mri in the characterization of soft-tissue tumors splice: sub-second diffusion-sensitive mr imaging using a modified fast spin-echo acquisition mode evidence that both fast and slow water adc components arise from intracellular space high-resolution diffusion imaging using a radial turbo-spin-echo sequence: implementation, eddy current compensation, and self-navigation condition number as a measure of noise performance of diffusion tensor data acquisition schemes with mri diffusion tensor imaging of neurodevelopment in children and young adults spin diffusion measurements: spin-echoes in the presence of a time-dependent field gradient usefulness of diffusion-weighted mri with echo planar technique in the evaluation of cellularity in gliomas diffusion tensor imaging in normal aging and neuropsychiatric disorders selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking the future for diffusion tensor imaging in neuropsychiatry evaluation of liver diffusion isotropy and characterization of focal hepatic lesions with two single-shot echo planar mr imaging sequences: prospective study in patients the spatial mapping of translational diffusion coefficients by the nmr imaging technique a quantitative method for fast diffusion imaging using magnetization-prepared turboflash mr imaging of high-grade cerebral gliomas: value of diffusion-weighted echoplanar pulse sequences test liquids for quantitative mri measurements of self-diffusion coefficient in vivo bloch equations with diffusion terms analysis and comparison of motion-correction techniques in diffusion-weighted imaging diffusion-weighted mri of the cervical spinal cord using a single-shot fast spin-echo technique: findings in normal subjects and in myelomalacia q-ball imaging high angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging effects of diffusion in nuclear magnetic resonance spin-echo experiments optimized isotropic diffusion weighting optimised diffusion-weighting for measurement of apparent diffusion coefficient (adc) in human brain (eds) handbook of biological effects of electromagnetic fields. crc, boca raton on the thermoregulatory consequences of nmr imaging risks and safety issues related to mr examinations thermoregulatory consequences of cardiovascular impairment during nmr imaging in warm/humid environments epidemiology of health effects of radiofrequency exposure standard practice for marking medical devices and other items for safety in the magnetic resonance environment athey tw ( ) a model of the temperature rise in the head due to magnetic resonance imaging procedures z-gradient coil and eddycurrent stimulation of skeletal and cardiac muscle in the dog. society for magnetic resonance in medicine sampling and evaluation of specific absorption rates during patient examinations performed on . -tesla mr systems estimation of heat transfer and temperature rise in partial-body regions during mr procedures: an analytical approach with respect to safety considerations induced alignment of flowing sickle erythrocytes in a magnetic field: a preliminary report static magnetic field effects on human subjects related to magnetic resonance imaging systems effect of static magnetic field exposure of up to tesla on sequential human vital sign measurements magnetic resonance procedures and pregnancy. in: shellock fg (ed) magnetic resonance procedures: health effects and safety basic principles of thermal dosimetry and thermal thresholds for tissue damage from hyperthermia cardiovascular responses to heat stress and their adverse consequences in healthy and vulnerable human polulations effects of heat on embryos and foetuses health effects of static magnetic fields - a review of the epidemiological evidence (eds) handbook of biological effects of electromagnetic fields specific absorption rates and induced current densities for an anatomy-based model of the human for exposure to time-varying magnetic fields of mri summary, conclusions and recommendations: adverse temperature levels in the human body magnetic field effects in biology -a survey of possible mechanisms with emphasis on radicalpair recombination effects of heat stress on cognitive performance: the current state of knowledge orientation of erythrocytes in a strong static magnetic field static and extremely low frequency electric and magnetic fields. iarc monographs on the evaluation of carcinogenic risks to humans guidelines for limiting exposure to timevarying electrical, magnetic, and electromagnetic fields (up to ghz) general approach to protection against non-ionizing radiation review of the scientific evidence on dosimetry, biological effects, epidemiological observations, and health consequences concerning exposure to static and low frequency electromagnetic fields ( - khz) survey of reproductive health among female mr workers cognitive, cardiac, and physiological safety studies in ultra high field magnetic resonance imaging sicherheitsaspekte zur vermeidung strominduzierter hautverbrennungen in der mrt untersuchungen über den einfluß statischer magnetfelder auf die pränatale entwicklung der maus cellular effects of hyperthermia: relevance to the minimum dose for thermal damage orientation of nucleic acids in high magnetic fields effects of static and time-varying ( hz) magnetic fields on reproduction and fetal development in rats interaction of nonmodulated and pulse modulated radio frequency fields with living matter: experimental results effects of static magnetic fields at the cellular level fetal development of mice following intrauterine exposure to a static magnetic field of . t orientation of sickled erythrocytes in a magnetic field effects of a . static magnetic field on fetal development in icr mice applied bioelectricity. from electrical stimulation to electropathology review of patient safety in time-varying gradient fields safety of strong, static magnetic fields physical interactions of static magnetic fields with living tissues physiological side effects of fast gradient switching hyperthermia-induced pathophysiology of the central nervous system radiofrequency energy-induced heating during mr procedures: a review patient monitoring in the magntic resonance environment. in: shellock fg (ed) magnetic resonance procedures: health effects and safety reference manual for magnetic resonance safety, implants, and devices: edn the magnetic resonance environment and implants, devices, and materials. in: shellock fg (ed) magnetic resonance procedures: health effects and safety physiological responses to mr imaging at an sar level of . w/kg development of mice after intrauterine exposure to directcurrent magnetic fields magnetically induced electric fields and currents in the circulatory system center for devices and radiological health. criteria for significant risk investigations of magnetic resonance diagnostic devices neurobehavioral effects among subjects exposed to high static and gradient magnetic fields from a . tesla magnetic resonance imaging system: case-crossover pilot study united nations environment programme/word health organisation/international radiation protection association: environmental health criteria , electromagnetic fields ( hz to ghz) risks and safety issues related to mr examinations grazioli l, morana g, kirchin ma, schneider g ( ) accurate differentiation of focal nodular hyperplasia from hepatic adenoma at gadopentate dimeglumine-enhanced mr imaging: prospective study. radiology : - grossman ri, rubin di, hunter g et al ( ) magnetic resonance imaging in patients with key: cord- -tuyac oq authors: kido, hidenori; kano, osamu; hamai, asami; masuda, hiroyuki; fuchinoue, yutaka; nemoto, masaaki; arai, chiaki; takeda, teppei; yamabe, fumihito; tai, toshihiro; kasahara, mizuki; suzuki, kenichi; shiraga, nobuyuki; sadamoto, sota; wakayama, megumi; takahashi, yukitoshi; iwasaki, yasuo; shibuya, kazutoshi; urita, yoshihisa title: kikuchi-fujimoto disease (histiocytic necrotizing lymphadenitis) with atypical encephalitis and painful testitis: a case report date: - - journal: bmc neurol doi: . /s - - - sha: doc_id: cord_uid: tuyac oq background: kikuchi-fujimoto disease is a self-limited clinicopathologic entity that is increasingly recognized worldwide. kikuchi-fujimoto disease is characterized by cervical lymphadenopathy occurring in young adults. neurologic involvement is rare, and testitis directly caused by kikuchi-fujimoto disease has not yet been reported. case presentation: a -year-old man was brought to our clinic with complaints of fever, headache, fatigue, and left lower quadrant pain that had persisted for weeks. on physical examination, painful cervical lymphadenopathies were observed. meningitis was suspected based on a cerebrospinal fluid examination, and left-sided orchitis was diagnosed based on findings from magnetic resonance imaging and ultrasonography. however, neither antibiotics nor antiviral drugs were effective in treating the patient’s symptoms. on the (th) day of hospitalization, the patient experienced a loss of consciousness, and brain t -weighted magnetic resonance imaging showed asymmetrical, high-signal intensities in both basal nuclei and the left temporal lobe. encephalitis was suspected, and the patient was treated with intravenous prednisolone pulse therapy ( g/day) for days and intravenous immunoglobulin therapy for days. a left cervical lymph node biopsy showed apoptotic necrosis in paracortical and cortical areas with an abundance of macrophages and large lymphoid cells, which had irregular nuclei suggestive of kikuchi-fujimoto disease; the pathological findings from a brain biopsy were the same as those of the cervical lymph node biopsy. the encephalitis and cervical lymphadenopathies followed a benign course, as did the testitis. conclusions: this is the first report of kikuchi-fujimoto disease involving painful testitis and pathologically proven asymmetrical brain regions. kikuchi-fujimoto disease should be included in the differential diagnosis when a patient presents with encephalitis, testitis, and fever of unknown origin. kikuchi-fujimoto disease (kfd), or histiocytic necrotizing lymphadenitis, is known to be a benign disease that usually resolves spontaneously. it is a rare disease and was first reported in japan in [ , ] . kfd usually affects female patients under the age of years and is characterized by regional lymphadenopathy with tenderness, predominantly in the cervical region, and is usually accompanied by mild fever and night sweats. it is of clinical importance because it is often misdiagnosed as tuberculosis, lymphoma, or systemic lupus erythematosus (sle); therefore, the diagnosis should be confirmed by biopsy study. diseases that generally accompany kfd are sle, arthritis, mixed connective tissue disease, and similar conditions; however, comorbid testitis has not yet been reported. neurological complications occur in about % of cases, as revealed by a review of cases in which a minority of cases evolved to developing encephalitis [ ] . brain magnetic resonance imaging (mri) includes symmetrical hyperintense t -weighted and flair (fluidattenuated inversion recovery) signals in the temporal lobes, pons, and periaqueductal gray matter [ ] [ ] [ ] [ ] . this is the first report of kfd occurring with testitis and pathologically proven asymmetrical brain regions. a -year-old man presented to our hospital with complaints of fever ( . °c), headache, fatigue, night sweats, and lower abdominal pain, which had been present for about month. for days, he had used anti-flatulent medications before presenting to our hospital. he had no history of close contact with pets, he did not travel often, and similar complaints were not present in his social circle. according to the patient's physical examination on admission, his general health status was good; body temperature, pulse, and blood pressure were . °c, beats/min, and / mmhg, respectively. he was alert, oriented, and cooperative. mobile, painful lymphadenopathies were observed on both sides of the cervical region, of which the largest was × . cm in size. bilateral cervical lymphadenopathy was present and involved a posterior group of cervical lymph nodes. cardiac, respiratory, and neurological examination revealed no abnormality; vegetation was not detected by transthoracic echocardiography. laboratory investigations showed leukopenia (total leucocyte count: cells/mm ). cerebrospinal fluid (csf) analyses were normal. no positive results that could explain the high body temperature were found during serological testing for epstein barr virus (ebv); cytomegalovirus (cmv); hepatitis a, b, and c; parvovirus; human herpesvirus; chlamydia trachomatis; mumps; human immunodeficiency virus; echo virus; coxsackie virus enterovirus; and measles spp. results of tests for rheumatologic markers (ferritin, anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, anti-cyclic citrullinated peptide antibodies, extractable nuclear antigen antibody panel, anti-double stranded dna, and rheumatoid factor) were also negative. results of tuberculosis polymerase chain reaction (pcr) and herpes simplex pcr were also negative in the csf. blood and csf cultures showed no growth after incubation for to weeks. brain t -weighted and flair mri sequences showed a slightly hyperintense signal of about mm in the left temporal lobe (fig. ) , and antibiotics and acyclovir treatment were begun because we could not rule out encephalitis. however, the patient's body temperature could not be reduced by routine anti-inflammatory drugs and intravenous paracetamol. thoracic and abdominal computed tomography (ct) and mri scans revealed a testicular lesion having no contrast effect (fig. ) ; lymph nodes were predominantly located on the right side of the cervical region, with the largest measuring cm in diameter. thus, one of the lymph nodes located in the right cervical region was removed and sent to pathology for analysis. on the th fig. axial t -weighted mri with gadolinium contrast (a) and flair-weighted mri (b) show mild enhancement and a highintensity area, respectively, in the left temporal lobe at onset (arrow heads). following periods of acute exacerbation on the th day, axial t -weighted mri with gadolinium contrast (c) showed slightly larger enhancement, and flair-weighted mri (d) revealed an asymmetrical hyperintense signal in the left temporal lobe and both basal nuclei. after months of hospitalization, the abnormal lesions became smaller (e, f) day of hospitalization, an excision biopsy of the cervical lymph node was performed. microscopic examination showed that the lymph nodes were expressed in paracortical and cortical areas of conspicuous apoptotic necrosis with an abundance of enlarged lymphocytes, which had prominent nucleoli in the absence of neutrophils and a proliferation of macrophages (fig. ) . results of tests using in situ hybridization to detect ebv with marked paracortical expansion due to a proliferation of immunoblasts were negative. on the th day of hospitalization, the patient's general status suddenly and temporarily worsened. the signal intensity on brain mri had changed and showed an asymmetrical hyperintense signal in the wider larger left temporal lobe and both basal nuclei ( fig. ) with slight gd-enhancement. csf protein levels and pleocytosis were increased (protein: mg/dl; pleocytosis: cells/μl), but csf cultures were negative, and cytology showed no malignant findings. anti-nmda, co, tr, gad , zic , titin, sox , rec, hu, yo, ri, ma- /ta, cv , and amp antibodies associated with auto-immune-mediated encephalomyelitis were all absent. oligoclonal bands were also not detected in the csf sample. since acute disseminated encephalomyelitis (adem) was suspected, the patient was managed with intravenous prednisolone pulse treatment ( g/day) for days and intravenous immunoglobulin treatment for days, and these therapies were repeated times every weeks. electroencephalography showed no waves characteristic of epilepsy, but levetiracetam mg/day was begun. on the th day of hospitalization, mri investigation of the brain revealed that the previous abnormalities were present and had not changed. since the cervical lymph node biopsy before steroid therapy did not reveal lymphoma, a brain biopsy of the temporal lobe was performed. steroids can obscure diffuse large b-cell lymphoma or intravascular lymphomatosis; however, no recurrence was experienced. the pathological results revealed many cd + macrophages and histiocytes, as in the cervical lymph node, suggestive of kfd (fig. ) . the cervical lymphadenopathies disappeared after months of hospitalization, and the previous abnormalities on mri became smaller during follow-up. the testicular mass that showed a contrast effect on mri and ct similarly was smaller (fig. ) ; therefore, we suspected that the testitis had been caused by kfd. his complaints of fever, headache, and fatigue gradually improved; he was discharged on the th day of hospitalization. he was followed for more than months in our clinic and did not show any recurrence. kfd was first described in japan in and has increasingly been recognized worldwide since fig. a axial t -weighted magnetic resonance image shows that the lesion has an isointense signal. b after administration of gadolinium contrast, material internal enhancement is not observed. c coronal t -weighted magnetic resonance image shows that the lesion has low signal intensity (arrow) fig. left cervical lymph node biopsy shows conspicuous apoptotic necrosis in paracortical and cortical areas with an abundance of macrophages and large lymphoid cells, which have irregular nuclei [hematoxylin-eosin staining × (left), × (right)] [ ] . according to a review [ ] that summarized kfd cases, the mean age was ( - ) years, and % were younger than years; % were men, and % were women. most of the cases were reported from east asia and the far east ( %), and the others were from europe ( %) and america ( %). as in the present case, the most common symptoms were fever ( %), fatigue ( %), and cervical lymphadenomegaly ( %) [ ] . our case did not show any evidence of sle, lymphoma, tuberculosis, arthritis, or viral disease based on laboratory findings and cervical lymph node biopsy. testitis has not been reported as a co-morbid disease in kfd. after diagnosing kfd based on results of the cervical lymph node biopsy, we could not explain the central nervous system (cns) involvement in this case. neurological involvement, including aseptic meningitis and encephalitis, is rare, and abnormal mri findings in kfd usually show symmetrical, hyperintense t and flair signals in the temporal lobes, pons, and periaqueductal gray matter [ ] [ ] [ ] [ ] . therefore, we considered the possibility of co-morbid adem. avkan-oguz et al. [ ] reported the co-existence of kfd and adem based on brain mri findings without a brain biopsy. our case did not show symmetrical lesions, which were reported in the previous kfd reports with cns involvement; hence, we evaluated brain pathology, and the results were consistent with those for kfd and showed a benign course. although the etiology of the disease remains unknown, infectious or autoimmune pathogenesis is thought to be responsible. the factors that likely result in the infection include herpes simplex virus, ebv, cmv, human herpes virus , varicella zoster virus, hiv, rubella, measles, coronavirus, coxsackie virus, hepatitis a and b, yersinia enterocolitica, toxoplasma, influenza viruses, mumps, streptococci, leptospira, and chlamydia. it has also been reported that the disease may occur after rabies, diphtheria-tetanus, poliomyelitis, hepatitis b, and influenza vaccines are injected [ ] . kfd may initially be mistaken for various benign and malignant diseases, such as tuberculosis, lymphoma, sle, limbic encephalitis, and sarcoidosis. on the other hand, with regards to clinical and laboratory presentations, kfd frequently mimics sle, arthritis, mixed connective tissue disease, aseptic meningitis, encephalitis, tuberculous lymphadenitis, malignant lymphoma, and some other benign and/ or malignant diseases [ , , ] . in addition to painful cervical lymphadenopathies and aseptic meningitis, our case showed testitis and encephalitis, which are not typical mri findings compared with those reported in a previous case report. previous papers reported that most cases of kfd had a benign course; therefore, it was difficult to evaluate the effect of our therapies, such as prednisolone and intravenous immunoglobulin treatment. the definitive method for confirming the diagnosis of kfd is with a lymph node biopsy, and therefore, physicians should not hesitate to perform one in order to diagnose the condition. in addition, if progressive cns involvement is observed, either steroid therapy or brain biopsy should be considered. thus, kfd may exist on a wide spectrum of diseases, and we suggest that kfd should be included in the differential diagnosis of lymphadenopathy, encephalitis, testis, and fevers of unknown origin. in conclusion, this is the first report of kfd involving testitis and pathologically proven asymmetrical brain regions. lymphadenitis showing focal reticulum cells hyperplasia with nuclear debris and phagocytosis: a clinicopathological study cervical sub-acute necrotising lymphadenitis. a new clinicopathological entity kikuchi-fujimoto disease: analysis of cases histiocytic necrotizing lymphadenitis (kikuchi-fujimoto disease) with cns involvement in a child brainstem encephalitis with kikuchi-fujimoto disease a case of fever of unknown origin: co-existence of kikuchi-fujimoto disease and acute disseminated encephalomyelitis (adem) encephalitis and csf increased level of interferon-alpha in kikuchi-fujimoto disease histiocytic necrotizing lymphadenitis without granulocytic infiltration post-infectious encephalitis in adults: diagnosis and management histiocytic necrotizing lymphadenitis (kikuchi's disease) with aseptic meningitis encephalitis associated to kikuchi-fujimoto's disease in a young woman: a case report none. not applicable in order to protect patient privacy.authors' contributions study concept and design: hk, ok. acquisition of data: hk, ok, ah. hk, ok, ah, hm, yf, mn, ca, t. takeda, fy, t. tai, mk, k. suzuki, ns, ss, mw, k. shibuya, yi and yu examined and evaluated the patient. yt contributed to the csf analysis. all authors read and approved the final manuscript. the authors declare that they have no competing interests. we obtained written informed consent from the patient for publication of this report and any accompanying images. a copy of the written consent is available for review by the editor-in-chief of this journal. submit your next manuscript to biomed central and we will help you at every step: key: cord- -us spoxu authors: cornelis, i.; volk, h. a.; van ham, l.; de decker, s. title: clinical presentation, diagnostic findings and outcome in dogs diagnosed withpresumptive spinal‐only meningoen‐cephalomyelitis of unknown origin date: - - journal: j small anim pract doi: . /jsap. sha: doc_id: cord_uid: us spoxu objectives: to summarise clinical presentation, diagnostic findings and long‐term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone. methods: medical records were reviewed for dogs diagnosed with presumptive spinal‐only meningoencephalomyelitis of unknown origin between and . results: dogs were included; the majority presented with an acute ( %) or chronic ( %) onset of neurological signs. ambulatory paresis was the most common neurological presentation ( %). neurological examination most commonly revealed a t ‐l myelopathy, and spinal hyperaesthesia was a common finding ( %). a spinal cord lesion was visible in % of cases on magnetic resonance imaging. eighteen lesions ( %) showed parenchymal contrast enhancement and lesions ( %) showed contrast enhancement of overlying meninges. all dogs were treated with immunosuppressive doses of glucocorticosteroids, sometimes combined with cytosine arabinoside. at time of data capture, / dogs ( %) had died or been euthanased because of the condition. overall median survival time was days. clinical significance: meningoencephalomyelitis of unknown origin should be considered in the differential diagnosis of dogs presenting with a progressive myelopathy. magnetic resonance imaging features can possibly help to distinguish presumptive meningoencephalomyelitis of unknown origin from other more common spinal diseases. overall, long‐term survival is guarded, approximately % of dogs will die or be euthanased despite appropriate therapy. pure myelitis (inflammation of spinal cord parenchyma) or meningomyelitis (inflammation of spinal cord parenchyma and surrounding meninges) are rare diseases in small animals but occur most often in combination with inflammatory brain disease (tipold & stein ) . viruses [canine distemper virus (cdv), feline coronavirus], bacteria ( staphylococcus species, et al . , csebi et al . , dewey et al . . apart from infectious causes, non-infectious meningoencephalomyelitis including granulomatous meningoencephalomyelitis, pyogranulomatous meningoencephalomyelitis and steroid-responsive meningitis-arteritis (srma) are described (meric , griffin et al . , parry et al . , dewey et al . . current terminology implies that dogs clinically diagnosed with non-infectious inflammatory myelitis without positive infectious disease testing, not classified as srma or eosinophilic meningomyelitis, and not histopathologically confirmed with alternative diagnoses are categorised as having meningoencephalomyelitis of unknown origin (muo), equivalent to dogs diagnosed with meningoencephalitis of unknown origin. a clinical diagnosis of muo is typically made by a combination of clinical presentation, mr imaging of involved part of the central nervous system (brain/spinal cord), and results of cerebrospinal fluid (csf) analysis (griffin et al . ) . currently, only one study has focused specifically on the clinical presentation, diagnostic findings and outcome in dogs with meningomyelitis caused by a variety of underlying aetiologies (griffin et al . ). of cases included, dogs were diagnosed with muo. clinical signs were reflected by the affected spinal cord segments, and younger dogs, toy breeds, and hound breeds were suggested to be predisposed for meningomyelitis. although results of myelography, ct, and ct-myelography have been reported, little is reported about magnetic resonance imaging (mri) findings in dogs with muo of the spinal cord. the aims of this study were therefore to describe the signalment, clinical presentation, diagnostic findings, including results of mri and long-term survival in dogs diagnosed with presumptive muo of the spinal cord without concurrent clinical signs of intracranial involvement. the electronic medical database was searched between march and february for dogs diagnosed with "mua," "muo," "gme," "myelitis," "inflammatory spinal cord disease." dogs were included based on the criteria used by granger et al . ( ) , if they had ( ) complete medical records available, ( ) a complete neurological examination performed leading to a spinal cord localisation, ( ) inflammatory csf analysis, ( ) mri of the spinal cord and if ( ) long-term follow-up information were available through revision of medical records or through contacting the referring veterinarian by telephone. dogs were excluded if ( ) the clinical records or imaging studies were incomplete or not available for review, ( ) dogs showed clinical or neurological signs of intracranial involvement at time of presentation, ( ) they had a peracute onset of clinical signs that were not progressive after to hours, ( ) they had signs of extradural or extradural/intramedullary spinal cord compression on mri and if ( ) they had positive infectious disease titres or if clinical presentation, csf analysis or necropsy findings were suggestive of srma or eosinophilic meningoencephalomyelitis (> % eosinophils in csf) (dewey et al . ) . typical clinical presentation for srma was considered to be a dog less than years of age of a typical breed (boxer, beagle, bernese mountain dog, nova scotia duck tolling retriever, golden retriever, german shorthaired pointer) presenting with pyrexia and cervical hyperesthesia. csf analysis in srma typically reveals a predominantly neutrophilic pleocytosis (dewey et al . ) . dogs with histopathological confirmation of the disease [granulomatous meningo(encephalo)myelitis (gme) or necrotising meningo(encephalo)myelitis (nme) only needed to fulfil inclusion criteria ( ) and ( ). information retrieved from the medical records included breed, gender, age at diagnosis, body weight, results of neurological examination including neuroanatomical localisation, duration of clinical signs prior to diagnosis, results of complete blood count (cbc) and biochemistry profile, results of csf analysis including total nucleated cell count (tncc), white blood cell differentiation and total protein (tp) concentration, treatment received and outcome. duration of clinical signs prior to diagnosis (days) was classified as peracute (< days), acute ( to days) or chronic (> days). for dogs that had csf analysis performed, site of collection (cisternal or lumbar), tncc, tp and cytological differentiation were recorded. tncc was considered normal if there were < cells/mm . protein concentration was considered normal for a cisternal collection if < · g/l and for a lumbar collection if < · g/l. the neurological status was classified from to according to the clinical examination (adapted from scott ): grade =neurologically normal; grade =spinal hyperaesthesia without neurological deficits; grade =ataxia, ambulatory para-or tetraparesis; grade =non-ambulatory para-or tetraparesis; grade =para-or tetraplegia with or with-out bladder control, and intact deep pain sensation; grade =para-or tetraplegia, urine retention or overflow, and deep pain sensation loss. possible neuroanatomical localisations included c to c , c to t , t to l or l to s spinal cord segments. dogs were diagnosed with a focal lesion if only one spinal cord segment was affected, and with a multifocal lesion if more than one spinal cord segment appeared to be affected on the neurological examination. magnetic resonance imaging mri was performed under general anaesthesia with a permanent . -t magnet (intera, philips medical systems, eindhoven, the netherlands) and all images were reviewed by the corresponding author using osirix dicom viewer (osirix foundation, v. . . geneva, switzerland). sequences varied, but included a minimum of t -weighted (t w) [repetition time (ms) (tr)/ echo time (ms) (te), / ] and t -weighted (t w) (tr/ te, / ) images of the affected spinal cord region in a sagittal and transverse plane. the t w images were acquired before and after intravenous (iv) administration of paramagnetic contrast medium with a dose of · mg/kg gadoterate meglumine (dotarem, guerbet). if mr images of the brain were available, they were reviewed concurrently. variables recorded were lesion intensity on t w and t w images, lesion localisation and distribution, lesion length and parenchymal and/or meningeal contrast enhancement. lesion length was measured using osirix dicom viewer, and performed on sagittal t w images for dogs that had focal lesions. lesion length was measured twice, and the mean value reported. to compensate for differences in body size, values were corrected with respect to the length of vertebral body of c (for cervical lesions) or l (for thoracolumbar lesions). vertebral body length was measured on t w sagittal images. for all dogs, the specific treatment protocol was recorded. during hospitalisation, all dogs underwent daily at least one general physical and complete neurological examination by a board-certified neurologist or neurology resident. the results of the neurological examination as well as response to treatment (improvement, deterioration or static) were systematically recorded on the kennel sheets. follow-up information during hospitalisation was collected from the medical records, and later through medical records of re-examination visits or telephone contact with the referring veterinarian. a successful outcome was defined as the dog being ambulatory, with faecal and urinary continence and, according to the owners, without overt spinal hyperaesthesia. an unsuccessful outcome was defined as ( ) deterioration in neurological status by one or more grades after diagnosis and treatment or ( ) if the dog was not independently ambulatory, possibly with previously non-existing or worsening faecal and/or urinary incontinence, or was experiencing spinal hyperaesthesia as defined by the owner. data analysis was performed with the aid of a standard statistical software package (prism, graphpad software inc). numeric variables were expressed as median and interquartile ranges (iqr). values of p< · were considered significant. survival analysis was performed using both a log-rank (mantel-cox) and gehan-breslow-wilcoxin test, resulting in median survival time (mst) calculation and a kaplan-meier survival curve. survival was defined as time from diagnosis to death or euthanasia, including whether this happened because of disease progression or due to unrelated causes, or time from diagnosis to last follow-up for dogs that were alive at time of data capture. dogs that died because of unrelated causes and dogs that were still alive at time of data capture were censored for survival analysis. twenty-one dogs were included in the study. represented breeds included french bulldog (n= ), jack russell terrier (n= ), lhasa apso (n= ) and one each of akita, bearded collie, boxer, bull mastiff, chihuahua, cross breed, english springer spaniel, giant schnauzer, labrador retriever, maltese terrier, rhodesian ridgeback, rottweiler, shih-tzu, west highland white terrier and yorkshire terrier. overall, median age at presentation was months ( to months). thirteen dogs ( %) were male and eight ( %) were female. compared to the general hospital population between march and february , there was no difference in sex distribution in the group of dogs with muo (fisher ' s exact test; p= · ). median duration of clinical signs prior to diagnosis was eight days (ranging from to days). one dog ( %) presented with peracute, nine dogs ( %) with acute and eleven dogs ( %) with a chronic onset of neurological signs. thirteen ( %) and eight ( %) dogs were diagnosed with a focal and multifocal spinal lesion on neurological examination, respectively. for dogs with focal spinal lesions (n= ), three were diagnosed with a lesion affecting the c to c spinal cord segments, two with a lesion affecting the c to t spinal cord segments, six with a lesion affecting the t to l spinal cord segments and two with a lesion affecting the l to s spinal cord segments. at time of diagnosis, no dogs presented as grade ; dogs ( %) were grade ; ( %) grade and ( %) grade . no dogs were paraplegic or tetraplegic at presentation. pain on direct spinal palpation was present in ( %) dogs. urinary retention was observed in two dogs ( %), and a combination of urinary and faecal incontinence was noticed in two dogs ( %). one dog ( %) developed seizures days after diagnosis of muo. clinical findings of the included dogs are summarised in table . as required by the inclusion criteria, csf collection revealed pleocytosis in all cases. overall, median tncc was cells/ mm (ranging from to ). tp measurement was performed in all but three csf samples, and was above reference values in / dogs ( %). the median tp concentration was · g/l (ranging from · to · g/l). cbc and serum biochemistry results were available in dogs ( %). leucocytosis was only present in two dogs ( %) and lymphopenia was present in six dogs ( %). infectious disease testing based on serology and/or polymerase chain reaction on csf for cdv, t . gondii , and n . caninum was not performed in two ( %) dogs and was negative in the remaining ( %) dogs. in the two dogs lacking infectious disease testing, full necropsy was performed, revealing gme. magnetic resonance imaging mri of the spinal cord was available in all cases, revealing a focal lesion in dogs ( %), a multifocal lesion in four ( %) and no lesion was visible on sagittal t w or t w images in two ( %). lesion length was measured in the focal cases only. median lesion/vertebral body ratio was · (ranging from · to · ). all visible lesions were ill-defined, intramedullary, hyperintense on t w images and isointense on t w images (figs and ). lesions showed parenchymal contrast enhancement in dogs ( %), and contrast enhancement of overlying meninges in ( %). in the two cases in which no lesion was visible on sagittal t w and t w images, there was also no observable parenchymal contrast, but one dog only showed meningeal contrast enhancement. in two dogs ( %) intracranial images were contained within the field of view of the cervical spinal cord images (t w transverse and sagittal images), revealing multiple t w hyperintensities in the forebrain and/or brainstem. neither of those dogs had clinical or neurological signs of intracranial involvement at time of diagnosis. the first dog, a -month-old jack russell terrier, did not recover from general anaesthesia after diagnostic procedures, and full necropsy revealed gme. the second dog, a -month-old rhodesian ridgeback, developed seizures days after diagnosis and was euthanased without further investigations. as required by the inclusion criteria, outcome was available in all dogs. as described above, one dog did not recover from general anaesthesia for mri of the spinal cord, and was censored for survival analysis. mean duration of hospitalisation was five days (ranging from to days), with dogs ( %) showing improvement in neurological status within that period. one dog ( %) remained neurologically stable (no improvement nor deterioration), and three dogs ( %) showed deterioration of their neurological status. all dogs were treated with immunosuppressive doses of glucocorticosteroids immediately after diagnosis. this consisted doses of · to · mg/kg/day dexamethasone in nine dogs ( %) iv and to mg/kg/day oral prednisolone in dogs ( %). fourteen dogs ( %) received additional treatment with cytosine arabinoside as a constant rate infusion (cri) of mg/m over eight hours in one dog ( %) and as four subcutaneous (sc) injections of mg/m every hours for two consecutive days in dogs ( %). twenty dogs ( %) survived to discharge. of these dogs, nine dogs ( %) were still alive at time of data capture. of these nine dogs, eight were neurologically normal according to the followup information and one dog still showed ataxia and ambulatory paraparesis. of the eight normal dogs, two were still receiving a dose of mg/kg cyclosporine every hours, one was receiving a dose of mg/m cytosine arabinoside every hours for two consecutive days every nine weeks, one was receiving a dose of · mg/kg prednisolone every hours, one was receiving doses of mg/kg prednisolone every hours and mg/m cytosine arabinoside every hours for two consecutive days every four weeks, and three dogs were not receiving any treatment at time of data capture. the dog that was still showing neurological abnormalities was receiving doses of · mg/kg prednisolone every other day and mg/m cytosine arabinoside every hours for two consecutive days every weeks. for the / dogs ( %) that were dead at the time of data capture, three had died or were euthanased because of disease progression, six were euthanased because of acute neurological deterioration after initial neurological improvement and two were euthanased because of unrelated causes (complications after stifle surgery and development of aggression). dogs that showed acute neurological deterioration after initial improvement did so within a median of days after diagnosis (ranging from to days). of those six dogs, one showed acute deterioration after discontinuation of prednisolone treatment and five were still receiving treatment doses of mg/kg prednisolone every hours, · mg/kg prednisolone every hours, mg/kg prednisolone every hours and mg/kg azathioprine every hours or mg/m cytosine arabinoside every hours for two consecutive days every seven weeks. overall, we can conclude that / dogs ( %) died or were euthanased because of muo. overall, the mst was days (ranging from to days) (fig ) . confirmation from post-mortem examination was available in three dogs, revealing gme in two and necrotising meningomyelitis in one dog. all clinical data are shown in tables and . this study evaluated the clinical presentation, diagnostic findings and long-term survival in dogs diagnosed with presumptive spinal muo. dogs had a median age of five years at time of pain on direct spinal palpation was present in % of dogs. spinal pain may reflect the involvement of the meninges, and/ or vertebrae (vertebral periosteum), and/or nerve roots or spinal nerves (da costa ). in the present study, the lesions showed meningeal contrast enhancement in / dogs, but there was no apparent association between spinal hyperaesthesia and meningeal enhancement on mri. mri of the spinal cord revealed no lesion on sagittal t w and t w images in % of dogs (n= ), which appears similar to the % described for the brain in dogs with muo (granger et al . ). in the retrospective study of griffin et al . ( ) , only one dog with meningomyelitis had mri performed, revealing no abnormalities. based on these findings, muo cannot be ruled out based on unremarkable mri findings. the first dog was a -month-old bullmastiff with a -month history of slowly progressive t to l spinal cord lesion. after diagnostic procedures, the dog was treated with oral prednisolone but continued to deteriorate and was euthanased after days. no post-mortem examination was performed. the second dog was a -monthold bearded collie with a -week history of a progressive multifocal spinal cord neuroanatomical localisation (t to s spinal cord lesion). the dog showed improvement on treatment with prednisolone and cytosine arabinoside (see table ) after diagnostic investigations, and was still alive without current treatment days after diagnosis. both dogs had inflammatory csf analysis (increased tncc and tp concentration). for both dogs, vascular, degenerative or neoplastic spinal cord lesions cannot be excluded. as both dogs had a progressive disease course, a vascular (ischaemic) lesion seemed less likely. a neoplastic lesion cannot be excluded, although this seems rather unlikely in the bullmastiff considering his very young age. the second dog had a lymphocytic pleocytosis on cfs analysis, but no signs of lymphoma on microscopical examination, although no specific test for clonality was performed. all mri-observed lesions were extensive, ill-defined, intramedullary, hyperintense on t w images and isointense on t w images. other spinal conditions, including acute non-compressive nucleus pulposus extrusions (annpe) and ischaemic myelopathy (im), are also associated with intraparenchymal hyperintensities on mri. however, these conditions are associated with other clinical and additional mri characteristics, which could potentially aid in differentiating between these conditions (cardy et al . , fenn et al . ). according to cardy et al . ( ) , in dogs presenting with spinal cord dysfunction, im [most commonly fibrocartilagenous embolic myelopathy (fcem)] and annpe are typically characterised by a peracute onset of non-progressive clinical signs and affected dogs do not commonly demonstrate overt spinal hyperaesthesia at time of admission. this is in contrast with the clinical presentation of dogs with spinal muo, which was characterised by an acute onset of progressive and mainly symmetrical neurological deficits, with pain on spinal palpation or manipulation in % of dogs (cardy et al . ) , which is comparable with the % of dogs presenting with spinal hyperaesthesia in the current study. although csf analysis in dogs with im is most often within normal limits, affected dogs can demonstrate an increased tp concentration and mild neutrophilic or mixed cell pleocytosis with a median tncc of cells/ µ l (de risio et al . ) . a marked pleocytosis with a median tncc of cells/mm was seen in the current study, although this conclusion should be treated with caution because csf pleocytosis was one of the inclusion criteria. to conclude, the presentation of a dog with an acute or chronic onset of a progressive and painful t to l myelopathy in combination with an extensive, ill-defined, intramedullary lesion plus parenchymal and/or meningeal contrast enhancement on mri, and marked pleocytosis on csf analysis, can be presumptively diagnosed with spinal muo. the importance of differentiating between these conditions is highlighted by the differences in treatment and prognosis between dogs with presumptive muo and dogs with annpe or im. a previous study demonstrated that short tau inversion recovery (stir) hyperintensities in the cervical epaxial musculature of dogs with meningoencephalomyelitis had a sensitivity of % and a specificity of % in predicting inflammatory csf results (eminaga et al . ). in the current study, stir images were unfortunately only available in / cases. adding this sequence to the protocol in dogs with presence of a focal or multifocal, illdefined t w intramedullary hyperintensity might be considered in the future. several studies have evaluated survival times of dogs diagnosed with muo (granger et al . , coates & jeffery . overall, dogs with muo appear to have a guarded prognosis. a large meta-analysis of dogs with muo revealed an overall reported mst of to days in dogs treated with corticosteroids plus any other immunosuppressive protocol, compared to a mst of to days for dogs receiving corticosteroids alone (granger et al . ). in the current study, dogs with presumptive spinal muo had a mst of days ( years), but ultimately, % of dogs died or were euthanased because of the disease, indicating a more guarded long-term prognosis. limitations of this study are the small sample size and retrospective character, which limited standardisation of patient assessment and treatment. although all dogs were treated with glucocorticosteroids, it cannot be excluded that specific differences in treatment may have influenced outcomes. despite including cases over a relative large period and from a busy referral hospital, only dogs were found through our record search. this could indicate that spinal muo should be considered a rare disorder, which is in agreement with previous reports (cardy et al . ) , suggesting that muo represents approximately % of all spinal disorders in dogs. presumptive spinal muo can be diagnosed in any type of dog of any age that is presented with signs of acute or chronic, possibly painful, myelopathy. although clinical signs can vary, affected animals most typically present with ambulatory paraparesis and ataxia, localising to t to l spinal cord segments. mri typically reveals an extensive, ill-defined and intramedullary lesion that appears hyperintense on t w images and isointense on t w images. most lesions showed parenchymal contrast enhancement and/or enhancement of the overlying meninges on post-contrast t w images which can possibly differentiate dogs with muo from other more common spinal diseases. in % of cases, no lesion was visible on sagittal t w and t w images. almost % of dogs died or were euthanased because of muo, with a mst of days. none of the authors of this article has a financial or personal relationship with other people or organisations that could inappropriately influence or bias the content of this paper. clinical reasoning in canine spinal disease: what combination of clinical information is useful? perspectives on meningoencephalomyelitis of unknown origin vertebral osteomyelitis and meningomyelitis caused by pasteurella canis in a dog -clinicopathological case report spinal pain magnetic resonance imaging findings and clinical associations in dogs with suspected ischemic myelopathy neurodiagnostics . in: practical guide to canine and feline neurology stir muscle hyperintensity in the cervical muscles associated with inflammatory spinal cord disease of unknown origin inter -and intraobserver agreement for diagnosing presumptive ischemic myelopathy and acute noncompressive nucleus pulposus extrusion in dogs using magnetic resonance imaging . veterinary clinical findings and treatment of non-infectious meningoencephalomyelitis in dogs: a systematic review of published cases from meningomyelitis in dogs: a retrospective review of cases canine meningitis -a changing emphasis imaging diagnosis -necrotizing meningomyelitis and polyarthritis hemilaminectomy for the treatment of thoracolumbar disc disease in the dog: a follow-up study of cases inflammatory diseases of the spine in small animals key: cord- - g kb authors: takao, masaki; abe, hirohito; sakai, takashi; hamada, hidetoshi; takahara, shiro; sugano, nobuhiko title: transitional changes in the incidence of hip osteonecrosis among renal transplant recipients date: - - journal: j orthop sci doi: . /j.jos. . . sha: doc_id: cord_uid: g kb abstract background immunosuppressive therapy for renal allograft recipients has changed substantially since the introduction of the anti-cd monoclonal antibody, basiliximab. we hypothesized that recent improvements in immunosuppressive treatment may reduce the incidence of osteonecrosis of the femoral head (onfh). this study aimed to investigate transitional changes in the incidence of ofnh among renal transplant recipients by mri. methods participants comprised patients who had undergone renal transplantation from to , during which time basiliximab was in regular use at our institute (recent group), and patients who had undergone rt between and (past group). we compared onfh incidence between the two groups and evaluated risk factors for onfh, including immunosuppressants (calcineurin inhibitors, basiliximab, and/or steroids) and postoperative renal function. results incidence of onfh was lower in the recent group ( %) than in the past group ( . %; p = . ). in the recent group, age was greater, abo/human leukocyte antigen incompatibility was worse, while steroid dose was decreased and post-transplant renal function was improved. cumulative methylprednisolone dose at postoperative week and delayed graft function were identified as risk factors for onfh. conclusion risk of onfh after renal transplantation has fallen with the advent of regular use of basiliximab, although this agent does not appear to be a factor directly associated with the incidence of onfh. study design clinical prognostic study (level iii case control study). osteonecrosis of the femoral head (onfh) is well recognized as a musculoskeletal complication after renal transplantation (rt). with advances in immunosuppressive therapy, improved posttransplant renal function and reduced corticosteroid dose are reported to have led to a decrease in the incidence of onfh [ e ]. however, according to recent screening studies using magnetic resonance imaging (mri), this incidence ranged from . % to . % [ , e ] , inferring that onfh remains a significant complication among renal allograft recipients. immunosuppressive therapy for renal allograft recipients has changed substantially since the introduction of the anti-cd monoclonal antibody, basiliximab (simulect; novartis, east hanover, nj). when administered as induction therapy during the early postoperative period, improvements in postoperative renal function have been reported [ e ] . decreases in the doses of steroids and calcineurin inhibitors have also been reported [ ] and indications for rt have therefore been expanded to include higherrisk patients with older age and increased human leukocyte antigen (hla) mismatch. however, the impact of basiliximab administration on the incidence of post-transplant onfh has not yet been determined, and few mri screening studies have been conducted since its introduction [ ] . we hypothesized that recent improvements in immunosuppressive treatment may reduce the incidence of onfh even with wider indications for rt. the purpose of the present study was twofold: ) to investigate transitional changes in the incidence of ofnh among renal transplant recipients by mri; and ) to investigate factors related to onfh for the entire cohort. the ethical review board of our institution approved the design of this study (registration number: ). the recent group included patients ( men, women; mean (±standard deviation) age, ± years, range, e years); mean body mass index (bmi), ( . ± . kg/m ) who underwent mri of both hips after rt between april and june (i.e., during the period in which basiliximab was regularly used). during the period, patients underwent rt. the past group included patients ( men, women; mean age, ± years; mean bmi, . ± . kg/ m ) who had undergone rt between january and march (i.e., prior to the regular use of basiliximab). during the period, patients underwent rt. there was no significant difference in the rates of mri screening between the groups. ( . % ( / ) vs . % ( / ), p ¼ . , chi-square test). all patients were notified about the reported incidences of onfh after rt, benefits and risks of mri, and possible treatment options, and given the opportunity to object. mri was performed months after rt using either a . -t superconducting magnet system (signa horizon lx . t; general electric medical systems, milwaukee, wi), or one of two . -t superconducting magnet systems (smt x; shimadzu, kyoto, japan or achieva . t a-series; philips healthcare, amsterdam, the netherlands). osteonecrosis was defined as an area of normal intensity demarcated by a low-intensity band on t -weighted imaging [ ] . t -weighted spin-echo images were obtained using a . -t system in the coronal and sagittal planes, with the following settings: repetition time (tr), e ms; echo time (te), e ms; and slice thickness, e mm. spoiled gradient-recalled echo pulse sequences were obtained using the . -t system in the coronal plane with the following settings: tr, . e ms; te, . e . ms; flip angle, ; and slice thickness, . e . mm with no interslice gap. the following items were evaluated: onfh incidence; patient demographic and background factors, including gender, age, bmi, and abo and hla incompatibility; duration of preoperative dialysis; type of renal graft (living/cadaveric donor); preoperative immunosuppressant use, including calcium inhibitors (cyclosporine a/tacrolimus) administered initially or at the time of hospital discharge; concomitant basiliximab administration; steroid administration at , , , and weeks after rt, as prednisolone (psl), methylprednisolone (mpsl), and total steroid doses (converted to psl-equivalent doses); postoperative renal function, including delayed graft function (dgf), blood urea nitrogen (bun) and creatinine (cr) levels at weeks after rt, and acute transplant rejection; and duration of hospitalization. psl-equivalent doses were calculated by adjusting the mpsl dose on the basis of antiinflammatory potency, using a conversion factor of . . acute transplant rejection was diagnosed as follows: a % increase in bun or a % increase in cr level compared with those at a previous sampling, daily urinary output ml, and diagnosis by biopsy. dgf was defined as a patient requiring hemodialysis in the first week after rt. we compared these items between the recent and past groups using the mannewhitney u-test, chi-square test, and fisher's exact probability test for statistical analyses. in addition, we investigated factors influencing the incidence of onfh for the entire cohort. uniand multivariate logistic regression models were used to identify significant risk factors for onfh for the entire cohort. the adjusted odds ratio (or) for predicting onfh was determined for each factor identified by univariate logistic regression analysis. spss for windows version . j statistical software (spss, chicago, il) was used for all statistical analyses. a % significance level was applied to all tests. no cases of onfh were recorded in the recent group ( %; % confidence interval (ci), %e . %), although eight cases of onfh were recorded in the past group ( . %; % ci, . e . %; one-sided fisher's exact probability test, p ¼ . ). intergroup comparisons of background and demographic factors revealed significant increases in age, bmi, number of patients with abo and hla incompatibilities, and living kidney donors in the recent group ( table ) . comparison of postoperative immunosuppressant use showed increased frequency of tacrolimus use, increased number of patients with concomitant use of basiliximab, and decreases in mpsl, psl, and total steroid dose at postoperative weeks , , , and in the recent group ( table ) . regardless of the increase in risk factors for rt such as older age and increased number of abo/hlaincompatible transplants among patients, decreases in steroid administration and improvements in postoperative renal function have been observed in the recent group. in addition, significant decreases were seen in the number of cases with dgf, concentrations of bun and cr at weeks after transplantation, incidence of acute transplant rejection, and duration of hospitalization over time ( table ) . the overall results were surveyed for risk factors for onfh. according to the analysis of individual factors, total mpsl dose at postoperative weeks , , , and , total steroid dose at postoperative weeks , , , and and dgf were identified as significant risk factors (table ) . psl administration at postoperative weeks , , , and was not a risk factor. we performed multivariate analysis (logistic regression analysis) for age, gender, and total mpsl dose at postoperative week , and dgf. significant risk factors for onfh were total mpsl dose at postoperative week (or, . ; % ci, . e . ; p ¼ . ) and dgf (or, . ; % ci, . e . ; p ¼ . ) ( table ) . when the mpsl doses at postoperative weeks , , and were selected as a risk factor rather than that at week , the following were the adjusted values: for week , or was . ( % ci, . e . ; p ¼ . ); for week , or was . ( % ci, . e . ; p ¼ . ); and for week , or was . ( % ci, . e . ; p ¼ . ). mpsl administration at week showed the highest adjusted or. the types of onfh according to japanese investigation committee classification, their natural course and surgical treatment were summarized in table . improvements in post-transplant renal function and reductions in corticosteroid dose may have led to a decrease in the incidence of onfh [ e ]. renal graft function after rt has been improving with advances in immunosuppressive agents such as cyclosporine a [ , ] and tacrolimus [ e ] . several other immunosuppressive agents including sirolimus, everolimus, mycophenolate mofetil, and basiliximab have been introduced in combination with cyclosporine a or tacrolimus and have also improved postoperative renal function [ ] . in contrast, few reports have been published about the influence of these new immunosuppressive agents on the incidence of onfh after rt. basiliximab, an anti-cd monoclonal antibody, is a very strong immunosuppressive agent that exerts its effects through competitive interleukin- antagonism [ ] . when administered as an induction therapy during the early postoperative period, in conjunction with one or more conventional immunosuppressive drugs, decreases in the incidences of acute transplant rejection and dgf and improvements in survival of the transplanted kidney have been reported [ e ] . decreases in steroid and calcineurin inhibitor doses have also been reported [ , , ] . these marked changes in immunosuppressive treatments and postoperative renal function may have reduced the incidence of onfh. the proportion of onfh patients receiving steroid treatment for renal transplantation has reportedly decreased recently according to the multicenter hospital-based sentinel monitoring system for onfh in japan [ ] , although the reasons for these decreases in the proportion of onfh patients receiving renal transplantation remain unclear. in addition, only a small number of reports since have described mri screening for onfh after rt, and the impact of the introduction of basiliximab on the post-transplant incidence of onfh has yet to be determined. we therefore investigated the incidence of onfh since the advent of regular basiliximab use and found that postoperative renal graft function had improved, and the mpsl dose and incidence of dgf as risk factors for onfh had decreased. in addition, the incidence of onfh had decreased. basiliximab seems likely to indirectly reduce the incidence of onfh by reducing the incidence of dgf and allowing reductions in mpsl administration. three main limitations need to be considered when interpreting the results from the present study. first, the number of renal transplant recipients with use of basiliximab might be too small to evaluate its effect on the incidence of onfh. the number of patients included in previous mri screening studies ranged from to [ , e ] , so the number of patients in the present study is comparable with the numbers in those studies. second, mri screening was not performed before rt, so we could not be sure that onfh had not been present prior to transplantation. nevertheless, because the incidence of onfh in our study was lower than that in any previous study evaluated using mri, the incidence was presumed to have also been low even before transplantation. third, the timing of mri screening was earlier compared to other mri screening studies. this might be one reason the incidence of onfh at our institute was lower than described in other reports performed during a similar period. we did not encounter any symptomatic cases with onfh in which mri had been negative at months after rt, so we considered that the incidence of onfh occurring after months after rt was unlikely to have been particularly high. onfh did not occur in any of the patients who underwent rt between april and june at our institution, despite the wider indications for rt in high-risk patients, such as older age and more severe abo and hla incompatibilities. in previous mri screening studies of onfh after rt performed between and without the use of basiliximab, incidences of onfh after rt were within the range of . e . % [ , e ] . although a downward trend was observed in those studies, no mri screening studies for onfh have been reported since , and the present study showed the lowest incidence of onfh after rt among all relevant studies (table ) . to elucidate the risk factors for onfh, all rt recipients who underwent mri screening at our institute were analyzed. the results showed that dgf and cumulative mpsl administration up to weeks after rt were significant risk factors. other risk factors for onfh reported after rt include daily oral steroid dose, bun level months after rt, accumulated steroid dose at months, accumulated steroid dose at weeks, ethnicity (african-american), history of peritoneal dialysis, rejection, delayed graft function, and cyclosporine a administration [ , , , e ] . to date, cumulative steroid dose as of weeks postoperatively has been reported as the shortest-term risk factor for onfh [ ] . the risk factors for onfh after rt in the present study were in accordance with past findings. this result suggests that onfh occurs mostly within the first weeks after rt, suggesting the importance of controlling postoperative graft function and reducing cumulative mpsl administration in the first weeks after rt using immunosuppressive agents that are appropriate for the prevention of onfh. a recent meta-analysis of onfh occurrences among patients taking corticosteroids reported positive associations between mean daily corticosteroid doses and onfh across all diagnoses, including severe acute respiratory syndrome, systemic lupus erythematosus, bone marrow transplantation and renal transplantation, although the correlation between mean daily corticosteroid dose and onfh incidence was not significant among renal transplant recipients [ ] . no evidence of a significant correlation between cumulative corticosteroid dose and incidence of onfh has yet been provided [ , ] . in renal transplant recipients, daily steroid dose is gradually tapered according to the immunosuppressive regimen, so reflecting an overall picture of steroid treatment using a mean value for daily steroid dose is difficult. in addition, duration of steroid treatment and overall cumulative steroid dose vary widely among renal recipients, and steroid administration after onset of onfh might be included in the regression analysis. we therefore focused on the correlation between steroid administration including oral steroid administration and pulsed steroid therapy in the weeks after renal transplantation and onset of onfh at months. the risk of onfh after rt has fallen since the advent of regular basiliximab use, although this agent does not appear to be a factor directly associated with the incidence of onfh. factors related to onfh incidence were found to be renal graft function and mpsl administration for up to weeks. since the introduction of basiliximab, immunosuppressive therapy has changed markedly and renal graft control has also been enhanced, which may have led to decreases in the incidence of onfh. this research is supported by the practical research project for rare/intractable diseases from japan agency for medical research and development, amed. in accordance with icmje criteria, ns and st designed the study and mt wrote the initial draft of the manuscript. ha contributed to the collection and interpretation of data and the assistance of the preparation of the manuscript. the literature data were searched and analyzed by mt and ha. all other authors contributed to the data collection and interpretation. all authors approved the final version to be submitted for publication and agree to be accountable for all aspects of the work. none. all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the declaration of helsinki and its later amendments or comparable ethical standards." informed consent was obtained in the form of opt-out on the web-site. those who rejected were excluded. maintenance immunosuppression use and the associated risk of avascular necrosis after kidney transplantation in the united states cyclosporin a and osteonecrosis of the femoral head incidence of hip osteonecrosis among renal transplantation recipients: a prospective study tacrolimus may be associated with lower osteonecrosis rates after renal transplantation early detection of avascular necrosis of the femoral head following renal transplantation initial changes of non-traumatic osteonecrosis of femoral head in fat suppression images: bone marrow edema was not found before the appearance of band patterns apparent avascular necrosis of the hip: appearance and spontaneous resolution of mr findings in renal allograft recipients initial mri findings of non-traumatic 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necrosis of the femoral head after renal transplantation rabbit-atg or basiliximab induction for rapid steroid withdrawal after renal transplantation (harmony): an open-label, multicentre, randomised controlled trial prolonged action of a chimeric interleukin- receptor (cd ) monoclonal antibody used in cadaveric renal transplantation monoclonal antibody basiliximab with low cyclosporine dose as initial immunosuppression a randomized, double-blind trial of basiliximab immunoprophylaxis plus triple therapy in kidney transplant recipients temporal trends in characteristics of newly diagnosed nontraumatic osteonecrosis of the femoral head from to : a hospital-based sentinel monitoring system in japan hospitalized avascular necrosis after renal transplantation in the united states corticosteroid administration within weeks after renal transplantation affects the incidence of femoral head osteonecrosis cyclosporine use and male gender are independent determinants of avascular necrosis after kidney transplantation: a cohort study high-dose corticosteroid use and risk of hip osteonecrosis: meta-analysis and systematic literature review etiologic classification criteria of arco on femoral head osteonecrosis part : glucocorticoidassociated osteonecrosis authors thank dr. hideki yoshikawa, dr. koji yazawa, and dr. naotsugu ichimaru for helpful advice. key: cord- -w tftva authors: suran, jantra ngosuwan; wyre, nicole rene title: imaging findings in domestic ferrets (mustela putorius furo) with lymphoma date: - - journal: vet radiol ultrasound doi: . /vru. sha: doc_id: cord_uid: w tftva lymphoma is the most common malignant neoplasia in domestic ferrets, mustela putorius furo. however, imaging findings in ferrets with lymphoma have primarily been described in single case reports. the purpose of this retrospective study was to describe imaging findings in a group of ferrets with confirmed lymphoma. medical records were searched between and . a total of ferrets were included. radiographs (n = ), ultrasound (n = ), computed tomography (ct; n = ), and magnetic resonance imaging (mri; n = ) images were available for review. median age at the time of diagnosis was . years (range . – . years). clinical signs were predominantly nonspecific ( / ). the time between the first imaging study and lymphoma diagnosis was day or less in most ferrets ( ). imaging lesions were predominantly detected in the abdomen, and most frequently included intra‐abdominal lymphadenopathy ( / ), splenomegaly ( / ), and peritoneal effusion ( / ). lymphadenopathy and mass lesions were typically hypoechoic on ultrasound. mild peritoneal effusion was the only detected abnormality in two ferrets. mild pleural effusion was the most common thoracic abnormality ( / ). expansile lytic lesions were present in the vertebrae of two ferrets with t ‐l myelopathy and the femur in a ferret with lameness. hyperattenuating, enhancing masses with secondary spinal cord compression were associated with vertebral lysis in ct images of one ferret. the mri study in one ferret with myelopathy was inconclusive. findings indicated that imaging characteristics of lymphoma in ferrets are similar to those previously reported in dogs, cats, and humans. l ymphoma is the most common malignant neoplasia in domestic ferrets, mustela putorius furo. following insulinoma and adrenocortical neoplasia, it is the third most common neoplasia of domestic ferrets overall. [ ] [ ] [ ] [ ] in ferrets, lymphoma can be classified based on tissue involvement, including multicentric, mediastinal, gastrointestinal, cutaneous, and extranodal. [ ] [ ] [ ] the presentation and organ distribution of lymphoma has been associated with the age of onset. , mediastinal lymphoma is more prevalent in young ferrets, particularly less than year of age. these ferrets tend to have an acute presentation and may present with dyspnea. ferrets with mediastinal lymphoma may also have multicentric involvement. , , ferrets years of age and greater have a variable presentation with multicentric disease being more prevalent. clinical signs in older ferrets may be chronic and nonspecific depending on organ involvement. some ferrets may have intermittent signs over several months, while others may be asymptomatic with lymphoma being diagnosed incidentally, detected either during routine physical examination or during evaluation of comorbidities. [ ] [ ] [ ] despite lymphoma being common in domestic ferrets and the use of radiography and ultrasonography being touted as part of the minimum database in the diagnosis of lymphoma, , imaging findings in ferrets with lymphoma have been limited to a few case reports. , , , , [ ] [ ] [ ] [ ] the goal of this retrospective study was to describe radiography, ultrasonography, computed tomography (ct), and magnetic resonance imaging (mri) findings in a series of ferrets with a confirmed diagnosis of lymphoma. medical records at the matthew j ryan veterinary hospital of the university of pennsylvania were searched for domestic ferrets with a diagnosis of lymphoma confirmed with cytology or histopathology that had radiography, ultrasonography, ct, or mri performed between january and april . signalment, clinical signs, laboratory findings, and any prior or concurrent disease processes were recorded. vet radiol ultrasound, vol. , no. , , pp - . radiographs, ct, mri, static ultrasound images, and when available, ultrasound cine loops were retrospectively evaluated, and abnormal findings were recorded by j.n.s. the imaging reports generated by a board-certified veterinary radiologist at the time the study was performed were also reviewed. ferrets were excluded if the imaging studies were unavailable for review. any imaging studies obtained after the reported start of clinical signs until a diagnosis was achieved were included. in addition to the reported ultrasonographic findings, the maximal splenic and lymph node thicknesses were measured from the available images if they were not reported. as splenomegaly is common in ferrets, most frequently due to extramedullary hematopoiesis, splenomegaly was subjectively graded as within incidental variation ("incidental splenomegaly") and larger than expected for "incidental splenomegaly." those with subjectively normal spleens or "incidental splenomegaly" were referred to as normal for the purposes of this paper, unless otherwise specified. retrieved ct images were reconstructed with a high-frequency high-resolution algorithm (bone algorithm with edge enhancement) in . mm slice thickness. the maximal lymph node thickness was measured on precontrast images. fourteen ferrets met the inclusion criteria. lymphoma was diagnosed from ultrasound-guided aspirates, surgical biopsies, and/or necropsy; three ferrets had two diagnostic procedures performed. ultrasound-guided aspirate cytology was performed in nine ferrets, surgical biopsy in three, and necropsy in five. both aspirates and biopsy were performed in two ferrets, and both aspirates and necropsy in one ferret. one ferret in this study was previously described. the median age at the time of lymphoma diagnosis was . years (range . - . years). eight of the ferrets were neutered males, and six were spayed females. prior disease histories included adrenal disease (n = ), cardiovascular disease ( ), cutaneous mast cell tumors ( ), diarrhea ( ), insulinoma ( ), cataracts ( ) , and one each of granulomatous lymphadenitis secondary to mycobacteriosis, renal insufficiency, and a chronic pelvic limb abscess. cardiovascular disease included second degree atrioventricular block ( ), systemic hypertension ( ), hypertrophic obstructive cardiomyopathy ( ) , and in one individual both aortic insufficiency and arteriosclerosis. for most ferrets, the time between the first imaging study and a diagnosis of lymphoma was day or less ( / ) . in one ferret each, the time between the initial imaging study and final diagnosis of lymphoma was days and . months. the duration of clinical signs prior to reaching the diagnosis of lymphoma ranged from less than day to months with a mode of less than day and a median of days. clinical signs include lethargy (n = ), diarrhea ( ) , inappetence ( ), weight loss ( ), ataxia ( ), lameness ( ), and vomiting ( ) . diarrhea was chronic in three ferrets and consistent with melena in two. two ferrets did not have overt clinical signs. physical exam findings included palpable abdominal masses ( ) , generalized splenomegaly ( ), palpable splenic nodules or splenic masses ( ), dehydration ( ), paraparesis and ataxia ( ), abdominal pain ( ), hypotension ( ), lumbar pain ( ), abdominal effusion ( ), inguinal and popliteal lymphadenopathy ( ), pyrexia ( ), urinary and fecal incontinence ( ), and a right femoral mass ( ). paraparesis and ataxia were attributed to t -l myelopathy in three ferrets and hypoglycemia in one. one ferret also presented with ptyalism and tremors, which resolved with dextrose administration. blood analyses, including a complete blood count and chemistry profile, were performed in of the ferrets. blood glucose evaluation alone was performed in one ferret. abnormalities included azotemia ( ), elevated liver enzymes ( ), nonregenerative anemia ( ), hypoglycemia ( ), hypoalbuminemia ( ), lymphocytosis ( ), hyperglobulinemia ( ), hypercalcemia ( ), and elevated total bilirubin ( ). two of the four ferrets with hypoglycemia had a previous diagnosis of insulinoma. radiographs were performed in / ferrets. each of these studies included the thorax and abdomen-six studies included a right or left lateral projection and a ventrodorsal projection and six included a left lateral, right lateral, and ventrodorsal projections. one ferret's radiographs were in an analog format (screen-film), and the remaining were digital (rapidstudy, eklin medical systems inc., santa clara, ca). ultrasound was performed in / ferrets using a - mhz linear transducer (ge medical logiq ultrasound imaging system, general electric medical systems, milwaukee, wi). abdominal ultrasonography was performed in / ferrets. ultrasonography of a rib mass and a femoral mass was performed in one ferret each. abdominal ultrasonography was performed twice in one ferret after the start of the reported clinical signs, but prior to the diagnosis of lymphoma. ultrasounds were performed by a board-certified radiologist or a radiology resident under direct supervision from a board-certified radiologist. in the one ferret with two ultrasounds performed prior to diagnosis of lymphoma, the later scan was used for measurements. computed tomography of the thorax and abdomen was performed in one ferret. the ferret was scanned under general anesthesia in dorsal recumbency using a -slice multidetector ct unit (ge brightspeed, general electric company, milwaukee, wi) in medium-frequency soft tissue algorithms ( . mm slice thickness, . pitch) before and immediately after iv administration of nonionic iodinated contrast (iohexol, mgi/ml, dosage mgi/kg, [omnipaque, ge healthcare, inc., princeton, nj]). contrast was manually injected through an iv catheter preplaced in a cephalic vein. one ferret underwent mri evaluation of the lumbar and sacral spine. magnetic resonance imaging was performed using a . t mri unit (ge medical system, milwaukee, wi) with the patient in dorsal recumbency under general anesthesia. image sequences included t weighted (t w) image series in a sagittal and transverse plane, t w fat-saturated images in a sagittal and transverse plane, and a sagittal single-shot fast spine echo. additional sequences including t weighted (t w) images and administration of gadolinium were not performed due to anesthetic concerns for the patient. radiographic and ultrasonographic findings are summarized in table . radiographic abnormalities were predominantly noted in the abdomen. decreased abdominal serosal detail was present in of the ferrets with radiographs. this was interpreted to be potentially due to a poor body condition in two ferrets. abdominal serosal detail was additionally mottled in seven ferrets. sonographically, peritoneal effusion was detected in / ferrets, and was considered mild in , moderate in , anechoic in , and echogenic in . the spleen was considered enlarged in out of ferrets radiographically and in out of ferrets in which abdominal ultrasonography was performed. the remaining five ferrets were considered to have "incidental splenomegaly" on ultrasound and were radiograph- ically considered normal (n = ) and enlarged ( ) . of the eight spleens sonographically considered abnormal, multifocal hypoechoic splenic nodules were present in six ferrets (fig. ) ; one of these six ferrets was considered to have a radiographically normal spleen. an isoechoic to hypoechoic mass with central hypoechoic nodules was present in one ferret. the spleen had a mottled echotexture in one ferret. three ferrets were sedated with butorphanol (torbugesic, fort dodge animal health, fort dodge, ia) and midazolam (hospira inc., lake forrest, il) prior to abdominal ultrasonography; sedation was not performed in any ferret prior to radiographs. all three sedated ferrets had enlarged spleens with one spleen having a mottled echotexture and the other two spleens having multifocal hypoechoic nodules. splenic cytology or histopathology was not performed in any of the ferrets that received sedation for ultrasound. cytology or histopathology was available in seven ferrets-aspirates were performed in / , necropsy in / , and both aspirates and necropsy in / . lymphoma was confirmed in three out of six ferrets with splenic nodules, the one ferret with a splenic mass, and one out of five ferrets with "incidental splenomegaly." in three of the five ferrets with "incidental splenomegaly," marked splenic extramedullary hematopoiesis with splenic congestion ( ) and without concurrent splenic congestion ( ) was diagnosed. the other seven ferrets did not have cytologic evaluation of the spleen. splenic thickness in ferrets where the spleen was considered within incidental variation ranged from . to . mm (median, . mm, mean . mm, standard deviation ± . mm; n = ), while in ferrets with splenomegaly splenic thickness ranged from . to . mm (median . mm, mean . mm, standard deviation ± . mm; n = ). single or multiple, round to oblong, soft-tissue opaque, abdominal masses consistent with enlarged lymph nodes were visible radiographically in / ferrets (fig. ) . one of these ferrets had a large cranial abdominal mass, which was subsequently confirmed to be a markedly enlarged pancreatic lymph node. one ferret had splenic lymphadenopathy detected on the radiographs retrospectively after evaluation of the sonographic findings. lymphadenopathy was reported in of the ferrets with abdominal ultrasonography and the one ferret in which whole body ct was performed. sonographically, abnormal lymph nodes were hypoechoic, rounded, variably enlarged, and surrounded by a fig. . ultrasound image of an enlarged hepatic lymph node in the same ferret as fig. . the hepatic lymph node is markedly enlarged and lobular. although the node is predominantly hypoechoic, there are patchy hyperechoic regions and smaller, round, hypoechoic, nodule-like regions within (arrow). the surrounding fat is hyperechoic, producing a halo around the lymph node (arrow heads). scale at the top of the image is mm between the major ticks. hyperechoic rim (fig. ). some lymph nodes had patchy hyperechoic regions within or a reticular, nodular appearance. abdominal lymph nodes involved included the mesenteric (n = ), hepatic ( ), sublumbar ( ), splenic ( ), gastric ( ), gastroduodenal ( ), colonic ( ), pancreatic ( ), ileocolic ( ), renal ( ), and inguinal ( ) lymph nodes. in one ferret other lymph nodes were reported to be involved in addition to the mesenteric and sublumbar nodes, but were not specifically identified. nine of the ferrets with abdominal ultrasound and the one ferret with ct had involvement of or more lymph nodes reported; / ferrets had only one reportedly abnormal lymph node ( splenic lymph node, mesenteric lymph node). lymph nodes measured from . to . mm thick (median . , mean . mm, standard deviation ± . mm). the lymph node thickness in ferrets with radiographically evident lymphadenopathy ranged from . mm to . mm with a median of . , and mean of . , and standard deviation of ± . mm (n = ). in ferrets in which lymphadenopathy was detected sonographically but not radiographically, lymph nodes measured . mm, . mm, and . mm thick (n = ). lymph node cytology or histopathology was available in seven ferrets-aspirates were performed in / ferrets, both aspirates and surgical biopsy in / , and necropsy in / . it was not clear if lymph nodes were histopathologically assessed in / ferrets in which a necropsy was performed. lymphoma was confirmed in / ferrets with sonographically abnormal lymph nodes (range . - . mm thick, median . mm, mean ± standard deviation . ± . mm). in / ferrets, lymphoid hyperplasia was identified postmortem ( . mm thick). cytologic evaluation of lymph nodes was not performed in the remaining ferrets. in ferrets with lymphadenopathy, eight had concurrent splenomegaly with fig. . ultrasound image of the gastric antrum. the wall of the gastric antrum, especially the muscularis layer, is circumferentially thickened (arrows). a small amount of fluid and gas (*) is present in the lumen. splenic nodules ( ), a splenic mass ( ), or a mottled splenic echotexture ( ) . lymphoma was identified in the liver of / ferrets by surgical biopsy ( ) and at necropsy ( ) . mild hepatomegaly with a normal echotexture was noted on ultrasound in the ferret with lymphoma diagnosed by biopsy. additional findings in this ferret included mild peritoneal effusion and lymphadenopathy. the ferret with hepatic lymphoma identified at necropsy had no radiographic or reported sonographic liver abnormalities. this ferret also had hepatic lipidosis. imaging findings in this ferret included an aggressive vertebral lesion, splenomegaly with splenic nodules, and lymphadenopathy. lymphoma was confirmed in each of these organs, as well as in the pancreas, which was reportedly normal on ultrasound. in addition to these two ferrets, hepatic histopathology from necropsy was available in four other ferrets. hepatic lipidosis was identified each of these four ferrets; one ferret also had extramedullary hematopoiesis. none of these four ferrets had radiographic or reported sonographic abnormalities. cytology or histopathology was not available in the remaining / ferrets. of these, / had no radiographic or sonographic abnormalities noted. mild hepatomegaly was noted radiographically in / ferrets; however, sonographic hepatic changes were not noted in these ferrets and cytologic evaluation was not performed. on ultrasound, one ferret had moderate hepatomegaly with a hypoechoic, mottled echotexture (radiography was not performed in this ferret). additionally one ferret had two hypoechoic cystic masses, one mass of which had central mineralization, detected with ultrasound (radiography was not performed in this ferret). gastrointestinal lymphoma was confirmed at necropsy in two ferrets. in one ferret, thickening of the gastric antrum up to . mm and blurring of wall layering was identified sonographically (fig. ) . (to the authors' knowledge, the normal gross or sonographic wall thickness of the gastrointestinal tract in ferrets has not been previously reported.) fig. . ultrasound image of the right kidney. there is a round, hypoechoic nodule in the parenchyma, which bulges from the renal contour. the calipers (+) denote the renal length ( ) and margins of the nodule ( , ). no abnormalities were noted in the small or large intestines. at necropsy, lymphoma was identified in the stomach and small intestines, in addition to a chronic ulcerative gastroenteritis. in the second ferret, aside from poor abdominal serosal detail attributable to poor body condition and mild anechoic peritoneal effusion, there were no other radiographic or sonographic abnormalities. in this ferret, lymphoma was identified postmortem in the descending colon. the colon was discolored, but there was no reported gross colonic wall thickening. renal masses were present in two ferrets. in each ferret, a single renal mass was detected with ultrasound and was well defined, hypoechoic, centered on the cortex, and protruded from the kidney. the mass was right-sided, rounded, and measured . mm in diameter in one of these two ferrets. in the second ferret, the mass was left-sided, lobular, and measured up to . mm in diameter. cytology of the right renal mass in the first ferret was not performed; however, the patient received chemotherapy for the treatment of lymphoma, confirmed from aspiration and biopsy of an enlarged lymph node, and the mass was seen to decrease in size during follow-up studies (fig. ) . although the masses in both ferrets had similar ultrasound characteristics, the renal mass in the second ferret was diagnosed as a spindle cell sarcoma. additionally that mass had been identified sonographically year prior to the diagnosis of lymphoma, was progressively increasing in size, and did not decrease in size following administration of chemotherapy for the treatment of lymphoma. concurrent sonographic changes in both ferrets included lymphadenopathy and peritoneal effusion. a large lobular retroperitoneal mass was present in one ferret. the mass was on midline, extending into the right and left sides of the retroperitoneal space, laterally displacing the right kidney. the left kidney was not visualized radiographically. in the right cranial retroperitoneal space, cranial to the right kidney, there was a cluster of heterogeneous mineral opacities in an adjacent second, smaller mass. sonographically the large retroperitoneal mass was heterogeneous, hypoechoic with patchy hyperechoic regions, and laterally displaced both kidneys. the smaller mineralized mass was confirmed to be an enlarged right adrenal gland sonographically. at necropsy, the retroperitoneal mass was confirmed to be lymphoma; however, a specific tissue of origin was not determined. as a normal left adrenal gland could not be identified sonographically or at postmortem, an adrenal origin for this mass was considered most likely, although adrenal tissue was not identified histopathologically within the mass. alternatively the mass may have arisen from a retroperitoneal lymph node or retroperitoneal adnexa. concurrent abdominal imaging findings considered incidental to the diagnosed lymphoma included renal cysts ( ) , cystic lymph nodes ( ), adrenomegaly in ferrets with diagnosed adrenal disease ( ), and pancreatic nodules in ferrets diagnosed with insulinoma ( ). on thoracic radiographs pleural fissure lines, consistent with a small volume of pleural effusion, were present in / ferrets. pericardial and pleural effusions were noticed during abdominal ultrasonography in one ferret. possible sternal ( ) and tracheobronchial lymphadenopathy ( ) were seen radiographically. in one ferret, sternal and cranial mediastinal lymphadenopathy were detected with ct. an interstitial pulmonary pattern was present in two ferrets, but was potentially attributable to the radiographic projections being relatively expiratory. aggressive osseous lesions were detected radiographically in three ferrets. the one ferret with a history of lameness had a soft-tissue mass involving the entire right femur with marked, multifocal areas of geographic to motheaten, expansile lysis throughout. smooth to mildly irregular periosteal reaction was present along the femoral diaphysis and greater trochanter. the adjacent acetabulum and ileum were questionably involved based on the radiographs. sonographically the soft-tissue components of the mass were homogeneously hypoechoic. cortical irregularities and disruption, consistent with lysis, were also present. histopathology of the mass following limb amputation was consistent with plasmablastic lymphoma. this ferret was previously described. vertebral lysis was apparent radiographically in two of the three ferrets with t -l myelopathy. in one of these two ferrets, there was geographic lysis of l involving the majority of the vertebral body and a pathologic fracture of the cranial end plate (fig. ) . other radiographic changes present in this ferret included splenomegaly and decreased abdominal serosal detail likely due to poor body condition. on ultrasound, peritoneal effusion, splenomegaly with splenic nodules, and lymphadenopathy were detected. at necropsy, intramedullary lymphoma was found in the l vertebra with epidural extension of the tumor. lymphoma was also found affecting the spleen, liver, pancreas, and fig. . right lateral radiograph cropped and centered on l . at l there is geographic lysis, including cortical thinning or loss, of the cranial two-thirds of the vertebral body and the cranial aspect of the pedicles (arrows). the cranial end plate of l has a concave indentation, presumptively secondary to a pathologic fracture (arrow head). mesenteric lymph nodes. in the second ferret with vertebral lysis, there was geographic lysis of the cranial two-thirds of the body and pedicles of t . there was also possible lysis of the cranial body and pedicles of l . the dorsal half of the left th rib was lytic and no longer visible. associated with this rib, there was a large, ill-defined, soft-tissue mass, which extended into the thoracic cavity. the adjacent ribs and vertebra were not appreciably involved. additional radiographic findings in this ferret included splenomegaly, hepatomegaly, and abdominal masses consistent with enlarged lymph nodes. with ct, expansile lysis of the left t vertebral body and pedicle was seen associated with a hyperattenuating (to muscle), strongly enhancing mass (fig. ) . the mass occupied the ventral two-thirds of the spinal canal and resulted in severe spinal cord compression. a possible pathologic fracture was present in the cranial endplate. at l , there was lysis of the left pedicle and body associated with a mildly compressive, hyperattenuating, contrast-enhancing mass. an additional, similar mass lesion was seen at t , with lysis of the midvertebral body and mild spinal cord compression. the rib mass was isoattenuating (to muscle), heterogeneous, mildly enhancing, and resulted in severe, expansile lysis. cytology of the rib mass obtained by ultrasound-guided fine-needle aspiration was diagnostic for lymphoma; cytological assessment of the other lesions was not performed in this ferret. one ferret with t -l myelopathy did not have gross skeletal pathology. radiographic changes included splenomegaly and poor, mottled serosal detail. sonographically, a mild peritoneal effusion was present, and the spleen was considered within incidental variation. an mri of the lumbar spine revealed an ill-defined area of suspect intramedullary t w hyperintensity within the spinal cord at the level of l . differential diagnoses for this lesion considered at the time included an artifact, prior infarct, gliosis, edema, myelitis, neoplasia, and hydromyelia. at the postmortem examination performed months after the mri, lymphoma was detected in the brain, meninges, choroid plexus, spinal cord, and extracapsular accessory adrenal tissue. additionally there was multifocal spinal cord malacia and hemorrhage. the lesions in the spinal cord were identified in histopathologic samples obtained at intervals from the cervical spine at c through to the lumbar spine at l , including at the level of l . specific correlation between the suspect mri lesion and histopathologic findings was not performed. splenic changes were consistent with congestion and extramedullary hematopoiesis. multicentric lymphoma was the most common presentation in this study. this is consistent with prior reports in which multicentric lymphoma is the most common presentation in ferrets older than years of age. , , , the most common imaging findings in this study were intraabdominal lymphadenopathy and splenomegaly with mildto-moderate peritoneal effusion. lymphadenopathy consisted of multiple enlarged, predominantly intra-abdominal lymph nodes, particularly including the mesenteric lymph node. only one ferret had peripheral lymphadenopathy, consisting of enlargement of the inguinal and popliteal lymph nodes, in addition to abdominal lymphadenopathy. lymph nodes greater than . mm thick sonographically were generally appreciable radiographically as round to oblong, soft-tissue nodules or masses in their respective locations. of the three ferrets in which sonographically detected lymphadenopathy was not appreciable radiographically, only one had a lymph node thickness greater than . mm. that ferret also had a large, retroperitoneal mass that likely accounted for a lack of visualization of the enlarged mesenteric lymph node due to silhouetting and displacement. previous studies in normal ferrets using ultrasound have reported the normal thickness of mesenteric lymph nodes as . ± . mm and . ± . mm. , given that some radiographically visible lymph nodes measured as small as . mm (which is within the reported normal ranges for mesenteric lymph nodes) it is possible that normal lymph nodes may be radiographically appreciable. in the authors' experiences, however, visualization of normal, small abdominal lymph nodes on radiographs of ferrets is uncommon. normal abdominal lymph nodes are not radiographically distinguishable in dogs and cats. , although some lymph nodes in this study that were considered abnormal measured within the reported normal ranges, there were other changes to those nodes to suggest pathology, such as hypoechogenicity. in dogs and cats, sonographic changes that have been associated with malignancy include an increase in maximal short and long axis diameter (enlarged), an increase in short-to-long axis length ratio (more rounded appearance), hypoechogenicity, hyperechoic perinodal fat with an irregular nodal contour, and heterogeneity. [ ] [ ] [ ] similar to previous reports, the spleen was the most common extranodal site of neoplastic infiltration with lymphoma in the current study. in a prior study splenomegaly was attributable to neoplastic infiltration in % of ferrets with lymphoma and extramedullary hematopoiesis in %. in general, splenomegaly secondary to extramedullary hematopoiesis is common in ferrets. to the authors' knowledge, there is no reference for normal splenic size in ferrets using ultrasound. grossly the normal spleen has been reported to measure . cm in length, . cm in width, and . cm thick. given that these are gross measurements, however, they were likely obtained postmortem. splenic size is variable and decreases postmortem, so these measurements may not be translatable to antemortem studies with sonographic measurements. the smallest splenic thickness in this study was . cm; using the gross measurement guidelines all spleens in this study would be considered enlarged. the degree of splenomegaly was therefore subjectively characterized as within incidental variation and larger than expected for "incidental splenomegaly" based on the authors' experiences. of the seven ferrets in which splenic cytology was available, lymphoma was confirmed in the four ferrets in which the spleen was considered abnormal and cytology was performed. of the three ferrets spleens in which cytology was performed and the spleen was considered within incidental variation, lymphoma was identified in one, and extramedullary hematopoiesis was confirmed in the other two. potential differential diagnoses for multicentric lymphadenopathy with splenomegaly in ferrets include reactive lymphadenopathy secondary to gastrointestinal disease with splenic extramedullary hematopoiesis, systemic mycobacteriosis, granulomatous inflammatory syndrome, and aleutian disease. , [ ] [ ] [ ] [ ] with systemic mycobacteriosis, ferrets can have other lymph nodes affected in addition to the abdominal lymph nodes, with the retropharyngeal lymph nodes being affected as commonly as the mesenteric lymph nodes. as with lymphoma, clinical signs of mycobacteriosis in the ferret depend on the organs that are affected and can include lethargy, anorexia, vomiting, and diarrhea; but as with other infectious diseases, changes in white blood cell counts can be seen. mycobacteriosis can be diagnosed on cytology and biopsy of the affected lymph node or organ. granulomatous inflammatory syndrome is a newly recognized systemic disease associated with coronavirus that causes inflammation in the spleen and lymph nodes. this syndrome results in a severe granulomatous disease that can affect the gastrointestinal tract, mesenteric lymph nodes, liver, and spleen. unlike lymphoma, it is usually seen in younger ferrets, but like lymphoma, clinical signs are nonspecific and depend on the organ that is affected. patients with this syndrome usually have polyclonal gammopathy that can also be seen with aleutian's disease virus and lymphoma. definitive diagnosis requires cytology or biopsy of the affected organs. aleutian's disease is a parvovirus that can cause lymphadenopathy and splenomegaly. as with lymphoma and granulomatous inflammatory syndrome, aleutian's disease can cause a polyclonal gammopathy. ferrets with this virus usually present with generalized signs of illness (lethargy, weight loss) as well as neurologic signs such as paresis or tremors. aspirates and biopsy samples of lymph nodes and the spleen can be difficult to interpret as the disease causes lymphoplasmacytic inflammation that can be easily confused with other diseases such as small cell lymphoma and epizootic catarrhal enteritis. in the one ferret with colonic lymphoma, there were minimal imaging findings including poor abdominal serosal detail and mild peritoneal effusion. at postmortem, lymphoma with mucosal erosions was detected in the colon. segmental lymphoplasmatic enteritis was identified in the small intestines. this ferret presented cachexic, hypotensive, anemic, had melena, and died within h of presentation. given that melena is referable to upper gastrointestinal bleeding, the clinical findings in this ferret could have been attributable to both helicobacter mustelidae gastritis and lymphoma. it is also possible that lymphoma was present in other portions of the gastrointestinal tract, but was not detected postmortem. after the spleen, the next most common extranodal sites of neoplastic involvement with lymphoma in ferrets have been reported to be the liver, kidneys, and lungs. in this study, two ferrets had confirmed hepatic infiltration-one of which had mild hepatomegaly on ultrasound (subjectively normal on radiographs) and the other of which had no reported hepatic abnormalities. hepatic lipidosis, identified in four ferrets, was not associated with radiographic or sonographic changes and may have been due to inappetence. given these findings, ultrasound does not appear to be sensitive for the detection of hepatic lymphoma in ferrets. sensitivity of ultrasound for hepatic lymphoma has also been reported to be low in dogs, cats, and humans. , one of two ferrets with renal masses had probable renal lymphoma based on the response to treatment. the second renal mass, a confirmed renal sarcoma, was not sonographically differentiable from the presumptive renal lymphoma. pulmonary involvement was not identified in this study. the small number of individuals in this study precludes extensive comparisons of the affected organ distribution to prior studies. the most common thoracic finding in this study was mild pleural effusion, which was present in four ferrets. there were no ferrets with a mediastinal mass in this study. mediastinal involvement, in general, is more prevalent in ferrets less than years of age, and has been reported to be the more common presentation of lymphoma in that age group with or without concurrent multicentric involvement. [ ] [ ] [ ] ferrets with mediastinal lymphoma may present for tachypnea or dyspnea secondary to the space-occupying effect of a large mediastinal mass, as well as concurrent pleural effusion. no ferrets in this study were less than years old, which may have accounted for the lack of mediastinal involvement in this cohort. additionally, although this institution also provides primary care to nontraditional small mammal species, it is also a tertiary care facility and the population of ferret patients may not have been representative of the general domestic ferret population. there may have been a selection bias for ferrets with more insidious signs, which tend to occur in ferrets greater than years of age, as opposed to younger ferrets, which may have a more acute and more rapidly progressive presentation. aggressive osseous lesions were present in three ferrets with skeletal lymphoma involvement. to the authors' knowledge, only three other ferrets with osseous involvement have been described previously. , in those ferrets, lytic lesions were present in the tibia, in the lumbar spine, and in the lumbosacral spine. , based on those ferrets and the ferrets in this study, it is possible that the lumbar spine is a predilection site for vertebral lymphoma; however, this remains speculative. an alternate possibility is that lysis may be relatively easier to detect in the lumbar spine where there is less superimposition of structures over the vertebrae, compared to the thoracic vertebrae where the ribs proximally are superimposed on the vertebrae. in humans with primary bone lymphoma, three radiographs patterns are described: the lytic-destructive pattern, which is predominantly lytic with or without a lamellated or interrupted periosteal reaction or cortical lysis; the blastic-sclerotic pattern in which there are mixed lytic and sclerotic regions; and "near-normal" findings in which there are only subtle radiographic changes and additional imaging (scintigraphic bone scans or mri) is required. osseous lesions seen in the ferrets of this study and the prior reports are similar to the lytic-destructive pattern, and had cortical disruption. this is also the pattern most typically seen in canines and felines with osseous involvement from lymphoma or other round cell neoplasms. diffuse central nervous system infiltration with lymphoma was present in one ferret. as lymphoma outside of the central nervous system was only detected in accessory adrenal tissues, this ferret presumably had a primary central nervous system lymphoma. primary central nervous system lymphoma in dogs and cats has not been reported to have an extraparenchymal vs. an intraparenchymal predilection. in humans, lesions with primary central nervous system lymphoma are most frequently intraparenchymal, and metastatic central nervous system lymphoma is more frequently extraparenchymal. , in this ferret, the meninges and choroid plexus were involved in addition to the brain and spinal cord. protracted clinical signs in that ferret consisted of variable paraparesis and lumbar pain over months from the start of clinical signs to the final diagnosis of lymphoma at necropsy. gradual progression of signs and the protracted clinical signs suggests a relatively slow-growing process. prednisone, administered for palliative treatment, was started approximately months after the initial clinical signs. radiographs and ultrasound, performed prior to starting prednisone, had minimal, nonspecific findings. magnetic resonance imaging, performed month after initiation of the prednisone regimen and months prior to the diagnosis of lymphoma, was inconclusive. administration of prednisone prior to the mri may have resulted in partial regression of lymphoma, therefore making it more difficult to identify; however, the ferret did not demonstrate improvement of the clinical signs so whether prednisone affected detection of neoplastic infiltration or not is speculative. additionally the mri was limited in that only t w images were obtained. perhaps if additional sequences were performed, particularly t w postcontrast images, or if a follow-up mri was performed at a later date, meningeal or parenchymal abnormalities may have been detected. also because the necropsy was performed months following mri, it is likely that the extent of the lesions seen postmortem had progressed com-pared to at the time of imaging. magnetic resonance imaging lesions in dogs and cats with primary central nervous system lymphoma (compared to white matter) have been reported to be predominantly t w hyperintense with indistinct margins, t w hypointense, contrast enhancing, had perilesional hyperintensity on flair consistent with perilesional edema, and had a mass effect. in humans, lesions have similar signal characteristics (compared to white matter) being t w hyperintense, t w iso-to hypointense, and contrast enhancing. , these findings are considered nonspecific in dogs, cats, and humans, and lesions may not be detected with mri at the onset of clinical signs. , two ferrets had no clinical signs referable to lymphoma. in one ferret, the owner palpated a markedly enlarged abdominal lymph node. radiographic and sonographic findings consisted of multicentric lymphadenopathy, peritoneal effusion, a renal mass, a hyperechoic liver, and "incidental splenomegaly." in the other ferret, progressive lymphocytosis was detected during routine treatment and monitoring of adrenocortical disease. lymphoma was identified in the peritoneal effusion of that ferret. additional sonographic findings included a multicentric lymphadenopathy, splenomegaly with splenic nodules, a cystic hepatic mass, and a renal mass (sarcoma). adrenal disease was a common comorbidity seen with lymphoma, as found in other studies. this is likely because adrenal disease is common in older ferrets in general. , , other relatively common comorbidities found in this study were cardiovascular disease and cutaneous mast cell tumors, both of which also commonly occur in older ferrets. , one ferret had a history of granulomatous lymphadenitis suspected to be secondary to mycobacteriosis. although this study describes the imaging findings in a small number of ferrets with lymphoma, it provides an important source of information for practicing clinicians. the small number of ferrets able to be included during the time frame of the study likely reflects that imaging is not performed in every ferret with suspected or confirmed lymphoma, and that a definitive diagnosis was not always attained prior to treatment in individuals with suggestive clinical and imaging findings. ultrasound-guided aspirates of lymph nodes, spleens, and aggressive osseous lesions performed in ferrets of this study were each diagnostic for or strongly suggestive of lymphoma. although aspirates are often the initial tissue sampling procedure, previous reports have cautioned the use of lymph node aspirates in the diagnosis of lymphoma as inflammatory and reactive changes may be misinterpreted as lymphoma. , this is particularly true of the gastric lymph node in ferrets with gastrointestinal signs. a false positive diagnosis of lymphoma is considered not likely to have occurred in the ferrets included for in this study. lack of a definitive diagnosis (i.e., false negative results) from aspirate samples likely resulted in exclusion of some individuals from this study. analysis of the frequency of misdiagnosis and nonconfirmatory aspirate samples in patients with lymphoma was not performed. this study was also limited in that histopathology was not performed on all organs in each individual, and therefore, whether or not the changes seen were each attributable to lymphoma cannot be confirmed. additionally, because ultrasound findings were based on the reports and images obtained; some structures were unable to be reassessed. this is particularly the case in which multiple lymph nodes were affected. images of each lymph node may not have been attained, the imaging report may not have been complete in describing which nodes were affected, and measurement performed retrospectively on the available static images may not have reflected the actual maximal nodal thickness in that individual. in conclusion, findings from the current study indicated that imaging characteristics of lymphoma in ferrets are similar to those previously reported for dogs, cats, and humans. lymphoma may most commonly be multicentric in ferrets. imaging findings frequently included intra-abdominal lymphadenopathy, splenomegaly, and peritoneal effusion. lymphadenopathy and mass lesions were typically hypoechoic on ultrasound. osseous lesions, when present, were predominantly lytic. lack of imaging abnormalities did not preclude the diagnosis of lymphoma. ferrets, rabbits, and rodents. saint louis: w.b. saunders hematopoietic diseases ferret lymphoma: the old and the new neoplastic diseases in ferrets: cases ( - ) clinical and pathologic findings in ferrets with lymphoma: cases malignant lymphoma in ferrets: clinical and pathological findings in cases ferrets: examination and standards of care diagnosis and treatment of myelo-osteolytic plasmablastic lymphoma of the femur in a domestic ferret t cell lymphoma in the lumbar spine of a domestic ferret (mustela putorius furo) t-cell lymphoma in a ferret (mustela putorius furo) malignant b-cell lymphoma with mott cell differentiation in a ferret (mustela putorius furo) cytomorphological and immunohistochemical features of lymphoma in ferrets anatomia ultrassonográfica dos linfonodos abdominais de furões europeus hígidos ultrasonography and fine needle aspirate cytology of the mesenteric lymph node in normal domestic ferrets (mustela putorius furo) bsava manual of canine and feline abdominal imaging. gloucester: british small animal veterinary association the peritoneal space characterization of normal and abnormal canine superficial lymph nodes using gray-scale b-mode, color flow mapping, power, and spectral doppler ultrasonography: a multivariate study observations upon the size of the spleen splenomegaly in the ferret. gainesville: eastern states veterinary association ferret coronavirus-associated diseases aleutian disease in the ferret mycobacterial infection in the ferret gastrointestinal diseases diagnostic accuracy of gray-scale ultrasonography for the detection of hepatic and splenic lymphoma in dogs ultrasongraphic findings in hepatic and splenic lymphosarcoma in dogs and cats primary bone lymphoma: radiographic-mr imaging correlation mri features of cns lymphoma in dogs and cats primary cns lymphoma in the spinal cord: clinical manifestations may precede mri delectability bienzle d. laboratory findings, histopathology, and immunophenotype of lymphoma in domestic ferrets the senior ferret (mustela putorius furo) key: cord- -hglp vpm authors: peña-solórzano, carlos a.; albrecht, david w.; bassed, richard b.; burke, michael d.; dimmock, matthew r. title: findings from machine learning in clinical medical imaging applications – lessons for translation to the forensic setting date: - - journal: forensic sci int doi: . /j.forsciint. . sha: doc_id: cord_uid: hglp vpm machine learning (ml) techniques are increasingly being used in clinical medical imaging to automate distinct processing tasks. in post-mortem forensic radiology, the use of these algorithms presents significant challenges due to variability in organ position, structural changes from decomposition, inconsistent body placement in the scanner, and the presence of foreign bodies. existing ml approaches in clinical imaging can likely be transferred to the forensic setting with careful consideration to account for the increased variability and temporal factors that affect the data used to train these algorithms. additional steps are required to deal with these issues, by incorporating the possible variability into the training data through data augmentation, or by using atlases as a pre-processing step to account for death-related factors. a key application of ml would be then to highlight anatomical and gross pathological features of interest, or present information to help optimally determine the cause of death. in this review, we highlight results and limitations of applications in clinical medical imaging that use ml to determine key implications for their application in the forensic setting. forensic radiology is not clinical radiology applied to a deceased person. in the forensic setting, findings that a clinical radiologist may not typically have encountered are commonplace [ ] , e.g. post-mortem gas formation [ ] . post-mortem computed tomography (pmct) is widely used in forensic investigations, where acquisition protocols used during clinical ct are not applicable due to rigor mortis and aversion to repositioning the decedent to avoid tampering with evidence. however, ct scans can be acquired with higher doses and there is no patient motion, therefore improving image quality. additionally, recent developments such as pmct angiography (pmcta) with specialized pumps allows the diagnosis of vascular lesions whilst maintaining the integrity of anatomic structures, thus preserving evidence integrity [ , ] . in order to overcome the limitations of soft tissue contrast and a lack of vascular visualization provided by pmct [ ] , postmortem magnetic resonance imaging (pmmri) is increasing in impact, albeit in a small way thus far. whilst pmmri offers improved soft tissue contrast, for vascular diagnoses it presents similar performance to pmcta, with higher associated cost. however, applications to cardiac imaging are an exception, due to improved visualization of the coronary arteries and myocardium [ ] . image processing typically involves segmentation, feature extraction, and classification. image segmentation refers to the partitioning of a digital image into multiple segments that are sets of pixels (or voxels) which usually represent discrete structures. approaches to image segmentation prior to ml included probabilistic atlases [ , ] , statistical shape models (ssms) [ , ] , graph-cut (gc) algorithms [ , ] , and multi-atlas segmentation (mas) [ ] . feature extraction is a dimensionality reduction technique used to efficiently represent parts of an image as a compact feature vector. feature extraction was traditionally performed through determining properties such as first order textures (e.g. mean or entropy) or correlations [ , ] . image classification is the process of taking an image or volume and predicting whether it belongs to a list of predefined classes. traditional approaches to classification included linear-and normal-discriminant analysis [ , ] . a variety of ml alternatives to each of these image processing tasks have now been proposed and pipelines that can automate many diagnostic and prognostic tasks have been introduced to reduce the burden on radiologists [ , ] . ml techniques can be categorized as supervised learning, unsupervised learning, and reinforcement learning. in supervised environments, data is composed of input-output patterns, and the task is to find a deterministic function that can predict the output from an observed input. unsupervised techniques are a type of self-organized learning that extracts structures from the training samples directly, without pre-existing labels [ ] . more recently, self-supervised techniques, a type of unsupervised learning where the training data is automatically labelled by exploiting the relations between different input signals, are being studied for better utilizing unlabeled data [ ] . reinforcement learning on the other hand is based on trial-and-error, where the algorithm evaluates a current situation, takes an action, and receives feedback from the environment; this feedback can be positive or negative [ ] . the most common ml techniques used in medical applications are summarized below. rfs operate by creating a multitude of decision trees (fig. ) that can be trained for classification and regression tasks [ , ] , where the output is obtained by majority vote. majority vote is a technique utilized to combine the outputs from multiple classifiers, with the voting rule following one of three forms: (i) unanimous voting, where all the individual votes must agree in one output class, (ii) simple majority, where the class with one more than % of votes is selected, and (iii) plurality or majority voting, where the class with the highest number of votes is chosen [ ] . in k-nn, the training samples are divided into classes, and the prediction of a new sample or test point is classified by a majority vote of its neighbors (fig. ) . the algorithm uses a distance measurement function to search the (defined by the user) closest training samples in the feature space, and assigns the case of the class that is the most common in the subset. artificial neural networks (anns) anns are inspired by the biological nervous system. anns contain a large number of highly interconnected nodes (called neurons) separated into layers (fig. ) , enabling the network to process different pieces of information while considering constraints to coordinate internal processing, and to optimize its final output [ , ] . cnns were inspired by the connectivity pattern of the animal visual cortex. neurons respond to stimuli only in a restricted region (receptive field) of the previous layer, where receptive fields of different neurons partially overlap until they cover the entire visual field (fig. ). unlike other ml techniques, the network learns the filters that are usually "hand crafted". also, cnns exploit the strong spatially local correlation found on images, allowing the features to be detected regardless of their position. in recent years, deep neural networks (dnns), which differ from anns by their depth (the number of neuron layers), have proven to be successful in solving diverse problems, mainly for their capacity to learn features from large datasets [ ] . it should be noted that in the following discussion, algorithmic performance is assessed in terms of dice's coefficient (dc), the modified hausdorff distance (mhd) and the area under the receiver operating characteristic curve (auc or auroc), where possible. the quantification usually starts with calculation of true positives (tps), true negatives (tns), false positives (fps), and false negatives (fns). tp refers to cases correctly classified as pertaining to the class, opposite to fp, when the case is wrongly classified. inversely, tn and fn refer to a case correctly and incorrectly classified as not belonging to the class, respectively. the dc quantifies overlap between the processed image from the technique with a defined ground truth, ranging from zero (no overlap) to unity (identical segmentation). mhd is a measure of similarity between two objects based on their shape attributes. auc combines information of the true positive rate or sensitivity, and false positive rate or fall-out. sensitivity measures the proportion of actual positives that are correctly identified, while fall-out indicates the proportion of cases wrongly classified as positives. inversely, the specificity measures the proportion of negatives that are correctly identified. recall is the ratio of tps to the sum of tps and fns, indicating the proportion of actual positives that are correctly identified. precision is defined as the ratio of tps to the sum of tps and fps, indicating the proportion of identified positives that are correct [ ] . in terms of the currently reported use of ml in forensic post-mortem imaging, it is in its infancy. ml has only been trialed in a few specific forensic applications including automatic forensic dental identification [ ] ; sex determination [ , , ] ; the automation of bone age assessment [ , ] ; prediction of bone fractures [ ] ; and the automatic detection of hemorrhagic pericardial effusion [ ] . as far as we are aware, none of these studies has translated into daily forensic practice, despite the potential to streamline case-work. the legally robust identification of a decedent is the first objective when their body is triaged for a postmortem. dental analysis and comparison of ante-mortem and post-mortem information is one of the recognized tools for determining a decedent's identity. this traditionally requires an odontologist to find the best match to an ante-mortem database, using features such as dental restorations, pathologies, and tooth and bone morphologies. zhang et al. [ ] proposed a new descriptor that encodes the local shape of a person's dental features. they subsequently used an rf classifier to match the features of the unknown person to those in the database (n= ). the result yielded % accuracy for complete (n= ) and incomplete (n= ) feature datasets. incomplete datasets were derived from cases involving trauma. the method presented was shown to be rotationally and translationally invariant, and was orders of magnitude faster than conventional d methods. it is important to note that the database was constructed using a surface laser scanner on plaster samples in contrast to pmct scans. accurate determination of the sex of a decedent also aides in the identification process. several different approaches have been used for sex estimation. arigbabu et al. [ ] utilized head pmct scans. they combined and evaluated six local feature representations, two feature learning, and three classification algorithms. this technique of combining multiple features and classifiers is often used in ml pipelines as it has been shown to improve accuracy and reliability. the best prediction rate was %, which was within the reported sex prediction range for applications that use cranial features. the small number of cases obtained only from south east asia limited the generalizability of the results. anderson et al. [ ] utilized morphological gray matter differences on mris to differentiate between male and female incarcerated offenders, with implications to cognitive neuroscience research. preprocessing steps were described, including realignment and image registration, to obtain the volume and density of the gray matter on each case utilizing statistical parametric mapping software (spm ; http://www.fil.ion.ucl.ac.uk/spm). source-based morphometry (sbm) was utilized to extract features from the gray matter spatial information, with sbm being able to identify distinct regions with common covariation between subjects. a number of ml classification approaches were trialed, however, only an svm and logistic regression were described due to present the highest classification accuracy of %. limitations included the use of volumetric brain data only, without accounting for other moderating variables and quantitative methods, such as age, functional activity, and structural and functional connectivity. ortiz et al. [ ] compared five different ml techniques in the assessment of panoramic radiographs. the ann outperformed the rest of the models, including k-nns and logistic regression, with an accuracy of %. only panoramic radiographs were used, limiting the statistical significance of the results. as with the identification of a decedent's sex, their estimated age is also an important parameter for streamlining the identification process. Štern, payer and urschler [ ] compared two ml approaches, rfs and dcnns to determine age (through regression) and distinguish minors from adults (classification) using bone ossification from mri scans of the hand/wrist. as a general note, dcnns are often compared with rfs as the dcnn can determine the most important features itself whereas the rf must be supplied with those deemed important by the user. to better study the impact of different input information on the decision process, three strategies were tested: the use of the whole hand, a cropped image with age relevant bones, or the hand-crafted filter-based enhanced epiphyseal gap. the best mean absolute error and standard deviation results with respect to the biological age (as estimated by radiologists) were . ± . and . ± . years for the dcnn using cropped structures and the rfs using enhanced images, respectively. the results were reported to achieve the new state-of-the-art accuracy compared with previous mri-based methods and their earlier work. furthermore, when the technique was adapted for d mri, the method was in line with state-of-the-art methods using x-ray data. limitations of this work included the requirement for age-relevant anatomical information, which implies a labor-intensive pre-processing step, and decreased accuracy for cases with biological ages greater than years. in an alternative approach, li et al. [ ] utilized pelvic x-ray images and a dcnn to create a bone age assessment pipeline which yielded a mean error of . years, . years better than the existing reference standard. this work used transfer learning from a cnn pre-trained on the imagenet database [ ] , achieving an appropriate accuracy for this type of input data. transfer learning is widely used in ml applications and is particularly useful when small or unbalanced datasets are available. limitations acknowledged by the authors included the lack of diversity in ethnicity of patients, and the exclusion of images with artefacts and diseases. many forensic institutions utilize pmct to guide the pathologist in their approach to the autopsy. pmct is particularly useful for identifying fractures due to the high attenuation of bone. heimer et al. [ ] used an undisclosed dcnn from a dedicated software (vidi, cognex, natick, ma, usa) to predict the presence of skull fractures using head pmct scans ( scans for each case: with and without fractures). the skulls were preprocessed through the generation of curved maximum intensity projections, so that the skull's surface could be unfolded onto a single image. deep learning was applied and the best-performing selected network yielded an auroc of . , a sensitivity of . % and a specificity of . %. an auroc of . defines a model that classifies at random, while . is a completely accurate model. pmct is also useful for assessing many aspects of cardiac condition prior to autopsy, e.g. the appearance of discontinuities of the aortic wall can be a direct sign of injury in the aorta, whereas the appearance of a blood collection within the chest cavity (hemothorax or hemopericardium) can be an indirect sign [ , ] . these signs, observed on plain film x-ray or pmct must be interpreted by radiologists and forensic pathologists. ebert et al. [ ] used two separated and undisclosed dcnns from a dedicated software (vidi) for the classification of images with or without hemopericardium and also the corresponding segmentation of the blood content in pmct. the average dc, recall, and precision for the classification task were %, %, and % respectively. for segmentation, the values obtained were %, %, and %, respectively. limitations of this study include the small number of training cases (n= cases with hemopericardium), while the use of a dedicated software restricted the training data to individual slices, losing sometimes crucial volumetric information. due to the dearth of information relating to the application of ml to forensic imaging, it is important to review the state-of-the-art and establish lessons learned from the significant body of literature describing its application to clinical image analysis. current clinical applications ml techniques have been used in the diagnosis and prognosis of diseases, as well as for segmentation, classification, and measurement of anatomical structures [ , ] . in this review, the ml applications have been grouped according to the tissue or organ studied, where brain, lungs, and skeleton were chosen to highlight results and limitations. each anatomical section concludes with a summary evaluating the key implications determined from the clinical literature and their application in the forensic setting. traditional atlas-based segmentations require registration to align the atlas images to the unseen image. whereas, ml approaches can learn the variability between patients, making them especially useful in forensics, where variance is greater than for clinical imaging. ml can also be used in combination with atlas-based approaches or in its own right. as an example of the former, srhoj-egekher et al. [ ] used atlas-based segmentation for pre-processing t -weighted mri neonatal brain images to obtain initial probabilities, subsequently refined using a k-nn approach. whilst this approach achieved dcs and mhds ranging from % to %, and . to . respectively, the assignment of a tissue classification to each voxel independently, post atlas registration, meant some voxels were attributed to more than one class, while background voxels were unclassified. conversely, zhang et al. [ ] opted for purely ml approaches that analyzed image patches for segmentation into white matter (wm), gray matter (gm), and cerebrospinal fluid (csf) of infant brains (n= ). four network architectures were tested and, in most cases, the cnn method significantly outperformed svms and rfs with overall dc scores and mhds of % and . , respectively. the cnn method also outperformed two other common image segmentation methods: coupled level sets (cls) and majority voting (mv). three further publications were found where the authors segmented similar structures within adult brains. van opbroek et al. [ ] applied an svm for pixel-wise classification to registered volumes from a variety of mri sequences for patients with diabetes and controls. the resulting segmentation of eight different tissue types demonstrated limited success ( table ) . the svm showed poor performance in low contrast areas, while atlas misregistration caused voxels to be improperly classified. moeskops et al. [ ] used cnns to process t -weighted scans to segment the same eight tissue types. with cnns, the use of different sized patches during training allowed for a smooth segmentation and analysis of local texture. in general, cnns delivered better segmentation (table ) , although this was a different patient cohort. a more recent application of d dcnns [ ] was used to identify brain structures in t -weighted mri scans (n= ). again, image patches were utilized as input to the network. however, spectral and cartesian coordinate information relating to the patches was added after the convolutional layers (e.g. see arrow in fig. ) in order to introduce spatial information, which substantially increased the segmentation accuracy. ml can also be used for the assisted diagnosis of neurodegenerative diseases. salvatore et al. [ ] used a combination of principal component analysis (pca) with an svm to classify morphological mri sequences as patients with parkinson's disease (n= ), progressive supranuclear palsy (psp) (n= ), or controls (n= ). the large cohort sizes, inter-class cohort balance, and separation between psp patients and other parkinsonian variants were identified as particular strengths, compared to other papers. the performance (accuracy, specificity and sensitivity were all > %) of the model was shown to be limited by the number of principal components ( to ) utilized for classification. this dependence is an important consideration when using dimensionality reduction techniques and was also demonstrated for approaches that classified alzheimer's disease [ ] . finally, ml techniques have also been used to segment and classify brain tumors. zacharaki et al. [ ] used conventional and perfusion mri from patients with a diagnosis of intra-cranial neoplasm to classify them by type and grade of tumor (n= ). their approach consisted of region of interest (roi) definition, feature extraction, feature selection, and classification by svms. for comparison, linear discrimination analysis (lda) and k-nn were also implemented. the mean classification accuracy was % for the svm approach, compared with % for lda and % for k-nn. some of the limitations were related to the lack of features selected that described deformation of healthy structures due to the tumor, and the utilization of rois which yielded inter-observer variability. once the presence of tumors is verified, one possible subsequent step would be segmentation of the pathology, which is challenging even for experienced neuroradiologists [ ] . to address this segmentation problem, a variant of cnns named u-net is often employed [ ] . beers et al. [ ] utilized two d u-nets connected sequentially to perform whole tumor, enhancing tumor, and tumor core segmentation, achieving mean dcs for the test set (n= ) of %, %, and %, respectively. when the methodology was implemented on patients from ongoing clinical trials, the mean dcs decreased to %, %, and %, respectively. the lower performances on the clinical trial patients were attributed to scans being post-operative, highlighting the importance of case selection for training. studies on brain tissues used mostly mri data due to the multi-modality information and a good softtissue contrast. whilst the specific pathologies discussed are not all relevant to the forensic setting, the general conclusions deduced from the segmentation and localization of anatomical abnormalities are. models that utilized dimensionality reduction techniques prior to classification were shown to yield performances dependent on the number of selected components. in addition, the identification of abnormalities in biological tissues required features capable of describing complicated deformations of the healthy structures. for cnns, the performance of the pipeline depended significantly on the training set adequately representing expected cases. in general, cnns outperformed algorithms such as svms, rfs, clss, and mv in segmentation and classification tasks. note that some studies used small datasets, which limited statistical power. in addition, as will be demonstrated throughout this review, a combination of the variability in reporting of metrics, the lack of reporting of a diagnostic odds ratio [ ] , the unavailability of datasets and reference implementations, and the effect of imbalanced data in the classification accuracy, common in medical datasets [ , ] , made it difficult to compare papers quantitatively. in forensics, pmct does not provide good resolution of internal cranial structures or brain metastases, and in general, the resolution is not sufficient to identify neurodegenerative issues, but degeneration can sometimes be observed in defined structures, e.g. in the caudate nucleus in huntington's disease. on the other hand, pmct is adequate in showing evolving brain infarcts and in displaying collections of blood, e.g. subdural hemorrhages (which are reasonably common). pmct can also show intraparenchymal hemorrhages and parenchymal hemorrhagic contusions. intra-parenchymal hemorrhages, e.g. hypertensive hemorrhage, classically involve distinct areas in the brain: basal ganglia, thalamus, pons, and cerebellar hemispheres. parenchymal hemorrhagic contusions are classically seen with contra-coup basal frontal lobe contusions (bleed within brain tissue occurring on the opposite side of the head to the primary injury site) when someone falls onto the back of their head (often associated with a skull fractureoccipital). in ml, feature learning refers to the automatic discovery of meaningful representations from raw data, in contrast to manual feature engineering, where the features have to be chosen by a domain expert. feature learning allows for end-to-end learning, where a complex system can be represented by a single model, bypassing the intermediate layers present in traditional workflow designs. learning a representation of any tissue is a useful process if subsequent classification is required, or if the goal is to find differences between samples in the training data. the representation quality is highly dependent on the learned features. a restricted boltzmann machine (rbm) is a generative neural network that can be used to perform automatic feature learning. li et al. [ ] used a gaussian rbm with a training dataset consisting of different sized patches obtained from high-resolution lung ct images (n= ), with the purpose of classifying five tissue types using svms. the best accuracy obtained was %, with a high rate of fps caused by the similarity between tissues. van tulder and de bruijne [ ] utilized convolutional rbms, adding learning objectives that helped the algorithm to extract features for description and training data classification. the training data consisted of ct scans (n= ) with five types of tissues classified. resulting accuracies were < % and - % for the classification of lung patches and airway centerlines, respectively. the low accuracies were attributed to small training sets and number of extracted filters due to computational restrictions. netto et al. [ ] utilized examinations (n= ) with identified nodules and an svm to classify the structure as nodule or non-nodule. the resulting accuracy was %, with a sensitivity of %. the largest errors were reported when the feature was very large or very small, where it could be mistaken for other structures or for being the continuation of one. hua et al. [ ] used images containing nodules from the lung image database consortium (lidc) ct dataset to train both a cnn and a deep belief network (dbn) constructed by stacking rbms. the performance of the two networks was then compared with two feature-based methods ( table ). the major limitation reported was resizing of the input images, which discarded size cues that were important indicators of malignancy. kumar et al. [ ] also classified the lung nodules in the lidc images (table ) using an autoencoder (ae) and a binary decision tree classifier (bdt). an ae is an unsupervised deep learning technique utilized for feature extraction, while a binary decision tree is a specialized implementation for classification where every node has only two branches. the false positive rate of % was attributed to the visual similarity between benign and malignant cases, which can be compared to a % rate obtained on the national lung screening trial (nlst) using low-dose ct (ldct) [ ] . a more recent study compared massive-training artificial neural networks (mtanns) against cnns [ ] using a database of ldct scans (n= ), consisting of slices. mtanns are an extension of anns, where a large number of overlapping sub-regions are created for each voxel of the original image and used as inputs to the network. the reported auroc was . for the mtann, and . for the best of the four cnn architectures. the mtann required a smaller number of training samples than the cnns for a better classification performance. this was attributed to the hierarchies of the learned features, where the mtann learned to detect lesions utilizing low-level features, while the cnns extracted low-, mid-and high-level features, increasing their reliance on irrelevant characteristics. a recent focus of attention was related to the use of ml for early diagnosis, assessment of severity, and differentiation between the novel coronavirus (covid- ) and community acquired pneumonia (cap) from ct scans. barstugan et al. [ ] utilized n= ct abdominal images from infected patients, five feature extraction methods, and an svm for the final classification, achieving a maximum accuracy of . %. the main limitation of their work was the manual selection of the patches obtained from the original images and used for the training, which restricts the usability and reproducibility of this approach. tang et al. [ ] assessed the severity (severe, non-severe) of the disease from chest ct images from patients, utilizing quantitative measures, e.g. the ratio between the volume of the whole lung and the volume of ground-glass opaque regions, with several rf models. the best performing rf yielded results of %, %, %, and % for the sensitivity, specificity, accuracy, and auc, respectively. to differentiate between covid- , cap, or non-pneumonia, li et al. [ ] collected chest ct exams from patients. a dcnn was utilized, with an architecture denoted covnet, able to classify the volumetric data with a sensitivity, specificity, and auc of %, %, and % for covid- cases, %, %, and % for cap cases, and %, %, and % for non-pneumonia cases, respectively. a limitation of this work included the lack of laboratory confirmation for each case, where covid- could have similar imaging characteristics as other viral pneumonias. studies on lungs generally used ct scans for the segmentation of tissues and tumors, and classification of nodules for early cancer diagnosis. due to the low contrast between different tissues in the lungs, the approaches reported were reliant on shape, texture, and feature size. the segmentation performance was poor for nodules at the size extremes. major findings included lower performances due to image resizing, and the importance of reporting fp rates, which can yield high values in applications that intend to determine nodule malignancy. potential applications to the forensic setting include detection of emphysema, consolidation of lung parenchyma (pneumonia), and if appropriate windows are used, interstitial changes. of crucial forensic interest is the presence of blood and fluid in the chest. furthermore, establishing the presence of a lung lesion (and especially more than one) independently of the cause of death may indicate the presence of occult malignancy. in such cases, the deceased's next of kin can be alerted, and the family contact nurses can organize appropriate follow up for family members if a cancer is found. it is important to note that the appearance of the lungs in pmcts can be affected by aspiration of gastric content that may occur in the process of dying, e.g. from a 'heart attack'. skeleton skeletal segmentation usually occurs before measurement and/or diagnosis of bone or articular diseases. koch et al. [ ] segmented mris (n= ) of the wrist using marginal space learning (msl) and rfs, where msl incrementally learned classifiers in marginal spaces of lower dimensions [ ] . the segmented images were used to compute the d model of every carpal bone, with aucs of . for both scan modalities. the approach was an order of magnitude faster than previous work using a semiautomatic method. similar literature did not report segmentation errors and could not be used for comparison. bone age assessment from plain x-rays is used in pediatrics by comparing the results to chronological age for the evaluation of endocrine and metabolic disorders. a fully automated pipeline was presented by lee et al. [ ] using a pre-trained cnn (transfer learning). both male and female test x-rays were assigned a bone age within year of the correct value over % of the time, and over % within years. x-rays have also been widely used for fracture detection, e.g. of the tibia [ ] , where texture and shape features were fed into three different ml algorithms: an ann, k-nn, and svm, and the outputs fused using a majority vote scheme. the combination of the classifiers using both types of features presented a significant improvement over using just one classifier, or only one feature type. reported accuracies, precisions, and sensitivities were above %. instead of fusing the results from the classifiers, multistage classifiers have also been used. wels et al. [ ] reported a fully automatic system using several rf stages, capable of detecting osteolytic spinal bone lesions from ct volumes, with an average sensitivity of %. the performance was affected by differences in contrast and noise characteristics in the data used for training and testing, however, values for accuracy were not presented for further interrogation. sharma et al. [ ] measured trabecular bone microarchitecture and used the information to discriminate between healthy cases (n= ) and patients with type gaucher disease (n= ). svms were used to classify different genotypes of the disease, achieving an average % classification accuracy, % sensitivity, and % precision. the structure of the trabecular bone obtained from mri have also been used classify knees with osteoarthritis [ ] . the characteristics found to relate to the disease were useful in classifying healthy from affected patients (n= ) with an auc of . , as well as predicting the risk of cartilage loss. in a similar study, the fractal analysis of x-ray images with svms enabled the automatic classification of osteoporotic patients (n= ) versus controls (n= ) with accuracies of up to % [ ] . reported limitations from the papers in this section include the small number of cases and the high percentages of patients at early stages of the disease. orthopedic ml applications include disease diagnosis, age assessment, and risk prediction e.g. osteoporosis, osteoarthritis. plain film x-ray and ct were most common; however, mri studies of joints are being increasingly reported. the performance of ml applications was shown to be affected by the number and selected features, which is significantly influenced by differences in contrast and noise characteristics in the datasets. comparison or ranking of the results was limited by reported performance metrics and the use of databases that were not representative of the disease stages studied. other limitations included small patient cohorts and the processing times. the most common skeletal disorders that could be picked up on pmct scans are osteoporosis and paget's disease, while fracture diagnosis, and then pattern of fracture diagnosis, e.g. a "hangman's fracture", extension/tear-drop fractures of the cervical spine, and spiral fracture of a long bone in an infant are of significant forensic interest. j o u r n a l p r e -p r o o f discussion typical goals of ml techniques in medical imaging include the differentiation of healthy from diseased patients or tissues and the localization of pathologies in anatomic structures. algorithmic performance can be significantly affected when trying to process a new sample that differs significantly from the training dataset. this characteristic is especially important when it comes to applications in forensic medicine, where there is a high variability in the structures and image acquisition protocols, and unclear definition of what normal implies, due to changes occurring because of circumstances of death, tissue decomposition, trauma, or incineration. however, some applications e.g. organ localization, can be immediately translated to the forensic setting by using the appropriate training data, or by using the clinical medical images for the initial training of cnns and then fine-tuning using forensic information. this is usually referred to as transfer learning. on the other hand, due to the size and availability of forensic databases, the opposite is also possible, with applications being trained in forensic data and then fine-tuned to the clinical setting. to improve the capabilities of ml techniques, the training data can be modified, or more informative features can be used as inputs to the algorithms. the selection of features can be optimized using learning objectives [ ] or by utilizing an unsupervised technique as a preprocessing step to the classification task [ , ] . the features selected can also be used to alleviate human labelling, by selecting more representative training data for the medical expert [ , ] . another approach to the improvement of ml performance is the combination of several techniques using a majority vote scheme [ ] , or the use of multi-stage classifiers [ ] for segmentation of different spatially related tissues. a wide range of implemented algorithms were found during the review process, where svms outperformed techniques such as lda and k-nn [ ] , however the trend in recent works has been the high performance of cnns [ , ] . the main disadvantage of classic ml approaches compared to cnns is the performance variability due to the quality of the features [ ] that must be hand-crafted by an expert according to the goal and dataset. the selected feature pool is commonly processed to lower its dimensionality before training the classifier by using techniques such as pca. it is important to note that the number of principal components or features selected at the end of this step plays a key role in the classification performance [ ] . the performance of the algorithms can also be significantly affected if the labelling process (diagnosis) is prone to error [ ] . furthermore, for medical and forensic applications, the common practice of resizing input images can yield to a loss of information that could be essential for diagnostic purposes [ ] . an additional consideration is that some authors use for example a radiologist to classify cases, then benchmark the performance of the algorithm against radiologists. rajpurkar et al. [ ] , for instance, presented a cnn that achieved radiologist-level pneumonia detection on a database [ ] for which no gold-standard label existed, and listed as limitation the lack of information in the database that affects the radiologists' accuracy. it is also important to note that the lack of reporting of a diagnostic odds ratio [ ] and the variability in reporting of metrics makes it difficult to compare papers. for the task of segmentation, both multi-atlas algorithms and dcnns with multiple patch sizes showed comparable results [ , ] , demonstrating cnns were most successful. patch-based techniques could be a good approach in forensic cases were organs or structures are not localized in the usual anatomic positions [ ] . furthermore, the use of different sized patches in segmentation tasks allows for both a smoother separation and the detailed analysis of local texture [ ] . three important results for the use of ml in clinically-related applications were found that can also be applied in the forensic setting: firstly, temporal efficiency through the use of transfer learning; secondly, improved accuracy through the combination of ml classifiers using majority voting techniques or multi-stage approaches; and finally, the addition of an active learning phase, where the human labor can be alleviated during labeling. one of the main issues that affects both the clinical and forensic settings is the lack of interpretability of predictions by black-box approaches such as neural networks. this is active area of current research and a current approach to addressing this concern is the use of visual explanations for the class label under consideration, obtained from the convolutional layer feature maps [ , ] , and attention mechanisms [ ] , able to determine the parts of the input images more relevant for a particular classification. furthermore, depending on the application, it is not required and could be counterproductive to completely automate a task, for which a human-in-the-loop can be beneficial by reducing the complexity through human input and assistance [ ] . some applications of ml already found in clinical medicine, that could be repurposed for forensic medicine, include segmentation and classification of organs and structures, including arteries, tiny blood vessels, the liver, spleen, stomach, gallbladder, and pancreas [ , ] ; computation of organ d models [ ] for virtual autopsies; detection of lesions and calcification on vascular cross-sections [ ]; identification of bone and joint atrophies or disorders [ , , , ] ; fluid volume and composition on body cavities (blood, pus, ascites) [ ] ; and organ volume estimation, e.g. heart size with respect to body size [ ] . tasks in forensic radiology that to our knowledge have not been tackled using ml include: segmentation and classification of foreign bodies, differentiation between ante-mortem and postmortem gases, calculation of body mass index, and determination of skeletal completeness after accidents. for the segmentation and classification of foreign bodies, e.g. bullets, metallic dental fillings, the main challenge becomes finding the object that does not belong inside the body. furthermore, metallic components can create artefacts such as beam-hardening on ct scans or field distortions in mri [ ] , which can also be addressed using deep learning [ ] . differentiation between ante-mortem and post-mortem gases can be difficult using the voxel values of ct scans or mri, so emphasis should be placed on understanding the expected location and evolution of these gases at different points in time [ ] ; also, differentiation between acute and remote infarction on the brain, which on a ct scan can be characterized by voxel values and tissue volume changes, can be tackled utilizing existing tissue classification techniques [ , , ] , with the addition of new classes to differentiate the types of infarction. in forensic anthropology, tasks that could be addressed using ml include: determination of skeletal completeness after accidents [ ] , e.g. plane crashes; d reconstruction of incomplete bones, that could be extrapolated from the work by hermoza and sipiran [ ] on incomplete archaeological objects; and d reconstruction of fractured skulls [ , , ] , used to infer a cause of death, or to perform facial reconstruction. in addition to the aforementioned applications traditionally related to medical imaging, there is the potential for the use of ct scans for facial identification [ , ] . as a final note, the release this year of the new mexico decedent image database (nmdid, https://nmdid.unm.edu/) [ ] should be acknowledged as a significant step forward for the development of tools that can be used to enhance the post-mortem workflow. j o u r n a l p r e -p r o o f conclusions ml techniques have been applied to a large number of tasks that can be used in clinical medicine, where the algorithms most widely utilized in applications with medical images include rfs, svms, and cnns. cnns have shown better performance in the literature. techniques to improve the ml performance in radiology include data augmentation, improved feature selection and algorithmic combination, e.g. majority voting. performance was shown to be affected by resizing of the input images and the accuracy of the labels provided with the training data. in addition, benchmarking was found to be difficult due to the lack of gold-standard labels, as well as the variability in reporting of metrics, and lack of reporting of a diagnostic odds ratio. ml applications investigated for clinical medicine could be repurposed to the forensic domain with careful consideration to account for the increased variability and temporal factors, e.g. decomposition, that affect the data used to train the ml techniques. due to the complexity of the autopsy process, a key application of ml to forensic radiology would be to streamline decedent identification and highlight and annotate areas of forensic interest. ml pipelines could be used to present information to optimally determine the cause of death, including differentiation between body cavity fluid accumulations (blood, pus, ascites) and their corresponding volumes, calculation of organ volumes and weights, percentage of coronary artery calcification, identification of subtle fractures especially in critical areas such as the cervical spine, and determination of skeletal completeness and skeletal commingling after mass fatality incidents. the artefacts of death: ct post-mortem findings imaging and virtual autopsy: looking back and forward postmortem ct angiography: capabilities and limitations in traumatic and natural causes of death post-mortem computed tomography angiography: past, present and future future prospects of forensic imaging niftynet: a deep-learning platform for medical imaging advanced machine learning in action: identification of intracranial hemorrhage on computed tomography scans of 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gaucher disease diagnosis of osteoarthritis and prognosis of tibial cartilage loss by quantification of tibia trabecular bone from mri osteoporosis diagnosis using fractal analysis and support vector machine deep features learning for medical image analysis with convolutional autoencoder neural network active learning based intervertebral disk classification combining shape and texture similarities interactive machine learning for health informatics: when do we need the human-inthe-loop? radiologist-level pneumonia detection on chest x-rays with deep learning chestx-ray : hospital-scale chest x-ray database and benchmarks on weakly-supervised classification and localization of common thorax diseases grad-cam: generalized gradient-based visual explanations for deep convolutional networks visual interpretability for deep learning: a survey an investigation of interpretable deep learning for adverse drug event prediction hierarchical d fully convolutional networks for multi-organ segmentation automatic detection of abnormal vascular cross-sections based on density level detection and support vector machines training and validating a deep convolutional neural network for computer-aided detection and classification of abnormalities on frontal chest radiographs multi-scale deep networks and regression forests for direct bi-ventricular volume estimation d surface and body documentation in forensic medicine: -d/cad photogrammetry merged with d radiological scanning deep learning methods to guide ct image reconstruction and reduce metal artifacts post-mortem ct and mri: appropriate post-mortem imaging appearances and changes related to cardiopulmonary resuscitation the human skeleton in forensic medicine d reconstruction of incomplete archaeological objects using a generative adversarial network reverse engineering-rapid prototyping of the skull in forensic trauma analysis fragmented skull modeling using heat kernels virtual reconstruction of paranasal sinuses from ct data: a feasibility study for forensic application case study: d application of the anatomical method of forensic facial reconstruction development of three-dimensional facial approximation system using head ct scans of japanese living individuals standardizing data from the dead this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. j o u r n a l p r e -p r o o f key: cord- -kibjwfad authors: ong, s. j.; renfrew, i.; gopinathan, a.; tan, a. p.; sia, s. y.; low, c. k.; hoon, h. x.; ang, b.w.l.; quek, s. t. title: sir helmet (safety in radiology healthcare localised metrological enviroment): a low-cost negative-pressure isolation barrier for shielding mri frontline workers from covid- exposure date: - - journal: clin radiol doi: . /j.crad. . . sha: doc_id: cord_uid: kibjwfad • low cost reusable acrylic and silicone rubber barrier shield design. • localised negative pressure environment simulating isolation rooms. • does not affect mri image quality even on the most sensitive sequences. • additional personal protective equipment for frontline healthcare professionals. covid- is a highly infective infectious disease caused by a novel coronavirus first identified in wuhan, china, in december . it has now evolved into a pandemic affecting at least countries. the precise incidence of stroke in covid- patients is unknown but is thought to affect up to . % of severely affected individuals [ ] . it is also being recognised as the first clinical presentation of covid- , especially in young patients [ , ] . although computed tomography (ct) is the first-line technique to assess patients presenting with acute stroke symptoms, many centres prefer to evaluate further with magnetic resonance imaging (mri) [ ] . hence, more patients with covid- are attending for mri examinations. in well-resourced hospitals, infective covid- patients are nursed within negativepressure rooms. even within these negative-pressure rooms, research has shown extensive environmental contamination when occupied by infected patients [ ] . although patients can be provided with filtering face piece (ffp) masks to reduce their infectivity, studies have demonstrated high rates (up to %) of poor fit of the face masks among untrained non-healthcare professionals [ ]. most mri rooms are not built with negative-pressure ventilation systems. in addition, there are limitations to the use of personal protective equipment (ppe) by both patients and staff within the magnetic field of the mri room. therefore, each time a patient with covid- undergoes mri, there is a real risk of mri room contamination and exposure of both staff and subsequent patients to the virus. to address the above problem, a low-cost physical barrier was designed and developed for use within the mri machine that could produce a localised negativepressure containment area around the patient's head. the barrier has been named "sir helmet" from safety in radiology healthcare localised metrological enviroment. the "helmet" can potentially reduce the spread of pathogens via the patient's breath. in addition to assessing its functionality, the present study also evaluates the impact of the shield on mri image quality. the sir helmet is a dome shaped, re-useable barrier that fits into mri machines with a bore size of ≥ mm. it is made of mm clear acrylic with chloroform used as the primary adhesive. the access port on the front of the "helmet" is covered with a . mm silicone rubber membrane with slits for access and clamped to the main structure with another layer of mm acrylic, held together by plastic screws (fig. ) . the calculated raw volume of the helmet is l with an effective net gas volume of approximately l or less depending on patient position within the barrier shield. negative pressure within the "helmet" is generated by connecting a standard medical gas wall vacuum using extension tubing via a port in the barrier shield. continuous for this study, two healthy volunteers were scanned in a t magnetom skyra mri unit (siemens, munich, germany) and a . t optima mri unit (ge healthcare, chicago, il, usa) using standard head and neck sequences (eight sets of examinations in total; four of the head and four of the cervical spine). each participant was scanned using each machine by the same senior mri radiographer with and without the "helmet". images were loaded onto a standalone staging picture archiving and retrieval system, centricity universal viewer (ge healthcare). the eight anonymised sets of images were reviewed on diagnostic-quality monitors by two consultant musculoskeletal radiologists, two consultant neuroradiologists, and two consultant clinical diagnostic radiologists, blinded to the acquisition history of the images. overall, eight examination sets were read independently by six different readers to provide total sets for scoring. images were scored on a scale of to regarding diagnostic quality, structural delineation, and severity of artefacts for each set of images as per ryu et al. [ ] with area for free-text comment. negative pressure airflow rates of > l/min was obtained with the underwater seal filter system and at l/min without. this allowed at least . full gas exchanges per hour for the underwater seal filtered system and at least . for the other one. there was consensus regarding scoring of all eight sets of images among all the readers with full points for diagnostic quality, delineation of structural margins, and complete lack of mri-related artefacts (fig. ) . post-scoring, the readers were informed that half of the image sets were performed with the "helmet", but they were not able to identify these sets from those scanned without the helmet. although transmission of covid- is predominantly via direct contact or aerosol inhalation, it may also occur via indirect delayed contact, for example, through the use of the same physical seat [ ] . droplet transmission enhanced by air-conditioning airflow creating super spreaders is also documented [ ] . hence, isolation of the most infective patients is essential [ ] . nevertheless, when an infected patient is brought outside their isolation ward to other clinical areas, such as radiology departments, this "isolation" is interrupted, creating potential opportunities for virus dissemination. as the covid- pandemic continues, there is high likelihood that more coronavirus-infected patients would present with stroke or stroke-like symptoms, thereby increasing the need to perform mri examinations in these patients. as a limited resource, it may not possible to reserve an mri machine exclusively to image covid- patients. hence, it is essential to explore alternative ways to control the spread of infection from transit of an infected patient through an mri room. the effort of thoroughly cleaning the shield between patients is much less than that of cleaning the bore of the mri machine. using the ubiquitous medical gas wall vacuum apparatus, the "helmet" can provide at least . full gas exchange per hour with the afore-described filtration system or . full gas exchanges per hour without filtration. this gas exchange rate is similar to or above that of the requirements of a negative-pressure isolation facility, which is usually to exchanges per hour. hence, use of this helmet would effectively provide frontline healthcare staff and patients with an added layer of protection against airborne pathogens. this can also avoid the cost and time required in installing negative-pressure ventilation systems within an mri room. use of the helmet without suction is not recommended due to concerns regarding carbon dioxide retention during long examinations. in an unvented system, there are also concerns of a high concentration of aerosolised pathogen that the mri technician would be exposed to, while removing the "helmet" from the patient. the decision to vent the suction via an underwater seal sterilisation scrub or directly to the wall vacuum port would depend on the local hospital infection-control policy and the underlying infrastructure of the vacuum system. to improve patient comfort and to reduce claustrophobia, the helmet was intentionally fabricated using flame-polished translucent acrylic, using the biggest arc possible to maximise the sense of space. given the multitude of different scanner and coil configurations, the length of the "helmet" was increased intentionally to fit across all the mri machines within our institution. if required, it is possible to customise this shield for individual scanners with shorter lengths to increase the air exchange rates. acrylic is cheap and can be fabricated quickly, and in addition, is suitable for cleaning with most of the usual disinfectants. the image quality of mri examinations was not affected by scanning with the helmet on. the adoption of this or similar barriers would provide frontline healthcare staff and patients with an additional level of protection without prohibitive financial costs to the institution. highlights: • low cost reusable acrylic and silicone rubber barrier shield design • localised negative pressure environment simulating isolation rooms • does not affect mri image quality even on the most sensitive sequences • additional personal protective equipment for frontline healthcare professionals covid- -related stroke large-vessel stroke as a presenting feature of covid- in the young covid- presenting as stroke imaging of acute stroke prior to treatment: current clinical feasibility of -min ultrafast brain mri compared with routine brain mri using synthetic mri: a single center pilot study investigation of three clusters of covid- in singapore: implications for surveillance and response measures covid- outbreak associated with air conditioning in restaurant rapid expansion of temporary, reliable airborne-infection isolation rooms with negative air machines for critical covid- patients key: cord- - x cb authors: claudi, carolin; ganser, joachim; andreisek, gustav; vrugt, bart title: a juxta-articular myxoma of the thumb a case report date: - - journal: j hand surg glob online doi: . /j.jhsg. . . sha: doc_id: cord_uid: x cb abstract juxta-articular myxomata are benign tumors which are mostly encountered in the vicinity of larger joints. few cases in the hand have been reported. we present a case of a juxta-articular myxoma at the metacarpophalangeal joint of the thumb in a year-old man. the preoperative diagnostic work-up included d mr-angiography and ultrasound. the histochemical examination of the resected tumor established the diagnosis definitively. a follow-up mri, scheduled without any clinical suspicion of tumor-recurrence, months postoperatively, did not reveal any obvious recurrence. at months, the patient has full motion without pain and declined any further imaging. juxta-articular myxomata (jam) are benign soft tissue neoplasms of mesenchymal origin. these cystic tumors resemble a ganglion, and tend to recur after resection thumb. initially, this tumor was hardly noticeable, but it grew slowly over the past year. as it was situated in the commissure between thumb and index finger, the pressure when grasping larger objects provoked mild pain. the clinical examination revealed a solid, circumscribed round mass of mm which was adherent to the ulnar-palmar aspect of the metacarpal joint of the thumb. it was scarcely visible as the texture and color of the skin were normal. the tumor did not adhere to the skin or tendons (figure ). the stability and mobility of the thumb joints were not compromised. the clinical impression of close contact to the joint was verified by ultrasound. it was by mri (figure - ) and d mr-angiography that the final diagnosis of a jam was suspected. as a well circumscribed, septated, scarcely vascularized (supported by duplex sonography) mass without any pathological tumor-feeding vessels, it could be distinguished from a myosarcoma. we forewent plain films as they seemed sufficiently replaced by mri and would only be useful to rule out any arthritic changes and bone infiltration. without suspicion of malignancy, we elected to proceed with marginal resection rather than a biopsy to avoid a second operative procedure in a delicate region. at surgery, the tumor could be completely resected without destruction of the joint ligaments, tendons, vessels or nerves (figures , ). the histological examination revealed non-malignant spindle cells, embedded in a myxoid matrix (figure ). the diagnosis was confirmed immuno-histochemically with the affirmation of cd and the exclusion of s and actin. the postoperative healing process was uneventful. the thumb regained full motion and became completely pain free. the regular follow-ups including ultrasound and mri examination were initially scheduled on a yearly basis. a first control-mri, conducted without any clinical suspicion of tumor- recurrence postoperatively months postoperatively, did not reveal any obvious recurrence. at months postoperatively, the patient is still pain and symptom free. compared with the contralateral side, he has full range of motion, equal power and normal sensibility in the thumb. the patient elected to defer additional imaging during the covid- pandemic. compliance with ethical standards conflict of interest: the authors declare that they have no conflict of interest. although classified as benign lesions, myxomata can be locally destructive and thus cause symptoms like pain or nerve palsy , . in the setting of local tissue destruction, one must consider malignancy in the differential diagnosis . macroscopically myxomata present as cystic formations of soft or friable consistency, white to yellow color, ranging from to cm in size . microscopically these tumors can appear like fetal wharton's jelly . few spindle-shaped fibroblast-type or stellate and fusiform cells are found within reticulin fibers and a myxoid matrix. the mucin consists of hyaluronic acid and mucopolysaccharides. vasculature is usually poorly developed , , . one report of an unusually large myxoma in the hand even showed hormone receptors . a few differential diagnoses should be considered when seeing a patient with a swelling on the hand or wrist like in our case. the most probable diagnosis would be a ganglion cyst however these are smaller than jam , show no septation on mri and have a less developed myxoid component . a hibernoma of the hand should also be considered, even as a rare cause for carpal tunnel syndrome. this tumor of brown fat tissue shows spindle cells and myxoid structures like a myxoma but would be positive for ps and cd . in cases of a rapidly growing mass, a sarcoma must always be considered , . unfortunately the diagnosis is often only confirmed by histologic examination after excision, so reoperation may be needed . careful preoperative planning including mri and even core biopsy should be considered in these cases. nodular fasciitis (nf) is a benign reactive myofibroblastic lesion that may occur after trauma. it also presents as a rapidly growing subcutaneous mass and is sometimes said to be a benign version of a sarcoma. microscopically spindle-shaped cells in myxoid matrix with collagen are found. nf is positive for alpha-smooth muscle actin, and negative for many other markers (beta-catenin, s- , cd , hmga , cytokeratin, ema, caldesmon, desmin) . lastly, an intramuscular myxoma should be considered in differential diagnosis. it is more common in women around and often affects large muscles in the thigh or shoulder. in contrast to jam it shows only minimal cystic changes and has a low recurrence rate even with incomplete resection , , . on ct, mri and ultrasound, they present with an intrinsic high water content and a surrounding rim of fat . activating missense mutations at the arg codon of the gs alpha gene leading to increased levels of cyclic adenosine monophosphate are detected in intramuscular myxomata (and also found in mccune-albright syndrome and sporadic fibrous dysplasia of bone), but not in jam . in our case, the diagnosis of a jam was confirmed after immuno-histochemical staining that was positive for cd but negative for s and actin. juxta-articular myxoma of the wrist: a case report juxta-articular myxoma of the palm recurrent myxoma of the hand myxoma and myxosarcoma of the soft tissues of the extremities juxta-articular myxoma: a clinical and pathologic study of cases musculoskeletal sarcomas in the forearm and hand: standard treatment and microsurgical reconstruction for limb salvage soft tissue sarcoma of the hand and wrist: epidemiology and management challenges imaging of soft-tissue myxoma with emphasis on ct and mr and comparison of radiologic and pathologic findings myxoma of the palm an intramuscular myxoma of the hand periosteal myxoma of the femur. a case report juxta-articular myxoma of the shoulder presenting as a cyst of the acromioclavicular joint: a case report juxta-articular myxoma of the tolhurst de. myxoma of the palm myxoma causing paralysis of the posterior interosseous nerve activating gs alpha mutation at arg codon does not occur in juxta-articular myxoma posterior interosseous nerve palsy caused by a myxoma. the british society for surgery of the hand editorial: myxoma of soft tissues myxoma of the dorsal hand carpal tunnel syndrome due to hibernoma of the wrist: case report intra-articular nodular fasciitis of the proximal interphalangeal joint of a finger: a case report the authors do not have any conflicting interests concerning this article. key: cord- -kzy hdb authors: lynch, sharon g.; rose, john w. title: multiple sclerosis date: - - journal: disease-a-month doi: . /s - ( ) - sha: doc_id: cord_uid: kzy hdb abstract multiple sclerosis is a chronic disease that begins in late adolescence or adulthood. it is highly variable in its expression and severity. it is believed to be autoimmune in nature. the cause is unknown; both genetic and environmental factors have been implicated in the pathogenesis. ms generally presents with the acute or subacute onset of neurologic abnormalities that may wax and wane over many years. diagnosis is generally made by means of observation of the clinical course in conjunction with a neurologic examination and laboratory tests. these tests may include magnetic resonance imaging of the head and spine, lumbar puncture, and evoked potentials. treatment is based on general supportive care, the use of corticosteroids for relapses, and symptomatic management of ongoing problems. the frequency of relapses can be reduced with interferon-β (betaseron). copolymer and interferon-β la are being evaluated by the u.s. food and drug administration for approval for use for reduction in the frequency of relapses in relapsing-remitting ms. treatment of chronic progression is often attempted with immunosuppressive agents such as corticosteroids, azathioprine, and cyclophosphamide. use of other agents is being investigated. multiple sclerosis (ms) is a chronic disease of the central nervous system that typically begins in late adolescence or early adulthood. the cause is unknown, although the disease is believed to be autoimmune in nature. both genetic and environmental factors have been implicated in the pathogenesis of ms. a viral cause has been postulated, but no single virus has been confirmed to be associated with ms. the pathologic features of ms include the presence of demyelinating areas in the white matter of the brain with perivascular in-flammation and relative sparing of the axons. plaques are commonly found in the periventricular areas of the cerebral hemispheres, in the optic nerves, the brainstem, the cerebellum, and the spinal cord. the presence of inflammation in ms plaques and the presence of oligoclonal immunoglobulin bands suggest an autoimmune basis of the disease. characterization of the inflammatory cells in the plaques and in the cerebrospinal fluid has revealed a predominance of t cells. this finding has focused a great deal of attention on the trimolecular complex, which consists of the major histocompatibility complex, the t-cell receptor, and the antigen. consistent associations with dr , drbl , dqb , and the dw haplotypes have been identified in white persons. studies of restricted use of specific t-cell receptor regions in the immune process have not revealed a specific receptor in this disease. the antigen remains unknown, although many investigators are working with myelin basic protein and other proteins associated with myelin. two animal models, experimental allergic encephalomyelitis and theiler murine encephalomyelitis, are valuable in testing experimental immunotherapies and other aspects of autoimmune mediated demyelination. ms generally appears with the acute or subacute onset of neurologic abnormalities that may wax and wane over many years. common early symptoms include numbness, double vision, paraparesis, monoparesis, bladder control problems, optic neuritis, ataxia, or tremor. common ongoing symptoms include those just mentioned, vertigo, increasing spasticity, depression, emotional lability, gait abnormalities, fatigue, dysarthria, quadriparesis, constipation, incoordination, fatigue, and pain. diagnosis is made by means of observation of the clinical course in conjunction with the neurologic examination and laboratory tests. magnetic resonance imaging of the head and spine can be valuable in the evaluation of suspected ms. the presence of an elevated immunoglobulin g (igg) index or oligoclonal bands in the spinal fluid also can be helpful. evoked potentials can help confirm subclinical involvement of the eyes, vestibular function, or sensory tracts. the differential diagnosis of ms includes other demyelinating syndromes, particularly the monophasic syndromes, such as postinfectious encephalomyelitis, postinfectious transverse myelitis, and isolated optic neuritis. some infectious diseases, such as lyme disease, syphilis, and htlv- myelopathy, can be confused with ms. other autoimmune conditions, such as systemic lupus erythematosus, behcet's syndrome, sarcoidosis, and sjogren's syndrome, can cause symptoms similar to those of ms. some leukodystrophies and hereditary degenerative syndromes can be confused with ms. ms is often classified by its clinical course. benign ms is charac-dm, january terized by mild intermittent relapses with nearly complete resolution. relapsing-remitting ms is the most common form of the disease. it is characterized by episodes of acute or subacute neurologic dysfunction followed by periods of improvement and stabilization. secondary progressive ms begins with a relapsing-remitting course, but the disease gradually worsens, causing slow accumulation of neurologic signs and symptoms. ms that never has a relapsing-remitting course but begins with a slow progression of signs and symptoms is classified as primary progressive ms. treatment of ms is based on the progression of an individual case. general health measures include exercise, physical and occupational therapy, a balanced diet, and aggressive treatment of fever and overheating. treatment of relapses is recommended for moderate to severe relapses. corticosteroids are choice of treatment of relapses. steroids should be used with caution because of the large number of side effects associated with long-term use. the frequency of relapses can be reduced with interferon-i lb (betaseron). copolymer and interferon la are being evaluated by the u.s. food and drug administration for approval for use in reduction of the frequency of relapses in relapsing-remitting ms. these drugs soon may be available for clinical use. treatment of chronic progression is often attempted with immunosuppressive agents such as corticosteroids, azathioprine, methotrexate, and cyclophosphamide (cytoxan). other agents under investigation are cladribine and intravenous immunoglobulin. symptomatic treatment of the chronic symptoms of ms is important. treatment of symptoms can help patients remain functional and comfortable even with relatively severe chronic problems. fatigue can be treated with rest breaks during the day, exercise, and energy-conservation techniques. medications that may help are amantadine hydrochloride and pemoline. spasticity is a severe problem that causes contractures, pain, insomnia, and increased fatigue. it can be treated conservatively with physical therapy, particularly stretching exercises. baclofen and diazepam can also be useful and are often used alone or in combination. in patients with severe spasticity, baclofen can be administered with an intrathecal pump. urinary dysfunction is a common problem. a urologist usually is needed to define the type of dysfunction present. a hypertonic, spastic bladder can be treated with anticholinergic agents. a hypotonic bladder may require intermittent or long-term catheterization. detrusor-sphincter dyssynergia may require a combination of anticholinergic agents and intermittent catheterization. urinary retention, which causes frequent bladder infections, may require acidification of the urine or long-term administration of antibiotics. patients with severe retention may require urinary diversion. sexual dysfunction often requires a multidisciplinary approach, including counseling, modification of sexual techniques, medication, or prosthetic devices for men. tremor can be a severe, intractable problem. medications include clonazepam, propranolol, acetazolamide, or diazepam. emotional problems are common in patients with ms. emotional lability may respond to tricyclic antidepressant medications. depression is treated with antidepressant agents and counseling. pain is a prominent concern in many patients with ms. dysesthetic pain can often be managed with tricyclic antidepressants, carbamazepine, phenytoin (dilantin), or valproic acid. musculoskeletal pain is treated with antiinflammatory medications and physical therapy. cognitive dysfunction can be a disabling and distressing component of ms. documentation with neuropsychiatric testing may be helpful in managing these problems. current investigations of ms center on the concept of autoimmunity, possibly mediated by a viral illness. studies designed to define the role of the immune system in ms may be useful. medications designed to reduce a specific autoimmune response and medications that assist in stimulation of remyelination or improvements in quality of life are being developed. over the past few years, great strides have been made in understanding the role of the immune system, in improving diagnostic capabilities, and in managing the problems associated with ms. as this trend continues, we may have more diverse and effective therapies for the management of ms. table . jean martin charcot's description of the clinical and pathologic features of ms is the foundation of our knowledge of the disease.l the historical aspects of ms are reviewed in previous publications. s we are now entering a new phase of understanding brought about by careful clinical trials and the capability of monitoring the disorder with longitudinal magnetic resonance imaging (mri). in an individual patient, ms can be described by means of clinical observation. current concepts of the clinical courses, their relative frequencies, and mri characteristics of ms are portrayed in table . investigations with mri have changed the concept of ms by demonstrating more evidence of disease activity than is expected from clinical examination. disease activity, as measured with mri, is particularly high among patients with chronic progressive disease. the acute lesions of ms can now be demonstrated with gadolinium-enhanced mri. the initial event is associated with local disruption of the blood-brain barrier (fig. ) . as the abnormality evolves, increased signal intensity becomes evident on t -weighted images (figs. and ). the lesion may grow larger over a few days and then the areas of high signal intensity may begin to recede. over time, the lesions may completely resolve on tzweighted images. with each relapse, which is defined by new or newly enhancing lesions on mr images, the older areas of involvement may be reactivated. reactivation is associated with the development of permanent lesions on mr images. clinical correlation is frequently observed with areas of contrast enhancement or abnormal signal intensity in the cerebellum, brainstem, or spinal cord. abnormalities in the cerebral hemispheres are frequently periventricular in distribution and only occasionally correlate with specific symptoms or signs. , the accumulation of lesions in the frontal lobes is associated with a decline in memory. in addition, a change in the number of lesions on cranial mr images correlates with a change in overall clinical status as measured with standard scales.g observations made with mri are having a marked impact on both our basic knowledge of ms and on therapeutic trialsjo mri studies will provide considerable insight into the natural history of the disease and will be an excellent independent variable in future clinical trials. traditionally ms is thought to have a relatively high incidence in the northernmost latitudes of the northern hemisphere.l* this theory is based on the incidence of the disease in scandinavia and the northern united states. a similar association is documented in the southern hemisphere in australia and new zealand. these observations are supplemented by data from m igration studies, which demonstrate a relation between age at m igration and assumption of disease risk for the location. risk is conferred by exposure to an environ- certain populations are susceptible to ms, and certain populations are resistant to ms. for example, lapps in scandinavia have a very low incidence of ms, even though they reside predominantly in the far northern latitudes. in north america the disease is infrequent among hutterites and native americans. ms is uncommon in japan. the incidence of the disease in first-degree relatives of patients with ms is times that of the general population, suggesting that genetic factors influence disease expression. the results of populatidn-based studies of twins offer evidence that environmental and genetic factors contribute to the development of ms. these investigations show that the concordance in monozygotic twins is greater than %. it is less than % in dizy- gotic twinp suggesting that although genetic factors are important, environmental exposure also is important for disease expression. it is now commonly accepted that multiple genes influence autoimmune diseases in both animals and human beings. therefore polygenic inheritance is postulated for ms. like other autoimmune diseases, ms is more frequent in women, with a ratio of :l. the pathologic features of multiple sclerosis were first described by charcot,l who recognized plaques in.the white matter (scleroses en plaque) during pathologic examination of brain sections. these plaques were demonstrated to lack myelin and to contain perivascular inflammation. these features were established as the pathologic hallmarks of ms. the following discussion centers on the typical findings in ms. comparisons are made between ms and other forms of inflammatory demyelinating disease. the distribution of plaques within the white matter is restricted to the central nervous system (cns). plaques are found frequently in a periventricular distribution in the cerebral hemispheres. some of these plaques may be associated with the distribution of terminal veins. j plaques may occur anywhere within the white matter. when plaques are near the cortex, sparing of the subcortical myelinated fibers is often observed. plaques adjacent to gray matter may at times spread into the gray matter, including the cortex and deeper nuclei. plaques are frequently found in the white matter of the optic nerves, the brainstem, the cerebellum, and the spinal cord. plaques in these locations more frequently correlate with symptoms. within a plaque, axons are frequently preserved. the evolution of a plaque is not known. mri investigations show that the blood-brain barrier is locally disrupted at the onset of symptoms. pathologists disagree as to whether demyelination precedes inflammation or is secondary to inflammation. at present the latter view predominates. in acute plaques, the inflammatory response of lymphocytes, plasma cells, and macrophages is capable of producing or augmenting demyelination by direct and indirect mechanisms. the inflammatory response is predominantly perivenular, with a lesser response at the edges of or within plaques. the macrophages associated with acute plaques characteristically contain myelin fragments or myelin breakdown products.lg lymphocytes may contribute to the pathologic process by means of direct or indirect pathways. direct mechanisms include antibodyand cell-mediated immunity. t-cell-mediated reactivity is favored because most inflammatory cells are t cells. indirect mechanisms include the secretion of lymphokines and cytokines. the ability of molecules such as tumor necrosis factor to damage myelin or oligodendrocytes is the focus of ongoing research. cytokines may influence macrophage activation, stimulating the phagocytosis of myelin. in addition, the release of heat shock proteins may result in stimulation of ty cells, resulting in increased cytotoxicity. the cns lesions of ms can be classified as early active, active, inactive, early remyelinating, and late remyelinating, according to histologic criteria. the features of these lesions are detailed in table . studies of oligodendrocytes early in the course of ms have demonstrated relative preservation of these cells in some patients,z , and remyelination is possible in these patients. other patients have a striking loss of oligodendrocytes, making remyelination unlikely. these differences may reflect the severity of the injury at a specific site of demyelination, or they may indicate that the pathogenesis of demyelination varies among patients with ms. this may imply that an autoimmune basis for ms has long been suspected because of the inflammation in the cns and the presence of oligoclonal bands in the cerebrospinal fluid (csf). the inflammatory response is primarily lymphocytic and mononuclear. ~ the predominance of t cells among the lymphocytes has led investigators to evaluate the role of the t-cell receptor and its recognition of antigen combined with major histocompatibility antigens (mhc). this has been named the trimolecular complex. the t-cell receptor recognizes antigen in the context of the mhc molecule. in the case of mhc class ii molecules such as drz, the antigen fragments are bound in a cleft, which is presented to the tcell receptor for recognition. with regard to the components of the in the context of the trimolecular complex, it is important to note that ms has been associated with certain mhc or human leukocyte antigen (hla) markers. a consistent observation is the association of dr , drbl , dqb , and the du haplotype with ms. different hla associations are reported within ethnic groups. the mhc molecules may contribute to genetic susceptibility to the disorder, but they are only one of a number of factors that confer risk for the disease. j the presence of oligoclonal bands in the csf of patients with ms is frequently observed (fig. ) . these abnormal immunoglobulins are identified in a high percentage of patients with clinically definite ms, and they are present in approximately % of patients at the clinical onset of the disease. the oligoclonal bands in ms are of unknown specificity. small percentages may bind to known viral antigens in some patients. consistent binding of these antibodies to specific viral polypeptides or viral oligopeptides with homology to myelin components has yet to be demonstrated. the oligoclonal bands are not specific to ms and can be observed in patients with cns infections such as syphilis, subacute sclerosing panencephalitis, viral encephalitis, or meningitis. , if the infection is self-limited, the oligoclonal bands may be a transitory abnormality. in comparison, chronic infections of the cns are associated with persistence of the oligoclonal bands. in these settings, the antibodies that compose the oligoclonal bands have pathogen specificity. oligoclonal bands can be observed in patients with autoimmune diseases such as systemic lupus erythematosus. the probability that an environmental factor is involved in the pathogenesis of ms has stimulated interest in a viral cause. although viral isolates are reported from the cns of patients with ms, - g there are no consistent observations. attempts to detect viral nucleic acids by means of in situ hybridization and polymerase chain reaction (pcr) are in progress. these techniques are extremely sensitive and require rigorous controls. careful confirmation of any future viral isolates or viral nucleic acids by multiple laboratories is required. [ ] [ ] [ ] [ ] [ ] [ ] [ ] recent studies of tropical spastic paraparesis demonstrate that the retrovirus human t-cell lymphotropic virus type i (htlv-i) is involved in the pathogenesis of this disorder, which shares some clinical features with ms. ga it is clear, however, that htlv-i is not a pathogen in ms. there remains the possibility that a retrovirus or endogenous retrovirus could contribute to the pathogenesis of ms. there is considerable interest in the possibility that exposure to a virus may lead to an immunopathologic condition that results in ms. of particular note are investigations that demonstrate the potential of molecular mimicry to produce autoimmunity. the term molecular mimicry arises from the demonstration of shared homology between normal human myelin proteins and viral polypeptides. if an immune response is mounted to such a viral epitope, then it may be perpetuated by exposure of the shared region on the normal human protein. in ms, homology between myelin antigens and viral peptides is established. thus this mechanism could result in cns demyelination after viral infection. autoimmunity could also result from superantigenic stimulation of t cells by viral or bacterial proteins. superantigens are capable of binding to specific t-cell receptor proteins, producing nonspecific stimulation of relatively large numbers of t cells, which might cause clonal expansion of t cells reactive to myelin or oligodendrocyte antigens. s animal mqdels of demyelinating disease cns demyelination associated with inflammation is present in animal models of experimental allergic encephalomyelitis (eae) and theiler murine encephalomyelitis (tme). these models provide an opportunity for the investigation of autoimmune and virus-associated disease, respectively. eae is an autoimmune disease of the cns and a model for immunotherapy. a cd + t-cell population specific for a myelin antigen, either mbp or proteolipid protein, is required for initiation eae. eae and ms share characteristics that include cns demyelination, perivascular t cells, association with mhc class ii antigens, and possibly restricted tcr v-gene utilization. g the murine adoptive transfer model has another important feature of ms: the chronic relapsing clinical course. g this clinical course is useful for investigations of the immune response and immunotherapy not only during onset of the disease but also during relapse. the pathologic features of this murine transfer model are inflammation and prominent demyelination. g- eae is not associated with an environmental factor. the tme model of immune-mediated demyelination is of particular interest because it has important parallels with postinfectious encephalomyelitis and ms. in this model, antecedent mild or even subclinical viral encephalitis is followed by a period of quiescence and the eventual onset of demyelination. the virus is persistent during the demyelinating phase of the disease. this implies that either low-level expression of viral polypeptides or immunologic cross-reactivity between virus and myelin antigens is crucial for initiating demyelination. the demyelination in the tme virus model is mediated by t lymphocytes. these t cells may have viral specificity but produce demyelination. this mechanism would be relevant to ms if the suspected environmental factor were one or several viruses. as in ms and eae, t cells appear to initiate immunemediated demyelination in tme.!~~z~~ experimental immunotherapies are evaluated in these animal models and provide a basis for clinical trials in human beings. examples of these investigational treatments include cytokine transforming growth factor-i , (tgf , lymphokine-toxin, anti-t-cell receptor vb-specific monoclonal antibody, , t-cell vaccination, blocking peptides, anti-adhesion molecule specific monoclonal antibodies, g and nitric oxide synthetase inhibition. these experimental models provide an invaluable resource for the study of immunotherapy. although these experimental models are not likely to mirror the pathogenesis of ms, they are extremely useful in the study of cns inflammation and demyelination. ms is primarily a disease of young adults. most patients report their first symptoms between the ages of and years. the disorder rarely appears before the age of years or after the age of years, although it has been reported to occur in both children and the elderly. the symptoms of ms in children are essentially the same as those in adults; ataxia, numbness, and visual disturbance are the most common presenting symptoms. in elderly persons, a progressive onset is more common. ms is characterized by episodes of neurologic dysfunction, followed by periods of stabilization or remission. symptoms, once they appear, may partially or completely resolve or may be permanent. these episodes tend to develop over hours or days. sometimes the symptoms occur with almost strokelike suddenness, or they may develop slowly over a few weeks. once the symptoms have developed, resolution generally occurs over weeks or months. certain signs and symptoms are more common in the early stages of ms. these include numbness, double vision, monoparesis, paraparesis, bladder control problems, optic neuritis, ataxia, or tremor (table ) . dm, january numbness can be difficult to evaluate. numbness that suggests early ms includes an ascending numbness beginning at the feet. this may be a sign of transverse myelitis. hemiparesthesia, bilateral hand numbness, and dysesthesia in both hands, both feet, or on one side of the body, also are early symptoms of ms. the numbness is usually present for days, weeks, or months. many patients describe numbness or paresthesia with no objective abnormalities. if objective sensory abnormalities occur, they are more commonly reduction of vibration, proprioception, or stereognosis rather than pain or fever. the diplopia that occurs with ms is frequently partial or complete internuclear ophthalmoplegia, which is often bilateral. a small percentage of patients have sixth nerve palsy" or, more rarely, third or fourth nerve palsy. ww sometimes monocular diplopia is a symptom of optic neuritis. optic neuritis is usually characterized by monocular blurred vision, sometimes with scotomata and often with alteration of color vision. retroorbital pain or headache is common in patients with active optic neuritis. the pain may intensify with eye movement. motor weakness is usually accompanied by upper motor neuron signs, such as hyperreflexia or the babinski sign. paraparesis is the most common early symptom, but the weakness also can occur as hemiparesis or monoparesis. spas.ticity can be a later manifestation. signs and symptoms that commonly occur as ms progresses include vertigo, tremor, incoordination, increasing spasticity, depression, mood swings, cognitive abnormalities, impotence or other sexual dysfunction, weakness, lhermitte's sign, gait abnormalities, constipation, urinary incontinence, optic nerve pallor, fatigue, quadriparesis, dysarthria, loss of upper extremity coordination, and dysesthetic pain (table ) . uncommon but important problems include seizures, atypical facial pain or tic douloureux (trigeminal neuralgia), bowel incontinence, swallowing problems, hearing loss, and dystonia. bell's palsy is sometimes seen in patients with ms (table ) . the classic course of ms is one of intermittent neurologic signs and symptoms over many years. as time progresses, chronic problems accumulate. the amount of total disability varies from patient to patient. after a number of years, a patient's condition may stabilize permanently, but this does not always occur. d&f, january subtypes of disease ms can be divided into subtypes according to the course of the disease. there is a continuum among the various subtypes, and the disease in some patients does not fit into a pattern. benign ms accounts for % to % of cases and occurs more often in young women. in this type of ms, symptoms are mild and often sensory. resolution of neurologic problems is nearly complete. over the years, these patients rarely experience considerable disability. relapsing-remitting ms is the most common form of the disease. it is characterized by episodes of neurologic dysfunction [variably called exacerbations, relapses, or attacks) followed by periods of improvement and stabilization (called remissions). during a remission, not all symptoms resolve completely. the patient may be left with permanent disabilities, which may vary in severity. the condition of % to % of patients with an initial relapsingremitting course begins to worsen gradually over time, and neurologic signs and symptoms accumulate. this form of the disease is classified as secondary chronic progressive ms or relapsing-progressive ms. the latter term is also used to describe disease in patients who have sudden deteriorations in a stepwise manner without clinically significant recovery. primaryprogressive ms occurs in % to % of patients. disease in these patients begins with a slow progression of neurologic deficits with no history of relapse and may also have periods of stabilization or subacute worsening. common problems that appear and gradually worsen with time include spastic paraparesis, cerebellar ataxia, and urinary incontinence. clinical findings although no neurologic findings are pathognomonic for ms, certain abnormalities found during a physical examination can be helpful in providing a clue to the diagnosis of ms. these include internuclear ophthalmoplegia, which is rarely seen in other diseases and is especially rare in young adults. hyperreflexia and the babinski sign are common in early ms. optic nerve pallor can provide a clue to subclinical or resolved optic neuritis. altered color vision in one eye and a marcus-gunn pupil also are signs of optic neuritis. nystagmus is a common finding in patients with ms. many types of nystagmus are identified, including pendular nystagmus, small-amplitude nystagmus, or gaze-evoke nystagmus. a a absent abdominal reflexes in a slender patient who has not undergone an abdominal operation may be a helpful sign. a mild intention tremor with or without past-pointing is also an early sign, as is a positive romberg sign or difficulty with balance with divz,january tandem gait. subtle motor weakness or spasticity may also be found. loss of vibratory or proprioceptive sensation in the lower extremities is common early in the course of the disease. ms should be strongly suspected in young or middle-aged adults who describe symptoms consistent with the lhermitte sign in the absence of obvious cervical cord abnormalities. the lhermitte sign consists of paresthesia or an electric shock-like sensation that radiates up the head or down the spine on neck flexion or extension. other important abnormalities are gait disturbances, persistent binocular double vision when looking in a particular direction, or a history of optic neuritis or transverse myelitis. fatigue and depression are not criteria for the diagnosis of ms. no laboratory test is universally diagnostic for ms. certain studies can be helpful in confirming the presence of separation of lesions in space and time. examination of the csf can be valuable for two reasons. first, the pattern of csf findings can help confirm the presence of demyelinating disease. the protein level is often slightly elevated but is rarely greater than . g/l unless the patient is experiencing a severe exacerbation, particularly optic neuritis or transverse myelitis. a modest elevation in cell count, generally less than /mm , is seen in some patients. the cell pattern usually consists mostly of mononuclear cells. if more sophisticated testing is conducted, most cells can be identified as t lymphocytes. qualitative analysis of proteins can be helpful in suggesting the diagnosis of ms. at electrophoresis oligoclonal immunoglobulin bands can be identified in the csf but not in the serum of many patients with ms , (fig. ) . the igg index, a comparison between igg levels in the csf and igg levels in the serum, is elevated in many patients with ms. , g although these findings suggest ms, they also are found in other diseases, most commonly other inflammatory diseases of the cns. these diseases include lyme disease, systemic lupus erythematosus, progressive multifocal leukoencephalopathy, encephalitis, and subacute sclerosing panencephalitis. the ver is abnormal in approximately % of patients with ms, regardless of whether there is a history of optic neuritis. a slowed ploo in a patient without a history of optic neuritis can be paraclinical evidence of a second lesion and can be used to confirm a diagnosis of ms (fig. ) . g the baer is more difficult to interpret than the ver and is abnormal in approximately % of patients with ms. in the baer, five d&z, january consecutive waves are identified; these are numbered i-v the wave interval i-iii is considered the peripheral system. abnormalities in this wave suggest a lesion in the peripheral auditory nerve. the wave interval iii-v is generated from the central hearing areas in the brainstem. slowing in this area suggests a brainstem lesion. abnormalities in waves iii-v are seen in approximately % of patients with ms. the sser is a technically more difficult study than the other responses, but it is useful for identification of slowed central conduction in the sensory pathway in the spinal cord and brain. the sser is abnormal in approximately % of patients with definite ms. the sser also is useful in the identification of peripheral lesions, suggesting that peripheral neuropathy rather than a central lesion is the cause of numbness. the development of mri has been extremely important in both making the diagnosis of ms and helping researchers understand the dynamics of ms in patients with the disease. mri findings should be interpreted with caution, however. abnormal mri findings alone are not sufficient to confirm a diagnosis of ms without clinical evidence. , in patients with ms, patchy areas of abnormal white matter are seen on t%weighted and spin-echo images. these are most commonly found in the cerebral hemispheres in the periventricular areas. in some patients, however, lesions also are identified in the brainstem and cerebellum. mri also helps identify lesions in the cervical and thoracic spinal cord. gadolinium enhancement can be seen around some lesions, particularly if a patient is having an exacerbation or fairly rapid chronic progression. gadolinium enhancement is considered a sign of an active lesion. (table ). - g mr images should be interpreted with caution, particularly in patients with chronic illness of any kind or in patients older than years. fazekas et a . attempted to differentiate the mr images of healthy persons older than years from those of patients with ms. they identified the following three criteria for the diagnosis of ms: lesions abutting the lateral ventricles, lesion diameter greater than . cm, and lesions present in the posterior fossa. if two of the three criteria were met, the specificity for ms was % and the sensitivity was %. a follow-up study in which consecutive mris were examined yielded a sensitivity of % and a specificity of %" these criteria may be useful in the interpretation of mri findings in some patients, but they should be used with caution for patients with other diseases that can affect mri, such as hypertension and diabetes mellitus. patients with those diseases were excluded from the study by fazekas et al. the size and area of the lesions present on mr images correlate poorly with the patient's disability. , many patients with large lesions on mr images have minor clinical findings, whereas some patients with small lesions have severe disability. one area in which mri may indicate the severity of the problem is in the cognitive status of the patient. an increase in the area of the lesions in the cerebral hemispheres or thinning of the corpus callosum may correlate with poor cognitive function. the presence of lesions in the spinal cord does not correlate with disease severity. a recent study in which body coil imaging was used showed that % of patients with ms had lesions in the spinal cord that were identified by this technique. although the presence of lesions and the area and number of lesions did not correlate with a patient's level of disability, the presence of spinal cord atrophy did correlate with greater disability. patients with partial or complete transverse myelitis who subsequently are found to have ms often have lesions on mr images that correspond to the level indicated by symptoms and the level of neurologic findings (simnad v, rose jw, manuscript in preparation). the use of mri for the follow-up evaluation of ms has become an integral part of research into the course of the disease. however, because mri findings do not correlate with a patient's clinical condition, new abnormalities on mr images in the absence of clinical worsening should not be treated as an exacerbation of the disease. new abnormalities can, however, indicate that the disease remains active. mri should be repeated in patients in whom the diagnosis has not been confirmed or in patients who have new symptoms that suggest a second disease. as the choice of treatments of ms increases, monitoring of disease activity may become useful in determining the course of treatment. optic neuritis is often seen as a first demyelinating episode in patients with ms. the diagnosis of ms should be considered in patients with optic neuritis, and a careful history and examination should be performed to exclude other neurologic abnormalities. however, many patients who have a single episode of optic neuritis never have other demyelinating episodes. one study of patientsgo found that ms developed in % of women and % of men within years of an attack of optic neuritis. transverse myelitis, inflammation of an area of the spinal cord causing ascending weakness and numbness up to the level of the lesion, can also be seen as the initial demyelinating event in ms. other causes include infectious, postinfectious, and postvaccinal demyelination. sometimes the cause is never determined. when transverse myelitis occurs, an imflammatory lesion can be identified on mri images of the cervical or thoracic spinal cord. estimates of the risk of ms after an isolated episode of transverse myelitis range from % to %.g -g im'z, january the use of the cranial mr images in patients with optic neuritis or transverse myelitis may be helpful in predicting which patients are more likely to have additional problems. one prospective study identified patients with a single demyelinating episode such as optic neuritis or transverse myelitis. patients with abnormal mri findings at the time of the first episode had a % risk of a second episode within years. patients with normal mri findings at the time of the first episode had a % risk of development of a second lesion in years.g a syndrome in which optic neuritis and transverse myelitis develop with no other demyelinating events is called devic's neuromyelitis optica. in this disorder, cranial mri findings remain normal. this is considered a monophasic illness-both abnormalities occur within a year of each other, and patients may never have another demyelinating event. this is a rare syndrome.g the following characteristics are associated with a favorable prognosis: ( ) female sex, ( ) early age at onset, ( ) onset of symptoms referable to a single neurologic system, ( ) substantial recovery from relapses, ( ) early symptoms of numbness rather than corticospinal or cerebellar symptoms. unfavorable prognosis is associated with chronic progressive disease (either primary or secondary), older age at onset, and male sex.g -g dlagnostic criteria because of the difficulties involved in the diagnosis of ms, several criteria have been published to standardize the terms used to describe the certainty of the diagnosis. the two primary sets of criteria are those of poser et a . g and shumacher et a . the poser criteria are more recent and are summarized in table . it is important to remember that no abnormality should be used as a criterion if it can be explained by another medical problem. other conditions may commonly be confused with ms and should be considered in the differential diagnosis. the differential diagnosis depends in part on the clinical and laboratory findings in an individual patient. postinfectious encephalomyelitis is a subacute syndrome, possibly caused by an autoimmune response to a viral infection. patients with this illness experience the acute or subacute onset of confusion, disorientation, gait abnormalities, loss of bowel or bladder control, weakness, or other symptoms. abnormalities in the white mat- ter can be seen with mri, and evidence of inflammation frequently is seen in the cse the patient's condition may or may not return to normal; recovery may take months or even years. lyme disease is a prominent concern and appears to be a cause of intermittent neurologic events, the most common of which is bell's palsy. encephalomyelitis may develop, with vague symptoms of numbness, fatigue, and memory deficit. abnormalities in the white matter may be seen with mri, and csf findings may resemble those in ms, including mild leukocytosis and oligoclonal bands. patients may have a history of a tick bite, a rash, or recent arthralgia. lyme titers or a lyme pcr in the blood or csf may be helpful to these patients. systemic lupus erythematosus is a well-known syndrome that may cause transverse myelitis, strokes, encephalopathy, and optic abnormalities. clues to the differential diagnosis are systemic abnormalities such as hematuria or leukopenia, arthritis, or an elevated antinuclear antibody titer, erythrocyte sedimentation rate, or other blood measurement. sometimes both systemic lupus erythematosus and ms occur in the same patient. primary cns vasculitis can cause a syndrome similar to ms. differentiating features include prominent headaches, confusion, and sudden strokelike episodes. an elevated erythrocyte sedimentation rate may be present in some patients, as may an elevated csf protein level. patients may have an abnormal cerebral angiogram. bi-opsy of the temporal lobe or meninges may be helpful in the diagnosis of this syndrome. the htlv-i, a retrovirus, causes a syndrome known as tropical spastic paraparesis or htlv-i-associated myelopathy. it may cause progressive spastic paraparesis or generalized white matter disease. htlv-i is relatively rare in the united states but is present in some patients who have resided around the caribbean sea. behqet's syndrome can cause mri findings identical to those in ms. cardinal features of behqet's syndrome include oral ulcers, genital ulcers, and uveitis. variable features include involvement of the skin, eyes, joints, lungs, intestines, and heart and venous thrombosis. neuropsychiatric symptoms, including quadriparesis, pseudobulbar palsy, cranial neuropathy, cerebellar ataxia, peripheral neuropathic lesions, or cerebral venous thrombosis may be present. g, sarcoidosis and sjggren's syndrome are autoimmune diseases that may show lesions on mr images that resemble those of ms. meningeal enhancement is a clue to cns sarcoidosis. a chest radiograph may show granulomatous lesions suggestive of systemic sarcoidosis. although igg levels are raised in the csf of patients with cns sarcoidosis, oligoclonal bands are found in some patients. csf angiotensin-converting enzyme determination may be used to further differentiate cns sarcoidosis from ms. vitamin b deficiency and syphilis can cause posterior column abnormali& and dementia. tests for these problems should be performed when a patient with these symptoms is seen. certain leukodystrophies may appear in adulthood. these include adrenal leukodystrophy, krabbe's disease, and metachromatic leukodystrophy. mri findings in these diseases show large areas in which no normal white matter is present. female carriers of the adrenal leukodystrophy gene may have an ms-like syndrome. ~ g hereditary degenerative syndromes, such as familial spastic paraparesis, olivopontocerebellar degeneration, and spinocerebellar degeneration, may be confused with ms, particularly with primary progressive ms. in these diseases, mr images may be normal or may show atrophy of the brainstem, spinal cord, or cerebellum. the csf is normal in these patients. studies support the concept that exercise is beneficial for the patients with ms.ggjoo simple measures such as walking, using an exercise bicycle, and swimming may be of considerable value. exercise should be performed in a cool environment whenever possible to prevent heat-associated transient declines in neurologic function. swimming and water aerobics in pools that are not overly heated are particularly valuable, because the patient is cooled while exercising. physical and occupational therapy are often invaluable for maintenance or improvement of neurologic function. bracing disabled portions of limbs, particularly the ankle, provides considerable benefit. exercise regimens tailored to the patient may help to maintain or improve strength, range of motion, and mobility. devices that provide assistance with walking can be important in reducing the risk of falls, allowing for greater independence and increased activity. other assistive devices can be helpful in reducing fatigue and increasing independent activity. careful consultation with a specialist in rehabilitative medicine can assist the patient with management of work and daily activities.l"o it is advisable for persons with ms to maintain a balanced diet. weight control is a prominent concern. overweight patients with motor, sensory, or coordination deficits that impair ambulation are at particular risk of falls, which may result in serious injuries, including fractures. patients who are overweight and whose strength is decreased lose any reserve strength they may have because of their weight. some patients with ms lose weight and require dietary supplementation. patients with dysphagia may require feeding tubes to help prevent aspiration pneumonia. although various diets have been advocated for ms, there are no substantial data from controlled trials to support the assertions. as a general health measure, it is commonly suggested that patients with ms restrict cholesterol and fat in the diet. diets that meet the requirements of the american heart association are likely to be useful, because most patients with ms live into middle age and beyond. pregnancy is a concern among young women with ms. many studies of the effect of pregnancy on ms have been undertaken. an increased risk of exacerbations in the first months postpartum has been reported.lol-la however, the risk of exacerbations during pregnancy appears to be unchanged or slightly reduced.lo overall longterm disability does not appear to be altered by pregnancy.lo j the increased relapse rate seen during the postpartum period has been postulated to be caused by an increase in immune tolerance during pregnancy, followed by a return to normal in the postpartum dm, january period. it has also been postulated that the relapses are secondary to the decrease in the level of female hormones after parturition.lo*-lo in addition to the physical effects of pregnancy, another major concern is the care of an infant or child by a person with physical problems. persons with ms need to consider carefully whether they can handle the additional work of caring for a child. persons with chronic physical problems may need special provisions, such as extra assistance in the home or special equipment. the physician should discuss pregnancy, delivery, and child care with women of childbearing age. increased core temperature, whether due to heat exposure or to a febrile response, may lead to a transient increase in neurologic symptoms.lo if the event is due to heat exposure, the patient simply needs to rest in a cool environment and await recovery. if an infection is responsible, the source of the infection should be determined and treated. an antipyretic medication such as acetaminophen can then be administered. many patients with ms are susceptible to urinary tract infections and may not have clinical manifestations of the infection. in some patients this is due to impaired sensory capabilities, and some patients have chronic urinary symptoms that may not change substantially with an infection. one study of ms exacerbations pointed to an association with antecedent infection.lo if a patient has persistent worsening after an infection that has been appropriately treated and resolved, steroid therapy should be considered in the event the infection recurs. a relapse is considered to be the onset of new neurologic symptoms or marked worsening of old symptoms lasting longer than hours. certain conditions may mimic an exacerbation and should be ruled out or treated before steroid therapy is considered. these include fever, infection (commonly urinary tract infection or viral illness), overheating, fatigue, severe emotional stress, or the effects of medications such as baclofen, which can increase weakness. if these problems are appropriately treated, the patient's condition usually improves. mild relapses may be best treated without steroid therapy. the symptoms include a mild numbness, mild changes in bladder function, mild optic neuritis (visual acuity better than / ), slight increase in spasticity, or a dysesthetic pain syndrome. any new abnormality that does not change a person's ability to perform his or her usual daily activities may not require steroid therapy. in these patients, rest is sometimes helpful. patients with more severe worsen-ing may benefit from steroid therapy. the symptoms include gait disturbances, severe numbness or paresthesia, moderate to severe paresis, moderate or severe optic neuritis, severe vertigo, or marked impairment of eye movement. it is often appropriate for the physician to observe the patient for a few days before making a decision about the use of steroids. standard therapy for many years, immunosuppression with corticotropin (acth) or steroids has been used in the treatment of the exacerbations of ms. the primary effect of these agents is to shorten the duration of an attack, and no benefit has been proven in the overall outcome from an attack. steroids should not be given until an abnormality resolves because this may never occur. acth was the first immunosuppressant to be widely used in ms.lo although it is still given to some patients who respond well to the medication, acth has been largely supplanted by other steroids, most commonly prednisone and methylprednisolone. many different regimens have been used. a typical regimen is units by intravenous or intramuscular injection once a day for days. prednisone is commonly used for mild or moderate exacerbations of ms. although low doses do not appear to have any effect on an exacerbation, larger doses do appear to shorten the duration of an ms attack.log there is no standard treatment regimen; a dose of at least mg/kg per day is commonly recommended and should be continued for to days. our regimen is mg once a day by mouth for days, then tapered by mg every days. other regimens range from days to weeks or longer. methylprednisolone with sodium succinate (solu-medrol) is often used in the treatment of severe relapses, or when the patient's condition continues to worsen after several days of high-dose prednisone.'lo typical dosages range from to mg/day and last from to days. a typical dose is mg in ml of % dextrose in water over minutes every hours to a total of doses. another is mg in ml of % dextrose in water over minutes every hours for doses. an oral prednisone taper over about days to weeks may be used afterward. one study of optic neuritis suggested that high-dose methylprednisolone produces more favorable results than oral prednisone for patients with poor visual acuity. this study showed only a faster recovery time; follow-up examinations at year did not show any difference in final outcome."l the study involved patients who did not necessarily have a diagnosis of ms. however, a follow-up evaluation with patients in whom ms subsequently developed did suggest that the methylprednisolone-treated group had a longer time interval to the development of a second demyelinating event than dm,january . those who received prednisone or placebo.l for this reason, some neurologists believe that all attacks of ms should be treated with intravenous methylprednisolone. the side effects of steroids are well known. these include nonspecific immunosuppression leading to opportunistic infections, induction of hyperglycemia, fluid retention, hypertension, emotional abnormalities, hypokalemia, peptic ulcers, occasional aseptic necrosis of the femoral head or other bones, and demineralization of bone. chronic use may lead to cataracts, osteoporosis, muscle wasting, hypertension, diabetes, increased susceptibility to infections, and a cushingoid appearance. steroids should be used with caution. we have found the,following precautions helpful: administration of calcium and possibly vitamin d during the administration of steroids and restriction of foods with a high sugar or sodium content. we encourage our patients to eat foods rich in potassium, such as bananas, orange juice, and tomatoes. patients who experience indigestion may benefit from the use of histamine blockers such as ranitidine. some patients may need sedation with diazepam or other agents because of severe mood swings, anxiety, or sleeplessness. patients who receive high doses of methylprednisolone should be observed for hypertension, electrolyte imbalance, and hyperglycemia. these problems should be treated appropriately. occasional psychiatric symptoms, including depression, psychosis, and severe anxiety, may necessitate cessation of steroid therapy. betaseron, a recombinant interferon-& has been approved by the u.s. food and drug administration (fda) for use in ambulatory patients with relapsing-remitting ms. this approval followed a year, controlled, double-blind study that showed in patients treated with million units of betaseron administered subcutaneously every other day the relapse rate was reduced to . relapse per year compared with . relapses per year in patients given placebo.l an mri study performed with the same population revealed fewer new lesions in the treatment group than in the control group.lo the drug did not improve ongoing symptoms. the study was limited to patients with relapsing-remitting disease, and the findings should not be extrapolated to patients with chronic progressive disease. a study of the use of betaseron by patients with chronic progressive ms is planned. patients whose condition is stable would not benefit from the use of betaseron. there are problems with the use of betaseron. although the drug may be helpful in patients with frequent relapses, it does have seri-ous side effects. almost all patients experience local reactions at the site of injection, and some patients have had tissue necrosis at injection sites. the injection site must be changed regularly to reduce the likelihood of ulceration. many patients have a flulike reaction, which may include fever, chills, malaise, and myalgia. this reaction resolves with time and commonly lasts only a few months; however, it may last as long as a year. these symptoms can be partially controlled with acetaminophen or ibuprofen. liver function studies may show abnormalities, and leukopenia may be present. fatigue and emotional disturbances have been reported. our patients have experienced episodes of acute depression and anxiety, and one patient had an episode of uncontrollable rage. depression may necessitate temporary or permanent cessation of betaseron treatment. however, antidepressants, such as fluoxetine, sertraline, and paroxetine hydrochloride, may help counteract the depression. in a few cases, ms appears to worsen when the patient is taking betaseron. acute weakness develops in some patients with the first few injections. this is not always associated with fever and may resolve with time. menstrual irregularities have been reported, and betaseron cannot be used during pregnancy. some patients tolerate the medication better if the full dose is titrated up over approximately month. periodic blood tests to check for leukopenia and abnormal liver function are suggested. clinical trials of other preparations of interferon-a and interferon- are nearing completion. one clinical trial involved administration of a weekly intramuscular injection of interferon la. the results suggested that this drug reduces the likelihood of progression in patients with early disease. a phase iii clinical trial of another investigational agent, copolymer , has been completed. this drug appears promising in reducing relapses and has a good safety profile. j these agents will likely be available in the near future, pending fda approval. although most treatment aimed at chronic progression remains experimental, the use of intermittent intravenous methylprednisolone has become a common practice. most commonly, patients who experience subacute worsening may respond to a course of highdose solu-medrol similar to that given for a severe relapse. the condition of some patients appears to stabilize, at least temporarily, with this course of therapy. some patients with progressive disease may respond to a single dose of mg of solu-medrol in ml of % dextrose in water given over hour once a month for to months. subsequent treatments may be given every to weeks. azathioprine has been used for the treatment of chronic progres-sion with some success. studies have shown a modest benefit of azathioprine, primarily in stabilizing the condition of some patients.l j patients who take this drug should be examined for leukopenia or hepatotoxicity. about % of patients are unable to tolerate azathioprine because of fever, rash, or nausea. patients with continued progression during therapy with azathioprine or solu-medrol may benefit from combined therapy. cyclosporine was evaluated in a multicenter clinical trial and was found to have modest clinical benefit.llg the prolonged use of cyclosporine in patients with chronic progressive ms was complicated by side effects, principally nephrotoxicity and hypertension. the use of cyclophosphamide in the treatment of chronic progressive ms is controversia . - the results of clinical trials of this agent in chronic progressive ms are contradictory. the drug may have use in rapidly progressive ms that does not respond to steroid therapy. further investigation with mri and neuropsychological testing and careful clinical assessment should resolve the controversy. a number of promising phase iii clinical trials of therapeutic agents for relapsing-remitting ms are being conducted. for two of these agents, the -year placebo-controlled phase has been completed. these are an interferon-& given once a week by intramuscular injection, and copolymer . both drugs reduce the frequency of relapses and favorably influence disability. the interferon-l is identical to human interferon- and differs from betaseron in that it has the sequence of amino acids and glycosylation of human interferon.l the results of a review of the safety profile of this drug compared with that of betaseron will be of considerable interest. copolymer appears to have activity similar to that of betaseron with regard to reduction of relapses in ms.l , the side-effect profile appears to be favorable compared with that of betaseron. laboratory investigations demonstrate additive effects of copolymer and interferon-l in vitro. because the drugs theoretically act through different mechanisms, combined therapy might be possible. because of the results of a pilot study, oral myelin is being tested in a phase iii clinical trial. lz in the pilot trial, the efficacy of the drug was observed in only a subgroup of patients (dr -negative men). two pilot studies of the use of methotrexate for ms have been performed. j methotrexate in low doses is used for the treatment of rheumatoid arthritis, psoriasis, and crohn's disease. similar therapy may be of benefit to patients with advanced ms.lz a phase iii controlled trial and dose response testing will be of considerable interest. methotrexate should be used in clinical settings that allow careful neurologic and laboratory follow-up evaluation. dm, january cladribine by intravenous administration appears to alter the progression of ms. lz the drug has relatively selective toxicity for lymphocytes; however, the side effects can be substantial. additional studies to evaluate dose and route of administration are being initiated. the clinical effects of repeated dosage with this medication also require study. immunoglobulin therapy may be useful in ms; however, controlled trials of intravenous immunoglobulin (ivig) must be completed.lz this therapy may be useful in relapsing disease and can be considered for patients with both ms and diabetes. ivig therapy is not necessarily benign and can be responsible for the transmission of viral hepatitis. several clinical trials of monoclonal antibodies are in progress. a number of monoclonal antibodies with specificities for either lymphocytes or adhesion molecules are being subjected to initial trials in human beings. a monoclonal antibody that appears to lower lymphocytes and have an appreciable effect on the lesions of patients with ms as seen on mr images is being studied.lz ,%klptomtic therapy one of the most important aspects of the treatment of ms is helping patients manage their ongoing symptoms. because of the chronic nature of the problems associated with ms, medication and adjustments in lifestyle are used to help patients cope with their disabilities. table gives a summary of possible symptomatic treatments. fatigue can be disabling in patients with ms. it is described in different ways by different patients. the classic description of fatigue is increased weakness with exercise or as the day progresses. the patient may walk fairly well in the morning but need a cane or walker by afternoon. other descriptions include sudden attacks of sleepiness or excessive chronic sleepiness, even though the patient has had enough sleep at night.lzg patients who describe fatigue should be questioned closely about their sleep habits and other symptoms of depression. many patients with fatigue may have poor sleep habits or insomnia, which lead to daytime fatigue. depression is a common problem in patients with ms. if the fatigue is a product of depression, treatment of the depression should be helpful. fatigue is sometimes managed without medication. patients may respond to one or two brief ( to minutes) naps during the day. if this is not helpful or not possible, amantadine may be given to help control the problem. the mechanism of action of amantadine is not known, but it is helpful in approximately % of patients.lzg side effects, such as dizziness, headaches, nervousness, or edema, may limit the usefulness of the drug. pemoline is a cns stimulant that may be helpful in some patients. it should be used in low doses and should generally be given early in the day because it may cause insomnia. anxiety and anorexia are other problems that may occur with this drug. liver function studies should be performed periodically to monitor for hepatotoxicity. fluoxetine (prozac) may be helpful both to increase energy and to treat depression.* d&z, january vertigo vertigo can be an intractable and disabling problem. vertigo can occur in sudden spells that last a few minutes, or it can be chronic and last for hours. some physical therapy techniques involve habituation exercises to help with vertigo. medications that may be helpful include meclizine, promethazine hydrochloride, and low-dose diazepam. oscillopsia may occasionally respond to clonazepam or baclofen. vertigo with nausea and vomiting may respond to metoclopramide. spasticity can appear in many different ways. it may be seen at direct examination as a "catch" in the muscles with passive rapid movement of the limbs, or it may cause severe stiffness or rigidity. some patients may have severe spasms of the affected limb, which may be precipitated by movement or occur at night. these are most common in the lower limbs and may be either flexor or extensor spasms. the spasms can be quite painful. primary treatment of spasticity includes physical therapy with stretching exercises, combined with medication. baclofen is the most commonly used drug for spasticity, although its mechanism of action is not known. the dose of baclofen should be low when treatment begins and should be titrated slowly and carefully. patients who take an overdose of baclofen experience weakness. the dose of baclofen is extremely variable-some patients with only moderate spasticity tolerate high doses, whereas others with severe spasticity tolerate only low doses. other limiting side effects include drowsiness, confusion, and nausea. use of baclofen should not be discontinued abruptly but should be tapered over a few weeks. * diazepam in combination with baclofen may be helpful for patients with severe spasticity or those who cannot tolerate high doses of baclofen but need to control spasticity. diazepam can be used alone for spasticity, but it is not as effective as baclofen. diazepam can be particularly helpful for flexor or extensor spasms at night. dantrolene has limited value because of its hepatotoxicity and the weakness that accompanies the muscle-relaxant effect. it may be helpful in intractable cases of spasticity. the baclofen pump was developed for use in patients with intractable spasticity. this device is an intrathecal pump with a subcutaneous reservoir of baclofen that administers continuous doses of baclofen directly into the spinal canal. this method of administration can be effective. with the lower dose delivered directly to the spinal cord, patients seem to have fewer side effects than with other routes of administration. dose levels can be programmed to change throughout the day, so patients with problems that are worse during the night or another part of the day can take increased doses of the drug during those times. tizanidine is an agent used outside the united states for spasticity. it is being studied in the united states and may become available in the near future. other agents that may be useful in the treatment of spasticity include carbamazepine, phenytoin sodium, methocarbamol, and cyclobenzaprine hydrochloride. clonidine patches may be used for adjunctive therapy in patients with persisting spasms who are taking other drugs. spastic dysarthria is an uncommon symptom in ms. speech is hesitant and stuttering, and breath control is difficult. baclofen sometimes is helpful in this condition. bladder dysfunction is an extremely common problem in ms. examination of postvoid residual urine volume and urodynamic testing are extremely important in delineating the causes of bladder dysfunction. other urologic examinations, such as cystoscopy, may help eliminate mechanical problems as the cause of urinary dysfunction. consultation with a urologist skilled in the evaluation of neurologic dysfunction of the bladder is essential to the best therapeutic outcome. the most common problem is a spastic bladder. this is a small, hyperactive bladder. symptoms of this type of bladder dysfunction are urgency, increased frequency, and incontinence in which the bladder empties completely with brief warning. this condition can be treated with anticholinergic agents such as oxybutynin or propantheline . j sometimes baclofen or amitriptyline can be of use in the control of this problem (table ) . detrusor-external sphincter dyssynergia is a common problem. in this syndrome, the bladder attempts to empty, but the urethra remains closed. symptoms may be urgency and hesitancy, double voiding, and increased frequency with a feeling of incomplete emptying. anticholinergic or tricyclic agents alone may be of help with this syndrome, but more commonly a combination of anticholinergic drugs and intermittent catheterization is needed to control the problem. the patient performs self-catheterization two to four times a day. a flaccid bladder is less common than the other types of bladder dysfunction. this is an enlarged bladder that empties poorly. symptoms include hesitancy, double voiding, a feeling of incomplete emptying, and dribbling incontinence. untreated urinary retention can result in hydronephrosis. urecholine can be of use in a few patients. frequently, however, a schedule of intermittent selfcatheterization may be needed (table ) . patients with flaccid bladder or sphincter dyssynergia may have frequent urinary tract infections. acidifying agents such as hippuric acid or vitamin c may be useful in the prevention of infections. longterm administration of antibiotics should be avoided to reduce the risk z patients with severe bladder problems that are unresponsive to noninvasive therapy may require a chronic indwelling catheter or urinary diversion. these techniques may be required by patients who cannot perform intermittent self-catheterization. sexual dysfunction is common in both men and women with ms. women often report decreased sensation, lack of vaginal lubrication, difficulty achieving orgasm, or painful muscle spasms in the legs or pelvis during intercourse. men report diminished sensation and difficulty in achieving or maintaining an erection or experiencing orgasm. there is no simple answer to the sexual problems that occur with ms. a multidisciplinary approach is needed in which the physical and psychological aspects of sexual problems are considered. for women, treatment of muscle spasms with medications for spasticity may allow intercourse with less pain. techniques to increase vaginal and clitoral stimulation may help women experience orgasm. other methods of increasing arousal may be helpful. men are interviewed to determine whether there are other causes of erectile dysfunction. medications that may affect erectile function should be eliminated if possible. yohimbine, an a- -adrenergic receptor antagonist, can sometimes help restore function in a patient with borderline function . other methods, including papaverine or phentolamine injections, a vacuum erectile device, or a penile prosthesis, may be considered. inappropriate affect can be a problem in patients with ms. many patients have severe mood swings that can affect both their work and their social relationships. low-dose amitriptyline or another tricyclic antidepressant is frequently helpful in controlling mood swings. g depression is a common problem in ms. j , the suicide rate among persons with ms is estimated to be . times that of the healthy population. whether the depression is a primary symptom of ms or a situational problem is not known. physicians should be alert to the possibility of depression in their patients. full-dose antidepressant medications and psychological counseling may be beneficial. tremor can be a limiting factor in many patients with ms. treatment with medications is frequently unsuccessful. agents that may be useful include clonazepam, acetazolamide, propranolol, primidone, and diazepam. isoniazid has been reported to be helpful in some patients. we have found clonazepam to be the most helpful of these agents in our patients, but treatment may be limited by drowsiness. a common misconception is that pain is not a symptom in patients with ms. the truth is that pain is often a problem and may be a prominent concern for patients with ms. this can be a primary factor in the disease, or it can be a consequence of disability associated with the disease. much of the pain reported with ms is musculoskeletal and is related to abnormal use of muscles and joints. for example, patients who use a wheelchair may experience wrist, shoulder, or elbow pain from manipulating the wheelchair. patients with paraparesis or ataxia may experience back or leg pain from poor posture and balance when walking. these problems should be treated with antiinflammatory medications and physical therapy. primary ms pain is often dysesthetic. z the patient describes a burning sensation or perhaps even electric shock-like pain. this pain can be in any location, but it is most commonly in the lower extremities. some patients experience tic douloureux or atypical facial pain. this primary pain may be controlled with tricyclic antidepressants, phenytoin, or carbamazepine. in patients with refractory pain, valproic acid can be tried. z headaches can become a problem in patients with ms. it is not known whether these headaches are caused by ms or are a separate problem. both tension and migraine headaches are common, and treatment is similar to the treatment of headaches in patients who do not have ms. retro-orbital pain is frequently observed in patients with optic neuritis. these patients may require steroid therapy. spasticity and muscle spasms can cause severe pain. treatment of the spasticity helps the pain. many patients with ms experience cognitive abnormalities. unlike the dementia of alzheimer's disease, the cognitive deficits seem to be more scattered and tend to be retrieval deficits rather than memory loss. patients can have substantial cognitive difficulties but still have normal mini-mental state examination findings. neuropsychological studies have shown that as many as % of patients may have some cognitive difficulties. these difficulties can be important in terms of disability and ability to cope with illness. only a minority of patients have severe cognitive abnormalities. mr images in patients with cognitive problems tend to show a larger number and size of lesions in the white matter of the cerebral hemispheres. frontal lesions are more common in patients with cognitive difficulties.* the corpus callosum may be thinner than normal, as seen on sagittal images. patients with cognitive problems should undergo careful neuropsychiatric testing. sometimes depression or anxiety can be contributing factors in these symptoms. the minnesota multiphasic personality index or the beck depression scale in conjunction with cognitive testing may be helpful in differentiating emotional problems from structural cognitive deficits. proper treatment of the anxiety or depression may lead to improved cognitive function. recognition of the areas and degree of cognitive difficulty in patients with ms may be helpful in the care of the patients. patients may be able to learn ways of working around a problem. problems with a job may be related to cognitive problems, and ways of altering the job may be found. patients may become disabled from working because of these problems. this testing also may help the family understand the need for helping the patient deal with problems that have become too difficult to handle alone. cognitive rehabilitation techniques are being tested for patients with ms in some centers. further investigation is needed to evaluate the efficacy of these techniques. careful assessment of the patient's abilities and disabilities is crucial for proper management. in many patients, chronic symptoms cannot be prevented. symptomatic therapies are often effective for alleviating the afflictions produced by ms and for allowing the patients to live a productive and comfortable life. the cause of ms is unknown. theories revolve around the idea that the disease is either autoimmune or virus-mediated. it is still reasonable to question which pathologic feature is the inciting event. much research is focused on the t cell and potential mechanisms by which these cells could initiate ms. hla associations are found in many populations; however, hla markers are neither necessary nor sufficient to confer disease susceptibility, and other factors that confer disease susceptibility are being sought. at this time there is no confirmed evidence of a viral cause of ms. investigations with in situ hybridization and pcr technology are being conducted in an attempt to identify viral nucleic acids in the cns. perhaps these techniques will assist in unraveling the pathogenesis of ms. an intriguing possibility is that molecular mimicry may be re-sponsible for the initial generation of autoreactive lymphocytes. this mechanism involves exposure to viral or bacterial antigens, which generates an immunologic response that consists of reactive t-cell populations. because t cells cross-react with myelin peptides, a potential for demyelination exists. this theoretic mechanism is known to cause demyelination in rabbits. an interesting investigation of human mbp-reactive t cells demonstrates that mbp-specific t-cell clones can recognize multiple viral polypeptides presented by dr or dql mhc antigens. this would imply that ms could be generated by exposure to any one of a number of antigenic stimuli, such as influenza viruses or herpesviruses or even bacterial antigens. selected activated t-cell populations that enter the cns could then recognize a myelin epitope and initiate the autoimmune response, which would persist long after the inciting infection was cleared. recent investigation with mr spectroscopy demonstrates that white matter outside ms plaques may be abnorma . " these findings may signify that there is a fundamental abnormality in the white matter. whether these findings are secondary to genetic, biochemical, autoimmune, or viral factors remains to be determined. despite the deficiencies in our understanding of disease pathogenesis, therapy for ms has advanced. phase iii clinical trials with interferon- and copolymer have demonstrated modest but definite benefit. the mechanisms by which these drugs favorably influence the clinical course of ms remain to be elucidated. recent studies of chemotherapeutic agents suggest that control of chronic progressive disease may be a real possibility. future clinical trials will attempt to define the efficacy of and parameters for these therapies. another question that remains unanswered is whether the use of multiple-drug therapy might be beneficial in the treatment of ms. for example, combined therapy with interferon-i lb and copolymer may produce more benefit than either drug alone. in chronic progressive disease, the use of solu-medrol in combination with another immunosuppressant such as azathioprine or methotrexate also should be explored. remyelination is another topic of interest for future research. research is being conducted into the use of ivig as a remyelinating agent. in addition, oligodendrocyte transplant experiments are being conducted in canine modes and may eventually be used for human patients. research involving medications to improve the symptoms that limit the lives of many patients with ms is ongoing and should continue. -amino-pyridine and , -diamino-pyridine are being studied as agents that may improve conduction through poorly myelinated areas. these agents may reduce double vision, improve strength, and possibly reduce tremor. more research is needed to evaluate these dm,january and other compounds that may improve the quality of life of many patients with ms. although the cause of ms remains a mystery, important advances have been made in the understanding and treatment of ms in the past few years. as this trend continues, we may have more diverse and effective therapies to offer patients with ms in the years to come. lectures on the diseases of the nervous system multiple sclerosis multiple sclerosis benign versus chronic progressive multiple sclerosis: magnetic resonance imaging features neuroimaging in multiple sclerosis acute vith cranial nerve dysfunction in multiple sclerosis genetic epidemiology of multiple sclerosis: a survey genetics of multiple sclerosis a population-based study of multiple sclerosis in twins: update genetic analysis of autoimmune type i diabetes mellitus in mice demyelinating diseases oligodendrocytes in the early course of multiple sclerosis allen iv pathology of multiple sclerosis tumor necrosis factor identified in multiple sclerosis brain histopathology and the bloodcerebrospinal fluid barrier in multiple sclerosis multiple sclerosis: oligodendroglia survival and proliferation in an active 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sclerosis: the cons intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the northeast cooperative multiple sclerosis treatment group double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis meydrech ee low dose oral methotrexate treatment of multiple sclerosis: a pilot study low-dose ( . mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis cladribine in treatment of chronic progressive multiple sclerosis open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis preliminary evidence from magnetic resonance imaging for reduction in disease activity after lymphocyte depletion in multiple sclerosis amantadine therapy for fatigue in multiple sclerosis depression and multiple sclerosis a double-blind, randomized crossover trial of pemoline in fatigue associated with multiple sclerosis new advances in symptom management in multiple sclerosis antispasticity drugs: mechanisms of action intrathecal baclofen for spasticity of spinal origin: seven years of experience safety and efficacy of tizanidine in therapy of spasticity secondary to multiple sclerosis management of bladder dysfunction in multiple sclerosis urological and sexual problems in multiple sclerosis the role of yohimbine for the treatment of erectile impotence treatment of pathologic laughing and weeping with amitriptyline suicide in the medical patient a controlled trial of isoniazid therapy for action tremor in multiple sclerosis pain syndromes in multiple sclerosis fujinami rs, oldstone mba. amino acid homology between the encephalitogenic site of myelin basic protein and virus: a mechanism for autoimmunity molecular mimicry in t cell-mediated autoimmunity: viral peptides activate human t cell clones specific for myelin basic protein fdg-pet, mri and nmr spectroscopy of normal appearing white matter (nawm) in multiple sclerosis key: cord- -ka wc authors: nan title: ecr book of abstracts - b - scientific sessions date: - - journal: insights imaging doi: . /s - - -x sha: doc_id: cord_uid: ka wc nan analysis of breast mri a dedicated cad software was used (computer-aided analysis). it enables semi-automatic analysis of enhancement characteristics of the whole tumour ( d analysis of early vs. delayed phase) and the "hot-spot" (i.e. voxel with highest washin/washout ratio). potential of breast mri characteristics vs. classical prognostic factors to predict disease-related death was investigated separately and in combination using cox regression. to identify significant and independent predictors for disease-related death, backward feature selection was applied (p entry /removal: < . /> . ). results: two-hundred and twenty-three patients were included (disease-related death: n= / . %; censored: n= / . %; loss to follow-up: n= / . %). mean follow-up was . years. if tested separately, cr analysis identified significant potential both for breast mri and classical prognostic factors to predict diseaserelated death (p < . ). if breast mri characteristics and classical prognostic factors were used in combination, predictive performance could be further increased significantly (p < . ): after feature selection five classical prognostic factors (tnm stage, tumour typing, her neu score) and six breast mri characteristics (hot-spot: time to peak enhancement, washout ratio; d analysis: tumour volume; tumour voxels showing washout plus weak/intermediate washin and tumour voxels showing plateau and weak washin) remained in this final model as significant and independent coefficients (p < . ). conclusion: breast mri has a significant potential to predict disease-related death in breast-cancer patients. it not only can be used as a stand-alone tool for this task but also adds significant predictive value to classical prognostic factors to stratify this endpoint. s a c d e f g b thursday metabolic syndrome, diabetes and cardiovascular disease. there is a need to find a biomarker which proves to be reliable, non-invasive and easy to perform in clinical practice. methods and materials: our aim was to know whether serum alanine aminotransferase (alt) is a reliable biomarker of liver fat content in nafld, and to determine if the current threshold of normality for alt is appropriate to assess the presence of liver fat. this is a cross-sectional, randomised, prospective, population-based study. we studied healthy subjects with alcohol consumption less than g/ week. quantification of liver fat content was by spectroscopy h mr t. % of liver fat content as the upper limit of normal for the diagnosis of hepatic steatosis. results: there was an excellent positive correlation between liver fat content and serum levels of alt (r = . , p < . ). results of the backward step-wise regression analysis showed that serum alt was the most important predictor of hepatic steatosis (ß coefficient= . ). all subjects with alt values > u/l had hepatic steatosis (ppv: %) and none of the subjects with alt < u/l had steatosis (npv: %). roc curves were created; the best cut-off value for the diagnosis of nafld was alt: u/l (sensitivity: . %, specificity . %, ppv: . %, npv: . %). conclusion: serum alt levels could be a reliable biomarker of nafld if the upper limit of normal for alt is set at u/l. absolute quantification of phosphorus compounds in the liver on a clinical t scanner purpose: hepatic energy metabolism plays an important role in insulin resistance and liver diseases. the aim was to establish a robust and fast method to detect and to quantify liver atp content in molar concentrations for use in a clinical setting, i.e. large cohort studies. methods and materials: healthy volunteers (n= ; ± years; bmi: . ± . kg/m²) consented to the approved protocol. all experiments were performed on a -tesla mri scanner (philips achieva . t x-series, the netherlands). p spectra were acquired using a -cm diameter p surface coil, with the built-in h body coil used for noe enhancement and decoupling (tr: sec; acquisition time: minutes). localisation in the liver was achieved using isis. separately, intra-and interday variability were measured on volunteers. the absolute quantification was established using matching phantoms and an external reference (mpa). results: all peaks were well resolved with the mean snr (γ-atp) of . the concentrations were found to be . ± . mmol/l (phosphomonoester), . ± . mmol/l (phosphodiester), . ± . mmol/l (inorganic phosphate) and . ± . mmol/l (γ-atp). the intra-and interday reproducibility was . %, respectively, % (pme) %, respectively, % (pde), %, respectively, % (pi) and %, respectively, % (γ-atp). conclusion: the absolute quantification for large cohort studies has been successfully established on a clinical scanner. the obtained concentrations from this study agree with the concentrations from previous studies. thus, the current method can reliably detect concentration changes above % in phosphorus compounds in human liver. differential portal venous flow response to terlipressin in normal and cirrhotic rats: non-invasive assessment using phase-contrast mri m. chouhan, a. bainbridge, n. davies, r. mookerjee, r. jalan, s. walker-samuel, m. lythgoe, s. punwani, s.a. taylor; london/uk (manil.chouhan@gmail.com) purpose: portal venous flow (pvf) measurement using phase-contrast mri (pc-mri) is technically feasible at . t. the purpose of this study was to assess the sensitivity of pc-mri to expected changes in portal flow after terlipressin administration and study the functional response in normal and cirrhotic rats. methods and materials: eight sprague-dawley rats were randomised to bile duct ligation (bdl) procedure (n= ) or sham laparotomy (n= ). after weeks, pvf was measured using respiratory-gated d pc-mri ( mm slice thickness, ° flip angle and cm/s velocity encoding) with a . t agilent system. terlipressin (known to reduce pvf) was administered intravenously at a dose of mcg/ g and pc-mri measurements repeated sequentially for - minutes post-administration. bulk pvf was normalised to explanted liver weight, obtained after termination of the experiment. data were analysed using paired and unpaired student t-tests. results: baseline liver weight normalised mean pvf in sham ( . ± . ml/ min/ g) vs bdl ( . ± . ml/min/ g) rats was not statistically significant (p= . ). the reduction in pvf post-terlipressin was significant in sham (mean reduction of . ± . ml/min/ g; p < . ), but not in bdl (mean reduction of . ± . ml/min/ g; p= . ) rats. significant differences in post-terlipressin nadir pvf in sham ( . ± . ml/min/ g) vs bdl ( . ± . ml/min/ g) rats were, however, demonstrated (p < . ). conclusion: expected reductions in pvf were detected non-invasively using pc-mri in both normal and cirrhotic rats. data are suggestive of a lower baseline pvf in cirrhotics, which go on to demonstrate a different, more labile haemodynamic response to terlipressin compared with normal rats. the incidence of biological effects from . tesla (t) mri compared to . t: an observational study in consecutive outpatients f. alghamdi, p. bertrand, l. barantin, m.a. lauvin, x. cazals, f. domengie, r. bibi, d. herbreteau, j.-p. cottier; tours/fr (faisal.gh. @gmail.com) purpose: to compare the acute biological effects of a . tesla (t) magnetic resonance imaging (mri) to . t mri methods and materials: after mri examination, patients ( with . t mri and with . t mri) were presented with a verbal rating scale questionnaire consisting of symptoms related to mri examination. chi-square tests were used to assess the relationship between the strength of the magnetic field (mf) and the incidence of the symptoms. a p value of <. was considered significant. results: there was no statistically significant relationship between the strength of the mf and the incidence of the symptoms related to static mf exposure, such as vertigo (p =. ), nausea (p =. ), headache (p =. ), and a metallic taste (p =. ). a warm feeling induced by radiofrequency (rf) was significantly higher in the . t mri (p <. ) with a significant correlation between the mean specific energy absorption rate (sar) and a warm feeling in the . t mri (p <. ). numbness/ tingling related to the gradient mf was significantly higher in the . t mri (p =. ). conclusion: the thermal effect induced by the rf and the numbness/tingling induced by the gradient field were significantly higher in the . t mri than in the . t mri. there was no statistically significant difference between the symptoms related to static mf exposure from the . t mri and . t mri. double echo sequences both effects can be separated one from the other. we present an extension of this concept to multi-echo measurements. methods and materials: brain perfusion measurements were performed in patients as part of an ongoing study investigating the reproducibility of perfusion parameters on a tesla mr scanner (siemens magnetom verio). three slices were recorded with a temporal resolution of s by means of a four echo flash sequence (tr = ms, te = . / / / ms, alpha = ¼ °). evaluations of contrast to noise ratios (cnr) during the bolus passage of omniscan (ge healthcare) through different tissues were done with an inhouse software written in idl (exelis vis). results: the cnr is improved by a factor of about . calculating delta-r * from four echoes compared to calculations based on two echos. signal intensity estimations for te = do not significantly benefit by the increased number of echoes. conclusion: multi-echo measurements allow for a larger dynamic range of t * shortening compared to single or double echo sequences, at the same time giving more signal. by extending the concept to keyhole and/or epi sequences, covering of entire tumours could be achieved. we select patients with uni-or bi-lateral endoprostheses from consecutive referrals for whole body (wb) pet/mr imaging (mmr, siemens healthcare). simultaneous wb-pet/mr scanning was performed at min p.i. of mbq [ f ]-fdg: min/bed including dixon water fat segmentation (dwfs)). mr-ac was performed using a) original mr-images (dwfs), b) as a) with implant-induced air-pockets filled with soft-tissue, c) as b) superimposed with co-registered endoprostheses from ct and d) as a) with implant-induced airpockets filled with metal. pet reconstruction after mr-ac (a-d) used aw-osem ( iterations, subsets, mm gaussian) on -matrices. mean/max standardised uptake value (suvbw) was calculated from interest volumes with % isocontour levels over the hips, pelvic muscle and bladder. results: in patients we found and uni-and bi-lateral endoprosthesis, respectively. associated mr artefacts were much larger than the implants: . % versus . % of the attenuating voxels in (a) of the central hip region. mr-ac using (b) and (c) recovered fdg-distribution pattern compared to uncorrected pet (noac) images and (a), while (d) resulted in severe overestimation (> % suvmax). the relative changes in suvmax/mean in the reference regions (bladder, pelvic muscle) from (b-d) compared to (a) were insignificantly small. conclusion: endoprostheses cause pet/mr artefacts and bias pet quantification. artefacts and bias can be corrected by automated inpainting with a single softtissue composition prior to mr-ac, thus restoring quantitative activity distribution. author disclosures: t. beyer: founder; cmi-experts gmbh. in vitro comparison of ultrasound-based elastography techniques s. franchi-abella , j.-m. correas , c. elie ; le kremlin-bicêtre/fr, paris/fr (stephanie.franchi@bct.aphp.fr) purpose: ultrasound elastography techniques are based on two different physical principal: strain and shear wave velocity (swv). the purpose of this study was to assess the performance of these two techniques in vitro on a calibrated elasticity phantom using five ultrasound diagnostic imaging system to improve clinical comprehension and use of elastography. an operator performed all acquisitions on a tissuemimicking phantom developed for elastography calibration (cirs a) containing spherical inclusions embedded in an homogeneous background (bg) of known elasticity ( ± kpa). two inclusions were harder than the bg and two were softer ( ± kpa, ± kpa, ± kpa and ± kpa). protocol was performed using high-frequency linear transducer on four different inclusions. qualitative assessment was done on elastograms. semiquantitative measurements were based on the ratio of strain or elasticities between the bg and each inclusion and were compared with theoretical ratio. quantitative evaluation was performed with swv techniques. results: all techniques are adequate when assessing whether or not an inclusion is harder or softer than the bg. semi-quantitative ratio of stiffness between two structures is not reproducible and strongly depends on the manufacturer. it is more accurate for swv techniques. direct quantitative evaluation of stiffness using swv exhibits biases for soft targets but can still be used to precisely measure stiffness if bias is taken into account. conclusion: limitations and advantages of the different elastography techniques must be known while performing an elastography acquisition in clinical practice. static magnetic fields in . and t mr scanners do not influence perception of pain and touch compared with placebo exposition a. pomschar, k. kamm, r. ruscheweyh, r. laubender, m.f. reiser, a. straube, b. ertl-wagner; munich/ de (andreas.pomschar@med.uni-muenchen.de) purpose: potential biological effects of static magnetic fields have been in the focus of public debate with the european physical agents (electromagnetic fields) directive / /ec having the potential to seriously limit mr imaging in europe. data on potential effects are still very scarce. we aimed to investigate the influence of homogeneous static magnetic fields in . and tesla mr scanners on pain and touch perception compared with placebo exposition. methods and materials: healthy volunteers (age: ± . years, females) underwent three experimental sessions on separate days in randomised order, using field strengths of t (placebo scanner), . t and t. participants were blinded to field strength. no imaging sequences were acquired. in each session, a quantitative sensory and pain testing programme was performed before and after a -min exposure to the static magnetic field. it included thresholds for mechanical detection, mechanical pain, pressure pain, heat pain and phasic heat pain intensity ratings. a linear mixed-effects model was used for statistical analysis. results: for . and t compared with the placebo control, statistical analysis revealed no significant effect of the magnetic field for all tested qualities, thresholds for mechanical detection (p= . / . ), mechanical pain (p= . / . ), pressure pain (p= . / . ), heat pain (p= . / . ) and phasic heat pain intensity ratings (p= . / . ). conclusion: short exposure to static magnetic fields in clinical . t and t mri scanners had no significant effect on pain and touch perception compared with a placebo exposure. plaque has formed correlating with cardiovascular risk factors. the present study aims at investigating whether there are differences in the carotid wall thickness and echogenicity between patients with ibd and well-matched healthy controls by high-resolution ultrasonography of the carotid arteries. methods and materials: ibd patients ( male, mean age: . yrs, crohn/ ulcerative colitis: / , smokers) and healthy controls ( male, mean age: . yrs, smokers) underwent high-resolution ultrasonography of the carotid arteries. the following variables were recorded in bilateral common carotid arteries: ) imt at , and mm from the carotid bulb, ) emt (the distance between the common carotid wall and the internal jugular vein) and ) ec. results: common carotid artery imt ( . < p < . , t-test) and emt (p < . , t-test) were significantly higher in ibd patients compared with controls. no difference in ec was found between ibd patients and controls. no difference in imt, emt and ec was found between crohn's and ulcerative colitis patients. smokers ibd patients had significantly higher imt and emt values than smokers controls ( . < p < . , t-test). conclusion: ibd appears to be a risk factor for development of early atherosclerosis as showed by greater values of carotid imt and emt in ibd patients compared with healthy controls irrespective of smoking history and type of ibd disease. purpose: to evaluate the accuracy of the preliminary ct interpretation made by the radiology residents in the emergency department. during four periods of consecutive days, attending radiologists prospectively recorded any disparity between their own ct interpretation (reference standard) and the preliminary interpretation delivered by the emergency radiology residents. disparities were recorded during both regular hours and on-call time. a misinterpretation was considered major when potentially life-threatening within hours after admission. the total number of ct performed during the survey was recorded and further classified into neuroradiological and body examinations. a rate of disparities was calculated for all ct examinations and also for body and neuroradiological cases. results: a total of emergency ct examinations were performed during the survey: ( %) were body ct and ( %) neuroradiological cases. disparities were reported in ( . %) of all ct examinations: . % ( / ) were major misinterpretations ( body, neuro). there were / ( . %) disparities reported in body ct versus / ( %) in neuroradiological examinations (p= . ). no significant difference was found when comparing disparities recorded during regular working hours ( / ( . %)) versus on-call period ( / ( %)), p= . . our results show that disparities occur most frequently in emergency body ct examinations, but major disparities represent a small proportion of all misinterpretations. the detailed analysis of our data allows comparison and purpose: detection of abdominal injury is a very important component in trauma management, so an accelerated assessment of liver and spleen injuries including their degree of severity is necessary. there is a good case to believe that in stress situations this subjective performance results in diagnostic mistakes. structured objective scores as the organ injury scale (ois) drawn up by the aast are a valuable guidance for objective trauma assessment. aim of our study was to evaluate retrospectively whether a structured approach using the ois differs to real-time-diagnosis. methods and materials: the ois was applied by an experienced radiologist on ct data of patients which underwent ct laparotomy after abdominal trauma. these results were correlated with the original text of the initial ct findings. finally, we compared both with the intraoperative findings gathered from the surgery report. results: regarding the original ct report we found a mean divergence of . ± . to the ois found in the surgery report for liver injuries ( . ± . for spleen injuries). in comparison with the structured approach, where we detected a divergence of . ± . ( . ± . for spleen injuries). there was no significant difference, but we detected a lower rate of over-diagnoses in both approaches. conclusion: a structured approach to abdominal trauma using an imaging checklist does not lead to a significantly higher detection rate, but reduces the rate of overdiagnoses and may be more precise in grading the severity grade plus streamlines the emergeny-ct-procedure. comparison of efficacy and safety between distal embolisation and augmented embolisation techniques for treating blunt splenic injuries with active haemorrhage within a two-year period, consecutive patients of bsi in whom haemodynamics was stable but ct showed contrast extravasation were included in this prospectively study. we randomised them into distal embolisation group and augmented embolisation group. they were followed up twice by ct at week and months after embolisation. we compared their demographics, injury grades, clinical parameters, hemograms, successful rates and splenic infarct volumes between the two groups. embolisation failure was defined as persistent hypotension that required surgery or detection of splenic contrast extravasation on follow-up ct. complication was defined as post-embolisation splenic infarct or splenic abscess. results: all underwent first follow-up ct, underwent second follow-up ct. of patients, received distal embolisation, received augmented embolisation. their basic demographics, ct injury grades, clinical parameters and hemograms did not differ. their mean systolic blood pressure was significantly elevated after embolisation. two ( / , %) of the distal embolisation group failed and required a second augmented embolisation. none of the augmented group failed but the difference did not reach statistical significance. the mean splenic infarct volume purpose: to evaluate whether radiographers' experience in breast imaging helps in reducing significant artefacts when acquiring dynamic breast-mri. methods and materials: one experienced radiologist prospectively evaluated a total of breast-mri examinations performed by three different radiographers (r , r and r ) over the period september -june ( examinations each). r had a -year experience in breast-mri and years of experience in breast imaging; r and r had no specific training in breast imaging, and -(r ) and -year (r ) experience in breast mri. for each examination the radiologist, who was blinded to radiographer's experience, was asked to assess the presence or absence of significant artefacts, defined as motion artefacts affecting image quality and/or diagnostic evaluation. the prevalence of significant artefacts in r , r and r examinations was tested with the chi-square test. results: significant artefacts were found in / examinations ( . %;ci %= . - . %). in particular, significant artefacts affected / examinations ( . %;ci %= . - . %) performed by r , / examinations ( . %;ci %= . - . %) performed by r and / ( . %, ci %= . - . %) performed by r , with a significant difference between r and r (p < . ). conclusion: artefacts potentially affecting image quality and diagnostic evaluation are less frequent in breast-mri examinations performed by those radiographers who combine experience in breast imaging with specific experience in breast-mri. a possible explanation is a better understanding of disease specific problems and of the importance of empathise with the patient. accuracy of ultrasonographic diagnosis of acute appendicitis in pregnant women n. kokhanovsky, a.-r. zeina, n. reindorp, a. levit-kantor, y. glick, a. nachtigal; hadera/il (nataliakoh@hotmail.com) purpose: to assess the reliability and value of the sonographic examinations in the diagnosis of acute appendicitis in pregnant women. we obtained sonographic examinations performed on pregnant women with suspected acute appendicitis retrospectively for months (sep. -feb. . the average age of study subjects was . years, with an average gestational age of weeks. sonography was the first imaging modality employed. surgery or clinical follow-up was the gold standard for the evaluation of sonographic performance. all examinations were performed using grey-scale graded compression in the left lateral decubitus position. the sonographic criteria for acute appendicitis were detection of a noncompressible, blind-ended, tubular, structure measuring greater than mm in maximal diameter. results: patients had positive sonographic findings of acute appendicitis ( . %). sonographic findings were correlated with surgical findings and clinical follow-up. the diagnosis was confirmed in all patients ( %). in the patients with negative sonographic findings of acute appendicitis, the result for patient ( . %) proved false-negative, whereas the remaining ( . %) improved on clinical follow-up. accordingly, sensitivity was . %, specificity was % and overall accuracy was . %. moreover, in out of the patients with negative sonographic findings for acute appendicitis, a different pathologic finding such as acute pyelonephritis was identified. conclusion: our experience suggests that ultrasonographic examination with the optimal study protocol is a highly accurate method for the diagnosis of acute appendicitis in pregnant women and should be performed as the first imaging test. purpose: to exploit the ever increasing quantity of routinely acquired imaging data generated in clinical practice for research, we propose an infrastructure for the automated anonymization, extraction and processing of image data stored in clinical data repositories. methods and materials: as proof of principle, we used this infrastructure to implement a pipeline for measuring brain volumes in clinical mri. this fully automated system consists of four steps: subject selection using pacs query, anonymization of privacy sensitive information and removal of facial features, quality assurance on dicom header and image information, and biomarker extraction. examinations were selected based on mri protocol: dementia ( ), multiple sclerosis ( ) and a general healthy elderly population study ( ) . we evaluated the effectiveness of the infrastructure in accessing and successfully extracting biomarkers from routinely acquired clinical imaging data. to prove the validity, we compared brain volumes from dementia and multiple sclerosis patients with the healthy population. results: success rates of . %, . % and % are achieved for the three protocol groups, respectively, indicating large amounts of routinely acquired clinical imaging data can be used for research purposes. in line with the literature, tive statistics, t-student tests for comparing groups, and mann-whitney tests for verifying hypothesis and item relations. results: most radiographers completely agree ( . %) or partially agree ( %) that evidence-based radiology makes part of their job requirements, but only . % consider it absolutely useful for developing their skills. most research projects and papers ( . %) are done by radiographers during their degree to develop their knowledge and quality of services rendered. age and academic degree do not have statistical significance (p < . ) for evidence-based radiology; however, there is a slight increase for radiographers with higher academic degrees and for those who have greater access to research papers and literature. conclusion: evidence-based practice is not applied by most radiographers as a work method; however, the underlying knowledge on this thematic suggests it would be well received and developed to enhance skill, knowledge and the department general quality. radiographers quality assurance work: resistance and cooperation r. gullien, j.g. andersen, a.e. haakull; oslo/no (uxraul@ous-hf.no) purpose: explaining the radiographer-chosen improvement initiatives in quality assurance work (qaw), adjustment and progression of these initiatives and changing possible resistance to cooperation. methods and materials: different implementation strategies and improvement initiatives were used in the qaw to prevent a feeling of insecurity, threatening, uneasiness, less valuable, to avoid conflicts and to enable education, training, self-assessment, improve oneself. manager implements measurements, strategies and improvement initiatives. the employees came up with suggestions of actions, brainstorm. voting was performed and top three were selected. combination of suggested and specific initiatives over time: continuous individual feedback over time (baseline, after implementation, follow-up), individual assessment measured by experience in mammography, theoretical and practical training, lectures, examples, individual positioning training, reading guidelines and articles, individual feedback on positioning technique, tailored training for new employees, different checklist for employees (new/"old", inexperienced/experienced), checklist for updating knowledge, self-study, workshops, training in self-evaluation, new internal guidelines, frequent feedback if necessary, practical training with supervisor, temporarily get another kind of work, meetings and discussions, inform about qaw when job interview. results: positive changes in cognition, self-knowledge, personal skills, confidence in the situation, comfortable, demystified, attitude change; related to knowledge and awareness. teamwork manager and employee with focus on improvement work and differentiate between work and employee. conclusion: using various strategies are beneficial, different methods to meet different needs. top-down, bottom-up, threat-relaxation, tentative-participation, resistance-cooperation. dialogue and cooperation between staff and management; between the radiographers are essential for success. radiographers' knowledge about adverse reactions to iodinated contrast media a. santos, l. capitolina, i. silva, a. saraiva; coimbra/pt (adelinosantos@estescoimbra.pt) purpose: eudravigilance-pharmacovigilance is a data processing network and management system for reporting and evaluating suspected adverse reactions of medicinal products in the european economic area. the main purpose of this paper is to assess the level of knowledge of radiographers relatively adverse reactions of iodinated contrast media (icm). methods and materials: an original electronic survey was used, which is composed of four dimensions of study to gauge radiographers' knowledge regarding the chemistry of icm (i), potential adverse reactions (ii), possible procedures to be taken in emergency situations (iii) and actions to be taken under the national pharmacovigilance system (iv), in a first phase. and throughout various european countries (northern, central and mediterranean), in a second stage. results: only . % of respondents were able to correctly answer the four questions on chemistry of icm. however, a significant relationship between those who know the classification of adr and who has knowledge of chemistry icm still exists. concerning the procedures to be taken in case of adr, we found that only . % of subjects were able to correctly identify usual emergency procedures in this type of situation and, regrettably, only % of the sample proved able to correctly identify all adverse reactions suggested by the questionnaire. the only method that enables epidemiological continuing surveillance safety of all drugs is the spontaneous reporting of adverse events. this pioneer b- : fast search for radiology cases in hospital systems via contentbased image retrieval g. langs , r. donner , m. holzer , d. markonis , h. mueller , e. birngruber ; vienna/at, sierre/ch (georg.langs@meduniwien.ac.at) purpose: efficient and quick access to comparable cases and corresponding radiology reports is crucial during radiological assessment and increases quality. currently, in most cases search queries within a pacs are limited to meta data. brain volumes (expressed as percentages of intracranial volume) were found to be significantly smaller in patients scanned under dementia ( . %) and multiple sclerosis ( . %) protocols, when compared with healthy controls ( . %). conclusion: this demonstrates that quantitative image biomarkers can be reliably extracted from routinely acquired clinical imaging data. this enables secondary use of clinical images for quantitative biomarker discovery at a hitherto unprecedented scale. interactive methods improve radiology long-term learning j.c. pueyo, j. etxano, p. slon, r. zalazar, j. ros, l. garcía del barrio, g. bastarrika, a. villanueva; pamplona/es (jetxano@unav.es) purpose: personal remote response systems (clickers) have shown to be an interesting tool to encourage participation. the aim of this study is to evaluate whether the use of clickers improves learning and retention of radiology within a group of medical students. methods and materials: medical students attended radiology lessons. each lesson was about radiological images. at the beginning of each lesson, students have a pdf with all the images corresponding to that day. at the end of each lesson, there were five interactive questions of those images using clickers. three months later, there was an examination with multiple-choice questions. half of the questions were images that had already been interactively worked with clickers. the other half were images of the pdfs not worked with clickers. incorrect answer value was - . . to evaluate the difference in the degree of learning achieved between both methods, we analysed the index of correct and false answers of each group. results: the averages of the correct answers were significantly higher in the group of interactive teaching than in the passive education group ( vs %, p < . ). the percentage of incorrect answers of the interactive teaching group was significantly lower than in the other ( . vs. . p < . ). the percentage of unanswered questions was significantly lower in the interactive group ( % vs . % p < . ). conclusion: interactive learning with remote response devices (clickers) is an effective method in teaching radiology, because it significantly improves learning and retention of knowledge. purpose: to evaluate diffusion-weighted (dwi) and dynamic contrast-enhanced (dce) magnetic resonance imaging (mri) for diagnosis of recurrent papillary thyroid cancer (ptc) in comparison to ultrasound and peroperative and histopathological findings. methods and materials: twenty-eight patients with suspicion for recurrent ptc underwent t mri, including dwi (b= - - - - - sec/mm ) and dce-mri ( runs; seconds each; pre-, during and post-contrast). interpretation criteria were: b -dwi for detection of soft tissue lesions and lymph nodes (ln); characterisation with apparent diffusion coefficient (adc) calculated from all (adcavg), low (adclow) and high b-values (adchigh); characterisation by dce-mri with arterial slope (as), area under the curve (auc) and c-peak. the adc and dce-parameters of tumoural and benign lesions were compared with a mann-witney u test. receiver-under-the-operator-curve analysis determined a threshold from which the accuracy of functional mr-imaging was compared to ultrasound in correlation to histopathology. results: only adchigh and as showed statistical difference between recurrent tumour and benign lesions (adchigh: p= . ; as: p < . ). per-neck region, b -dwi combined with as yielded highest sensitivity of % with % specificity. ultrasound showed a sensitivity of % and specificity of %. per patient, functional mri corrected ultrasound in only patients for diagnosing tumour recurrence. however, functional mri findings correctly changed treatment planning in of patients [excluding tumour recurrence (n= ), mediastinal metastatic ln (n= ), laryngeal metastasis (n= ), ipsilateral nodal skip metastasis to level ii (n= ), contralateral nodal metastases (n= )]. conclusion: combining b -dwi with dce-mri may show additional value to ultrasound for diagnosing and planning treatment in recurrent ptc. diagnostic evaluation of patients with squamous cell cancer of the head and neck after free flap reconstructions -the usefulness of functional imaging techniques m. członkowski, a. trojanowska, p. trojanowski, j. klatka, a. drop; lublin/pl (m.czlonkowski@interia.pl) purpose: to evaluate patients operated on head and neck squamous cell cancer and reconstructed using free tissue transfer flaps methods and materials: we evaluated patients with t tumours of oral cavity, oropharynx, hypopharynx and larynx. all patients underwent surgical resection of the tumour and reconstruction with free tissue transfer flap: musculocutaneous, fasciocutaneous, osseous and osseocutaneous. patients underwent post-operative radiotherapy. in the whole group we performed ct and/or mr study , and months after the completion of therapy. in patients suspected for recurrence based on ct/mr findings, mr diffusion-weighted imaging and ct perfusion were additionally performed. in case of positive findings these patients were qualified for surgery. results: in out of patients imaging study was suggestive for recurrence ( nodal and local). in this group additional functional imaging was performed. mr dwi and ct perfusion findings were indicative of nodal recurrence in two cases and patients were operated on. recurrence was not proven on histology in either case. in patients with suspected local recurrence additional functional imaging was performed in cases and the recurrence has been proven histologically in cases. conclusion: we have to be aware that functional imaging may be of little value in patients reconstructed with free flaps. although diagnostic imaging plays a prime role in post-treatment follow-up, positive findings must be evaluated with caution. careful reading together with ent surgeon is vital. purpose: chronic bronchitis (cb) is usually caused by smoking and characterised by chronic inflammation and remodelling of the airway wall, commonly in large airways. the study purpose is to determine differences in airway wall thickness (awt) and wall area percentage (wa%) between subjects with and without cb symptoms. methods and materials: heavy smokers with cb symptoms (cough, mucus, dyspnoea and wheezing) and heavy smokers without cb symptoms were randomly selected from , participants in a lung cancer screening trial. airway walls were measured on images in thin-slice low-dose ct with a dedicated software tool, for airways with a luminal diameter ³ mm in selected bronchi (rb , rb , rb , lb + and lb ). differences in measurements between the groups were assessed by t-test. the association between cb symptoms and awt and wa% was analysed using multiple linear regression adjusted for age, body mass index, smoking habit, amount of emphysema, and lung function. results: mean awt measured at bronchi was . ± . mm and . ± . mm in subjects with and without cb symptoms, respectively (p < . ). wa% was ± % and ± %, respectively (p < . ). with adjustment for confounders, a significant positive association between both airway wall measurements (awt and wa%) and cb symptoms was found for airways with a luminal diameter from to mm (p < . ). in airways with a luminal diameter ³ mm, no significant association was found (p> . ). conclusion: patients with chronic bronchitis symptoms have thicker airway walls of airways between and mm diameter, not in larger diameter. value of inspiratory and expiratory lung volume und lung density for detection of bronchiolitis obliterans syndrome ( ). there was a significant lower variation between the different kernels using ir when compared to fbp. image noise was reduced by % when compared to fbp. conclusion: variation of quantitative emphysema chest ct parameters between different reconstruction kernels is significantly reduced with ir when compared to fbp and may increase the robustness for therapy planning. assessing pulmonary perfusion in emphysema: automated quantification of perfused blood volume in dual-energy ctpa f.g. meinel, a. graef, s.f. thieme, f. bamberg, c. neurohr, m.f. reiser, t.r.c. johnson; munich/ de (felix.meinel@med.uni-muenchen.de) purpose: to determine whether automated quantification of lung perfused blood volume (pbv) in dual-energy computed tomography pulmonary angiography (de-ctpa) can be used to assess the severity and regional distribution of pulmonary hypoperfusion in emphysema. we retrospectively analysed consecutive patients (mean age ± years) with pulmonary emphysema, no cardiopulmonary comorbidities and a de-ctpa negative for pulmonary embolism. automated quantification of global and regional pulmonary pbv was performed using the syngo dual-energy application (siemens healthcare). we further quantified the global and regional percentage of voxels with a ct density <- hu. emphysema severity was rated visually and pulmonary function tests were obtained by chart review. results: global pulmonary pbv showed a moderate but highly significant negative correlation with residual volume (rv) in % of predicted rv (r=- . , p= . , n= ) and a positive correlation with forced expiratory volume in second (fev ) in % of predicted fev (r= . , p < . , n= ). global pbv values strongly correlated with diffusing lung capacity for carbon monoxide (dlco, r= . , p < . , n= ). pulmonary pbv values decreased with visual emphysema severity (r=- . , p= . , n= ). moderate negative correlations were found between global pbv values and parenchymal hypodensity in a per-patient (r=- . , p < . , n= ) and per-region analyses (r=- . , p < . , n= ). conclusion: de-ctpa allows simultaneous assessment of lung morphology, parenchymal density and pulmonary pbv. in patients with pulmonary emphysema, automated quantification of pulmonary pbv in de-ctpa can be used for a quick, reader-independent estimation of global and regional pulmonary perfusion, which correlates with pulmonary function tests. author disclosures: t.r.c. johnson: equipment support recipient; siemens healthcare. research/ grant support; bayer healthcare. purpose: brain death has adverse effects on lung perfusion and ventilation with possible damage of lung parenchyma pre-transplantation. we wanted to assess brain dead subjects treated with a new drug regime with hrct as a pre-transplant work-up. methods and materials: eleven pigs were decapitated (dc) assuring brain death, attached to ventilator and treated with a new drug regime optimising circulation thereby preventing lung edema. thirteen non-decapitated pigs (n-dc) attached to ventilator, supported with conventional treatment served as controls. all were monitored h and thereafter examined with chest hrct. images were analysed by two radiologists using a pre-defined questionnaire assessing parenchymal and airway changes. in consensus, an overall conclusion inferred presence of edema, infection/atelectasis or airway pathology. severity was estimated with a subjective scale. results: after h there were no significant differences between the groups regarding mean arterial pressure (map), arterial oxygen/fraction of inspired oxygen (pao /fio ), amount of infused fluid, urine production or clinical signs of edema. out bos. lung volume (vol), mean lung density (mld), th , th , th , th , th percentile (p -p ), peak, full width half maximum (fwhm), percentage of high (>- hu, hav) and of low attenuation values lav) were assessed with dedicated software (mevis pulmo). measurements of patients with/without bos and patients without bos with normal (fev > % of baseline, bos )/slightly reduced values for fev (fev - % of baseline, bos -p) were compared with independent t-test. results: vol, mld, p , p , p , p , peak, and fwhm (p² . ) in expiration scan as well as difference in volume between inspiration and expiration (p < . ) were significantly different in patients with/without bos. in inspiration, p (p= . ), fwhm (p= . ) and lav (p= . ) showed significant differences at higher levels. comparing patients with bos and bos -p, p might be used for distinction (p= . ). conclusion: expiratory lung volume and density showed significant differences in patients with/without bos. p value might be used as an imaging biomarker for early detection of bos. author purpose: the aim of this study was to prospectively evaluate the diagnostic value of density mappings for detection of bos following lung transplantation. methods and materials: ct examinations were carried out in lung transplant patients in full inspiration / expiration using a -row mdct ( kvp, rotation time . s, pitch . , collimation . mm, reconstruction increment mm, standard reconstruction kernel). / examinations were performed in patients with / without bos (bos : , bos p: , bos : , bos : , bos : ). the assessment of at was performed using both, a threshold-based method in expiration (hu range: - hu to - hu) and density mappings of hu values in inspiration and expiration after registration applying a threshold of - hu to - hu and hu differences ² hu between expiration and inspiration. with both methods, measurements of patients with / without bos were compared with independent t-test. results: at quantified with density mappings was significantly different in patients with / without bos. mean at was % in patients with bos and % in patients without bos. comparing patients with and without bos at might be used for distinction (p= . ). at quantified with the standard threshold-based method also showed differences between both groups, but with a lower significance (p= . ). conclusion: measurement of at with density mappings of hu-values showed a significantly better distinction between patients with / without bos than the standard threshold-based method. non-invasive focal therapy of organ confined prostate cancer: phase i study using magnetic resonance guided focused ultrasound technology and excision pathology for efficacy assessment a. napoli, v. panebianco, m. anzidei, f. boni, v. noce, l. bertaccini, g. cartocci, f. ciolina, c. catalano; rome/ it (alessandro.napoli@uniroma .it) purpose: to assess safety and initial effectiveness of non-invasive high-intensity t mr-guided focused ultrasound (mrgfus) treatment of localised prostate cancer in a phase i, treat and resection designed exploratory study. methods and materials: on the basis of a power analysis, patients with biopsyproven focal t prostate cancer (low-to-intermediate risk: gleason max + ), confirmed on a previous multiparametric mr exam, including dynamic contrast enhanced (dce) imaging, underwent mrgfus. all patients were scheduled to laparoscopic prostatectomy; mrgfus treatment was carried out on mr identifiable lesions (max ) using a patient-specific energy and real-time mr thermometry monitor for correct location. non-perfused volume (vpv) in the post-ablative mri was than compared with excision pathology for necrosis assessment. results: no significant complications were observed in all subjects during or immediately after the procedure. procedure was validated by pathologist that demonstrated extensive coagulative necrosis at the site of sonication surrounded by normal prostatic tissue with inflammatory changes; these features positively compared with immediate post-ablative mri scan and npv. at histology patients were free of residual viable tumour within the treated area; in the remaining patient, % of residual tumour was observed within the npv. there was a variable amount of isolated cancer tissue within non-treated parenchyma that was identifiable neither at mri nor at biopsy. to determine the impact of axial traction during mr imaging of the ankle cartilage at . t in volunteers with respect to motion artefacts, image quality and cartilage surface delineation. methods and materials: optimised coronal and sagittal t -weighted (w) turbo spin echo (tse) sequences with a drive pulse (in-plane spatial resolution . mm), a sagittal fat-saturated intermediate-weighted (imfs) tse sequence and a d gradient echo sequence were acquired at . t in volunteers with and without axial traction of kg. joint space width was measured at four locations in the tibiotalar joint. motion artefacts, general image quality, delineation of the cartilage surface, cartilage matrix and the confidence of diagnosing cartilage pathology were evaluated independently by two radiologists. differences were assessed using a wilcoxon test. results: with axial traction, joint space width increased significantly ( . ± . mm vs. . ± . mm). consequently, delineation of the cartilage surface was rated superior in / volunteers (p < . ). no differences were found in motion artefacts, general image quality, and artefacts within the cartilage matrix (p> . ). comparing the different sequences, cartilage surface and matrix was best visualised by the t -w tse sequences with a drive pulse (surface average of all regions and readers in sag t -drive vs. imfs on a four-point scale . ± . vs. . ± . , p < . ). conclusion: axial traction of kg increases the joint space width at the tibiotalar joint, and thus better visualises the articular cartilage surface. highest spatial resolution and visualisation of both cartilage surface and matrix were achieved by a t -w tse sequence with a drive pulse. s c a d e f g b results: all affected subjects were women between and years old (mean age: ). ischiofemoral space was significantly narrower in patients with ischiofemoral impingement when compared with control subjects ( . ± . mm vs . ± . mm, respectively; p < . ). quadratus femoris space was also significantly narrower in affected subjects ( . ± . mm vs . ± . mm; p < . ). inclination angle was not statistically different (p> . ). the degree of oedema and fatty infiltration was inversely proportional to values of ischiofemoral and quadratus femoris space. the interobserver agreement (ĸ) was . for ischiofemoral space, . for quadratus femoris space and . for inclination angle. conclusion: ischiofemoral impingement can be accurately diagnosed following anatomic and imaging mr criteria. us-guided viscosupplementation of the hip: therapeutic efficacy in patients affected by femoro-acetabular impingment c. martini , f. lacelli , e. fabbro , g. ferrero , g. serafini ; genoa/it, pietra ligure/ it (chiarapio@libero.it) purpose: us-guided viscosupplementation is a safe and effective therapy for symptomatic osteoarthritis (oa) of the hip and it allows to replace nsaids therapy and to delay prosthetic intervention. femoro-acetabular impingement (fai) is a cause of oa. the purpose of this work is to evaluate the efficacy of viscosupplementation as therapy of oa in patients affected by femoro-acetabular impingement. methods and materials: patients selected by orthopaedists for hip pain and plain films signs of oa (degrees ii-iv of k-l) underwent viscosupplementation ( ml of intermediate weight hyaluronic acid for three times every days). each patient was evaluated before the treatment and , , and months after the treatment by means of vas and oxford score. hence, these patients were divided into responsive (increase oxford score=/> and/or reduction vas /> ) and non-responsive (increase oxford score< and/or reduction vas < ). then we retrospectively evaluated the plain films of the hip these patients had done before the therapy, in order to find the signs of fai. results: / ( . %) patients were included into the "responsive" group; / ( . %) in the "non-responsive" one. in the "responsive" group we found signs of fai on the plain films of / patients ( . %); in the "non-responsive" in / ( . %). conclusion: despite viscosupplementation is an effective therapy of oa, there is an high prevalence of non-responsive among patients affected by fai. a new way to measure lower limb length and alignment using d models based on biplanar linear radiography: a comparison with measurements on supine ct scans and upright full-length radiographs r. guggenberger, c.w. pfirrmann, p. koch, f. buck; zurich/ch (romanguggenberger@yahoo.de) purpose: to compare lower limb length and alignment angle on supine computed tomography (ct), upright full-length radiography (ufr) and d models based on upright biplanar radiography (blr). methods and materials: irb-approved study involving consecutive patients ( male, female; mean age . years; range - years) scheduled for total knee replacement. lower limb length and alignment angles were measured on ct, ufr and d models based on blr using standard and extended length measurements by two independent readers. measurements of different modalities were compared by paired t-tests, pearson correlation coefficients and bland-altman analyses. results: mean limb lengths were mm (sd± . mm, range - mm), mm (sd± . mm, - mm), mm (sd± . mm, - mm) and mm (sd± . mm, - mm) for ct, ufr and d models using standard and extended measurements, respectively. mean alignment angles were . ° (sd± . °, range - °- °), . ° (sd± . °, - °- °), . ° (sd± . °, - °- °), respectively. length and angle measurements differed significantly when comparing standard d models to ct and ufr, respectively (p < . ). pearson correlation coefficients were . , . , . and . for limb length and . , . and . for angle measurements in ct, ufr and d models, respectively. bland-altman analyses for ct and ufr compared to d models showed a small positive mean difference in length using standard measurements ( . mm, sd± . ; . mm, sd± . ) and a small negative mean difference in angle measurements (- . °, sd± . ; - . °, sd± . ). no bias for length measurements was seen using extended measurements. conclusion: upright d models allow for lower limb length and alignment angle measurements comparable supine ct scans and ufr. stable or unstable tear of the medial meniscus of the knee: can weight-bearing mri solve the problem? a. la marra, s. mariani, e. costantini, a. conchiglia, a. barile, c. masciocchi; l'aquila/ it (alicelm@hotmail.it) purpose: to assess the role of . t, dedicated low-field standard and upright-mri in the evaluation of stable or unstable tears of medial meniscus in comparison with arthroscopy. we retrospectively reviewed and analysed mri exams (group a) of normal knee and mri exams (group b) of knee with clinical evidence of tears of the medial meniscus. in the same session, after conventional . t and "dedicated" . t supine mri exam, the patients underwent upright weight-bearing examination with the same dedicated mri unit. in all cases sagittal and coronal se t -w were used. all patients underwent arthroscopy within days from mri exam. results: in group a, no statistically significant anatomical modifications of shape, intensity and position of the medial meniscus between standard . t, dedicated supine and upright mri were observed. in group b, the images acquired in the supine position (dedicated and . t mri) documented in cases a traumatic tear (group b ) and in cases a degenerative tear (group b ). in group b , weightbearing mri showed presence of unstable tear only in out cases. in group b , weight-bearing mri showed a degenerative unstable meniscal tear only in out of cases. arthroscopy confirmed weight-bearing mri diagnosis in all cases. conclusion: our preliminary results show that upright weight-bearing mri has wide potentials for the study of dynamic modifications in case of meniscal stable or unstable tear. periosteal high volume image-guided injection of recalcitrant medial collateral ligament injuries: a retrospective case series analysis o. drumm, o. chan, p. malliaras, d. morrissey, n. maffulli; london/uk (odrumm@yahoo.co.uk) purpose: we evaluate a novel injection method, periosteal high volume imageguided injection, in the management of recalcitrant medial collateral ligament (mcl) injury of the knee. the injection, comprising ml of local anaesthetic with - mg of hydrocortisone, is directed at the periosteal attachment of the mcl. patients in total received the intervention between june and november at a london hospital. each was asked to complete a study-specific questionnaire including a visual analogue scale (vas) and the international knee documentation committee (ikdc) subjective knee form (to describe symptoms pre-injection and at follow-up). results: % of patients responded (n= ). three patients were omitted according to the exclusion criteria. . % of patients (n= ) were professional athletes. mean duration of symptoms was . (sd= . ) months. patients reported a mean improvement on the vas of . % (sd= . ). there was a significant improvement in ikdc scores (mean difference of %, sd= . ) pre-and post-injection (p= . ). . % of patients (n= ) had returned to their previous level of sport at follow-up including all the professional athletes. knee symptoms returned to normal in % (n= ), and improved substantially in a further . % (n= ). the remaining . % (n= ) experienced an initial improvement but symptoms recurred. conclusion: periosteal high volume image-guided injection is a useful treatment for recalcitrant mcl injury, a common sports injury that can result in lengthy periods of missed training and competition. results are encouraging, particularly amongst the professional athletes studied. ischiofemoral impingement, do you want to believe? r. prada, r. oca, a. rocha, l. fernández, m. costas, g. tardáguila; vigo/es (roqueoca@hotmail.com) purpose: to find out if there are anatomic and imaging mr criteria to diagnose ischiofemoral impingement. methods and materials: mris of the hip were retrospectively reviewed from august to september . a total of ischiofemoral impingement were diagnosed and normal patients were included as control. ischiofemoral space, quadratus femoris space and femoral inclination angle were measured independently by two blinded musculoskeletal radiologists. the degree of oedema and fatty infiltration in the quadratus femoris muscle were also assessed visually. differences in ischiofemoral space, quadratus femoris space and femoral inclination angle were studied between pathological and control cases. the interobserver reliability was obtained for quantitative variables. purpose: to assess the value of oral effervescent powder administration for ct evaluation of the oesophagus, quantitatively and qualitatively. methods and materials: patients ( m/ f, mean age y) referred for thoracoabdominal staging ct were included in this prospective irb-approved study. contrast-enhanced imaging was performed on a -slice ct-scanner after oral administration of g effervescent powder immediately before image acquisition. oesophageal distension was assessed at three levels (proximal/middle/distal) by volumetry of the inner (id) and outer diameter (od). two blinded readers separately evaluated oesophageal distension in the corresponding segments on a three-point scale. at an interval of two weeks, both readers in consensus decided on the number of diagnostic oesophageal segments in each patient in terms of the possibility to decide upon a potentially underlying pathology. findings were compared with results from a matched control group. quantitative and qualitative results were compared (t-test, mann-whitney u test). inter-observer variability was calculated (weighted-cohen-κ). results: id and od were significantly larger in all oesophageal segments after effervescent powder administration as compared to the control group (p < . ; mean id: . vs. . , mean od: . vs. . ). further, oesophageal distension was rated significantly better, with a good inter-observer variability (mean weighted κ= . ). at consensus evaluation, oesophageal segments ( %) were rated as diagnostic in the effervescent group, versus segments ( %) in the control group (p < . ). conclusion: correctly timed oral administration of effervescent powder results in good distension of the oesophagus, allowing readily assessment of the wall at contrast-enhanced ct as compared to studies without effervescent powder. de (marcandre.weber@med.uni-heidelberg.de) purpose: to prospectively evaluate whether dynamic contrast-enhanced (dce) mri can assess vascularity within pseudarthrotic clefts and predicts clinical outcome better than the clinical non-union scoring system (nuss). methods and materials: sixty-four patients (mean age, . years) with nonunion of an extremity fracture in computed-tomography received -tesla mri including dce (coronal t -weighted fat-saturated vibe, tr/te= . / . ms, measurements, mm slice thickness) after . mmol/kg body-weight of gadoterat. we assessed vascularity within the pseudarthrotic cleft using a region-of-interest analysis. signal intensity curves were subdivided into those with more intense contrast-agent uptake in the pseudarthrotic cleft than in normal adjacent muscle tissue (vascularised non-union) and those with similar or less uptake. the pharmacokinetic parameters of the tofts model (ktrans, kep, iauc, ve) were correlated to the clinical outcome at one-year follow-up (n= ). results: despite inserted osteosynthesis material, dce parameters could be evaluated in n= at first visit. sensitivity/specificity of vascularised non-unions as indicator of good clinical outcome was . %/ . % compared to . %/ . % using nuss. logistic regression revealed non-significant impact of nuss on clinical outcome (p= . , odds ratio= . ). at first examination, median iauc (initial area under the enhancement curve) was . in patients with good outcome compared with . in non-responders (p= . ), while ktrans, kep, and ve were not significantly different. using a receiver operating characteristic analysis, sensitivity/specificity of iauc at the optimal cut-off value of . to predict outcome was . %/ . %. all pharmacokinetic parameters did not change significantly at the one-year control (n= ). purpose: imaging-guided thermal ablation has become the therapy of choice among the different treatment strategies of symptomatic osteoid osteoma lesions. in this descriptive, prospective study, our objective was to evaluate typical post-procedural mr-imaging characteristics following mr-guided laser ablation of osteoid osteoma. methods and materials: patients with osteoid osteoma treated with mr-guided laser ablation underwent follow-up mr-imaging immediately after the procedure as well as after , , , , and months. imaging protocol included fatsaturated t w spir tse, non-contrast and contrast-enhanced t w tse images and subtraction images. mr images were jointly reviewed by two radiologists, regarding the appearance of treated areas, nidal enhancement and presence of side effects such as bone oedema and soft tissue enhancement. imaging was correlated to clinical status. results: mean follow-up time was . months. patients showed a postprocedural target-sign appearance with subsequent "positive inward fusion" of the different zonal compartments. post-procedural mr-imaging can support evaluation of therapeutic success. characteristic mr findings correlated well with the clinical status. conclusion: interpretation of post-procedural follow-up mr-imaging after laser ablation of osteoid osteoma may contribute to understanding of histopathological post-therapeutic changes and cornerstones of therapeutic success. s c a d e f g b results: the mean value of dmax obtained by surgical specimen was . mm (range - ) versus . mm (range - . ) of dmax measured through mdct. if the dmax values were stratified into three groups (group smaller than mm, group between and mm, group bigger than mm), a correlation with mdct results of . , . and %, respectively, was found. conclusion: mdct is an accurate technique to obtain an appropriate preoperative definition of dmax, within the limits of tumour bigger than mm. the revaluation of each case with dmax smaller than mm will supply additional information about the discrepancy (retraction of the stomach following immersion into formalin, diffusion in the submucosal layer). percutaneous endoscopic gastrostomy (peg) and jejunostomy (pej) placement guided by ct fluoroscopy with or without simultaneous endoscopy in otherwise untreatable patients c. de (christoph.trumm@med.uni-muenchen.de) purpose: percutaneous endoscopic gastrostomy (peg) or jejunostomy (pej) is substantial for patients with swallowing disorders to maintain enteral nutrition or to palliatively decompress intractable small bowel obstruction. endoscopic placement can be impossible due to previous (gastric) operation, obesity, hepato-splenomegaly, peritoneal carcinosis, inadequate transillumination or obstructed passage. computed tomography (ct) fluoroscopic guidance with or without endoscopy can enable the placement of a peg/pej if endoscopically guided placement fails. methods and materials: consecutive patients were referred to our department for feeding support (n= ) or decompression (n= ). reasons were: ent tumour (n= ), oesophageal cancer (n= ), mediastinal mass (n= ), and neurological disorders (n= ). decompression tubes were placed because of cancer (n= ) or crohn's disease (n= ). the following approaches were chosen: i. ct fluoroscopy and simultaneous gastroscopy (n= ), ii. ct fluoroscopy and inflation of the stomach via nasogastric tube (n= ), and iii. direct puncture under ct fluoroscopic guidance (n= ). results: ct fluoroscopy-guided peg/pej was feasible in of patients. no procedure-related mortality was observed. one tube was misplaced into the colon in a patient with a history of gastrectomy. no complication was seen after removal. minor complications were dislodgement (n= ), peristomal leakage (n= ), wound infection (n= ), superficial skin infection (n= ) and tube obstruction (n= ). conclusion: ct fluoroscopy-guided peg/pej is feasible and safe, and provides adequate feeding support or decompression. it offers the benefits of minimally invasive therapy even in patients with contraindications to established endoscopic methods, combining the advantages of both techniques. long-term complications -mainly tube-related problems -are easily treated. ct assessment of post-resection arterial stumps for right-sided colorectal cancer: a potential marker of quality of resection? t.l. kaye, d.g. jayne, n.p. west, d.j.m. tolan; leeds/uk (thomas.kaye@leedsth.nhs.uk) purpose: there is evidence that the quality and extent of colonic resection affects tumour recurrence rates and patient survival. this is currently evaluated by pathological analysis of the resected specimen. analysis of post-resection arterial stumps via routine follow-up ct could act an alternative in vivo marker. methods and materials: staging and follow-up ct scans from patients with right-sided colorectal tumours were analysed. pre-operative arterial anatomy and post-operative arterial stumps were demonstrated using multi-planar reformats and volume rendering techniques. methods of stump identification, stump length and stump orientation were recorded. results: ileocolic ( . %), middle colic ( . %) and right colic artery ( . %) identification was comparable with catheter angiogram studies. mean time interval between staging and analysed follow-up ct was months. post-resection ileocolic stumps were consistently identified ( . % of cases). in the vast majority of cases this was via a thrombosed vessel ( %). there was a wide variation in ileocolic stump length ( . - . mm, mean . mm, standard deviation . mm). conclusion: to the best of our knowledge this is the largest study to date demonstrating arterial stumps post colonic cancer resection. it is the first to consistently identify stumps years after colonic resection using routine surveillance (portal venous) ct. ct-based stump length analysis may therefore have potential as an in vivo marker of extent and quality of surgical resection. prospective study of using balloon duodenography catheters in ct enteroclysis for small bowel diseases k.c.h. lau, l.m.f. tee; hong kong/hk purpose: to determine the usefulness of using balloon duodenography catheters (bdc) for ct enteroclysis (cte), with a comparison of small bowel distension in using bdc and nasogastric catheters (nc). one of the limitations of cte is the suboptimal distension of the bowels, especially the distal ileum. using bdc, there is less reflux of contrast into the stomach and should have more contrast in the distal small bowel. the study protocol was approved by the ha kwc research and ethics committee and all patients gave written informed consent for the examination and this study. from may to july , cte was performed in consecutive patients with random allocation of patients using bdc and patients using nc. all catheter insertions and cte examinations were performed according to department protocol. small bowel distension was differentiated into four regions (proximal jejunum, distal jejunum, proximal ileum and distal ileum) and given a score from to ( -< mm, - - mm, -> mm). results: distension of proximal and distal ileum was better with bdc than nc (p < . : statistically significant difference). no significant difference was present for others sites (p> . ). conclusion: our study shows statistically significant better distension of the proximal and distal ileum, with the use of bdc when compared with nc. this is of particular use, as the distal ileum is a common site of small bowel diseases. with better bowel distension, this would suggest that using bdc would help to further improve the accuracy of cte. role of preoperative imaging with multidetector computed tomography (mdct) in the management of patients with gastroesophageal reflux disease (gerd) symptoms, candidate to sleeve surgical revision m. rengo, d. caruso, f. vecchietti, m.m. maceroni, g. silecchia, a. laghi; latina/ it (marco.rengo@gmail.com) purpose: to evaluate if multidetector computed tomography (mdct) can be helpful and useful in the decision-making process in sleeve patients with gastroesophageal reflux disease (gerd) symptoms and to demonstrate the reproducibility and accuracy of the technique. methods and materials: twenty-three patients submitted to lsg, complaining upper gi symptoms and/or weight regain and scheduled for a sleeve surgical revision were investigated. all patients underwent mdct scan, upper gi barium swallow study and endoscopy. mdct was compared with barium and endoscopy features as concern: oesophageal dilatation, neo-fundus development and volume, hiatal hernia, sleeve size in toto and atrum dilatation. all patients underwent laparoscopic sleeve revision. surgical findings were considered "as gold standard". results: a total of patients with hiatal hernia, neo-fundus or sleeve dilatation underwent surgical correction. all findings identified at mdct were confirmed by intraoperative findings. the presence of hiatal hernia was significantly underestimated by both barium and endoscopy with a sensitivity of . % and %, respectively (p= . , p= . ). conclusion: mdct is an accurate method for the detection of hiatal hernias and quantification of gastric volumes and can be considered as non invasive method to guide surgery. purpose: the maximum tumour diameter (dmax) is a prognostic factor in patients with gastric cancer, considering its dependence on the depth of invasion. the aim of our work has been to evaluate the accuracy of mdct in the preoperative definition of dmax in patients with gastric cancer, assuming surgical specimen measurements as gold standard, in order to obtain a pre-surgery prognostic evaluation. methods and materials: pre-surgery ct examinations of patients (mean age . , range - ) with diagnosis of gastric cancer were evaluated retrospectively and in a blind fashion by a radiologist with expertise in the oncologic field. the dmax measured was obtained through d multiplanar curved reconstruction (adw . ge healthcare). the results were compared with macroscopic data after surgery. s a c d e f g b thursday b- : pilot study to assess the diagnostic performance of mri in the identification of adhesions between the abdominal wall and small bowel loops, using a time-efficient protocol a. gupta, a. hansmann, p.f.c. lung, r. tandon, r. ilangovan, m. marshall; purpose: abdominal adhesions following surgery are the commonest cause of small bowel obstruction and may complicate subsequent surgery. accurate identification of adhesions has been reported using mr fluoroscopy sequences. we report our results utilising a time-efficient protocol. methods and materials: patients scheduled for open colorectal surgery and who had undergone previous abdominal surgery were recruited over months (mean age , range - ). the abdomen was divided into segments prior to mr and surgery enabling accurate correlation. using a . t scanner (siemensavanto), t sagittal, axial, sagittal true-fisp s cine sequences were obtained (slice thickness cm), in inspiration, expiration and abdominal strain. scanning time was min. adhesions were identified by finding angulation, fixation or altered peristalsis. readers analysed the images independently, providing a consensus opinion on the number and location of adhesions. laparotomy was the gold standard. results: abdominal segments were evaluated with adhesions identified in % at laparotomy and % on consensus mr. segments demonstrated adhesions on mr; % correlated at surgery, whilst the remainder were found in adjacent segments ( %). using a x table, sensitivity was %, specificity %, with positive and negative predictive values of % and %, respectively. overall accuracy was %. conclusion: our results suggest utilisation of a time-efficient mr protocol in identifying adhesions between the bowel and anterior abdominal wall is feasible in a busy unit, and may represent a non-invasive application in the research of adhesion-preventative techniques. reader performance rose during our study and further improvements may be realised in a larger trial. : - : room f oncologic imaging new biomarkers for tumour quantification purpose: patients with lung cancer often suffer additional chronic lung diseases, and often these patients present with fdg avid mediastinal lymph nodes due to inflammatory reasons rather than malignancy. fdg-pet is the leading imaging modality for n-staging in lung cancer patients; however, in patients with doubtful fdg-pet status, d ct histogram analysis might give an additional value to diagnostic imaging. in this investigation d ct histogram analysis was used to identify metastatic lymph node involvement in lung cancer patients in correlation to fdg-pet/ct. methods and materials: lymph nodes from patients aged - years diagnosed with lung cancer were investigated. fdg-pet/ct was performed prior to surgery/biopsy according to clinical schedule. lymph node assessments were acquired using fdg-uptake and d ct histogram analysis on the basis of non-enhanced ct scans. for computing the histograms, the lymph nodes were segmented by a semi-automatic algorithm; the segmentation result was corrected manually if required in certain cases. both imaging findings were correlated with the results from the histological gold standard study. results: positive and negative histologically proven lymph nodes were successfully analysed by d ct histogram. the histological positive lymph nodes presented a median ct hu value of . while histological negative lymph nodes presented a median ct hu value of . . findings were independent of the fdguptake value. conclusion: d histogram analysis seems to be a very promising and valuable imaging surrogate for n-staging stratification in patients with lung cancer with doubtful glucose uptake in fdg-pet. evaluation of crohn's disease recurrence in patients with ileocolic anastomosis: value of computed tomography enterography with water enema f. paparo, m. revelli, c. puppo, i. garello, l. bacigalupo, l. rollandi, r. piccazzo, a. garlaschi, g.a. rollandi; genoa/ it (francesco.paparo@galliera.it) purpose: to investigate the value of computed tomography enterography with water enema (cte-we) in the assessment of the status of the anastomotic site in patients with crohn's disease (cd) who had previously undergone ileocolic resection. were retrieved from our institutional radiology database, and reviewed in consensus by two gastrointestinal radiologists. the presence of cd anastomotic recurrence and its phenotype (inflammatory, stricturing, penetrating) , and the presence of inflammatory lesions involving other bowel segments beside the anastomotic site were recorded. endoscopy and medical records were used as reference standards. results: ct signs of cd recurrence were detected in patients, including: ( . %) isolated anastomotic recurrences, ( . %) anastomotic recurrences + synchronous inflammatory lesions (sils), ( . %) inflammatory lesions not involving the anastomotic site. phenotypes of the cd anastomotic recurrences were: ( . %) inflammatory (non-stricturing non-penetrating), ( . %) stricturing, ( . %) penetrating. no relation was found between the phenotype of cd recurrence and the type of the anastomosis (ll, tl, tt) (p = . ; chi-square test). conclusion: cte-we allowed a complete characterisation of the anastomotic site and the detection of sils, which had a relatively high prevalence in our study cohort ( . %). crohn's disease activity: correlation of inflammatory mediators with overall small-bowel motility s. bickelhaupt , s. pazahr , j.m. froehlich , r. cattin , h. bouquet , g. rogler , p. frei , a. boss , m. patak ; zurich/ch, biel/ch, berne/ch purpose: active crohn's disease (cd) increases the level of inflammatory markers of which c-reactive protein (crp) and calprotectin are commonly used to monitor disease activity. the aim was to evaluate the correlation between crp and calprotectin levels and overall small bowel motility in patients with crohn's disease assessed with mri. methods and materials: patients with crohn's disease ( f/ m, mean y) were included in this irb-approved prospective study. mri ( . -t, philips achieva) was performed after a -h preparation of ml mannitol-solution ( %). cine t w- d-ssfp motility acquisitions (tr . /te . / ms slice repetition time) were performed in free breathing over - sec. randomly chosen small-bowel segments were analysed in two abdominal quadrants using dedicated mr-motility assessment software (motasso). contraction frequency, amplitude, luminal diameter and amplitude diameter ratio (occlusion ratio, adr) were evaluated as well as crp (ngl/ul) and calprotectin (ug/g) levels. pearson's correlation was calculated. results: calprotectin was determined in mean days (sem± . ) before, crp days (sd± . ) before mri. a significant inverse linear correlation was found between the contraction frequency and both the level of crp (r=- . , p= . ) and calprotectin (r=- . , p= . ). expansion of the mean small bowel diameter significantly correlated with calprotectin levels (r= . , p=< . ) but not with crp (r= . , p= . ). the absolute amplitude of the contractions did not correlate neither with the level of crp (r=- . , p= . ) nor with calprotectin (r=- . , p= . ). the ratio describing relative luminal occlusion during contraction (adr) significantly correlated with calprotectin (r= . , p= . ) and with crp (r= . , p= . ). alterations of overall small bowel motility during active phases of cd significantly correlate with the level of calprotectin and crp. author disclosures: h. bouquet: employee; fromer employee of sohard ag. s c a d e f g b measured on fdg-pet. treatment response was evaluated after three cycles of platinum-based chemotherapy, according to recist. the predictive value of texture and pet parameters have been investigated by multivariate analysis. results: fourteen out of patients were non-responders ( progressors, stable disease). combining heterogeneity and suv in a unique parameter (heterogeneity*suv), the latter was significantly higher in responders than in non-responders (medians . vs . , respectively; p < . ) and showed a high predictive value: odds ratio (probability of response) of third vs first tertile was (p . ). responses in first tertile were / , in the second / , in the third / (p . , p for trend . ). tumour heterogeneity alone showed a significantly weaker predictive value, while suv alone was not predictive of treatment response. conclusion: the combination of texture features of tumour heterogeneity on cect and the metabolic information provided by fdg-pet has the potential to be an independent predictor of response to first-line chemotherapy in advanced nsclc. in particular, tumour suv combined with heterogeneity provides an additional value compared with tumor heterogeneity alone. purpose: to assess whether tumour heterogeneity, quantified by texture analysis on contrast-enhanced ct (cect), can predict the response to chemotherapy in advanced non-small cell lung cancer (nsclc). fifty-three pre-treatment cect studies of patients with advanced nsclc who had undergone first-line chemotherapy were retrospectively reviewed and analysed. treatment response was evaluated after three cycles of platinum-based chemotherapy, according to recist. tumour uniformity on ct images has been assessed by a three-step method: image thresholding; multiscale filtering by laplacian-of-gaussian filter; quantification of texture features on filtered images using first-order statistics. the predictive and prognostic values of resulting texture parameters have been investigated by multivariate analysis. results: thirty-one out of patients were non-responders ( progressors, with stable disease). average overall survival was months ( - ), minimum follow-up was months. in the adenocarcinoma group (n= ), the tumour uniformity multiplied by the grey-level of unfiltered images (gl*uni index) has been shown to be the unique independent variable predictive of treatment response. dividing the gl*uni index ( . - . ) into tertiles, lesions in the second and the third tertiles had a -fold higher probability of treatment response compared to those in the first (p . ). tnm stage, sex, age and performance status did not show predictive value. no association between texture features and response to treatment was observed in the non-adenocarcinoma group. gl*uni index was not prognostic. conclusion: texture features of tumour heterogeneity on cect images in advanced lung adenocarcinoma has the potential to be a predictive indicator of response to platinum-based chemotherapy. textural analysis of lymphoma on unenhanced computed tomography: initial evidence for a relationship with tumour glucose metabolism, stage, end of treatment status and survival s. babikir, b. ganeshan, a.m. groves, i. kayani; london/uk (b.ganeshan@ucl.ac.uk) purpose: to provide initial evidence in lymphoma for a relationship between tumour heterogeneity, as assessed by ct texture analysis (ctta), and tumour glucose metabolism, stage, end of treatment status (eots) and survival. methods and materials: this retrospective, pilot study comprised consenting lymphoma patients with consecutive routine f-fluorodeoxyglucose (fdg) pet-ct scans. texture analysis using texrad, (a commercially available texture analysis software), of non-contrast-enhanced ct images with lesions involved: ) image filtration extracting fine, medium and coarse texture-scales, and ) texture quantification using proportion positive pixels (ppp), standard-deviation (sd), and kurtosis (k). corresponding tumour fdg uptake (standardised uptake value (suvavg and suvmax)), clinical-stage and eots from pet-ct and clinical reports were collected. survival was assessed by optimised kaplan-meier analysis. results: , , and patients had stages i, ii, iii and iv, respectively. fine to coarse textures correlated with suvavg (baseline-scan: sd at coarse-scale, rs= . p= . ; interim-scan: ppp at medium-scale, rs=- . p= . ) and clinical-stage (baseline-scan: k at fine-scale, rs= . p= . ). baseline coarse textures predicted eots (ppp at coarse-scale, p= . ; k at coarse scale, p= tumour vascularization imaging without contrast agents: the potential of ivim-mri m. iima , o. reynaud , t. tsurugizawa , l. ciobanu , j.-r. li , f. geffroy , b. djemai , d. le bihan ; kyoto/jp, gif-sur-yvette/ fr (mamiiima @gmail.com) purpose: to investigate the potential of ivim mri to evaluate perfusion and diffusion in a l glioma rat brain tumour model using a . t mri scanner. methods and materials: fischer rats were studied. ivim mri images were acquired with b values ( b values; to s/mm², b values; . to s/mm², and b values; to s/mm²). the signal attenuation curve was first fitted using a biexponential diffusion model to estimate slow and fast components fraction (fslow, dfast and dslow) of the pure diffusion part of the signal (for b> s/mm²). then, the diffusion component was removed from the signal and the remaining signal was fitted using the ivim model for b< s/mm² to get estimates of perfusion fraction, f, and pseudo-diffusion, d*. fitting was performed on a roi basis and on a pixel-by-pixel basis to generate diffusion and perfusion maps. all rats were killed and histology (cd ) was obtained for comparison with ivim parameters. results: ivim maps clearly highlighted areas with high and low fraction perfusion within tumours which were generally heterogeneous, as confirmed by histology. interestingly, we found a negative correlation between the ivim perfusion fraction and fslow, suggesting that cell density in high perfused areas is less than in other tumour parts and normal brain tissue. conclusion: this study confirms that ivim mri can delineate high perfusion areas in tumours and provide information on tissue structure from diffusion parameters. intravoxel incoherent motion (ivim) diffusion-weighted mri for monitoring the therapeutic efficacy of a vascular disrupting agent (ckd- ) in rabbit vx liver tumours i. joo, j. lee, j. han, b. choi; seoul/kr purpose: to evaluate the diagnostic value of intravoxel incoherent motion (ivim) diffusion-weighted imaging (dwi) in the quantitative assessment of therapeutic efficacy of a vascular disrupting agent (vda) (ckd- ) in rabbit vx liver tumours. in vx liver tumour-bearing rabbits ( in the treated group and in the control group), ivim-dwis were performed at a t scanner using b values before and hours, hours, days, and days after ckd- administration. apparent diffusion coefficient (adc) and true diffusion coefficient (d), pseudo-diffusion coefficient (d*), and perfusion fraction (f) of tumours were compared between the control and treated groups and among time points. correlation between change in tumour size and ivim-dwi parameters was analysed to determine which ivim-dwi parameters can be predictors for tumour response. the treated group showed a significantly larger increase in adc at hours, a decrease of d* at hours, and a decrease of f at hours and hours, than did the control group (p < . ). in the treated group, compared to baseline values, d* and f significantly decreased at hours and then recovered at hours and d significantly increased at hours (p < . ). in addition, the greater decrease in f at hours correlated with the smaller increase in tumour size during the days (rho= . , p= . ). conclusion: the therapeutic effect induced by vda could be effectively evaluated using ivim-dwi, and f could be an early predictive indicator for tumour response. texture analysis on contrast-enhanced computed tomography combined with fdg-pet in predicting the response to chemotherapy of advanced non-small cell lung cancer m. ravanelli, f. ferraroni, d. farina, m. morassi, p. tessitore, p. rossini, r. maroldi; brescia/ it (marcoravanelli@hotmail.it) purpose: to assess whether tumour heterogeneity, quantified by texture analysis on contrast-enhanced ct (cect), combined with fdg uptake at pet-ct can predict the response to chemotherapy in advanced non-small cell lung cancer (nsclc). pre-treatment cect studies and fdg-pet studies of twenty-six patients with advanced nsclc who had undergone first-line chemotherapy were retrospectively reviewed and analysed. tumour heterogeneity was measured by texture analysis on cect images; mean suv from each patient was s a c d e f g b thursday b- : scatter amplitude is a good landmark for tumour localisation and treatment assessment in time-domain diffuse optical tomography during neo-adjuvant chemotherapy in breast cancer m. van purpose: neo-adjuvant chemotherapy response may be monitored in a noninvasive way using multi-spectral diffuse optical tomography (dot). a clinically feasible measurement method in these d volumes is proposed and compared with previously published whole breast measurements. methods and materials: twelve breast cancer patients were included, which received neo-adjuvant chemotherapy. four dot scans were obtained: before therapy, after and weeks and pre-operative ( weeks) . deoxyhaemoglobin (hb), oxyhaemoglobin (hbo ) and percentages water and lipids were measured in volumes as measured in dce-mri scans before therapy, centred on areas of high scattering amplitude and approximate location in pre-treatment dce-mri and/ or x-ray mammography. patients were divided in responders and poor responders based on post-operative pathological assessment. results: responders (r) and poor responders (pr) showed statistically significant (p < . ) different development of hb values at , and weeks within measurement volumes relative to the first dot scan: . / . (r/pr, weeks), . / . ( weeks), . / . ( weeks) . for hbo results were similar, but only significant for and weeks: . / . ( weeks), . / . ( weeks), . / . ( weeks) . percentages water and lipids were not significantly different. whole breast measurements did not show statistically significant differences for hb and hbo between responders and poor responders. conclusion: using the scatter amplitude to determine the tumour location in dot volumes enables the measurement of hb and hbo such that these parameters differ significantly between responders and poor responders. this potentially allows effectiveness assessment of neo-adjuvant treatment in breast cancer patients already at weeks. software validation of metastatic sarcoma lesion assessment using ct volumetric density tumour trajectory l.r. purpose: recent studies suggest that tumour assessment methods accounting for both tumour density and volume (sact, mass, choi) add value beyond assessing axial dimensions (recist) or selective regions of interest (roi). we have developed a comprehensive tumour response method termed total volume of viable tumour (tvvt) that assesses rate of change in hounsfield unit (hu) density over treatment course (tumour trajectory), thereby quantifying viable tumour burden as a volume of interest (voi). steeper trajectories may translate to earlier determination of response versus progression. we evaluated the efficacy of experimental volume/hu (tvvt) software and criteria within our picture archiving and communication system (carestream health, rochester, ny) to circumscribe, segment and characterise volumetric density distribution throughout all parts of measurable lesions on ct. comparison of response and tumour trajectory assessment between recist criteria and tvvt was performed in a test set of patients with various sarcomas under radiologist supervision. histograms depicting range and absolute hu for whole tumor volumes were analysed on a subset of patients. results: preliminary investigation shows feasibility of semi-automatic segmentation to outline and quantify density distribution in whole tumour volumes. initial assessment of our set of metastatic lesions suggests that hypervascular sarcomas are a worthwhile study cohort. histogram shifts appear to correlate with qualitative visual estimates of tumor necrosis whereas recist diameters demonstrate little or no differences. conclusion: comprehensive tumour analysis using volumetric density algorithms such as tvvt should more accurately reflect tumour burden and trajectory over selective linear or roi measurements, leading to improved image-based tumour staging and response assessment. semi-automated quantification of whole tumour burden should decrease inter-observer measurement variability, enabling more convenient, reliable imaging results for multiple contiguous vascular metastases. . ). median (range) overall and disease-free survival was ( - ) and ( - ) months, respectively. medium texture-scale predicted overall (baseline-scan: k, p= . , interim-scan: k, p= . ) and disease-free survival (baseline-scan: k, p= . , interim-scan: k, p= . ). suvmax predicted disease-free survival (baseline-scan: p= . ). clinical-stage did not predict eots and survival. conclusion: evidence provided suggests that ctta offers an objective measurement of lymphoma severity on ct. the potential risk stratification and prognostic assessment implications may allow optimal selection of pet-ct candidates in lymphoma. author disclosures: b. ganeshan: shareholder; shareholder and director of texrad ltd, an imaging software company that is developing and commercialising the texture analysis software considered in this study. improvement in both sensitivity and specificity of readers with next generation of mammography cad v. nikitin, i. lossev, a. filatov, n. bagotskaya; longmont, co/us (vadim.nikitin@parascript.com) purpose: the purpose of the study was to compare radiologist performance for screening mammography with and without parascript® accudetect® computeraided detection (cad) software. each of mammography cases (including cancer cases and normal cases) was reviewed by radiologists without and with cad (accudetect, version . ). the mammography cases were obtained with ge senographe essential and philips microdose mammography l full-field digital mammography systems. each radiologist initially interpreted a case without cad noted the findings and assigned bi-rads category , or to the case. for each radiologist, the unassisted interpretation was "locked" before the radiologist turned on the cad marks. after turning on the cad marks, the radiologist could add, remove or adjust the findings noted on the unassisted interpretation as well as change the bi-rads score for the case. sensitivity and specificity calculations for unassisted and cad-assisted interpretations were based on the bi-rads category assignment dichotomization: (bi-rads = ) versus (bi-rads = or ). results: average increase in sensitivity due to assistance of cad is . %, which translates into . % of those initially missed cancers that were recognised with cad assistance. average increase in specificity due to assistance of cad is . %. both increases in sensitivity and specificity are statistically significant. the study demonstrates that both sensitivity and specificity of radiologists increased with assistance of accudetect cad system. assessing the contribution of hypoxia to r * differences between cancerous and normal prostate tissue a. johnson, a. latifoltojar, v. hamy, h. fitzke, k. shmueli, s. punwani; london/ uk (aj @cam.ac.uk) purpose: r * bold mri is proposed as a potential tool for mapping tumour hypoxia in prostate cancer. however, r * has a complex relationship with tissue oxygenation that remains unexplored in prostate cancer. r * is the sum of r (primarily reflecting tissue structure) and r ' (highly sensitive to static magnetic field inhomogeneities, e.g. from deoxyhaemoglobin). whilst r * changes are observed for prostate cancer, they may reflect tissue structure or oxygenation differences. this study aimed to clarify the nature of r * change by quantifying and comparing r * and its components (r and r ') for cancerous and normal prostate tissue. methods and materials: twenty patients underwent . t multi-parametric (mp) prostate mri (dwi, dce and t -weighted), supplemented by dual echo-time t * and t quantitation and followed by biopsy. tumour and healthy regions of interest (identified on mp-mri and confirmed by biopsy) were contoured in consensus by two experienced observers on matched t -and t *-weighted images. mean r *, r and r ' were calculated and compared between cancerous and normal tissue using the student's t-test. results: r * and r were significantly greater for cancer than normal tissue (r *: ± s- [mean ± sd] vs. ± s- respectively, p = . ; r : ± s- vs. ± s- respectively, p < . ). no significant difference was found in r ' ( ± s- vs. ± s- respectively, p = . ). conclusion: prostate tumour r * values predominantly reflect differences in r (tissue structure) and not r ' (tissue hypoxia). s c a d e f g b men for diagnosis, especially when receptors have to be studied in defining the origin of axillary lymph node metastases. purpose: aim of this study was to determine the diagnostic performance of gadofosveset-enhanced mri for axillary lymph node staging in breast cancer patients. methods and materials: ten women diagnosed with invasive breast cancer underwent both non-enhanced and gadofosveset-enhanced dt -weighted mri. a radiologist, blinded for clinical data, evaluated all lymph nodes with regard to size, morphologic features and gadofosveset uptake. lymph nodes depicted on mri were matched with nodes removed during surgery. nodal status was investigated by a blinded pathologist. sensitivity, specificity, ppv, and npv values were calculated. results: a total of lymph nodes were extracted during sentinel lymph node biopsy or axillary lymph node dissection of which were matched with lymph nodes depicted on mri. histopathological examination resulted in macro-metastases and micro-metastases. with contrast-enhanced mri, lymph nodes were rated as true positive, as true-negative, as false positive, and as false negative. this resulted in an overall node-by-node sensitivity, specificity, ppv and npv of, respectively, % ( % ci - ), % ( % ci - ), % ( % ci - ) and % ( % ci - ). if ignoring micro-metastases, mri showed a sensitivity of % ( % ci - ) and a specificity of % ( % ci - ). calculated ppv and npv were % ( % ci - ) and % ( % ci - ), respectively. conclusion: this feasibility study concerning gadofosveset-enhanced mri of axillary lymph nodes showed promising initial results. these results warrant larger studies to confirm these promising results. to assess sensitivity and specificity of prone breast fdg-pet-ct for detection of lymph node metastases and to compare it with t ce-mri of the breast. methods and materials: patients with breast cancer were included in this irb-approved prospective study. all patients underwent t ce-mri and fdg-pet-ct of the breast in the prone position. patients were injected with ca. mbq f-fdg. ct data were only used for attenuation correction. in mri lymph nodes were considered positive for malignancy if there was enlargement > cm, thickened cortex, loss of fatty hilum, matted nodes or an irregular node contour. in pet-ct a lymph node was classified as positive when fdg-uptake was greater than blood-pool activity. the evaluation of nodes was performed on a patient-bypatient basis. all nodes were histopathologically verified. results: fdg-pet-ct achieved a sensitivity of % and a specificity of %. ppv was . (ci . - . ), and npv was . (ci . - . ). diagnostic accuracy was . . ce-mri had a sensitivity of % and a specificity of %. ppv was . (ci . - . ) and npv was . (ci . - . ). diagnostic accuracy was . . nodes were positive and nodes were negative for malignancy. the mean suvmax of lymph node metastases was . (range . - . ). conclusion: fdg-pet-ct improves identification of lymph node metastases as compared with t ce-mri. in patients with lymph nodes classified as malignant by fdg-pet-ct of the breast a sentinel lymph node biopsy can be omitted and surgeons can proceed immediately to alnd. purpose: to evaluate accuracy of us and us-guided-fnab for diagnosing axillary metastasis in breast carcinoma patients and to determine applicability of the bi-rads categorisation. we retrospectively reviewed data on patients who underwent preoperative or prechemotherapy axillary us for axillary staging from january to december . us-guided fnab was performed if lymph nodes showed any suspicious findings according to the bi-rads categorisation: even cortical thickening with preserved hilum, category a (c a); even cortical thickening with compressed hilum or uneven cortical thickening with preserved hilum, c b; uneven cortical thickening with compressed hilum, c c; hypoechoic mass with loss of hilum, c . us and fnab findings were compared using sentinel lymph node biopsy (slnb) and axillary lymph node dissection (alnd) data. results: of patients, ( . %) showed suspicious nodes on us and underwent us-guided fnab. of these patients, ( . %) showed positive, ( . %) showed negative, and showed insufficient findings on fnab. of patients, patients either with normal axillary us (n = ) or without positive findings on fnab (n = ) underwent slnb. of these patients, ( %) had metastatic lymph node. of patients with positive fnab findings, underwent neoadjuvant chemotherapy and underwent alnd. the sensitivity, specificity, ppv and npv of us were . %, %, . % and . %, respectively. the ppv of us was . % in c a, . % in c b, . % in c c, . % in c . the sensitivity, specificity, ppv and npv of us-guided-fnab were . %, %, % and . %, respectively. conclusion: axillary us showed high specificity and npv. a categorisation similar to bi-rads could be applicable for assessing axillary metastasis in breast cancer patients. improving diagnostic yield in axillary lymphadenopathy sampling: core biopsy and vacuum-assisted core biopsy r. salvador, x. salvador, i. miranda, o. dominguez, l. romero; barcelona/es (rafasalvador@telefonica.net) purpose: to analyse and compare the tolerance of the method and the results obtained by sampling axillary lymph nodes with two different devices: large-needle (cb) and vacuum-assisted core biopsy (vacb), directed to patients where previous fine needle aspiration (fnab) has failed to obtain material, or those with different cancers to determine the origin of the metastasic node. methods and materials: consecutive patients, suspicious or proved to have breast cancer were included, all of them with enlarged lymph nodes and signed the informed consent. the two groups were alternatively sampled by large needle ( g) core biopsy and vacuum-assisted needle ( g) biopsy to obtain cylinders in each procedure. eleven patients in each group. the size of the sample (weight), as well as the time of the procedure from the injection of anaesthetic to the final collection of the samples was recorded. discomfort, as well as the acceptance of the method was also recorded and scored in a -grade scale. results: the size of the samples obtained by vacuum-assisted method was bigger than that by core-needle (between twice and three times bigger). but the time for both procedures was similar (always - minutes). no differences were found in pain or any discomfort and tolerance of the method. conclusion: vacuum-assisted axillary lymph node biopsy is a procedure to obtain samples at least as safely as with core-needle biopsy and deserves bigger speci-s a c d e f g b thursday methods and materials: breast cancer patients between and underwent preoperative axus. suspicious nodes as per protocol were biopsied, negative axillae proceeded to sentinel lymph node biopsy (slnb). patients were stratified based on number of abnormal nodes identified on axus ( , , > nodes) and the number on final histology was noted. sensitivity, specificity, positive predictive and negative predictive values for axus-fnac/core biopsy were calculated. results: ( . %) patients had positive axillary nodes on final histology with detected by axus-fnac (sensitivity . %, specificity %, ppv %, npv . %). patients with nodal metastases identified by axus-fnac had a mean nodal burden of . nodes on histology (sem= . , % ci= . - . ; node identified on axus= . nodes on final histology, nodes on axus= . nodes, > nodes= . nodes) with correlation between axus and histology node numbers (r= . , % ci= . - . , p-value< . ). axus-fnac detected . % of node positive patients. mean nodal burden of patients diagnosed on slnb with negative axus or fnac was . nodes. the z trial questioned the role of axus in preoperative axillary staging of breast cancer in cases with ² positive sln. in this study, a single fnac positive node correlated with . nodes on final histology suggesting that axus continues to be essential in guiding appropriate management of the axilla in breast cancer. would have undergone mastectomy due to ci, while mri determined additional mastectomies, increasing mastectomy rate from % to % (p < . ). in the ci group, patients had multifocal, multicentric, synchronous or bilateral cancers, ( %) at mammography and ( %) at ultrasound; mastectomies were due to false positives at both conventional tests ( / , . %). in the ci and mri group, patients had multifocal, multicentric, or synchronous bilateral cancers, ( %) at mammography, ( %) at ultrasound, and ( %) at mri ( only mri-detected synchronous bilateral cancers) (p < . ); mastectomies were due to mri false positives (rate / , . %, not significantly different from ci group, p= . ). conclusion: mri was more sensitive than ci for multifocal, multicentric, or synchronous bilateral cancers. the additional mastectomy rate due to mri was %. adding mri, the percentage of young patients conservatively treated remained near to %. by using solely ci or using ci and mri, the inappropriate mastectomy rate was equal or lower than %. imaging features in mammography and breast ultrasound are related to her- receptor over-expression of primary invasive breast cancer a. adams , k.g.a. gilhuijs , k.e. pengel , c.e. loo , w.p.t.m. mali , s.g. elias ; utrecht/nl, amsterdam/nl (a.adams@umcutrecht.nl) to investigate what mammography and ultrasound imaging features are related to over-expression of the her- receptor in invasive breast cancer. these features could give insight in molecular basis of imaging phenotype, facilitate prebiopsy patient recruitment for early-phase her- targeting molecular imaging trials, and ultimately aid in predicting therapy response and prognosis. methods and materials: mammography and breast ultrasound imaging features of early invasive breast cancers were scored according to the th edition of the bi-rads lexicon, her- status was determined on surgical specimens. relevant imaging features to predict her- over-expression were first identified by conducting a systematic review and meta analysis, and then applied in multivariable logistic regression models. results: her- over-expression was found in cancers ( %). on multivariable analysis, the presence of microcalcifications (or . , % ci . - . ) on mammography, and posterior mass attenuation (or . , % ci . - . ) on ultrasound were strong, independent predictors. less strong predictors were breast density category / (or . , % ci . - . ) and mass presence (or . , % ci . - . ) on mammography, and circumscribed mass margin (or . , % ci . - . ) imaging of axillary lymph nodes in breast cancer patients: how do enhancement kinetics of contrast-enhanced lymph nodes apparent on dynamic mr-mammography correlate with standardised uptake value of f-fdg pet/ct? j. krammer, c.g. kaiser, a. schnitzer, s.o. schönberg, k. wasser; mannheim/ de (julia.krammer@umm.de) purpose: focusing on contrast-enhanced lymph nodes (ln) apparent on dynamic mr-mammography (dmrm) we intended to answer the following questions: ) is there a correlation between the maximum standardised uptake value (suvmax) of f-fdg pet/ct and maximum signal-intensity increase as well as type of signal-intensity curve ( - ) on dmrm? ) do contrast-enhanced ln negative on f-fdg pet/ct have a significantly lesser signal-intensity increase and/or lower curve grading on dmrm compared to f-fdg pet/ct positive ln? methods and materials: breast cancer patients who underwent both f-fdg pet/ct and dmrm were analysed. the mean study interval between the examinations was days. the signal-intensity increase and curve type of axillary ln ³ . cm in short-axis and with predominant contrast enhancement on dmrm were analysed and correlated with the suvmax on f-fdg pet/ct. results: ln in patients were f-fdg pet/ct positive. there was no correlation between the maximum signal-intensity increase and suvmax of these ln (r= . , p= . ). ln in patients did not show an appropriate correlate on f-fdg pet/ct (not visible or suvmax²blood pool). these ln did not reveal a significantly lower curve grading or lesser signal-intensity increase compared to ln positive on f-fdg pet/ct. there is no association between the uptake of f-fdg and the vascularisation of axillary ln on contrast-enhanced dmrm as signal-intensity increase and curve type do not correlate with suvmax. unspecific contrast-enhanced ln on dmrm negative on f-fdg pet/ct can frequently show enhancement kinetics equivalent to those rated positive on f-fdg pet/ct. ultrasound elastography in the diagnostic assessment of axillary lymph nodes in women presenting to a breast imaging centre l. sim, l. leong; singapore/sg (gdrssj@sgh.com.sg) purpose: to evaluate the performance of elastography in distinguishing benign and metastatic axillary lymph nodes. methods and materials: women with sonographically visible axillary lymph nodes undergoing biopsy at our breast imaging centre were evaluated independently with conventional ultrasound, elastography and combined ultrasound and elastography (ceus). the elastogram was classified as benign or malignant, based on the strain pattern, the length and area ratios of the lesion seen on elastography versus ultrasound. validation of radiological diagnosis was by histopathology. the sensitivity, specificity, ppv, npv and accuracy of each test were compared individually and with ceus. to obtain a parameter for diagnostic performance, roc curves were plotted. results: of the axillary lymph nodes biopsied, had metastases and were benign. the sensitivity, specificity and accuracy of conventional ultrasound were . %, . % and . %, respectively. the sensitivity, specificity and accuracy of elastography were . %, . % and . %, respectively, and that of combined ultrasound and elastography were %, . % and . %, respectively. the sensitivities of all tests were similar but the specificity and accuracy obtained by elastography and ceus were significantly better than conventional ultrasound (p < . ). elastography correctly diagnosed % of histologically benign lymph nodes which were deemed malignant on ultrasound. conclusion: the use of elastography alone or combined with ultrasound has a higher specificity and accuracy than conventional ultrasound in evaluating axillary lymph nodes. given the high specificity of elastography, biopsy could have been avoided in % of cases classified as malignant on ultrasound but benign on elastography. the z respiratory syncytial virus-related encephalitis: brain mr study with diffusion imaging a. pak, s. suh, g. son, y. lee, h. seo, k. kim, b. eun, n. lee, h. seol; seoul/kr (suppy@korea.ac.kr) purpose: respiratory syncytial virus (rsv) is a common pathogen of acute respiratory infection causing significant morbidity and mortality in childhood. among the major complications, encephalitis has been sporadically reported. we describe the incidence, clinical and mri imaging findings of rsv-related encephalitis in this report. we retrospectively reviewed the medical records and imaging findings of patients with rsv-positive enzyme assay, admitted at the paediatric department in three urban tertiary-care hospitals of our medical centre for years. there were cases with a diagnosis of rsv-bronchiolitis. among them, ( / , . %) had taken brain mri due to neurologic symptoms. of ( . %) showed positive imaging findings. of positive mr imaging cases revealed non-rsv related pathology such as sdh, diffuse brain atrophy due to status epilepticus, periventricular leukomalacia, pre-existed ventriculomegaly, hypoxic brain injury. results: there were three rsv-related encephalitis. the incidence of this entity is . % ( / ) for rsv positive enzyme assay, . % ( / ) for brain mri examination, and . % ( / ) for abnormal mri findings. the imaging findings of rsv-related encephalitis are as following: rhombenmesencephalitis pattern, rhombenmesencephalitis with acute disseminated encephalitis pattern, and limbic encephalitis pattern. conclusion: encephalitis rarely occurs with rsv bronchiolitis. however, when brain mr is needed in suspicion of neurologic involvement, rsv encephalitis is not uncommon among abnormal mr cases and mimics other viral and limbic encephalitis on imaging study. physicians should be aware of this entity for proper diagnosis and neurologic care of rsv-positive patients. cortical-juxtacortical lesions in clinically isolated syndromes: distribution and diagnostic value j.p. salazar, c. auger, d. pareto, r. mitjana, m. tintore, j. corral; barcelona/es purpose: to evaluate presence and spatial distribution of cortical-juxtacortical lesions in patients with a clinical isolated syndrome (cis) by using mri-based lesion probability maps and to determine its impact to demonstrate lesion dissemination in space (dis) according to the mcdonald criteria for multiple sclerosis (ms). methods and materials: cis patients aged between and years old (mean . years) who underwent brain and spinal cord t mri within the first five months after symptoms onset. the following sequences were obtained: ) pd and t -weighted; ) t -fast flair; ) un-enhanced and contrast-enhanced t -weigthed; and ) d double inversion-recovery. cortical-juxtacortical lesions in each patient were identified, manually outlined and segmented into a binarized mask. a cortical-juxtacortical mri-based lesion probability map was obtained. the mcdonald criteria for dis were assessed in each patient. results: cortical-juxtacortical lesions were identified in patients ( %). frontal lobe was the most affected area with an incidence of % of the lesions. temporal and parietal lobes had also a significant incidence ( % and % purpose: the aim of this study is to explore whether cns hemodynamic disturbances, detected in patients with clinically isolated syndrome (cis), correlate with executive function. methods and materials: thirty cis patients and forty-three healthy subjects matched for age, gender, education level, fsiq, and place of residence were administered computerized tests of visuomotor learning and set-shifting ability. regional cerebral blood volume (cbv), cerebral blood flow (cbf), and mean transit time (mtt) values were estimated using the dynamic susceptibility contrast-and irregular mass shape (or . , % ci . - . ) on ultrasound. the area under the roc curve was . ( % ci . - . , p < . ), and . after adjustment for over-optimism. post-test probabilities of her- over-expression were - % for cancers with calcifications, without posterior mass attenuation, and - % for cancers without calcifications, with posterior mass attenuation. conclusion: microcalcifications on mammography, and posterior acoustic attenuation of masses on ultrasound were predictors of her- /neu over-expression, indicating that imaging characteristics reflect molecular expression patterns in breast cancer. purpose: to study regional changes in brain metabolites during early hiv infection compared with later stage hiv infection and hiv-seronegative controls. enhanced t *-weighted mri (dsc-mri) technique in regions of interest in normal appearing white matter (nawm) and normal deep grey matter (ndgm) structures bilaterally, that serve as integral components of brain circuits responsible for visuomotor learning and executive functions. results: cis patients showed significantly elevated reaction time (rt) on both tasks, while their cbv values were globally increased. significant, positive correlation coefficients were found between error rates on the inhibition condition of the visuomotor learning task and cbv values in both thalami and occipital, and periventricular nawm, bilaterally. on the set shifting condition of the respective task significant positive associations were found between cbv values in the semioval centre and periventricular nawm bilaterally and error rates, between cbf values in both thalami and error rates, and between cbf values in the left parietal nawm and right caudate and rt. conclusion: impaired executive function in cis patients, including inhibition and set shifting abilities, correlated positively with elevated regional cbv values thought to reflect active widespread brain inflammatory processes. the "central vein sign": is there a place for susceptibility-weighted imaging in possible multiple sclerosis? t. kau, m. taschwer, m. schönfelder, j.r. weber, k.a. hausegger; klagenfurt/ at (t.kau@gmx.at) purpose: susceptibility-weighted imaging (swi) may have the potential to depict the perivenous extent of white matter lesions (wmls) in multiple sclerosis (ms). we aimed to assess the discriminatory value of the "central vein sign" (cvs). in a lesion-based t mri study, wmls in patients were prospectively included applying the following criteria: ) at least one circumscribed lesion > mm, ) not more than eight non-confluent lesions > mm. flair images served as gold standard for the identification of wmls which were classified as periventricular, subcortical, or infratentorial. only defined wmls with a maximum diameter of > mm were correlated with their swi equivalent for cvs evaluation. results: five patients fulfilled the revised mcdonald criteria for ms and nine patients were given an alternative diagnosis with non-ms-wmls most probably representing focal gliosis. a total of lesions > mm ( ms-wmls and non-ms-wmls) were detected. consensus reading found a central vein in out of ms-wmls ( %) and in one out of nine non-wmls ( %), respectively. the cvs proved to be a highly significant discriminator (p < . ) between ms-wmls and non-ms-wmls with a sensitivity, specificity, positive and negative predictive values, and accuracy of %, %, %, %, and %, respectively. the frequency of cvs positive lesions was highest in the periventricular zone ( / ), even more markedly in ms-wmls alone ( / ). inter-rater agreement was good (kappa= . ). conclusion: even though the cvs is not exclusively found in ms-wmls, swi may be a useful adjunct in patients with possible ms. single-and multi-voxel proton spectroscopy in patients with pyogenic brain abscess p. the study was primarily designed to find the optimal dose range of br to detect malignant focal liver lesions. secondary objectives were the evaluation of the safety profile and comparison with contrast-enhanced mri (ce mri). methods and materials: patients ( f, m, mean age: y) with known hcc or liver metastases were examined in three centres during a time period of three months. each patient underwent a baseline and at least three contrast-enhanced us (ceus) with ascending dose levels ( . ml, . ml, . ml) of br . ce mri was done weeks prior or post-study examination. lesions were recorded in on a liver map, with respect to localisation, size and suggested lesion type. examination quality was documented and safety parameters were assessed. results: the number of lesions detected with br ceus increased with dose, while the number of missed lesions and the lesion size decreased. despite the increasing contrast enhancement no other image quality parameter showed a substantial difference. no significant changes were found for the analysed safety parameters and no serious adverse events were reported. conclusion: we finally conclude that the recommended dose level of br is between . ml and . ml for which the lesion detection was comparable to the ce mri. in addition, we found a higher number of especially small lesions with higher doses of br which might be due to a higher sensitivity of ceus for the detection of liver metastases. however, this is an interesting and debatable finding. histopathological characteristics of the primary hcc and recurrence were obtained by a review of the pathologic reports. the association between the variations in histopathological and imaging characteristics of primary and recurrent hcc was estimated using linear regression analysis. the initial recurrence was extrahepatic in ( . %, lung, bone, lymph nodes, brain, spleen, adrenal), intrahepatic in ( . %) and both intrahepatic and extrahepatic (peritoneum, lung, bone, lymph nodes) in ( . %) patients. of patients with initial or late intrahepatic recurrence, ( . %) showed a variation in imaging characteristics between the primary hcc (hypervascular) and the recurrence (hypovascular), ( . %) showed a variation in histopathological char- during - patients with - hccs were treated with radiofrequency ablation (alone or combined with ethanol injection) . patients had complete ablated tumours at mo. ct was followed-up serially, using alternated ceus (one sulphur hexafluoride-based microbubbles injection per lobe) and ct every months. the following patterns of recurrence were considered: a, enhancing tissue within the lesion; b, enhancing tissue adherent to the lesion; c, enhancing tissue within the same liver segment of the treated nodule; d, enhancing tissue within a different segment (progression heidelberg/de (gregor.pahn@med.uni-heidelberg.de) purpose: quantitative assessment of image quality and radiation exposure reduction potential of a next-generation solid-state mdct detector with fully integrated readout electronics in comparison with its predecessor. methods and materials: using standard ct image quality phantoms and an automated quantitative image quality analysis software developed in-house, image quality and radiation exposure (re) of an mdct system (somatom definition flash, siemens) either equipped with ufc™ or new "stellar" detectors has been assessed for different combinations of acquisition and reconstruction parameters. subsequently, measurements and analysis were repeated for "stellar" detectors without altering parameters apart from noise-weighted reduction of tube currenttime product resulting in image noise levels equal to those achieved when using their predecessor. results: image noise of both detectors was comparable for small absorption crosssections (Øwater= cm) while being - % lower for large ones (Øwater= cm) when using "stellar" detectors. ct number stability and uniformity declined with increasing subject cross-section, particularly at kvp, though not as much for "stellar" detectors. when noise of "stellar" acquisitions was increased to ufc™ levels, re reduction of - % was achieved. for the "stellar" detector cnr was slightly higher (same re) or slightly lower (reduced re), while spatial resolution was always equal for both detectors (up to lp/cm at mtf %). conclusion: overall image quality improves when a next-generation mdct detector is employed instead of using its predecessor. for acquisition settings intrinsically acteristics (from moderate to poor differentiation), but no association was found between imaging and histopathological variations. the most common pattern of recurrence was extrahepatic location, followed by intrahepatic recurrence and both intrahepatic and extrahepatic diffusion. variations in dynamic-imaging characteristics of intrahepatic recurrence were not associated with variations in histopathological characteristics. films strips were scanned before and after irradiation with the epson perfection v photo scanner in reflective mode. the reference dosimetry system was calibrated in terms of air kerma in air. the measured reflectance change is converted into air kerma using a calibration curve. air kerma was converted into absorbed dose using the appropriate ratio of mass-energy absorption coefficients water-to-air for a given beam quality, defined by half-value layer following the aapm tg- protocol. results: dose values for each of the five ctdi phantom film positions were obtained by averaging dose profiles from each film piece over the length of cm, and were used to calculate weighted ctdivol. the average difference for six scanners between calculated and listed ctdivol was . % with a maximum observed difference of . %. conclusion: in contrast to ionisation chamber measurement, the proposed method requires only a single exposure, does not need stem effect correction, and provides an acceptable accuracy in comparison to ct scanner listed ctdi values. measured dose profiles allow for measurements of dlp and peak doses at the same time. associated with high image noise the new detector exhibits much lower noise levels, offering great potential for radiation exposure reduction without adversely affecting overall image quality. munich/de (zsuzsanna.deak@med.uni-muenchen.de) purpose: to evaluate the dose reduction potential of hir and ir in comparison with fbp. methods and materials: an anthropomorphic cardiac phantom (qrm corp., germany) was scanned using a -row mdct scanner (ct hd; ge-healthcare, usa). the phantom's calcification insert was replaced with a model simulating a stented aortic aneurysm with endoleak and intraluminal thrombus. images were obtained at tube voltages of kv, kv and kv using automated tube current modulation with incrementally increasing noise indices (ni= , , , , , , ) adjusted to a primary reconstruction slice thickness of . mm. after acquisition, images of . mm slice thickness were secondarily re-reconstructed with fbp, hir (asir® with % blending, ge-healthcare) and ir (veo®, ge-healthcare). twenty-one radiologists blinded to image reconstruction methods independently analysed the detectability of simulated vascular pathologies (endoleaks < cm² and intraluminal thrombus < mm). contrast-to-noise ratio was measured for the stented aorta. a two-by-two purpose: to compare two low-dose scanning protocols, and to estimate effects on the signal, noise, effective radiation dose (ed), quality of acquired data. methods and materials: patients were divided into three groups. the scanning protocol was kvp mas in first group, kvp mas in second group, and kv mas in third group, special reconstruction algorithms have not been used. for quantitative and qualitative evaluation we used visual scores ( - ), mean arterial attenuation, noise, contrast-to-noise ratio (cnr) in three arterial segments and ed. results: the bmi ranged from to kg/m and were not significantly different between groups (p= . , . , . , respectively). the mean intraarterial attenuation in , , groups was ± hu, ± hu, ± hu, respectively, but significantly higher in second group (p= . ). noise in second group ( ± hu) was significantly higher than that in third group ( ± hu, p= . ), and first group ( ± . hu, p= . ). the cnr in second ( . ± . ) and third ( . ± . ) groups was significantly lower than that in first group ( . , p= . ). image quality was comparable between three techniques, except aorto-iliac segment in second group. effective dose was . ± . mzv, . ± . mzv and . ± . mzv, respectively, differences were significant (p= . ). conclusion: average radiation dose reduction up to % was achieved using " kv" and " mas" protocol providing sufficient image quality. application of the kv protocol in people with bmi> is limited, especially in evaluation of aorto-iliac segment due to higher noise and attenuation levels. while at mas protocol such limitation is not observed. this allows to recommend it as the preferred protocol for low-dose runoff cta in case of special reconstruction algorithms. purpose: to assess the quality of ct images reconstructed with sinogram affirmed iterative reconstructions (safire) and comparing their performances with iterative reconstructions in image space (iris) and standard filtered back projection (fbp) algorithms on a siemens somatom definition flash. results were used to optimise a dual energy (de) abdominal protocol. methods and materials: fbp, iris and the strength levels in safire (s -s ) reconstructions were characterised in contrast, noise and spatial resolution for medium-smooth filters using a tungsten wire in air, water and catphan phantoms. standard deviation (sd), contrast-to-noise ratios (cnr), noise power spectra (nps), modulation transfer function (mtf), and the non-prewhitening matched filter signal-to-noise ratio (snrnpw), a quasi-ideal observer metric in the frequency domain assumed to be the most reliable image quality reference, were calculated for all kernels and used for dose saving evaluations. results: the highest cnr in de protocol resulted with a composition factor of . . compared to fbp, the average sd reductions were ± % with safire s and ± % with iris kernels. a shift towards low frequencies in the nps was found for all iterative filters, giving to images a different texture. differences between mtf values were within % in all fbp-iterative coupled filter comparisons. the optimal kernels, from snrnpw analysis of abdominal protocol, resulted i -s for safire and i- for iris with a potential dose reduction of % and %, respectively. conclusion: iterative reconstructions and de acquisition strongly improve image quality reducing the noise and improving the contrast without affecting the spatial resolution. the impact of tube voltage, scan direction and beam collimation on the performance of automatic tube current modulation systems in paediatric and adult ct n. buls , j. schoenaers , g. van gompel , k. nieboer , j. purpose: to reduce the radiation dose exposure and contrast medium volume using low-kv ct angiography protocol ( kv; ml) in the evaluation of abdominal aorta, maintaining high diagnostic performance. a total of patients with abdominal vascular disease were prospectively enrolled. all patients underwent mdct scan examination of abdominal aorta (brilliance ict, philips). patients were scanned using lowdose radiation protocol ( kv; automated tube current modulation) and ultralow-contrast volume ( ml; ml/s; mgi/ml) and a control group of patients underwent standard ct-angiography protocol ( kv; automated tube current modulation) and standard contrast volume ( ml). density measurements were performed on abdominal aorta, renal arteries and common iliac arteries. the radiation dose exposure (dose length product, dlp), the intravessels density and the signal-to-noise ratio (snr) were calculated, compared and statistically analysed. results: all exams were considered diagnostic, allowing the correct visualisation of main aortic branch and vascular wall. higher density measurements were obtained in low-kv protocol: mean attenuation value of abdominal aorta hu, renal arteries hu and common iliac arteries; in comparison to control group: mean value of abdominal aorta hu, renal arteries hu and common iliac arteries hu. a reduction of % (p < . ) of radiation dose exposure in low-kv protocol ( dlp; . ctdivol) was obtained among control group ( dlp; . ctdivol). conclusion: low kv protocol and ultra-low contrast medium volume ( ml) reduce the radiation exposure (over %) and the renal damage, allowing a relevant reduction of contrast material volume, enabling to evaluate more easily young patients or patients with renal failure. an international multi-centre comparison of the non-contrast mr angiography technique time-spatial labelling inversion pulse (time-slip) against contrast-enhanced ct angiography for assessing renal artery stenosis: the renal artery contrast-free trial ( (t.vogl@em.uni-frankfurt.de) purpose: to compare contrast-enhanced magnetic resonance angiography (mra) with conventional digital subtraction angiography (dsa) for detecting stenoses and planning of therapy in patients with peripheral artery occlusion disease (paod). in this retrospective study, patients ( women/ men; mean: years) with established paod underwent both imaging modalities in a maximum interval of days. dsa was the standard of reference. the pelvic and leg arteries were divided into anatomic segments, which were graded on a scale from to ( =no stenosis, =stenoses < %, =stenoses ³ %, =occlusion). the pelvic and leg vessel systems were categorised with the tasc ii-score into five grades (none, tasc-a, tasc-b, tasc-c and tasc-d) for detecting whether the therapeutic consequences would be the same for both imaging modalities. iodine load reduction in ct aorta angiography with gemstone spectral imaging: comparison with standard ct aorta angiography x. luo, j. wu, j. sun, m. chen; yangzhou/ cn (luoxianfu@gmail.com) purpose: to compare quantitative and subjective image quality between computed tomographic aorta angiography (ctaa) with a gemstone spectral imaging (gsi) technique with reduced iodine load and standard ctaa. methods and materials: patients underwent ct scanning on hdct (discovery ct hd, ge healthcare). all cases were randomised into two groups: standard ctaa ( - kvp) with mg/kg per body weight of iodine (n= ) and gsi scanning ctaa (image reconstruction at kev) with the same injection volume as in the standard protocol but composed of contrast medium and saline in a : . fashion (n= ). signal intensity and noise of aorta were measured; signal-to-noise ratio (snr) and contrast-to-noise ratio (cnr) were calculated. a five-point scale was used to subjectively evaluate vascular enhancement and image noise. results: compared with standard ctaa, gsi ctaa demonstrated higher signal intensity in all aorta arteries (all p < . ), inferior noise only in segmental arteries (p < . ), higher snr and cnr (both p < . ), and compatible effective dose (p > . ). the five-point score was higher in the standard ctaa protocol (p < . ). the inter-reader agreement regarding the dichotomized diagnostic versus nondiagnostic scale was similar (p > . ) between two groups. conclusion: gsi ctaa with image reconstruction at kev allows a significant reduction of % iodine load while improving intravascular signal intensity, maintaining snr and with comparable radiation dose. >/= % and cta . ). post-interventional avr did not correlate with pre-procedural measured as and av (both p> . ). patients with post-procedural avr showed no significant differences in as and av than patients without evidence of avr after tavi ( thursday target noise sd . and fbp reconstruction) and referred to follow-up chest ct within two months were enrolled. aec (sd ) integrated with aidr d was used in follow-up chest ct protocol (group b), the raw data of which were reconstructed again with fbp (group c). the max/min mas of each subject and their correlation with bmi were investigated to validate whether system could personalise tailor tube current. the chest images were divided into upper, middle and lower parts which were evaluated separately by two radiologists with -point scale ( -good, -acceptable, -poor). image noise was measured in these parts with -mm diameter roi placed on specific anatomic structures. effective dose (ed) was compared. . mpr and d reconstruction images were created, and reviewed by two experienced radiologists with blinded, who measured the tracheal lumen to determine the presence of central airways narrowing. the d reconstruction of confidence was graded on a -point scale from (no confidence) to (highest of confidence. the mpr noise was assessed by measuring the sd of the pre-sternal soft tissue. the dlp was used to compare radiation doses. results: the mpr image noise was ranked higher for ct images of kv protocol than kv protocol. there was no significant difference in confidence between kv and kv protocol (p > . ). excessive central airway collapse (reduction > %) was seen in patients with tracheomalacia and remaining subjects had centre airway stenosis. dlp of kv protocol was . mgy.cm and kv protocol was . mgy.cm. the -slice dynamic volume ct is a promising method for diagnosing central airway narrowing. the kv protocol performs as well as the kv protocol for the d dynamic imaging in small bmi objects. purpose: the purpose of this study was to examine the influence of different arm positioning on automatic tube current modulation of multi-slice ct on chest image quality and radiation dosage. methods and materials: sixty patients underwent scanning by using care dose d thorax ct protocol in which both arms were raised above the shoulder region using standard-position (group ) and postural manoeuver (group ), respectively. objective and subjective image quality was assessed. individual recorded the ctdiv values and the tube current-time product per exposed section. effective radiation dose was calculated. results: compared with the image quality in the standard-position group, the image quality in the postural manoeuver group was decreased on subjective image quality but within acceptable diagnostic limits. the average effective dose in the postural manoeuver group was . msv; the dose in the standard-position was % lower than this. conclusion: both arms were raised above the shoulder region scanning using care dose d thorax ct protocol can reduce the overall dosage to patients and the image quality without adverse influences, and may be more feasible in clinical practice. the effectiveness of lead apron for radiation protection in ct n. weber, p. monnin, c. elandoy, s. ding; lausanne/ch (nicolas.weber@hesav.ch) purpose: to determine the effectiveness of lead shielding for radiation protection in ct. methods and materials: three -cm diameter ctdi (pmma) phantoms, of cm long, placed side by side, were scanned over a length of cm with a ge ct scanner. absorbed dose was estimated with thermoluminescent dosimeters positioned in the middle, and at two levels in periphery of the phantom ( cm inside): top and bottom. additionally, the dose was measured on the surface of the phantom ("skin dose"). tld were placed over a length of . cm, with . cm in the scatter field. three acquisitions were performed: ) without lead apron, ) with a lead apron at cm from the edge of the primary field and ) with a lead apron at . cm. results: in scattered radiation, no significant difference of dose was found between without shielding and with the apron at cm, in the middle of the phantom. however, in the presence of the apron the dose is lowered by as much as % at the bottom of the phantom, whereas the skin dose is increased by % (tunnel effect). this indicates that the scanner a retrospective study was conducted in two radiology departments from public hospitals using a sample of patients under years submitted to head ct examinations between and , performed with different equipments: somatom emotion (n= ), somatom emotion (n= ) and somatom emotion (n= ). the influence of patient age and cephalic perimeter were considered. multiple data analysis was used in order to assess radiation dose levels and the concordance of these with diagnostic reference levels. the results were obtained for four different paediatric groups, divided according to patient age: less than year; to years; to years and to years. the mean values obtained of dose length-product from some groups are lower than the diagnostic reference levels ( mgy.cm from to years and mgy.cm from to years). however, until years the values are higher than the recommendations ( mgy.cm for less than year and mgy.cm from to years). conclusion: this work identifies possible gaps and all possible methods should be applied to reduce the radiation dose provided without deteriorating image quality. a set of recommendations are needed to optimise the radiation dose since the children have a superior radiosensitivity. dose values in eye lens in paediatric brain computed tomography: influence of different protocols c. carriço , m. inácio , a. kristiansen , m. larsen , j. santos , s. holm , g. paulo ; coimbra/pt, odense/dk (catarina.carrico@hotmail.com) purpose: the number of head computed tomography (ct) examinations in paediatrics had an exponential increase. taking into account the highest radiosensitive of children tissues and organs, radiology departments should permanently optimise ct protocols in order to minimize exposure, especially to more radiosensitive thursday body mask is classified into classes (fat, water, air, and outliers) by a multivariate gaussian intensity model, regularized by a markov random field. to increase robustness to image variability, the statistical model parameters are automatically updated with the em algorithm. the air voxels are rejected from the mask and the adipose tissue segmentation is refined using a new -class gaussian intensity model. to separate sat from vat, an intra-abdominal mask is created by calculating the convex hull around the water tissue (water fraction of at least %). the adipose tissue quantification is, even under heavy motion, visually satisfactory. it is, moreover, highly consistent over the two datasets of each subject, as demonstrated by the high icc (r= . ) and the small difference in fat, sat, and vat percentage of total body volume of . %, . %, and . %, respectively. conclusion: an automatic adipose tissue quantification method based on spatially regularized multivariate gaussian mixture models is demonstrated to provide consistent measurements for sat and vat. computational texture analysis in interstitial lung disease: comparison of descriptors and classification accuracy j. ofner , c. purpose: to evaluate and compare sequential ct to spiral ct examinations of the brain in terms of radiation dose and image quality. the study was carried out prospectively on patients referred for brain ct. radiation dose and image quality data were gathered from an equal number of ct examinations performed with either sequential (n= ) or spiral (n= ) techniques. radiation dose data in terms of ctdivol and dlp were recorded by the scanning radiographers at the end of each examination. a ct brain image evaluation set was compiled which was evaluated by four radiologists. the radiologists evaluated the quality of the images by visually grading the reproduction of anatomical structures as outlined in eur : european guidelines on quality criteria for ct. results: mean ctdivol and dlp readings were significantly higher (p < . ) for sequential scans over spiral scans (ctdivol: . mgy vs. . mgy and dlp: . mgycm vs. . mgycm). the mean image quality grading scores for all criteria for the sequential technique were significantly (p < . ) higher than those obtained by the spiral technique. conclusion: spiral acquired ct brain images have lower radiation doses. the quality of the images produced using this technique, however, produces images of a lower quality to those obtained using the sequential technique. further research is recommended investigating whether the level of image quality produced by the spiral technique is sufficient for diagnosis in order for patients to benefit from associated radiation dose reductions. termined the number of alerts triggered, based on the currently used, exclusively study description-based threshold method. the default setting of this threshold is twice the median for each separate descriptor. then, logical combinations of study description and protocol were made and linked by a rsna radlex elements, for a total of % of all examinations. the mapped data sets were then used to determine the number of alerts triggered when using a threshold method based on a combination of study description and acquisition protocol. the impact of both strategies on relevant dose information was assessed. results: considering only the relevantly mapped scans, we found a % decrease, from to alerts, using the radlex-based alert triggering. of these, ( %) were not previously reported by the old method. the new alerts could all be attributed to patient or examination-related factors. of the alerts ( %) that were no longer reported, none were found to have any clinical relevance. the combination of study description and acquisition protocol in the threshold method for ct dose measurements helps to decrease the number of alerts, while maintaining patient safety. purpose: to optimise ct protocols and parameter settings, by comparing the radiation dose between different ct scanners of the same type. methods and materials: using dedicated software (dosewatch®), dose information from ct examinations performed on two -slice lightspeed vct scanners over an -month period was prospectively evaluated. we compared the administered radiation doses for equivalent acquisition protocols on the machines, and identified acquisition protocols in which there was a significant dose variation. for these protocols, we performed a rigorous imaging parameter check, including comparison of the number of examinations, acquisition types, number of irradiation events, ma, kvp, scanning length, exposure time and pitch factor. these data were then linked to the protocol setup. results: we found significant parameter variations in out of ct acquisition protocols. in cases, the variations could not be attributed to a difference in the acquisition protocol set-up, and a thorough inspection did not lead to any improvement. for acquisition protocol (helical skull), we found that the noise index was erroneously configured on one of the ct machines. after correction of this parameter, the median dose length product (dlp) on this machine was reduced from mgy.cm to mgy.cm ( % decrease), based on measurements during months prior to correction ( cases) and months after correction ( cases). the use of a patient dose managing system for ct can identify suboptimal parameter settings, and helps to significantly reduce the radiation dose without loss of relevant diagnostic information. it (marco.moschetta@gmail.com) purpose: to assess the reliability of d analysis ct software in determining urinary stones volume and density. methods and materials: ct images of patients for a total of urinary stones ( calyceal, pelvic, ureteral) were evaluated. all exams were performed using a mdct with a low dose protocol and without injection of contrast material. ct scans were independently evaluated by two expert radiologists. for each stone, volumetric [sv (stone volume) = l (length) x w (width) x t (thickness) x π x . ] and densitometric [selecting a roi on axial plane] measurements were calculated. the obtained data were then compared with the measurements performed by the d analysis ct software (vitrea fx . ). differences between the two systems were evaluated by the analysis of variance (anova) test. the interobserver agreement was calculated using the cohen's kappa (k) test. the volumetric and densitometric measurements of urinary stones obtained without d analysis software showed a lower interobserver agreement (k = . ) than that resulting from the use of the software (k = . ). statistical significant differences were found between volumetric and densitometric measurements as performed with and without the d software for each urinary stone (p < . ). conclusion: volumetric and densitometric evaluation of the urinary stones provided by d analysis software is reliable and reproducible and could significantly influence the therapeutic choices. the dslicer open-source platform for segmentation, registration, quantitative imaging and d visualisation of biomedical image data s. pujol , s. pieper , r. . overall image quality, identifiability of vessels and homogeneity of liver parenchyma were graded by two experienced radiologists in consensus using a -point rating scale with a true non-contrast ct (tnc) scan as standard of reference ( =no difference; =minimal, non-relevant difference; =visible but diagnostically irrelevant difference; =relevant difference; =obvious difference). image noise was measured in liver parenchyma, retroperitoneal fat and aortic lumen. wilcoxon signed-rank non-parametric test was used to assess statistical significance. the nvnc was superior compared to the standard vnc regarding overall image quality and identifiability of vessels ( . vs. . /p < . and . vs. . /p < . ), whereas no significant difference was observed concerning the homogeneity of the liver parenchyma (nvnc: . /svnc . ). there was no significant difference regarding image noise with an average value of . hu (nvnc) and . hu (svnc), respectively, compared to . hu (tnc). the new algorithm provides a better image quality and an improved assessment of vessels and small structures. the nvnc images represent adequate substitutes for tnc images, rendering an omission of non-contrast acquisitions feasible, corresponding to a substantial dose reduction. image quality of monoenergetic low-kev datasets for lower extremity dual-energy ct angiography s. sudarski, d. schneider, p. apfaltrer, s.o. schönberg, t. henzler; mannheim/ de (sonja_sudarski@gmx.de) purpose: to compare image quality of conventional -kev polyenergetic images (peis) and monoenergetic images (meis) for dual-energy ct angiography (de-cta) datasets of the lower extremity. we retrospectively evaluated de-cta datasets obtained from patients ( men, ± years). meis were calculated in -kev intervals from to kev using the -and -kev image data. attenuation and image noise were measured in the external iliac, femoral, popliteal and one lower leg artery. contrast-to-noise ratio (cnr) and signal-to-noise ratio (snr) were calculated for each vessel. differences in these parameters were compared between the different monoenergetic datasets. the two best meis were compared to -kev-peis. results: snr and cnr of -and -kev meis were highest when compared to other low-kev meis. in -kev meis, cnr in external iliac, femoral and popliteal arteries was higher compared to peis (+ %, + % and + %; p < . ), while cnr did not change in lower leg arteries (p> . ). snr in external iliac and lower leg arteries was equal in -kev meis and peis, while in femoral and popliteal arteries it was lower (- %, - %; p < . ). -kev meis showed a higher cnr in lower leg arteries compared to peis (+ %; p < . ), while snr did not differ (p> . ). in the other three arteries, -kev meis showed significantly not only higher cnr but also lower snr. purpose: persistent sub-centimetre ggo are pre-malignant. hrct improves detection of small nodules and low dose ct (ldct) reduces patient exposure but both decrease cnr essential for characterisation of small ggo. we investigate the use of adaptive iterative dose reduction (aidr) in low dose hrct (ld-hrct) for diagnosis of small ggo. methods and materials: ldct ( kv, mas, x . mm) was used in stages: ) computer-simulated lung nodules , and mm spheres each of ct# , - and - hu; ) identical synthetic nodules, placed in an anthropomorphic chest phantom and ) in vivo pulmonary nodules ( ggo, solid); . mm diameter ( . - . ), mean ct# - hu ( to - ). raw data reconstructions are as follows (slice thickness/overlap mm): . / . , / , / , / , / , / , / , / . and / with fbp. in vivo images were also reconstructed with aidr. ct# and cnr were determined for each protocol. results: ct# accuracy decreases with increased slice thickness for all nodules: / reconstructions decrease ct# > - hu for mm solid (+ hu) nodules and ~ - hu for mm ggo (- hu and - hu), spearman's coefficient = - . , p < . . hrct (< . / . mm) has accurate nodule ct# (error< % purpose: to investigate whether optimisation of volume-doubling time (vdt) cutoff for fast-growing nodules in a lung cancer screening trial can improve accuracy of lung cancer diagnosis. methods and materials: all subjects underwent at least two low-dose computed tomography (ct) scans during the baseline-round screening and regular secondround screening in year of the nelson lung cancer screening study and were referred to a pulmonologist because of a solid nodule with volume ³ mm and vdt < days. histology was the reference for diagnosis, or, to confirm benignity, stability of the nodule volume on subsequent ct scans for at least two years after referral to a pulmonologist. nodule volume and vdt were semi-automatically calculated by software. reduction of false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with the vdt cut-off of days as reference. results: fast-growing nodules were included ( individuals), of which nodules ( %) were malignant. mean follow-up of non-resected benign nodules was . (range . - . ) years. the optimal vdt cut-off for the -month follow-up ct in the baseline round was days. using this cut-off, false-positive referrals reduced by % ( versus false-positive referrals). for the regular secondround screening, vdts varied more among malignant nodules, precluding lowering of the vdt cut-off of days. conclusion: lowering the vdt cut-off of the -month follow-up ct in baseline lung cancer screening from to days may reduce false-positive referrals, without apparent loss in sensitivity. mia, invasive adenocarcinoma, and the extents of invasive carcinoma component were quantified. association between imaging parameters and pathologic classification was examined. results: patients ( %) were pathologic stage a, and were b and the other one was a. of all tumours, were ais ( %), were mia ( %), and were invasive adenocarcinoma ( %). based on univariate analysis, tumour size in lung setting, uniformity, and entropy were able to significantly separate tumours according to pathologic classification, whereas tdr, volume, mass, or suvmax were not. on multivariate analysis, uniformity and entropy were remained as independent factors to stratify the pathologic subgroups of patients (odds ratio [or] = . , p =. , and or = . , p =. , respectively). conclusion: texture parameters on ct imaging metrics, reflecting tumour heterogeneity, appear to help stratify pure ggn lung adenocarcinoma. non-solid, part-solid or solid? classification of pulmonary nodules in thoracic ct by radiologists and a computer-aided diagnosis system c. purpose: classifying pulmonary nodules into solid, part-solid and non-solid is crucial for patient management. a computer algorithm is compared to a radiologist on a large data set obtained from a multi-center lung cancer screening trial. methods and materials: low-dose chest ct scans ( x . mm, - kvp, mas) with part-solid, non-solid, and solid nodules with a diameter between and mm were randomly selected from two sites participating in the dutch-belgian nelson lung cancer screening trial. the set contained scans, including part-solid, non-solid and solid nodules. the nodule-type recorded in the screening database was used as a reference standard. an automated classification system for characterisation of nodules was designed using morphometric features. the accuracy of the computer algorithm was evaluated in three ways: classifying nodules ( ) as solid or subsolid, ( ) as solid, part-solid or non-solid, and, ( ) for the subsolid lesions only, as part-solid or non-solid. an experienced thoracic radiologist independently performed the same classification. the accuracy of the automated system to differentiate between solid and subsolid nodules was . , compared to . for the radiologist. the computer classified the nodules as solid, part-solid or non-solid with an accuracy of . versus . for the radiologist. the software reached an accuracy of . in differentiating part-solid from non-solid nodules, where the radiologist had an accuracy of . . conclusion: a novel automated characterisation tool for pulmonary nodules shows promising performance and could aid radiologists in selecting the appropriate workup for pulmonary nodules. ( ), additional to bled aneurysm ( ) and additional coiling ( ). aneurysms ranged in maximal size between and mm (mean/median mm). aneurysms were located in the cavernous sinus (n= ), supraclinoid internal carotid artery (n= ), anterior communicating artery (n= ), middle cerebral artery (n= ), pericallosal artery (n= ) and posterior circulation (n= ). patients were preloaded with aspirin and clopidogrel (multiplate test control). clinical and angiographic follow-up was done at -to -month intervals after treatment. results: single stents were placed in cases, stents in and flow-diverter stents in . in cases no additional coil aneurysm occlusion was performed. seventeen procedural complications occurred ( %): thrombo-embolic, in-stent thrombosis, haemorrhages, side-branch occlusions and technical device problems. most had no clinical sequel, but patients died ( %) and patients had permanent neurological deficit ( %). five aneurysms ( %) needed second additional stenting during follow-up. mean follow-up was months (range - months). conclusion: endovascular intracranial aneurysm occlusion with stent assistance is a delicate procedure with a higher complication rate compared to regular coil occlusion. however, this technique is useful in complex otherwise difficult or untreatable intracranial aneurysms. in-stent restenosis occurred in / cases ( . %) and solved with angioplasty in / cases ( %) or re-stenting in / ( %). primary patency rate was . %; secondary patency rate %. neurological events occurred in . % of cases. results were analysed correlating neurological complications with the operator's experience, plaque morphology and patient's age. neurological disorders were . % in asymptomatic patients and . % in symptomatic ones (p= . ) and they proved to be higher in older patients (> y) . % vs . % of patients < years (p < . ). the overall neurological adverse events were . % in the presence of complex plaque morphology and . % in case of stable plaques (p < . ). friday within months after the procedure. a total of high signal lesions on dwi were serially numbered and the signal change on conventional mri in the follow-up was evaluated. the quantitative parameters on dwi (location, volume and value of apparent diffusion coefficient: adc) for each lesion were measured. we used fisher exact test and the mann-whitney u test to compare differences between two groups; statistical significance was assigned when p < . . results: there was statistically significant difference in the presence of dwi lesions (multiple: % versus single: %, p= . ). in each lesion, the volume was significantly small ( . ± . cm versus . ± . cm , p= . ) and the permanent signal change was less observed in multiple antiplatelets use ( . % versus . %, p= . ). there was negative correlation between the volume and the value of adc (r=- . , p <. ). conclusion: periprocedural use of multiple antiplatelet agents is expected to reduce the volume of thromboembolism and permanent signal change in the follow-up. purpose: the treatment of vertebral split fractures remains controversial, consisting of either corset or internal fixation. the aim of this study was to evaluate ct-and fluoroscopy-guided percutaneous vertebroplasty in the management of vertebral split fractures. methods and materials: institutional review board approval and informed consent were obtained for this study. sixty-two consecutive adult patients who had posttraumatic vertebral split fractures (a according to the ao classification) without neurological symptoms were prospectively treated by percutaneous vertebroplasty. all these procedures were performed by an interventional radiologist under computed tomography (ct) and fluoroscopy guidance using only local anaesthesia. postoperative outcome was assessed using the visual analogue scale (vas) and oswestry disability index (odi) scores. results: vertebroplasty was performed on thoracic and lumbar vertebrae. the filling of the vertebral body was satisfactory in % of the patients, with seven discal cement leakages ( %). the mean vas measurements ± standard deviation (sd) significantly decreased from . ± . preoperatively to . ± . at day, . ± . at month, and . ± . at months (p < . ). the mean odi scores ± sd had also a significant improvement: . ± . preoperatively and . ± . at the -month follow-up (p < . ). radiological union was observed within the months following vertebroplasty in all the cases. the results of our study showed that type a vertebral fractures could be successfully treated by ct-and fluoroscopy-guided percutaneous vertebroplasty with an excellent functional recovery. long-term results of microsurgical and endovascular therapy of intracranial aneurysms in patients following subarachnoid haemorrhage k. bojanowski , j. baron , b. kostkiewicz , m. zawadzki , j. walecki ; warsaw/pl, katowice/pl (jerzy.walecki@cskmswia.pl) purpose: the aim of this paper was to evaluate long-term clinical outcomes and radiologic findings in patients following microsurgical treatment and endovascular embolisation of intracranial aneurysms. methods and materials: a total of subjects aged - ( women and men) were evaluated. patients were divided into two groups according to the type of procedure they underwent: patients had open surgery and patients had undergone endovascular embolisation. the assessment was performed from months to years after treatment. all patients underwent a follow-up cerebral arteriography and clinical evaluation. results: a total occlusion or a neck remnant was discovered in a majority of patients following microsurgical procedures and endovascular treatment ( % and % in contrast to % and %, respectively). no recurrent aneurysms were revealed. the mann-whitney u test did not reveal any statistical significance in long-term treatment results regarding self-reliance (p-value= . ). the amount of blood extravasated following the rupture of an aneurysm was a significant independent factor influencing the clinical outcome and determined the long-term results in both groups (p-value< . ). a correlation between a patient's age and the clinical outcome following a microsurgical procedure was proved. the outcome was better in younger patients (p-value< . ). this was not observed in patients after endovascular treatment. conclusion: microsurgical and endovascular therapy are comparable methods for treating cerebral aneurysms; however, embolisation is correlated with a higher rate of complications in elderly patients. the final clinical outcome depends on the amount of extravasated blood following a subarachnoid haemorrhage. embolisation of cerebral aneurysms with hydrogel-coated coils: systematic review and meta-analysis a. pałys, z. serafin, w. lasek; bydgoszcz/pl (serafin@cm.umk.pl) purpose: hydrogel-coated coils for endovascular treatment of cerebral aneurysms were developed to reduce the risk of aneurysm recurrence and the rate of retreatment. the aim of this review was to verify the efficacy and safety of hydrogel-coated coils. methods and materials: a literature search was performed by two independent researches for papers published up to august on follow-up results of intracranial aneurysm embolisation with hydrogel-coated coils. analysis included aneurysm presentation at follow-up compared to initial treatment result, the rate of rebleeding and retreatment, and specific complications. pooled rates of major recurrences and total recurrences were calculated. results: of articles on the use of hydrogel-coated coils for embolisation of cerebral aneurysms, ( aneurysms) were included. significant heterogeneity was found regarding patients populations, methods of aneurysm coiling, follow-up schedules, and recurrence definitions. a cumulative follow-up rate was % ( % ci, - %, range - %). pooled major recurrence rate was % ( % ci, - %, range - %) and pooled total recurrence rate was % ( % ci, - %, range - %). control groups consisting of aneurysms treated with bare platinum coils were analysed in only in four articles ( aneurysms). pooled major recurrence rate for bare platinum coils was % ( % ci, - %) and was significantly higher than this for hydrogel-coated coils. conclusion: embolisation of cerebral aneurysms with hydrogel-coated coils results in lower rate of major recurrence, than with bare platinum coils. more high-quality standardised prospective studies are needed to define specific indications for the use of hydrogel-coated coils. effect of antiplatelet therapy on radiographic outcome of positivity on diffusion-weighted imaging in elective endovascular coiling of unruptured cerebral aneurysm t. . males (n= ) were followed retrospectively over months; males (n= ) were followed prospectively over weeks. the diagnosis of pt was confirmed with ultrasound and power doppler (average thickness of prospective subjects . mm, average neovascularisation . on modified ohberg scale). all subjects were injected under real-time ultrasound guidance with ml of . % marcaine mixed with mg hydrocortisone followed by a mean of ml normal saline at the interface between the pt and hoffa's body, adjacent to the area of neovascularisation. the same supervised rehabilitation programme was followed by all patients. the visa-p questionnaire was administered for pre-injection severity and at follow-up. results: there was instant resolution of neovascularisation in all subjects. the visa-p score statistically significantly improved from a mean of . to . for (p < . ), which is likely to be clinically significant. the retrospective data increased by . points compared to . in the prospective subjects followed over a shorter time period. over % of the prospective subjects agreed/strongly agreed that their symptoms/strength had improved, with over % returning to their required level of sport within weeks. purpose: our aim was to investigate the potential impact of visceral fat assessment by dxa in the clinical management of patients submitted to different therapeutic programs for obesity. we prospectively recruited patients affected by obesity and submitted to medical and/or surgical treatment. body mass index (bmi) and body composition were analyzed with anthropometric and whole-body dxa evaluations simultaneously performed at baseline and after one year. a new software available to estimate android visceral fat was applied to last-generation dxa equipment. results: ninety-one patients ruled out the study. among patients ending the follow-up period ( -males, -females, . ± . -year-old, . ± . -kg/m ) bmi decreased in / - . % controls, while regained in / - . %. an opposite trend between bmi and total fat mass/non-bone lean mass (tfm/tlm), android ratio (afm/alm), and android visceral/subcutaneous fat (v/s) was found in / - . %, / - . % and / - . %, respectively. bmi was significantly correlated with tfm/tlm and afm/alm (r= . and . respectively), while it was far from a statistically significant connection with v/s (r= . , p= . ). although slightly better correlations were demonstrated between tfm/tlm (and afm/alm) and v/s, these were extremely low (r= . , p= . purpose: to prospectively evaluate dual gradient-echo mri with dixon-based generation of fat-/water-images (mridixon) for quantification of the muscle-fat content (mfc) in-vitro and in patients with achillodynia compared to asymptomatic volunteers. methods and materials: mridixon was used to measure the mfc of phantoms containing titrated mixtures of organic muscle/fat from - % as well as of the gastrocnemius (dixongastro) and tibialis anterior (dixontibialis) muscles in patients ( women; mean age, ± years) with achillodynia and in matched asymptomatic volunteers ( women; mean age, ± years) at . t. accuracy of mridixon in quantification of mfc was assessed in-vitro as well as in-vivo using single-voxel mr-spectroscopy (mrs) as the standard of reference. dixongastro and dixontibialis were related to visual grading of the mfc (grades - ) in both muscles (visualgastro and visualtibialis). results: correlation of mfc derived from mridixon, phantoms and mrs was excellent with correlation coefficient (r ) ranging from . to . and mean measurement bias ranging from - . to + . %. mean dixongastro/dixontibialis was . ± . / . ± . in patients and . ± . / . ± . in volunteers. visualgastro/ visualtibialis ranged from to / to and to / to , respectively. no significant difference was seen for dixontibialis between patients and volunteers (p=. ), whereas dixongastro was significantly higher in patients (p <. ). both, visual-gastro and visualtibialis did not differ in patients and volunteers (all, p>. ). conclusion: mridixon allows for accurate quantification of mfc and demonstrates a significantly higher fat content in the gastrocnemius muscle in patients suffering of achillodynia than in asymptomatic volunteers, outer performing visual assessment of mfc. and disappeared after more than months. the unloading-findings were more severe at the patella and femur than at the tibia (p < . ). high scores of severity were associated with confluent and patchy patterns (scr= . , p < . and kt= . p < . ). conclusion: bone marrow changes at the knee related to disuse are most prominent - months following unloading when both patchy and confluent hyperintense patterns are present. manifestations of unloading are most prevalent within the patella and the femur and associated with increased vascularity. methods and materials: from whole body f-fdg pet/ct datasets including a dedicated head and neck investigation protocol of consecutive patients (mean age: ± years) with histopathologically proven pharyngeal and laryngeal malignancies virtual d f-fdg pet/ct panendoscopies were reconstructed using an investigational software application. the feasibility to completely assess specific spaces of the upper airways by a virtual "fly-through" and to detect primary tumours was tested; the time for an automated segmentation of the virtual f-fdg pet/ct panendoscopies was measured. the nasopharynx, oropharynx, laryngopharynx, epiglottis, subglottis and the tracheobronchial tree were accessible in all , the laryngopharynx, aryepiglottical folds, piriform sinus, glottis, and oral cavity in , , , and patients, respectively. in all patients with restricted fiberoptical evaluation due to a primarily intubation the subglottical space was entirely accessible via virtual panendoscopy. the primary tumour was depicted in / patients ( %). the mean processing time for virtual f-fdg pet/ct panendoscopies was ± s. conclusion: virtual f-fdg pet/ct panendoscopy of the upper airways is technically feasible and can detect pharyngeal and laryngeal malignancies. the tool allows for a complete evaluation of the subglottical space when optical panendoscopy is incomplete due to intubation. it may be used for planning endoscopy-guided biopsies and surgery in the future. centrations were determined dynamically before and after exercise using a whole body mri-system (achieva, t, philips healthcare). point-resolved spectroscopy (press) was used to acquire spectra from a voxel in the m. vastus lateralis. the total creatine (t-cr) peak was used as internal reference. post-exercise acquisition of spectra started approximately minutes after cycling. results: exercise-induced elevations of acetylcarnitine levels were similar in both groups (Δpost-pre . ± . mmol/kg wet weight (ww)). however, post-exercise acetylcarnitine kinetics were significantly different (p < . ). in sedentary subjects, the concentration continued to increase during recovery towards a plateau at minutes ( . ± . mmol/kgww). in contrast, the acetylcarnitine concentration started to decrease from . ± . mmol/kgww at minutes after exercise in the trained subjects towards . ± . mmol/kgww at minutes. conclusion: we demonstrate the dynamic character of acetylcarnitine in a situation of changing substrate demand/supply. the current protocol can differentiate between two metabolically different groups, which opens a window towards investigation of acetylcarnitine in relation to metabolic flexibility and insulin resistance. in vivo differentiation of muscle precursor cells using mr relaxometry n.c. chuck, f. azzabi zouraq, d. eberli, a. boss; zurich/ch (natalie.chuck@usz.ch) purpose: to assess the differentiation process of muscle precursor cells (mpcs) applying magnetic-resonance-imaging (mri) relaxometry and diffusion measurements in a mouse model in correlation with histology, immunohistochemistry and organ bath. methods and materials: human mpcs were isolated from biopsies of the m.rectus abdominis. the mpcs were mixed with a collagen carrier and injected subcutaneously in nude mice. animals with collagen-only-injections served as controls. mri was conducted on a . t small-animal-scanner (bruker biospec) at time points between day and post-injection. relaxometry measurements comprised t and t measurements using multi-echo-spin-echo (te - ms) and saturationrecovery-sequences (recovery time - ms) and t * quantification with a multi-echo-gradient-echo-sequence (te = . ms, Δte = ms, echoes). diffusion imaging was performed with a spin-echo-sequence including diffusion gradients with b= . and s/mm . relaxation times and adc values were measured in the skeletal muscles. evaluations were performed with custom-made matlab scripts. animals were harvested after days and the engineered muscle tissue was assessed by histology, organ-bath and immunofluorescence. results: relaxation and diffusion properties of the engineered tissue could reliably be measured at all time points. relaxometry measurements revealed a decrease of t , t and t * relaxation-time during differentiation (initial measurement: t . ms± , t : . ms± , t *: . ms± ; final measurement: t : . ms± , t : . ms± , t *: . ms± . ), thereby approaching the physiological relaxation properties of muscular tissue. adc showed a decrease from . mm / s± . to . mm /s± . . cell differentiation and myofibre formation was confirmed by histology, immunohistochemistry and contractility confirmed by organ bath. conclusion: we demonstrated that mri relaxometry measurements are able to describe the differentiation of muscle precursor cells. this method might offer the possibility to non-invasively assess the effectiveness of cellular therapies for muscular disorders in near future. purpose: to evaluate diagnostic accuracy of diffusion-weighted magnetic resonance imaging (dwi) in predicting response to neo-adjuvant chemo-radiotherapy (ncrt) in patients with locally advanced cervical carcinoma using apparent diffusion coefficient (adc). cervical lesions adc were correlated with post-surgical histopathology. methods and materials: women (figo>ib bulky) underwent mri and dwi prior to, after weeks and at the end of ncrt, using . t scanner. cervical lesion volume and adc were measured at each assessment. radical hysterectomy was performed weeks after mri. treatment response was determined based on histopathology and was classified as complete response (cr), residual (rd) or stable disease (sd). mean adcs (madc), adc increase and volume reduction (vr) rates were compared using histopathology as reference standard results: according to histology, / ( %) had cr, / ( %) had rd < cm. patients presented sd. before therapy, in the study population madc was . ± . x -³ mm²/s but it was lower in sd ( . ± . x -³ mm²/s). after weeks of ncrt, madc correlated with tumour response: a) in cr with % percent change ( . ± . x -³ mm²/s vs . ± . x -³ mm²/s; p < . ); b) in rd with % percent change ( . ± . x -³ mm²/s vs . ± . x -³ mm²/s; p < . ). tumour volume decreased in cr and rd with reduction rate of % and %, respectively. at the end of crt, no significant differences on adc between for comparison of quality data, chi-square and odds ratio were used. results: in subjects ( %), benign ( . %) and malign ( . %) lesions were detected. six subjects underwent operation ( %) for adrenal carcinoma, renal carcinoma, pancreatic mucinous cystadenoma, intradural schwannoma ( ), and enchondroma of the femur. in one subject, tuberculosis pneumonia was detected and medical treatment was given. in subjects focal nodular hyperplasia of the liver, and in one an unclassified solid mass in spleen were encountered and they are in follow-up. the most common incidental lesions were liver cyst ( ), liver haemangioma ( ), renal cyst ( ), and thyroid nodule ( ). no significant difference was observed for the incidence of benign and malign lesions between subjects aged ³ years and < years (p= . and p= . , respectively). conclusion: % of the population screened by wb-mri underwent further surgical and medical treatment. wb-mri is a useful and non-invasive tool for the detection of incidental lesions in asymptomatic subjects. purpose: to assess the value of elasticity parameters on breast sonoelastography by influence of menopause factor. methods and materials: female patients (premenopausal vs postmenopausal: vs ) with breast lesions were conducted routine ultrasound and elastographic ultrasound preoperatively. the elastic parameters of strain ratio (sr, sr was calculated using the same-level and normal-appearing breast region as reference; sr was calculated using the subcutaneous fat as reference) were then obtained, with the pathologic diagnosis served as golden standard. the sensitivity, specificity, and area under the curve were analysed by receiver operating characteristic (roc) curve with or without the influence of menopause factor. purpose: to assess if stiffness as measured by shear-wave elastography (swe), could be an early biomarker of response to chemotherapy in a breast cancer model. a human invasive ductal carcinoma was implanted subcutaneously in athymic female mice. after weeks of growth, tumours were removed for baseline pathological analysis and were treated by oral chemotherapy during weeks. ultrasound was performed every week before and during treatment, using a superficial -mhz probe. maximum diameter and mean elasticity value of the tumor were measured. kinetics of changes in diameter and elasticity before and under treatment were calculated as the slope of diameter or elasticity over time. at the end of the treatment, tumours were removed for pathological analysis. results: before treatment, we observed a progressive stiffness increase along tumour growth (slope: . kpa/week). under chemotherapy, we observed an early stabilisation of tumour stiffness (slope: - . kpa per week). furthermore, a significant decrease of elasticity values was seen after four weeks of treatment (p= . ). we also observed an early progressive decrease of diameter showing that there was a good response to treatment. after five weeks of treatment, we observed modifications of the pathological features of the tumor, i.e. mainly a decrease of cellular density. conclusion: in our model, we observed an early stabilisation of tumour elasticity with an inversion of elasticity slope under treatment showing that swe could be an interesting tool to assess early tumor response to chemotherapy. purpose: shear wave elastography (swe) can differentiate benign from malignant solid breast masses. small, low-grade cancers can have benign (low) mean stiffness values but often show a ring of slightly stiffer tissue around the lesion. we aimed to establish whether taking the presence of a ring sign to indicate malignancy improves the discriminatory performance of swe in screen detected solid breast masses. the ring sign was defined as the presence of stiffer borders on at least aspects of the lesion. the presence or the absence of the ring sign was independently assessed by two breast radiologists, blinded to pathology outcomes, in a consecutive series of screen-detected solid masses. a third radiologist arbitrated in discordant cases. the discriminatory performance of swe using a threshold mean stiffness value of kilopascals (kpa) was compared with taking either a threshold mean stiffness of kpa or a ring sign as positive. results: of masses, were benign and were malignant. in ( %), the ring sign findings of two radiologists were concordant. for mean stiffness threshold of kpa, sensitivity was % and specificity was %. when either mean stiffness over kpa or a ring sign was counted as positive, sensitivity was % and specificity was %. the increase in sensitivity was statistically significant (fisher's exact test, p= . ). the drop in specificity was not (p= . ). the ring sign can improve the sensitivity of shear wave elastography in differentiating benign from malignant screen-detected solid breast masses. purpose: the purpose of our study was to investigate arterial spin labelling (asl) mri for functional assessment of transplanted kidneys at . t and t. methods and materials: renal allograft recipients (mean age . ± . years) were included in this study. asl mri was performed at . t (n= ) and t (n= ) using a single-slice paracoronal fair truefisp sequence ( averages, inversion time ms, slice thickness mm, matrix x ). for quantification of asl perfusion, t relaxation times were determined at . t and t using the variable flip angle approach. rois were drawn by a single reviewer on asl parameter maps for quantification of cortical perfusion. asl perfusion was correlated with allograft function as determined by the estimated glomerular filtration rate (egfr) and compared between patients with good or moderate allograft function (group a; egfr > ml/min/ . m²) and patients with heavily impaired allograft function (group b; egfr ² ml/min/ . m²). results: asl perfusion and egfr were comparable at . t ( . ± . ml/ min/ . m² and ± ml/ g/min) and t ( . ± . ml/min/ . m² and ± ml/ g/min). asl perfusion was significantly higher in group a ( . ± . ml/ g/min) as compared to group b ( . ± . ml/ g/min) (p < . ). asl perfusion values exhibited a significant correlation with egfr (r= . , p < . ). a total of patients were enrolled at centers in japan. all patients provided written informed consent before entering the studies. unenhanced ultrasound, contrast-enhanced ultrasound, and contrast-enhanced mr images were independently assessed by three blinded reviewers, who viewed the different images in a randomised sequence and were also blinded to subject characteristics. the observation period for safety assessment was days after the contrast agent administration. results: among patients included in the diagnostic analysis, the accuracy of contrast-enhanced ultrasound ( . %) was significantly higher than that of unenhanced ultrasound ( . %) and contrast-enhanced mri ( . %) (both p < . ). sensitivity and specificity of contrast-enhanced ultrasound ( . %, . %) were also superior to unenhanced ultrasound ( . %, . %) and contrast-enhanced mri ( . %, . %) (sensitivity: p= . and p= . ) (specificity: both p < . ). the incidence of adverse events was . %, with adverse drug reactions in . % (all mild). conclusion: compared with unenhanced ultrasound and contrast-enhanced mri, contrast-enhanced ultrasound with sonazoid ® (perflubutane) microbubbles achieved significantly better diagnostic accuracy and specificity for breast lesions without causing serious adverse reactions. methods and materials: in a retrospective study, patients with non-tumorous increased signal intensity of the kidneys on dwi sequences (b= s/mm ) and corresponding adc-decrease was identified. as a control group served patients without clinical signs of renal infection. all patients underwent routine mri-protocol of the abdomen including epi-sequence for the dwi (b. / / ), t w haste, t w vibe post-contrast (dotarem). confirmation of renal infection was established on the basis of clinical criteria. t w-and t w-images were assessed and compared to dwi for the presence of altered signal and the degree of the visibility of pathology was graded on an three-point scale. in all patients with positive dwi-findings, a renal infection could be confirmed while none of the patients in the control group showed a suspicious signal pattern on dwi. t w-imaging and contrast-enhanced t w-imaging displayed obvious pathologic signal in / ( %) and / ( %) patients, slightly pathologic signal in / ( %) and / ( %), respectively. no pathologic change was seen in / ( %) and / ( %). the median visibility score of for the dwi-imaging and the t w-images was significantly higher than the median visibility score of for the t w-imaging (p= . (dwi vs. t w) and p= . (t w vs. t w). no significant differences were found between the visibility scores of t w imaging and dwi. conclusion: dwi of the kidneys seems to be highly sensitive for the detection of infections within the kidney. purpose: to investigate feasibility dynamic-contrast-enhanced (dce)-mri assessment of kidney function and renal masses on a single slice compared with investigation of the whole organ or tumour. methods and materials: fourteen patients with renal tumours ( renal cell carcinomas, angiomyolipoma, oncocytoma) before and after partial nephrectomy underwent dce-mri at t (magnetom verio, siemens healthcare sector) with a time-resolved angiography with stochastic trajectories (twist)-sequence (voxelsize . x . x . mm , temporal resolution . mm) with half-dose gadobutrol (bayer healthcare pharmaceuticals). kidney datasets and tumour datasets were assessed using in-house built idl-software pmi . . using -compartment-models with semi-automated segmentation, renal perfusion and filtration as well as tumour perfusion and permeability were calculated for a single central region-of-interest on a single slice or the whole organ or tumour. statistical analysis was performed with paired t-tests and pearson´s correlation coefficient. results: there were no significant differences between single slice / whole kidney (plasma-flow . ± . vs. ± . ml/ ml/min, plasma-volume . ± . vs. . ± . ml/ ml, glomerular-filtration-rate . ± . vs. . ± . ml/ ml/ min) as well as between single slice/ whole tumour (plasma-flow . ± . vs. . ± . ml/ ml/min, plasma-volume . vs. . ml/ ml and permeabilitysurface-product . ± . vs. . ± . ml/ ml/min). correlations between single slice and whole organ/ tumour was were excellent and significant for all parameters (r = . to . , p < . ). conclusion: single slice assessment of kidney function and renal masses with dce-mri does not show significant differences to the more time-consuming analysis of the whole organ/ tumour. incorporation of single slice analysis of dce-mri data in future studies appears feasible and justifiable. in vivo sodium ( purpose: renal allograft rejection is associated with chemokine ligand (ccl )dependent glomerular and interstitial macrophage recruitment. ccl blockade with the oligonucleotide/spiegelmer mnox-e - 'peg inhibits leucocyte recruitment. the purpose of this study was to evaluate mr renography and diffusion-weighted imaging (dwi) for assessment of this novel chemokine-directed therapy in an experimental murine animal model. methods and materials: an orthotopic renal transplant mouse-model with acute allograft rejection (balb/c into c /bl ) was used. animals were treated with low-dose cyclosporin a in combination with mnox. animals did not receive treatment. syngenic controls (c /bl into c /bl ) were performed. imaging was conducted at t with a dedicated mouse coil. diffusion-weighted imaging was performed with b values ranging to s/mm . mr renography was performed with a twist-sequence with a temporal resolution of . seconds following a bolus of µl gadobutrol in µl nacl. significance between subgroups was assessed with wilcoxon´s rank-sum test. results: syngenic allograft showed substantially higher plasma flow ( . ± . ml/ ml/min) and significantly lower (p < . ) adc ( . ± . mm /s) than native kidneys ( . ± . ml/ ml/min and . ± . mm /s). allograft-adc of treated animals ( . ± . mm /s) was substantially higher than of untreated animals ( . ± . mm /s). cortical plasma flow ( . ± . ml/ ml/min) was significantly lower (p < . ) for untreated animals compared to treated animals ( . ± . ml/ ml/min). volume of distribution and mean transit time did not show significant differences between the subgroups. conclusion: chemokine-directed treatment ameliorates acute renal allograft rejection. functional mri is able to non-invasively assess these therapy effects in this experimental model and holds high potential to become an alternative to invasive organ biopsy. assesment cisplatin-induced interstitial nephropathy using diffusion-weighted mri r. del vescovo, f. giurazza, r.l. cazzato, c.l. piccolo, r.f. grasso, b. beomonte zobel; rome/it (r.delvescovo@unicampus.it) purpose: to assess the potential of noninvasive diffusion-weighted magnetic resonance imaging (dw-mri) to depict interstitial kidney changes in patients (pts) under cisplatin-based chemotherapy. we analysed adc maps of oncologic patient ( woman and men; mean age years; % affected by advanced lung cancer) treated with cisplatin-based chemotherapy comparing with age-and sex-matched control group's adc maps. the creatinine clearance (crcl) used to determinate renal function was based on the formula of crockfort (normal value > ml/min). the adc values were calculated using a roi positionated manually on the cortex of each pole in axial and coronal images. for statistical analysis t-test was used. a p value of less than . was considered significant. results: there was no anatomical difference visible with conventional mr imaging of the cortex and medulla relationship. in pts treated with cisplatin there was a reduction of adc values in the cortex, but no significant changes in medulla. the adc values of healthy volunteer were significantly higher comparing with patients treated with cisplatin (p < . ). there was no significant difference between the adc values of left and right kidney in each patient except in one who present a unilateral ureteral obstruction. no significant correlation was found between the creatinine clearance and adc values obtained in both groups. conclusion: dw-mri may allow a noninvasive detection of changes in kidneys in pts with interstitial nephropathy during and after chemotherapy treatment. purpose: to investigate the feasibility of reconstructing anatomic connectivity of sacral plexus using t-mr diffusion tensor imaging (mr-dti) with three-dimensional ( d) tractography approach. t-mr-dti was performed on women volunteers. the sequence was acquired on oblique axial plane parallel to the sacrum, from the level of the l nerve to the coccyges. main diffusion directions reflecting the fibre orientation were determined using a sense-ssepi with diffusion-sensitised gradients (b mm s- ) along directions. a deterministic bre-tracking algorithm was used to show fibre architecture, compared with anatomic atlas. three rois were placed at different levels of the spinal cord nerves: one in the middle of each tract-of-interest, accompanied by "and" selection rois at both ends of the nerve tract roi. diffusion-weighted ssh-epi images are processed on a dedicated workstation for data pre-processing with medinria deterministic software. results: tractography of the sacral plexus was feasible for all volunteers, giving d insight into the general anatomy and organisation of the nerves l to s . main artefacts in fibre reconstruction, caused by bladder over-distension, by presence of air in rectum and by constant small movements due to breathing and/or spontaneous contractions of pelvic organs, never invalidate the feasibility of tractography. fibres were reconstructed from medulla to the pelvic course of main branches of sacral-plexus nerves. emerging branches of pudendal nerve were found in volunteers. conclusion: t-mr-dti allows a precise anatomic reconstruction of lumbar-sacral plexus. these findings are encouraging for using dti as a mean to investigate sacral-plexus, especially in female pelvis. te= . ms to . ms; tr= ms; averages; measurement time= : min). all hr images were corrected for inhomogeneous sensitivity of coil. the na-snr values are given on a pixel-by-pixel basis for mm from the renal cortex in the direction of the medullary pyramid. the t * maps were calculated by fitting the na signal decay mono-exponentially on a pixel-by-pixel basis using least squares fitting routine written in idl. results: the mean cortico-medullary na-snr for all healthy kidneys increased from the renal cortex ( . ± . ) towards the renal medullary pyramid ( . ± . ). the cortico-medullary increase ranged inter-individually from . to . %. the mean na-t * of all volunteers was . ± . ms. the feasibility of ultra-high field, hr na-mri of healthy human kidneys was demonstrated. moreover, high na-snr provided by . t allowed the in vivo measurements of na-t * times in human kidneys for the first time. arterial spin labelling for the prostate: initial experience at t mri s. takahashi , n. aoyama , t. kimura , k. kitajima , y. ueno , s. sato , k. sugimura ; kobe/jp, otawara/jp, osaka/jp (staka@med.kobe-u.ac.jp) purpose: to assess the value of asl-perfusion mri for the prostate using dynamic contrast-enhanced (dce) study findings as the reference standard. methods and materials: male patients (mean age . ± . years) with suspected prostate cancer were prospectively included in this study. single-slice d-pulsed asl images were acquired during our routine prostate screening protocol on a t mri unit, including the dce study. first, roi was drawn for the obturator muscle on a control image of asl sequence (scont.ref). then, rois were drawn for the femoral artery, the obturator muscle, the normal pz and the regions where dce showed early enhancement on the tagged asl image. these values were divided with scont.ref, yielding an asl ratio (aslr). analysis of the variance was performed to assess differences in aslr for each tissue or region. a radiologist scored the degree of enhancement on dce and compare to the contrast ratio of aslr and the visual assessment of asl signals. results: a mean aslr of the femoral artery was . ± . %, where those of the normal pz and the obturator muscle were . ± . %, and . ± . %, respectively. on the other hand, the enhanced regions on dce showed a mean aslr of . ± . %. visual assessment of the asl image detected out of well-enhanced regions. contrast ratio of aslr demonstrated significant positive correlation to the degree of enhancement on dce (spearman; r= . , p=. ). conclusion: asl may allow detecting the region of the higher tissue blood flow in the prostate without contrast materials. purpose: aim of this study was to investigate the feasibility of contrast-enhanced tesla mri of the female pelvis. methods and materials: healthy female volunteers were examined on a t whole body mr system (magnetom t, siemens) utilising an -channel transmit/ receive radiofrequency body coil. the examination protocol included ) t w fs d flash, ) dynamic t w fs d flash, ) t w tse sequences. for qualitative image analysis of t w mri, the delineation of pelvic anatomy, pelvis vasculature, tissue contrast and overall image quality was assessed and for t w mri the zonal anatomy of the uterus and the conspicuity of the ovaries were evaluated (fivepoint-scale analysis: = excellent to = non-diagnostic). image impairment due to various artefacts was assessed. contrast ratios between junctional zone and myometrium were obtained via roi analysis for t w mri. results: of all three sequences, d flash mri offered best overall image quality (mean contrast-enhanced . ) and highest tissue contrast (mean contrastenhanced . ). for the t w sequences, d flash imaging was rated with higher scores for all assessed structures than d flash mri. t w tse imaging provided a moderate to high conspicuity of the zonal anatomy of the uterus with mean scores ranging from . for endometrium to . for myometrium. overall image impairment was rated strongest for t w mri ( . ) and least for d flash mri (mean . ). our results indicate the successful transformation of the associated high snr into high spatiotemporal resolution t w pelvis mri at t and valuable non-contrast diagnostics of pelvis vasculature. de (david.schneider@stud.uni-heidelberg.de) purpose: high vessel attenuation as well as a high contrast-to-noise (cnr) ratio is a prerequisite for highly diagnostic cervical and cerebral ct-angiographic examinations. the purpose of this study was to evaluate the value of calculated low-kv-monoenergetic dual-energy ct (dect) angiographic datasets. methods and materials: patients ( men, mean age ± ) that underwent dect-angiography of the cervical (n= ) or cerebral vessels (n= ) were retrospectively included in this study. and -kv dect data were used to calculate low-kv monoenergetic image datasets from to kev ( -kev intervals). vessel and soft tissue attenuation and image noise were measured in various regions of interest and the cnr was subsequently calculated. differences in image attenuation and cnr were compared between the different monoenergetic datasets. vessel attenuation and cnr of the best monoenergetic datasets were then compared to conventional -kv polyenergetic datasets. results: in comparison to conventional polyenergetic -kv datasets, above all, -kev monoenergetic cervical datasets yielded to a significant increase in vessel attenuation and cnr (+ %, + %; all p < . ). for cerebral vessel assessment, in particular -kev monoenergetic datasets improved vessel attenuation and cnr (+ %, + %; all p < . ) when compared to conventional -kv datasets. conclusion: calculated -kev monoenergetic image data significantly improves vessel attenuation as well as the cnr of cervical dect-angiographic studies, whereas -kv monoenergetic datasets are favourable to improve vessel attenuation and the cnr of cerebral dect-angiographic studies. thus, lowering the amount of iodinated contrast-material might become feasible using monoenergetic-low-kv images, which is particularly important for combined perfusion and angiography protocols. purpose: single case reports suggest that black blood mri (t -weighted fat and blood suppressed sequences with and without contrast injection; bb-mri) may visualise intracranial vessel wall contrast enhancement in primary angiitis of the central nervous system (pacns). in this single-centre observational pilot study we prospectively investigated the value of bb-mri in the diagnosis of large artery pacns. methods and materials: in this prospective, mono-centric study patients with suspected large artery pacns received a standardised diagnostic programme including bb-mri. patients without any evidence of pacns and without intracranial stenosis served as control group. vessel wall contrast enhancement was graded (grade - ) by two experienced readers blinded to clinical data and correlated to the final diagnosis. results: four of included patients received a final diagnosis of pacns. all of them showed moderate (grade ) to strong (grade ) vessel wall contrast enhancement at the sites of stenosis. a moderate (grade ) vessel wall ce grade was also observed in of the remaining patients in whom alternative diagnoses were made: arteriosclerotic disease (n= ), intracranial dissection (n= ), and moyamoya disease (n= ). none of the patients in the control group had vessel wall contrast enhancement. conclusion: our pilot study demonstrates that vessel wall contrast enhancement is a frequent finding in pacns and its mimics, but it is absent in patients without evidence of intracranial vascular disease. larger trials will be necessary to evaluate the utility of bb-mri in the diagnostic workup of pacns. purpose: the availability of endovascular services is increasing, but still not available in the majority of tpa centres. the aim of this study was to describe the relations between nihss and large vessel occlusions in patients with hyper-acute ischaemic stroke. a prospective single hospital registry based on consecutive patients admitted for tpa work up with routine cta was started on july , ; this analysis is based on patients admitted before december . bispebjerg university hospital has a tpa-service with a catchment area of app. . mio. inhabitants on even dates. ct scans are performed using -section mdct (brilliance- , philips healthcare) with cta from the aortic arch to the vertex. all images were systematically reviewed by a blinded neuroradiologist; sensitivity, specificity, positive predictive value and negative predictive value were calculated at all levels of nihss. results: five-hundred and seventy-three patients with acute ischaemic stroke were entered into the registry. at a nihss score equal to or larger than , the sensitivity was equal to . %, the specificity was . % the positive predictive value was . % and the negative predictive value was . % in predicting an acute occlusion. conclusion: if the cut off is set at nihss , there is a % risk of missing an occlusion and a % risk of transporting a patient with a tpa drip for no reason. the relation is between occurrence of large vessel occlusions and nihss is a continuum. contribution of the temporal maximum intensity projection ( purpose: the goal of retrospective study was to compare possibilities to measure the extent of mca occlusion (thrombus length) in patients with acute stroke and predictive value for recanalization and clinical outcome after systemic therapy. we analysed patients with mca occlusions ( males, average age . years, range - years) detected with multimodal ct examination (non-contrast ct, perfusion ct and conventional cta). conventional cta (slice . mm) and temporal maximum intensity projection (tmip) datasets (slice . mm) reconstructed over the full time span from volume ct perfusion were used for thrombus length measurement. results of used techniques were compared and correlated with results of systemic thrombolytic therapy ( hours recanalization and -month clinical outcome). results: there was no statistically significant difference in measurement results using conventional cta and tmip, but in subjects ( %) measurement of thrombus was not possible using conventional cta due to unclear peripheral border of thrombus. we proved statistically significant correlation of whole extent of thrombus and recanalization success (p= . ). the involvement of m section was main negative factor for recanalization (p= . ). the strong significant correlation of thrombus length and -month clinical outcome was proved (p= . ) with cut-off value of mm. conclusion: our results confirm the benefits of detailed evaluation of cerebral arteries using tmip datasets, which enable to measure thrombus length in all subjects in comparison to conventional cta. the thrombus length was established as negative factor for recanalization and clinical outcome after systemic thrombolytic therapy. that with an optimised mr-protocol, mural inflammatory changes of superficial extracranial and intradural arteries can be detected in patients with gca. methods and materials: patients with suspected gca underwent . tesla mri, including fat saturated (fs) t w scans pre-and post-contrast, optimised for assessment of intradural vwe, and high-resolution fst w scans to evaluate superficial extracranial vessels. temporal artery biopsies were available in cases. vwe of intradural and extracranial vessels was evaluated by two observers results: in patients, gca was diagnosed clinically, in biopsy proven. a clear vwe of superficial extracranial vessels was detected in cases. clear vwe of the intradural internal carotid artery (ica) was detected in cases, with corresponding vessel wall thickening. slight enhancement of the right medial cerebral artery was seen in case. in one patient with gca, no vwe of intradural or extracranial vessels was detected. one patient who did not receive a temporal artery biopsy presented with vwe of intradural and extracranial arteries, but the final clinical diagnosis was connective tissue disease. conclusion: vwe of extracranial vessels is a frequent finding in gca. additionally, vwe of intradural arteries, mainly the ica, can be found. therefore, high-resolution mri seems to be a feasible technique to visualise vasculitic involvement of the extra-and intracranial arteries in gca. purpose: to measure cerebrovascular reserve using fmri (cvr fmri) in patients with severe stenosis of the middle cerebral artery (mca) to identify those at risk of haemodynamical stroke. methods and materials: among patients with severe intracranial arterial stenosis, patients ( females; . ± . years) had a stenosis of the right (n= ) or left (n= ) mca only. cvr fmri was performed using bold contrast with a block-design hypercapnic challenge (co %) at t. averaged end-tidal co pressure (etco ) was used as regressor for statistical analyses. we measured %bold/mmhg etco on segmented grey matter of mca territories. we calculated a laterality index with limca =(left_cvr-right_ cvr)/(left_ cvr+right_ cvr). li were compared to those obtained in volunteers that provided a % confidence interval for | limca |< . . basal perfusion was measured using dynamic susceptibility contrast. results: basal perfusion measurements were symmetrical in all patients. no adverse reaction to hypercapnia was detected. cvr values ranged from . to . with m±sd= . ± . . among these patients, three patients had a normal |limca|< . ranging from . to . ( . ± . ), and four patients had an abnormal |limca|> . ranging from . to . ( . ± . ). all abnormal li values identified the mca territory ipsilateral to the stenosis. conclusion: these preliminary results show that among patients with severe stenosis of mca, several patients have abnormal |limca| in the territory ipsilateral to the stenotic artery, suggesting significant cvr impairment that might be at risk of haemodynamic stroke. cvr fmri should be considered to better define treatment strategy, including intravascular stenting. purpose: in this study, we aimed to evaluate the endothelial functions in patients with nonalcoholic fatty liver disease (nafld). in this observational case-control study, a total of patients with nafld and age and sex-matched healthy controls were enrolled. in both patients and controls, levels of asymmetric dimethylarginine (adma), systemic endothelial function (brachial artery flow-mediated dilation) (fmd) and carotid artery intima-media thickness (c-imt, mm) were measured. endothelial functions of the brachial and carotid arteries were evaluated by vascular ultrasound. results: carotid intima media thickness was significantly higher in patients with nafld than controls ( . ± . versus . ± . mm, p < . ). the average c-imt measurements were found in groups of control, simple steatosis and nafld with (borderline and definitive) nash as . ± . , . ± . and . ± . mm, respectively. the differences between groups were significant (p < . ). measurement of brachial artery fmd was significantly lower in patients with nafld compared to controls ( . ± . versus . ± . %, p < . ). fmd measurements in groups of control, the simple steatosis and nafld with nash as . ± . , . ± . and . ± . %, respectively, and the differences were statistically significant (p < . ). the increase in c-imt and decrease in fmd were independent of metabolic syndrome and it was also more evident in patients with simple steatosis and nash compared to controls. conclusion: our data suggested that nafld is associated with endothelial dysfunction and increased early atherosclerosis compared to healthy subjects. purpose: this study aimed to assess image quality and radiation dose of ct angiography (cta) in kidney donors obtained with automated kvp selection and sinogram-affirmed iterative reconstruction (safire), using scans with fixed kvp and filtered back projection reconstruction algorithm as the comparison. methods and materials: mean attenuation, contrast-to-noise ratio (cnr) and signal-to-noise ratio (snr) at abdominal aorta, right renal artery (rra) and left renal artery (lra) were measured in kidney donors who had undergone cta with tube current modulation, kvp, filtered back projection reconstruction algorithm (group a) and were compared with bmi-matched kidney donors who had undergone cta with automated kvp selection and safire (group b purpose: cerebral small vessel disease (svd) is a common cause of cognitive impairment. white matter hyperintensities (wmh) and lacunar infarcts are the commonest magnetic resonance imaging (mri) parameters observed in clinical practice. the relationship between these findings on mri and cognitive impairment remains unclear. the aim of our study was to determine the relationship between lacune count, total lacune volume and location of lacunes with cognition. methods and materials: patients with lacunar stroke and wmhs were recruited to the prospective scans study. baseline data (n= ) was used for this analysis. multimodal mri and neuropsychological testing were performed. lacunes were identified and counted by a neuroradiologist on a t image, then mapped using an automated region growing technique. lacunar volume was calculated from the resulting masks, and lacunar location automatically determined by projection onto standard atlases. t wmh volume and brain volume were also measured. results: in multiple regression controlling for wmh volume and brain volume, both the lacune number and the total volume were related to a significant decrease in executive function (number: beta=- . , p < . ; volume: beta=- . , p < . ) and processing speed (number: beta=- . , p < . ; volume: beta=- . , p < . ). lacunes in the thalamus were associated with impaired processing speed performance (p < . ). one can infer a number of things relating to cognitive impairment when looking at an mri scan of a patient with cerebral small vessel disease. ) the number of lacunes are a better predictor of cognitive status than diffuse wmh and ) thalamic lacunes, in particular, are associated with impaired processing speed. purpose: to perform qualitative and quantitative analysis of altered haemodynamics of liver cirrhosis patients after tips-stent-graft implantation and volunteers using time-resolved flow-sensitive d mri at t. our study group consisted of liver cirrhosis patients including an examination before and after stent-graft implantation as well as volunteers. d liver flow characteristics in the arteries and portal vein were evaluated using flow-sensitive d mri at t mri with a spatial resolution of . x . x . mm³ and temporal resolution of . ms. hepatic flow visualisation was performed using d streamlines and time-resolved particle traces. quantitative evaluation included retrospective extraction of regional maximum and mean velocities, flow volume, vessel area as well as pulsatility and resistance indices. results: d streamlines and particle traces visualisation in the arterial and portal venous system could successfully be performed for almost all patients and volunteers. quantitative results reveal maximum and mean velocities tend to be lower in mri compared to doppler ultrasound, area showed significant lower values for us (p < . ). comparing the changes after tips-stent-graft implantation the data results demonstrated an increase of velocities and flow volume in the venous system as well as hepatic artery. conclusion: flow-sensitive d mri enabled a qualitative and quantitative evaluation of arterial and portal venous haemodynamics of liver cirrhosis patients before and after tips-stent-graft implantation including a volunteer group. flow-sensitive d mri may be a standardised method with complete volumetric and functional coverage of the blood flow haemodynamics providing additional information in patients after tips-stent-graft implantation. on a -point-scale. signal-to-noise ratio (snr) and contrast-to-noise ratio (cnr) was calculated with roi measurements. results: snr of the common carotid artery and middle cerebral artery was . ± . and . ± . (group a) versus . ± . and . ± . (group b). cnr was . ± . and . ± . (group a) compared to . ± . and . ± . (group b). subjective iq was excellent in both groups (mean score . ± . versus . ± . ). differences between the two groups were not significant. the osdr algorithm xcare™ does not compromise iq of head and neck cta. its application can be recommended for cta in clinical routine to protect the thyroid gland and ocular lenses from unnecessary high radiation. precision of pulmonary vein diameter measurements assessed by ce-mra and steady-state-free precession imaging f. henes, p. bannas, m. regier, j. buhk, k. müllerleile, g. adam, m. groth; purpose: to evaluate inter-and intraobserver reliability of pulmonary vein (pv) diameter measurements by contrast-enhanced magnetic resonance angiography (ce-mra) and ecg-gated d unenhanced steady-state-free precession sequences (ssfp). methods and materials: ce-mra and ssfp of pv in patients were evaluated. pv diameters were measured in transverse and coronal orientation at predefined levels by two independent readers. intraclass correlation coefficient (icc) and bland-altman analysis (ba) were used to assess inter-and intraobserver reliability and variances. f-test was performed for comparison of intra-and interobserver variances. pearson´s correlation coefficient and ba were used to compare ce-mra and ssfp. a t-test was used to determine possible significant differences between the measurements. results: there was moderate correlation (r = . , transverse; r = . , coronal) without significant difference in diameter measurements between ce-mra and ssfp (p = . , transverse; p = . , coronal). intraobserver limits of agreement (lag) ranged between ± . cm (transverse) and ± . cm (coronal) for ce-mra versus ± . cm (transverse) and ± . cm (coronal) for ssfp. interobserver agreement showed lag ranging between ± . cm (transverse) and ± . cm (coronal) for ce-mra versus ± . cm (transverse) and ± . cm (coronal) for ssfp. only transverse ssfp measurements revealed icc > . . intra-and interobserver variances did not reveal significant differences between ce-mra and ssfp in any orientation (all p-values > . ). conclusion: ssfp and ce-mra enable comparable precision of pv diameter measurements. however both methods revealed a wide range of intra-and interobserver agreement, which has to be thoroughly considered in the clinical use. the application of ct angiography with whole brain perfusion imaging in the evaluation of patients with transient ischaemic attack h. shi, f. yang, x. ma, w. guo, s. dong, m. qiao; beijing/cn (shihuiping@yahoo.com) purpose: to investigate the -row low-dose volume ct perfusion imaging combined with ct angiography in the evaluation of cerebral microcirculation changes of transient ischaemic attack (tia). sixteen cases of tia patients (male , female ) underwent row of dynamic volume ct perfusion imaging combined with ct angiography during ml mgi/ml contrast agent injection and acquired the blood flow perfusion parameters such as regional cerebral flow (rcbf), regional cerebral volume (rcbv), mean transit time (mtt), time to peak (ttp) and delay time (dly) and dynamic d-cta images. the measured region including the ischaemia side local lesions and the corresponding healthy side brain tissue perfusion parameters. the dynamic d-cta images were reconstructed to show vascular stenosis site and vascular collateral circulations. the stenosis of one side middle cerebral artery in cases, one side posterior cerebral artery in cases. the cbf, cbv, mtt, ttp and dly in stenosis and healthy side had statistically significant difference (p < . ) and the parameters were . ± . and . ± . ml/ ( g •min), . ± . and . ± . ml/ g, . ± . and . ± . s, . ± . and . ± . s, . ± . s and . ± . s. the one-stop ctp/cta imaging technique significantly improves the accuracy and efficiency in the evaluation of cerebral arteries stenosis, infarct localisation and abnormal blood perfusion and is a perfect imaging tool for the tia diagnosis. comparison of high pitch ( ) and standard pitch ( . ) ct angiography using -slice dual-source ct in patients with peripheral arterial disease k. choo, j. park, j. kim, j. roh; busan/kr (speedsmile@hanmail.net) we investigated the effect of high-pitch ( ) ct angiography with good image quality on qualitative and quantitative parameters and reduced the radiation dose in patients with peripheral arterial disease. methods and materials: eighty patients were divided into two groups; the protocol was high pitch in patients group and standard pitch in the other patients group. for quantitative analysis we calculated the mean arterial attenuation, the mean difference between maximum and minimum attenuation values, contrast-tonoise ratio (cnr) and figure of merit (fom). in addition, visual scores were used for qualitative evaluation. results: there were no significant intergroup differences in mean arterial attenuation (high pitch vs. standard pitch: . ± . vs. . ± . hu) and in the mean difference between maximum and minimum attenuation (high pitch vs. standard pitch: . ± . vs. . ± . hu). both the mean cnr and the mean fom were not significantly different (high pitch vs. standard pitch: . ± . vs. . ± . , . ± . vs. . ± . , respectively), and there was no significant intergroup difference in visual scores. the mean dose-length product was significantly lower at high pitch than at standard pitch ( . ± . vs. . ± . . mgy·cm). the high-pitch protocol ct angiography with -slice dual-source ct allows for reduction of the radiation dose by approximately % versus standard pitch protocol ct angiography with -slice dual-source ct without deterioration of vascular enhancement and image quality. differential diagnosis of cervical artery dissection and intra-arterial thrombosis using mri and mra m. dreval, m. krotenkova, l. kalashnikova, l. dobryinina, r. konovalov; purpose: this study aimed at exploring mri and d-tof mra in differential diagnosis of intra-arterial thrombosis and cervical artery dissection (internal carotid artery and vertebral artery) in different periods of disease using the contrast index. a total of patients with extracranial artery dissection manifested by ischaemic stroke or isolated headache ( men, woman, mean age . ± . years) and patients ( men, woman, mean age . ± . ) with ischaemic stroke due to intra-arterial thrombosis were studied. scanning protocol included d-tof mra sequence for extracranial internal and vertebral arteries and t fat suppression (f/s) sequence for neck in axial plane. mrt/mra were carried in dynamics and obtained data were analysed in time intervals: - days, - days, - days, - days, - days and - days. intramural haematoma (imh), intra artery thrombus (iat) and m. sternocleidomastoid signal intensity was measured and contrast index calculated. results: after statistical analysis of the data with the use of non-parametric statistical methods (mann-whitney u test) it was revealed that value of the contrast index of imh was higher than that of iat within - time interval ( to days) (p < . ). the contrast index did not differ significantly within first days and during months. the subjective visual analysis showed the same results. conclusion: mri sequences as t f/s and d-tof mra could be useful for differential diagnosis of imh and iat within the interval of days to months of the disease. impact of organ-specific dose reduction on image quality of head and neck ct-angiography r.s. lanzman, l. schimmöller, p. purpose: assessment of coronaries on patients with high heart rate (hr) using present generation ct is challenging due to an increase of vessel motion. the purpose of this study was to evaluate the performance of a novel coronary motion compensation algorithm on patients with a hr > bpm. prospective or retrospective ccta scans on patients with minimum hr of (mean: ) where acquired using a discovery ct hd (ge healthcare, waukesha, wi) and reconstructed using conventional ccta reconstruction algorithm (std) and novel coronary motion compensation algorithm, snapshot freeze (ssf). two senior cardiovascular radiologists evaluated diagnostic image quality of coronary segments in a blinded manner using a -grade scale ( non-diagnostic, excellent). coronary segments were assessed. results: overall number of diagnostic segments was higher using ssf compared with std ( % vs. %). overall average score of ssf reconstructed segments was significantly higher compared with std reconstruction ( purpose: to evaluate the feasibility and imaging quality of double prospectively ecg-triggered high-pitch spiral acquisition mode for coronary computed tomography angiography (ctca) in patients with atrial fibrillation (af). methods and materials: patients ( women, men; mean age . ± . years) were enrolled for ctca examinations using a dual-source ct with × × . mm collimation, . s rotation time and a pitch of . . double high-pitch mode was prospectively triggered first at % and later at % of the r-r interval within two cardiac cycles. image quality was evaluated using a four-point scale ( = excellent, = non-assessable). results: from coronary artery segments, . % ( / ) was rated as score of , . % ( / ) as score of , . % ( / ) as score of and . % ( / ) was rated as 'non-assessable'. the average image quality score was . ± . on a per segment basis. mean dose-length product (dlp) for ctca was . ± . mgy·cm, the effective dose was . ± . msv ( . - . msv). in patients with af, double prospectively ecg-triggered high-pitch spiral acquisition could be a feasible and valuable scan mode for ctca with a consistent dose below msv as well as diagnostic imaging quality. coronary artery calcium scoring from dual-source chest ct: purpose: to assess the concordance between ungated, high-pitch (thoracic) and ecg-gated (cardiac) examinations in the assessment of coronary artery calcium (cac) score. methods and materials: smokers (mean heart rate: . bpm) underwent dual-source ct examinations with acquisition of two sets of images during the same session: (a) an ungated, high-pitch scan over the entire thorax (pitch: . , temporal resolution: ms) (group ); (b) a prospectively ecg-gated scan over the cardiac cavities (group ). two operators independently analysed the cac load on both examinations and categorised the population according to the agatston score. results: the interobserver reproducibility was good for both techniques (group : kappa= . , group : kappa= . ). the mean absolute values of the agatston score did not significantly differ between groups (p= . ). there was good reproducibility between the two techniques in classifying the population according to the commonly used cutoffs (kappa: . ). the ungated technique adequately categorised out of the patients ( ); in the discordant cases ( / ; ), the ungated studies yielded lower scores than gated studies, with no more than one score category misplaced by the ungated studies. bmi and heart rates did not significantly differ between concordant and discordant scores (p= . , p= . , respectively). differences in cac scores between techniques were correlated to differences in the cac scores at the level of the right coronary artery (r= . ; p=. ). conclusion: despite the mean heart rate of the studied population, a good concordance in assessing the cac scores was found between ungated, high-pitch and ecg-gated examinations. diagnostic accuracy of free-breathing coronary cta using dualsource ct high-pitch acquisition: comparison of single and double scans with conventional angiography m.c. so , w.l. chin , c.m. wong , c.w. tai , m.w. leung ; hong kong/hk, singapore/sg (ninamc_so@yahoo.com.hk) purpose: to retrospectively investigate whether two subsequent prospectively ecg-gated high-pitch ct acquisitions can increase the diagnostic accuracy of coronary ct angiography (ccta) for free-breathing patients compared with a single acquisition and conventional angiography. methods and materials: twenty-one patients ( male, female, mean age . years) with heart rates < bpm unable to hold their breath underwent two immediately subsequent free-breathing ccta scans in dual-source ct prospectively ecg-triggered high-pitch mode, followed by conventional angiography within month. ccta data and conventional angiograms were evaluated by segment by two different observers. ccta image quality was rated on a four-point scale ( = excellent to = unevaluable) with ³ % diameter stenosis considered significant. purpose: radiation exposure reduction in cardiac cta using a novel iterative reconstruction algorithm (aidr d) with automatic exposure control (aec). methods and materials: patients were examined on a -row detector ct (aquilionone, toshiba medical systems) using kv, - cm z-axis, ms acquisition time, . mm slice thickness and mm fov. contrast medium injection was performed using a standardised protocol with . mg iodine per kg body weight. group (g ) consisted of patients (bmi= . ± . kg/m , hf= . ± . bpm) examined using bmi adapted tube current ( - ma) and a fbp reconstruction algorithm in combination with advanced noise reduction filters. in group (g ) patients (bmi= . ± . kg/m , hf= . ± . bpm) were examined using the novel reconstruction algorithm aidr d. for aec a target noise of hu was predetermined. analysis was performed using circular regions of interests placed into the descending aorta (da), left ventricular lumen (lv) and myocardial wall (mw). signal-and contrast-to-noise-ratio (snr, cnr) were calculated. doselength-products (dlp) were recorded and effective doses were estimated. results in g and g were compared using an unpaired t-test. results: both snr and cnr differed significantly in both groups: snr in g and g were . ± . and . ± . , respectively, in da (p= . ) and . ± . and . ± . , respectively, in lv (p < . ). cnr in g and g were . ± . and . ± . , respectively (p < . ). effective dose was in g ( . ± . msv) % less than in g ( . ± . msv; p < . ). conclusion: aidr d with aec allows for significant radiation dose reduction compared with advanced fbp reconstruction with bmi-adapted exposure. image quality parameters in the aidr d group were superior to the reference group indicating further dose reduction potential. purpose: the verbal interaction between the child and the radiographer in the radiographic examination is an unexplored, but important area of clinical practice. the aim of this study was to investigate the nature of that interaction between child and radiographer and the extent to which it varied as a function of the child's age. the participants in the study were female radiographers and children ( - years) examined for acute injuries. the verbal interactions of child and radiographer during the examination were videotaped and analysed using the roter interaction analysis system (rias). descriptive and non-parametric statistics were used to analyse the interaction data. the results revealed that % of the verbal interaction was carried out by the radiographer either to the child or to an escorting parent, while % was carried out by the child and % by the parent. of the radiographers' communication directed to children, % was categorised as task-focused exchange and % as socio-emotional exchange. of children's utterances, % was categorised as a task-focused exchange and % involved socio-emotional exchange. the distribution of task-focused and socio-emotional utterances varied with regard to children's age. more frequent utterances and more frequent socio-emotional exchange were found for interactions involving younger children. conclusion: these findings reinforce the need for radiographers to be flexible and sensitive in their interactions with children and to recognise the child's individual and developmental capabilities when engaging them in radiographic procedures. requesting x-rays at the right time to utilise the capacity of the radiology department: an everyday challenge m. mowinckel-nilsen; os/no (milh@helse-bergen.no) purpose: historic data shows that delayed ordering of x-rays makes it difficult to optimally utilise the capacity of the radiology department in a small orthopaedic hospital. what could be done to improve this? methods and materials: a method called patient-focused redesign (developed by leicester royal infirmary, adapted to norwegian conditions by ringerike hospital hf) was used as a tool to find a better workflow in ordering x-rays. a multidisciplinary team was assembled, and a project outline was made with a process demarcation. the team prepared a communication plan, mapped the current workflow, had a creative phase redesigning a new workflow, and measured the situation before the new workflow was tested in the hospital. an analysis of the old and new workflow was made. evaluation was done after the new workflow had been in place for . years; new measurements were done to see the effects of the changes in the workflow. results: numbers of steps in the workflow were halved, saving time for several professions. x-ray examinations not ordered on time were reduced by . %. examinations ordered a week or more before the images were taken, which is within the desired timeframe, were increased by . %. conclusion: patient-focused redesign is a good method for finding better and more efficient workflows; it can save time, increase the exploitation ratio of the equipment, and ultimately increase the quality of the radiographic service. discrepancies between ct and conventional angiogram results were resolved by consensus together with a third observer. sensitivity, specificity and accuracy of single and double high-pitch scans were calculated on a per segment basis. estimated effective radiation doses were calculated using dose length product x . . results: ccta images were diagnostic for % ( / ) and % ( / ) of segments for single and double scans, respectively, and sensitivity, specificity and accuracy were %, %, % and %, %, %, respectively. the mean estimated effective radiation dose was . msv and . msv, respectively. in patients with heart rates ² bpm, free-breathing ccta using dual source ct double scans in high-pitch acquisition mode was associated with high diagnostic accuracy for the assessment of coronary artery stenosis at a very low effective radiation dose. author disclosures: w.l. chin: employee; siemens medical solutions. one beat coronary ct angiography using slices multidetector ct scanner in patients with atrial fibrillation to evaluate image quality and ionising radiation doses of ct coronary angiography using -slices multidetector ct in patients with atrial fibrillation (af). methods and materials: patients that have persistent af with median heart rate of bpm underwent coronary ct angiography using -slices multidetector ct with adaptive iterative dose reduction system. all ct examinations were performed using a one-beat prospective gating; in patients, that presented heart rate > bpm, was used a broad phase window width ( - % of r-r). the effective dose was assessed for every patient. coronary arteries were subdivided into segments using the american heart association's (aha) model. image quality was evaluated by two expert radiologists on a workstation (vitrea, toshiba) using a -score grading system: score (absence of motion artefacts), score (presence of mild artefacts), score (presence of moderate artefacts) and score (presence of severe artefacts). median score of both radiologist and inter-rater reliability (k coefficient) were assessed. results: image quality was judged excellent (score ) in . % of coronary artery segments ( / ), good (score ) in . % ( / ), fair (score ) in . % ( / ) and low (grade ) in . % ( / ). mean effective dose was . msv (range between . and . msv). inter-rater reliability was excellent (k= . ). conclusion: high image quality and low ionising radiations effective doses demonstrate that the newest generation of ct scanner overcome the limitation at coronary ct angiography that atrial fibrillation poses so far. influence of aidr on accuracy of plaque characterisation and lumen assessment during ct coronary angiography a. ursani, h. mehrez, h. kashani, n. paul; toronto, on/ca (ali.ursani@uhn.ca) purpose: to determine the impact of adaptive iterative dose reduction (aidr) on accurate lumen assessment in a custom-built arterial plaque phantom. methods and materials: custom-built cm coronary artery phantom with x . mm (g ) and x mm (g ) vessels, lumen stenosis , , , , and % due to hu and hu plaque; and x . mm (g ) and x mm (g ) vessels with lumen stenosis , , % due to - hu and hu plaque. the lumen measured + hu. volume ct (vct) was performed; spatial resolution μm with low-and high-resolution kernels (fc , fc , fc ), kvp and ma. . / . mm axial images were reconstructed ± aidr. in-line histography mapped average plaque ct# (hu) and average lumen ct# (hu) and vessel profile. in was measured and image contrast (c) calculated. results: lumen stenosis contrast data for soft filter kernel fc and calcified plaque hu: without aidr: g : %= / ; %= / ; % = / ; % = / ; g : % = / ; % = / ; %= / ; %= / . with aidr: g : %= / ; %= / ; %= / ; %= / . g : %= / ; %= / ; %= / ; %= / aidr improved mean contrast ~ % for calcified plaque and % for non-calcified plaque for all reconstructions with - % luminal stenosis (paired t-test, p² . ). aidr improved accurate representation of % lumen stenosis in . mm vessels. conclusion: aidr improves plaque image contrast by - % and visualisation of high-grade stenosis in . mm coronaries. this promises superior performance for accurate coronary plaque characterisation and lumen assessment. results: analysis of the results for the area under the curve (auc) demonstrated statistically significant differences in the accuracy of fracture identification between groups (p value < . ), when categorised with respect to post-graduation clinical experience. radiographers with greater and less than years clinical experience scored mean az scores of . and . , respectively. a trend in increased performance and increased clinical experience was also demonstrated with a mean increase of . % and . % in terms of sensitivity and specificity, respectively. conclusion: radiographers with increased clinical experience performed the most accurately with respect to auc, sensitivity and specificity findings. hospital category did not influence the radiographer's performance in this investigation: university teaching centre versus large regional centre. the acceptable standard following post-graduate image interpretation training is - % in terms of accuracy of skeletal fracture identification. graduate training programmes/cpd modules in clinical decision making are recommended as is a survey on a national scale to incorporate a larger sample size. purpose: to accurately measure the workload of radiographers and sonographers for the first time in the uk and compare them with that of consultant radiologists in a dgh. reporting data for sonographers, radiologists and reporting radiographers at a large dgh was taken from electronic records. these were converted into an rvu score using an adapted version of the pitman-jones rvu system. reporting workload was calculated by dividing the total rvu scores by the number of pa spent reporting images by members of each group. results: there were sonographers working . pa/week, reporting radiographers worked pa/week, and consultant radiologists working . pa/ week during the period april -march . sonographer workload amounted to , . rvu per pa per year (rvu/pa/year). radiographer workload was to , rvu/pa/year. crude consultant radiologist workload was , rvu/pa/ year, but they spend . % of their time on non-reporting activities, giving a net score of , rvu/pa/year. the reporting radiographers and sonographers make a valuable and significant contribution dealing with the increasing radiology workload. however, radiologists are more productive per pa. differences in pay grades makes costeffectiveness between the groups more equal. radiographer's expectations for role development: a national survey in view of radiography students in final year of graduation c.m. mendes, a.f.c.l. abrantes, r.p.p. almeida, l.p.v. ribeiro, s.i. rodrigues; purpose: to investigate the role development expectations of graduate radiographers with a view to predicting the potential impact of a misalignment of these expectations on quality of the service delivery and staff retention. a self-applied questionnaire development by williamson and mundy ( ) in uk was validated for the portuguese language by the backtranslation method with permission of the authors and assigned to radiography students in final year of graduation in the portuguese health schools. a total of valid questionnaires, in the likert scale format, utilised attitude questions in relation to main themes of research (expectation, valence and knowledge) and were interpreted and statistically analyzed through descriptive statistics and spearman's rho correlation. the radiography students stated an expectation for role development opportunities with . % indicating that these expectations would be realized within ( . %) and ( . %) years of graduation. a significant and strong positive correlation (r= . , p= . ) between job satisfaction and expectation for role development in years after graduation was seen. farther, there were no significant differences between the health schools for the expectation, valence and knowledge. conclusion: there is an expectation and value assigned for role development opportunities. expectation is seen to be intrinsically linked with job satisfaction suggesting that misalignment of this would have a potentially negative impact on motivation and retention of the future radiography workforce. however, there is risk management in computed tomography using an incident reporting system m. antoniutti, s. doratiotto; treviso/it (sdoratiotto@alice.it) purpose: improving the management of patient safety by adopting best management practices for the governance of the system and the corporate network. methods and materials: analysis of the critical situation in the diagnostic computed tomography (ct) performed in - with incident reporting system (ir) using the instrument of audit and definition of improvement actions. results: improving actions have been taken together with a method of monitoring the most critical issues with greater severity or frequency of occurrence in the ct process. critical areas: high number of booking errors from the radiological studies of central booking, inappropriate requests by general practitioners (gps). improvement action (ia): organization of the audit with gps, the final shared document has been spread through the internet site. high number of patients not adequately prepared for the examination (non-hydrated, non-fasting, incomplete clinical information, and incomplete filling of the informed consent form examination). ia: a letter from the chief of radiology was sent to all departments to alert that requests for ct must be sent in. radiology correctly completed and audit with gps. errors found in pacs. ia: correction of pacs errors and permanent organization of audit. conclusion: this project helped the development of effective interventions closely related to the understanding of the organization's critical work in the ct process with the need to streamline the planning ct scan of the list to avoid an incongruous workload and to give each patient the right welcome. internal audits and permanent working groups have been proposed to actuate effective remedial actions. is a radiographer-led immediate reporting service for emergency department referrals a cost-effective initiative? m. hardy , b. snaith ; bradford/uk, wakefield/uk (m.l. hardy @bradford.ac.uk) purpose: demand for both emergency department (ed) and radiology services continues to increase across the uk while simultaneously, healthcare organisations are being asked to evaluate the quality of care provided and constrain service costs. national guidance on radiograph reporting times recommends ed radiographs are reported on day of patient attendance but in practice, delays in reporting persist. this study considers whether a radiographer-led immediate reporting service for ed referrals could provide a cost-effective service improvement solution. a pragmatic multi-centre randomised controlled trial was undertaken. patients were recruited and randomly assigned to an immediate or delayed reporting arm and treated according to group assignment. patient health gain was measured in terms of change in utilities derived from eq- d responses at baseline and -week follow-up. resources used and the costs of an immediate reporting service were analysed at the patient level and compared to standard reporting practices. results: radiographic examinations were performed ( patients). discordant radiographic interpretations were identified (n= / ; . %). interpretive errors were significantly reduced within immediate reporting arm. no significant difference was noted in the relative improvement in patient perceived health status between the arms of the study. the average cost saving per patient in the immediate reporting arm £ . . conclusion: radiographer-led immediate reporting of ed radiographs is a cost-effective service development and its universal introduction could make a significant contribution to the current drive to increase service productivity within current budget constraints. an investigation into the ability of irish radiographers: in the identification of wrist and scaphoid fractures a.p. tyrrell , l. rainford ; kilkenny/ie, dublin/ie (louise.rainford@ucd.ie) purpose: to investigate the ability of irish radiographers in identifying and locating wrist/scaphoid fractures, to add to the evidence base for role expansion. in total, radiographers across two university teaching and two large regional hospitals in ireland participated. the computer application ziltron demonstrated plain film wrist radiographs in a free-response operating characteristic (froc) study. the data set contained abnormal images (fracture (s) present) and normal (non-fracture). "truth" was determined by the radiology report. fracture were categorised: obvious to subtle. statistical analysis was performed by jafroc application. friday provides insight into the influence of technology on the professional development and practice in this field. in august , a postal questionnaire was distributed to hospital sites across the uk operating both a radiography and trauma service. information was sought relating to: the type of trauma and radiography service operated; details of the rads operated, including education and audit to support radiographer participation; the mandatory/voluntary status of the rads; and the imaging technology operating within the organization. results: a total of (n= / ; . %) responses were received within the defined timeframe. analysis of the data is ongoing but will include a descriptive summary of current practice across the uk with regard to "red dot", commenting and reporting by radiographers and assessment of the impact on the implementation of digital imaging technology across the uk on service levels compared to an earlier survey undertaken in . conclusion: radiographer contribution to the interpretation of trauma images is an expectation of uk radiographer practice. whether the profession has moved forward in its readiness to progress beyond "red dot" and embrace commenting is yet to be seen and this presentation will provide an insight into practice boundaries and variations that exist. : purpose: diagnostic value of dynamic contrast-enhanced perfusion mri in detection and characterisation of endometrial cancer, correlated with tumour grading, being the histopathological analysis as the standard of reference. a total of patients with histologically proven endometrial carcinoma underwent a dedicated pelvic mri examination ( . t system, achieva, philips), using high-resolution pelvic phased array multicoil. each patient scan a lack of social recognition of the radiographer, suggesting the need to promote measures to increase the profession recognition. job satisfaction among radiographers in switzerland: a national survey n. richli meystre, p. lehmann, n. mamboury; lausanne/ch (nicole.richli@hesav.ch) purpose: the technological improvements in radiology over the past decade have resulted in an important rise in demands for radiological examinations and treatments. an increasing number of well qualified radiographers are needed and healthcare authorities are worried about the growing shortage of radiographers. job (in)satisfaction has been highlighted as a contributing factor to turnover, respectively, to long-time retention. the aim of this survey was to appreciate workplace conditions and job satisfaction among radiographers. methods and materials: all radiographers working in switzerland were invited to participate with an online questionnaire. different factors contributing to job satisfaction were scored from - (very unsatisfied) up to + (very satisfied). results: radiographers completed the questionnaire. the response rate is estimated at %. % are working in diagnostic, % in nuclear medicine and % in radiooncology. % are working for more than years in the same place. the overall job satisfaction level was scored at . . the highest levels were reached for the diversity of job activities (+ . ), the quality of radiology facilities (+ . ), teamworking (+ . ) and autonomy (+ . ). the lowest levels were reached for collaboration with radiologists (+ . ), salary (+ . ) and career opportunities ( ). conclusion: radiographers in switzerland are rather satisfied about their job and the workplace conditions. in order to avoid shortage, efforts should be taken to increase the number of radiographer students and in supporting returnees. jobenrichment measures are seen as a necessity for retention in a profession with low career opportunities. progression of quality improvement works in radiography by radiographers r. gullien, j.g. andersen, a.e. haakull; oslo/no (uxraul@ous-hf.no) purpose: to visualise the ongoing progression over years in quality improvement work in radiography by radiographers and share our experiences. methods and materials: ) as a basis through the entire improvement work, the national quality assurance manual (qam) that specifies how to measure the quality assurance work was used. ) practiced the method in the department as basic measurement individual and overall measurements (static/snapshot). ) individual and overall measurements recorded several times over a period to see changes (dynamics/moving range) (local). ) implemented targeted improvements. ) measured inter-variability among the quality control (qc) radiographers. ) training the qc radiographers to avoid differences between them. ) national meeting with representatives from all counties (national). ) comparison across the counties and input to the audit of the qam. ) cooperation with hospital outside norway, benchmarking the system, comparison across countries (international). results: radiographers were trained by self-assessment: their knowledge was updated, their skills were developed, their attitude to regular audit was changed and improved, their own performances against international and national standard and objectives were reviewed. targeted initiatives against unacceptable variances in performance are necessary. time set aside to allow radiographic quality assurance work, analysing, evaluating and act accordingly. qc radiographers have the responsibility of ensuring the essential quality improvement and assurance work. conclusion: progression is from snapshot/static to dynamics/moving range, from general to focused measures, from local to national, from national to international. quality improvements became more and more complex over time. advancements and developments are important in addition to the continuous implementation of basic training and instructions. radiographer contribution to the interpretation of trauma radiographs: a survey of uk practice b. snaith , m. hardy , e. lewis ; wakefield/uk, bradford/uk (bev.snaith@midyorks.nhs.uk) purpose: radiographer abnormality detection schemes (rads) were introduced in the uk in the mid- s with the development of the "red dot scheme". this presentation reports the findings of a new survey and establishes the current position of rads (including "red dot", commenting and reporting) across the uk and was with the obturator in cases and with the internal pudendal in one case. the angle of origin of the uterine artery on the right side showed a mean of . ° (sd: . , range: °- °). on the left side the angle showed a mean value of . ° (sd: . , range: °- °). the uterine artery arises typically directly from the iia anterior division. atypical origins like origin from the iia main stem or from the iia posterior division should be searched for when the artery could not be found in its typical location. fibre tracking evaluation of sacral nervous pathways d architecture in women affected by endometriosis m. sergi, v. vinci, s. bernardo, p. sollazzo, m. saldari, l. manganaro; rome/it (mariaeleonora.sergi@gmail.com) purpose: to evaluate feasibility of tractography to study sacral nerves in women affected by pelvic endometriosis. we enrolled groups of patient: women with us diagnosis of endometriosis and a control-group of women. with t mri, we reconstructed nervous pathway postprocessing dti images. we analysed main parameters: d architecture of nervous pathways and fractional anisotropy values (fa). we analysed fibres length and branches morphology, thereafter we assigned to each a range of values obtaining main classes of pathways: st class (normality, - ), nd class (mild alteration, - ) and rd class (severe alteration, - ). results: analysing d nervous pathways, we obtained a homogeneous distribution of the control group ( pt) in the first class (normal pathways). all cases of endometriosis of the posterior compartments ( / patients) presented an abnormal pathway ( rd class), while remaining cases with anterior-medial localisation were equally distributed in st and nd class. we obtained low fa values in both groups; however, in case-control group range values were included between . and . while in patient groups fa values were lower between . and . . conclusion: fibre tracking allowed a complete evaluation of the female pelvis defining the global situation of the patient and leastly formulating a potential explanation to symptoms. fibrotic reaction, adhesions and nerves growth stimulation factors may explain both of the altered branch morphology and the lower fa values. we suggest tractography as a complementary tool for the female pelvis study, representing the only non-invasive way to study nervous pathways. purpose: to verify whether mri accuracy in diagnosing deep infiltrating colorectal endometriosis (dice) can be improved using an association of two selected findings. laparoscopy or histopathology was taken as the gold standard. methods and materials: imaging database of our institute was retrospectively reviewed. t -weighted mr images were evaluated by two experienced radiologists using two criteria. first, not thickened or thickened intestinal wall surrounded by fat-plane interface represents a normal result; nodules/hypointense plaque-like lesions in the adjacent fat-plane joint to thickened intestinal wall are considered an abnormal result. second, not thickened or thickened intestinal wall surrounded or not by fat-plane interface represents a normal result; nodules/hypointense plaque-like lesions in the adjacent fat-plane joint to thickened intestinal wall showing "radiating retracting shape" are considered an abnormal result. a third radiologist looked in medical history for laparoscopy and histopathology. mri results were compared with laparoscopy or histopathology findings by x tables and were statistically analysed (k statistics). . years) with clear symptoms attributable to pelvic floor dysfunction. all patients were given a questionnaire designed to obtain physiological data (age, gender, bmi) and pathological (diabetes, comorbidities, previous pelvic surgery). the mri provided a morphological study with t -weighted sequences in the axial sagittal and coronal plane and an cinematic fiesta (fast imaging employing steady-state acquisition) in the sagittal plane at rest and during the phase of maximum straining, to measure the line pubo-coccygeal (pcl), the line h (pelvis diastasis) and the m (lower pelvis). results: bmi correlated significantly with h (p = . ) and pcl (p = . ), while age correlated with h (p = . ) and m (p = . ). the parity but not the number of children causes a significant increase in pelvic lowering (p = . ) as well as previous pelvic surgery (p = . ). the pathophysiological changes are predictive of morphometric parameters obtained with mri. because of its fast acquisition a cinematic sequence could be advisable in all study protocols of female pelvis. origin of the uterine artery in females using three-dimensional reconstructed contrast-enhanced mr angiography before uterine purpose: to describe the patterns of origin of the uterine artery from the internal iliac artery (iia) before uterine artery embolisation (uae) using three-dimensional ( d) reconstructed contrast-enhanced mr angiography (ce-mra). the study was retrospectively performed on females (mean age . year). pre-embolisation ce-mra was performed before uae. d images were reconstructed using syngo-vesselview application. for each uterine artery the point of origin was identified and the angle which the artery makes with its main stem of origin was calculated. the uterine artery was detected in ( . %) of the ( patients) arteries. the artery originated directly from the iia anterior division in arteries of the detected arteries ( . %), from the iia bifurcation point in arteries ( . %), from the iia main stem in arteries ( . %) and uterine artery ( . %) originated from the iia posterior division. the uterine artery originated indirectly from the anterior division with a common segment in arteries ( . %). the common origin friday measured on the mr console and compared among positions. the obstetric conjugate and the sagittal inlet and outlet were both assessed in the midsagittal plane. results: mr pelvimetry in the different positions proved feasible in all subjects, yielding diagnostic quality images in every volunteer and pregnant woman, although the hand-to-knee positions were found difficult to maintain. in the hand-to-knee position, pelvic inlet reduced from . cm to . cm and obstetric conjugate from . cm to . cm. in contrast, sagittal midpelvic diameter enlarged from . cm to . cm, pelvic outlet anteroposterior diameter from . to . cm and sagittal pelvic outlet diameter from . cm to . cm. our results showed that a hand-to-knee birthing position expands sagittal midpelvic diameter, pelvic outlet anteroposterior diameter and sagittal pelvic outlet diameter, suggesting facilitation of labour and delivery. retrospective analysis of elements that can predict short-and longterm outcome in patients affected by uterine leiomyomas and treated with mrgfus purpose: to retrospectively evaluate predictive factors to obtain an optimal treatment of uterine fibroids treated using magnetic resonance guided focused ultrasound (mrgfus). methods and materials: fibroids ( ± mm) in symptomatic women (age average ± ) were treated using mrgfus (exablate ) combined with a t mr unit (ge). t si and t si of fibroids were measured on pre-treatment examination before and after administration of gadolinium (gd-bopta, bracco); also the distance between centre of myoma and skin, skin thickness, maximum diameter and volume of fibroids were recorded. the day of treatment the non-perfused volume (npv) was recorded at the end of the treatment. it was considered treatment time in terms of energy (j) used and duration of single sonication. all parameters were related to final npv and volume shrinkage at months to established short-and long-term results of treatment. results: difference between t si of the fibroids and healthy myometrium significantly correlates with volume shrinkage ( %) and npv ( %, r= . ). t si on pre-treatment studies, distance between skin surface and centre of myoma ( ± mm) and skin thickness ( ± mm) show a mild correlation with volume reduction at months ( + mm, respectively r=- . p= . and r= . p= . ).moreover, there was positive correlation between measured parameters, sonication duration and energy necessary to obtain a > % npv ( ± %, r= . , p= . ). conclusion: si ratio on t w of uterine fibroids and myometrium on screening mri should be considered as predictor of positive outcome for mrgfus treatment. : purpose: we evaluated feasibility of t system in the detection of endometriosis implants in the douglas pouch, in order to offer a precise preoperative diagnosis of deep infiltrative endometriosis involving this particular region. methods and materials: from october and april , we enrolled women coming with either ultrasound or anamnestic suspect of endometriosis. pelvic mri examination was performed on t system. we theoretically divided female pelvis in three compartments and concentrated on the posterior one, evaluating, in particular, the uterosacral ligaments and the specific signs of posterior cul-de-sac obliteration. results: mri diagnosed posterior cul-de-sac obliteration in / patients. we detected in / cases nodular endometriosis implants in pcs; signs of fibrotic plaque on the uterine serosal surface were identified in / cases; / cases showed a tethered appearance of the rectum, / cases presented an elevation of the posterior vaginal fornix. in / cases strands between uterus and intestine was clearly depictable, at last, involvement of utero-sacral ligaments (usls) and signs of utero-sacral ligaments involvement were identified in / cases. moreover, glandular-like collection localised behind uterus was identified in / cases. mri findings were compared with laparoscopy, thus obtaining a sensitivity value of %, and specificity value of % conclusion: precise preoperative mapping of posterior cul-de-sac region is essential for a preoperative planning. in our work t mri revealed excellent in the evaluation of posterior cul-de-sac obliteration associated with an optimal evaluation of the utero-sacral ligaments, due to the higher contrast spatial resolution. diffusion-weighted magnetic resonance imaging of the female pelvis: do apparent diffusion coefficient values of the fat tissue change over the menstrual phases? purpose: to establish whether the apparent diffusion coefficient (adc) measured with dwi in the pelvic fat tissue of healthy reproductive-age women significantly varies from the proliferative to the periovulatory phase of the menstrual cycle. methods and materials: women ( - years) , not assuming oral contraceptives nor referring any vaginal discharge or abnormalities of their menstrual cycles, underwent pelvic dwi ( . t, -channel coil, sagittal scans, b values: and mm/sec ) both at the th day after the beginning of the menstruation and repeatedly every day in the periovulatory phase; among these latter examinations, the one corresponding to the th day before the subsequent cycle was retrospectively selected. an adc value resulting from the average of three measurements obtained at slightly different position was calculated for each examination within a circularshaped, -mm diameter region of interest totally included in the adipose tissue of the ischiorectal fossa. the statistical significance of the differences between the adc values measured in the two menstrual phases was determined using the student's t-test per paired data. the adc values measured in the pelvic adipose tissue in the proliferative phase of the menstrual cycle (mean: . mm /sec, range: . - . ) were higher than those obtained in the periovulatory phase (mean: . mm /sec, range: . - . ). the difference was highly significant at statistical analysis (p < . ). the adc values measured with dwi in the pelvic adipose tissue of healthy reproductive-age women are significantly higher during the proliferative than in the periovulatory phase of the menstrual cycle. purpose: to evaluate alzheimer's disease premature diagnosis based on spectroscopy mri. we carried out a prospective study on patients ( women and men) whose ages ranged to years (mean age ± ). every patient presented mild or moderate cognitive impairment according to reisberg score ( - grade). standard brain mr and spectroscopy brain mr were performed using a t intensity mri device (archieva tx, philips healthcare, best, the netherlands). spectroscopy mr was focused in posterior parietal and frontal lobes gray substance using a unique volume ( x x mm) and two different echotimes, te ( and ). morphology and volume of temporal lobes were evaluated through flair coronal images which were used to quantify temporal horn width and so classify patients in four groups. jmrui (java magnetic resonance user interface) was used to calculate quantitative parameters in mr spectroscopy. mr was used to measure: calculation of naa (n-acetyl aspartate), cr (creatinine), cho (choline) and mi (myo-inositol) metabolites ratios. we used analysis of variance to compare metabolite ratios between the different patient groups previously defined. results: we found significant differences (p ² . ) between groups in naa/cho concentration (p= . ), both in long and in short eco times and frontal and parietal anatomical regions. no other significant differences between groups were found. conclusion: mr spectroscopy could increase efficiency in alzheimer's disease premature diagnosis as well as turning out to be a useful additional tool for the clinician next to clinical history. differentiating multiple system atrophy and parkinson's disease on t mri: a novel use of decision tree s. rajandran nair, l.k. tan, n. ramli, s.y. lim, k. rahmat, h. mohd nor; kuala lumpur/my purpose: differentiation of multiple system atrophy (msa) and parkinson's disease (pd) remains a clinical challenge. the purpose of this study was to develop a decision tree using parameters obtained from standard mri and diffusion tensor imaging (dti) to distinguish these clinical entities. we performed standard mri brain and dti at . t on pd and msa patients. linear, volumetry and dti (fractional anisotropy, fa and mean diffusivity, md) of putamen, substantia nigra, pons, middle cerebellar peduncles (mcp) and cerebellum were measured. a three-node decision tree was developed, with the aim of % specificity at node , % sensitivity at node and highest combined sensitivity and specificity at node . results: mean mcp width, anteroposterior diameter of pons and mean fa mcp with cut-off values of . mm, . mm and . respectively, were selected for the decision tree from nine parameters (mean width, fa and md of mcp; anteroposterior diameter of pons; cerebellar fa and volume; pons and mean putamen volume; mean fa substantia nigra compacta-rostral) that showed statistically significant (p < . ) differences between msa and pd. the decision tree accurately classified out of msa patients with an overall % sensitivity, % specificity, % ppv and % npv. the decision tree could be used as a diagnostic algorithm in the differentiation of msa and pd. subthalamic nuclei tesla t -relaxometry correlated to updrs scores in pre-deep brain stimulation ( purpose: degeneration within the subthalamic nucleus (stn) in parkinson's disease (pd) is a potential marker for targeting dbs. we aimed to investigate whether pre-and postoperative unified parkinson's disease rating scale (updrs) scores are related to t relaxation (t r) of the stn and whether there is a correlation of laterality between clinical assessment and t r. methods and materials: patients and controls were examined at tesla by a multicontrast spinecho sequence. stn and control volumes relaxation times were analysed updrs scores were determined during "on" and "off" pre-and postoperatively. follow-up checks (median years) subjects had stable disease (sd), had progression of disease (pd) and developed ad. baseline metabolic ratios ( h mrs) between the groups of patients indicated significant differences in the left frontal lobe in mi/h ratio, between patients with sd ( . ) and dp ( . ) (p = . ). in groups of patients with dp and ad there was a significant difference in naa/cr ( . vs. . ), (p = . ). conclusion: mi and naa seem to be very sensitive biomarkers for conversion from mci to ad. the significance of our metabolic ratio results needs further study. purpose: uric acid has been associated with focal vascular brain disease such as lacunar infarcts and white matter lesions. however, it is unknown whether uric acid also relates to global brain changes such as brain atrophy. we therefore studied the relation of uric acid with brain atrophy and whether this is coupled with worse cognitive function. in persons of the population-based rotterdam study (mean age . years), we studied the relation of uric acid levels with brain tissue atrophy and cognition, using linear regression models, adjusted for age, sex and putative confounders. brain atrophy was assessed using automated processing of mri. cognition was assessed using a validated neuropsychological test-battery and we computed compound scores of cognitive domains. results: higher uric acid levels were associated with white matter atrophy (difference in z-score of white matter volume per standard deviation increase in uric acid: - . ( % confidence interval: - . ; - . )). this was particularly marked when comparing hyperuricaemic to normo-uricaemic persons (z-score difference: - . (- . ; - . )). worse cognition was primarily found in persons with hyperuricaemia (- . (- . ; - . )). conclusion: hyperuricaemia is related to white matter atrophy and worse cognition. the neural correlates of anomia in the conversion from mild cognitive impairment to alzheimer's disease e. pravata' , j. tavernier purpose: language impairment is frequently observed in patients with alzheimer's disease (ad; in this study, we investigated the extent and distribution of brain atrophy in subjects with conversion from mild cognitive impairment (mci) to ad with and without naming difficulties. methods and materials: this study was approved by the institutional review board and was hipaa compliant. all subjects or their legal representatives gave informed consent for participation. ninety-one subjects from the alzheimer's disease neuroimaging initiative (adni) with (n= ) and without (n= ) naming impairment as per the boston naming test (bnt) underwent brain magnetic resonance (mr) imaging months before and at ad diagnosis. structural mr images were processed using voxel-based morphometry. longitudinal and cross-sectional comparisons between groups were performed to assess differences in gray matter (gm) loss patterns. results: during the -month prior to diagnosis, ad patients with naming difficulties showed distinct areas of greater gm loss in the temporal lobes, cingulate gyri, and precunei than patients without naming difficulties. gm volume in the left fusiform gyrus (brodmann area ) was greater in patients without naming impairment. this study provided evidence of distinct patterns and dynamics of brain atrophy in ad patients with naming difficulties when compared with those with intact language, as early as months prior to ad diagnosis. language deficits and their neuroanatomical correlates should be taken into account in the design of a structural imaging biomarker for the early detection of ad. gender differences in grey matter atrophy patterns in the mild cognitive and early alzheimer's disease m. spampinato , e. pravata' , b. langdon , k. patrick , r. parker ; charleston, sc/us, gainesville, fl/us (emanuele.pravata@gmail.com) purpose: to investigate gender-specific differences in grey matter (gm) volume loss patterns in amnestic mild cognitive impairment (amci) patients with and without progression to alzheimer's disease (ad) using mr voxel-based morphometry (vbm). we included amci patients ( males, females; age ± years), with (n = ) and without (n = ) conversion to ad, from the alzheimer's disease neuroimaging initiative (adni) cohort. three-dimensional mprage brain scans obtained one year before conversion from amci to ad and at ad diagnosis were available. the general linear model was performed to evaluate for differences over time in cognitive decline from the clinical dementia rating (cdr) scale. optimised vbm with spm was used to assess gm volume differences by performing cross-sectional and longitudinal group comparisons with two-sample and paired t-tests. results: both male and female ad converters showed significant cognitive decline at cdr (p < . ). total gm volumes significantly differed between all groups of males and females (p < . ). compared to stable amci, male ad converters showed atrophy progression one year prior to ad diagnosis in the limbic, temporal, parietal, frontal, insular lobes and deep gray nuclei, while female ad converters showed only one area of significant gm loss in the right uncus (p < . fwe-corrected). the extent and distribution of regional gm volume loss in amci to ad converters is strongly influenced by the gender. this finding has potential implications for therapeutic approaches in ad and should be taken into account in clinical trials. purpose: excessive daytime sleepiness (eds) is an important non-motor symptom of parkinson's disease (pd). the underlying neuropathological mechanism accounting for eds is not well understood. the purpose of the present study was to determine regional grey matter (gm) volume changes in pd patients with eds. scale ess ³ ) (eds-pd), age and disease duration-matched pd patients (epworth sleepiness scale ess ² ) and age-matched healthy controls were enrolled in the study. the χ and student's t tests were used to test for differences in demographic and clinical characteristics between groups. differences in gm volume between groups were evaluated by applying the voxel-based morphometry (vbm) method. results: total calculated levodopa equivalent dose was higher in eds-pd when compared to pd patients (p < . ). comparison of eds-pd with pd patients and controls showed increased gm volume bilaterally in the hippocampus, the parahippocampal gyrus, the fusiform gyrus and in cortical areas in the temporal, frontal and parietal lobes (p < . ). conclusion: eds-pd patients present increased regional gm volume in the mesolimbic/mesocortical dopamine pathway, which is activated during sleep. drug-induced gm volume increase through a process of neuronal plasticity may represent the underlying mechanism. purpose: olfactory dysfunction is the second most frequent feature of pd, occurring in - % of patients. recent studies suggest that the olfactory system is among the earliest brain regions involved in pd. diffusion-weighted imaging (dwi) and diffusion tensor imaging (dti) consent quantitative measures of the microstructural integrity of nuclei and fibre tracts. our aim was to assess fractional anisotropy (fa) changes of the olfactory tract in early pd patients (hoehn ed yahr stage - . ) and to correlate fa values with the clinical score of the olfactory deficits methods and materials: a case control study was conducted on pd patients responding to uk pd society brain bank for probable pd and healthy controls that underwent mri ( . t, avanto, siemens, erlangen, germany). we performed t weighted mprage, t and pd weighted tse and epi (on non-collinear directions at b and s/mm to assess dti) sequences. fa was computed with standard formulas. all subjects underwent upsit (university of pennsylvania smell identification test) results: we found a significant difference between fa values of the gyrum rectum subcortical white matter of pd patients and healthy controls ( . ± vs. . ±; p < . ). a significant difference was also found in upsit values between the two groups (p < . ). our results suggest that early olfactory dysfunction in patients with pd may be a primary consequence of damage to the olfactory tract. diffusion tensor imaging reaches the diagnostic sensitivity to assess early olfactory dysfunction in pd patients quantitative evaluation of myocardial perfusion reserve at and . tesla in comparison to invasive measurement of fractional flow reserve for detection of coronary artery disease t. walcher, k. ikuye, w. rottbauer, j. woehrle, p. bernhardt; ulm/ de (peter.bernhardt@uniklinik-ulm.de) purpose: fractional flow reserve (ffr) is considered as the standard invasive diagnostic tool to determine haemodynamic significance of coronary artery disease (cad). adenosine-perfusion cardiac magnetic resonance imaging (cmr) at . and tesla has been proven to be capable to noninvasively determine myocardial perfusion reserve, but has not been compared against each other and validated against ffr as standard reference. methods and materials: patients ( . ± . years) with suspected cad were included into the study. all patients were scanned at both field strengths, . and tesla, including adenosine and rest perfusion imaging. coronary x-ray angiography including ffr measurement in the left anterior descending (lad), circumflex (cx) and right coronary artery (rca) was then performed in all patients. myocardial perfusion reserve was calculated in myocardial segments for each field strength and compared to the ffr measurement of the supplying coronary artery. ffr ² . was regarded as relevantly reduced. in coronary arteries ( lad, cx, rca) a ffr ² . was found. receiver operator curve analysis yielded higher area under the curve for t in comparison to . t cmr ( . vs. . , p < . ) resulting in higher sensitivity ( . vs. . ) and specificity ( . vs. . ). conclusion: quantitative evaluation of myocardial perfusion reserve at and . tesla is capable to detect haemodynamic significance of coronary artery stenosis. in our cohort, the diagnostic accuracy at t seems to be superior to . t. dynamic stress computed tomography perfusion imaging for the detection of functionally significant coronary lesions purpose: to evaluate the performance of hyperaemic myocardial blood flow (mbf) derived from stress computed tomography perfusion (ctp) imaging in the detection of functionally significant coronary lesions defined by fractional flow reserve (ffr) ² . in a prospective cohort of patients with stable chest pain. coronary computed tomography angiography (ctca) and ctp were performed in patients ( males/ females; mean age ± years) referred to invasive angiography. a second-generation dual-source ct scanner (somatom definition flash, siemens) with a dynamic ecg-triggered axial shuttle mode was used. this technique provides an arterial input function and myocardial time-attenuation curves fitted to a -compartment model to give mbf. hyperaemia was induced by infusion of adenosine ( µg/kg body weight). three to minutes into the infusion, ml of contrast were injected. gantry rotation time was ms, collimation x . mm, tube voltage kv and the tube current-time product was mas/rotation. purpose: the use of ct-scans in assessment of coronary artery disease is rapidly growing. more selective referral of stable angina patients with intermediate probability of coronary artery disease (cad) to ct coronary angiography (ctca) may temper the health care spending on cardiac ct-scans. the value of updated algorithms using "in-office-evaluation" and calcium score (casc) is investigated. we evaluated retrospectively symptomatic stable angina patients who underwent "in-office-evaluation", unenhanced ct-scan for calculation of casc and ctca. outcome of our study was non-invasive diagnosis of obstructive cad (³ % lumen diameter narrowing) by ctca. two algorithms were developed. first algorithm used "in-office-evaluation" consisting of chest pain typicality, sex, age, risk factors and ecg. the second algorithm used both "in-office-evaluation" and casc. discrimination of both models was tested using the area under the roc curves (auc). patients were classified to low (< %), intermediate ( - %) and high pre-test probability (³ %) of obstructive cad. testing with casc or ctca was deemed appropriate in patients intermediate probability of cad. net reclassification improvement (nri) of algorithm was calculated in patients with intermediate probability of cad according to algorithm . results: discrimination of cad was significantly higher using algorithm compared with algorithm (auc: . vs. . , respectively). the "in-office-evaluation" algorithm reduced both unenhanced ct-scan and ctca by %. an additional % of ctca-scan was reduced using algorithm subsequently with nri of %. conclusion: updated algorithms using both "in-office-evaluation" and casc may reduce referral of stable angina patients to ctca by %. dynamic ct perfusion imaging for the detection of myocardial ischaemia: a first experience with a d semi-automated evaluation software u. ebersberger , r.p. marcus , u.j. schoepf , p. blanke , y. wang , l. geyer , a. purpose: to evaluate the performance of a d semi-automated evaluation software for its accuracy and time saving potential for ct perfusion myocardial blood flow (mbf) and blood volume (mbv) assessments compared to manual evaluation as well as to spect. methods and materials: dynamic, time-resolved myocardial perfusion ct datasets acquired using a dual-source ct system (somatom definition flash, siemens healthcare, forchheim, germany) were assessed both manually and by use of the semi-automated prototype for mbf and mbv, based on the aha -segment model. time required for each assessment was recorded. results were compared to spect as the standard of reference. results: segments were evaluated. ( . %) were excluded due to insufficient coverage. a comparison of mbf and mbv measurements using the prototype versus manual assessment showed high correlation (spearman's rank correlation coefficient = . / . , p < . ). mean evaluation time for mbf and mbv analysis was . ± . minutes with manual assessment and . ± . minutes with the use of the prototype (p < . ). conclusion: d semi-automated assessment of dynamic myocardial perfusion ct highly correlates with manual assessment. significantly decreased assessment time appears promising for the integration of myocardial perfusion ct in clinical workflows. friday protocol (adp): clinical examination, mdct-ca; the positive cases were recovered and underwent ca. if mdct-ca was negative for significant cad the patient was dismissed from the ed and taken under follow-up for years. the costs of every protocol and the amount of costs for individual methods were calculated. based on the results, the two diagnostic paths were compared about cost/effectiveness ratio. results: at timi score only % of the patients resulted with high risk, whereas mdct-ca was judged positive in % of the cases. mdct-ca compared to ca revealed an accuracy of . %, ppv and npv were % and %. the adp revealed lower costs than the protocol with only hospitalization ( € against €), and showed better cost/effectiveness ratio. at -year follow-up . % of the patients resulted well being. the adp can help better than timi score to rule out patients with undifferentiated chest pain. moreover, cost analysis demonstrated a better cost effectiveness ratio in comparison to the hospitalization, also confirmed with a long-term follow-up. purpose: transient ischaemic dilation (tid) in the setting of abnormal spect myocardial perfusion imaging (mpi) has been linked with increased cardiovascular risk. however, the significance of tid in the setting of an otherwise normal mpi study has not been clearly established. coronary computed tomography angiography (ccta) was utilised to evaluate the prevalence of atherosclerotic lesions and the severity of coronary stenosis in patients with tid with or without associated myocardial perfusion defects on spect-mpi. the study population consisted of patients who had undergone both ccta and stress/rest cardiac spect. in patients with tid coronary cta was used to evaluate each coronary segment for the presence and composition of atherosclerotic plaque and the degree of coronary stenosis. findings were compared with a : matched-pair control cohort without tid. results: tid was identified in a total of patients from a screening population of consecutively imaged patients. findings demonstrated that compared to tid negative risk-factor matched controls (n= ), tid positive patients had no significant differences in the presence and extent of atherosclerosis or the degree of coronary artery stenosis as evaluated by ccta. similarly, there were no significant differences in ccta measures of coronary artery disease (cad) in tid positive patients with normal perfusion compared to tid negative patient with a normal perfusion study (n= ). these results suggest that the presence of tid with an otherwise normal spect study does not reliably predict an increased risk for or the extent and severity of coronary artery disease. - ] ) underwent wb-cta ( x . mm) with an adapted contrast injection protocol (iomeprol- , mgi/ml; + ml@ ml/s). coronary arteries were divided into segments and the extra-coronary arteries into segments, detected stenoses were graded using a -point scale. an atherosclerosis burden score (abs) was generated for each individual and correlated to traditional cv (framingham risk index; fri). abs and fri were compared using kaplan-meier analysis, roc analysis and stepwise multivariable cox regression models. results: at baseline mean abs was . ± . and mean fri was ± . ; . ± . m after wb-cta all patients received an interview to determine health status. according to kaplan-meier curves, mean event-free time was of . ± . m for abs< , . ± . m for mm, distance to neurovascular structures at least mm, potential access, absence of articular involvement and planned cryoablation covering the entire lesion volume. characteristics of patients eligible for cryoablation were comparing with not selected patients. results: mean tumour size was mm ( - ). most frequent histological subtypes were unclassified sarcomas (n= ), liposarcomas (n= ), or myxofibrosarcomas (n= ). surgical treatment consisted in wide excision (n= ), or combined treatment (n= ). after surgery, the severe complications rate was . %. since relapse, mean follow-up was . months with a median overall survival of . months and median recurrence-free survival of . months. a subgroup of patients was identified and comparison with other patients showed that trunk, shoulder and pelvic girdle locations (p = . ), locally aggressive (p= . ) and deep (p= . ) tumours, ² cm (p= . ), and liposarcoma and myxofibrosarcoma subtypes (p= . ) were indicative of eligibility for cryoablation. conclusion: eligibility criteria as defined are useful for plan cryoablation as a technically feasible alternative to surgery for treatment of local relapse of sts. robot-assisted radiofrequency ablation of liver tumours: early experience b.j.j. abdullah, c.h. yeong, k.l. goh, b.k. yoong, g.f. ho, c. yim; kuala lumpur/my (basrij@ummc.edu.my) we report our preliminary experience of rfa of the liver tumours using a robotic-assisted guidance system. methods and materials: patients with lesions were treated using the robio ex (perfint healthcare, ma, usa) robotic positioning system. all the lesions were smaller than . cm diameter. all the procedures were performed under general anaesthesia. following baseline ct scans, the lesions were identified. the puncture site and trajectory were then determined on robio ex workstation. the angulation of the needle, depth of lesion, the fluoroscopic dose as well as the accuracy of placements was determined. the performance level of procedures was documented for each biopsy on a five-point scale ( - : excellent-poor). results: all the tumours were targeted successfully. one lesion in patients required minor readjustment. patients ( lesions) had needle placement with no cranio-caudal angulation, whereas patients ( lesions) had cranio-caudal angulation of up to . the orbital angulation ranged from to . the depth of needle ranged from . to . cm from skin surface. performance levels were all except in one patient ( ). the fluoroscopic (dlp) and total dose (ctdivol) for the entire procedure were ± mgy.cm and . ± . mgy, respectively. post-rfa ct scans showed successful ablation of the targeted lesions. no immediate complications were noted. conclusion: robotic-assisted planning and needle placement appear to be technically easier, it requires fewer number of needle passes, fewer check scans using logistic regression, ccs more than was the predictor of presence of oms (odds ratio . , . - . in % confidence interval). the prevalence of oms was significantly higher in patients with more than % stenosis and in patients with mixed and non-calcified plaques. the prevalence of oms on de-mri and significant coronary disease on ctca are not uncommon even in asymptomatic patients with type diabetes. ccs more than is the only predictor of oms. author epicardial fat volume and coronary artery disease at ct: racial differences in african american and white patients with acute chest pain p. apfaltrer , a. schindler , u.j. schoepf , j. nance , u. ebersberger , r. vliegenthart ; mannheim/de, charleston, sc/us (paul.apfaltrer@umm.de) purpose: thoracic adipose tissue likely promotes coronary artery disease (cad). possibly, differences in cad risk between races are influenced by racial differences in thoracic adipose tissue. we compared ct-derived measures of thoracic fat and potential correlations with cad between african american and white patients. methods and materials: age-and-gender-matched black and white patients ( black: mean age ± yrs, % men; white: mean age ± yrs, % men) who underwent thoracic dual-source ct for chest pain evaluation were retrospectively included. epicardial adipose tissue (eat) volume and mediastinal adipose tissue (mat) volume were quantified using an automated analysis algorithm. peri-coronary fat thickness (pft) was measured on reconstructed sections orthogonal to the right coronary artery centreline. non-calcified and calcified plaque volume was quantified by applying a threshold-based automated algorithm. cad was defined as % or greater coronary artery stenosis. patients with cad showed significantly higher eat than those without cad ( . ± . cm vs. . ± . cm , p < . ). significant correlations were observed between eat measurements and calcium volume (r= . ; p < . ). the relationship between race and extent of adipose tissue remained significant after adjustment for cardiovascular risk factors. conclusion: measures of thoracic fat were generally higher for symptomatic white than for black patients suggesting a differential relationship between thoracic adipose tissue and cad pathophysiology by race. purpose: the imactis navigation system with electromagnetic needle holder tracking was developed to allow interactive display of the needle trajectory in a d volumetric ct volume, allowing the radiologist to choose optimal entry point and track to the target during ct-guided percutaneous interventions. the ctnav trial compares the accuracy of the needle placement using standard ct procedure (ct group) and using the navigation system procedure (nav group). methods and materials: prospective, randomised, comparative, open, controlled study conducted between june and january in grenoble university hospital on patients who had to undergo a percutaneous ct procedure. patients were randomised to have normal procedure (ct group) or navigation system assisted procedure (nav group). the main outcome was the distance between the planned trajectory and the effective needle trajectory after the first placement attempt. significance was set at . friday dynamic contrast-enhanced mri (dce-mri) and histology, we assessed the impact of this therapeutic approach on the tumour vasculature. methods and materials: rats bearing breast cancer bone metastases were imaged using vct and dce-mri prior to and days after the onset of therapy; untreated (n= ) and treated (integrin inhibitor monotherapy; n= ) or together with antiresorptive agent (combination therapy; n= ) to assess osteolysis and functional mri parameters, respectively. mean vessel diameter and sma and collagen-iv-positive vessel area fraction were assessed histologically. results: compared to the control group, bone defect healing at the osteolytic site occurred in rats receiving monotherapy and even more frequent after combination therapy as shown by vct. in addition, we observed a profound effect of mono-and combination therapy on the tumour vasculature determined by dce-mri parameters amplitude and exchange rate constant. both therapy regimens induced elevated vessel permeability/perfusion in bone metastases, but opposite to monotherapy, combination of agents additionally elevated the blood volume. immunofluorescence analysis of osteolytic lesions revealed more tumour blood vessels after combination therapy and equally immature vasculature as compared to monotherapy. conclusion: upon treatment with integrin inhibitor monotherapy or in combination with an antiresorptive agent, vessel remodelling could be assessed by dce-mri. interestingly, the degree of vessel remodelling could be correlated with bone defect healing, so we conclude the existence of a strong interaction between tumour angiogenesis and bone turnover in lytic osseous lesions. purpose: islet transplantation is a less invasive/safer/repeatable option than surgical pancreas transplantation for type diabetic patients; it can be performed after kidney transplantation (iak), alone (ita) in patients without chronic renal insufficiency, or as an autotransplantation (iat) after pancreatectomy (immunosuppression unnecessary). steatosis is a consequence of islet engraftment: its meaning is controversial. our longitudinal study aimed to assess steatosis incidence at ultrasound after islet auto-and allo-transplantation, and to identify any relationship with graft function. ultrasound was performed at baseline/ / / months in islet-transplanted patients ( iak/ ita/ iat). steatosis first detection/ prevalence/duration/distribution were recorded. steatosic (s) and non-steatosic patients (ns) were compared for the following parameters at baseline/ / / months: insulin independence rate, ß-score, c-peptide, glycated-haemoglobin, exogenous insulin requirement, fasting plasma glucose, infused islet mass. results: steatosis was found in / patients, % ( / ) allo-transplanted, % ( / ) auto-transplanted (better outcome), with first detection at months, highest prevalence at year ( cases). s-patients had a significantly higher infused islet mass (ie/kg: s= . ; ns= . ) and worse basal metabolic conditions (ß-score: s= . ± . ; ns= . ± . ), but better islet function at the time of steatosis first detection (ß-score: s= . ± . ; ns= . ± . ), after which a progressive islet exhaustion, along with steatosis disappearance, was observed. conversely, in ns patients these parameters remained more stable in time. conclusion: steatosis at ultrasound is significantly less detectable in auto-transplanted-patients with better clinical outcome. it seems to be related to stressed islets' overworking activity (higher ß-score values when steatosis appears), and a higher infused islet mass. steatosis presence precedes metabolic alterations and (structural insight) was adapted in order to allow calibrated bone density and bone structure analyses of the vertebral bodies, using an underlying light weight calibration phantom with design for coronary calcium scoring (image analysis phantom® purpose: to validate a magnitude-based method, transposable on any imaging system and for all current clinical fields ( . and . t) for liver fat volume fraction (fvf) quantification without dominant component ambiguity problems. methods and materials: mr imaging was performed at . and . t using a multiple-angle multiple-gradient echo acquisition. a quantification algorithm correcting for relaxation time effects using a disjointed estimation of t and t * of fat and water and accounting for the nmr spectrum of fat was developed. validations were performed in a prospective comparative study with histology on patients with chronic liver diseases. results: mr-estimated fvf and histological results were strongly correlated (ρ= . ). roc analysis showed that fvf allowed the diagnosis of a mild (cut-off = . %) and a moderate steatosis (cut-off= . %) with a sensitivity/specificity of %. water relaxation times (t and t *) were found significantly reduced in patients with iron deposition (p < . ), whereas water t was found significantly increased in patients with cirrhosis (p < . ). conclusion: this method that can be performed at . and . t on all imaging systems provide an accurate quantification of the fvf in patients with chronic liver disease. fvf could be a relevant biomarker for the clinical follow-up of patients with nafld as well as to quantify steatosis in the full spectrum of chronic liver diseases. interestingly, thanks to the separated estimation of fat and water relaxation times, detection of cofactors such as iron deposition or cirrhosis in patients with nafld could be achieved. combination of liver intravoxel incoherent motion imaging with mr fat quantification at . t to distinguish between pure steatosis and nash purpose: to evaluate the combination of liver intra-voxel incoherent motion imaging (ivim) and a mri fat quantification method at . t to make the distinction between nash and pure steatosis. a multi-angle multi-gradient echo acquisition combined with a dedicated algorithm was used to quantify liver fat volume fraction (fvf), corrected for water and fat relaxation times and accounting for the nmr spectrum of fat. ivim was performed using a single-shot se-epi sequence, in free breathing, with b-values ( - - - - - - - - - - s.mm - ) and a weighted signal averaging procedure. three orthogonal diffusion gradients were sequentially applied. a ms tr, ms minimum te; axial slices of mm thick; × mm² fov; × matrix were used. ivim parameters (pure molecular diffusion coefficient (dslow), perfusion-related diffusion coefficient (dfast) and perfusion fraction (f)) were estimated. mr imaging was performed on a healthy volunteers group (n= ), and on patients with histologically confirmed pure steatosis (n= ) or nash (n= ). results: wilcoxon test showed that dslow was significantly lower when fat is present (fvf > . %) (p < . ). dslow and dfast were found significantly reduced between subjects with pure steatosis (brunt= ) and nash (brunt> ) (p < . ). conclusion: fat vesicles in pure steatosis restrict molecular diffusion without modification of micro-perfusion. in nash, fibrosis still increase the restriction of molecular diffusion compared to patients with pure steatosis and decrease the microperfusion as illustrated by the decrease of perfusion-related diffusion coefficient. these preliminary results suggest that combining mri fat quantification and ivim could be a none invasive mean to distinguish between pure steatosis and nash. quantification of steatosis hepatitis and liver iron overload in a population-based study using magnetic resonance imaging j.p. kühn , d. purpose: to describe hepatic biochemistry in biopsy-proven nafld states using p-mrs and to evaluate its diagnostic performance for distinguishing non-alcoholic steatohepatitis (nash). methods and materials: the cohort consisted of healthy controls (n= ), and nafld patients with liver biopsy, as follows: simple steatosis (ss, n= ), nash with non-significant fibrosis (nash-nsf, n= ) and nash with significant fibrosis (nash-sf, n= ). p-mrs was performed on a t mri to obtain signal intensities for phosphomonoesters (pme), phosphodiesters (pde) and component glycerophosphocholine (gpc), total adenosine triphosphate (atp) and component α-atp, and inorganic phosphate (pi). these were expressed as percentages relative to total phosphate and compared using one-way anova with post hoc bonferroni test. receiver operating curve (roc) analysis was performed to determine cut-off values with highest youden index. statistical significance was declared at α< . . results: compared with controls, all nafld groups had higher pde (p < . ). ss and nash-nsf had decreased pme (p= . - . ), increased gpc (p < . ), normal total atp (p= . - . ) and decreased pi (p= . - . ). nash-sf had normal pme (p= . ) normal gpc (p= . ), decreased total atp (p= . ) and normal pi (p= . ). α-atp was significantly decreased in both nash groups and identified as a potential diagnostic marker. the computed area under the roc was . , and an α-atp threshold of < . % gave a % sensitivity and % specificity for the identification of nash. conclusion: p-mrs shows observable spectroscopic patterns within the nafld spectrum. α-atp is a potential diagnostic marker for distinguishing nash from ss. clinical implications of fatty liver on hepatic diffusion-weighted imaging studied in healthy subjects h. dijkstra, a. handayani, p. kappert, m. oudkerk, p.e. sijens; groningen/nl (h.dijkstra @umcg.nl) purpose: to evaluate the diagnostic implications of fatty liver on dwi by assessing the hepatic fat fraction (hff) and t * of healthy subjects in eight liver segments in order to eliminate patient-related confounding factors such as cirrhosis and fibrosis. methods and materials: eleven healthy volunteers were examined with dwi (seven b-values) and two series of in-and out-of-phase dual-echo spoiled gradient echo sequences (spgr) to obtain the hff (dixon's method). a third spgr series was acquired to calculate t * relaxation. dwi data were analyzed using the ivim model: molecular diffusion (dslow), microperfusion (dfast) and the respective fractions (fslow/fast). for each subject, four circular regions-of-interest (ø . mm) were drawn in each segment according to the couinaud-bismuth classification. data with low snr< were excluded. ivim parameters were compared between groups of low (² . %), intermediate ( . ²hhf< %) and high hhf (> %). linear correlations between hhf, dwi parameters, and t * were assessed. results: in each segment, dslow decreased with increasing hff. dslow averaged over all segments differed significantly (p < . ) between low ( . × - mm /s), intermediate ( . × - mm /s) and high hff ( . × - mm /s). both dslow and t * decreased with hff (r = . ; r = . ). dfast and fslow/fast showed small intergroup differences (p < . ). conclusion: increasing hepatic fat fractions caused significant reduction of the molecular diffusion and shortening of t *. this implies that hepatic dwi hindered by fat leads to apparent fluctuations of the molecular diffusion and hypointensity on dwi images; this may induce false diagnoses such as fibrosis or cirrhosis. (p < . /p < . ), whereas there was no significant correlation between bat volume and the amount of subcutaneous adipose tissue (p= . ). bat activity was an independent, negatively influencing variable for liver fat content (p= . ). conclusion: bat significantly correlates with body fat composition, especially visceral fat mass considered relevant for the development of metabolic syndrome, and seems to be an independent regulator of hepatic steatosis. in-phase/opposed-phase mri and mr spectroscopic measurements for the quantification of liver fat content in morbidly obese patients h. agreement for the three individual liver segments (ii, iv and vii) had upper/lower limits of + . /- . %, + . /- . % and + . / - . % and insignificant biases of . % (p= . ), - . % (p= . ) and - . % (p= . ), respectively. conclusion: ip/op imaging and mrs are reliable methods for the assessment of lfc. ip/op imaging is superior in terms of processing time and liver coverage and provides information for cases with larger regional fat differences and is helpful for lipid assessment in the left liver lobe where mrs is impractical. purpose: pancreatic islets transplantation (islets-tx) is a promising treatment for patients with type- diabetes. neoangiogenesis of transplanted islets is a crucial phenomenon for engraftment and was investigated with dce-mri in mice. the aim was to use dce-mri in clinical islets-tx to evaluate the relationship between early vascular changes, islets loss and long-term clinical outcome. methods and materials: diabetic pts were enrolled. dce-mri was performed at baseline and days after islet-tx with a d-t w-tfe dynamic sequence (temporal resolution: sec; dynamics) acquired during gadolinium bolus injection. k-trans was assessed by dce-mri datasets. three patients received ferucarbotran labelled islets and were monitored with t *sequences (before islets-tx, days and each month after). unlabelled islets were infused in the remaining three patients. glycated haemoglobin, blood glucose, daily insulin request and stimulated c-peptide were monthly assessed in order to calculate beta-score ( - ) purpose: brown adipose tissue (bat) mass and activity is considered a significant factor for the development of adiposity and metabolic syndrome in humans, and represents a natural target for the modulation of energy expenditure. we evaluated the correlation of bat activity and active volume as detectable on fdg-pet/ct scans with abdominal body fat composition and liver fat estimation. methods and materials: fdg-pet/ct examinations in individual patients were screened for bat, resulting in patients and controls for subsequent analysis, matched for exam date and therefore ambient temperature, age, and gender. in addition to bat volume and activity, an automated segmentation was used to determine visceral fat and subcutaneous fat as well as lean tissue in the abdomen. liver fat was estimated in patients with non-contrast-enhanced ct. spearman rank correlation between parameters and a multi-variate model for liver fat excluding influencing parameters was calculated. results: bat volume and activity showed a significant inverse correlation with total adipose tissue (activity p < . /volume p= . ) and visceral adipose tissue in studies, which were mainly underpowered and of heterogeneous study design, different parameters were studied. most frequently studied parameters were tumour diameter or volume, ktrans, kep, ve, and apparent diffusion coefficient (adc). other parameters were analysed in only two or less studies. tumour diameter, volume, and kinetic parameters did not show any pretreatment differences between responders and non-responders. in two studies, pretreatment differences in adc were observed between study groups. at early response monitoring significant and non-significant changes for all parameters were observed for most of the imaging parameters. conclusion: evidence on distinguishing responders and non-responders to neoadjuvant chemotherapy using pretreatment mri, as well as using mri for early response monitoring, is weak and based on underpowered study results and heterogeneous study design. thus, the value of breast mri for response evaluation has not yet been established. s a c d e f g bfriday the role of magnetic resonance imaging in assessing residual disease and pathologic complete response in breast cancer patients receiving neoadjuvant chemotherapy: a systematic review r. prevos , m. smidt , v. gadovist®) was injected intravenously at a dose of . mmol/kg bw and six dynamic t w gre sequences (vibe) were collected. the contrast kinetics of all malignant lesions were analysed quantitatively on a pixel by pixel basis using a computer-aided detection system (icad). the signal enhancement pattern was coded by three colour intensities and three colour hues. pharmacokinetic changes were analysed based on the tofts model including vascular permeability and extracellular volume fraction. results: in comparison to the baseline mri, follow-up examinations showed a significant tumour size reduction of % on average. a decrease of colour hues and colour intensities demonstrated significant changes in contrast kinetics. vascular permeability revealed a statistically significant decrease (p < . ). however, extracellular volume fraction changes revealed only a slight decrease under chemotherapy (mean decline of %). the cad analysis provides a reliable evaluation of tumour size, contrast kinetics, vascular permeability and extracellular volume fraction within a reasonable time. this form of cad analysis provides a fast and reliable assessment of early treatment response, enabling a fast modulation of therapy for non-responders. purpose: to assess the use of recist, mrecist and volumetric measurements in patients with invasive ductal carcinoma (idc) with initially marked necrosis on neoadjuvant chemotherapy (nact). in prospective analysis of patients, patients were selected based on marked intralesional necrosis and examined times on mri: before the beginning, after the nd cycle and upon completion of nact (anthracycline/taxane-based regimen). the lesions were measured in axial plane according to recist and mrecist. the volumes of the entire lesion and of the viable tissue were computed. results: the longest diameters measured according to recist and mrecist and the appropriate volumes were significantly different initially, after the nd cycle and upon the completion of nact (p < . for all). the size of the lesions was significantly different with/without the necrotic areas. differences in tumour diameter and volume change (delta; %) between recist and mrecist were not significant after the nd cycle and upon completion of nact (p> . for both). according to either recist or mrecist, including the volume measurements, the same number of patients were classified in the same response category, i.e., early response -pr ( . %); late response -pr ( . %). conclusion: to our knowledge, this is the first trial testing the use of mrecist in extrahepatic setting. there was no significant difference in changes of diameters or the corresponding volumes according to recist vs. mrecist. further research in larger groups needs to assess the use of the tools in the follow-up of new nact protocols. purpose: to assess the potential value of fibrosis quantification using t mapping in hypertrophic cardiomyopathy (hcm) in comparison to late contrast enhancement imaging, circumferential strain and lv thickness. methods and materials: seventeen patients with hcm, and controls subjects were prospectively included. all patients underwent cardiac mr with the following sequences: ) cine sequence, ) tagging sequence cspamm tr/te= . ms/ . ms; matrix , fov , temporal resolution . ms, distance between tag: mm, short axis. ) molli sequence (tr/te= . ms/ . ms; matrix - , thickness: mm) acquired before and , , min after gadolinium injection (dotarem, . mmol/kg). ) late gadolinium enhanced sequence min after injection. t values were assessed in blood and in the segments of the mid-lv slice. statistical analysis were performed for patients and for segments with (+) and without (-) enhancement on lge. r , Δr , Δr ratio were calculated (partition coefficient of gd, λ). results: in hcm, λ was significantly different between patient with ( . ± . ) and without ( . ± . ) enhancement on lge (p < . ). no significant difference was measured in λ value between control and hcm without delayed enhancement (p= . ). we did not found any correlation between lambda and circumferential strain (r= . ; ci (- . ; . ); p= . ). on the other hand, we found a significant correlation between lv wall thickness and circumferential strain ( . ; ci ( . ; . ); p < . ). in hcm, fibrosis is a focal process. in our study, there were no correlation between the presence of fibrosis and circumferential strain, but we found a significant correlation between lv wall thickness and circumferential strain. purpose: there is no consensus on surveillance strategies of reconstructed breasts after breast cancer, and it is routinely based on clinical examination alone. this study aims to assess the incidence and radiological presentation of breast cancer recurrences after deep inferior epigastric perforator (diep) flap reconstruction for women with a history of breast cancer. methods and materials: consecutive women who underwent diep flap reconstruction after breast cancer from to were included in this retrospective study. all had annual screening for recurrence and we reviewed their follow-up records in our institution. the date and site of recurrences -ipsilateral or controlateral to the reconstructed breast, regional and metastatic disease -were retrieved. clinical and radiological presentations -on mammography, ultrasound, and mri -were further analysed. results: of patients presented relapses, with a mean delay of . years (sd= . ) after diep reconstruction; ( %) were ipsilateral, while ( %) were controlateral and ( %) metastatic. ipsilateral recurrences had a tendency to occur earlier ( . years, sd= . , p= . ) and presented at a clinically patent stage. purpose: to assess the potential value of segmental quantification of myocardial fibrosis using t mapping in dilated cardiomyopathy (dcm) in comparison to late contrast enhancement imaging and circumferential strain. methods and materials: seventeen patients with dcm, and controls subjects were prospectively included. all patients underwent cardiac mr with the following sequences (parameters set according to recommendation of the scmr): ) cine sequence, ) tagging sequence cspamm tr/te= . ms/ . ms; matrix , fov , temporal resolution . ms, distance between tag: mm, short axis. ) molli sequence (tr/te= . ms/ . ms; matrix - , thickness: mm) acquired before and , , min after gadolinium injection (dotarem, . mmol/kg). ) late gadolinium enhanced sequence min after injection. t values were assessed in blood and in the segments of the mid-lv slice. statistical analysis were performed for patients and for segments with (+) and without (-) enhancement on lge. r , Δr , Δr ratio were calculated (partition coefficient of gd, λ). results: in dcm, λ was not significantly different between patient without ( . ± . ) and with at least one segment showing enhancement on lge ( . ± . ; p= . ). in all dcm, λ was significantly higher compared with the value obtained in control subject (p < . ). we found a significant correlation λ and circumferential strain in each segment (r= . ; ci ( . ; . ); p < . ), and between λ and lvef (r= - . ; ci (- . ;- . ); p < . ). conclusion: in dcm, fibrosis was a diffuse process involving all the myocardium. there was a correlation between the quantity of fibrosis, circumferential strain and lvef. . ). the correlation between us and cmr end-dyastolic and stroke volume indexes was significant but with a very low coefficient, while the correlation for the ejection fraction was acceptable. the icc was unsatisfactory for all volumes and good for the ejection fraction. the widest bland altman plot range was found for the end-diastolic volume index. in conclusion, metrics of lv volume index and function showed significant systematic inter-modality differences. in particular, the us volumes were systematically underestimated. this suggests that serial measurements of volumes and function in ti should be performed using the same method and, if available, the more reproducible cmr technique. author disclosures: c. tudisca: research/grant support; the miot project receives "no-profit support" from industrial sponsorships (chiesi farmaceutici s.p.a., apopharma inc. and bayer-shering). this study was also supported by: "ministero della salute". . obtained min after injection of . mmol/kg of gadolinium. lge was quantified automatically and defined as area of myocardium with signal intensity sd above the mean signal of remote myocardium. indexed end-diastolic left ventricular mass (iedlv mass) was assessed and lge extension was defined as percentage of total iedlv myocardium mass. patients were followed prospectively for a mean of . ± . months, during which period occurrence of vt and icds were recorded. purpose: noncompaction of the left ventricle myocardium (lvnc) is a rare cardiomyopathy characterised by multiple and excessive trabeculations, deep intertrabecular recesses and thickened ventricular myocardium. this condition is considered mostly congenital but acquired forms have also been described. aim of the present study is to assess lvnc prevalence in β-thalassaemia patients and its potential association with cardiac siderosis methods and materials: transfusion-dependent patients with β-thalassaemia ( major and intermedia, mean age . ± . years, mean bsa . ± . kg/m ) presenting for cardiac and abdominal iron assessment by mri ( . t scanner, avanto, siemens-germany) were studied. cardiac iron overload was assessed by t * black-blood gradient-multiecho sequences; cardiac functional and morphological characteristics were evaluated using ssfp acquisitions. risk factors for lvnc were noted and none of the patients had neuromuscular or congenital heart disease. results: patients ( %) fulfilled the preassigned strict criteria for lvnc on cardiac mri. there were no statistically significant differences between patients with and without lvnc with respect to demographics, haemoglobin levels, splenectomy status, systemic, hepatic, and cardiac iron overload indices, iron chelation therapy. patients with lvnc showed a significant lower cardiac functional performance (ejection fraction; volumes impairment). conclusion: patients with β-thalassaemia have a higher prevalence of lvnc than normal individuals suggesting an underlying iron deposition mechanism to explain this condition in absence of conventional risk factors. these data seem to be crucial regarding an entity with adverse cardiac outcomes, especially in patients with β-thalassaemia where cardiac disease remains a primary cause of mortality. ranged from . mm to . mm (mean = . mm). involvement of internal carotid artery (n = , %) was more common than external carotid artery (n = , %). petrous segment of ica was the most commonly involved segment (n = , %), followed by cervical segment of ica (n = , %) and maxillary artery (n = , %). conclusion: carotid blowout syndrome following rt were more common in our study subjects with advanced t and n stage of npc, local recurrence and repeated rts. pseudoaneurysms were identified in most patients. ica involvement was more common and petrous segment of ica was the most commonly involved segment. of the patients with involvement of pns, one presented with orbital extension. nasopharyngeal and oropharyngeal involvement was seen in two cases. in cases ( %), the primary tumours seen as diffuse enhancing mucosal thickening. in five cases ( %), the primary tumours seen as an enhancing mass lesion. in one case ( %), the primary tumour was undetectable. bone destruction was noted only in cases ( %). conclusion: nasal-type nk/t-cell lymphomas of the sinonasal regions often presents with diffuse mucosal thickening rather than mass lesion. and they can mimic inflammatory disease such as sinusitis. radiologists should be familiar with these findings indicative of the possibility of nktl, and should perform a histopathologic confirmation to establish a diagnosis. results: a significant relationship between symptoms and morphological manifestations was found (disk displacement (p < . ), osteoarthritis (p < . ) and effusion (p = . )). in the group without reduction there were significant increases in the risk of experiencing symptoms (p = . ) in the group with reduction the risk was marginal (p = . ). significant correlation between age and osteoarthritis (p = . ) and age and effusion (p = . ) was found. there was no correlation between sex and morphological manifestations. significant increases in the risk of experiencing symptoms were found in the group with morphological manifestations (disk displacement (p = . ), osteoarthritis (p < . ) and effusion (p < . )). statistically marginal results were verified with multivariate analysis. conclusion: mri morphological manifestations of the tmj correlate with the presence of symptoms, therefore mri has a crucial role in the diagnosis of treatment of tmj dysfunction. purpose: to compare image quality of fbp, asir and veo reconstructed ct images of the neck in tumour patients with a contrast-enhanced scan. methods and materials: consecutive regular contrast-enhanced tumour staging ct-scans (discovery hd , ge; helical, . s, kv, - ma mod., ni ) of the neck were reconstructed using fbp, asir and veo; n= . image quality at three defined heights (lymph node levels=lnl , , ) were independently rated by radiologists blinded to the reconstruction algorithm. readers rated image quality including artefacts, contrast and noise using a semi-quantitative scale of to (lower than was defined as non-diagnostic) yielding a summary score for each height. wilcoxon´s test was used for statistical testing. icc was calculated. purpose: maxillary sinus pyocele is a true chronic abscess found in drugrefractory sinusitis. the purpose of this study is to define this new entity and its mri-characteristics. we retrospectively reviewed mri datasets for patients with "pseudotumoral sinusitis" on ct (including bilateral cases). the mri datasets were scored by two radiologists for morphological features, t and t -weighted signal intensities, contrast enhancement and the degree of impact on the sinus mucosa and the retromaxillary fat. these features were compared with per-operative findings. results: we observed a content presenting t low signal ( %), heterogeneous t low signal ( %), a capsule with contrast enhancement ( %) containing microabscesses ( %), a mass effect on the lateral nasal wall ( %) and retromaxillary fat stranding ( %). eighteen pyoceles were treated endoscopically, with confirmation of a maxillary sinus abscess in all cases. furthermore, we suggest a staging system for maxillary sinus pyocele. conclusion: maxillary sinus pyocele presents specific mri characteristics. this entity must be suspected on sinus ct scan and recognised on mri. surgical endoscopic sinus surgery is needed. these findings therefore merit further investigation. purpose: to compare mr imaging at . -and . -t in the same individuals for performance in the diagnosis of cartilage lesions of the knee. this prospective study was approved by our institutional review board, and informed consent was obtained from all patients. from december to february , mr examinations of the knee at both . -and . -t were performed in symptomatic patients ( men, mean age y, range - y) who underwent subsequent knee arthroscopy. three blinded independent readers graded all articular surfaces seen at mr using the noyes classification system. with arthroscopy as the reference standard, the sensitivity and specificity of the . -and . -t mr protocols for detecting cartilage lesions were calculated. differences between the . -and . -t exams were compared using bootstrapping statistics (p < . ). results: for all readers and grades of cartilage lesions combined, the respective sensitivity, specificity, and accuracy of mr for detecting cartilage lesions (n= ) were %, %, and %, respectively, at . -t and %, %, and %, respectively, at . -t. for detecting and correct grading of cartilage lesions, the readers performed significantly better with . -t than with . -t (p= . ). conclusion: a comprehensive mr protocol at . -t significantly improves diagnostic performance for evaluating the articular cartilage of the knee in symptomatic patients, when compared with a similar protocol performed at . -t. purpose: the purpose of this study is evaluation of correlation between relative signal intensity of mr images in retrodiscal tissue, superior and inferior heads of pterygoid muscle in tmd patients with types of anterior disc displacement and condylar flattening. in this cross-sectional study, mr images of patients who had anterior disc displacement were evaluated. after relative signal intensity measurement for retrodiscal tissue, superior and inferior head of lateral pterygoid muscle, the correlation between relative signal intensity and types of anterior disc displacement and also condylar flattening was evaluated. results: the correlation between relative signal intensity of mr images and type of anterior disc displacement in retrodiscal tissue (p-value= . ), superior head of lateral pterygoid muscle (p-value= . ) and inferior head of lateral pterygoid muscle (p-value= . ) was not significant. there was also no statistically significant correlation between relative signal intensity of mr images and flattening of condylar head in retrodiscal tissue (p-value= . ), superior head of lateral pterygoid muscle (p-value= . ) and inferior head of lateral pterygoid muscle (p-value= . ). we found that although mri is a non-invasive procedure in the diagnosis of tmd, probably relative signal intensity of mr images in retrodiscal tissue, superior and inferior head of pterygoid muscle is not a good predictor for type of anterior disc displacement and flattening of condylar head. it seems that this cannot be used as a diagnostic marker for tmd progression. high resolution d mr imaging of the temporomandibular joint: feasibility and comparison with d sequences u. navarro, m. ravanelli, d. farina, e. botturi, r. maroldi; brescia/it (navarrougo@gmail.com) purpose: to assess the feasibility of high-resolution d mr imaging of the temporomandibular joint (tmj) and to compare d and standard d techniques. methods and materials: ten volunteers underwent a tmj mr study with surface coils including a proton density (pd) fat-saturated d sequence "space" and d pd fat-saturated sequences acquired on parasagittal and paracoronal planes. twenty tmj were imaged and analysed. the contrast between articular disk (ad) and bilaminar zone signals was measured on parasagittal images and normalised by the ad signal. capability of d sequences to depict eight small anatomical structures of the tmj ( on parasagittal and on paracoronal plane) was assessed and compared to that of standard d sequences. results: contrast between bilaminar zone and ad in d and d sequences was . and . , respectively (p . ). fifty-eight out of structures assessed in parasagittal plane were detectable on d sequences, / on d sequences (p . ). among the structures assessed on paracoronal images, were recognised on d sequences, on d sequences (p . ). conclusion: high resolution d mr imaging of tmj is feasible with d pd fatsaturated space sequences. the detectability of anatomical structures, potentially key for joint functionality (ligaments) is enhanced in comparison to standard d sequences, especially on paracoronal plane. results: aea was identifiable in / on the axial plane, / on coronal and / on sagittal. in % of patients, the aea canal run inside the skull base (condition # ), in % of cases a pneumatised cell was interposed between the canal and the skull base (condition# ), % of the pneumatised cells above the aea canal were supraorbital cells, % supra-bullar recesses and % frontal sinuses. in these cases, the average distance between the aea canal and the skull base was . mm (range . in patients with kl grade - knee oa, dgemric was acquired at t using a d-spgr sequence before and months after ha treatment. to evaluate patient symptoms, the knee injury and osteoarthritis outcome score (koos) questionnaire was recorded at baseline and follow-up. we analysed matching anatomical rois in the medial and lateral knee compartment in both examinations, using the t relaxation times as a measure of cartilage quality. outcomes of dgemric and koos at baseline and follow-up were compared using paired testing to evaluate the symptomatic and potential structural effects of ha. results: outcomes of dgemric at follow-up (pooled median t ms) did not improve significantly compared to baseline (pooled median t ms) in any of the analysed anatomical cartilage rois. patient complaints improved significantly in koos subscales: pain, daily-, and sports activities. conclusion: using dgemric, no improvement in articular cartilage quality can be detected months after ha. however, patient complaints decreased significantly after ha. therefore, the results of this study suggest that the working mechanism of ha is not acting through an improvement of sgag content in the cartilage. purpose: to analyse the spatial resolution of different reconstruction kernels and acquisition protocols including a prototypic high-resolution protocol in flat-panel (fp) and multi-detector (md) ct to evaluate contrast and cartilage depiction quality of fpct and mdct arthrography. a cone-beam image quality phantom was used to compare resolution and different reconstruction kernels of standard mdct ( and kv), standard binned ( x ) and prototype high-resolution unbinned ( x ) fpct protocols ( s and s runs each). with the resulting fpct kernel best matching the standard mdct kernel (u u), joint phantoms with differently sized cartilage defects were scanned. ct numbers and noise in iodine contrast and phantom cartilage tissue were measured, and contrast-to-noise ratios (cnr) were calculated. depiction quality of cartilage defects was qualitatively rated by two independent radiologists. results: a sharp reconstruction kernel for all fpct protocols best matched the resolution of the standard mdct kernel. high-resolution s x binning fpct showed superior resolution in higher frequencies than . lp/mm. the cnr were highest in s fpct, followed by s fpct binned and mdct protocols. interreader agreement for depiction quality of cartilage defects was substantial and high in joint phantoms ( . and . , respectively; p < . ). the best ratings of cartilage defect depiction quality were seen in fpct s, followed by fpct s and mdct acquisitions. conclusion: fpct arthrography offers superior cnr and cartilage defect depiction quality to mdct, and spatial resolution for small structures is higher when applying high-resolution acquisition protocols. subjects with risk factors for oa (incidence cohort) and subjects from the control cohort. right knee t mris were analysed at baseline and months. coronal flash sequence was used to measure cartilage volume at baseline, multi-echo spinecho sequence to generate t maps at baseline and months. regression models were adjusted for age, gender and bmi and were applied to compartments (medial femur, lateral femur, medial tibia and lateral tibia). results: global t measurements increased in all cohorts over months. baseline t were significantly greater in the progression cohort compared to incidence and control cohort (p < . ), whereas -month follow-up data showed significantly greater measurements in the incidence cohort (p < . ). most pronounced t changes over time were observed in the incidence cohort (p < . ), changes in the progression cohort were not significant. mean volume did not significantly differ between the cohorts, but progression cohort subjects showed the highest volumes in all compartments. purpose: the goal of the study was to demonstrate the benefits of t mapping to the assessment of lumbar disc repair after the adct. methods and materials: patients, male and female, age range - , with a single-level degenerative disc disease (ddd) were studied. all patients had a standard lumbar microdiscetomy performed and - weeks after the surgery underwent the adct. prior to the surgery, one month later and , and months after the adct each patient had a mr examination on the . t mr scanner. patients completed a -month long follow-up protocol. t mapping revealed the level of ddd and the adjacent levels. the evaluation of signal intensity was carried out using pixel value software. results: each patient during the -month long follow-up reported a significant relief of pain: vas score ranged - , odi score - %. in the mr examination held after the adct, changes in signal intensity seen on t -weighted mr images were reported. t mapping showed signs of the disc repair regardless of the lack of changes in disc dimensions. mild increase of t with improved homogeneity of the structural morphology of the nucleus pulposus was observed on t after the adct. conclusion: t mapping may be used for evaluating the changes of the molecular composition and structural integrity of the intervertebral disc after the adct and other novel restorative therapies. it has also the potential to be valuable in the detection of the early degeneration in the intervertebral disc. purpose: to evaluate the feasibility of t * and t gd mapping to assess glenohumeral cartilage, and to establish baseline values of healthy glenohumeral cartilage at t. methods and materials: forty asymptomatic volunteers (mean age: . ± . years) without shoulder abnormality were included. the mri protocol comprised a three-dimensional ( d) double-echo steady-state (dess) sequence for morphological cartilage evaluation, a d gradient-echo (gre) multiecho sequence for t * assessment, and a dual-flip-angle d gre sequence for t gd mapping. statistical assessment involved descriptive statistics establishing mean t * and t gd values ± standard deviation and the one-way analysis of variance (anova) to identify any significant differences between the t * and t gd values of various regions of the glenohumeral joint. intra-class correlation (icc) analysis comparing repetitive t * and t gd measures of ten randomly selected individuals was used to assess intra-and inter-observer reliability. purpose: to evaluate the efficacy of the treatment of uterine adenomyosis using magnetic resonance imaging-guided focused ultrasounds (mrgfus) with a new specific technical plan. twenty-four patients aged between and years (mean age . ), with symptomatic adenomyosis and uterine fibroids were treated with mrgfus in our department, from october to july . this study evaluates the findings on patients affected by adenomyosis alone. symptomatology was assessed through the symptom severity score questionnaire. one single treatment was performed with an average energy delivered to each patient equal to j (with a minimum value of j and maximum of j). the longest treatment duration was minutes. the plan employed was characterised by high density and reduced size of the spot length (ranging from to mm) with the shortest cooling time between the sonifications. results: the evaluation of the non-perfused volume on the c.e. t -weighed sequences performed weeks after treatment, measuring each single slice, showed a maximum retraction of the necrotic area of % and a minimum of % with a mean value of . %. after six weeks, the symptomatic score showed a reduction of about % if compared to the pre-treatment one. the treatment with mrgfus allows a resolution of the symptoms and a reduction of the treated area, maintaining the integrity of the uterus, in a pathology which, up to now, has limited therapeutic perspectives. is uterine artery embolisation in large sized myoma as efficient as in normal sized myoma: a retrospective comparative study in patients h. choi , g. jeon , m. kim , j. lee , j. yoon , s. hwang ; seongnam/kr, seoul/kr (piscean @hanmail.net) purpose: the purpose of this study was to evaluate the effectiveness, safety and complications of uterine fibroid embolisation (ufe) when applied to myomas of large volume. a total of retrospectively collected patients who underwent ufe for symptomatic uterine fibroids without adenomyosis between january and february were included in this study. patients were divided into two groups: patients were selected with large fibroid burden group, defined as a dominant fibroid with a longest axis ³ cm or a uterine volume of ³ cm and remaining patients with control group. fibroid infarction and volume reduction with mri, complications and patients' satisfaction score were evaluated. results: the large fibroid group consisted of (mean age . ± . ) women and (mean age . ± . ) women included in control group. there were no statistical difference in average % volume reductions of dominant fibroid as % in large group and . % in control group, the mean satisfaction score at immediate follow-up (average . months) and mid-term follow-up (average . months) and procedure related complications or major surgery following ufe. conclusion: uterine fibroid embolisation is a safe and effective treatment method which can be utilised in the treatment of myomas of large volume. the size of myoma is not a definite contraindication or poor prognosis factor for embolisation. : leiomyomas in women (average age . years) were treated with mri-guided focused ultrasound (mrgfus). the treatment is carried out using the ablative properties of the hifu system under t mri guide. symptoms were scored using severity score (ss) and quality of life was determined using the ufs-qol score. pre-treatment measurements of leiomyoma volume were obtained by mr images. after treatment, non-perfused volume (npv) was calculated from t -w contrast-enhanced mr sequences. the average volume of treated fibroids was . ± . mm . follow-up images were obtained , and months after treatment and served to determine leiomyoma shrinkage. qualitative and quantitative relations between fibroid volume, npv ratio at treatment, and -month shrinkage were measured. results: mrgfus treated patients demonstrated a significant change in usf-qol score: mean ss score values were . ± . (pre-treatment), . ± . (threemonths follow-up), . ± . (six-months follow-up) and . ± . (twelve-months follow-up). fibroids volume changed from . ± . mm (before treatment) to ± . mm (at months follow-up). we encountered a statistically significant difference between the two values (p = . ). mean post-treatment vnp was . ± . mm , about % of total fibroid volume (p= . ). conclusion: mrgfus therapy of leyomioma results in a significant relief of symptoms and greater than % total fibroid ablation. the procedure is carried out in a totally non-invasive manner and features a high-safety profile. results: mri-guided focused ultrasound treatment was technically successful in of patients ( . %). in patients treatment was not possible due to bowel loops in the beam pathway that could not be mitigated (n= ), patient movement (n= ) and system malfunction (n= ). average non-perfused volume ratio was ± % (range, to ). mean applied energy level was ± j, and mean number of sonications was ± . no major complications occurred. two cases of first degree skin burn resolved within one week after the intervention. of the baseline characteristics analysed, only the planned treatment volume had a statistically significant impact on the non-perfused volume ratio. purpose: placenta percreta (pp) is a recognised cause of severe postpartum haemorrhage, with high risk of blood transfusions and emergency hysterectomy with maternal morbility and mortality. our purpose is to evaluate the role of bilateral occlusion balloon catheter insertion in to both internal iliac arteries (iia) before elective caesarean to prevent haemorrhage and to preserve the uterus. this is one of the longest cohort of women treated with prophylactic balloon occlusion and prevents caesarean hysterectomy in abnormal placentation. methods and materials: twenty-two pregnant women who were identified as having a pp by us were treated prophylactically with bilateral occlusion balloon catheters placed in the anterior trunk of both iia prior to elective caesarean. the balloons were inflated immediately after the baby delivery and deflated four hours later. patients with peri-operative bleeding were treated with uterine artery embolisation (uae), blood transfusion or hysterectomy. for each patient, estimated volume of blood lost and transfusion required was recorded. results: abnormal placentation was confirmed histologically as percreta ( ), acreta ( ) and increta ( ). estimated median blood lost during the delivery was noted . l (range . - l). postpartum haemorrhage occurred in nine patients, six had successful embolisation and three required hysterectomy. no foetal or mother death occurred. conclusion: prophylactic occlusion balloon catheter insertion in both iia prior to elective caesarean deliveries in patients with abnormal placenta contributes to successful treatment, reduced blood lost and preserved the uterus in this high risk group of women. results: a total of transcatheter embolisation procedures of bilateral uterine arteries with or without extra-uterine feeding arteries were performed as the firstline treatment, and with a technical success rate of % ( / ). embolisation was incomplete in two patients who had an extra-uterine blood supply or a dominant draining vein; the former recovered from menorrhagia during our close observation, while the latter underwent a successful second embolisation procedure. clinical success was achieved in the remaining eight patients after a single procedure and there was no recurrence of bleeding. only one minor complication occurred: rupture of the proximal ua. recovery to their normal menstrual cycle was seen in all eight of the clinically successful patients, one of whom subsequently had an uneventful intrauterine pregnancy carried to term. . years ± . years) underwent a pre-therapeutic fdg-pet/ct scan and a fdg-pet/ct after the second cycle of nact. histopathology served as the reference standard. suvmax of cancer lesions before and after the second cycle of nact were measured. two evaluation algorithms were used: (a) pcr: sinn score and , npcr: sinn score - ; (b) pcr: sinn score , npcr: sinn score - . the absolute and relative decline of the suvmax (Δsuvmax, Δsuvmax (%))was calculated. differences of the suvmax and of the suvmax decline between pcr and npcr lesions were tested for statistical significance (p <. ). to identify the optimal cut-off value of Δsuvmax (%) to differentiate between pcr lesions and npcr lesions a receiver operating curve (roc) analysis was performed. results: using evaluation algorithm a the Δsuvmax was . (pcr group) and . (npcr group) (p = . ); the Δsuvmax (%) was % and %, respectively (p = . ). on roc analysis an optimal cut-off Δsuvmax (%) of % was found. using evaluation algorithm b the Δsuvmax was . (pcr group) and . (npcr group) (p = . ); the Δsuvmax (%) was % and %, respectively (p = . ). on roc analysis an optimal cut-off Δsuvmax (%) of % was found. conclusion: fdg-pet/ct early differentiates between pcr and npcr after two cycles of nact. in our study we prospectively enrolled consecutive patients (m:f= : , mean age years) affected by hcc: patients at presentation and at restaging. in all cases we performed a whole body cho-pet and compared findings with referring ct (n= ) and/or mri scanning (n= ), for a total of paired scans. the reference standard for validating imaging results was either histology ( patients), or a multidisciplinary work-up. for every modality we determined diagnostic accuracy on a scan-based and on a site-based analysis. results: on a scan-based analysis cho-pet and ct/mri demonstrated an accuracy of . % and %, respectively, whereas on a site-based analysis the two modalities demonstrated a sensitivity and accuracy, respectively, of . % and . % for pet, and . % and % for ct/mri. in both analyses, no statistically significant difference was found on t-test. in / patients, hcc showed either loco-regional involvement (n= ) or distant metastases (n= ). all extra-hepatic lesions were properly detected by cho-pet (accuracy %), whereas ct/mri missed a large part of them (accuracy . %) and this most likely due to the limited field of view during acquisition. in cases ( . %), pet information determined a change in treatment planning. conclusion: according to our findings, cho-pet has a comparable accuracy with ct/mri in hcc. the principle advantage of the modality appears its ability to detect extra-hepatic lesions, which can lead to treatment modification. furthermore, in-/opposed-phase sequence (dixon) used for attenuation correction in mr/pet were evaluated. in all images, the diagnostic confidence in identification of nodules was rated on a -point scale ( =certain; =uncertain). additionally, the involvement of each lung lobe (primary/metastatic) was assessed. ct scan in inspiration served as reference. the diagnostic performance of each modality was compared in a lesion-and lobe-based analysis. the diagnostic confidence was compared using wilcoxon test. results: lung nodules were evaluated. in the lesion-based analysis, sensitivity (false negative rate) of ctex, vibein, vibeex and dixon was % ( %), % ( %), % ( %) and % ( %). in the lobe-based analysis reflecting the clinical assessment, sensitivity (false negative rate) was % ( %), % ( %), % ( %) and % ( %), respectively. in ct and mri diagnostic confidence was rated higher in inspiration (mean score ctin/ctex . purpose: to evaluate the relationship between quantitative ct-perfusion parameters and tumour volume with glucose metabolism parameters, in staging of lung cancer patients with fdg pet/ct whole body study. methods and materials: thirty-one patients with biopsy-proven lung cancer, referred for cepet/ct staging, were prospectively enrolled in our study. ctp was performed with following parameters: kv; mas; scan , during intravenous injection of ml of contrast-agent, flow rate: ml/sec. ctp and cepet/ct data were used to calculate a range of tumour vascularity parameters (blood flow, blood volume and mean transit time) and tumour glucose uptake (suvmax), and finally correlated with tumour volume using a commercially available software. four patients were excluded due to the advanced stage of the tumour. ct perfusion parameters were then statistically analysed and compared with those of fdg-pet. results: perfusion parameters were calculated with a dedicated software (perfusion . ; advantage; ge) and a quantitative map of arterial perfusion was generated. patients were divided into two groups according to tumour volume, with a cut-off of cm . linear regression was performed among two groups and statistically significant correlations (p < . ) were found between bf and suvmax (negative correlation) and between mtt and suvmax (positive correlation) for tumours with volume > cm . these findings may be due to the inadequate blood inflow typical of larger tumours, with a significant increase of anaerobic metabolism and glucose consumption. conclusion: cepet/ct perfusion is a feasible technique that offers informations related to the biological tumour behaviour that can be used for planning treatment and for an accurate evaluation of tumour response after therapy. retention as pib positive (pib+) or pib negative (pib-). data of the unidirectional influx k_ from a subset of ad patients and controls were used for correlative analysis. data were analysed using regions of interest (roi) analysis. results: we found a strong, positive correlation across brain regions between k_ and epib (r= . ; p < . ). epib values were significantly lower in posterior cingulate (p < . ) and parietal cortices (p= . ) in pib+ subjects compared with pib-although the group difference were stronger for rcmrglc in cortical areas (p < . ). strong positive correlations between epib and rcmrglc were observed in all cortical regions analysed, especially posterior cingulate and parietal cortices (p < . ). this study suggests that a single dynamic pib-pet scan may provide clinical estimates of pathological (amyloidosis) and functional changes (impaired blood flow) in ad. this dual information might be valuable both in early diagnosis of ad and evaluation of treatment strategies, but our results emphasise the need for further research. purpose: to assess the diagnostic accuracy of diffusion kurtosis imaging (dki), dynamic susceptibility-weighted imaging (dsc) and short echo time chemical shift imaging (csi) for grading gliomas, as separate techniques and in a multimodal approach in order to determine the best discriminative parameter (s). methods and materials: patients with cerebral gliomas ( f/ m; age range: - , median age: ) underwent dki, dsc and csi on a t mr scanner. diffusion parameters: mean diffusivity (md), fractional anisotropy (fa), mean kurtosis (mk); perfusion parameters: mean relative regional cerebral blood volume (mean rrcbv), mean relative regional cerebral blood flow (mean rrcbf), mean transit time (mtt) and relative decrease ratio (rdr), and twelve csi metabolite ratios were compared between high-grade gliomas and low-grade gliomas (mann-whitey-u, p < . significance, bonferroni corrected). sensitivity, specificity, diagnostic accuracy and optimal thresholds were determined for the techniques separately and combined. results: mk, md, mean rrcbv, mean rrcbf, rdr, lips/cho, lips/cre, myo/sum and cre/sum showed statistically significant differences among tumour grades, with mean rrcbf as the best discriminative parameter. the combination of mean rrcbf, mk and myo/sum to grade gliomas showed diagnostic accuracy, sensitivity and specificity of %, whereas combining mean rrcbv, md and lips/cho gave a diagnostic accuracy, sensitivity and specificity of %, % and %, respectively. conclusion: combining the parameters mean rrcbf, mk and myo/sum to determine the glioma grade was pathognomonic in this study. the best performing parameters, when used individually, were found to be mk and mean rrcbf. additive value of arterial spin labeling in differentiating primary central nervous system lymphoma from glioblastoma multiforme: an observer performance study k. yamashita, t. yoshiura, a. hiwatashi, o. togao, k. kikuchi, k. yoshimoto, h. honda; fukuoka/jp (yamakou@radiol.med.kyushu-u.ac.jp) purpose: to determine whether asl has an additive diagnostic value to the conventional mr images in differentiating primary central nervous system lymphomas (pcnsls) from glioblastoma multiformes (gbms). methods and materials: mr images of patients including with pcnsl and with gbm were retrospectively studied. two independent neuroradiologists took part in reading sessions. in the first session, the observers read only conventional mr images (t -weighted image, t -weighted images, post-contrast images, and dwi with apparent diffusion coefficient maps). in the second session, they read asl cerebral blood flow (cbf) maps along with the conventional images. the confidence level for the diagnosis (pcnsl versus gbm) was graded on a -point scale. interobserver agreement as well as sensitivity, specificity, accuracy, positive predictive value (ppv), and negative predictive value (npv) were assessed for the two readers. purpose: organ-based tube-current modulation (obtcm) is a technique developed to lower ct radiation dose to anterior dose-sensitive organs. this irb-approved observational study aimed to establish the location of breast tissue in a female patient in supine position with arms raised over their shoulders. a secondary purpose was to look for possible thresholds of chest diameter and woman's age below or above which the breasts lie in a central location with subsequent possible benefit from obtcm. methods and materials: informed consent was obtained in consecutive women included. from standard chest ct acquisitions, one / mm image set with fov of mm and x and y coordinates at were obtained. from the gantry rotation centre (x=y= ), the outer and inner angles limiting the breast tissue were measured and compared to the angles ( °), where obtcm delivers lowered and increased dose to the organs. results: outer angles of breast tissue were < ° for one breast in only two patients. inner breast angles were > ° in / patients for at least one breast. no threshold of chest diameter or age was found to predict a central enough location of the breast for obtcm to be beneficial. conclusion: our data show that the angular position of breast tissue is higher than the limit where reduced versus increased radiation dose is delivered in obtcm. this system should therefore not be applied to ct chest examinations in adult women lying supine. purpose: to evaluate the effect of an organ-based tube-current modulation (obtcm) and bismuth shielding on image quality and breast radiation dose in women undergoing low-dose chest ct. methods and materials: low-dose chest ct was obtained from women, who were randomly assigned to a control, obtcm, breast shield, or breast shield plus obtcm group. axial slice images from aortic arch, carina, and inferior pulmonary vein were used to analyse image quality. three radiologists scored the image quality in terms of artefact and noise, and then designated the overall image quality as optimal (does not affect the diagnostic accuracy) or suboptimal (affects the diagnostic accuracy). noise levels were measured in the anterior and posterior lung in each image. a phantom dose study was conducted to measure the radiation dose. results: images with artefacts or noise were more frequently obtained in the breast shielded groups. the overall image quality was not significantly different among the four groups. measured noise levels in the anterior lung were significantly higher in the breast shielded groups than the control group; however, no statistical significance was found among the four groups in the posterior lung. in the phantom dose study, a - . % dose reduction in the breast was achieved using the breast shield and/or obtcm protocol. the radiation dose in the female breast may be reduced using the breast shield or obtcm during low-dose chest ct with acceptable image quality. the obtcm reduced the radiation dose in the breast without inducing image quality deterioration. the solid parts of gliomas and compared between high-and low-grade gliomas. all the parameters were also normalised to the corresponding values in contralateral normal appearing white matter (nawm) and compared between high-and lowgrade gliomas. a receiver operating characteristic (roc) analysis was performed for statistical analysis. results: there were significant differences in adcfast and adcslow values between high-and low-grade gliomas (p < . ). the α value was significantly lower in high-grade gliomas than that in low-grade gliomas (p < . ). in addition, the adcfast, adcslow and α values that were normalised to the values in the contralateral nawm were all significantly different between high-grade and low-grade gliomas (p < . ). conclusion: ivim imaging with biexponential and stretched-exponential model is a useful tool in grading cerebral gliomas. the α value may be the best parameter for distinguishing high-from low-grade cerebral gliomas. purpose: this study aimed to determine which combination of acquisition and iterative reconstruction parameters for low-dose mdct at low tube voltages yields image quality and diagnostic confidence equivalent to current clinical standards in thoracic imaging. methods and materials: thoracic images of eight sedated and mechanically ventilated pigs were acquired with mdct during mid-inspiratory breath hold using standard ( kvp, mas) and low-dose protocols at low tube voltages ( / kvp) and current-time products ( / / mas). using lung and soft-tissue kernels, images of all acquisitions were reconstructed with filtered backprojection (fbp); low-dose acquisitions were also reconstructed iteratively (levels and , idose, philips healthcare). three independent blinded readers sorted the resulting image data sets per animal according to diagnostic image quality (best to worst), and sorted images were statistically clustered. additionally, ct numbers and noise have been determined in lung parenchyma, liver, muscle and aorta of all image data sets. results: interreader-agreement was moderate-high (κ= . - . ). for any fixed set of acquisition parameters fbp-images were ranked lowest while those reconstructed iteratively (idose ) were ranked highest independent of reconstruction kernel. the image series could be clustered into homogeneous clusters of equivalent diagnostic quality: iteratively reconstructed images acquired at kvp/ mas (idose / ), kvp/ mas (idose ) or kvp/ mas (idose ) were ranked equivalent to fbp-images acquired using standard protocol. iterative reconstruction did only affect ct numbers at very low dose ( kvp/ mas) while image noise could be reduced by up to ~ %. conclusion: using low-kvp and low-mas protocols combined with iterative image reconstruction, radiation exposure of thoracic mdct could be reduced by - %. purpose: to determine utility of adaptive iterative dose reduction using threedimensional processing (aidr d) for pulmonary nodule identification on low-dose -detector-row ct using different scanning methods in phantom study. a chest ct phantom including simulated pulmonary nodule was scanned on a -detector-row ct using non-helical wide volume scan (wvs) and helical scans as -detector-row ct ( hs) and -detector-row ct ( hs) at nine different tube currents. all data sets were reconstructed using aidr d and filter back projection (fbp). to determine the capability of overall identification, two chest radiologists independently evaluated lesion conspicuities by five-point scoring system. at the each scanning method, gold standard was defined as the data set of standard tube current ( ma) reconstructed by fbp. interobserver agreements of detection and the capability for radiation dose reduction on each scan method were assessed by kappa statistics and roc analyses. results: interobserver agreements were almost perfect or substantial at all data sets (κ> . ). when applied aidr d, area under the curves of data sets equal to or higher than ma on wvs, ma on hs, and ma on hs had no significant difference with standard data sets (p> . ). on the other hand, when applied fbp, radiation dose reduction was limited in comparison with the data sets applied aidr d at all scanning methods. conclusion: aidr d was more useful for low-dose chest ct examination for nodule screening than fbp, and wvs can reduce more radiation dose than hs and hs on -detector-row ct. methods and materials: ctpa studies planned with frontal topogram only (protocol ) were compared with ctpa studies planned with frontal and lateral topograms (protocol ).optimal scan length was defined from lung apex to lung base. excess scan length beyond these landmarks was measured. mean organ doses to thyroid, liver and stomach were estimated using standard conversion factors. results: the mean excess scan length was significantly lower in protocol compared with protocol ( . ± . mm vs . ± . mm,p < . ). the mean excess scan length below lung bases was significantly lower in protocol cohort compared with protocol ( . ± . mm vs . ± . mm,p < . ), as were the mean organ doses to stomach ( . ± . mgy vs . ± . mgy,p < . ) and liver ( . ± . mgy vs . ± . mgy,p < . ).a trend towards reduced over-scanning above the apices in protocol was observed compared with protocol ( . ± . mm vs . ± . mm,p= . ), with a trend towards lower mean thyroid organ dose in ( purpose: volumetric measurement of a nodule is more sensitive in the detection of tumour growth than axial diameter measurement. the purpose of this study was to assess the accuracy of lung nodule volumetry using adaptive iterative dose reduction (aidr) d in comparison with filtered back-projection (fbp) in an anthropomorphic thoracic phantom on -detector row ct. conclusion: pulmonary haemorrhage during fine-needle lung biopsy is a frequent event. it protects against pneumothorax in patients with pre-existing comorbidities, especially for long needle trajectory, for bleeding greater than mm developing along the needle track. feasibility and safety of ct-guided percutaneous radiofrequency, microwave or cryoablation of the pulmonary and mediastinal unresectable tumours adjacent to the heart and large vessels c. pusceddu, l. melis, g. meloni; cagliari/it (clapusceddu@gmail.com) purpose: to verify the feasibility and safety of radiofrequency ablation (rfa), microwave ablation (mwa) and cryoablation (cra) under ct guidance in the treatment of cancer adjacent to the heart and large vessels. methods and materials: patients (mean age of years) with unresectable primary and secondary pulmonary and mediastinal tumours ( nsclc, invasive thymoma, mesothelial sarcoma and metastases) were treated by ct-guided rfa ( cases), mwa ( cases) and cra ( cases). all the tumours were in contact or distant from the large vessel wall or the pericardium less than cm. all ablations were performed under conscious sedation and local anaesthesia. vital signs of the patients were non-invasively monitored continuously. the therapeutic outcomes were evaluated by contrast-enhanced ct after month. in two patients, an electrode is penetrated in the pericardium without any consequences. results: in all cases, the procedure was technically successful. no intraprocedural arrhythmia occurred. morbidity consisted of cases of pneumothorax, cases of pleural effusion and case of asymptomatic thickening of the pericardium. in the ct control after month, there was a complete necrosis in cases and a partial (from to %) necrosis in the remaining cases. conclusion: indifferently from the energy source used to obtain the tumour necrosis, the treatment of the pulmonary and mediastinal unresectable tumours adjacent to the heart and large vessels is feasible and safe because the blood flow cause a "heat-sink" effect adjacent to such structures that prevent undesired thermal damage. factors influencing local tumour control in patients with neoplastic pulmonary nodules treated with microwave ablation ( were placed in lateral position with the biopsy side down (group b). statistical analysis was performed comparing pneumothorax rate between the two groups. the rate of pneumothorax requiring intervention was also assessed. the effect of other variables (patients demographic characteristics, lesion characteristics, lesion distance from the skin and biopsy technique) was evaluated in both groups. results: pneumothorax occurred in group a ( . %) versus ( . %) in group b (p= . ). pneumothorax requiring treatment was noticed in cases ( . %) in group a, versus ( %) in group b. emphysema and lesion size were independent risk factors for pneumothorax in group a. emphysema was also independent risk factor for pneumothorax necessitating a drainage catheter insertion in group a. no independent risk factor was recognised for pneumothorax or pneumothorax requiring intervention in group. purpose: the aim of this study was to evaluate the feasibility of percutaneous transthoracic needle biopsy of pulmonary nodules under xperguide cbct navigation guidance. between february to july , we evaluated patients with a pulmonary lesion. all patients had a diagnostic conventional chest ct and after underwent percutaneous transthoracic needle biopsies of pulmonary nodules under xperguide cbct navigation guidance.the mean size of the lesion was on average . cm. immediately after fnab an additional cbct was performed to evaluate any complications; moreover, a follow-up expiratory chest radiograph was obtained. calculation of radiation dose of the procedure and statistical analysis were performed. results: technical success rate was achieved in % of cases. forty-six lesions were diagnosed as malignant, were benign, and were indeterminate. all malignancies diagnosed by fnab were confirmed by history and imaging. the overall accuracy, sensitivity, specificity, positive predictive value and negative predictive value were . %, %, %, % and %, respectively. in the patients with a lesion equal or less to cm undergoing xperct-guided lung biopsy the average effective dose was . msv (range . purpose: this study aimed at reviewing the results and the safety of embolisation in patients affected by haemoptysis of pulmonary arterial (pa) origin. all consecutively patients treated for haemoptysis of pa origin during years ( to ) were reviewed. age, underlying disease, and haemoptysis volume were recorded. ct-scan and pulmonary angiography of each patient were reviewed for the description of the pa lesion (aneurysm, false aneurysm, irregularity of the pa or abrupt interruption) and the material of embolisation used for the treatment. results: forty-three patients ( women, men; mean age: years) were treated during this period. aetiologies were tuberculosis (n= ), lung cancer (n= ), necrotizing pneumonitis (n= ), aspergillosis (n= ), behcet disease (n= ) and others (n= ). five abnormalities of pa were found: pseudo aneurysm of the pa (papa) (n= ), aneurysm of the pa (apa) (n= ), irregularity of pa (n= ), early interruption of pa (n= ), one pavm, and no abnormalities in patients. materials used for embolisation were coils (n= ), onyx (n= ) and covered stent (n= ). two early recurrences, short-term recurrences, and one long term recurrence after embolisation were recorded. they were treated by surgery (n= ) percutaneous microwave ablation of lung tumours c. pusceddu, l. melis, g. meloni; cagliari/ it (clapusceddu@gmail.com) purpose: to assess the feasibility and safety of percutaneous ct-guided lung tumour microwave ablation. methods and materials: consecutive patients ( men, women, mean age years) underwent ct-guided percutaneous microwave ablation (mwa) of unresectable lung tumours ( primary nsclc and metastases) mean size . cm ( . - cm). the study cohort was selected according to the following criteria: ) maximum tumour size less than cm in diameter, ) less than metastatic tumors, ) patients with a normal coagulation status and ) provision of written informed consent. all procedures were performed with ct guidance under conscious sedation and local anesthesia. one or two straight microwave antenna ( or -gauge) were placed directly into the tumour for - minutes. follow-up included contrast-enhanced ct at , , months and then at -month intervals; stable or reduction size and the absence of tumour enhancement ct images were considered indicative of complete tumour necrosis. results: in all cases, the procedural was technically successful. morbidity consisted of cases of partial pneumothorax ( . %) which were resolved spontaneously within days. at a mean follow-up of months (range - ), we recorded a . % of complete response (tumour necrosis = %) and a . % of partial response (tumour necrosis range %- %). our preliminary results show that percutaneous ct-guided microwave ablation is feasible and safe for the treatment of primary and secondary lung tumour. further follow-up and a prospective controlled trial is necessary to validate the procedure. week before the ablation and at hours, , , and months post ablation. thin section ct volumetric measurement of the lesions was performed at the same time periods as a second parameter for comparison. the lesion mri enhancement intensity in each study was estimated, and the ratio to the paraspinal muscle enhancement intensity at the same level was measured (lesion muscle signal (lms ratio). the correlations between post ablation follow-up ct volume of tumours and ce-mri lms ratio at the follow-up periods were assessed. results: the preablation tumour volumes ranged between . and . cm (mean: . cm³, sd: . ). lms ratio was noted in preablation due to high contrast enhancement of the tumour and in -h post ablation due to the inflammatory response associated with the thermal ablation and due to tumour residue or progress. weak correlation was detected between the lms-ratios and ct-volumetric changes in -h post ablation. strong correlation between the lms ratios was estimated between the follow-up periods of months (spearmanr: . ,p= . ), months (spearmanr: . ,p= . ), months (spearmanr: . ,p < . ) and months (spearman r: . , p < . ). conclusion: ce-mri follow-up of the mw ablated lung tumours can be used effectively to assess the tumour response to ablation using lms ratio as a parameter of assessment. purpose: to compare image quality between standard-dose filtered back-projection (fbp) and low-dose iterative reconstruction (ir) protocols in computed tomography (ct) of the cervical spine. methods and materials: forty patients investigated by ct of the cervical spine for chronic neck pain and/or cervical radiculopathy were prospectively randomised into two groups: standard-dose ct ( kvp, mas) with fbp, or low-dose ct ( kvp, mas) with ir. image noise, signal-to-noise (snr) and contrast-tonoise (cnr) ratios were measured. two radiologists, blinded to ct parameters, independently assessed the following anatomical structures at c -c and c -c levels, using a four-point scale: intervertebral disc, content of neural foramina and dural sac, ligaments, soft tissues and vertebra. they subsequently rated overall image quality using a ten-point scale. volume ct dose index (ctdivol) and doselength product (dlp) were recorded. imaging quality of reduced radiation dose lumbar spine ct with iterative reconstruction c.-j. lin, s. hung, w. guo, t. wu; taipei/tw (bcjlin@gmail.com) purpose: the purpose of our study was to investigate the diagnostic accuracy of ct scans of the lumbar spine (ctls) acquired with lower mas and kilovoltage reconstructed with an ir algorithm. we prospectively recruited patients for ctls. patients were classified into three groups. the radiation dose reduction was set to % of the original estimated dose with alternative tube currents and kv in group a, and kv in group b. images were reconstructed with idose level reconstruction algorithm. for group c, the standard mas and kv with filtered back projection (fbp) algorithm was employed. the snr of the intervertebral disc (ivd), dural sac (ds) and psoas muscle (pm), and the cnr of the ivd and ds were compared across groups. two radiologists independently rated the quality of each reduced-dose image as either equivalent (' ') or inferior (' ') to the rater's subjective 'standard' ctls. results: there were decreased snrs of all rois in group a but only ds showed statistical significance. there were significant decreased snrs in ivd, ds, and ps in group b. there was a weak correlation between snr and bmi in all groups. the cnrs for groups a, b and c were . + . , . + . and . + . , respectively. the mean image quality scores for groups a, b and c were . , . , and . , respectively. conclusion: with the aid of the ir algorithm, it is feasible to provide diagnostic ctsl imaging with a % radiation reduction using lower mas. multidetector computed tomography of the cervical spine: optimisation of iterative reconstruction strength levels purpose: it was reported previously that trabecular bone structure parameters could add significant information for predicting bone strength beyond bone mineral density. in the past, trabecular bone structure analysis was limited by the spatial resolution of clinically available mdct scanners. recent technical improvements have made it possible to determine trabecular bone structure parameters of the spine using clinical mdct. therefore, the purpose of this study was to assess trabecular bone structure parameters obtained from clinical mdct as well as xtreme-ct (hr-pqct) as standard of reference and to investigate whether clinical mdct can predict vertebral bone strength. methods and materials: fourteen thoracic vertebral bodies were harvested from formalin-fixed human cadavers ( women and men; age: ± years). all specimens were examined using xtreme-ct (isotropic voxel size of μm³) and a clinical whole body mdct (interpolated voxel size: x x μm³, spatial resolution: x x μm³). trabecular bone structure analyses (histomorphometric and texture measures) were performed in the xtreme-ct as well as mdct images. vertebral failure load was determined in an uniaxial biomechanical test. results: xtreme-ct and mdct-derived trabecular bone structure parameters showed correlations ranging from r= . to r= . (p < . ). correlations between trabecular bone structure parameters and failure load amounted up to r= . (p < . ) using the xtreme-ct images, and up to r= . (p < . ) using the mdct images. correlation coefficients obtained with xtreme-ct and mdct were not significantly different (p> . ). the spatial resolution of clinically available whole body mdct scanners is suitable for trabecular bone structure analysis of the spine and to predict vertebral bone strength. contrast-to-noise (cnr) ratios were measured. two radiologists independently and blindly evaluated the following anatomical structures at both c -c and c -c levels, using a four-point scale: intervertebral discs, content of neural foramina and dural sac, ligaments, soft tissues and vertebrae. they ultimately rated the overall diagnostic image quality using a ten-point scale. as the strength level of irs increased, the image noise decreased linearly, while the snr and cnr both increased linearly (all p² . ). for the intervertebral discs, the content of neural foramina and dural sac, and for the ligaments, the subjective image quality scores increased linearly with increasing ir strength levels (all p² . ). in contrast, for the soft tissues and vertebrae, the image quality scores decreased linearly with increasing strength level of irs (all p < . ). finally, the overall diagnostic image quality scores increased linearly with increasing ir strength levels (both p < . ). the optimal strength level of irs in cervical spine mdct depends on the anatomical structure to be analysed. for the intervertebral discs and the content of neural foramina, high ir strength levels are recommended. relationship among facet joint fluid ( years) affected with low back pain underwent mri of lumbar spine using sagittal t -and t -weighted fast spin-echo and axial t *-weighted gradient-echo sequences. for each level from l to s , disk degeneration was graded using the thompson scale ( - ), while the fjf was graded as (absent), (monolateral), or (bilateral): per-patient disk degeneration and fjf were calculated summing the scores of the spine levels. spearman correlation coefficient, multivariate regression analysis, friedman mcnemar tests were used. data were reported as median and interquartile interval (ii). the degeneration of l /l (median ; ii - ) was lower than that of both l /l (median ; ii - ; p= . ) and l /s (median ; ii - ; p= . ). the fjf of l /s (median ; ii - ) was lower than that of both l /l (median ; ii - ; p= . ) and l /l (median ; ii - ; p= . near-perfect correlations of suv values were found for the myocardium (suvmax/ mean: r = . / . ); good correlations were found for the liver (r = . / . ), subcutaneous fat (r = . / . ), bone marrow (r = . / . ), psoas muscle (r = . / . ) and the suvmax of the blood-pool (r = . ). correlations between mrac and ctac were non-significant for suvmax and suvmean of the lung and the suvmean of the blood-pool. the mean suvmax and suvmean in mrac-pet compared to the respective ctac values was significantly lower in all organs (p < . ) but in the myocardium (suvmax) and the psoas muscle (suvmax/mean). results: sixty-three patients were referred for a pre-treatment fdg pet-ct; age range was - years (mean age years). pet-ct had a major impact on patient management in %, a minor impact in % and no impact in %. in patients with a major impact; had unsuspected nodal involvement, had occult metastases, had synchronous tumours and had negative nodes on pet-ct. these findings either altered radiotherapy treatment planning or treatment intent. during the follow-up period until august , % developed disease recurrence following completion of therapy ( % isolated local relapse and % distant (± local) disease). conclusion: fdg pet-ct can have a major impact on patient management in locally advanced cervical carcinoma, by detecting occult disease or characterising indeterminate findings on mri, resulting in an alteration in radiotherapy treatment planning and/or treatment intent in up to one-third of patients. is there a role for standard uptake value in the prognostic evaluation of lung nodules? purpose: we report about our approach in imaging patients with cervical cancer using an integrated simultaneous pet/mri device. goals were the introduction of a stable and effective protocol for whole body and dedicated pelvic examination and rating of image quality. methods and materials: ten patients with primary (n= ) cervical carcinoma or tumour recurrence (n= ) were included. patients underwent a simultaneous pet/ mr, pet/ct and conventional mr examination. mr and pet image quality were rated on a likert score system ( - ) by three radiologists and a nuclear physician. pet data were simultaneously visually compared by two nuclear physicians and a radiologist. purpose: brca and bra mutation carriers may be more susceptible to radiationinduced cancer because of their role of tumour suppressor genes in radio-induced dna damage repair and signalling. heterozygous mutations of a tm , a major kinase initiating the response to radio-induced dna double-strand breaks, is likely to be involved in lymphoma as well as in breast cancer in high-risk patient (hrp) treated for a hodgkin disease. thus the standard two-view mammographic screening annually recommended with mri in hrp must be adapted. recent literature data were analysed. individual radiosensitivity was assessed by radiobiological effects and epidemiological studies. radiophysical and radiological mammographic data about calcifications detection and reduction of exposures were also taken into account. high-resolution diffusion-weighted imaging of pancreatic ductal adenocarcinoma using d reduced field of view single-shot echo planar imaging at . tesla c. ma, y. li, h. wang, s. chen, j. lu; shanghai/cn (mengqihi@gmail.com) purpose: to demonstrate the feasibility of high-resolution dwi of pancreas using d reduced field of view (rfov) single-shot echo-planar sequence in the evaluation of pancreatic ductal adenocarcinoma. methods and materials: normal volunteers and patients with histopathologically proven pancreatic ductal adenocarcinoma by surgery were included in the study. high-resolution dwi of pancreas was obtained using a multi-section d rfov single-shot echo-planar sequence on the axial plane (fov × cm , matrix × ). adc of the normal pancreas in control group and pancreatic ductal adenocarcinoma group were measured. mann-whitney u-test has been used to compare adc values between tumoral tissues and normal pancreatic tissues of the volunteers. results: on the high-resolution dw images, all pancreatic ductal adenocarcinoma demonstrated high signal intensity relative to the surrounding pancreatic parenchyma. the mean and standard deviations of the adc values (× - mm /s) were as follows: pancreatic ductal adenocarcinoma (n = ), . ± . ( . - . ), and normal pancreas in normal volunteers (n = ), . ± . ( . - . ). adc of the pancreatic ductal adenocarcinoma were significantly higher compared with those of normal pancreas (u = . , p = . ). conclusion: rfov dwi shows advantages in higher resolution ( . × . mm ) and blurring reduction compared to full fov dwi of the pancreas. it makes a statistically significant difference on the adc measurements of the pancreatic ductal adenocarcinoma when comparing to the control group. this approach is promising to benefit the early diagnosis of pancreatic cancers. purpose: to prospectively evaluate the application of arfi implemented with virtual touch tissue quantification in the study of pancreatic cystic lesions, using different analysis methods, compared with the final diagnosis (pathological or by mri/eus findings). methods and materials: patients with pancreatic cystic focal lesion (diameter > cm and located at a depth < . cm) were included in the study and underwent conventional us. for every patient measurements with virtual touch quantification roi were performed. in order to distinguish mucinous (potentially malignant) from serous cystic lesions (mainly benign) the result "xxxx/ " was considered meaning simple liquids (reportable to water), and the accuracy of virtual touch tissue quantification in differentiating cystic-pancreatic lesions was calculated. to consider the lesion as containing complex fluids (potentially mucinous), two different reading methods have been applied: at least two numerical values when performing five measurements; prevalence of numerical values irrespective of the number of measurements. sensitivity, specificity, positive and negative predictive values and accuracy were calculated for the differential diagnosis between mucinous versus non-mucinous cystic lesions. results: sensitivity, specificity, ppv, npv and accuracy in the group of cystic lesions using the first reading method were, respectively, . %, . %, . %, . %, . %. sensitivity, specificity, ppv, npv and accuracy in the group of cystic lesions using the second reading method were, respectively, . %, %, %, . %, . %. conclusion: arfi with virtual tissue touch quantification can have a role in noninvasive characterisation of pancreatic cystic lesion during the conventional us examination. purpose: to evaluate the efficacy of ct perfusion for detection of malignancy in pancreatic masses. methods and materials: patients (pts) who presented with a mass in the pancreas were enrolled in this institute review board-approved prospective study after informed consent and underwent biphasic cect with perfusion ct of the pancreas. pts were followed up and results of cytopathological diagnosis obtained. final diagnosis consisted of malignancy (adenocarcinoma) in , various benign masses in and neuroendocrine tumour in pts. control group consisted of pts who were referred for ct for an indication other than pancreatic pathology. perfusion parameters were calculated using software mistar . (apollo imaging software). ct perfusion parameters were compared between the control and study groups as well as results of cytopathological diagnosis using anova and dunnett -sided t-test for statistical analysis. results: all perfusion parameters except extraction (e) were significantly different between adenocarcinoma and benign groups. all perfusion parameters except permeability (ps) were also statistically significantly different between adenocarcinoma group and controls. blood flow (bf), blood volume (bv), extraction fraction product (efp), ps and peak enhancement intensity (pei) showed decreasing trend in values, whereas rest of the parameters showed an increasing trend from normal to benign to adenocarcinoma. neuroendocrine tumours had different perfusion values with significantly elevated bf, bv, pei and earlier time to peak (ttp). one patient with pancreatic tuberculosis had perfusion values paralleling adenocarcinoma but with relatively earlier ttp. conclusion: perfusion ct seems to be a useful tool for differentiating between malignant and benign pancreatic masses. comparison after the acquisition of axial t w and t w sequences and coronal mrcp, diffusionweighted mr imaging was performed using an axial respiratory-triggered spin-echo echo-planar sequence with multiple b values ( , , , sec/mm²) in all diffusion directions. adc value was calculated by using a dedicated software fitting the curve obtained from the corresponding adc for each b value. fitted adc values were calculated by two observers in conference for each cystic pancreatic lesion and for normal pancreatic parenchyma. imaging results were correlated with surgery, ercp, and/or imaging follow-up. results: final diagnoses included intraductal papillary mucinous tumour (ipmt) (n= ), serous cystoadenoma (n= ), and mucinous cystoadenoma (n= ). fitted adc value was . x - mm /sec for normal pancreatic parenchyma, . x - mm /sec for ipmt, . x - mm /sec for serous cystoadenoma, . x - mm / sec for mucinous cystoadenoma. fitted adc values were significantly higher in mucinous neoplasms than in serous cystoadenomas (p < . ). our results suggest that diffusion-weighted t mr imaging with b-multiple se-epi may be helpful to differentiate mucinous from serous cystic pancreatic lesions. further investigations in larger series of patients are necessary to confirm our data. purpose: cardiac magnetic resonance imaging (cmr) using a comprehensive approach consisting of adenosine perfusion and late gadolinium enhancement (lge) at . tesla has established for detection of relevant coronary artery disease (cad). little is known about the potential advantages of tesla cmr to detect relevant cad. aim of our prospective study was to compare a clinical routine cmr protocol performed at both . and tesla in patients with suspected cad undergoing coronary x-ray angiography. methods and materials: patients ( . ± . years) with suspected cad were included into the study. all patients were scanned at both . and tesla including functional imaging, adenosine stress and rest perfusion, and lge. cmr images were analysed by two blinded readers in consensus. x-ray angiography served as the reference method. results: diagnostic accuracy of the combined analysis of perfusion and lge imaging yielded better values at . and tesla than the analysis of perfusion images alone. sensitivity and specificity at tesla were superior to . purpose: the purpose of this study was to evaluate the prevalence of pathological cardiac mri findings in subjects with mild coronary calcifications. methods and materials: asymptomatic volunteers were selected from a large population-based screening study in accordance with their agatston calcium score (group : agatston score: , n = , age . +- . ; group : agatston score: - , n = , age . +- . ). all subjects underwent cardiac mri at . t. the mri protocol included a) functional assessment of the left ventricle, b) assessment of adenosine stress-/rest perfusion and c) quantification of late gadolinium enhancement (lge). results: a stress-induced perfusion deficit was present in / subjects ( . %), whereas lge was seen in / subjects ( . %). group (agatston score: ): in this group none of the subjects showed a perfusion deficit, whereas in seven subjects lge was observed ( . %). two of the seven subjects showed an ischaemic-type pattern of lge ( . %) indicating chronic infarction. group : median agatston score of group was (q , ; q , ). in this group a perfusion deficit could be observed in one subject ( . %), whereas lge was observed in ten subjects ( . %). however, all of these lge patterns were assessed as non-ischaemic. the prevalence of stress-induced myocardial ischaemia in subjects with mild coronary calcifications score is low, whereas the frequency of non-ischaemic lge is relatively high. long-term follow-up will clarify whether these cardiac mri findings contribute to cardiovascular risk stratification in asymptomatic subjects. purpose: to determine the feasibility of ct-based myocardial perfusion imaging to differentiate ischaemic and infarcted myocardium as compared to magnetic resonance imaging (mri). we prospectively enrolled subjects with suspected coronary artery disease, who underwent adenosine-mediated stress myocardial perfusion imaging by dynamic dual-source ct ( kv, mas/rot) and t-mri. myocardial blood flow and volume (mbf and mbv, respectively) were derived from ct images, using a model-based parametric deconvolution method for myocardial segments. these were related to perfusion defects visually assessed during rest/stress and delayed mri acquisitions. conventional measures of diagnostic accuracy and differences in mbf/mbv were determined in a blinded fashion. results: among enrolled subjects, (mean age ± years, % men) completed the protocol. the prevalence of ischaemic and infarcted segments detected by mri was moderately high ( . % and . %, respectively purpose: patients with extra-cardiac arterial disease (ecad) are at high risk of coronary heart disease. we examined the prevalence of silent, significant coronary artery disease in patients with stenotic or aneurysmatic ecad. methods and materials: cardiac asymptomatic ecad patients without contraindications for computed tomography (ct) and magnetic resonance imaging (mri) underwent coronary ct angiography (ccta) and adenosine perfusion mri (apmr). calcium scoring was performed based on non-contrast ct. ccta was positive when ³ % lumen diameter stenosis in a coronary artery was found. patients were referred to a cardiologist when ccta showed a stenosis in the left main coronary artery (or equivalent), or when apmr showed inducible myocardial ischaemia. results: in total, patients (mean age yrs; % male) were included. patients were divided into categories: stenotic (n= ) and aneurysmatic ecad (n= ). ccta was positive in % in stenotic and % in aneurysmatic ecad. no ccta was performed in % due to excessive calcium. two patients, stenotic and aneurysmatic ecad had left main stenosis. apmr was positive in % in stenotic and % in aneurysmatic ecad. eighteen percent of stenotic and % in aneurysmatic ecad have been referred to the cardiologist. a cardiac intervention was performed in % of stenotic and % in aneurysmatic ecad. significant stenosis or high calcium score was found in % in stenotic, compared to % in aneurysmatic ecad. none of these outcomes were statistically significant. conclusion: silent, significant coronary artery disease is highly prevalent in patients with ecad, either stenotic or aneurysmatic. purpose: to evaluate non-linear image blending in comparison with linear image blending in late phase dual-energy computed tomography (dect) for the visualisation of delayed myocardial contrast enhancement in acute myocardial infarction (mi) and to identify optimal parameters for non-linear image blending. methods and materials: acute reperfused mi was induced in seven pigs by temporary occlusion of the left anterior descending or left circumflex artery. two hours after reperfusion contrast-enhanced late phase dect ( kv/ kv) was performed. dect data were post-processed with linear and non-linear image blending techniques. contrast and percentage signal difference between healthy and infarcted myocardium as well as the blood pool of the left ventricle were computed for the linear and non-linear techniques including the low and high kv images. data were compared using repeated measures anova and post hoc t-tests. results: non-linear blending showed the highest signal differences for all contrasts and analyses. repeated measure anovas confirmed these differences to be statistically significant for the different post-processing techniques (p-value ranging from < . to . ). paired-samples post hoc t-tests proved the significance of these results (p-value ranging from < . to . ). the ideal settings for nonlinear image blending can be deduced from the ct values of the regions of interest in the linearly blended images with the weighting factor . . conclusion: non-linear image blending improves the visualisation of acute mi in dect. non-linear image blending in late phase dect of acute mi is superior to linearly blended images as well as source images obtained at kv or kv. purpose: to assess feasibility and reliability of the juvenile arthritis mri scoring system (jamris) for the wrist to evaluate early-stage disease activity, and to compare reliability of jamris for the wrist for early-stage disease with the validated paediatric-targeted mri scoring system (ptmris) for children with more progressive stage of disease. methods and materials: mri datasets from juvenile idiopathic arthritis (jia) patients with wrist involvement were evaluated independently by three readers using jamris and ptmris. assessment of early-stage disease activity in jamris was achieved through extending soft tissue scoring items (synovial hypertrophy, tenosynovitis) and specifying the grading of bone scoring items affecting < % of the bone (bone marrow changes, bone erosions). intraclass correlation coefficient (icc) or cohen's kappa was used to assess inter-and intrareader reliability. icc of each jamris scoring item was compared with the icc of its equivalent in ptmris. results: three jamris scoring items (synovial hypertrophy, bone marrow changes and bone erosions) showed moderate to good reliability: icc varied from . to . for interreader reliability and . - . (reader ) and . - . (reader ) for intrareader reliability. reliability of tenosynovitis was moderate to poor with cohen's kappa varying from . to . (interreader) and . to . (intrareader). jamris and ptmris showed similar results of interreader reliability. conclusion: early jia disease activity in the wrist can be reliably evaluated with three-out-of-four features of the simple and accurate jamris scoring system. correlating clinical disease assessment and responsiveness to change will be needed to validate jamris for the wrist as outcome measure and disease monitoring tool. showing equivocal findings or a bone injury outwith the clavicle. in those found to have clavicle fractures, follow-up radiographs were performed in individuals ( %). orthopaedic fixation was not performed in any of the identified cases. conclusion: despite a high pick-up rate of fractures, clavicle radiographs do not appear to substantially alter clinical management. in our centre, immobilization is the usual management for suspected traumatic clavicle injury, regardless of radiographic appearance. we suggest that, in the context of an experienced paediatric emergency department team, radiographs are reserved for patients causing concern at follow-up and are not required routinely at presentation. (an) is an eating disorder characterised by alteration of bone metabolism (osteopenia) and of body composition (reduction and abnormal distribution of fat mass-fm and lean mass-lm), due to oestrogen deficiency and self starvation. the aim of our study was to address bone metabolism and body changes in a cohort of patients with an by using dual-energy x-ray-absorptiometry (dxa). prospective study on patients with an, submitted to dxa at baseline-t and after months-t . we evaluated total and regional fm and lm percentages, as well as lumbar bone mineral density-bmd and z-score, linking them to clinical variables: menarche/amenorrhea/hormonal therapy and physical activity. results: among the / - . % patients that completed the study the t clinical condition was as follows: bmi= . ± . kg/m , low levels of fm percentage ( . ± . %), osteopenia (z-score:- . ± . sd, with higher values related to physical activity-p= . ). at t : significant increase in bmi-p= . , with lm reduction and fm increase (more evident in the trunk-p < . ); regarding bone, no significant changes were observed, though a tendency in terms of improvement associated with resumption of menses was manifested. after one year, significant conclusions on bone metabolic condition could not be reached. by contrast, weight recovery was associated with the increase of fm and a distortion of its distribution, more evident in trunk region (potential and adjunctive risk factor for the relapse of the psychiatric condition). the complexity of these clinical findings suggested that dxa, a low-dose and low-cost technique, could have a key role in long-term monitoring of an patients. replacing conventional spine radiographs with dual-energy x-ray absorptiometry (dxa) in children with suspected reduction in bone density e. adiotomre, l. summers, p. broadley, i. lang, g. morrison, a. offiah; purpose: children have greater lifetime risks of radiation-induced complications compared to adults. in children with osteogenesis imperfecta conventional radiographs are obtained to assess spine morphometry, while dxa assesses bone density. in adults dxa is used for both. we aim to establish whether idxa can replace spine radiographs in assessment of paediatric vertebral morphometry. methods and materials: an -month prospective study of consented children ( to years old) with and without suspected reduction in bone density, who had lateral spine radiographs and lateral dxa scans on the same day, was conducted. three observers will independently assess all images (blinded to corresponding results of radiographs and dxa) using a modified abq technique. random images will be interpreted twice. diagnostic accuracy and inter-and intraobserver reliability of dxa will be compared to the gold standard of radiography. patient/carer experience, dxa radiation dose compared to radiographs and health economics will be assessed. results: interim analysis of the first recruited patients showed had or more vertebral fractures. the fracture detection sensitivity for dxa was . % and specificity . %. the overall accuracy for vertebral fracture detection with dxa was . %. the overall agreement between radiographs and dxa was . %. the modified abq technique has limitations in children and a more reliable scoring system is required. compared to radiography dxa does not appear to be worse for morphometry and given the reduced dose and comparable image quality, dxa should be recommended for morphometry in children pending more robust analyses. (n= ) had ddh necessitating or more ultrasound examinations, of which % (n= ) required treatment. there was one case of missed hip dislocation, representing . % of unexamined patients. no patients with iic hips at presentation with conservative management represented with a dislocated hip. radiographs in the treated group demonstrated a satisfactory outcome in %. one patient represented with a dislocated hip following erroneous cessation of harness treatment and went on to develop early avascular necrosis. two patients were lost to follow-up. conclusion: a delayed approach to managing ddh in infancy allows those patients with ultrasonographically immature hips the opportunity to develop normally without invasive treatment and identifies patients which would most benefit from treatment. this reduces the demand on resources that a ddh screening programme which treated patients more promptly would incur. within the same financial constraints, this allows more patients to be selected for screening. a delayed approach results in a satisfactory outcome with no subsequent late dislocation in those treated appropriately. purpose: in cases of hip complaints in the paediatric population it is common practice to acquire both ap and frog-leg lateral (fl) radiographs. the combination of these views has a diagnostic yield, but also doubles the radiation exposure. in our observation, the fl view alone is often diagnostic. we therefore investigated the diagnostic accuracy of obtaining a solitary fl view as compared to a combination of the ap and fl views. methods and materials: children aged - years who were sent in for hip radiographs between september and january were included in the study. cases of related trauma or a history of hip pathology were excluded. radiographs were retrospectively assessed by two independent radiologists. radiologists were blinded for the ap radiograph while assessing the fl radiograph and vice versa and radiographs were presented in a random order. we used the kappa test to calculate interobserver agreement and agreement between the assessment of both views and the solitary fl view. results: children (mean age . yrs) met the study criteria and were included for analysis. children had a normal exam and were considered abnormal. calculated interobserver agreement using the kappa test was . . agreement between the solitary fl view and the combination of the ap/fl view was . . the diagnostic accuracy of the fl radiograph in case of hip complaints in children is as high as the current standard of both ap and fl views. and healthcare centres. statistical analysis was made using descriptive statistics, mann-whitney and kruskal-wallis tests in order to verify correlation between items. results: radiographers consider that it is essential the implementation of a quality control program in the radiology department, but there is lack of information in this field, and . % do not know what a quality control program is. % of radiographers claim their institutions do not have quality control programmes or accreditation. however, . % had received education on quality and % make regular personnel radiation measures. also, despite there is no lack of radiological protection equipment in most departments, . % claim they are in poor condition. conclusion: quality control programs are essential to the radiology department and radiation safety guidelines must be implemented. despite that some radiology departments have radiological protection equipment often applied by radiographers, their effectiveness and condition must be checked regularly. purpose: applying control charts to demonstrate the importance of implementing a radiological imaging quality control system. research conducted in a public hospital comprising a total of randomly selected exams ( chest studies, abdominal studies and foot studies) grouped in samples, each one with exams. the conformities and non-conformities found were used to establish three types of quality control charts based on the evidence collected, namely the proportion of conformities and non-conformities (p), the total number of non-conformity exams (np) and the total number of non-conformities in each sample (c) in order to suggest corrective actions for improvement. results: considering all exams, % are non-conformities and % are within conformities. of chest studies, % were within conformities and % were non-conformities; of abdominal studies, % were within conformities and % were non-conformities. foot studies had an almost even distribution of conformities and non-conformities with and %, respectively. conclusion: this research allowed the identification of different types of nonconformities found in radiological images which have impact on imaging quality. therefore, the existence of adequate quality control of radiographic imaging is essential. a review of diagnostic imaging frequency to aid research exploring the issue of consent for higher dose paediatric examinations j.l. portelli , j. mcnulty , s. mohan , p. bezzina , l. rainford ; msida/mt, dublin/ie (jonathan.portelli@um.edu.mt) purpose: concerns have grown in recent years in relation to potential radiationrelated risks associated with diagnostic imaging examinations performed on paediatrics (< years). this retrospective cohort study aims to provide an insight into the use of potentially higher dose computed tomography (ct) and fluoroscopyguided examinations in paediatrics, in two national clinical centres of comparable catchment areas in malta and ireland. methods and materials: retrospective data, of higher dose diagnostic imaging examinations performed in paediatrics in , was collected from departmental logbooks and radiology information system (ris) databases of the participating centres. this data included details pertaining to patient's age, type of examination and relevant examination kv, mas, dap, fluoroscopy time, ctdi and dlp (if available). data were categorised according to age and examination type, and effective dose estimates for ct were calculated. results: in alone, at least , ct examinations, , fluoroscopy-guided procedures and cardiac catheterisation interventions were performed on paediatrics across both centres. particular complex fluoroscopy-guided interventions had an associated dap exceeding , cgy.cm , while effective dose estimates for ct examinations indicated that some paediatric patients may receive a moderate (> - msv) or high radiation dose (> - msv). conclusion: paediatric patients may undergo examinations that potentially involve a high dose of ionising radiation. further research to explore the debated issue of benefit-risk communication and consent in paediatric imaging is therefore justified and encouraged, particularly as the study's findings also indicate that repeat or multiple imaging examinations of different anatomical areas are commonly performed in ct. purpose: to estimate the lifetime attributable risk (lar) of cancer incidence for individual organs following radiation exposure during pci in the context of two opposite sides of angiographic spectrum of coronary occlusive disease: st-elevation myocardial infarction (stemi) and chronic coronary total occlusion (cto). we identified all consecutive patients treated with pci for stemi (n= ) and for cto (n= ) in a tertiary care centre in years. the lars of cancer incidence for six organs (colon, liver, lung, red bone marrow, stomach and thyroid) were estimated using the biological effects of ionising radiation (beir) vii model. the estimated lars of cancer incidence for individual organs was found to markedly increase as the age of the patient decreases and was significantly higher for the lung (additional risk up to / . person's lifetime exposure in cto and / . in stemi patients, respectively, p < . ) and for the red bone marrow (up to . / . and . / . , respectively, p < . ). in both the groups, the estimated lar of cancer incidence for stomach, colon, liver and thyroid was similar and very low. conclusion: in pci procedures, the lung was the organ with the highest radiation absorbed. according to beir-vii model, the number of additional cancer cases for individual organs was on average two times higher in patients treated with pci for cto and the highest lars were for lung and red bone marrow cancers. project retake: quality assurance of radiation hygiene by maintaining image quality purpose: to reduce the extent of retake while maintaining image quality. the research was conducted in two digital x-ray labs, data for six months were analysed by quantitative method. patient data: id, information of retakes was stored at modality, post-examination. random patients, undergoing standard x-ray examinations, were selected each month. a standard examination contains two or three exposures, front oblique and/or lateral. radiographers were encouraged to choose a cause for retake. analysis contained: type of examination, number of projections, number of exposures and retake reason per patient. the causes are systemised in the modality, ready to select if there is a retake. reject options were radiographer, patient or student failure. there was an average of retaken images out of examinations. that is to say, % margin of error. % of the standard examinations were retakes; the reject option was radiographer failure. rest % was patient or student failure. as a result of this a pgmi test is established for the digital labs to test quality assurance. results after this quality assurance give a reduction of retakes per month. a reduction of % retakes due to radiographer failure. conclusion: environment, method, monitoring and feedback, influence radiographer result and radiation dose to patients. radiographers using digital x-ray need quality assurance as in mammography. pgmi usage will give feedback to maintain image quality and reduce radiation dose. implementation purpose: to evaluate the importance that radiographers give to quality control programs, radiological protection and the verification of radiological protection criteria. a -item quality control assessment and radiological protection questionnaire was applied to radiographers working on public hospitals s a c d e f g b saturday viability was tested by performing two tests on the lateral position of the lumbar spine, with a phantom. the results obtained using the aluminum filter resulted in a reduced variation in relative dose rate ( %) compared to not using the filter as well as a % reduction in dose to the entrance surface of the skin. regarding the image quality, it has been found that the use of filter presents significant reasons the optimisation of this parameter. these results indicate that the use of the filter should be considered as a good practice in the lumbar spine radiography to achieve dose reductions. antero-posterior (ap) pelvic radiography: collimator errors and their effects on radiation dose h. brookfield , a.s. manning-stanley , a. england ; liverpool/uk, salford/uk (aengland@liverpool.ac.uk) purpose: to investigate the range of collimator errors in x-ray rooms and to calculate their possible effects on the radiation dose for ap pelvis examinations. a collimator test tool was suspended at three heights ( , and cm) above the table bucky in nine x-ray rooms. heights corresponded to the patient thickness (mean, ± sd) in patients. the x-ray beam was visually collimated to the inner boundary of the test tool and exposed to radiation. differences between the visualised field size and the resultant x-ray field size (corrected for magnification) would indicate any collimator errors. on the pelvic phantom minimum textbook collimation was set and then changed in order to simulate a range of possible collimator errors. phantom examinations used a standard technique with exposure termination using outer aec chambers. dose-area-product (dap) was recorded. results: out of nine x-ray rooms all but one produced a smaller irradiated area than was visually set. errors ranged from a % reduction in irradiated field size to a slight over irradiation by . %. with the possibility that these errors could be larger in other institutions a range of (- % to + %) errors were simulated. increasing the field size by cm (superior/inferiorly) increased the dap by %. laterally, a cm increase caused a % rise. increases of cm in both planes raised dap by %. in this study collimator errors were minimal and favoured under irradiation. small errors can affect dap and are more dose significant in the superior/inferior plane. breast shielding significantly reduces breast dose during lumbar spine radiography n. mekiš, d. Žontar, d. Škrk; ljubljana/si (nejc.mekis@zf.uni-lj.si) purpose: as use of protective shielding for the patient in conventional radiography varies widely in practice, the study aimed at providing objective answer about the effect of lead rubber sheet shielding for a specific case of breast dose during the lumbar spine radiography. influence of the body mass index on the breast dose was also investigated. the study was conducted both on an anthropomorphic phantom and on a cohort of female patients, randomly divided into two equal groups. in both cases lumbar spine imaging was conducted in ap and lateral projection with and without the lead shield (in case of the patient study the shielding was used in one group only). the dose was measured by thermoluminescent dosimeters (tld) placed at the centre of the breast. results: using the lead shielding dose to the right breast was reduced from . ± . mgy to . ± . mgy (p < . ) and the dose to the left breast from . ± . mgy to . ± . mgy (p < . ), compared to the unshielded breast. on average, the breast dose was reduced by approximately %. no correlation between the body mass index (bmi) and the breast dose was found. conclusion: based on the results, we can conclude that the use of breast shielding is recommended in lumbar spine radiography. despite the low-dose exposure even without shielding, the dose can be further reduced. moreover, the quality of the x-ray image is not affected by the use of the lead shield. an approach for portuguese diagnostic reference levels for bedside chest radiography a. sousa, s. serém, j. santos, g. paulo; coimbra/pt (sarajoanacs@hotmail.com) purpose: bedside chest radiography represents the most commonly performed examination. taking into account the different protocols and equipments it is important to develop diagnostic reference levels, in order to promote a patient safety culture and consequently health care best practice. this research was carried out in two imaging department centres from the same geographic region (hospital a and hospital b). in phase one, the exposure parameters and entrance skin dose (esd) value of bedside standard patients' chest radiography were collected. to optimise the obtained dose values in hospital b more bedside standard patients' chest radiography were collected on phase two, using parameters of hospital a, that had already went through an optimisation process. results: in phase one hospital a esd value was statistically lower ( . μsv) in comparison to hospital b ( . μsv). in phase two hospital b decreased significantly the esd value ( μsv) in comparison with the phase one, but with no significant differences with hospital a. conclusion: patients in hospital b at phase one were % more exposed to ionising radiation than patients from hospital a for the same procedure. the implementation of optimised protocols at phase two reduced the dose levels in . % in the hospital b. the regional drl for bedside chest radiography was set at μsv. an investigation into the relationship between the exposure index value and image quality m.-l. butler, l. rainford; dublin/ie (marielouise.butler@ucd.ie) purpose: 'exposure creep' is a documented phenomenon in computed radiography (cr) where radiation dose is given unnecessarily to patients due to cr's processing capabilities. manufacturers have responded by developing an exposure index (ei), which is a measurement of detector dose and hence relates to noise in the image. this study aimed to identify how the ei value relates to image quality in clinical practice. methods and materials: three imaging suites and five radiographic examinations were included: ankle and wrist series (antero-posterior (ap) and lateral); ap and lateral lumbar spine; ap pelvis and postero-anterior (pa) chest projections. in total, examinations were documented with a minimum of patients for each projection. twelve patient images representative of each projection were selected according to their agfa lgm value; low, median and high lgm values and images recording lgm values closest to the manufacturers' guidelines. three observers, experienced radiographers (minimum of years working clinically), reviewed the images for noise and overall exposure of the image. in addition the observers indicated what ei value they judged appropriate to image presentation. results: no significant difference in image quality was noted across the categories of lgm when considering noise (chi-square ( )= . , p= . ) or exposure (chi-square ( )= . , p= . ). lgm values judged by observers as representative of image quality were lower than those recorded clinically. no correlation with lgm and clinical image quality was identified in this study. further research is recommended to include additional manufacturers and radiographic examinations. attenuation of anode heel effect with an aluminum filter and their influence on patient dose in lumbar spine radiography j. soares, r. dores, p. sousa, s.i. rodrigues, l.p.v. ribeiro, a.f.c.l. abrantes, r.p.p. almeida; faro/pt (joana.soares. @hotmail.com) purpose: study the attenuation of anode heel effect with an aluminum filter, thereby optimising the image quality, without increasing the patient dose exposure. this study was performed in a radiology department with a conventional radiology equipment. the filter construction was based on the radiographic study of the lumbar spine in a lateral position, and used the following technical parameters: kv, ma, ms and . cm of sid. experiments were performed to study the behaviour of anode effect along the longitudinal anodecathode axis. measurements of dose rate using the detetor unfors xi rf was carried out. this detector also allowed performing the equipment quality control. in order to standardise the variation in beam intensity of x-ray filters were used with different thicknesses of aluminum to reduce the value of the dose rate and to determine the thickness of the filter construction. after construction of the filter, the stereological approach enables the quick estimation of rv parameters with high accuracy and reproducibility from mr images. automated computerized software for diameter and volume measurements of pulmonary metastatic disease: preliminary evaluation e. lotan, d. aharoni, s. raskin, b. boursi, r. berger, e. konen; ramamt gan/il purpose: serial ct scans of metastatic tumours are vital in assessing the efficacy of cancer treatment. we evaluated the performance of a novel automated computerized software system that integrates registration, segmentation and tumour measurement into a single process to expedite recist measurement with the addition of volume measurement. methods and materials: measurements of long and short-axis of lung metastatic lesions in sequential patients with metastatic renal cell carcinoma were manually obtained twice by radiologists. those measurements were compared with automated software measurements (carestream health, rochester, ny). in addition, the software automatically identified the lesions' contours and volumes; the readers could accept the automated measurement or correct it manually. intraobserver correlation was assessed by intraclass correlation coefficient (icc), and interobserver reliability by the concordance correlation coefficient (ccc) and bland-altman limits of agreement. purpose: clinical guidelines for follow-up of pulmonary nodules depend on nodule type and therefore accurate characterisation of nodules is important. a novel computer-aided diagnosis (cad) system to distinguish solid, part-solid and nonsolid nodules is presented and evaluated on a large data set from a lung cancer screening trial. methods and materials: the automated characterisation system is based on a previously published nodule segmentation algorithm. four different parameter settings were used to extract the solid part, non-solid part and solid core of the lesion. for each segmentation, volume, mass, average density, th percentile and th percentile of densities inside the segmentation were used as features. a k-nearestneighbour classifier was used to classify nodules. the accuracy of the system to differentiate between solid and subsolid nodules, between solid, part-solid and non-solid nodules and between part-solid and non-solid nodules was evaluated. a data set consisting of low-dose chest ct scans ( x . mm, - kvp, mas) with solid, part-solid and non-solid nodules was collected from a screening trial. the nodule type recorded in the screening database was used as the reference standard. experiments were performed in leave-one-nodule-out cross-validation. the accuracy of cad to differentiate between solid and subsolid nodules was . . differentiation into solid, part-solid and non-solid nodules gave an accuracy of . . cad had an accuracy of . in differentiating part-solid from non-solid nodules. automated characterisation of pulmonary nodules shows good performance. this can aid radiologists to decide on appropriate workup in clinical practice. author purpose: right ventricular (rv) volume and ejection fraction (ef) assessment is of clinical value. this procedure, based on manual delineation of the endocardial contours on mr images, is time-consuming due to ventricle's complex shape. we introduce a stereological method for estimating rv parameters from mri data without the need for image segmentation. methods and materials: twenty-two consecutive patients with coronary artery disease underwent cardiac mri. stereological estimations involved the automatic placement of a systematic grid of test points with random orientation over shortaxis images. all points hitting the rv were counted using the semiautomatic point selection process. the optimum point spacing of the grid was defined. the software automatically provided the rv volumes and ef. two independent observers evaluated the measurement reproducibility. stereological estimations were compared with those determined by manually tracing rv contours. results: acceptable estimations of rv parameters with a mean coefficient of error of . ± . % were obtained by counting an average of only points per image. the mean time of stereological analysis was . ± . min, whereas the intraobserver and interobserver variability was . - . % and . - . %, respectively. the mean differences between stereology and manual tracing for estimating the end-diastolic volume, end-systolic volume and ef were small and equal to . ± . ml, . ± . ml and - . ± . %, respectively. the parameters obtained by the two methods were not significantly different (p> . ), and they were strongly correlated (r> . ). performed after standardised preparation. d-motility-acquisitions (dynamic- d-t -fiesta; tr . /te . /fov / mm) covering the entire small bowel were performed in free breathing over sec. image analysis for the assessment of small bowel motility was performed both manually and with the software. the time consumption and reproducibility were compared using coefficient of variance and paired student`s t-test. results: single regions of interest were analysed two times by hand and two times using motasso with a dedicated displacement provider. mean small bowel contraction frequency was . contractions per minute (sd+- . ) for manual and . (sd+- . ) for motasso analyses; the mean luminal diameter was . mm (manual, sd+- . ) and . mm (motasso, sd+- . ), respectively. the variability of repetitive measurements (coefficient of variation) was . % (sd+- . ) for manual and significantly lower (p < . ) for motasso-assisted measurements ( . %, sd+- . ). the mean duration needed for a single small-bowel motility assessment was . min for manual (sd+- . min, range - min) and high significant lower (p < . ) for motasso-assisted measurements ( . min, sd+- . , range - min). the use of motasso proves highly reliable and fast measurements of small bowel motility in free breathing mri. reproducibility was significantly higher for motasso-assisted than for manual measurements, while the time needed for the single measurement could be tremendously reduced using motasso. purpose: plaque treatments carry considerable risk, and hence, adjunct techniques are necessary to help doctors in making a confident decision about the necessity of such procedures for a patient. mostly, symptomatic patients face a greater risk of cardiovascular diseases, and hence, classification of the plaque into symptomatic and asymptomatic is necessary. therefore, we have developed a non-invasive computer-aided diagnostic technique for the same. methods and materials: carotid artery images were acquired using multi-detector row ct angiography (mdcta). the region of interest (roi) was segmented manually from the images, and the rois were used to extract texture-based and discrete wavelet transform-based features. significant features were used to train and test support vector machine (svm) classifiers of various kernel configurations. the svm classifier with a polynomial kernel of order presented the highest accuracy of %, sensitivity of . %, and specificity of . %. we formulated a riskscore, which is a combination of all the features, in order to monitor the variations in features, and also to more objectively classify the two classes. conclusion: a technique that uses the ct images to identify symptomatic and asymptomatic plaques would add more value to this modality in the area of atherosclerosis management. we have proposed and demonstrated the efficiency of one such technique in this work. the classification accuracy is high, and the technique is non-invasive, fast, highly objective, cost-effective and user-friendly. therefore, it can serve as a valuable adjunct tool that can be used by clinicians in deciding treatment options for patients. automated labelling framework applied on full and partial spine ct scans d. major, j. hladuvka, f. schulze, k. bühler; vienna/at (david.major@vrvis.at) purpose: the spine is often a frame of reference for diagnosis. for this purpose its parts have to be labelled in upper body ct scans which is a time-consuming task. an automated framework is introduced for detecting intervertebral disk and vertebra centre points and its labels in ct data containing the spine fully or partly considering clinical resource constraints. the framework uses a machine learning-based classification approach for detecting spinal canal centre point candidates as a first step. intervertebral disk-, rib-and sacrum centre point candidates are extracted next to the spinal canal by the same classification approach. intevertebral disk centre point labelling is started relative to either ribs or sacrum depending on detection certainty. the labelling run is done iteratively along the spine by obtaining best matches of trained local appearance models to detected three intervertebral disk and spinal canal centre point candidate clusters. vertebra centres/labels are derived from the intervertebral disk ones. the framework has been trained on and tested on solutions. accordingly, dedicated software was developed. we evaluated its clinical performance in a series of brain tumours imaged with state-of-the-art t-mri. methods and materials: seventeen enhancing brain tumours were investigated (magnetom trio/ t; dynamic t -weighted-sequence/twist: temporal-resolution: . s, in-plane-resolution: . * . * . mm , ml dotarem@ ml/s; anatomicsequence/mprage: in-plane-resolution: . mm ). post-processing was performed to test a dedicated commercially available cad-tool. amongst other pre-processing features it implements [ ] elastic d-motion-correction (dynamic-contrastenhanced scans), [ ] co-registration of dce-and anatomic-scans ( d and d), [ ] identification of regions-of-interest ( d-roi), [ ] identification of appropriate arterial-input-function (aif). output data include quantitative pharmacokineticparameters (two-compartment tofts-model: k trans , k ep , ve, etc). and fitted/unfitted enhancement-curves ([mmolgd/l]). all pre-preprocessing features and the quality of fitted curve-data were evaluated by an experienced neuroradiologist and scored on confidence-scales ( =not appropriate to =excellent). pharmacokineticparameters were correlated with final diagnosis (benign/malignant: roc-analysis). results: motion-correction was technically successful in all cases. co-registration in d (mean-score[ms]: . ) and d (ms= . ) as well as identification of the aif (ms: . ) reached excellent ratings. placement of d-rois was difficult in one lesion (score= ). yet, in total it was performed appropriately (ms= . ). overall quality of fitted curve-data reached good scores (ms= ), resulting into a high diagnosticaccuracy for the differentiation of benign vs. malignant tumors (auc= % [k ep ]). the software showed an excellent clinical performance. this should help to further promote quantitative pharmacokinetic-analyses and might broaden its application in clinical practice in the future. rapid semi-automated volumetry of pleural effusion in mdct m.p.f. botelho, f.d. gonzalez-guindalini, h. chalian, v. yaghmai; purpose: to evaluate precision and reproducibility of volumetric semi-automated quantification of pleural effusions in mdct. this study was irb approved. we evaluated consecutive pleural effusions in adult patients undergoing contrast-enhanced mdct of the chest. two independent blinded readers used a semi-automated segmentation software for estimation of volume and recorded quantification time. manual volumetry was obtained as the reference. we evaluated the volumetry for precision, time for assessment and inter-rater agreement, as well as percentage of over-and under-segmentation. statistical analysis encompassed paired t-test, bland-altman plot and lin's concordance correlation coefficient. the mean semi-automated and manual volumes were . ml (sd . ml) and . ml (sd . ml), respectively (p= . ). semi-automated volumetry showed significant inter-rater agreement, with bland-altman precision of . % (upper and lower limits of . % and - . %, respectively). the mean semi-automated volumetry was accurate when compared to manual volumetry, with bland-altman precision of . % (upper and lower limits of . % and - . %, respectively), and lin's concordance correlation coefficient (ρc) = . . there was a mean of . % over-segmentation using the semi-automated software. the average user time for semi-automated volumetry was . sec/case, whereas those for manual volumetry were sec/case (p < . ). conclusion: rapid and accurate semi-automated volumetry of pleural effusions in mdct is feasible and reproducible. purpose: to present a paradigm shift in computer-assisted image interpretation and to assess its application in ct colonography. a novel segmentation-free scheme has been developed with the hypothesis that accurate colon segmentation is neither necessary nor an end clinical objective for delivering efficient support such as colon centreline, electronic colon cleansing (ecc) and computer-aided detection of lesions (cad). methods and materials: thick regions are expanded until they encompass statistically significant representations of the colon wall and its surroundings (air, tag, soft/hard tissue). from these regions, a coarse colon centreline is inferred through topological analysis guided by anatomic constraints; ecc is obtained by determining a transposing function depicting the distribution of voxels in a given air-region, and applying said function to tag-regions depicting statistically similar colon wall surroundings; unlike surface shape analysis, a cad identifies local hyper-density concentrations from implicit surfaces flux, at a given depth related to the targeted lesion size. the complete schemes were retrospectively tested on and patients datasets for {centreline; electronic cleansing} and cad, respectively. results: colon centreline extraction was accurate in % of combined cathartic and tagged datasets. cad performance was similar to that in the literature, specifically a sensitivity of % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] for lesions at least mm featuring a false-positive rate less than per-patient. the presented novel paradigm in computer-assisted image interpretation prevents traditional limitations arising from "accurately segmenting" a specific organ for further processing. to our best knowledge, this is the first attempt to design and validate such a paradigm shift in ct colonography. purpose: the role of mesorectal vasculature in rectal cancer is poorly understood. aim of our study was to determine impact of tumour growth as well as neoadjuvant chemoradiotherapy on mesorectal vasculature. methods and materials: ten patients with locally advanced rectal cancer underwent (re)staging mri. dynamic contrast-enhanced mri with blood pool contrast agent (gadofosveset) was performed. maximal intensity projections (mips) were used to assess macrovascular structure. number, diameter and length of vascular branches were determined in mesorectum surrounding tumour and normal rectal wall. same parameters were used to compare pre-and post-chemoradiotherapy mips. the mesorectal microvascular function was studied using relative enhancement-time curves, and expressed as area under the initial minutes of the enhancement curve (auc). results: a significantly higher number of vessel branches was found in tumourneighbouring mesorectum compared to mesorectum around normal rectal wall (p= . ). furthermore, vessel diameter in tumour surroundings was . mm larger (p= . ). the average auc in tumour-neighbouring mesorectum was also higher ( . and . , respectively (p= . )). comparison of pre-and post-crt mips revealed % lower vessel branching after crt (p= . ). moreover, the vascular diameter of . ± . mm at the primary staging was significantly decreased to . ± . mm after crt (p= . ). in contrast, crt resulted in significantly increased auc values. conclusion: there is a significantly enhanced vascular structure and function in the tumour-surrounding mesorectum, which may have an important prognostic value for rectal cancer patients. furthermore, chemoradiotherapy induces remodelling of the mesorectal vasculature. value of d fse cube sequence at t mri in preoperative local staging of rectal cancer r. scandiffio, p. vagli, p. bemi, a. mantarro, l. faggioni, r. balestri, p. buccianti, e. neri, c. bartolozzi; pisa/it (rossellascandiffio@libero.it) purpose: to compare a standard t w imaging, based on d acquisitions, with d fse cube sequence in the local staging of rectal cancer at t mri. methods and materials: patients with rectal cancer were prospectively evaluated at t mri before and after neoadjuvant chemotherapy. sagittal, coronal, axial and oblique d t w fse images and an additional d t fse cube sequence were obtained. each d dataset was processed with multiplanar and curved planar reconstructions along the rectal centreline. two experienced radiologists, using, respectively, d or d sequences evaluated t and n parameters, with specific attention to measurement of the distance lesion-puborectal muscle and mesorectal fascia, and lesion extension. all t and n parameters were evaluated independently and grouped for statistical analysis. linear cohen k values were calculated to quantify agreement between mri and histopathological data. image quality was evaluated using a linear qualitative scale. results: global sensitivities for t parameters were % and % for d and d images, while n category lesion accuracy values were % and %, respectively. accuracy in measuring the distance from pubo-rectal muscle to lesion border was % and % for d and d, respectively. image quality was considered very good on d images, and good on d images. conclusion: no significant differences between d and d images were observed for t and n staging. t w fse cube demonstrated higher accuracy than d in determining the distance between lesion and pubo-rectal muscle, which represents a key factor in planning surgical resection. purpose: spatial vascular heterogeneity decreases from periphery towards tumour core in solid tumours and is related to cancer viability. this pattern is not present in rectal tumours. the aim of this study was to determine whether rectal tumour spread into layers of rectum, affects tumour vascular function compared to that of normal rectal wall. tumours were segmented into luminal, mural and extramural regions. normal tissue counterparts were defined (mucosa, muscularis propria and mesorectal fat). initial slope (slopei) and area under the first s of enhancement curve (auc ) were determined from relative signal enhancement-time curves. pixel parameter values and mean parameter values were compared per patient and for entire patient group. the correlation between kinetic parameters of tumour segments and of corresponding normal tissues was determined. results: for each patient, both the slopei and auc were significantly higher for luminal tumour pixels compared to mural and extramural tumour pixels (p < . ). mural pixel parameter values were significantly higher than the extramural pixels (p < . ). for the patient group the mean auc for the luminal, mural and extramural tumour region was ± , ± and ± , respectively. there was a strong and significant correlation between the parameters of tumour segments and those of corresponding normal tissues (pearson's correlation coef-ficient= . , p= . ). purpose: patients with complete response (cr) after crt might be considered for less aggressive treatment like a wait-and-see strategy. few studies investigated the value of dwi-mri for predicting cr after crt, but none included lymph nodes in the analysis (ypt n ). the aim of the present study was to retrospectively determine the additional value of dwi-mri to conventional (t -weighted) mri for predicting cr after crt. methods and materials: eighty locally advanced rectal cancer patients underwent crt followed by restaging mri and operation. mri consisted of conventional sequences and dwi. two readers with different levels of experience independently scored conventional images for cr and, in a second reading, combined conventional and dwi-mri images. a -point confidence level score was used to generate roc curves. differences in performance were calculated by comparing areas under the roc curves (auc). interobserver agreement, sensitivity, specificity and positive predictive values (ppv) were calculated. histology served as reference standard. results: ten of patients ( %) had a pathologic complete response (ypt n ). comparison of the roc curves showed significant improvement of the auc only for the experienced reader from . to . (p= . ). sensitivity improved from - % to - %. specificity and ppv improved only for reader from to %, resp., to %. interobserver agreement improved from . to . . conclusion: adding dwi to conventional mri improves diagnostic performance of experienced readers and increases interobserver agreement for identification of cr. sensitivity and ppv remain low, with a considerable risk of over-and undertreatment. purpose: transanal endoscopic microsurgery (tem) is a minimal invasive technique for local resection of t and selected t tumours and is also an emerging option for good-responders after chemoradiation. in most centres follow-up includes regular mri. this study aimed to describe the mr morphology of the rectal wall during follow-up in patients that received tem. methods and materials: forty-nine patients underwent a post-tem mri in our centre. for patients only one post-operative mri was available. for patients > mris were available. the mr morphology of the tem-site was studied on the consecutive mr examinations. patients were primary treated with tem, patients underwent chemoradiation followed by tem. results: we identified three morphological patterns: ( ) rectal wall thickening with or without fibrosis, ( ) a notch at the tem-location, and ( ) irregular delineation of the rectal wall. multiple patterns could occur within one patient. patients ( %) had rectal wall thickening, patients ( %) a notch, and patients ( %) irregular delineation of the rectal wall. in addition to these patterns, oedema (due to chemoradiation) persisted in post-chemoradiation tem-patients. ten patients had dehiscence after tem post-chemoradiation (n= %). six luminal recurrences occurred; had rectal wall thickening, a notch, and an irregular rectal wall. sinogram-affirmed iterative reconstructed simulated ecg-gated ultra high pitch ct pulmonary angiography in the acute setting: effect on dose and image quality s.j. co , s. nicolaou , j. mayo , t. liang , d. hou , k. krzymyk ; vancouver, bc/ca, topanga, ca/us (co.steve@gmail.com) purpose: to evaluate the effect of a simulated ecg-gated computed tomographic pulmonary angiography (ctpa) at kv on image quality and radiation dose. retrospective study includes patients referred for ctpa with pitch . . patients were scanned with a standard kv protocol and patients were scanned with a simulated ecg-gated kv protocol that introduces a specialized cardiac bowtie filter. all other scanning parameters were kept constant. images were reconstructed with filtered back projection and iterative reconstruction (safire, siemens). central pulmonary vessel attenuation and background noise were quantitatively measured and signal-to-noise (snr) and contrast-to-noise (cnr) were calculated. two radiologists performed qualitative assessment grading visualisation of the pulmonary vasculature and noise level (likert scale). volume ct dose index and dose length product were recorded and effective dose was calculated. purpose: to evaluate the impact of iterative reconstructions on the diagnosis of acute pe on low-dose ct angiograms. methods and materials: patients were prospectively enrolled in a study designed to compare low-dose and full-dose images simultaneously available from the same dataset. the examinations were acquired with (a) both tubes set at similar energy ( kvp) and (b) the total reference mas (i.e., mas) split up in a way that % was applied to tube a while % was applied to tube b. three series of images were generated: (a) full-dose images (generated from both tubes), reconstructed with fbp (group ), used as the standard of reference, (b) low-dose images (generated from tube a; % dose reduction) reconstructed with fbp (group ), then with an iterative reconstruction algorithm (safire) (group ). results: all patients showed significant decrease of qs (mean . to . , p <. ), rlr and aopa between initial and f/u ct-pa. in / patients complete pe lysis was found. there was good correlation between reduction of qs and regression of rlr (r=-. ; p <. ) and aopa (r=-. ; p <. ), respectively. rlr and aopa changes (r=. ; p=. ) correlated poorly. patients with initial qs > showed higher reduction of qs at f/u, but no significant difference was found concerning the reduction of rlr between patients with initial qs > and ² (p=. ). the time interval between initial and f/u ct-pa differed between patients with and without complete lysis ( . vs. . weeks, p=. ). conclusion: clot resolution is associated with improvements of rlr and aopa, but the time to complete resolution is variable and not predictable. rlv and aopa are independent markers of right heart burden in patients with pe, but they correlate poorly with each other. clinical significance of high density thrombi on non-enhanced ct scan in patients with pulmonary thromboembolism k.s. beck, b. lee, h. kim, d. han; seoul/ kr (sallahbar@gmail.com) purpose: to evaluate the incidence and significance of occasionally detected high density thrombi of pulmonary embolism (pe) on non-enhanced chest ct scans. we retrospectively evaluated the non-enhanced and enhanced ct findings of patients with pulmonary embolism, and the incidence of high density thrombi was calculated. then in both iso-density thrombi (group ) and high-density thrombi (group ) groups, embolic burden score, ventricular septal bowing, and diameter of right ventricle (rv) and left ventricle (lv) were evaluated and compared using independent sample t tests. purpose: to investigate the general applicability of a kv protocol for routine ct pulmonary angiography (ctpa) in unselected patients. methods and materials: thirteen patients suspected of having pulmonary embolism underwent ctpa with a novel kv protocol ( mas, pitch . ) on a -slice ct device. ten patients who were investigated with the standard protocol ( kv, mas, pitch . ) served as the control group. images were reconstructed with sinogram affirmed iterative reconstruction with medium regulation strength in both groups. ml of contrast material ( mgi/ml) was injected at ml/s. ctdivol, dlp, signal intensity in the pulmonary trunk and segmental arteries and corresponding snr values were compared. images were assessed for diagnostic quality and artefacts. results: chest diameter was not significantly (p> . ) different between the groups. ctdivol ( . vs. . mgy) and dlp ( vs. mgycm) were by % and % lower at kv (p < . ); iodine attenuation was significantly higher (e.g. segmental arteries vs. hu), but so was image noise, resulting in no significant differences in snr. photon starvation artefacts from dense contrast material in the venous system and high image noise in bigger patients were the main drawbacks at kv. conclusion: kv ctpa seems feasible in clinical routine and results in a dose reduction of more than % compared to a kv protocol at equal snr; however, patient selection is advisable. artefacts from inflowing contrast material will require dedicated injection protocols or the use of low-iodine contrast material. purpose: pulmonary hypertension (ph) is a disease characterised by an elevated pulmonary arterial pressure (pap) and is diagnosed invasively via right heart catheterization (rhc). we explored whether timing measures from dynamic contrast-enhanced computed tomography (ct) can be used as a non-invasive method to determine ph. methods and materials: patients ( with and without ph) were examined with a novel dynamic contrast-enhanced ct sequence following their diagnostic or follow-up rhc. x-ray attenuation over time curves were recorded for several regions of interest (rois) in the main pulmonary artery and in the ascending aorta and subsequently fitted with a spline fit. time differences between the contrastmaterial bolus peaks were measured. distances between the rois were measured in a simultaneously acquired thorax ct to calculate the bolus propagation speeds. we compared our results to haemodynamic parameters acquired during rhc. results: time differences between peaks showed good correlation (spearman correlation coefficients ³ . ) with mean pap, pulmonary vascular resistance and gas exchange parameters. discrimination between patients with and without ph was achieved by evaluating time differences (sensitivity/specificity %/ %, % confidence intervals: - % and - %, respectively) and bolus speeds (sensitivity/specificity %, % confidence intervals: - % and - %, respectively). ) . lesions located in the vertebral body were excluded, while lesions in proximity to joints or neurovascular bundles were included. treatment success was determined at clinical and imaging follow-up at , , and months post-treatment. a visual analog pain score (vas) was used to assess changes in symptoms. results: treatment was carried out using a variable number of sonications (mean ± . ) with a mean energy deposition of ± j. there were no treatment-or anaesthesia-related complications. a statistically significant (p= . ) difference was noted between the overall pre-and post-treatment mean vas scores ( . ± . and . ± . , respectively). six of the treatments were conducted on patients with typical osteoid osteoma and all were completely clinically successful. the patient with giant osteoma had pain recurrence after weeks, requiring surgery. at imaging, oedema and hyperemia associated with typical osteoid osteoma gradually disappeared in all lesions. no apparent relationship between nidus vascular extinction and successful outcome was found. conclusion: mrgfus ablation represents an effective and totally non-invasive therapeutic option for osteoid osteoma management, without treatment-related adverse events. purpose: radiographic damage was recently identified as a feature of poor prognosis in polyarticular juvenile idiopathic arthritis (pjia). however, most radiographic studies did not differentiate pjia from other subtypes of jia and little is known in pjia persisting into adulthood. we set out, therefore, to describe radiological peripheral involvement in young adults with pjia as compared to rheumatoid arthritis (ra) patients. methods and materials: all consecutive pjia patients followed in a transition program were included. age, sex, disease duration, and treatment information were collected. laboratory tests and standard radiographs of the hands and wrists, feet and hips were then analysed by two independent radiologists blinded to the diagnosis. a ra control group (< years), matched for sex and disease duration, was recruited. düsseldorf/de (rotem.lanzman@med.uni-duesseldorf.de) purpose: the purpose of our study was to investigate changes in kidney perfusion following renal denervation using arterial spin labelling (asl) mri at . t. methods and materials: patients (mean age ± years) undergoing interventional renal denervation were included in this study. in each patient, between and ablations were performed per renal artery. asl mri was performed at . t using a single-slice fair truefisp sequence in the coronal plane ( averages of label and control pairs, inversion time ms, slice thickness mm, matrix x ) prior to and within hours following renal denervation. patients refrained from fluid intake for at least hours prior to the examination. following post-processing, rois were drawn by a single reviewer on asl parameter maps for quantification of cortical perfusion. both kidneys of each patient were used for statistical analysis. results: image acquisition was completed successfully in all patients and perfusion was determined for kidneys in patients. in patients, asl perfusion increased by at least % following denervation, while in one patient asl perfusion decreased following intervention. mean asl perfusion following renal denervation ( . ± . ml/ g/min) was significantly higher than prior to denervation ( purpose: to evaluate trochlear morphology as a potential risk factor for patellofemoral osteoarthritis, determined by morphological and quantitative measurements of cartilage degeneration using t magnetic resonance imaging (mri) of the knee. methods and materials: mr images of right knees of randomly selected subjects, aged - years, from the osteoarthritis initiative (oai) progression cohort were screened for trochlear dysplasia, defined by a pathological trochlear depth. out of subjects, n= demonstrated a shallow trochlea (depth ² mm; %). in these, and also in a random sample of controls with normal trochlear depth (n= ), we calculated the facetal ratio and assessed knee structural abnormalities using a modified whole-organ-mr-imaging score (worms). cartilage segmentation was also performed and t relaxation times and patellar cartilage volume were determined. anova and multivariate regression models were used for statistical analysis of the association of mri structural measures and trochlear morphology. results: knees with a shallow trochlea showed higher patellofemoral degeneration (worms mean ± standard deviation, . ± . versus . ± . ; multivariate regression, p < . ) and lower patellar cartilage volume than controls ( ± mm versus ± mm , p < . ). knees with a pathological facetal ratio showed increased patellofemoral worms scores ( . ± . versus . ± . , p < . ). t values at the patella were significantly lower in the dysplasia group. however, significance was lost after adjustment for cartilage volume (multivariate regression, p= . ). conclusion: trochlear dysplasia, defined by a shallow trochlea, is associated with higher worms scores and lower cartilage volume, indicating more advanced osteoarthritis at the patellofemoral joint. reliability of tomosynthesis for semiquantitative assessment of knee osteoarthritis features by radiologists with different levels of expertise purpose: to describe early x-ray findings in the hands and evaluate progression of destruction after five years correlated to clinical parameters in early psoriatic arthritis (psa). in men and women with psa fulfilling the caspar criteria hand x-rays were available from the -year follow-up and either inclusion or the -year visit. x-rays were scored by the wassenberg scoring system. results: median symptom duration at inclusion was months. % had polyarticular and % mono/oligoarticular psa. at the first evaluation % had wassenberg score zero. at the -year visit median score was . in patients ( %) the score was still , in between and , in between and , in between and , and patient each had a score of , , , and . at baseline women had significantly higher disease activity than men, but similar x-ray score. at years men had improved considerably in function and disease activity score, but had greater x-ray progression ( % vs %, p= . ). male gender was a significant predictor of x-ray progression. longer symptom duration at entry predicted x-ray progression (p= . ) and prevented minimal disease activity (p < . ). conclusion: after years of psa, most patients still have no or very little hand joint destruction. symptom duration at inclusion and male gender were the main predictors of x-ray progression, preserved function at baseline was protective. despite worse clinical outcome with higher disease activity scores, women had less x-ray progression than men. purpose: cortical thickness mapping is a technique that uses clinical computed tomography (ct) imaging to plot the distribution of cortical bone thickness in d. given our understanding of their relationships with bone mineral density, we performed a study to investigate the effects of age, weight, and osteophytes on cortical bone distribution in the proximal femur. we analysed ct imaging data from a cohort of women aged ± years, selecting one hip from each randomly according to side. a dicom analysis tool (stradwin) was used to contour each hip semi-automatically and create a d surface mapped with individual cortical thickness values. statistical parametric mapping was then performed to investigate model effects of age, weight and osteophytes on cortical thickness. results: cortical thickness was generally thinner with advancing age, but was preserved in characteristic load-bearing regions at the medial femoral neck and lateral subtrochanteric cortex. greater weight was also associated with significantly thicker cortex per kilogram at these same sites. including osteophytes in the model showed that increasing severity was detected as increasingly thick cortical bone around the articular margin at the femoral head-neck junction. conclusion: these results demonstrate, for the first time, the effects of age, weight and osteophytes on cortical bone thickness in the proximal femur. it will be essential for future analysis of bone in this region to take these effects into account. conclusion: raw-data-based iterative reconstruction significantly improved image quality in very-low-dose prospectively ecg-triggered coronary dsct angiography when compared to standard reconstruction using fbp. along with substantial reduction of radiation exposure, iterative reconstruction also shows a trend towards higher accuracy in coronary stenosis detection compared to fbp. methods and materials: patients underwent evaluation of the rv function on . t employing a -element coil. acquisition was performed using a real-time radial ssfp sequence ( projections) in a multislice breath-hold and free-breathing setting with a spatial resolution of x mm (matrix ; slice mm) and a temporal resolution of ms (tr . ms). through-time radial grappa reconstruction was performed off-line (matlab) incorporating fully sampled ( projections) calibration data acquired prior to the undersampled datasets. segmented cartesian cine ssfp was acquired at identical slice positions in multiple consecutive breath-holds with a spatial resolution of . - . x . - . mm, mm slices and ms temporal resolution (tr ms). free-breathing and breath-hold real-time datasets were evaluated for rv size and function and compared with segmented cine ssfp. this hipaa-compliant study was approved by the institutional review board and patients gave informed consent. patients underwent delayed phase cardiac ct on a second-generation dect scanner. late iodine enhancement data were compared with late gadolinium enhancement images from t cardiac mri. dect greyscale images were reconstructed as kv, kv and weighted-average (wa; linear blending) images from low and high kv data incorporating %, % or % of kv data. in addition, a colour-coded map of myocardial iodine distribution was calculated from dect data. two independent blinded radiologists reviewed all images for late enhancement areas in standard cardiac views and rated subjective image quality. results: dect data from kv, wa- % and wa- % showed identical results for the correct identification of myocardial scarring ( % sensitivity, % specificity and % accuracy). however, wa- % received the best subjective image quality rating and average measured infarct size correlated best with mri. colour-coded iodine distribution maps were prone to artefacts ( % sensitivity, % specificity, % accuracy), overestimating quantity of scars while underestimating lesion size by % compared to mri. conclusion: linear blending of delayed phase cardiac dect data improves image quality for the detection of myocardial scar tissue compared to mri. colour-coded myocardial iodine distribution maps were prone to artefacts and showed inferior diagnostic performance. influence of iterative reconstruction on coronary calcium score in cardiac computed tomography k. jaspers , j.a.c. van osch , j.m. groen , m.j.w. greuter ; groningen/nl, zwolle/nl (m.j.w.greuter@umcg.nl) purpose: to investigate the relation between the percentage of iterative reconstruction (ir) and coronary calcium score in cardiac computed tomography (ct). a phantom containing cylindrical calcifications with varying size and density was inserted into a thorax phantom (qrm thorax, qrm, germany) with artificial lungs and spine. the phantom was scanned with a clinical acquisition protocol on a -slice ct (lightspeed vct xt, ge). each scan was repeated five times. the images were reconstructed with filtered backprojection (fbp) and increasing percentages of ir of - %. the amount of calcium was determined as an agatston score. the influence of percentage ir on both total agatston score (tas) of the phantom as well as the individual calcium score (ias) for each calcification was investigated. purpose: to demonstrate that diffusion-weighted imaging (dwi) is able to pick up intracranial recurrences of medulloblastoma (mb) with higher sensitivity than contrast-enhanced (ce) series. methods and materials: all mri examinations of children with histologically proven mb were retrospectively evaluated. routine follow-up examinations were performed initially months after operation and thereafter, every months for the next years. then, controls were done yearly. concomitant cranial and spinal mri included t , t , and flair in the axial plane, followed by t after gadolinium (gd) in orthogonal planes for the brain. additional dwi was performed. subsequent spinal imaging included sagittal t -en t -weighted images. results: eleven recurrences were observed in patients. in patients recurrent disease was observed at the resection site in of which subarachnoid spread was also observed, with recurrence in loco only in patients. five patients had recurrent disease away from the resection cavity, of them in the frontal areas and intraventricular recurrences at the supratentorial level. in patients ce-series scored better than dwi; in patients results on dwi and ce-series were equivocal. in patients, recurrences were better demonstrated on dwi; some of them were only observed in retrospect. the results of our retrospective study demonstrate that dwi is a powerful technique allowing for early diagnosis of recurrent disease in mb patients. dwi especially demonstrates non-enhancing metastatic lesions earlier than celesions. dwi should therefore be included in surveillance imaging protocols of mb patients, especially in the group of high-risk patients. radiation-induced telangiectasia in the long-term survivors of intracranial germ cell tumours: whole-ventricle vs whole-brain radiation l. li, s. mugikura, t. murata, t. kumabe, k. jingu, t. fujii, e. mori, s. takahashi; sendai/jp (liliyanzhen @gmail.com) purpose: telangiectasia on mr images were reported to be seen in patients who received intracranial radiation. to determine the relationship between the radiation field/dose and the prevalence of telangiectasia on mr images, we compared whole-ventricle alone (wv) and whole-ventricle plus whole-brain (wb) radiation groups in the long term survivors (more than years) of intracranial germ cell tumours (gct). we compared the number of telangiectasia on t *weighted mr images (t *wi) between wv (n= ) and wb (n= ) groups. total dose of radiation between two groups was not significantly different ( . evaluation of diffusivity in pituitary adenoma in the sella turcica with d turbo field echo with diffusion-sensitized driven-equilibrium preparation: initial experience a. hiwatashi , t. yoshiura , o. togao , k. yamashita , k. kikuchi , h. honda , m. obara ; fukuoka/jp, tokyo/jp purpose: to evaluate the feasibility of d turbo field echo (tfe) with diffusionsensitized driven-equilibrium (dsde) preparation, which is a novel non-epi technique for diffusion-weighted imaging, for pituitary adenoma in sella turcica. methods and materials: this prospective study included thirteen patients ( females and males, age - years) with pituitary adenomas were imaged with d tfe with dsde preparation. among them four were prolactin-producing (prl), three were growth hormone-producing (gh) and six were non-functioning tumours (non). motion probing gradients were conducted at one direction (a-p) with b values of and s/mm . the imaging voxel size was . x . x . mm . the apparent diffusion coefficients (adcs) were measured in the pituitary adenoma and the normal pituitary gland. results: in each patient, a pituitary adenoma was clearly visualised on d tfe with dsde preparation and adc maps without obvious geometrical distortion. adc of the pituitary adenoma ranged from . to . x - mm /s (mean ± standard deviation, . ± . x - mm /s), and was higher than that of the normal pituitary gland ( . ± . x - mm /s) without statistically significant difference (p > . ). adc in prl ( . ± . x - mm /s) was significantly higher than that in gh ( . ± . x - mm /s) and in non ( . ± . x - mm /s) (p < . ). conclusion: with its insensitivity to field inhomogeneity and high spatial resolution, d tfe with dsde preparation was feasible to evaluate the diffusivity in the pituitary gland. adc measurement using this new technique may help characterise hormone activity of pituitary adenomas. author disclosures: m. obara: employee; makoto obara. and . gy in wb groups). in the wb group, axial sections of the ventricular level were considered to have received significantly higher dose of radiation ( . gy, high-dose field) than the other upper and lower levels ( . gy, low-dose fields). in the wb group, we compared the number of telangiectasia on t *wi between ventricular level and the other upper and lower levels. results: telangiectasias were observed in ( %) patients. the number of telangiectasia in the wb group was significantly higher than the wv group (average . in wb and . in wv, p = . ). in wb group, the number of telangiectasia was significantly higher in the ventricular level than the other upper and lower levels (p < . ). conclusion: radiation-induced telangiectasia appears to occur in at least % of patients who undergo cranial irradiation. larger radiation exposure and higher radiation dose were associated with higher number of telangiectasia lesions. preoperative classification of cerebral tumours by applying whole brain vpct: which parameter to use in order to achieve the highest prognostic value? results: typical features of fibroadenomas were "lobulated shape" (or= . ), "sharp margin" (or= . ), "internal septations" (or= . ), "hyperintense signal in t w" (or= . ) and "persistent curve-type" (or= . ; all: p < . ). diagnostic accuracy increased significantly (p < . ), if features were assessed in combination. highest values were then observed, if the following feature combinations were present: "sharp margin and persistent curve type" (or= . ), "plateau and internal septations" (or= . ). overall accuracy of breast mri for the differential diagnosis of fibroadenomas vs. breast cancers revealed excellent auc ( . , cross-validated sample). conclusion: in breast mri fibroadenomas show typical morphologic and dynamic characteristics. particularly, if multiple breast mri characteristics are assessed in combination, differential diagnosis vs. breast cancer is possible with excellent accuracy. purpose: to compare lesion detection and characterisation by the combination of one-view breast tomosynthesis (dbt) and one-view digital mammography with two-view digital mammography (mx). the study included consenting women with breast lesions classified as suspicious at mammography and/or ultrasound. a clinical performance study comparing two-view (cc, mlo) mammography, and the combination of dbt in mlo view and mx in cc-view (dbt+mxcc) was conducted with six breast radiologists. data were analysed per-lesion, using lesion localisation fraction -llf (the percentage of lesions correctly localised). lesion detection was determined by calculating the total number of lesions rated above bi-rads . lesion characterisation was evaluated by counting malignant lesions rated above bi-rads and benign lesions scored bi-rads or . lesion detection and characterisation for all lesions, and stratified for malignant and benign lesions, were compared between dbt+mxcc and mx using analysis of variance (anova). p-values < . were considered statistically significant. the non-inferiority margin was set at %. results: overall, dbt+mxcc was superior to mx alone in terms of number of lesions correctly detected and characterised (llf difference: + . %, - % ci: + . %; p-value = . ). dbt+mxcc superiority was confirmed for benign lesions (llf difference: + . %, - % ci: + . %; p-value < . ), while noninferiority was achieved for malignant lesions (llf difference: + . %, - % ci: - . %; p-value < . ). purpose: to estimate the inter-reader reproducibility of dbt added to d-dm in comparison to that of d-dm alone. a series of breasts ( women, aged ± years) underwent dbt (giotto, ims, italy) as an adjunct to d-dm. after an agreement on how to report d-dm and dbt, independent readers (r , r , r ) with > years of experience in d-dm and > year of experience in dbt evaluated all studies. each reader evaluated the breast density and assigned a bi-rads score using only d-dm. after days, they repeated the evaluation adding dbt to d-dm. the inter-reader reproducibility was estimated using the quadratically weighted cohen's kappa. the breast density reported at d-dm by the most experienced reader was: % in ( %). considering the b , b , b , b , and b bi-rads scores, the same reader assigned the followings: , , , , and using d-dm; , , , , and using d-dm plus dbt. for each pair of readers, d-dm plus dbt resulted in a higher inter-reader reproducibility than that of d-dm alone: kappa value for d-dm ranged from . to . while that for d-dm plus dbt ranged from . to . . purpose: based on a novel approach, digital breast tomosynthesis (dbt) may simultaneously acquire d and d images of the breast. variable dose geometry is used to give a sufficient dose in the central projection for that image to be a d mammogram ( d-cp). we investigated whether d central projection ( d-cp) obtained with dbt is equivalent to digital mammography (dm) in terms of image quality. we retrospectively evaluated asymptomatic patients who underwent dm and dbt with d-cp for screening. two experienced radiologists in consensus reviewed the dm and d-cp images in separate sessions. readers were asked to subjectively score image quality on a - scale in terms of a) artefacts ( =absent to =significant artefacts), b) noise ( =absent to =very high noise) and c) fibro-glandular-breast-tissue-to-fat-contrast ( =poor to =excellent). the comparison between d-cp and dm scores was performed with a wilcoxon signed-rank-test on a per-breast basis. results: there was no significant difference between dm and d-cp in terms of artefacts, with median scores of . for both techniques (p> . ). a significant difference (p < . ) was found between dm and d-cp concerning noise and contrast (median were vs and vs , respectively). conclusion: although dm is superior to d-cp in terms of image noise and contrast, both techniques showed a reduced incidence of artefacts. clinical studies should be performed to assess whether this qualitative difference has clinical relevance. the role of additional ultrasound and tomosynthesis after normal digital mammography: comparison between both techniques p. slon, j. etxano, i. purpose: to increase the diagnostic accuracy of mri in the detection and local staging of bladder tumours by using fluid-attenuated inversion recovery (flair) sequences. methods and materials: patients with bladder tumours detected by us underwent mri using . t superconductive magnet. we performed tse t -weighted and t -weighted and flair sequences on axial scans. the contrast to lesion ratio was always evaluated. all the patients underwent cystoscopy with transurethral biopsy and had subsequent cystectomy. in comparison with other sequences, flair sequence was more sensitive in the detection of bladder neoplasms. this sequence demonstrates the hyperintense signal of bladder neoplasms from the filled bladder lumen with no signal. the sensitivity in the identification of bladder neoplasms was % with flair sequences, . % with tse t -weighted sequences and . % with tse t -weighted sequences. that was due to the higher signal-to-lesion ratio of flair sequences in comparison with the others. in fact, on flair sequences the mean value of contrast to lesion ratio of bladder neoplasm was . while on se t -weighted sequences and tse t -weighted sequences was, respectively, . and . . flair sequences allowed the detection of small papillomas (< mm). tse t -weighted sequences were more sensitive than other sequences in the study of bladder wall infiltration. conclusion: flair sequences were more sensitive in the detection of bladder neoplasms, thanks to their higher contrast-to-lesion ratio and were helpful in the visualisation of small papillomas, especially when multifocal. while the inter-reader reproducibility of d-dm resulted only moderate, the adjunction of dbt allowed to reach a substantial reproducibility. the use of dbt added to d-dm can reduce inter-reader variability and allow for more reliable readings from different radiologists. the oblique coronal scans were parallel to the plane of the bladder neck. patients underwent also voiding mr-cystourethrography performed with t -weighted spoiled d gradient-echo acquisitions on sagittal plane performed after the filling of bladder lumen with contrast-material-enhanced urine. the entire mr examination lasted no longer than minutes. we detected patients with abnormality of smooth muscular structures of the bladder neck and with bladder neck cyst. mri allowed a perfect evaluation of the different smooth detrusor muscles of the bladder neck. in patients with urinary bladder neck dysfunction, we detected hypertrophy of posterior smooth muscular structures of bladder neck and kyphosis of prostatic urethra. patients were able to perform voiding mr-cystourethrography that showed the characteristic radiological features. conclusion: mri with voiding mr-cystourethrography could be performed in male patients with bladder outlet obstruction in order to visualise the aspect of the b- : purpose: the non-invasive investigation of urinary bladder carcinoma by magnetic resonance (mr) virtual cystoscopy was evaluated by us and compared with conventional cystoscopy. methods and materials: thirty consecutive patients, presenting with gross haematuria and trans abdominal ultrasound suggestive of mass in the bladder were taken up for study. all patients underwent conventional cystoscopy and ciss d mr imaging and the images reconstructed for virtual cystoscopy using volume rendering technique. lesions were detected and the number, size, location and morphologic features of lesions were noted. subsequently, patients underwent conventional cystoscopy, and the findings were noted. the final diagnosis of the cases was established by histopathology. results: sixty-five lesions were seen in mr virtual cystoscopy and in conventional cystoscopy. the smallest lesion identified on mr virtual cystoscopy was mm. overall sensitivity and specificity of mr virtual cystoscopy for lesion detection were . and %, respectively. for lesions greater than mm, the detection rate was %.pearsons correlation test showed a good between virtual and conventional cystoscopy for maximum and minimum diameters of the lesion ( . and . , respectively). location of the lesions and their morphological characteristics were found to correspond by both methods. conclusion: mr virtual cystoscopy is an effective tool in the detection of urinary bladder tumours, especially those larger than mm. when bladder lesion is less than mm a sessile conventional cystoscopy is better than mr virtual cystoscopy. purpose: to evaluate the diagnostic accuracy of a diagnostic imaging technique called voiding mr cystourethrography. methods and materials: normal volunteers and male patients with bladder outlet obstruction (evaluated with urine-flow velocity recording) underwent voiding mr cystourethrography. the mr examination was performed with . t superconductive magnet. the filling of the urinary bladder with paramagnetic contrast agent was obtained by the i.v. administration of furosemide followed by ¾ of the normal dose of a paramagnetic contrast agent. during the micturition two consecutive t -weighted spoiled d gradient-echo acquisitions on sagittal plane were performed. d row images were post-processed with mip algorithm. patients performed retrograde and micturating conventional cystourethrography in the month preceding mri. results: homogeneous opacification of the bladder lumen was always obtained. patients were unable to perform the mr examination. in all the volunteers and in all the patients studied ( pts), a perfect evaluation of the male urethra with mri was obtained and its visualisation with mip reconstructed images was considered comparable to that obtained with conventional cystourethrography. site, length and number of urethral strictures were accurately determined. the analysis of d sagittal scans allowed a better evaluation of the morphology of the urethral strictures in comparison with conventional cystourethrography. conclusion: voiding mr cystourethrography demonstrates the morphology of the bladder neck and urethra during the micturition and can substitute standard cystourethrogram, avoiding radiation exposure to the gonads and urinary catheterization. image quality on liver ct based on sinogram-affirmed iterative reconstruction algorithm b. schulz, b. bodelle, p. siebenhandl, m. beeres, f. al-butmeh, c. frellesen, t.j. vogl; frankfurt a. main/de (mail@borisschulz.com) purpose: to evaluate efficiency of sinogram-affirmed iterative reconstruction technique, regarding noise and image quality on contrast-enhanced computed tomography (ct) of the liver. methods and materials: ct examinations were performed upon patients ( slice ct, kv, mas, activated tube current modulation, . mm collimation). each examination was reconstructed at standard filtered back projection (fbp) and different safire strengths in mm images in transversal direction with soft tissue kernel. image noise was defined as standard deviation (sd) of hounsfield units (hu) in air, and signal-to-noise ratio (snr) of the liver was defined as mean liver hu per liver sd. subjective image quality was evaluated by three raters using a -point scale ( =non-diagnostic image quality, =excellent image quality). results: average image noise was . hu (fbp), vs. . hu (safire ), vs. . (safire ) . hu (safire ), . hu (safire ), . hu (safire ). snr of the liver consecutively increased when using the iterative reconstruction algorithms from . (fbp) to . (safire ) to . (safire ) to . (safire ) to . (safire ) to . (safire ). the differences in image noise and snr of each safire-strength to fbp was statistically significant (p < . ). subjective image quality was voted . (fbp) vs. . (safire ) vs. . (safire ) vs. . (safire ) vs. . (safire ) vs. . (safire ). conclusion: sinogram-affirmed-based iterative reconstruction technique significantly reduces image noise and increases snr for examinations of the liver. however, subjective image quality decreases with strong iterative strengths. bladder neck. these anatomical information are useful to determine the causes of voiding obstruction and diagnose urinary bladder dysfunction. mri findings of radiation-induced changes in the urethra and periurethral tissues in patients with prostate cancer c. marigliano , o.f. donati , o. akin , d. goldman , j. eastham ; rome/it, new york, ny/us purpose: the aim of this study was to assess radiotherapy (rt)-induced changes in the urethra and periurethral tissues in patients with prostate cancer (pca). this retrospective study included men (median age, y; range, - y) who underwent external-beam radiotherapy (ebrt) and/or brachytherapy for pca. on endorectal-coil mris of the prostate obtained within d before rt and - months (median, months) after rt, two readers independently measured the urethral length (ul) and graded the margin definition (md) and signal intensities (sis) of the urethral wall, the levator ani and obturator internus muscles and the muscles of the genitourinary diaphragm on -point scales. results: mean ul decreased significantly from pre-to post-rt mri for both readers (from . to . mm and . to . mm, [p < . , both]). inter-reader agreement for ul was excellent for pre-and post-rt mri (icc= . and . , respectively). both readers found significantly decreased md and increased si in the urethral wall and pelvic muscles on post-rt mri (p? . ). inter-reader agreement was fair for md (?= . , pre-and post-rt) and si of the urethral wall (?= . , pre-and post-rt) and ranged from slight to moderate for si of the pelvic muscles (?= . - . , pre-rt and?= . - . , post-rt). si changes in the obturator internus muscle were greater after ebrt (p= . - . ), while si changes in the levator ani muscle were greater after brachytherapy (p= . ). conclusion: after rt of the prostate, mri shows urethral shortening, decreased urethral margin definition and increased si of the urethral wall and pelvic muscles. mri anatomic evaluation in patients with persistent urinary incontinence after advance male sling: a work in progress study with a t system v. zampa, d. pistolesi, s. ortori, l. faggioni, m. marletta, c. bartolozzi; pisa/it (virnazampa@hotmail.com) purpose: retrourethral transobturator sling is a new functional treatment of stress urinary incontinence after prostatectomy consisting in repositioning the urethral sphincter into the pelvis. overall success rate is - %; however, a failure rate of - % is reported. the aim of this study was to retrospectively analyse morphologic changes visible on mri after sling procedure in incontinent patients and compare with the continent ones, in order to detect possible factors explaining the different clinical outcome. methods and materials: patients treated with advance sling were enrolled: / had clinical recovery while / had persistent incontinence. mr protocol performed with a t system included d t w sequence (cube) and a high temporal resolution fiesta for dynamic mri. on the t w sequence, the length of the bulbus posterior to the sling and the distance of the sling from a line parallel to the symphysis pubis (lsp), were measured. mann-whitney test was used to analyse the results. results: in the incontinent patients the length of the bulbus posterior to the sling was < mm (range - mm) while in the continent ones was > mm ( - mm) (p < . ). the sling position was located posterior to the lsp in / incontinent patients ( - mm) and almost coincident in / continent patients (p= . ). conclusion: based on our results, the length of the bulbus posterior to the sling seems to strongly correlate with continence. although our results must be confirmed in a larger series, surgeons should consider this element in planning the proper position of the device. of the patient and type of examination semiautomatically. in addition, abdominal ct examinations were performed with a standard tube potential of kvp. radiation doses (ctdivol) were noted for all examinations. signal-to-noise ratio (snr) was determined in the contrast-enhanced lumen of the abdominal aorta (a), liver (l) and spleen (s). subjective iq (lesion detectability, diagnostic confidence) was rated on a -point scale ( _non diagnostic; _excellent) by two readers. results: whereas noise level was slightly elevated when using tps algorithm compared to the standard protocol ( . vs. . hu, p < . ), no significant differences in snr ( . ± . vs. . ± . [a], . ± . vs. . ± . [l], . ± . vs. . ± . [s]) were observed between the two protocols. subjective iq (mean score of . versus . , respectively) was good to excellent in all examinations. tps lowered the ctdivol significantly as compared to standard abdominal ct ( . ± . mgy vs. . ± . mgy, p < . ). conclusion: attenuation-based tps lowers the dose of abdominal ct in clinical routine by up to % while maintaining high subjective and objective image quality. second generation dual-energy ct of the abdomen: radiation dose comparison with -and -row single energy acquisition c.n. de cecco, a. darnell, n. macias, g. muscogiuri, c. ayuso, a. laghi; rome/it (g.muscogiuri@gmail.com) purpose: this study was designed to compare the radiation dose in abdominal dual-energy (de) and single energy (se) acquisitions obtained with a dual-energy ct (dect) and a -row ct (sect). a total of patients divided into two groups underwent precontrast and portal abdominal -row ct examination. in group a, de portal acquisition was performed; group b underwent se portal acquisition. group c was compound of subjects from group a studied with -row sect. in each group, the portal phase dose length product (dlp) and radiation dose (msv) were calculated. results: a significant radiation dose increment (p < . ) was observed in group a . ± . msv in comparison to group b . ± . and group c . ± . msv. no significant difference (p> . ) was reported between se -and -row acquisitions. a significant positive correlation between radiation dose and bmi was observed in each group (group a, r = . , p < . ; group b, r = . p < . ; group c, r = . , p= . ). in clinical practice, abdominal de modality delivers a significant higher radiation dose to the patient compared to -and -row se acquisition. the radiation increment can be justified if a real advantage in patient diagnosis is obtained using de information. can iterative reconstructions improve the detection of small hypervascular liver nodules with dual-energy ct? l. facchetti , l. berta , l. mascaro , f. pittiani , l. romanini , r. maroldi ; brescia/it, milan/it (facchettil@gmail.com) purpose: to optimise dual-energy ct (dect) protocols with sinogram iterative reconstruction (safire) algorithms for improving small hepatocellular carcinoma (hcc) detection. a dect arterial acquisition of a cirrhotic patient was reconstructed using the standard filtered back projection (fbp-b f) and iterative reconstructions both for the whole dose protocol (de composition . ) and for -kv acquisitions. each one of the iterative medium-smooth filter (i -i -i ) was reconstructed at different strengths (s -s -s ) for a total of image series. for each series, virtual spherical lesions were simulated in random positions on the liver. a lesion-to-liver contrast (llc) of + hu was selected for de-composition . and + hu for kv, according to a preliminary study on hccs acquired with dect. four expert radiologists performed a detectability test and rated the overall quality, noise and sharpness ( -point scale) in all images. results: / lesions were detected with fbp-b f. in all the iterative reconstructions, the strength- kernels led to detect ± . / lesions. the highest image quality ratings were . ± . (b f), . ± . (i -s de-composition . ) and . ± . for i -s de-composition . , without a statistical difference (anova test). all subjective ratings in the kv series were defined as suboptimal ( . ± . ). conclusion: iterative reconstructions increase the sensitivity of the detection of sub-centimetric low-contrast lesions, even in the -kv series delivering half dose. the i -s reconstruction was considered the best for the routine protocol. efficacy of a liver detection algorithm for noise reduction in abdominal ct n. ardley , k. buchan , k. lau ; clayton/au, melbourne/au (nicholas.ardley@southernhealth.org.au) purpose: the liver, an inherently low contrast structure, appears 'noisy' on routine ct of abdomen. this may impede liver lesion detection. the development of a specific ct liver detection algorithm delivers higher radiation exposure to the liver with the aim of improving quantum noise, and correspondingly less radiation to the remaining abdomen. the aim of this study was to assess the efficacy of this algorithm on reducing noise in the liver. methods and materials: consecutive patients for abdominal ct with same level of iterative reconstruction were included. there was no exclusion. the ct liver detection algorithm was enabled in the last of these patients. region of interest in hounsfield units and standard deviation (sd) were measured in the left and right lobes of liver, spleen, psoas and bladder for all patients. radiation doses were also recorded. the results of the two groups were compared. results: sd reflected noise. in the liver detection algorithm group, there was a sd reduction by . % in the right liver, . % in the left liver and . % in spleen. no significant change of sd was seen in psoas and bladder. a . % overall radiation dose reduction was noted in this group. the application of this newly developed ct liver detection algorithm demonstrated a reduction in noise in the liver and spleen with no significant noise changes in the remaining abdomen. there was an added benefit of overall radiation dose reduction. author disclosures: k. buchan: employee; philips healthcare. impact of modified abdominal ct protocols for obese patients with filtered back projection and hybrid iterative reconstruction technique on image quality, radiation dose and low-contrast detectability: a phantom study s.t. schindera , d. odedra , d. mercer , s. thipphavong , p. chou , z. szucs-farkas , p. rogalla ; basle/ch, toronto, on/ca, biel/ch (sschindera@aol.com) sunday data were collected in a time period of - minutes for the t w sequences. volunteers underwent subsequent t w respiratory-gated mrc on a t mri. for qualitative analysis a -point scale was used. contrast ratios were calculated for quantitative assessment. results: contrast-enhanced t w mrc at t showed a homogeneous depiction of the intra-and extrahepatic biliary tract with a maximum enhancement minutes post-contrast. vibe and flash ir provided a good image quality for the intra-(vibe . , flash ir . ) and extrahepatic bile ducts (vibe . , flash ir . ). quantitative analysis revealed high cr values for flash ir (cr . intrahepatic and . extrahepatic) due to a strong signal decrease of hepatic tissue and vessels. t w tse at t revealed a poor image quality without diagnostic potential ( . intrahepatic, . extrahepatic). t vibe and flash provided superiority in the depiction of the intrahepatic bile ducts, while t mrc was superior in the delineation of the extrahepatic biliary tract. conclusion: our results demonstrate the feasibility of contrast-enhanced imaging of the biliary ducts at t, particularly t w flash with inversion recovery enables high-quality assessment of the biliary tract. purpose: volume rendering d-magnetic resonance imaging (mri) is able to show auditory pathways between the cochlea and the cerebellopontine angle in children with negative auditory brainstem responses and cochlear nerve structures undetectable by conventional high-resolution (hr) mri. methods and materials: twelve children (mean age ± . mo) with confirmed severe hearing loss by abr (auditory evoked brainstem responses) underwent hr-ct and hr-mri of the petrous bone. in addition, three-dimensional t -weighted turbo spin-echo axial slices were obtained at . t and maximum intensity projections and d volume reconstructions were performed for visualisation of the cochlear anatomy. results: abnormal cochleovestibular anatomic findings such as incomplete partition type i (n= ), incomplete partition type ii (n= ), narrow internal auditory canal (n= ), splitting of the internal auditory canal and concomitant anomalies of the posterior labyrinth (n= ) were detected by hr-ct and hr-mri. interestingly, volume-rendered d inner ear reconstructions detected varying but communicating structures of the cochlea and the brainstem in all cases. after cochlear implantation all twelve children showed obvious hearing reactions. conclusion: in contrast to conventional hr-mri, d-mri volume-rendering reconstructions are useful to detect aberrant and even tiny auditory path structures derived from the cochlea. children with severe hearing loss and hr-mri-based findings of missing cochlear nerve structures should be further screened with volume rendering d-mri during cochlear implantation evaluation. purpose: cochlear nerves aplasia represents a rare but possible congenital cause of sensori neural hearing loss (snhl) in children. early identification and accurate diagnosis are mandatory to correctly select auditory brainstem implantation (abi) candidates. the purpose of the study was to evaluate the contribution of a complete pre-operative radiological assessment based on ct and mri to prevent misdiagnosis and erroneous treatments. purpose: to correlate patient diameters and subjective image quality in low-voltage and standard-voltage ct of the upper abdomen in the same patient population, with the goal of identifying cutoff patient diameters for selecting patients for lowvoltage scans. methods and materials: patients underwent mdct of the abdomen with arterial phase at kv with angular dose modulation on -row mdct (test group). this was compared to a previous -kv scan on the same scanner. mean interval between scans was days. patient transverse and sagittal diameters were measured at celiac axis level, and the mean was calculated. two radiologists by consensus graded image quality on a -point scale ( =excellent; =good; =moderate; =poor; =non-diagnostic; was the chosen cutoff quality). image quality was correlated to the transverse, sagittal and mean diameter by means of an anova test. results: patient diameters were unchanged across exams (all p=ns). in -kv scans, image quality was significantly correlated to sagittal (p= . ) and mean diameters (p= . ), while a trend to significance was observed for transverse diameter (p= . ). in -kv scans, image quality was not significantly correlated to patient diameters (all p=ns), and all patients received grade or . in -kv scans, a subjective grade corresponded to a transverse diameter of mm and a sagittal diameter of mm. conclusion: subjective image quality in low-voltage scans appears to be more influenced by patient size than at standard voltage scans. for our protocol, cutoff diameters for adequate image quality are transverse mm and sagittal mm. author disclosures: g.a. zamboni: speaker; guerbet. preliminary application of spectral ct imaging in the differentiation of hepatic tumours w. chen, x. ye, c. zhou; beijing/ cn (wenchen @yahoo.com.cn) purpose: to investigate the value of spectral ct imaging in differential diagnosis of hepatic tumours. this prospective study was institutional review board approved with patient consent. thirty-eight patients with hepatic tumours ( men, women, lesions), including patients with hepatocellular carcinoma (hcc), with hemangioma (hh) and with metastatic tumour (mt), underwent plain scan of spectral ct imaging and conventional contrast ct scan. contrast-to-noise ratio (cnr) of different energy levels and homologous kev of optimal cnr were calculated by the spectral analysis software. the authors also chose three regions ( - kev, - kev and - kev) and calculated the slope rates of spectral curves. one-way anova followed by lsd post hoc tests were performed to compare parameters among hcc, hh and mt groups. the homologous kev of optimal cnr of hcc, hh and mt groups were . ± . , . ± . and . ± . , respectively. the slope rate of - -kev region in hcc group ( . ± . ) was significantly higher than that in hh group ( . ± . ). there were significant differences between hcc, hh and mt groups in the slope rates of - -kev and - -kev regions (p < . ). the slope rates were . ± . , . ± . and . ± . , respectively, in - -kev region and . ± . , . ± . and . ± . , respectively, in - -kev region. the - -kev monochromatic imaging of spectral ct imaging is the best for detection of hepatic tumours and slope rates of spectral curves may be useful in differentiation of hepatic tumours. purpose: to assess the feasibility of magnetic resonance cholangiography (mrc) using biliary secreted gadoxetic acid at tesla (t) and to compare it to t -weighted (w) mrc at t. methods and materials: healthy volunteers were examined on a t mr-system. t w tse, t w vibe and flash with inversion recovery (ir) were acquired in coronal orientation. for dynamic imaging gadoxetic acid was administrated and s c a d e f g b -gkr= * a.u. (p < . ); wipi values were: b-gkr= * cm /sec, -gkr= * cm /sec (p> . ), -gkr= * cm /sec (p < . ). -gkr mean diameters decreased in / patients, -gkr ceus parameters (pe, wir, wipi) decreased in all patients. conclusion: a reduction in pe, wir and wipi at months after gkr suggested a depletion in tumour vascularization due to radiotherapy-induced necrosis. our preliminary results showed the feasibility of ceus perfusion analysis for um, which could provide reproducible, reliable and earlier parameters for the assessment of tumour response to gkr. evaluation of lacrimal drainage system obstruction using combined multidetector ct and instillation dacryocystography m. shweel, a. elshafaey, m. nasar, r. mohyeldien; elminia/eg (mohshweel@yahoo.com) purpose: to assess the use of combined multidetector computed tomography and instillation dacryocystography (ctdcg) in detection of the level of lacrimal drainage system (lds) obstruction. methods and materials: twenty-one patients with one-sided epiphora were our candidates for ctdcg. axial source and post-processing images were assessed for clear viewing and the ability to detect the level of lds obstruction. to our knowledge, no previous studies used this combination in the assessment of the lds obstruction. results: all patients tolerated the examination well. various levels of lds obstruction were detected, common canaliculus in ( %) patients, lacrimal sac in ( . %), junction between lacrimal sac and nld in ( . %) and nld obstruction in ( . %) patients. the most common ctdcg findings were dilated opacified lacrimal sac with no opacification of the nasolacrimal duct (nld) in / ( . %) patients. curved planner reformation (cpr) was excellent to detect the nasolacrimal duct (nld) obstruction. conclusion: ctdcg is a non-invasive patient friendly procedure that adds benefit in documentation and preoperative planning. parotid gland tumours shear wave elastography: a preliminary study s. espinoza-boireau, i. khettab, a. lacan melki, p. halimi; paris/fr (sophie.espinoza@gmail.com) purpose: to assess the feasibility of parotid gland tumours shear wave elastography. to establish normal parotid gland elasticity. to evaluate elasticity for the most common benign parotidian tumours (pleomorphic adenoma, warthin's tumour) and malignant tumours. methods and materials: prospective study including consecutive patients with parotid gland tumour. they all underwent share wave elastography to measure tumour elasticity and contralateral normal parotid gland elasticity. the results were confronted with histological analysis or fine-needle aspiration cytology. results: elasticity measure was feasible in all cases. mean normal parotid gland elasticity was kpa (n= ; - ). benign tumours elasticity was . ± kpa (n= ). malignant tumours elasticity was ± kpa (n= ). pleomorphic adenomas elasticity was . ± kpa (n= ). warthin's tumours elasticity was . ± . kpa (n= ). conclusion: benign and malignant tumours seem to behave differently under shear wave elastography. complementary studies are required to establish relevant threshold values allowing proper elastography lesions discrimination. does heterogeneous echogenicity of the thyroid parenchyma influence the detection of multifocality and bilaterality for papillary thyroid carcinoma on preoperative ultrasound staging? s. herh, e.-k. kim, h. moon, j. kwak; seoul/kr (jinnyhs@hanmail.net) purpose: this study was to evaluate whether heterogeneous echogenicity of the thyroid parenchyma can influence the diagnostic performances of ultrasonography (us) in detection of multifocality and bilaterality of papillary thyroid carcinoma (ptc). between december and january , patients had preoperative staging us for ptc, and underwent total or near-total thyroidectomy. seven experienced radiologists performed preoperative us for t and n staging. underlying parenchymal echogenicity of the thyroid gland, multifocality, and bilaterality of the thyroid nodules were also evaluated. patients were divided into two groups according to the underlying echogenicity of thyroid parenchyma on us. to evaluate the diagnostic accuracy of preoperative staging us according to the underlying thyroid echogenicity, diagnostic performances including sensitivity, with cochlear implantation without benefits. all the children performed pre-operative functional tests, temporal bone ct and brain/cerebellum-pontine angle (cpa) mri. results: mri showed in all cases the absence of the cochlear branch of the eighth nerve bilaterally ( / ). unilateral facial nerve aplasia was present in one patient. associated inner ear malformations were present in / patients, in particular common cavity in / , incomplete partition type in / and semicircular canals malformations in / . no brain anomalies were showed. ct scans better depicted the labyrinthine malformations, adding information about facial nerve canal and internal auditory canal (iac) size. / ct showed normal inner ear structures and iac size. providing accurate information about cochlear nerve and brain anomalies is crucial in the pre-operative assessment of snhl patients. mri is the only radiological technique that is able to directly demonstrate the presence or the absence of cochlear nerves. ct is not fundamental and provides complementary information; a negative ct pattern cannot exclude a cochlear nerve malformation. purpose: to test whether the size of the cochlear nerve measured in the internal auditory canal using three dimensional ( d) and multiplanar reconstruction (mpr) high-resolution mri affects the speech recognition outcome following cochlear implantation. the study was retrospectively performed on patients with longstanding hearing loss (mean age of . years). mri was performed using a t -weighted space sequence. mpr and d reconstructions were performed using d and inspace applications, respectively. the preoperative cross-sectional surface area of the cochlear nerve was measured by drawing a region-of-interest around the circumference of the nerve. speech recognition (sr) was tested using the freiburger-monosyllabic-words (mswt) and numbers-tests (nt) preoperatively, postoperatively, at -, -and -month follow-up. sr and size assessment were performed in a double-blinded fashion. the correlation between the sr and nerve size were tested using spearman's rank correlation test. purpose: gkr efficacy in the treatment of um, a hypervascular tumour, is conventionally assessed by clinical and ultrasound findings. previous reports showed that, in case of hypervascular lesions (hcc, melanoma metastasis, etc). changes in vascularization precede diameters reduction after treatment. hence, our aim was to evaluate ceus in the quantitative assessment of tumour response to gkr. methods and materials: ten patients, who underwent gkr, were enrolled. ceus was performed (sonovue bracco) with iu- atl (philips) and - mhz linear probe at baseline, at and months after gkr (bgkr, -gkr, -gkr). two main tumour diameters and different quantitative parameters related to blood volume (area under the curve in the wash-in phase; wash-in perfusion index -wipi; peak enhancement -pe) and blood flow (mean transit time; wash-in rate -wir; rise time -rt; time to peak) were evaluated using a dedicated software (sonotumor bracco). purpose: to determine the value of semiquantitative strain elastography for the evaluation of chronic thyroiditis. the study was conducted on consecutive patients with chronic autoimmune thyroiditis and healthy controls. semiquantitative strain elastography was performed to calculate the strain index value (strain ratio of the strap muscles to the thyroid parenchyma) to assess thyroid stiffness. for each lobe, measurements were obtained from upper, middle and lower part of the thyroid parenchyma. mean strain ratio values of patients and healthy controls were compared by the mann-whitney u-test. validity was analysed by receiver operating characteristic (roc) curves. the median strain ratio value of patients with chronic autoimmune thyroiditis ( . ) was significantly higher than that of healthy controls ( . ; p < . ). the optimal cut-off value for the prediction of diffuse thyroid pathology was . . for this cut-off value, thyroid stiffness had % sensitivity, . % specificity, % positive predictive value (ppv) and . % negative predictive value (npv) for the presence of diffuse thyroid pathology. this cut-off point was exceeded by . % of the patients with and . % of the subjects in control group. si values showed mild positive correlation with the tsh levels (spearman r coefficient = . ). however, this difference did not reach statistical significance (p= . ). conclusion: semiquantitative strain elastography seems to be a useful method for the assessment of chronic thyroiditis. further studies are warranted in larger patient groups to determine the reliability of sonoelastography in patients with chronic thyroiditis. purpose: to retrospectively assess the detection rate of intracranial hematomas achieved with the use of curved mips of the meningeal spaces, compared to reading transverse ct sections only. this retrospective study was approved by the institutional review board of our institution, which waived informed consent. consecutive patients who underwent ct imaging for cranial trauma (n = ; men and women; mean age, ± y; range, - y) were included. four curved mips of the meningeal spaces with different thicknesses were rendered for each patient. four radiologists independently evaluated all cases. hematomas of less than mm thickness were considered 'thin' throughout this study. the radiologists were blinded to patient names, and patient and group order was randomised. the results were compared to a standard of reference built by two experts. logistic regression with repeated measurements was used for statistical analysis. results: intracranial hematomas were confirmed in patients. for all readers, the reading time for hematoma detection was significantly shorter ( - times, p <. )) for curved mips. the mean lesion-based detection rate of all readers was % ( / ) for transverse sections and % ( / ) for curved mips. for thin hematomas, the mean detection rate rose from % ( / ) with transverse sections to % ( / ) with curved mips. specificity, positive predictive value (ppv), negative predictive value (npv), and accuracy were calculated and compared among the two groups. results: of the patients, underlying echogenicity of thyroid was heterogeneous in patients ( . %), and homogenous in patients ( . %). forty-four ( . %) of the patients had multifocal lesions in one lobe, and ( . %) had bilateral lesions on pathologic examination. diagnostic performances of preoperative staging us did not show significant differences in detecting multifocality and bilaterality between patients with homogenous and heterogeneous parenchymal echogenicity. conclusion: heterogeneous echogenicity of underlying thyroid parenchyma does not significantly influence the detection of multifocality and bilaterality for ptc on preoperative us staging. role of elastography in the characterisation of thyroid nodules f. sogaro, p. tessitore, a. scrimieri, f. pittiani, a. borghesi, r. maroldi; purpose: this study aimed at evaluating the reliability of elastography in predicting malignancy of thyroid nodules. methods and materials: patients with thyroid nodules, who underwent to grey-scale ultrasonography (us), elastography and fnc (fine-needle cytology), were prospectively enrolled from february to august . for each nodule, grey-scale us parameters (hypoechogenicity, absence of halo sign, absence of colloid) were examined. findings at elastography were classified according to rago criteria ( ). cytological diagnosis were classified according to the siapec-iap criteria in tir , tir , tir , tir and tir . the diagnostic performance of grey-scale us and elastography were compared with cytological findings. tir and tir with indeterminate cytology were excluded from the study. results: nodules were included: tir , tir and tir . according to rago criteria nodules were score , nodules score and nodules score . the sensitivity, specificity, positive predictive value (ppv), negative predictive value (npv) of elastography were %, %, %, %, respectively. the combination of grey-scale us parameters (hypoechogenicity with absence of halo sign and colloid) showed % sensitivity, % specificity, % ppv and % npv. conclusion: elastography is not useful in the differentiation of malignant and benign thyroid nodules. however, elastography had a high probability in predicting cytological benign diagnosis (high vpn). moreover, elastography demonstrated a superior performance than the combination of grey-scale us parameters. the new approach to thyroid elastosonography -time-strain curvesmay aid the differentiation of nodules r.z. slapa, b. migda, w.s. jakubowski, j. bierca, j. slowinska-srzednicka; warsaw/pl (rz.slapa@gmail.com) purpose: to evaluate a new linear/non-linear approach to strain elastosonography of thyroid nodules, based on the analysis of time-strain curves and to compare it with classical elasticity score and thyroid strain ratio methods. methods and materials: during - , patients scheduled for thyroidectomy ( with multinodular goitre and with single thyroid nodule) were evaluated with b-mode and power doppler ultrasound of the whole thyroid. during ultrasound examination, dominant nodules were examined with strain elastosonography with aplio xg with linear - mhz transducer. the stiffness of each thyroid nodule was evaluated with classical features of strain elastosonography qualitatively (with elasticity scores) and semi-quantitatively with thyroid tissue strain/nodule strain ratios with application of elasto q. moreover, a novel, original approach to elasticity data based on evaluation of time-strain curves was applied. results: papillary carcinomas, benign nodules. classical elastosonographic analysis with elasticity score and elasticity ratio on statistical analysis did not show significant difference between cancer and benign nodules (p-value, respectively, . and . ). on linear/non-linear analysis of time-strain curves excellent differentiation (p= . x - ) was possible with new parameter: the relative length of non-linear relaxation. with threshold . : sensitivity %, specificity . %, area under roc= . . the analysis of linear and non-linear elastosonography data may greatly improve differential diagnosis of thyroid nodules. further large-scale studies evaluating the usefulness of linear/non-linear elastosonography phenomena (involving evaluation of vioscoelasticity, e.g. shear wave spectroscopy) in differential diagnostics of thyroid cancer are warranted. methods and materials: this hipaa compliant retrospective study was irb approved. we included patients who had undergone emergent ct scans of the abdomen and pelvis for abdominal pain with tube current modulation, automated kvp selection and safire (scan a) and compared their abdomen and pelvis ct scans with tube current modulation, kvp, filtered back projection reconstruction algorithm (scan b). ctdivol, dlp, effective dose (dlp x k) and image noise values were compared between two protocols. paired samples wilcoxon test was used for analysis and p < . was considered significant. results: the median ctdivol were . mgy and . mgy for scans a and b, respectively (p= . ); the median dlps for scans a and b were . mgycm and . mgycm (p < . ), respectively. the median effective dose was . % lower with scan a compared with scan b ( . msv vs. . msv, p < . ). the median image noise was significantly lower with scan a using safire ( . vs. . , p < . ). results: kv were automatically selected in patients, kv in patients and kv in patients of the autokv group. patient diameters increased with higher kv settings. the average ctdivol ( . vs. . mgy) and dlp ( vs. mgycm; p < . ) in the entire autokv group were %/ % lower than in the group with fixed kv. this effect was even more pronounced in the patients in whom kv were selected (ctdivol . mgy, - %; dlp mgycm, - %). enhancement of parenchymal organs gradually increased with lower kv, while image noise was at a stable level. conclusion: software-based automated selection of the tube potential allows for significant dose savings in thoraco-abdominal trauma ct while image quality is maintained or even improved. especially younger patients involved in accidents may benefit the most from this development. usefulness of low-dose ct with or without adaptive statistical iterative reconstruction ( purpose: to determine the usefulness of low-dose ct in the diagnosis and exclusion of acute appendicitis and to compare with low-dose ct taken with asir. conclusion: curved mips of the meningeal spaces have the potential to shorten the detection time for epi-and subdural hematomas, increase sensitivity, especially for thin hematomas, and reduce the required operator experience for detection. author disclosures: h. ringl: patent holder. simple and easy way using time-intensity curve of perfusionweighted images to find penumbra in stroke patients within . hours of onset due to the carotid artery occlusion t. mori, t. iwata, y. miyazaki, m. nakazaki, y. takahashi; kamakura/jp (morit-koc@umin.net) purpose: the aim of our study was to investigate whether or not time-intensity curve (tic) of pwi can find penumbra in stroke patients with acute carotid artery occlusion. methods and materials: included were patients ) who were admitted within . hours of onset between january and january , and ) in whom emergency mra suggested the affected carotid artery occlusion. we assessed, nihss on admission (nih adm), dwi-aspect score, tic types, successful recanalization (sr), nihss on the th day (nih th ), and in-hospital death. early neurological improvement (eni) was defined as nih adm-nih th > . tics were generated on region of interests set at symmetrical positions of the bilateral mca territories. according to the time to peak (tp) and the peak signal (ps) comparing the affected side (a) with the contralateral side (c), we classified tic into four types and defined type as tpa>tpc and psatpc and psc/ tpc and psa>psc, and type as tpa=tpc. relationship between tic types, in-hospital death and eni were assessed. results: eighty-seven patients were analysed. there were , , and patients in tic type , , and , patients underwent reperfusion therapy (rt) and sr was achieved in patients, and patients died. tic type was the only determinant of in-hospital death (p < . ) and sr coupled with tic type was the determinant of eni (p < . ). conclusion: tic type means penumbra and type predetermines poor clinical outcome. author purpose: iterative reconstruction (ir) is a promising noise reducing technique with the potential to reduce radiation-dose with preserved study interpretability or improve image-quality at similar radiation-dose. one of the major drawbacks of ir is a longer reconstruction time which may be problematic in the emergency setting. the purpose of the current study was to compare reconstruction time and speed of ir and filtered back-projection (fbp) in two commonly encountered emergency imaging scan-protocols: total body trauma ct and pulmonary cta. methods and materials: fifteen patients underwent a total body ct after a traumatic event and twenty-five adults underwent a cta for evaluation of pulmonary embolisms on a -slice ct-scanner. all data were reconstructed using fbp and two ir-levels (idose , philips healthcare). quantification of reconstruction time and speed was done with a self-written plug-in for imagej (us national institutes of health). the mean delay in reconstruction time on total body trauma cts was . ± . and . ± . seconds for idose -levels and , respectively, and on pulmonary ctas . ± . and . ± . seconds for idose -levels and , respectively. the mean reconstruction time and speed for total body trauma cts were . ± . , . ± . and . ± . seconds, and . ± . , . ± . and . ± . slices/s for fbp, idose -levels and , respectively, and for pulmonary munich/de (sonja.kirchhoff@med.uni-muenchen.de) purpose: in the past years the number of clinical-pathological autopsies decreased significantly due to various reasons. forensic autopsies are disposed not only with regional differences but, however, also with on an average decreasing frequency. especially in patients who died during trauma room management or emergency operation during critical care, no imaging could possibly be performed. therefore, after termination of all clinical procedures a critical analysis of death and evaluation of the standards of medical care is often not possible, although especially regarding medical quality management it is highly desirable. at least to partly close this information gap we performed a post mortem computed tomography (pmct)study. in this prospective study whole body pmct was performed in patients who died during trauma room management or emergency surgery leaving all installed foreign material, e.g. tube, drainage in place. the pmct findings were compared with clinical findings and if available with autopsy reports as well. results: between and patients were enrolled, of whom underwent additional autopsy. the major clinical diagnosis which had finally led to the termination of resuscitation procedures was confirmed by the pmct findings. the autopsy report showed a high correlation in the corresponding cases to the pmct-findings. conclusion: pmct offers the possibility to improve quality management during trauma room management regarding the decision for terminating resuscitation efforts by verifying the important clinical findings. in addition, pmct findings support specifically the autoptic reporting. purpose: to assess how the portrayal of radiology in medical tv shows is perceived by the general population. a survey was conducted among adult patients scheduled for a radiological examination, technologists and radiologists. the survey gathered information regarding tv watching habits and interest in medical tv shows. questions addressing the accuracy in portraying radiology in comparison to reality ( - scale), appearance of radiological examinations and radiological staff were asked in regard to house m.d., er, and grey's anatomy. the online survey conducted among radiologists and technologists from two different academic institutions served as reference standard. results: a total of patients and professionals ( technologists, radiologists) participated. a moderate and significant correlation was found between the interest in medical tv shows and the perception that clinical reality was accurately portrayed in the group of patients (r= . , p= . ) and technologist (r= . , p= . ) but no correlation was found for radiologist (r= . ). while > % in all survey groups noted the appearance of radiological examinations regularly to > /show, the appearance of radiological staff was perceived by . - . % of patients, . - . % of technologists and . - . % of radiologists. er was ranked more accurate than grey's anatomy or house m.d. the more interest in medical tv shows prevails in patients and technologists, the more are modern medical tv shows perceived as accurate in the portrayal of radiology. radiological examinations are frequently utilised, but imaging is less often performed by radiological staff. this retrospective study includes patients under years-of-age with clinically suspected acute appendicitis, who underwent unenhanced low-dose ct on a mdct. patients (group a) underwent a low-dose ct patients (group b) underwent a low-dose ct with asir. results: normal appendix was identified in ( . .%) in a versus ( . %) in b. in a ( . %) versus ( . %) in b were diagnosed with appendicitis. in a ( . %) studies versus ( . %) studies in b the appendix was not identified. in those where the appendix was not identified a conventional ct was performed. no one had appendicitis during one month follow-up for negative studies. the sensitivity and specificity of ct low-dose were . % and %, respectively, and for low-dose ct with asir . % and %, respectively. the sensitivity increased to % for the total protocol for both techniques. the effective dose mean was . msv ± . instead of . msv ± . . conclusion: the low-dose ct is a suitable technique for the diagnosis or exclusion of acute appendicitis in young or middle-aged people, making possible inclusion as a radiological imaging test in the diagnostic algorithm of acute appendicitis. introduction of the asir improves the low-dose ct technique with a higher sensitivity for appendix evaluation which increased the diagnostic confidence, slightly lowering the dose. the purpose: to evaluate image quality of paediatric chest ct acquired at kv. methods and materials: consecutive children undergoing chest ct studies on a dual-source ct system were prospectively evaluated with a -kv scanning protocol. all scanning parameters were kept similar to those usually selected for standard -kv protocols, except the milliamperage. always selected according to the patient's weight, ref mas were increased by a factor of . to maintain comparable levels of radiation dose between newly introduced -kv and routine -kv protocols. image quality at kv (group ) was compared to that of a paired paediatric population (group ) based on the age (± yr), weight (± kg) and administration of contrast material, previously scanned at kv on the same ct unit and prospectively stored in our database. group and group images were reconstructed with filtered-back projection. results: objective noise in group was significantly lower than that measured in group ( . ± . hu vs . ± . hu; p= . ). subjective image quality of lung and mediastinal images in group did not significantly differ from that of group (p= . ). in group , the mean dose-length-product was . ± . mgy.cm (< yr; mean weight: . kg) (n= ); . ± . mgy.cm ( - yr; mean weight: . kg) (n= ), . ± . mgy.cm ( - yr; mean weight: . kg) (n= ) and . ± . mgy.cm ( - yr; mean weight: . kg) (n= ). conclusion: paediatric chest ct at kv provides similar objective and subjective image quality to that achievable at kv. results: from the records in the database, various anthropometric data were extracted, e.g. body mass and body length of more than patients, thoracic diameters and the volumes, densities and masses of lungs and mammalian glands of more than patients of all age groups. these data were compared to the anthropometric data of the mathematical mird phantoms provided by the finnish centre for radiation safety stuk. it can be shown that in mathematical mird phantoms of all age groups, body mass, body length and thoracic diameters are overestimated, whereas lung volumes and lung masses are underestimated. purpose: to assess the radiation dose delivered during dual-source chest ct examinations. we prospectively recorded the dose-length-product (dlp) of consecutive children, evaluated in age groups: group (< yr; n= ; %) (mean weight: . ± . kg), group ( - yr: n= ; %) (mean weight: . ± . kg), group ( - yr: n= ; %) (mean weight: . ± . kg) and group ( - yr; n= ; %) (mean weight: . ± . kg). all ct examinations were performed with a dual-source ct system using a dual-source, single-energy scanning protocol obtained with thin collimation, high pitch and high temporal resolution, a weight-adapted selection of the kilovoltage and milliamperage, and systematic reconstruction of images using filtered-back projection. results: patients were scanned with a pitch of . (n= ; %) or . (n= ; %), at kv (n= ; %) or kv (n= ; %) with a milliamperage ranging between and mas. the mean duration of data acquisition was . ± . ms. ct examinations consisted of contrast-enhanced (n= ) and noncontrast (n= ) studies, obtained in the context of acquired (n= ; %) or congenital (n= ; %) bronchopulmonary disease, cystic fibrosis (n= ; %), cardiovascular disease (n= ; %), oesophageal atresia (n= ; %) and miscellaneous causes (n= ; %). all examinations were of diagnostic image quality. the mean dlp value in each age category was . ± . mgy.cm ( purpose: to standardise the scan protocol for ct scanners of participating centres in a multi-centre study (clinicaltrials.gov nct ) for the prevention of radiologically defined bronchiectasis in cf infants by ensuring the maximum image quality at the minimum radiation dose. methods and materials: three different sized phantoms (qrm, germany) were used to assess scanners' performance of automatic exposure control (aec). ctdi and dlp were recorded. the phantoms contained various inserts to assess slice-sensitivity-profile, in-plane spatial resolution, noise and the hounsfield unit (hu) scale. scans were made for several dose levels and reconstruction kernels. images were analysed with custom-made software (matlab, usa) to obtain the standard deviation of the noise, point-spread-function (psf) and slice thickness. results: eight different scanners with slices or more from manufacturers (ge, philips, siemens and toshiba) were assessed. despite differences in aec's performance, we obtained approximately the same dose level at each center by recommending site and age-specific aec reference levels. a constant image quality was only possible by matching the different reconstruction kernels measured psfs at full-width-at-half-maximum. in fact, large part of the differences between scanners was related to reconstruction kernels. the relatively high noise images corresponded with reconstructions using a kernel with edge enhancement such as the siemens b kernel or the ge lung kernel that are routinely used in chest imaging. conclusion: objective measurements on ct images allowed for matching of scan protocols among ct scanners of different manufacturers. use of routine protocols might introduce a bias in the (automated) image analysis. cystic fibrosis lung disease in children: correlation between mri and hrct scores c. purpose: high-resolution computed tomography (hrct) is known to be a sensitive means of detecting lung disease in cystic fibrosis (cf), with a significant radiation exposure. magnetic resonance imaging (mri) becomes increasingly important in the assessment of cf lung disease. the aim of this study was to establish the agreement between mri and hrct scores in a paediatric population. methods and materials: hrct and t and post-contrast t mri images were acquired on the same day from cf patients (median age . years; range . - . years). two radiologists with either > (hdlp) or years (cs) of ex-were analysed and compared with the corresponding real scan length. for selected ct scanners, radiation doses achieved during the scanograms were reconstructed using mathematical mird phantoms. results: depending on the patients´ age, many scanograms considerably exceed the real scan region, thus unjustifiably raising the radiation exposure of the patient. the radiation doses due to ct scanograms are not neglectible as, e.g. the whole body dose achieved during a thorax scanogram can exceed the whole body dose caused by a conventional chest x-ray examination by a factor of . conclusion: an optimisation of scanogram lengths by defining specific anatomical landmarks for standard ct protocols, the optimisation of scanogram exposure parameters in paediatric ct examinations and their implementation into national and international guidelines seems to be necessary to fulfil the alara concept in paediatric ct. we established reference values for cardiac valve diameters in extreme preterm infants, based on bsa. biological variation, inaccuracy in assessment of patient characteristics, inter-operator variability, and limited spatial resolution may account for substantial variability in heart valve diameters found in this cohort. asymmetric lung perfusion in congenital heart disease: impact of differential pulmonary arterial anatomy and pulmonary vascular resistance o. kondrachuk, t. yalynska, r. tammo, i. iershova, n. rokytska; kiew/ua purpose: asymmetry of lung perfusion is relatively common in patients with congenital heart disease. the aim of the study was to evaluate the influence of differential pulmonary arterial anatomy and pulmonary vascular resistance on blood flow distribution in patients with asymmetric lung perfusion. we retrospectively identified consecutive patients with congenital heart disease who had asymmetry of lung perfusion on phase-contrast mri. the mri examinations were performed on . t scanner. results: fourteen patients had left lung hypoperfusion (blood flow to the left lung < %) and three patients right lung hypoperfusion (blood flow to the right lung < %). branch pulmonary artery (bpa) regurgitant fraction (rf) was significantly greater in lung with decreased perfusion ( . ± . % vs. . ± . %, p < . ). there was moderate negative correlation between bpa rf and bpa differential pulmonary blood flow (r = - . , p = . ). moderate positive linear relationship between bpa size and bpa differential pulmonary blood flow was also found (r = . , p = . ). there was no significant correlation between bpa rf and bpa size. conclusion: both bpa anatomy and bpa rf are the significant factors for determining right and left lung flow split. according to prior reports, bpa rf reflects differential pulmonary vascular resistance. consecutively at kvp, kvp, kvp and kvp, respectively, with constant mas settings using a dual-source ct. differences in calculated dual-energy ratios (deratio) between the tissues and iodine or gold were determined for different de spectra. the attenuation of gold has increased at higher kvp-settings compared to kvp, while the attenuation of all other specimens decreased. the calculated de ratios at / kvp, / kvp and / kvp, respectively, were . , . and . for iodine, . , . and . for gold, . , . and . for compact bone, . , . and . for muscle. the difference between the de ratios / kvp, / kvp and / kvp, respectively, were . , . and . for iodine and bone, . , . and . for gold and bone, . , . and . for iodine and muscle, . , . and . for gold and muscle. conclusion: de ratio of gold remains relatively stable along the energy spectrum of diagnostic ct and allows a reliable material differentiation between gold and bone at contiguous low tube voltage settings ( kv and kv). thus, gold might have potential as a contrast agent for dect. potential use of intra-articular diluted high-relaxivity gadoliniumbased contrast agent for magnetic resonance arthrography ( purpose: gadobenate dimeglumine (gd-bopta) is a high-relaxivity contrast agent that tightly binds to plasmatic proteins, currently used in several clinical applications. our aim was to test in-vitro different concentrations of gd-bopta to be potentially used to perform mra. methods and materials: gd-bopta (multihance, bracco) was diluted in saline (nacl . %) to achieve different concentrations ( mmol/l, mmol/l, mmol/l, . mmol/l, . mmol/l). five ml of these solutions was injected in sterile pipes and was added with . ml of fresh synovial fluid withdrawn from a -year-old male knee. in a separate pipe (reference), . ml of synovial fluid and ml of gadopentetate dimeglumine mmol/l (gd-dtpa; magnevist) were injected. pipes were imaged using a t -weighted sequence (te= . msec, tr= msec, slice thickness . mm, fov x mm) at . t. for each pipe on each slice, signal intensity (si) was calculated. results: mean gd-dtpa si was ± . mean gd-bopta si was ± (+ % to reference) at mmol/l; ± (+ %) at mmol/l; ± (+ %) at mmol/l; ± (+ %) at . mmol/l; ± (- %) at . mmol/l (p <. ). at post hoc analysis, all one-to-one comparisons were significantly different with exception of and mmol/l (p=. ). conclusion: versus gd-dtpa, a + % peak si was achieved with half gd-bopta concentration. a similar si between the two agents was achieved at . mmol/l. gd-bopta high relaxivity and its potential binding with synovial fluid glycoproteins could explain these results. this may improve visibility of intra-articular tears when evaluated using gd-bopta mra. purpose: to optimise the contrast injection protocol for ct coronary angiography (ctca) to achieve more efficient utilisation of contrast agent by investigating the impact of reducing the volume of contrast agent on the attenuation of coronary arteries and sinus. methods and materials: a total of subjects with low heart rate (² beats/min) and suspected coronary artery disease were randomly divided into three groups with subjects in each group. the patients in groups a, b and c were injected with a volume of . , . , and . ml/kg of contrast agent, respectively. in all cases, injection rate was . ml/s, followed by ml saline flush at the same rate. ct values within the ascending and descending aorta, left main and right coronary artery orifices and coronary sinus were measured and the differences of contrast enhancement among the three groups were evaluated. the mean injection volume of contrast agent in groups a, b and c were . , . and . ml, respectively (p < . ), and the scan delay time were . , . and . s, respectively (p < . ). the ct values within the coronary sinus were . , . and . hu for groups a, b and c, respectively (p < . ), perience in paediatric pulmonary disease scored independently hrct, using the scoring system developed by helbich et al, and mri using two scoring systems developed by helbich et al and eichinger et al. readers were blinded to clinical and functional data and to the other reader's findings. the agreements were assessed using the intraclass correlation coefficient (icc) and the bland-altman plot for the two readers and the two methods. the inter-reader agreement was excellent for the hrct scores (icc= %), good for mri with the eichinger score (icc= %), but less for mri with the helbich score (icc= %). there was a very good correlation between hrct and mri-eichinger scores (icc= %), but less between hrct and mri-helbich scores (icc= %). the good inter-reader agreement and the high correlation between hrct and mri-eichinger scores support the use of lung mri for the follow-up of lung disease in paediatric cf patients. methods and materials: a total of consecutive patients, with clinical vascular aortic disease, were evaluated on mdct slices scan (philips-brilliance p, nl) using low-kv protocol ( kv), high pitch ( . ) and automated tube current modulation. low contrast medium volume ( ml) was administered at ml/s. density measurements were performed at abdominal aorta, renal arteries and common iliac arteries. we also calculated the radiation dose exposure (dose length product, dlp). our results were compared with patients investigated with standard contrast medium volume ( ml) and standard ct-angiography protocol ( kv; mas). the noise level (signal-to-noise ratio, snr), the radiation dose (expressed as dlp) and amount of iodinate contrast were analysed and statistically compared between two different groups. results: in all of the patients we obtained an adequate vessel opacification of aorta and renal arteries. mean attenuation value in aorta was hu, in iliac arteries was hu and in renal arteries was hu, without significant attenuation difference with the control group (aorta hu; iliac arteries hu; renal arteries hu). the radiation dose exposure (meandlp: ) was significantly lower (reduction of the %) in the low-kv protocol than standard examinations at kv (mean-dlp: ). the noise level calculated in low-kv protocol (meansnr ) was not significantly higher than the value obtained in standard protocol (meansnr ). conclusion: low-dose ct-angiography protocol represents a feasible technique that allows a significant reduction of contrast material and radiation dose exposure without losing diagnostic accuracy being useful also in these patients with renal failure. purpose: the use of low concentrated contrast material might be advantageous in terms of viscosity. therefore, the purpose of this study was to evaluate the use of low concentrated contrast material ( mg iodine/ml) for coronary ct angiography in routine patients. methods and materials: consecutive patients who were referred for routine coronary cta were scanned on a nd generation dsct scanner (definition flash, siemens). patients received a standard contrast injection protocol as follows: iopromide mg/ml (ultravist, bayer) with an injection rate of ml/s (iodine delivery rate . g i/s) followed by a saline chaser with the same flow rate. contrast enhancement in the coronaries was measured proximal and distal in all coronaries. results were compared to our standard protocol with iopromide mg/ml and flow rate of . ml/s (iodine delivery rate . g i/s). start delay was evaluated for both groups using the test bolus method. comparison between both groups was performed using sample t-test. results: coronary enhancement reached diagnostical attenuation in both protocols. overall comparison between enhancement with mg/ml (mean hu ± hu) revealed no statistical significant differences with mg/ml (mean hu ± hu) (p= . ). attenuation levels in lad dist and cx dist were significantly higher in the low concentrated contrast material group (lad dist vs hu, p < . and cx dist vs hu, p= . , respectively). conclusion: the use of low concentrated contrast material is feasible in coronary cta. higher flow rates are necessary, but lower viscosity might improve attenuation in the distal segments. the impact of mr contrast agent concentration on bolus geometry g. jost, h. pietsch; berlin/ de (gregor.jost@bayer.com) purpose: in contrast-enhanced mr-angiography, the luminogram is obtained during the first passage of gadolinium-based contrast agents (gbca). the bolus concentration in conjunction with the r -relaxivity determines the vascular signal enhancement. the aim was to investigate the impact of a molar gbca concentration on bolus geometry compared to a . molar agent, systematically. methods and materials: göttingen minipigs were injected intravenously with gadobutrol and gd-dtpa in a crossover setting ( . mmol/kg, ml/s). dynamic ct measurements ( kv, maseff, Δt= . s) at the thoracal region were performed without table feed. time-density curves were determined and fitted by a gamma-variate function in the vena cava, the pulmonary artery and the ascending and descending aorta. ct-signals were transformed to gd-concentrations on the basis of phantom measurements. the administration of molar gadobutrol led to a narrower (significantly lower full width half maximum) and steeper (significantly higher peak values) bolus and ct values within the ascending and descending aorta, and the coronary artery were higher than hounsfield units in all three groups. conclusion: application of the . ml/kg protocol in ctca, a steady contrast enhancement in coronary artery, can be achieved using -slice volume ct. the influence of the contrast media protocol and the scan mode on arterial enhancement in cardiac ct e. talakic, d. stocker, p. täubl, r. maderthaner, f. quehenberger, h. schoellnast, m. tillich; graz/ at (emina.talakic@medunigraz.at) purpose: to assess the influence of contrast media protocol and scan mode on arterial enhancement in cardiac ct. methods and materials: patients (mean age, ; range, - years) who underwent cardiac ct were retrospectively divided into groups related to scan mode ( -slice helical ct or -slice volume ct) and contrast media concentration ( , or mgi/ml) -group :, helical, ( ml); group : helical, ( ml); group : helical, ( ml), and group : volume, ( ml). injection rate was ml/sec in all patients. roi measurements were performed in the aorta (coronary arteries level) and cardiac chambers to assess enhancement, and in the superior vena cava (svc) to measure the standard deviation of the attenuation values for assessment of inflow artefacts. spearman correlation and wilcoxon test were used for comparison. results: patients in group showed significantly higher mean aortal enhancement than patients in group or ( hu versus hu and hu). group showed significantly higher aortal enhancement than group ( hu). group showed significantly lower enhancement in the right atrium and ventricle than group . no significant difference in the standard deviation of attenuation was seen within the svc. conclusion: in cardiac ct, the volume mode led to significantly higher aortal enhancement and lower contrast within right atrium and ventricle compared with helical mode. scan mode, iodine dose and flow rate had no influence on heterogeneity of contrast within the svc. multislice ct angiography with direct intra-arterial ultra-low-dosecontrast injection for the evaluation of renal graft failure: initial study m. guzinski, j. kurcz, j. garcarek, m. sasiadek; wrocław/pl (guziol@wp.pl) purpose: to present initial experience with direct intraarterial ultra-low-dosecontrast ct angiography (ia-cta) and its application in assessing renal graft artery in patients with renal graft failure. methods and materials: ia-cta of renal graft was performed in patients with renal graft failure (gfr m/s. pig-tail catheter f was placed in ipsilateral common iliac artery via common femoral artery. subsequently, spiral cta of pelvis was performed simultaneously to intraarterial administration at ml/s of - ml of contrast diluted with saline to - ml. results: excellent contrast enhancement of renal graft arterial tree was observed in all patients. no complications associated with arterial access occurred. mean creatinine/grr levels prior to the ia-cta were . mg/dl and . ml/min, respectively. on the th day following the study, mean creatinine/gfr levels amounted to . mg/dl and . ml/min, respectively. renal function deterioration was demonstrated on the rd day after the procedure (creatinine . ml/dl, gfr . ml/min); nevertheless, it was not statistically relevant (p < . ). contrast-induced nephropathy occurred in only one patient ( . %) with transient creatinine elevation by %. after detailed vessel analysis graft arterial stenting was performed in patients, which improved renal function. the remaining patients were treated conservatively. conclusion: trans-catheter ultra-low-dose-contrast ia-cta for imaging of renal graft arteries can be an effective method with low-risk of nephrotoxicity, which allows detailed graft arterial tree imaging, especially prior to interventional treatment of arterial-related renal graft insufficiency. feasibility in low kv ct angiography of the abdominal aorta: assessment of image quality, radiation exposure and contrast material volume c.r.g.l. talei franzesi, d. ippolito, p.a. bonaffini, v. bartolo, c. trattenero, s. sironi; monza/it (ctfdoc@hotmail.com) purpose: to assess the image quality, dose reduction and amount of iodinate contrast injected using low-kv ct angiography protocol for the study of abdominal aorta disease. shape compared to . molar gd-dtpa in all investigated vessels. the respective gd-concentrations (mggd/ml) for gadobutrol vs. gd-dtpa were . ± . vs. . ± . (vena cava), . ± . vs. . ± . (pulmonary artery) and . ± . vs. . ± . (ascending and descending aorta). the area under the bolus curve analysis yielded no significant differences between the gbcas. conclusion: a molar gbca concentration leads to a more compact bolus shape with significant higher peak concentrations in the major thoracal vessels compared to a . molar agent. this might be especially relevant for the acquisition of d angiograms and for quantification of tissue perfusion. author disclosures: g. jost: employee; bayer pharma ag. h. pietsch: employee; bayer pharma ag. transarterial chemoembolisation (tace) in malignant liver metastases: evaluation of a fast c-arm ct acquisition protocol with a robotic multi-axis c-arm system t.j. vogl , m. von roden , e. mbalisike , s. zangos ; frankfurt a. main/de, forchheim/ de (t.vogl@em.uni-frankfurt.de) purpose: to evaluate potential contrast savings and reduction of motion artefacts in c-arm ct acquisitions with a higher rotational speed during interventional procedures. methods and materials: patients (mean . yrs, range - ) were treated with transarterial chemoembolisation (tace). prior to the injection of the embolisation material, a c-arm ct with a new, fast acquisition protocol was performed. a robotic multi-axis c-arm angiographic system (artis zeego, siemens-healthcare, forchheim/germany) was used with a rotational speed of up to °/s. in this configuration, a c-arm-ct with a rotational trajectory of ° was acquired in s versus s in a commercially available c-arm system. two different injection protocols were applied and evaluated regarding sufficient tumour visualisation and spatial resolution of the vessel tree in the resulting d-dataset. results: injection protocol ( ml contrast, ml nacl, flow rate ml/s, x-ray delay s, injection site: common hepatic artery) resulted in d images with a very good spatial resolution of the vessel trees but poor visualisation of tumours/metastases. injection protocol ( ml contrast, ml naacl, x-ray delay s) resulted in d images with excellent spatial resolution and good visualisation of tumours/ metastases. from prior experience with a standard s protocol the corresponding c-arm ct acquisition would have required a contrast load of ml and . ml, respectively. thus, the contrast saving of the fast acquisition protocol was % and %, respectively. the fast c-arm ct acquisition protocol provides an interesting possibility to save contrast media during tace with excellent spatial resolution of the vessel tree and good visualisation of hypovascular tumours. purpose: functional mri of cerebrovascular reserve (cvr fmri) using vasoreactivity to hypercapnia may identify patients at risk of haemodynamical stroke among those with severe stenosis of the middle cerebral artery (mca). however, quantification remains challenging because of numerous methodological settings and their limitations. we aimed to provide a laterality index (limca) to better identify abnormal cvr in clinical practice. methods and materials: volunteers ( females; . ± . years) without cervico-encephalic arterial stenosis had a cvr fmri using bold contrast with a block-design hypercapnic challenge (co % mixed with: o % (n= ) or air (n= )), using nasal canula (n= ) or mask (n= ), . t (n= ) or t (n= ). averaged end-tidal co pressure (etco ) was used as a physiological regressor for statistical analyses with a general linear model (spm ). we conducted regions of interest (roi) measures of %bold signal change/mmhg etco on segmented grey matter of the mca territories. we calculated a laterality index with limca=(left_cvrmca-right_ cvrmca)/(left_ cvrmca +right_ cvrmca). % confidence intervals ( %ci) were calculated. no adverse reaction to hypercapnia, including panic, anxiety, headache, or fatigue, was detected during and after cvr fmri. cvr values ranged from . to . with m±sd= . ± . %bold/mmhg etco . the mean laterality index was . with an interval of fluctuation that covered . . the standard deviation was . . thus, %ci was ± . for mca. li values were independent of age, gas mixture, sex, inhalation modality, and mr strength. conclusion: subjects without cervico-encephalic arterial stenosis have an absolute value of limca below . with a % probability. in purpose: non-invasive quantitative phase contrast mr angiography (qmra) has been utilised for several clinical indications, e.g. intracranial stenosis and aneurysms. the aim of this study is to validate the flow measurements of qmra (nova, vassol inc., chicago) by comparing the obtained velocities with qmra and doppler ultrasonography (dus) in-vivo. to our knowledge, no previous reports have addressed this issue. methods and materials: we retrospectively examined consecutive patients ( women, men; mean age years, range - years) with stenosis of arteries supplying the brain using qmra and dus. velocities were measured in a total of arterial segments ( extra-and intracranial). results: overall there was a good correlation between velocity measurements with both techniques being statistically significant in all six extracranial and five out of seven intracranial segments. velocities were % higher in extracranial and % higher in intracranial segments obtained with dus comparing to those with qmra. the reversal of flow direction in the aca was detected consistently with both methods. conclusion: this preliminary study shows a rather good correlation between the velocities employed with qmra and dus. qmra represents a robust mri technique for flow measurements in a reasonable time, which can be integrated in the cerebrovascular mri work-up, especially when intracranial dus is technically not feasible. however, further in-vivo and in-vitro studies are needed to assess the need for technical optimisation of this technique. purpose: sensitive documentation of ischaemia is needed in clinical tia. we aimed to compare the sensitivity of dti, dwi and asl in the detection of acute ischaemia and further to investigate if chronic ischaemic changes after weeks in the form of gliosis always follow. methods and materials: the first consecutive patients included during first months of an mri-protocol (dwi, dti and asl within hours of symptoms) and weeks follow-up protocol (t and dwi). patients were included by stroke consultants. lesion volumes on dwi, dti and follow-up t were compared. hyper-or hypoperfusion on asl was recorded. one senior neuroradiologist assessed the sequences in random order to prevent bias. results: fourteen patients had acute ischaemic lesions: in the posterior fossa and in the cerebral hemispheres corresponding to % of referred patients. thirteen of these developed gliosis in the affected area and of these was noted only on dti and only as post-ischaemic hyper-perfusion on asl. mean lesion volume was . ml. mean difference between volume on dwi and gliose volume was . ml = % and between dti and gliose volume . ml= % and dti volume were significantly closer (p= . ). conclusion: these preliminary results indicate that tia causes a gliosis lesion consistently, and that the initial lesion as well as the extent of the permanent changes is better described using dti. asl seems to be able to contribute to the detection of tia as this may be sole mri-sign in some patients increasing detection rates with %. monday parameter for assessment of ischaemia. we analysed the ability of ttp maps to predict eventual infarcts in patients with mild stroke presentations. we retrospectively reviewed consecutive patients presenting with acute stroke in less than hours from onset. patients presenting with a nih stroke scale score < were subjected to subgroup analysis. ttp perfusion deficit with delays of more than seconds was considered significant for underlying ischaemia. the perfusion parameters were compared to follow-up imaging at to hours. results: patients met inclusion criteria. patients had identifiable thrombus. the ttp map had the highest sensitivity in detecting the small infarcts ( %), followed by cbv and cbf. importantly, ttp analysis provided very high negative predictive value ( %). however, there was a relatively lower specificity ( %) and a tendency to overestimate the infarct size. conclusion: ttp perfusion is highly sensitive in predicting small regions of ischaemia. high negative predictive value is helpful in differentiating stroke from mimics. purpose: to study the influence of the temporal sampling rate of ctp acquisitions on cerebral perfusion maps with noise-free synthetic data sets created with a digital phantom. methods and materials: noise-free synthetic data sets were created with a digital phantom which consists of a skull derived from a human skull phantom combined with arterial input and venous output functions, white matter (wm) and grey matter (gm) time-attenuation curves (tac) obtained from patients. by manipulating the time tags ctp protocols with a total scan duration of s and a temporal sampling rate of -, -, -and s were simulated. the -s protocol was used as reference standard. the -, -and -s protocols were shifted with s to measure the influence of missing peak points of the curve, resulting in , , extra data sets, respectively. cbf, cbv and mtt maps were calculated using pma (asist-japan). mean values of gm and wm of the protocols were compared with the reference protocol. de (kolja.thierfelder@med.uni-muenchen.de) purpose: our aim was to evaluate if the extent of volumetrically determined blood flow-volume mismatch in recently introduced whole brain ct perfusion (wb-ctp) can predict if a stroke is younger than . hours (time window for thrombolysis). we retrospectively analysed cerebral blood flow (cbf) and volume (cbv) maps and clinical data of acute stroke patients. ct perfusion images were acquired with extended brain coverage of cm in the z-axis. mismatch extent was defined as the fraction of cbf perfusion deficit without corresponding cbv abnormality and was determined volumetrically using osirix v. . imaging software. a logistic regression analysis was performed to predict time from symptom onset of < . hours. four mismatch extent categories, cbf perfusion deficit and cbv infarction volume were entered as predictors into the model. results: mean time from symptom onset was min± min. mean mismatch extent was . %± . %. after correcting for age and gender, a mismatch extent of ³ % was highly predictive for a symptom onset of < . hrs (n= , or: . , p= . ). other categories of mismatch extend (³ % (or: . , n= , p= . ), < % (n= , or: . , p= . ), < % (n= , or: . , p= . ) as well as cbf perfusion deficit volume (p= . ) and cbv infarction volume (p= . ) failed to predict time from symptom onset. conclusion: a large (³ %) volumetrically determined mismatch in wb-ctp is a predictor for the time from symptom onset in the critical time window. wb-ctp mismatch might, in these cases, help to identify patients eligible for thrombolysis when symptom onset is unknown (e.g. wake up stroke). whole brain ct perfusion: volumetric assessment of perfusion deficits in patients with acute ischemic stroke k.m. thierfelder , l. purpose: whole brain ct perfusion (wb-ctp) eliminates the major drawback of restricted brain coverage in standard -slice ctp. our aim was to assess reliability and reproducibility of a newly introduced volumetric assessment method of perfusion deficits in wb-ctp in patients with acute ischemic stroke. methods and materials: consecutive patients underwent -row wb-ctp with extended scan coverage of . cm in the z-axis using adaptive spiral scanning technique. volumetric analysis of cerebral blood volume (cbv), cerebral blood flow (cbf), mean transit time (mtt), time to peak (ttp), and time to drain (ttd) was performed twice by two experienced readers using dedicated imaging software with at least -week intervals between readings. inter-and intrareader agreement for individual perfusion parameter maps was assessed by intraclass correlation coefficients (icc) and bland-altman analysis. results: interreader agreement was highest for ttd (icc: . ), followed by cbf ( . ), mtt ( . ), cbv ( . ), and ttp ( . ). intrareader agreement was also highest for ttd (icc: . ), followed by mtt ( . ), cbf ( . ), cbv ( . ), and ttp ( . ). the perfusion deficits showed the highest absolute mean volume in the time-related parametric maps and did not differ significantly within this group, while mean cbf perfusion deficit volume was significantly smaller (each with p < . ). conclusion: volumetric assessment in wb-ctp in acute stroke patients is reliable and reproducible. it therefore might serve for a more accurate assessment of prognosis of stroke outcome and definition of flow-volume mismatch. ttd had the highest agreement and therefore might be a suitable parameter to define tissue at risk. time-to-peak (ttp) maps using whole brain ct perfusion in minor stroke: a diagnostic tool beyond penumbra measurement s. chakraborty, m.e. ahmad, j.k. wasserman, k. keyhanian, d. dowlatshahi, g. stotts; ottawa, on/ca (santanoo@gmail.com) purpose: the use of thrombolysis in minor stroke or fluctuating symptoms is controversial. treatment decisions may be influenced by identifying patients with large areas of tissue at risk and distinguishing stroke mimic. whole brain ct perfusion in toshiba aquilon® ct scanner allows possible assessment of these parameters and is not limited to selective brain coverage as in previous generations of ct scanners. dynamic chest x-ray examination for regional ventilation function must be equivalent to lung scintigraphy. performance evaluation of automatic chest radiograph reading for detection of tuberculosis (tb): a comparative study with clinical officers and certified readers on tb suspects in sub-saharan africa p. maduskar , l. hogeweg , b. van ginneken , h. ayles ; nijmegen/nl, london/uk (p.maduskar@rad.umcn.nl) purpose: digital chest radiography (cxr) is used in high burden countries for suspect screening, active case finding and in prevalence surveys for tb diagnosis. an observer study was conducted to compare performance of automatic software with that of clinical officers and certified expert readers. a dataset of digital cxrs ( × , . mm, delft imaging systems, the netherlands) was collected at kanyama clinic, lusaka, zambia. sputum culture was used as reference. an observer study was conducted with four clinical officers who read x-rays in kanyama clinic, and with two readers certified to read cxrs according to crrs standard (university of cape town, south africa). a software system for detection of tb (cad tb- . , diagnostic image analysis group, the netherlands) analysed all the cases. human readers and software scored all the images between and . we report area under the receiver operating characteristics curve (az) with % confidence intervals and pairwise comparisons from bootstrap estimates. p < . was considered significant. there was no significant difference between any reader and the software, except for one clinical officer who performed significantly worse than automatic reading. conclusion: automatic computer reading has similar performance as clinical officers and certified readers. the software has potential of being used as a point-of-care decision tool, to diagnose tb or select subjects that should undergo further tests. diagnostic imaging costs before and after digital tomosynthesis implementation in patient management after suspected thoracic lesions on chest radiography e. quaia, e. baratella, g. grisi, r. cuttin, g. poillucci, s. kus, m. cova; purpose: to evaluate diagnostic imaging costs before and after digital tomosynthesis (dts) implementation in patients with suspected thoracic lesions on chest radiography (cxr). over a period of four years four-hundred-and-sixty-five patients ( males, females; age, . ± . years) with suspected thoracic lesion (s) after cxr underwent dts. two readers prospectively analysed in consensus dts images. each patient underwent ct when a pulmonary non-calcified lesion was identified by dts, while ct was not performed when a benign pulmonary or extrapulmonary lesion or pseudolesion was identified. diagnostic imaging costs (including material, staff, and imaging system depreciation) were evaluated during the -month preceding dts implementation and during the -month after dts implementation. the average imaging cost per patient was calculated by normalising the costs before and after implementation of dts by the number of indeterminate cxr examinations in each of these periods. results: in / patients who underwent dts after suspicious cxr, dts showed thoracic lesions and pleural lesions, while in the remaining / patients lesions were ruled-out as pseudolesions of cxr. in the -month preceding dts implementation, the proportion of patients who presented suspected thoracic lesions and underwent ct was / ; after dts implementation, this proportion became / . the average differential per-patient costs of cxr, dts, and ct examinations were . , . , and . euros, respectively. the perpatient change in diagnostic imaging costs before vs after dts implementation was - . euros. conclusion: per-patient diagnostic imaging costs decreased after dts implementation in patients with suspected thoracic lesions. within each cross-sectional image the mean (adcmean), minimum (adcmin) and maximum adc (adcmax) was determined by two independent radiologists. an additional roi was placed into the cerebrospinal liquid and set as the reference tissue. statistical analysis included the wilcoxon test and p-values < . indicated statistical significance. results: the highest adc values were determined for the group of adenocarcinomas (adcmean, . x - mm /s; adcmax, . x - mm /s). significantly lower mean adcs were found for the squamous cell carcinomas (adcmean, . x - mm /s; p < . ) and small cell lung cancers (adcmean, . x - mm /s; p= . ). determination of the adc values did not reveal any difference between squamous cell and small cell carcinomas (p> . ). conclusion: diffusion-weighted mri with adc measurement at . t reliably enables the differentiation of adenocarcinoma from other histological subtypes in primary lung cancer and might therefore be of distinct value in the preoperative management of patients suffering from primary lung cancer. non-contrast-enhanced perfusion mri for preoperative assessment of lung function in patients with non-small-cell lung cancer ( purpose: knowledge about lung function defects is important for predicting functional outcome and optimising surgery in nsclc. fourier decomposition mri (fd-mri) has been introduced as a method to assess regional lung perfusion without contrast agents. this study evaluates fd-mri for preoperative assessment of lung perfusion in nsclc patients with dynamic contrast-enhanced mri (dce-mri) as standard of reference. methods and materials: patients with nsclc were examined at . t. timeresolved images of the lungs were acquired in coronal and sagittal plane using a d-bssfp sequence. fourier decomposition was used to detect and separate periodic changes of lung proton density caused by respiratory and cardiac cycles. perfusion-weighted images were calculated by pixel-wise integration of the cardiac spectral line. fd and dce data were analysed visually for perfusion defects. perfusion proportions of pulmonary lobes were calculated quantitatively by regions-of-interest analyses. results: fd-mri provided diagnostic quality in cases, but failed in one patient. sensitivity, specificity and accuracy of fd-mri for visual detection of perfusion defects were %, %, and %. quantitative evaluation of perfusion proportions provided good linear correlation between fd-mri and dce-mri for both upper lobes and both entire lungs (r= . - . ). accuracy of fd-mri in the lower lobes (r= . - . ) and the middle lobe (r= . ) was compromised by artefacts from cardiac pulsation. conclusion: fd-mri is useful to detect regional lung perfusion defects in nsclc patients before surgery. for perfusion quantification, fd-mri is sufficiently accurate in both upper lobes and for bilateral comparison, but, in its present form, inaccurate in the middle lobe and both lower lobes. lung ultrasound in the elderly population: investigating the limit between physiological and pathological patterns a. chiesa, f. ciccarese, g. gardelli, f. feletti, u. regina, m. zompatori; bologna/it (ciccarese.f@gmail.com) purpose: the senile lung undergoes paraphysiological changes which have been described in several radiological and ct studies, but never investigated through ultrasound. the aim of the present study was to evaluate a group of elderly-nonsmoker-healthy patients in comparison with young subjects, by using ultrasound examination. methods and materials: elderly subjects (> years-mean age: . ± . ) and young subjects (< years-mean age: . ± . ) were submitted to lung ultrasound examination. we analysed the anterior, lateral and posterior surface of each lung to evaluate the presence/absence of a-lines and b-lines. fisher test was chosen to compare data obtained in the two groups. results: absence of a-lines was found in / - . % of elderly versus / - . % of young subjects (p < . ). presence of b-lines was detected in / - . % of elderly, with a higher prevalence in posterior lung fields; the number of b-lines was² per field (pf) in / - . %, > pf in / - . %; both ² and > pf-depending on the evaluated field in / - . %. by contrast, / - . % young subjects showed b-lines (² pf in all of cases)-p= . . to avoid misdiagnosis, we should consider that physiological ultrasound lung findings could be different among old and young people. the majority of old individuals did not present a-lines; moreover in a high percentage, b-lines were observed (² pf in most of them). these results could be explained by a reduction of impedance between lung parenchyma and soft tissue (absence of a-lines) and by an increased thickness of interlobular septa (presence of b-lines). further studies should be proposed to define a cut-off between normal and pathological pattern. digital x-ray optical densitometry in assessment of respiratory function in patients with copd exacerbation n. gorbunov, v. laptev; novosibirsk/ru (n_gorbunov@hotmail.com) purpose: to evaluate respiratory function in patients with exacerbation of chronic obstructive pulmonary disease (copd) before and after treatment by means of a digital x-ray optical densitometry. the study group comprised patients ( females, males; mean age ± . years, range - years). all of them were admitted to the clinic with an exacerbation of copd with different ( - ) stage. high-resolution digital radiographic device with a line x-ray sensitive silicate receiver was used. lowdose digital x-ray examination of the chest was performed both in inspiration and in expiration phases before and after treatment. regional and common pulmonary optical density was evaluated with further quantitative analysis of respiratory function. for these purposes the optical density gradient (odg) was used. all results were verified by high-resolution computed tomography (hrct). the optical density gradient before and after treatment has been changed. there was a . - . times increasing value of optical density gradient due to treatment of copd exacerbation. for patients with the first stage of copd the . % odg increasing was estimated. for the second stage of copd odg increasing was . % and for the third stage of copd it was . %. there was a significant correlation between pulmonary optical density gradient and hrct density gradient before and after treatment (r> . ; p < . ). a digital x-ray optical densitometry by means of functional highresolution digital radiography allows optimising an evaluation of therapy response in patients with copd exacerbation combined with radiation exposure reduction. diffusion purpose: despite the improvement in technique/expertise, pancreatic surgery remains burdened with a high complication rate. our aim was to report our year single-centre experience about the clinical relevance and the interventionalradiological management of the early postoperative complications (treatment/ prevention) on patients submitted to pancreatic surgery. in - , patients were submitted to pancreatic surgery (duodenum-cephalopancreatectomy, total-pancreatectomy, distal-pancreatectomy). patients were classified on the basis of the complication severity into classes (clavien-dindo-classification): class- =none, class- / =conservative treatment, class- a=endoscopic/interventional-radiological, class- b=surgery, class- =intensive care, class- =death. interventional-radiological management was as follows: ptc/biliary-drainage in case of biliary-fistulas (bile in surgical drainage, normal bilirubin levels, undilated biliary ducts at us) under us/fluoroscopic-guidance (right approach, puncturing along the course of the sixth-segment portal branch with g chiba-needle, or left approach if aerobilia/ adequate volume of left hepatic lobe); embolisation (microcoils/pva-particles) or covered-stenting (viabahn-gore) in case of bleedings of gastroduodenal/splenic arteries; percutaneous drainage (us/ct-guidance) of liquid/infected collections. pancreatic-islet-intraportal-autotransplantation was performed in case of totalpancreatectomy to prevent diabetes. results: patients were classified as follows: / ( %) class- , / ( %) class- , / ( %) class- , / ( %) class- a, / ( %) class- b, / ( %) class- , / ( %) class- . / (class- a) and were successfully treated as follows: / ptc/biliary-drainages, / liquid/infected collection percutaneous-drainages, / bleedings ( embolisations, coveredstenting), / endoscopic-procedures. / underwent pancreatic-isletintraportal-autotransplantation. one bleeding/ biliary-fistula needed treatments. conclusion: in experienced centres of pancreatic surgery, complication rate can be reduced. complications can be, however, successfully diagnosed, managed and prevented by interventional-radiological procedures, limiting their clinical relevance and avoiding a high-risk surgical re-treatment. purpose: to evaluate technical feasibility and clinical efficacy of retrievable covered stents in treating post-surgical biliary leakage. methods and materials: from april to date, patients ( males, females; mean age years, range - years) were retrospectively studied. patients underwent placement of retrievable covered stents for treat post-surgical bile leaks. in cases the procedure was performed by interventional radiologist using percutaneous trans hepatic access and in cases by means of hybrid procedure (ptbd + ercp) with both interventional radiologist and endoscopist. the leaks involved cystic duct stump (n = ), common bile duct anastomosis (n = ), left extra hepatic duct (n = ), right extra hepatic duct (n = ) and biliary confluence (n = ). results: technical success with correct stent releasing was achieved in cases; case required post-dilatation ballooning. immediate clinical and lab test improvements were observed in all patients. post-operative imaging proved leak resolution in all cases. no early complications were observed. in case late stent migration was reported days after the procedure. twelve stents were removed without complication after a mean time of days, with complete leak resolution. one stent comparison of assessment of preoperative pulmonary vasculature in non-small cell lung cancer patients by non-contrast-enhanced and d contrast-enhanced mr angiography at t and by contrastenhanced thin-section mdct using a -detector row system y. ohno , s. seki , m. nishio , h. koyama , t. yoshikawa , s. matsumoto , s. satou , k. sugimura ; kobe/jp, ohtawara/jp (yosirad@kobe-u.ac.jp) purpose: to prospectively and directly compare pulmonary vasculature assessment before surgical treatment of non-small cell lung cancer (nsclc) patients by non-contrast-enhanced (non-ce) mr angiography, d ce-mr angiography and thin-section ce-ct. methods and materials: a total of consecutive pathologically proven and clinically assessed stage i nsclc patients ( males, females; mean age: years) underwent thin-section ce-ct, non-ce-mr angiography and ce-mr angiography, and surgical treatment. the capability for anomaly assessment of the three methods was independently evaluated by two reviewers using a -point visual scoring systems, and final assessment for each patient was made by consensus of the two readers. interobserver agreements for pulmonary arterial and venous assessment were evaluated with the kappa statistic. assessment of variations in overall pulmonary vasculature by the three methods was compared by means of receiver operating characteristic analyses on a per-patient basis. finally, sensitivity, specificity and accuracy for detection of anomalies were directly compared among the three methods by means of mcnemar's test. results: interobserver agreements for pulmonary artery and vein assessment were substantial or almost perfect ( . ²κ² . ). for pulmonary arterial and venous variation assessment, non-ce-mr angiography, d ce-mr angiography and thinsection ce-ct showed no significant differences (p> . ) in terms of area under the curve, sensitivity, specificity and accuracy. conclusion: pulmonary vascular assessment of nsclc patients before surgical resection by non-ce-mr angiography can be considered equal to that by d ce-mr angiography and thin-section ce-ct. in vivo micro-ct and f-fdg micro-pet imaging of spc-raf and spc-myc transgenic mouse models of lung adenocarcinoma t. rodt, c. von falck, m. luepke, k. hueper, r. halter, s. dettmer, c. boehm, j. borlak, f. wacker; hannover/de (rodt.thomas@mh-hannover.de) purpose: to report on micro-ct and micro-pet imaging of spontaneously developing lung tumour in spc-raf and spc-myc transgenic mice. technical considerations regarding periprocedural management and imaging technique are addressed; tumour quantification techniques are presented. dosage measurements are reported and potential adverse effects discussed. methods and materials: wild-type control, spc-raf and spc-myc transgenic mice were examined in vivo using micro-ct (n= ) and f-fdg micro-pet (n= ). specific periprocedural management was established. different respiratory gated and ungated micro-ct protocols were compared. a quantification routine for tumour load and growth was validated and examined in a follow-up study. f-fdg micro-pet of orthotopic lung tumour was obtained; quantification was performed on lesion and lung region basis. findings were correlated to histology. thermoluminescence dosemeter measurements and dosage calculations for micro-ct and micro-pet were performed. results: no procedure-related deaths occurred for up to days of follow-up. respiratory gated micro-ct protocols yielded better image quality compared with ungated protocols. intra-and inter-observer variability of the quantification routine were . and . %, respectively. tumour quantification showed significant difference (p= . ) between spc-raf transgenic and control animals in follow-up. longitudinal tumour development correlated to cross-sectional histological data from literature. micro-pet yielded a tumour-to-non-tumour ratio of . in spc-myc transgenic animals. micro-ct dosage ranged from to mgy. the estimated dosage calculated for micro-pet was mgy. conclusion: micro-ct and f-fdg micro-pet provide quantitative data on morphology and metabolism in orthotopic lung tumour. the techniques can safely be applied in animal model phenotyping and therapeutic studies. monday pancreatic cancer). watts for minutes was applied using bipolar endoluminal rf device (habib™ endohpb, emcision ltd., london, uk), placed in a block using guidewire technique. rfa is followed by self-expanding or balloon-mounted metal-stent (ms) placement. drainage catheter was repositioned for follow-up. results: duct patency restorated in ( . %) cases; in ( . %) case procedure filed because of guidewire conduction failure. all cases of balloonoplasty required the repeated procedure followed by stenting. biliary patients maintained stent patency as long as they are alive. the mean stent patency was . ± . ( - ) days. there was no -day mortality, haemorrhage or pancreatitis following rfa. one complication (bile duct perforation) was observed in a post-balloonoplasty patient on repeated (rfa&stenting) procedure; this case was managed percutaneally. percutaneous rfa treatment appears to be safe and effective in the management of inoperable biliary and wirsung duct block. randomised studies with prolonged follow-up are warranted. conclusion: viatorr plays an important role in tips scenario but its outcomes are strictly related to technical aspects such as intrahepatic tract completely covered, no concern about liver transplant, device never advanced in the portal vein for more than cm, -mm viatorr has to be considered the best compromise. was removed days after the procedure, during an open re-do for intra-abdominal bleeding. three stents are still in place. conclusion: placement and removal of retrievable covered stents appear to be technically feasible and could represent an excellent option in treating biliary disorders. bioabsorbable biliary stent in the percutaneous treatment of benign biliary stricture: preliminary experience g. mauri, c. michelozzi, v. pedicini, d. poretti, m. tramarin, f. melchiorre, g. cornalba, g. brambilla; milan/it (vanni.mauri@gmail.com) purpose: to report the outcome of patients treated with a novel bioabsorbable biliary stent for benign biliary strictures. methods and materials: ten bioabsorbable polydioxanone biliary stents (ella-dv biliary stent, ella-cs, czech republic) were deployed in patients with increased level of bilirubin due to postsurgical benign biliary stricture. this stent is made of polydioxanone, a material that allows to obtain a high radial force, but that is reabsorbed by the body within months. all patients had stricture recurrence after multiple standard bilioplasty ( to ). all patients were followed with clinical visit, ultrasound and serum bilirubin level. the procedure was successfully performed in all patients and immediate restoration of the normal caliber of the biliary duct was obtained. no immediate or late complications occurred and no patients had recurrence of the initial stricture (median follow-up months, range - months). conclusion: percutaneous bioabsorbable biliary stent placement is feasible and effective in the treatment of benign biliary strictures and in which standard bilioplasty has failed. in the future, this novel treatment may replace percutaneous bilioplasty a retrievable biliary stent placement as soon as long-term follow-up data will be available. to have a y-configuration for the biliary drainage of both lobes of liver, we used two pieces of covered stent system: one covered main piece stent and one contra-lateral covered stent. before and days after y-covered stent insertion, cholangiograms were obtained through the ihd for the evaluation of biliary drainage of both lobes of liver. we checked the blood bilirubin levels before, week after and every month after the stenting. results: they were patients including women and men. they had inoperable intrahepatic cholangiocarcinomas in and two metastatic biliary obstructions due to breast and stomach cancers. obstructive types were in i, in ii, in iiia and in iv. the placement of the y-shaped covered stent was successful in all cases. the mean follow-up period was about months. all cases had showed adequate biliary drainages in the follow-up tubograms. the bilirubin levels had been normalised weeks after being the y-covered stent inserted except one patient. there were no clinical infectious signs during the follow-up period. mean patency rate was about . months ( days). a newly designed y-shaped covered stent would be clinically effective for the palliative treatment of hilar obstructive malignant carcinoma of liver. the comparison of balloon-occluded retrograde transvenous obliteration for gastric varices using liquid and foam sclerosants j. koizumi , k. myojin , c. itou , n. mori , t. sekiguchi , t. hara , t. ichikawa , y. imai , b. janne d'othée ; isehara/jp, baltimore, md/us (jkoizumi@is.icc.u-tokai.ac.jp) purpose: liquid ethanolamine oleate which has been used traditionally for balloonoccluded retrograde transvenous obliteration (brto) of the gastric varices (gv) may cause severe complications including haemolysis, allergy, etc. if overdosed. thus, we introduced foam sclerotherapy to reduce the dose and compared the safety and efficacy of brto using liquid and foam sclerosants. methods and materials: forty-three patients with gastric varices were performed brto since october ' . of these, three patients were excluded because simultaneous tace or pse was performed. twenty patients using liquid ethanolamine oleate with iodine contrast (eoi) before march ' and twenty patients using polidocanol foam (pof) after may ' were included in this study. the success rates, side effects and complication rates were compared among the two groups. results: complete stasis of the gastric varices was obtained in all patients of both groups. abdominal symptoms during brto were significantly (p < . ) higher in eoi ( %) than pof ( %). postprocedure fever (> . ) was also significantly (p < . ) higher in eoi ( %) than in pof ( %). in both groups total bilirubin increased and platelet counts decreased significantly (p < . ). however, the decrease ratio of platelet counts was significantly (p < . ) higher in eoi (- . ± . %) than pof (- . ± . % purpose: digital linear tomosynthesis has recently been introduced not only for mammography but also for chest and musculoskeletal indications. the clinical utility in musculoskeletal applications has been validated in only a few reports. the purpose of the current study was to evaluate the clinical utility of tomosynthesis in suspect occult hip fracture. in a retrospective review tomosynthesis hip examinations on women and men performed for further evaluation of suspect hip fracture were retrieved from the radiology archive. three observers scored the tomosynthesis scans separately from the radiography examinations, into the categories no proximal femur fracture, suspect proximal femur fracture (femoral neck, trochanteric, or greater trochanteric avulsion) or definite proximal femur fracture. ct, mri or clinical outcome was used as reference. results: observer variation was moderate to substantial for three observer pairs regarding radiography (k= . - . ) and improved to substantial to almost perfect for tomosynthesis (k= . - . ). eleven patients were operated on for femoral neck fracture. tomosynthesis detected ten of these, and the eleventh patient was operated on without diagnostic confirmation from any imaging modality. one patient had been operated with dynamic hip screw for intertrochanteric fracture. the remaining trochanteric fractures were incomplete and were treated conservatively. there were no false-positive tomosynthesis diagnoses reported. there were no significant falsenegative tomosynthesis diagnoses. the distinction between incomplete/complete trochanteric fractures and greater trochanteric avulsions is sometimes difficult. purpose: advanced core decompression (acd) is in clinical evaluation for patients with avascular necrosis (avn) of the hip. in opposition to standard core decompression, acd uses an expandable reamer allowing optimal debridement of necrosis after drilling a core to the femoral head. the bone defect is filled with a bone graft substitute. we aimed to constitute the therapeutic success of acd based on mri. methods and materials: twenty patients ( males, females, mean age . years) underwent t mri of the hip prior to, days and . - years after acd. the protocol included tirm, pd/t w tse, high-resolution t w, dess and t w vibe sequences. sequences were evaluated regarding delineation of necrosis, bone, graft and transformation zone in between. the volume of necrosis was measured before and after acd. results: avn prior to acd as well as the defect filled with the graft after acd and the residual necrosis could be imaged with reproducible high quality at t. t w and pdw sequences provided best contrast to measure the volume of necrosis. each patient showed a reduction of necrosis after acd ( . % to . %, mean . , sd . ). the granulation zone around the graft could especially be visualised by t w tirm and pdw sequences. the arrangement of different layers correlated with histological findings. conclusion: structural changes and reduction of necrosis after acd can be monitored by mri. acd does significantly reduce the volume of necrosis in avn of the hip. the mre study after oral administration of peg solution provides an accurate assessment of small-bowel involvement, allowing an evaluation of disease activity in patients with known cd, reducing the radiation exposure in young patients. metal artefact reduction in hip prosthesis with iterative reconstructions f. morsbach , s. bickelhaupt , g. wanner , a. krauss ; b. schmidt , h. alkadhi , zurich/ch, forchheim/de purpose: to evaluate the effect of a novel iterative frequency split-normalised (ifs) metal artefact reduction (mar) on image quality of computed tomography (ct) in hip-prosthesis. in the first study-part, an artificial hip-phantom with steel and titan-based shafts, using three inlays of water, fat and contrast-media placed in the pelvis, was used to test and optimise the ifs algorithm. image quality and accuracy of ct number measurements of inlays were determined. in the second study-part, consecutive patients with unilateral (n= ) or bilateral (n= ) hipprosthesis were included. datasets using filtered back projection (fbp), ifs and a previously published mar algorithm using linear-interpolation were reconstructed. two readers evaluated axial, coronal and sagittal ct image reformations for overall image quality and evaluated image quality of pelvic organ depiction; ct numbers in the urinary bladder, gluteal muscle and subcutaneous fat were measured. results: ex-vivo experiments revealed the best image quality for ifs. measurements of ct numbers of the inlays were more accurate for ifs. in patients, we found a significant improvement in overall image quality for all reformations (p < . ) and a significantly increased image quality of pelvic organs (p < . ) for the ifs algorithm. ct numbers of the bladder (p < . ) and muscle (p= . ) were significantly less variable for ifs as compared with images reconstructed with fbp and the linear interpolation mar algorithm, whereas we found no significant difference for fat (p= . ). the ifs algorithm significantly reduces metal artefacts from hipprostheses, increases image quality and improves measurement accuracy of ct numbers as compared with fbp and linear interpolation mar algorithms. purpose: computed tomographic (ct) colonography is a technique for detecting bowel cancer or potentially precancerous polyps. because retained fluid and stool can mimic pathology, ct data are acquired with the patient in both prone and supine positions. radiologists then match endoluminal locations between the two acquisitions to determine whether pathology is real. this process is hindered by the fact that the colon can undergo large deformations that often occur during repositioning of the patient. automated registration between datasets could potentially improve efficiency and diagnostic accuracy. we have developed software to establish correspondence between prone and supine endoluminal surfaces. an initialisation step generates image patches at the positions of haustral folds using depth map renderings and is optimised by virtual camera registration. additional neighbourhood information is then included in a markov random field model to establish landmark-based correspondences. subsequently, the complexity of the registration task is reduced by mapping both prone and supine surfaces onto a cylindrical domain in which correspondence is established using non-rigid image registration. monday recurrences in patients ( hepatic and lung metastases) but missed a mm sessile polyp and flat lesions. ctc quality was inadequate in the % of patients. conclusion: ctc can be effective and represents a valid alternative to colonoscopy for surveillance for colorectal cancer recurrence after surgery. ct colonography: comparative study of experienced vs nonexperienced radiologists using d flythrough approach with and without cad software f. vecchietti, m. rengo, d. caruso, c.n. de cecco, d. bellini, a. laghi; latina/it (fabrizio.vecchietti@gmail.com) purpose: to compare performances of different experienced readers using a primary d flythrough approach with and without the use of a cad analysis. methods and materials: three readers evaluated patients with endoscopically proved polyps (ranging from mm to mm) and different colonic preparations ( fluid tagging, full cathartic preparation). dataset analyses were performed on a ge adw . workstation equipped with vcar colon software. per-polyp sensitivity, inter-reader agreement, mean reporting time and false positive were evaluated for each approach. results: less experienced readers increased per-polyp sensitivity, respectively, from % and % for d analysis to % and % for primary d+cad analysis with a significant difference (p= . and p= . ) while no significant differences were found for the expert reader (p= . ). less experienced readers were faster when assisted by cad but no significant differences were found on mean reading time for all readers (p= . / . / . ). mean false-positive findings for cad standalone analysis were (+- ). all readers decrease false positive when assisted by cad especially less experienced ones. inter-reader agreement was higher among all readers when assisted by cad ( methods and materials: seventy-five consecutive patients were prospectively randomised into two groups. both groups followed a low residue diet for two days before the examination. both preparations were based on fluid tagging, using a iodinate contrast medium (gastromiro). group received ml of fluid tagging agent the day before the study. group received ml of fluid tagging agent the day of the exam and ml of a laxative agent (lovol-esse) the day before the study. patient acceptance was evaluated using a visual assessment scale. quality of bowel preparation was evaluated using quantitative (tagged fluid density and number of untagged residue per segment) and qualitative (homogeneity per segment on a point scale) scores. results: bowel preparation was complete in all patients. no statistical significant differences for tagged fluid density, number of residue and tagging homogeneity between the two groups were founded. a significant higher patient acceptance was founded in group (p= . ). the preparation based on the combination of a laxative and a fluid tagging agents was better accepted. adding a laxative agent to a fluid tagging preparation did not improved image quality but was associated with an higher patient acceptance. moreover, the if a laxative agent is added to a fluid tagging bowel preparation the amount of iodine can be reduced. considering the latter as a reference method, ctc examinations were retrospectively and blindly initialisation, the method significantly improved the cylindrical registration (p < . ), achieving a mean error of . mm measured at reference points. the proposed method can successfully establish correspondence between prone-supine locations on the endoluminal surface derived from ct colonography. the ability to rapidly and automatically match polyps between acquisitions will facilitate ct colonography interpretation. (t.n.boellaard@amc.uva.nl) purpose: to evaluate whether a single intravenous alfentanil bolus has a clinically relevant analgesic effect compared with placebo in patients undergoing elective ct colonography. a prospective multi-centre randomised double-blind placebo-controlled trial was performed in consenting symptomatic or surveillance patients scheduled for elective ct colonography. patients were randomised to receive either a bolus of . μg/kg alfentanil (n= ) or placebo (n= ). the primary outcome was the difference in maximum pain during colonic insufflation on an -point numeric rating scale (one-sided t test). we defined a clinically relevant effect as a maximum pain reduction of at least . points. secondary outcomes included total pain and burden of ct colonography ( -point scale), most burdensome aspect, side effects and recovery time measured by the aldrete score. results: maximum pain scores during insufflation were lower with alfentanil as compared with placebo, . versus . (p < . ). total ct colonography pain and burden were also significantly lower with alfentanil ( . vs. . and . vs. . , respectively). with alfentanil fewer patients rated the insufflation as most burdensome aspect ( . % vs. . %; p= . ). no clinically relevant desaturations occurred. episodes with desaturations < % spo and dizziness were more common with alfentanil ( . % vs. . %; p < . and . % vs. . %; p < . ). aldrete scores in the alfentanil group were significantly lower immediately after the procedure, but similar at and minutes. purpose: to evaluate the accuracy of contrast material-enhanced computed tomographic colonography (ctc) for follow-up after curative surgery for colorectal cancer without evidence of disease recurrence. methods and materials: patients underwent ctc and colonoscopy (within months) after colorectal cancer surgery. patients with the suspicion of disease recurrence underwent pathologic confirmation. patients performed bowel cleansing and faecal tagging; bowel distention was achieved using co . both prone and supine scans, one after intravenous contrast material administration during the portal phase, were obtained using a -detector ct ("brilliance" philips with idose). images were reconstructed with a section thickness of . mm, transferred to a workstation and interpreted by one radiologist with experience reading several hundred ctc cases. sensitivity, specificity, positive predictive value (ppv), and negative predictive value (npv) of ctc for anastomotic and non-anastomotic colonic lesions (metachronous or flat lesions and polips) were determined and compared to endoscopy. results: ctc detected all anastomotic recurrences, all metachronous lesions (sensitivity and specificity= %) and a perianastomotic recurrence. in patients ctc depicted / polips > mm (sensitivity= . %, specificity= %, vpp= %, vpn= . %, accuracy= . %) and in patient detected of flat lesions (sensitivity= . %, specificity= %). ctc enabled detection of extracolonic prevalence and distribution was related to patient gender (p> . ). in sigma, advanced disease (grade / ) shows a significant positive correlation with reduced colonic distension (p < . ). no correlation was found between severity of sigmoid diverticula and symptoms onset. conclusion: prevalence and severity of diverticular disease increased over time in all colonic segments. an elevated number of asymptomatic diverticula is present in the right colon. an high percentage of patients with severe sigmoid diverticular disease remain asymptomatic. accuracy of water enema-mdct in colon cancer staging: a prospective study c. feasibility study of low-dose ct colonography using model-based iterative reconstruction: preliminary findings in patients v. vardhanabhuti, c. roobottom; plymouth/uk (vvar@me.com) to compare image quality on computed tomographic (ct) images acquired at standard dose (sd) and low dose (ld) using adaptive statistical iterative reconstruction (asir) and model-based iterative reconstruction (mbir) techniques. methods and materials: patients were prospectively recruited for the study with informed consent. they underwent standard dose (sd) and low-dose (ld) ct colonography. low-dose parameters were based on our phantom study with using vendor-specific automatic tube current modulation known as noise index. both sets of scans were reconstructed with asir and mbir. objective and subjective image qualities were assessed as well as diagnostic accuracies for significant lesions (e.g. polyps, cancer, etc). effective doses for each scans were recorded. results: objective image analysis supports significant noise reduction and superior contrast-to-noise ratio with low-dose scans using mbir technique (p < . ) despite being acquired at lower doses. subjective image parameters were equivalent for ld mbir and sd asir for both colonic and extra-colonic findings. diagnostic accuracies for polyp detection and other significant lesions were comparable. dose recorded were substantially lower for mbir (range - % reduction compared with asir) with mean average being . msv in our population group. conclusion: mbir shows superior reduction in noise whilst maintaining image quality and most importantly substantial dose reduction can be achieved. more patients are being recruited to substantiate diagnostic accuracies data with full results to be presented at the ecr . reviewed by two readers separately respectively having a degree of initial and advanced experience (for both primary d view). calculated values were sensitivity, specificity, nvp, pvp for patient-to-segment and both without and with the use of the cad system (im d-turin) as the second reader. ]of sensitivity, specificity, nvp, pvp reported by the novice radiologist were respectively: %, %, % and %, while the values obtained by the radiologist with advanced experience were equal to %, %, %, %. with the use of cad as a second reader the novice player has achieved an improvement of the sensitivity to %, while the skilled reader did not obtain a significant increase of' diagnostic accuracy. the sensitivity and npv of ctc for flat lesions depend on the experience of the radiologist reader. cad seems to be an effective aid for the novice radiologist only. (thomas.knogler@meduniwien.ac.at) purpose: to predict early treatment response with three-dimensional texture features (tf) in patients with hodgkin lymphoma (hl) after radio-chemotherapy extracted from contrast-enhanced ct. methods and materials: patients with histologically proven hl were included in this study. contrast-enhanced ( )f-fdg pet/ct was obtained on a dedicated pet/ct scanner. volumes-of-interest and long-and short-axis diameter were manually defined on hl manifestations prior and post-radio-chemotherapy on the ct image stack. three-dimensional texture features derived from the grey-level histogram, co-occurrence matrix, run-length matrix and absolute gradient were calculated for the vois. a stepwise logistic regression with forward selection was performed to find classic radiologic features (i.e. lesion diameter, lesion volume) and tf, which correctly classify treatment response (i.e. full response and partial response). classification in pet/ct was used as reference. results: difference in short axis diameter best fit as classic feature with a sensitivity of %, a specificity of . % and an accuracy of . %. combination of "s_ _ _ _entrp" and difference of "vertl_fraction" best fit as tf with a sensitivity of . %, a specificity of . % and an accuracy of . %. conclusion: texture features extracted from contrast-enhanced ct in patients with hl are superior in differentiation between responders and non-responders without the need for pet examinations, compared to classical radiological features. however, pet/ct as state-of-the-art imaging technique has a sensitivity and specificity > %, so that further research with larger patient number is needed to investigate this new method. (melvin.danastasi@med.uni-muenchen.de) purpose: to evaluate the agreement between true tumour volume and tumour volume derived from (i) a new formula based on longest lesion (recist) diameter, (ii) a new formula based on longest diameter and longest orthogonal (who) diameter. methods and materials: baseline and follow-up cts were available in patients with metastastic colorectal cancer from the randomised phase ii multicenter ciox trial. target lesions were defined at baseline and followed over time. lesions were evaluated by (i) semi-automated volumetry using siemens syngo.via and (ii) volumetric assement using a newly developed formula based on manual measurement of the longest diameter and the longest orthogonal diameter. true, who-and recist-based volumes were calculated. we compared the agreement of the true volume to the who-and recist-based volume. we also compared the agreement between 'true' and who-based volume relative changes by means of the intraclass correlation. results: a total of lesions were evaluated. using a variance components model it was shown that the difference between true and recist-based volume is statistically significant (p < . ) indicating a substantial constant bias. purpose: tumour treatment by retargeted truncated protein derivatives of the human tissue factor (ttf) results in tumour vessel infarction, necrosis and subsequent tumour growth retardation and regression. a novel method of gadofosvesetenhanced mri, that enables the visualisation of the response to this treatment in real-time, is introduced. methods and materials: dynamic gadofosveset-enhanced mri ( t) was performed in eight tumour-bearing (u ) nude mice. in the course of an ultrafast t -weighted gradient echo sequence, a gadolinium-based blood pool contrast agent (gadofosveset trisodium) was injected intravenously via a tail vein catheter. after the maximum contrast intensity inside the tumour was obtained, µl of ttf-ngr (a retargeted ttf derivative which binds to cd -overexpressing tumour endothelial cells) were injected intravenously via a second tail vein catheter (n = ; saline solution as control: n = ), and the contrast behaviour of the tumour was monitored by region of interest (roi) analysis. results: following the injection of ttf-ngr (approx. sec. after the beginning of the sequence), the contrast intensity inside the tumours of the treated mice decreased more instantly and more strongly than in the tumours of the control mice (auc . ± . vs. . ± . au). conclusion: gadofosveset-enhanced mri allows for the visualisation of the therapeutic response of tumours to anti-vascular treatment in real-time. considering the intended clinical application of ttf-ngr, this method might be a simple and quick surrogate parameter for the monitoring of the therapeutic response to vascular disrupting agents in humans. purpose: the specific growth pattern of pleural mesothelioma along the pleural surface makes therapy monitoring using common measurement criteria, such as recist . , difficult. therefore, byrne et al. developed modified recist criteria for pleural mesothelioma. in this study we evaluated the accordance between experienced and less experienced readers for recist . , recist . , mre-cist, and who. methods and materials: a total of baseline and follow-up-ct scans from patients from a clinical multi-centre pleural mesothelioma trial were retrospectively evaluated by different experienced radiologist (about year and more than years), who selected target lesions independently according to mrecist, recist . , recist . and who criteria. ct scans were then re-measured after an interval of greater than one month. the inter-and intra-reader variability using the different response criteria was analysed. results: both, the intra-reader-and inter-reader variability were best when using mrecist ( % limits of agreement of - . / . and of - . / . ) compared 'with recist . , recist . and who. further, regarding the objective response (pr = partial response, sd=stable disease and pd = progressive disease), mre-cist showed the most reliable intra-observer outcome with only one differently classified examination and the most reliable inter-observer outcome with four differently classified examinations. conclusion: our results suggest that mrecist is most reliable for treatment response evaluation of pleural mesothelioma between experienced and less experienced readers compared with recist . , recist . and who. to confirm these findings, the inclusion of further readers and more patient data is warranted. use of multimedia structured reporting for tumour response assessment d. munich/de (wieland.sommer@med.uni-muenchen.de) purpose: the aim of this study was to define the role of mri in the pretherapeutic prediction of treatment response in patients with liver metastases of neuroendocrine tumours (net) undergoing radioembolisation. in patients with proven hepatic metastases net, mri was performed at baseline ( t mri scanner, gd-eob-dtpa). furthermore, pet-ct examinations with somatostatin-specific tracer ga-dotatate were performed at baseline. the following imaging predictors were defined: patient age/gender, proliferation marker ki- , tumourload (%), vascularisation of metastases, tumour necrosis and haemorrhage. the status of somatostatin receptor was defined by analysing mean and maximum suv in pet-ct. as primary end point we defined the progression-free survival (pfs) using recist criteria in mri follow-up examinations (every months). the effects of the predictors on the progression-free survival were analysed using kaplan-meier statistics. results: the mean follow-up time was ± days. the mean pfs was days ( %ci - ). hypovascular metastases showed significant earlier progress ( vs. days; p < . ). a proliferation marker < % was significantly associated with a longer pfs than a proliferation marker between - % and > % (p < . dimensions system d (hologic®). the distribution among the acr density patters was studied. all women underwent a "combo" study, which consisted of a d-dm ( projections) and d-dbt ( projections). the increase in the detection of additional breast cancers due to the d-tomosynthesis studies has been evaluated. chi-square test with spss for windows ( . chicago, il) has been used to evaluate if there were any statistically significant differences (p < . was considered statistically significant). the clinical, radiologic and pathologic findings are described. results: among all acr density pattern, breast cancers were diagnosed with the d-dm studies (detection rate . %). additional cancers were diagnosed due to the d-dbt imaging findings (four in acr density patter , one in acr density pattern and two in acr density pattern ). the global detection rate increased to . %. no statistical differences were found regarding the detection rate among all density patterns. conclusion: in our group of patients the use of d-dbt combined with conventional d-dm increased the rate of breast cancer diagnosis from . to . %. no statistical significant differences were found among all acr density patterns. d-dbt may be useful not only in dense breasts (acr and ) but also in medium density breasts (acr ). exams. we present a structured reporting system, called vision, which captures a radiologist's measurements and key images in an efficient manner to generate disease timelines and automate the calculation of recist. we analysed serial radiology reports from ten patients with cancer to determine if radiologists reported tumour measurements, saved measurements in pacs, and whether there was correlation of tumour metrics between exams. in addition, we created a structured reporting solution that uploads screen captures and audio descriptions of image findings to a computer server where each finding is labelled with anatomy and pathology terms, presented in a multimedia structured report, and can be used to calculate recist. results: the analysis of baseline and subsequent radiology reports revealed that radiologists reported measurements in % of cases, saved measurements in % of baseline and % of follow-up studies, and correlated measurements between exams in only %. the application of vision enabled a means to record tumour measurements in % of cases by providing a visual record of where target lesions were previously measured, facilitating the linking of image findings between examinations and displaying the findings in disease timelines. the vision structured reporting system provides a means for more reproducible tumour response assessment. to identify the potential of breast mri vs. standard prognostic factors to predict tumour recurrence after successful treatment of primary breast cancer. methods and materials: consecutive patients receiving staging mri and subsequent guideline-approved therapy of primary breast cancer at our academic breast centre were investigated. standard prognostic factors including tnm staging, tumour typing, tumour grading, progesterone/estrogen receptors, her neu score and associated dcis component were assessed. follow-up was performed (endpoint: "tumour-recurrence" after complete remission). for analysis of breast-mri a dedicated cad software was used (computer-aided analysis). it enables semi-automatic analysis of enhancement characteristics of the whole tumour ( d analysis of early vs. delayed phase) and the "hot-spot" (i.e. voxel with highest washin/wash-out ratio). potential of breast mri characteristics vs. standard prognostic factors to stratify the endpoint separately and in combination was investigated using logistic regression. to identify significant and independent predictors, backward feature selection was applied (p entry /removal: < . /> . ). results: patients were included (endpoint: n= / . %, loss-to follow-up: n= / . %). if tested separately, logistic regression identified moderate potential for breast mri (aucmri= . , p= . ) and standard prognostic factors (auc-standard= . ; p= . ) to stratify the endpoint. if breast mri characteristics and standard prognostic factors were combined, predictive performance could be increased considerably (auccombined= . , p < . , sensitivity= . %, specificity= . %). feature selection identified one standard prognostic factor (m-stage) and four breast mri characteristics (hot-spot: wash-in, washout-ratio; d-analysis: tumour voxels showing wash-out plus weak wash-in, tumour voxels showing plateau and weak wash-in) as the most significant and independent predictors of tumour recurrence. purpose: to estimate the influence of breast density on diagnostic performance of dbt added to dm (dm+dbt), focusing on recall rate reduction. methods and materials: seventy-five women were recalled for findings on dm screening examination and further investigated according to usual protocols (additional dm views, ultrasonography, and/or core needle biopsy). the final conventional assessment was: cancers ( invasive ductal carcinoma, invasive lobular carcinomas) and negative/benign cases. before this conventional work-up, -or -view dbt was obtained (giotto, ims, italy) for an off-line further evaluation. two independent readers, blinded to final conventional assessment, retrospectively assigned a bi-rads score to each lesion on both dm only and dm+dbt. breast density was scored according to acr categories from to . χ test was used. results: none of the cancers was missed on dm+dbt by each of the two readers; of readings, ( %) had an increased bi-rads score. of readings of benign/negative cases, density was acr in ( %), acr in ( %), acr in ( %) and acr- in ( %); the bi-rads score was increased in ( %), unchanged in ( %) and decreased in ( %). bi-rads was decreased for / ( %) acr , / ( %) acr , / ( %) and / ( %) acr (p= . ). conclusion: breast density does not influence the capability of dbt, as added to dm, to decrease the bi-rads score of negative/benign cases recalled for further assessment at screening dm. recall rate reduction by adding double reading digital breast tomosynthesis (dbt) to digital mammography (dm) l.a. carbonaro , r.m. trimboli , n. verardi , k. khouri chalouhi , g. di leo , f. sardanelli ; san donato milanese/it, milan/ it (luca.carbonaro@gmail.com) purpose: to estimate the reduction in recall rate induced by adding double reading dbt to dm. methods and materials: during weeks of screening-activity, women with at least one mammographic suspicious finding were further investigated according to usual protocols (additional views, ultrasonography, and core needle biopsy). before this standard exams, -or -view dbt was acquired (giotto, ims, italy). of a total of , dm screening-exams, were initially recalled (recall rate of . %) for suspicious findings. two independent readers (who did not perform initial standard reading and blinded to final diagnosis) retrospectively evaluated dm and dbt. each lesion was scored according to bi-rads classification, considering , a-b-c, and as recalls. results: two dbts (two findings) were excluded for technical problems. at combined dm+dbt evaluation each of the two readers recalled / ( %) women; considering each case judged as bi-rads - by at least one of the two readers as recalled (double reading), a total of cases were recalled with a reduction in recall rate of / ( %). of readings of cancers ( idcs, ilcs), we had bi-rads upgrade for ( %), confirmation for ( %), and downgrade for ( %). of readings of negative cases, we had a bi-rads upgrade in ( %), confirmation in ( %), and downgrade in ( %). no cancers were missed. the use of double reading dbt as an adjunct to dm could allow for a reduction of recall rate by %, from . % to . %. detection rate for suspicious lesions of digital breast tomosynthesis in combination with digital mammography or d central projection imaging c. zuiani , p. clauser , v. londero , c. molinari , r. girometti , a. taibi , s. vecchio , m. bazzocchi ; udine/it, ferrara/it, bologna/it (clauser.p@hotmail.it) purpose: based on a novel approach, digital breast tomosynthesis (dbt) may simultaneously acquire d and d images of the breast. variable dose geometry is used to give a sufficient dose in the central projection ( d-cp) for that image to be a d mammogram. we aimed to assess the detection rate for suspicious lesions (acr-birads - ) of dbt associated with digital mammography (dm) or d-cp. methods and materials: asymptomatic women who performed dm and dbt with d-cp as screening examinations were included. two experienced radiologists, blinded to final diagnosis, evaluated images in separate sessions according to two different strategies of reading: dm+dbt (set-a) and d-cp+dbt (set-b). they assessed breast lesions as benign or suspicious in case of acr-bi-rads scoring of - and - , respectively. discordant cases were reviewed in consensus. purpose: the aim of this study was to demonstrate the diagnostic significance of digital mammography with tomosynthesis ( d) versus digital mammography ( d) in the group of histologically proven multicentric breast cancer. in the group of patients examined in this study, -d mammography showed suspicious breast lesions. all patients were sent to the oncology institute of vojvodina for further examination and biopsy. at our institution after initially clinical breast exam, d and d mammography were performed in the same act. all imaging procedures were performed on hologic selenia dimensions equipment. two radiologists independently read mammograms and core needle biopsy were performed in all birads and groups. all patients had fibroglandular or heterogeneously dense breasts (acr and acr ). results: in the group of patients, pathologic findings revealed unifocal and multicentric cancers for a total of malignant foci. all unifocal cancers were detected by both methods. with d mammography, additionally suspicious lesions were found and using d mammography suspicious mass were found. both d and d mammography showed the same lesions but d mammography showed "new" lesions which were obscured on d mammography. overall sensitivity was % ( / ) for d mammography and % ( / ) for d mammography (p < . ). results showed that in % of multicentric foci were in situ carcinomas (dcis). conclusion: d mammography was more sensitive than d mammography for the detection of multicentric foci in fibroglandular or heterogeneously dense breasts. the role of tomosynthesis after normal mammography according to acr density patterns j. etxano, p. slon, i. after a standardised preparation with l of oral water over min, the patient is asked to empty the bladder. initially the patient receives intravenously (iv) mg of furosemide. contrast administration consists of a fixed iv volume of - ml iobitridol mgi/ml followed by ml saline solution injected at a rate of - ml/s. after min and subsequently every min first low-radiation scouts are acquired breast tomosynthesis versus digital mammography: evaluation of diagnostic potential in women with abnormal screening mammograms m. a. shaaban; cairo/eg (marwaadelmm@hotmail.com) purpose: to compare the diagnostic potential of digital mammography with tomosynthesis. methods and materials: women with abnormal screening mammograms, findings, and definite imaging or histopathological diagnosis were included. the screening mammography interpretation consisted of direct comparison of the tomosynthesis (dbt) examination with full field digital mammography (ffdm) images. the study radiologists subjectively rated the equivalence of the image quality of both the dbt and the ffdm examinations with no use of additional mammography, magnification views or comparison mammography. the next step was categorising the findings in both ffdm and dbt separately according to birads classification and the statistical analysis evaluated the p values of dbt and ffdm as well as their sensitivities. results: all findings categorised as birads according to mammography showed reduction in number,particularly for masses, when examined with tomosynthesis. the image quality of tomosynthesis was subjectively rated as equivalent ( . %) or superior ( . %) to digital mammography in . % of the total of findings; the test was highly significant (p < . ). for masses, tomosynthesis image quality was rated as equivalent in . % or superior in . % of findings. masses were % of findings in which tomosynthesis had superior image quality. the ffdm sensitivity was of . % compared with . % for dbt. the diagnostic potential of digital breast tomosynthesis is superior to that of full-field digital mammography by evaluating their image quality and their sensitivity. based on a subjective analysis, dbt showed a significantly higher image quality compared with digital mammography in all finding types, especially in the characterisation of masses. purpose: to compare discordant screen-detected cancers in ffdm (" d-mode") versus d plus tomosynthesis ( d+ d or "combo-mode") in a population-based screening program. methods and materials: oslo tomosynthesis screening trial (otst), a large prospective study comparing ffdm with d plus tomosynthesis in breast cancer screening, is part of the norwegian screening program. women - are invited biannually to mammography using independent double reading. the two main arms of otst have independent double reading. one d arm is modified with cad and one combo-arm with synthetic d. the four arms are read by independent radiologists. from . . to . . , screen-detected cancers were found. results: cancers detected: arm a (conventional ffdm) , arm b ( d+cad) , arm c ( d+tomo) , and arm d (synthetic d+tomo) . merging arm a and b (" d-mode") and c+d ("combo-mode"), cancers were detected by " d-mode" and by "combo-mode" ( . % relative increase). discordant rate (screendetected cancer with tp score by only one reader) was . % ( / ) for " d-mode" and . % ( / ) for "combo-mode". for cancers manifesting as spiculated mass or distortion (n= ) the discordant rate was . % ( / ) for " d-mode" and . % ( / ) for "combo-mode". for cancers with microcalcifications the values were . % ( / ) and . % ( / ), respectively. conclusion: combined ffdm and tomosynthesis showed a % relative increase in cancer detection as compared with ffdm. discordant cancer rate was approximately the same or higher for "combo-mode" as compared with " d-mode". independent double reading should be the standard of care when tomosynthesis is implemented into mammography screening. purpose: within narrow limits, the ct estimated size influences the prognosis for spontaneous passage of a ureteral calculus. in the present experiment, we tried to reduce the inter-reader variability in urinary calculus size estimation by measuring the variability before, immediately after and late after a training session. a retrospectively generated anonymous urinary calculi ct image data bank consisting of unenhanced ct-stacks demonstrating ureteral or kidney calculi was used. eleven readers, radiologists and residents (mean experience years) independently estimated the largest axial diameter of the calculi in three sessions: baseline, post-training and follow-up. immediately before the post-training session each reader received training on eight calculi aimed at reducing inter-reader variability without affecting the mean reader size estimate. follow-up session was performed four to eight weeks later without further training. results: per-calculus standard deviation between readers was . , . and . mm and inter-reader limits of agreement were ± . , ± . and ± . mm for baseline, post-training and follow-up session, respectively. friedman test showed significant difference for per-calculus standard deviation (p < . ). pairwise wilcoxon signedranks test showed increased variability in follow-up session compared to baseline (p < . ) and post-training session (p < . ). the small reduction in variability in post-training session compared to baseline was not statistically significant. the small statistically non-significant reduction of inter-reader variability from the tested training protocol had no long-term effect, where an increase in variability was seen. other approaches such as reader-independent urinary calculus size estimation seem more promising for reduction of inter-reader variability. purpose: to assess the added value of functional sequences, using diffusionweighted imaging and apparent diffusion coefficient value, to conventional mri imaging examination in the differential diagnosis from benign and malignant focal liver lesions. methods and materials: a total of patients with known focal liver lesions including benign ( angiomas, fnh, abscesses) and malignant ( metastases, hccs, cholangiocarcinomas) underwent . -t mri examination (achieva, philips). the study was performed with a phased array multi-coil using a conventional protocol that included also diffusion-weighted imaging (dwi) with different b-values. the rois were manually drawn on focal liver lesions and on surrounding normal hepatic parenchyma in adc maps, and statistical analysis of adc mean values was performed. results: lesions were proved either by follow-up (benign lesions) or biopsy (malignant lesions).following mean adc values were obtained for different types of benign lesions: angiomas ( . ± , x - mm /sec), fnh ( . ± , x - mm /sec), abscesses ( ± , x - mm /sec) while in the neoplastic lesions were: metastases ( , ± x - mm /sec), hccs ( , ± , x - mm /sec) and cholangiocarcinomas ( ± x - mm /sec). in normal hepatic parenchyma, mean perfusion values were ( , ± , x - mm /sec). a statistical higher values (p < . ) were obtained in diffusion parameters among benign than those of malignant lesions ( ± , vs ± , x - mm /sec). conclusion: diffusion-weighted images offer useful quantitative information (by evaluation of adc maps) that differs significantly in solid and malignant liver lesions, due to tumour different vascularity and cellularity. purpose: to identify the best mr sequences for pancreatic adenocarcinoma conspicuity and determine whether mr signal and apparent diffusion coefficient (adc) values correlate with pathological findings. methods and materials: consecutive patients with pathologically proven pancreatic adenocarcinoma who underwent mri ( . or t) before surgical resection were included. fat-suppressed (fs) t -weighted gradient-echo (gre), fs t -weighted fast-recovery fast spin echo, d fs dynamic t -weighted gadolinium-enhanced gre during arterial, portal and delayed phases and diffusion-weighted imaging (dwi) with b values of and or sec/mm were obtained. two observers reviewed mr sequences for size, signal characteristics and lesion conspicuity using a four-point rating scale. adc of tumours were calculated. histological characteristics (differentiation, fibrosis, necrosis) were correlated with mri features. results: % of pancreatic adenocarcinomas were hypointense on d fs t gre arterial phase, which was the best sequence for tumour conspicuity, followed by portal phase. dwi was not useful for delineating % of tumours. maximum diameter at pathological examination ranged from to mm (mean mm). it was best correlated with mr tumour size on dwi. no correlation was found between adc (mean value : . x - mm /sec) and differentiation, fibrosis or necrosis. all homogeneous hyperintense lesions on delayed phase ( % of tumours) were predominantly fibrous tumours. conclusion: d fs t gre arterial phase sequence is superior to dwi for pancreatic adenocarcinoma conspicuity but it underestimates the size of the tumour. dwi is the best sequence for size evaluation when the tumour is correctly delineated. quantitative data analysis of the diffusion-weighted mr-images in the differential diagnosis of metastatic liver disease of colorectal and pancreatic aetiology y. savchenkov, s. bagnenko, g. trufanov, v. fokin; st. petersburg/ru (yura_savchenkov@mail.ru) purpose: to develop differential diagnosis metastatic liver disease on the basis of quantitative data analysis of dwi. methods and materials: metastatic liver lesions colorectal ( lesions) and pancreatic ( lesions) aetiology were analysed in patients. we used dwi with the factors b- , , , , s/mm . all measurements were carried out within a single axial slice (for each pulse sequence separately). we used the coefficients, calculated on the basis of the ratio measured values in several organs, in different parts of the liver or in one and the same region of the liver. the most informative in the native study is the ratio of si lesionb /si aorta b , si lesionb /si aortab и si lesionb /si liverb (р< . ). somewhat less informative demonstrated is the ratio of si lesionb /si liverb и adc lesion - - (р< . and р= . purpose: in clinical practice, the apparent diffusion coefficient (adc)-map is supposed to eradicate the t -shine-through effect (t -ste) potentially affecting the diffusion-weighted (dw) signal of focal liver lesions (flls) at higher b-value. we investigated whether this assumption is valid. methods and materials: included were forty-five patients with focal liver lesions ( malignant and benign) detected on a . t system (cysts and haemangiomas were excluded from analysis). dw examination was performed using a single-shot echoplanar sequence with b values of , and sec/mm , leading to the generation of (a) the adc-map, using a -point regression analysis and (b) the exponential adc-map (e-adc-map), using the b /b images ratio, which provides a diffusion-weighted image with complete eradication of t -relaxation time effects. by performing an analysis of differential signal patterns, two experienced radiologists in consensus estimated the prevalence of the t -ste when combining dw images with the adc-map or e-adc-map. purpose: to develop a novel spectral reconstruction algorithm for digital breast tomosynthesis (dbt) that results in reduced artifacts and improved image quality. methods and materials: current reconstruction algorithms assume that the xray source emits a mono-energetic x-ray beam, resulting in artifacts and possibly sub-optimal image quality. to avoid this, a mathematical model of dbt acquisition that includes the spectral nature of the x-ray source was developed, resulting in a large scale non-linear inversion problem which we solve using an iterative, gradient descent method. the resulting algorithm was tested using breast phantoms with lesions resembling masses and calcifications. the breast phantoms were imaged with a clinical dbt system using the automatic exposure control system. the resulting spectral reconstructions were compared to the system's filtered backprojection (fbp) reconstruction, which assumes a mono-energetic x-ray source. the signal difference-to-noise ratios of the masses in the spectral reconstruction were all superior to those of fbp by a mean factor of . . in addition, the masses exhibited better homogeneity and no artifacts in the direction of x-ray tube travel, typically seen in dbt images. the microcalcifications also resulted in improved signal difference and without artifacts seen in the fbp reconstructions. subjective comparison of images of heterogeneous breast phantoms showed an overall improvement in image quality, substantial reduction of artifacts, and lower noise. conclusion: spectral reconstruction can improve image quality and reduce artifacts in dbt images. this new algorithm also allows for investigation of novel acquisition techniques that could result in further improvements in dbt imaging. purpose: phase-contrast radiography is an emerging technique for producing medical imaging with more soft tissue contrast than traditional absorption radiography. the goal of this study is to evaluate the feasibility of phase contrast imaging using grating interferometer for clinical use. we developed a prototype of phase contrast x-ray imaging system using micro-focus x-ray source, grating interferometer and cmos detector. the source contains a tungsten anode x-ray tube that can operate from kv at . ma and focal spot size of . mm. a specification of phase grating was . um period, ni . um height and x mm area; and analyser grating was . um period, au . um height and x mm area. with application of phase retrieval algorithm, phantoms such as acryl ball, honey bee and goldfish images were obtained. we compared with images of conventional absorption radiography and evaluated the phase intensity by phase stepping method. results: phase contrast image shows a detailed view of the edge of the acryl ball. on the phase contrast image there are dark and light lines running along the hole. these lines represent the phase-contrast edge enhancement effect. a similar effect is evident at the honeybee and goldfish images. the phase contrast edge enhancement effect is visible in the phase contrast radiography, but not in either of the absorption contrast image. the phase contrast imaging using grating interferometer will ultimately provide a novel x-ray imaging system that enables with high contrast, which can be valuable in medical imaging such as breast, cartilage and vessels. first in-vitro results of microbubbles as a scattering contrast agent for x-ray dark-field imaging measured at a first pre-clinical x-ray phase-contrast and dark-field ct scanner purpose: dark-field and phase-contrast imaging, which generate contrast from ultra-small angle scattering and refraction of x-rays in matter, have been shown to increase soft-tissue contrast and provide complementary information to conventional absorption-based imaging. to further improve image quality and explore possible alternatives to commonly applied iodine-based contrast agents, the use of microbubble-based ultrasound contrast agents as an x-ray scattering dark-field contrast medium was investigated. methods and materials: using the first pre-clinical phase-contrast and dark-field ct scanner with polychromatic x-ray source and grating interferometer installed on a rotating gantry, absorption, phase-contrast and dark-field images of microbubblebased contrast-agent samples were acquired in-vitro. for quantitative comparison, the contrast-to-noise ratio relative to a reference was calculated for varying detector resolutions ( - micrometer) in absorption and dark-field images. results: it was possible to generate an improved contrast-to-noise ratio in the darkfield image compared to the absorption-based image ( . versus . , pixel size micrometer) by exploiting the x-ray scattering through microbubbles. with larger pixel sizes ( micrometer), the relative contrast gain increased to . for dark field, whereas, with . , it remained in the same order of magnitude for absorption. the proved feasibility of microbubble-based dark-field contrastenhancement with clinically compatible pixel sizes, together with the large potential of the introduction of grating interferometry into a clinical environment as shown by the successful implementation of the technology into a rotating gantry, strongly promote the use of microbubbles as a dedicated dark-field x-ray contrast agent and warrant further investigation in an experimental in-vivo setting. images. four thicknesses of the combined phantoms were imaged with a digital mammography unit. of each thickness, four images were acquired under automatic exposure control. images were displayed under standard clinical conditions: first on two megapixel medical grade monitors calibrated to the dicom gsdf standard, then on a megapixel colour monitor, displaying the images in green-scale. greenscale was chosen as this wavelength matches a peak in human visual response. reading was performed with the sara software which displays each cdmam cell under random rotation, reducing reader memorization. readers performed a -alternative forced choice task; five readers scored all images. results: threshold gold thickness (tgt) increased as beam quality and thickness increased, indicating a reduction in object detectability with increasing object thickness. results obtained for the grey-scale display had a higher tgt compared to green-scale results; tgt values obtained with green-scale display were between % and % lower than grey-scale display tgt. p values for the different diameters obtained from wilcoxon matched pairs tests ranged from < . to . for cm and < . to . for cm. conclusion: observer performance measured by c-d curves was equal or better for images displayed in green-scale rather than grey-scale, indicating potential benefit for using green-scale displays in medical applications. volumetric breast-density measurement using spectral mammography purpose: volumetric breast density (vbd) quantification is useful for assessing diagnostic accuracy and the risk of developing breast cancer. the purpose of this study is to evaluate spectral imaging as a method to improve the accuracy of vbd measurements compared to conventional non-spectral methods. the vbd is the volumetric fraction of fibro-glandular tissue in the breast. to measure vbd in a conventional non-energy resolved mammogram, assumptions have to be made on the breast thickness. spectral imaging, on the other hand, enables simultaneous measurement of breast thickness and glandularity by employing the spectral difference in x-ray attenuation between adipose and fibro-glandular tissue. spectral mammograms were acquired in a single exposure using a photon-counting mammography system. the vbd was measured by material decomposition based on calibration to tissue-equivalent material. for reference, vbd was measured with a conventional non-spectral method in a similar group of patients. results: spectral mammograms of patients, aged - years, were examined. the correlation in vbd between contralateral breasts was r= . . patients were examined with conventional methods, which returned a correlation between contralateral breasts of r= . . the vbd distribution was similar in the two groups as measured with the two different methods. conclusion: spectral imaging provides an efficient measure of vbd. the vbd distributions over the group of patients were comparable in the spectral and nonspectral measurements, but the correlation between contralateral breasts was tighter using spectral imaging, which indicates higher consistency. purpose: the feasibility of monochromatic dual-energy x-ray absorptiometry (dexa) using multilayer reflector for precise measurement of bone mineral density (bmd) was examined. methods and materials: a multilayer mirror was fabricated to select an x-ray peak with an energy of kev and . kev generated from an x-ray tube with a tungsten target. experimental set-up of monochromatic dexa was installed by dual-energy of monochromatic x-rays source and czt detector. the performance of the system was evaluated using a dexa phantom, spectrometer and radiation dosimeter. we compared the image quality and the attenuation reduction characteristics of the phantom to determine precision of bmd on conventional polychromatic and monochromatic dexa. purpose: high vessel attenuation and a high contrast-to-noise (cnr) ratio are prerequisites for highly diagnostic abdominal ct angiography (cta) examinations. we compared image-quality of standard kev polyenergetic images (peis) with calculated low-kev monoenergetic images (meis) in dual-energy cta studies of the abdomen. methods and materials: datasets of fifty patients ( men, ± years) who underwent abdominal dual-energy cta were retrospectively evaluated. the -and -kev dual-energy image data was used to calculate meis in -kev intervals from kev to kev. vessel attenuation and image noise were measured in three regions-of-interest (infrarenal aorta, external iliac artery and superior mesenteric artery) and the signal-to-noise ratio (snr) and cnr were subsequently calculated. differences between measurements in meis and peis were evaluated using the student's t-test. results: snr and cnr of -kev meis were highest compared to meis at other low-kev levels. when comparing meis at kev to peis, vessel attenuation and image noise were significantly higher in meis in all three regions-of-interest (+ %, + %, + %; p < . and + %, + %, + %; all p < . ). snr was slightly increased in -kev meis (+ %, + %, + %; p < . ). cnr was also significantly higher in meis when compared to peis (+ %, + % and + %; p < . ). purpose: it was shown in mice the exposure to a high fat (hf) diet during early development increased the susceptibility to high-fat diet-induced hepatic steatosis and decreased markers of hepatic mitochondrial function. we aim to investigate whether early exposure to a hf diet also increases the susceptibility to cardiac fat storage and diminishes cardiac mitochondrial function and ejection fraction. methods and materials: male and female c bl mice were fed a hf diet ( % kcal fat) or standard chow diet ( % kcal fat (lf)), starting at least weeks before conception and continuing during gestation and lactation. from weaning onwards, all offspring were fed the hf diet, generating two groups: hf/hf and lf/ hf. cardiac function and myocardial fat content were measured in male offspring at weeks of age (n= ) using magnetic resonance imaging and spectroscopy on a t mr system (bruker biospin gmbh). cardiac mitochondrial respiration was determined in parallel groups (n= ), using high resolution respirometry (oroboros instruments). results: at weeks of age, the hf/hf group showed significantly higher cardiac lipid content (p= . ) compared to the lf/hf group. no significant differences in cardiac mitochondrial function and ejection fraction were detected. conclusion: mice exposed to hf feeding during early development were more susceptible for high-fat diet-induced cardiac lipid accumulation. this was not (yet) accompanied by decreased mitochondrial function and/or decreased ejection fraction. cardiac and hepatic iron and heart function by mr in thalassaemia major patients treated with combined deferiprone and desferrioxamine regimen versus monotherapies: a multi-centre, observational and prospective study c. lge was significantly smaller in follow-up compared to the first examination (p= . ). in multivariate regression analysis, rv oedema was the only parameter that was associated with a significant improvement of rv-ef. conclusion: the significant decrease of lge in the follow-up examination implies that the area of hyperenhancement might represent necrosis. we furthermore conclude that the extend of rv scar is too small to permanently impair rv-ef function in the majority of patients in follow-up. purpose: the factors governing periprocedural myocardial injury (pmi) and its influence on the prognosis at follow-up are not completely clear. we used delayed enhancement magnetic resonance imaging (lge mri) to assess myonecrosis after pci. methods and materials: forty-three patients with stable coronary artery disease were studied with . t mri before and after (within h) stenting of bifurcation lesions. the left ventricular function and lge were assessed. we performed angiographic measurements of the vessel diameters, and bifurcation angles pre-and post-intervention. systolic-to-diastolic increase of t was above average in lateral (p < . ) and apical (p < . ) segments. conclusion: t relaxation times of normal myocardium differ significantly between diastole and systole at . t. their strong correlation facilitates translation of diastolic and systolic t normal values. regional deviations from the mean systolic-to-diastolic increase of t might be associated with regional differences in myocardial perfusion. author disclosures: g. reiter: employee; siemens. a. greiser: employee; siemens. are the preferential patterns of myocardial iron overload preserved at the cmr follow-up? results: for each group there was a significant improvement in the global as well as in regional t * values. for the whole patient population as well as for both groups, at basal the mean t * value over the anterior region was significantly lower than the mean t * values over the other regions, and the mean t * over the inferior region was significantly lower than the t * values over septal and lateral regions. the same pattern was present at the fu, with a little difference for patients with mild-moderate mio. in conclusion, a preferential pattern of iron store in anterior and inferior regions was present at both basal and fu cmrs, with an increment of t * values at fu due to a basal cmr-guided chelation therapy. the anterior region seems to be the region in which the iron accumulates first and is removed later. the effect of partial volume averaging on peak velocity measurements in phase contrast magnetic resonance angiography (pcmra) j.c.l. rodrigues , k. minhas , g. pieles , c. bucciarelli-ducci , r. tulloh , n.e. manghat , c.j. occleshaw , m.c.k. hamilton ; bristol/uk, auckland/nz purpose: ecg-gated pcmra is an established non-invasive in vivo method to measure blood flow. by default, the siemens argus pcmra flow analysis software calculates a voxel averaged peak velocity. the voxel with the highest velocity in the data set is first determined. this value is then averaged with this the velocities of its neighbouring voxels to generate the voxel averaged peak velocity. this may underestimate peak velocity. the aim of this study was to determine if voxel averaging leads to a lower calculated peak velocity. methods and materials: peak velocity measurements in different anatomical locations in subjects (healthy volunteers, congenital and acquired heart disease patients) were analysed by default voxel averaging method and single voxel technique and compared. the effects of flow velocity, scan protocol (breath hold versus free breathing) and scanner type (siemens symphony versus siemens avanto) were also assessed. statistical significance was defined as p < . . results: there was a highly significant mean percentage increase in peak velocity of . % when peak velocity was calculated by single voxel compared with voxel averaging technique (p < . ). significant increases in peak flow were observed by single voxel compared with voxel averaging regardless of patient type, anatomical location, cmr scanner or scan technique in terms of breathing command (p < . ). disabling the voxel averaging technique had no effect on the volume of flow recorded. the use of voxel averaging produces a consistent underestimation of peak velocity. at peak velocities > m.s - , the error may be clinically significant, e.g. misclassifying the severity of aortic stenosis. for this reason, it is recommended that for the assessment of peak velocity by pcmra voxel averaging should not be used. purpose: to evaluate foetal brain maturation during twin pregnancies complicated with twin-to-twin transfusion syndrome (ttts). methods and materials: over a period of years, we retrospectively evaluated mris of women with monochorionic twin pregnancies complicated with ttts. mri scans were realized at an average of weeks of gestation. all pregnancies complicated with ttts and successfully treated with fetoscopic laser were included. eighty-eight foetal brains were analysed and compared with an mri brain atlas and with the co-twin. biparietal brain diameter, cerebellar transverse diameter, sulcation, operculation, and myelination were analysed. results: among the foetuses, ( . %) developed severe brain damage (unilateral brain atrophy, clastic lesion of corpus callosum with cyst) and showed unusual delay of brain maturation. in others cases of successfully treated ttts, we found no difference in brain maturation between twins. conclusion: brain maturation during twin pregnancies with treated ttts is well preserved except in cases with a severe vascular complication. purpose: very preterm infants suffer a wide range of neurodevelopmental disabilities. the purpose of the study was to assess the relationship between body growth and white matter (wm) microstructure maturation, in very low-birth weight, extremely preterm infants. methods and materials: twenty-seven extremely premature infants (gestational age: . ± . weeks) with normal brain us studies and normal mri at term equivalent age ( . ± . weeks) were enrolled in the study. using a diffusion-weighted sequence, fractional anisotropy (fa) was measured bilaterally in fibre tracts with the region-of-interest method. the effect of sex and the relationship between somatometric measurements (birth and body weight, crown to heel length and head circumference) and fa was evaluated using a general linear model. two-tailed student's t-test was used to assess differences between small for gestational age (sga) and appropriate for gestational age (aga) infants. results: a positive correlation was found between body weight and fa in the anterior corona radiata, the posterior limb of internal capsule, the external capsule, the inferior fronto-occipital fasciculus, the superior longitudinal fasciculus, the middle cerebellar peduncles and the fornix. decreased fa was observed in the superior longitudinal fasciculus and the fornix in sga infants (p < . ). conclusion: in extremely premature infants body growth correlates with changes in wm microstructure. compromised growth at term equivalent age is associated with microstructural abnormalities in areas related to attention, language, memory and executive functioning. the "tail sign" in the differential diagnosis of vermian pathologies in foetuses under weeks: role of foetal mri p. relationship between body growth and regional brain volume changes in extremely premature small for gestational age babies l.c. tzarouchi, a. drougia, a. zikou, a. charisiadi, p. kosta, l. astrakas, s. andronikou, m.i. argyropoulou; ioannina/gr (ltzar@cc.uoi.gr) purpose: extremely low birth weight and/or low gestational age has been associated with alterations in brain development. the purpose of the study was to assess whether early body growth catch-up reflects regional brain volume (rbv) changes by evaluating small for gestational age (sga) extremely premature babies (gestational age< weeks) at term equivalent age. methods and materials: twenty-five extremely premature infants (ga: . ± . weeks) with normal brain us studies and normal mri at term equivalent age ( . + . weeks) were enrolled. thirteen were appropriate for gestational age at birth and at term (aga), sga at birth and aga at term (sga+) and sga at birth and term (sga-). t -weighted high-resolution d images were segmented using the spm . and volumes of individual gm areas were calculated using the ibaspm toolbox. two-tailed student's t-test was performed to test for differences in rbv between groups. results: there was no difference in rbv between aga and sga+ (body growth catch-up at term). in sga-(persistent body growth restriction at term), areas of late maturation (frontal lobes, caudate nucleus) presented lower rgmv. there was no difference in rbv between aga and sga-in brain areas of early maturation (occipital cortex, thalami) (p < . ). in extremely premature babies, body growth catch-up is associated with rbv catch-up at term equivalent age. rbv changes start from areas with great potential for early maturation. quality control in digital mammography: radiographers practice at hospitals of lisbon c. tomás, c. gonçalves, c.i.s. reis; lisbon/pt (claudiatomas @gmail.com) purpose: to investigate quality control/(qc) guidelines in use for digital mammography/(dm) in hospitals, to identify radiographer's practice in qc concerning dm and to identify the causes of exam rejection/repetition. methods and materials: questionnaires were developed and applied to radiographers working in dm (computed-radiography or direct-digital-mammography/ (ddm)) in hospitals to characterise the qc practices (guidelines in use, performed tests, tests frequency). rejected/repeated analyses was performed in one hospital with ddm equipment using the checklist proposed by the international atomic energy agency/(iaea). results: guidelines for qc are followed by % ( ) of the radiographers: % follow american-guidelines, % the portuguese, % the european/euref and % other guidelines. there is more than one guideline followed by radiographers in three institutions. the qc tests performed by radiographers in the same institution (proposed by iaea to test image acquisition and display systems) were not the same and in the right frequency. the main causes for mammography image rejection/repetition were improper positioning in % of the analysed images due to non-inclusion of pectoral muscle in mediolateral oblique projection and inner and outer quadrants asymmetry for craniocaudal projection. conclusion: in this group of hospitals with dm, there is no uniformity of qc practices. this can have impacts in mammography costs. this may be justified by the absence of certification programs concerning mammography departments. continuous education and training programs frequency to work with dm are not mandatory and also qc is not required by law in portugal. an investigation into the psychological anxiety of maltese women before and after a mammogram c. falzon; sta lucija/ mt (valeview@maltanet.net) purpose: to investigate whether there is a difference in anxiety levels between maltese women with and without a family history of breast cancer, before and after a mammogram. the study involved the participation of maltese women aged years and over. the women were divided into two groups; group without and group with family history of breast cancer. anxiety levels pre-and finally, mri made correct diagnosis in of foetuses with expansive formations, whereas in one of these cases we suspected a choledochal cyst and it was a gastric duplication and in another patient we diagnosed an ascites and it was an intrabdominal cystic lymphangioma. conclusion: our preliminary results suggest that mri has a supplemental value to sonography in anatomic evaluation and characterisation of gi abnormalities. ultrafast imaging sequence mri is helpful to confirm, refine or exclude us diagnosis. it also provides useful informations in prenatal counselling and perinatal management. purpose: in order to achieve high image quality with breast cancer screening mammography, the european guideline recommends training programs dedicated to radiographers. those training programs are very helpful for practitioners but back at their workplace it might be difficult for them to apply the achieved knowledge in their daily practice. to support radiographers to transfer good mammography practice in their daily screening activity, an online portfolio is realized by each radiographer during the following months after the training session. methods and materials: every month, the trainee radiographer posts about mammography examinations including the quality self-assessment on a dedicated electronic platform. experienced radiographers from the screening program of western switzerland comment the picture quality as well as the accuracy of the self assessment. tips and tricks, to improve quality, are also given. results: actually portfolios have been completed. the majority of the radiographers appreciated the personalized comments given by the experts. they found the tips very helpful and they say the portfolio helped them to continuously improve the quality of the performed mammograms. nevertheless, some radiographers were upset because of the high time investment necessary to the realization of this kind of portfolio. conclusion: in western switzerland, where there are many decentralized breast cancer screening units, the online portfolio is an interesting tool to support radiographers with the development and the transfer of competences in their daily practice. purpose: this study aimed at measuring patient satisfaction in mammography exams and satisfaction-related factors. methods and materials: research was conducted in several private practice clinics with a total of subjects using the myasthenia gravis questionnaire for assessing patient satisfaction concerning four dimensions: structure (physical environment), process (performing the exam), discomfort (physical and psychological) and general satisfaction (present and future). results: overall patient satisfaction was high ( %), with technical performance (process) and psychological discomfort having the major influence on patient satisfaction. exam costs and age had very low, or no impact, on satisfaction. also, the greater patient's education levels, the greater were their demands for process requirements, unlike patients with lower education levels which presented higher satisfaction levels. the great amount of patients of high age groups and respective pathologies may have influenced results when related to satisfaction and education level. the numbers of mammography exams have increased over the years and therefore it is essential to assess patient satisfaction so that improvements can be made. impacts of digital mammography in radiographers practice l. painho, t. . the anode-filter combination always used was w/rh. global iq was p (perfect) for cc, while in mlo the mean was g (good). the radiographers experience varied between and years. the compression force depends on breast compressed thickness. it can vary between and n for breast thickness range of to mm. the technique suffered changes when the analogue was compared with digital technologies: the energy is higher, the intensity is lower and the anode-filter has changed from mo/mo to rh/rh and w/rh. breast symmetry absence on cc projection, inframammary folds absence and skin folds presence were the criteria not achieved more frequently in this study, according to european guidelines on quality criteria for diagnostic radiographer images. iq of all exams was classified as appropriated (perfect and good ( out )). nevertheless, it is noticeable that some variation exists concerning the radiographer practice when comparing breasts with the same features. the radiographers experience and training can also affect the results. imaging ethics b. hofmann; oslo/ no (b.m.hofmann@medisin.uio.no) purpose: the benefits of modern medical imaging technology are obvious. however, the ethical challenges are less acknowledged. the purpose of the study is to highlight and to address core ethical challenges with modern medical imaging. a review of literature in radiology reveals a series of ethical challenges in modern medical imaging that are analysed with standard methods in modern bioethics. the ethical challenges are divided into four categories, i.e. challenges with ) existing, and ) new imaging techniques, ) altered use of existing imaging techniques, and ) challenges with basic concepts and end points in diagnostic imaging. a series of ethical challenges are identified within these categories, such as (radiation) safety, rationing, and justice ( ), implementation without evidence-based outcome ( ), reduced diagnostic accuracy, patient autonomy ( ), and challenges with underuse, overuse, and futile imaging ( ). conclusion: behind great benefits of modern imaging, a series of ethical challenges can be identified. while praising the benefits, the challenges need to be appraised to maintain confidence and trust in the profession, as well as a sound and fruitful development in the field. post-mammogram were measured using the well-established state and trait inventory for adults (stai) developed by c.d. spielberger. results: there was a significant difference (p . ). a negative correlation was obtained when the mean s-anxiety scores (pre: group , r=- . and group , r=- . and post: group , r=- . and group , r=- . ) of both groups were compared with age. the factor causing anxiety in women was mainly related to the procedure because their anxiety diminished significantly after the mammogram. the correlation showed that those who scored high pre-mammogram anxiety also scored high post-mammogram anxiety. no significant difference in the anxiety levels between the two groups existed before and after the mammogram. a negative correlation existed between age and s-anxiety of the women, resulting in younger women being more anxious than older women. ergonomic and environmental assessment in digital mammography room: impact on radiographers' activity s. costa, e. oliveira, f. serranheira, s. viegas, c.i.s. reis; lisbon/pt (stefaniebcosta@gmail.com) purpose: to investigate ergonomic-characteristics of the equipment, environmental conditions and its impact on radiographers' activity and to identify opportunities to optimise the practice and reduce the probability of wrmsds occurrence. radiographer's mammography procedures were observed and organized in tasks time-scale-graphic. interviews were applied to radiographers working in digital-mammography to characterise the practice (work patterns, mammographic equipment, exam room, environmental conditions) and to identify the presence of wrmsds symptoms. postural analyses were evaluated through video and pictures acquired during mammography positioning. measurements of angles were done with meazure . . software and classified according to the european standard/en - : +a : . results: the task-time scale showed that the average duration of each exam is minutes and also that the task which took more time was the indications given to the patient. . % of the radiographers referred that the most exhaustive procedure is the positioning of mlo-view and short-stature patients ( . %). in this specific case, the anatomical areas that can suffer more wrmsds are neck, arms and back presenting an angle of . º, . º and . º, respectively. the visual contact with the patient was compromised only during the right-mlo-view acquisition. considering the environmental conditions the illuminance values are not in accordance with the guidelines. the ergonomic characteristics of the equipment do not provide comfort to the radiographers. in order to reduce the probability of work-related musculoskeletal disorders in mammography positioning and patient safety, new equipment features should be developed. environmental conditions are adequate concerning the international references for temperature and humidity but not for illuminance. accuracy of students, and radiographers, with and without, mammography post-graduation in interpretation of mammography images r.b.j. cópio , k.b. azevedo , a.f.c.l. abrantes , l.p.v. ribeiro , r.p.p. almeida , c.a. silva ; faro/pt, evora/pt (rita.copio.rc@gmail.com) purpose: to evaluate the sensitivity, specificity and diagnostic accuracy of radiographers with and without mammography post-graduation and last year students of the radiography course in the interpretation of mammography images. a grid of socio-demographic characteristics and view-dex software (viewer for digital evaluation of x-ray images) for the interpretation of mammography images by participants were used. each of the cases was built with the four basic images. after viewing images, the participants showed their level of confidence about the presence of abnormal radiological findings in relation to the case. the results obtained showed values of sensitivity of %, % and % for the last year students, radiographers without post-graduation and post-graduate radiographers, respectively. for specificity, the values were %, % and % for the same groups, respectively. with regard to diagnostic accuracy, the values obtained were % for the group of students in the last year, % for the group of radiographers without post-graduation and % for post-graduate radiographers. the mean response time was . seconds to the last year students, . seconds for radiographers without post-graduation and . seconds to post-graduate radiographers. the sensitivity, specificity and diagnostic accuracy varies between each group. however, there are not significant differences between them. also, participants with a higher formation have higher average response time. purpose: to compare different formats of llama-derived nanobodies as alternatives to monoclonal antibodies for specific in vivo near-infrared fluorescence (nirf) imaging of lymphomas in a mouse model. we used ecto-enzyme art on lymphoma cells as model target and compared three different formats of art -specific nanobodies with a conventional antibody ( kd): a monovalent llama nanobody ( kd), a bivalent diabody ( kd), and a bivalent fc-fusion protein ( kd). all constructs were labeled with alexafluor and injected in nude mice, bearing art -positive and art negative tumors. circulating and excreted conjugates were monitored in plasma and urine and in vivo nirf-imaging was performed over h. tumor tissue penetration and target binding were analysed by facs and fluorescence microscopy. results: in vivo nirf-imaging revealed specific labeling of art -positive tumors but not of art -negative tumors with all af -conjugates. the smaller nanobody and diabody revealed rapid renal elimination with highest signal-to-background ratios of art -positive tumors. the larger fc-fusion protein and conventional antibody revealed long circulation times in plasma, resulting in unspecific background signals. facs and immunohistochemistry of tumors revealed deeper penetration and more homogenous labeling of tumor tissue with the nanobody and diabody than with the fc-fusion protein and conventional antibody. conclusion: renally excreted small nanobody-formats (< kd) can be used for specific in vivo imaging of lymphomas with a significantly higher signal-tobackground ratio than larger antibody-constructs (> kd) that are retained in circulation. therefore, single domain and bivalent nanobodies seem particularly suited for short-term diagnostic imaging, whereas reformatted nanobody-fc fusion proteins appear suited for long-term applications. the design of a dual-functional imaging contrast agent for targeting to tumour endothelial marker (tem ) q. quan , x. huang , j. xie , y. yan , h. gao , g. zhang , x. in control kit+/+ mice, the fmt signal for annexin v peaked at hours after myocardial infarction with subsequent decrease at hours and days after onset of ischemic injury. kitw/w-v mice revealed an increased and prolonged in-vivo apoptosis signal, which was associated with progressive decline in heart function. bone marrow reconstitution was able to reduce cardiomyocyte apoptosis and rescue kitw/w-v mice from progressive heart failure. in-vivo apoptosis signal was verified after killed by apoptosis staining using immunohistochemistry (tunel) and flow cytometry (caspase- ). hybrid acquisition of x-ray computed tomography allowed exact localisation of the fmt signal to the left-ventricle and facilitated organ segmentation and attenuation correction. flow cytometry and determining the dissociation constant. for detecting apoptosis in vivo, cal- tumour-bearing mice were treated with pdt and injected with the annexin v probe two days and two weeks after therapy. the fluorescence intensity of the tumours was evaluated semiquantitatively over time. the annexin v probe showed nearly the same absorption ( nm) and emission ( nm) spectrum like the free dye and possessed a high binding affinity to apoptotic cells (kd-value nm). therapeutic efficiency of pdt could be detected in vivo in the tumours via apoptotic cells shortly after therapy. our probe accumulated significantly stronger in treated tumours at two days in contrast to two weeks after therapy. conclusion: in summary, we could successfully image the therapeutic efficiency of pdt with the new designed fluorescence optical annexin v probe. apoptotic cells could be detected in the tumour short time periods ( days) but not longer time ( weeks) after pdt. bimodal nirf nanoparticles as an optical and mri contrast agent for imaging cells of the mononuclear phagocyte system j. purpose: even though approaches for multimodal imaging of targeted structures like in tumours have been suggested, fewer investigations have been made on bimodal optical and mr-imaging of inflammatory diseases via passive targeting of cells of the mononuclear phagocytic system (mps). however, non-targeted nanoparticles (np) could represent a simple and effective labelling tool being rapidly phagocytized from the blood stream by mononuclear cells which are then migrating to the site of inflammation. for the production of bimodal np iron oxide cores were enclosed by a near infrared (nir)-fluorochrome (ir ) and surrounded by a starchmatrix. the spectroscopic and mr-imaging properties of the bimodal particles were determined in agarose phantoms and in vivo using a near infrared fluorescence (nirf) small animal imaging system and . and t-mri, respectively. in vivo optical and mr-imaging was performed on mice with hind leg oedema. results: a specific nirf-(average fluorescence signal . scaled counts/s for µg/ml np) and mr-signal ( . t: r = mm- * sec- , r = mm- * sec- , r *= mm- * sec- ) was detected for the bimodal np in vitro. in vivo-mr and nirf-imaging studies confirmed specific signalling of the particles within oedema. conclusion: our bimodal non-targeted fluorescent iron oxide np successfully labelled cells of the mps in vitro and in vivo without specific target recognition by antibodies. additionally, the ability of specific nir-signalling and mr-tracking of mononuclear cells makes them suitable for application as a simple and potent nirf-optical and mri contrast agent for visualisation of inflammatory diseases. purpose: quantitative t -weighted perfusion imaging is promising. however, current software solutions are still semi-automatic and results are therefore potentially prone to observer-related bias. surprisingly, this aspect of dce-mri is still poorly investigated. we aimed to systematically address this matter using a dedicated imaging protocol and semi-automatic workflow for quantitative pharmacokinetic analysis. an ultra-fast high-spatial and high-temporal resolution protocol was used for t -weighted perfusion imaging (magnetom aera @ . t; dynamic view-sharing d gradient-echo-sequence/twist: temporal-resolution: . s, in-plane resolution: . mm , ml gadovist @ ml/s, acquisition time: s). for the assessment of pharmacokinetic parameters (k trans , two-compartment tofts-model, fast arterial-input-function) a dedicated semi-automatic software solution was used. enhancing intracranial tumours were independently evaluated two times by one experienced neuroradiologist (> mri, -year experience in dce-mri). results of pharmacokinetic parameters for each reading were documented in a database. variability of k trans measurements was assessed by means of reproducibility (concordance correlation coefficient), precision (pearson ρ), accuracy (bias correction factor/cb), reliability (intraclass correlation coefficient), repeatability (coefficient of repeatability/cr) and systematic bias (bland-altmann plot: regression coefficient/rc). methods and materials: patients (mean age years, range - ) gave informed consent for this prospective research ethic committee-approved study and underwent two consecutive brain ct-scans, with normal radiation dose (nd) (ctdivol mgy, . msv) and % reduced dose (rd). nd scans were reconstructed using filtered backprojection (fbp), while rd scans were reconstructed using fbp and two idose levels, id and id . image quality was assessed with grading and ranking by six neuroradiologists. mean hounsfield units (hu) and noise were measured. data were analysed using linear mixed models, and the tukey method for multiple comparisons. results: for all reconstructions image quality was graded adequate for clinical use. image quality was graded good/excellent in % of cases for nd, % of cases for id , % for id , and % for rd. for all quality parameters id and id were graded better than rd (p < . and p < . ) but worse than nd (p << . ). pooled ranking results were equivalent despite considerable variation in individual assessments. hu were identical between reconstructions. image noise was similar in nd, id and id but higher in rd. purpose: to determine whether mri susceptibility-weighted imaging can assist in discriminating between inflammatory pathologies and high-grade glioma. methods and materials: susceptibility-weighted imaging (swi) was performed at . t (siemens medical systems) and images were reviewed retrospectively in patients with cerebral inflammatory pathologies and patients with histologically proven high-grade gliomas. only gliomas without mr findings of haemorrhage on t wi were included in the study. the morphological pattern of the susceptibility signal and the anatomic positional relationship between the contrast enhancement areas and susceptibility signals were retrospectively reviewed by consensus of reviewers. the swi morphological pattern was scored as: patchy, nodular, dot-like or linear and designated as inside or outside the zone of contrast enhancement. results: in total, clinically proven inflammatory diseases ( parasitic granulomas, inflammation-demyelinating and neurovasculitis) and lesions were reviewed. patchy, nodular, dot-like susceptibility were demonstrated in both inflammatory and neoplastic lesions, whereas linear susceptibility signals were only identified in the inflammatory diseases. nine of ( %) susceptibility signals were situated outside the contrast enhancement areas in inflammatory pathologies with no susceptibility signals found outside the border of the contrast enhancement areas among all the high-grade gliomas. conclusion: on swi, linear susceptibility signal and/or susceptibility signal located outside the area of contrast enhancement was more frequently presented in inflammatory processes and not found with the high-grade gliomas. this finding may reflect a different pathophysiologic mechanism and distinction of bleeding/ microbleeding occurrence and presentation in inflammatory pathologies compared to high-grade gliomas. inter-session reproducibility of cerebral blood flow ( the morphology of s - disc, l and s body and lumbar spinous processes were evaluated. the positions of aortic bifurcation (ab), right renal artery (rra), superior mesenteric artery (sma) and conus medullaris (cm) were described. comparing with wsl, the diagnostic error in numbering vertebral segments on lumbar mri was evaluated. in lumbarisation, all patients revealed a well-formed s - disc with squared s body. a rhombus-shaped l body in sacralisation and a rectangular-shaped s body in lumbarisation were found. l had the longest spinous process. the most common sites of spinal and paraspinal structures were ab at l body ( . %), rra at l body ( . %) and l - disc ( . %), sma at l body ( . %) and t -l disc ( . %), and cm at l body ( . %). they were located higher in sacralisation and lower in lumbarisation. on lumbar mri, the diagnostic error in evaluation of vertebral segmentation was . %. purpose: the presence of intravertebral gas in the lumbar and thoracic spine, usually secondary to trauma, is a well-recognised radiological phenomenon (kümmel's disease). however, intravertebral gas within a cervical vertebral body is a common but unknown process. we present a series of patients with gas in the cervical vertebral bodies, not associated with traumatism. the aim of this study is to describe this radiological finding and its possible aetiology. methods and materials: our study group included patients who underwent a routine neck ct examination for reasons not related with the cervical spine. all the patients presented air within a cervical vertebral body. we analysed several factors such as age, sex, location of the gas, history of radiotherapy, chemotherapy, the presence of degenerative disease, previous infections or corticosteroid therapy. results: the mean age was years (age range - ), men and women. the main affected body was c ( %), followed by c ( %). most of the lesions were adjacent to the inferior endplate of the vertebral body. most subjects showed degenerative changes ( %), although none had gas within intervertebral discs. % of the patients received radiotherapy. none of the patients had a history of trauma, infection or treatment with corticosteroids. the presence of gas within a cervical vertebral body seems to be a common but unknown process. this phenomenon could be related with cervical degenerative disease. further studies should be conducted to verify this hypothesis and to elucidate the nature of this finding. the study comprised of n= intracranial tumours, among these meningeomas (n= ), solitary metastasis (n= ), as well as who grade ii -iv tumours (n= ). compared to reference tissue, meningeomas were significantly stiffer. metastases were either slightly firmer or softer than reference tissue. who grade ii and iii tumours (n= ) were softer than white matter in all cases. the highest loss of tissue stiffness was represented by who grade iv tumours. viscoelasticity parameters were supplemented by a histopathology work-up. in summary, high who grade tumours were significantly softer than tumours of lower staging, the range of metastatic viscoelasticity was slightly higher than primary brain tumours. mre was well tolerated by all patients. conclusion: mr elastography of cerebral tumours at tesla reliably quantifies tissue firmness for preoperative planning. according to our histology correlated preliminary results, tumour viscoelasticity may be an additional diagnostic parameter for non-invasive tumour differentiation. intra-and inter-scanner test-retest reliability of whole-brain arterial spin labeling perfusion mri b. wu, x. wu, x. lou, m. ge, l. ma; beijing/cn ( @qq.com) purpose: perfusion mri can be used to identify and monitor patients with acute ischaemic stroke. the objective of this study was to investigate whether it is possible to pool together whole brain arterial spin labelling (asl) perfusion imaging data at different times, or from different scanners, located at two different sites. eight healthy subjects were scanned on two different . t scanners with d pseudo-continuous labelling technique. scans were repeated intra-session and inter-session after - days. the asl data with two postlabelling delay time (pld) of . and . seconds were acquired. high-spatial-resolution whole brain t -weighted images were also acquired for image registration and normalisation into a standardised space within the spm . the cerebral blood flow (cbf) values of grey matter, white matter, frontal lobe, parietal lobe, occipital lobe, temporal lobe, putamen, posterior cingulate, and thalamus were extracted for comparison, using wfu pickatlas tool. the intra-and inter-scanner reliability was evaluated with the intraclass correlation coefficient (icc purpose: to quantify the changes of myocardial transverse relaxation times (Δt *) induced by hyperoxic respiratory challenge at different field strengths in an intraindividual comparison of healthy volunteers. methods and materials: blood oxygen level-dependent (bold) cardiovascular magnetic resonance (cmr) data were acquired in ten healthy volunteers ( women; men; median age years, range - years) at . t and . t. medical air ( % o ), pure oxygen and carbogen ( % o , %co ) were alternatively administered in a block-design temporal pattern to induce normoxia, hyperoxia and hyperoxic hypercapnia, respectively. parametrical t * relaxation time maps were computed, average t * values were derived from region-of-interest analysis by two independent and blinded readers in standard myocardial segments on short axis slices per patient. results: inter-and intra-reader correlations of t * measurements were good (icc= . and icc= . , both p < . ). under normoxia, the mean t * values were . + . ms at . t and . + . ms at . t. both hyperoxic gases induced significant (p < . ) relaxation time increases Δt * (oxygen: . t, . + . ms; . t, . + . ms; carbogen: . t, . + . ms; . t, . + . sm). as opposed to . t, the magnitude of Δt * response was higher at . t and under carbogen as compared with oxygen breathing (p < . ). the myocardial Δt * response to hyperoxic respiratory challenge can reliably be quantified with bold cmr. the magnitude t * increases significantly with a higher field strength as well as with carbogen as compared to oxygen breathing. future studies are warranted to investigate the potential diagnostic role of bold response in assessing patients with coronary cardiomyopathy. we retrospectively reviewed the imaging features and enhancement pattern of the selectively involved white matter tracts in sixteen ( ) genetically proven cases of leukodystrophy with brainstem and spinal cord involvement and elevated brain lactate (lbsl). all patients were presented with slow progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. mri of the brain and spine and mrs of the brain were done to all patients. results: in all cases, mri showed signal abnormalities in the sensory and pyramidal white matter tracts in addition to inhomogeneous signal abnormalities in the periventricular and deep white matter, brain stem, cerebellar connections and dorsal columns of the spinal cord. the subcortical u fibres were spared in all cases. proton mrs showed consistent elevation of the lactate within the abnormal white matter. in eleven cases, diffusion restriction was found in most of the length of the corticospinal and sensory tracts in addition to involvement of the superior and inferior cerebellar peduncles and the mesencephalic trigeminal tracts. these parts of the white matter tracts also displayed heterogeneous enhancement after gadolinium administration. purpose: the purpose of this study was to evaluate the role of dti in assessing cervical spondylotic myelopathy (csm). we prospectively evaluated patients with symptomatic csm. the joa (japanese orthopedic association) myelopathy score was used to assess the clinical situation, dividing patients into groups with minimum myelopathy (mim), moderate myelopathy (mom) and severe myelopathy (sem). all patients underwent examination on a . t mri scanner (verio, siemens). dti of the spinal cord was performed in directions (b-value of and ). fractional anisotropy (fa), apparent diffusion coefficients (adc), eigenvalues (e , e . ) were measured. results: mean patient age was . y/- , sd. according to the joa classification, patients were classified into the mim group and into the mom and into the sem group. significant differences were seen in adc ( . ± . vs . ± . ) values and fa ( . ± . vs . ± . ) when comparing normal with pathological levels as well as in e ( . ± . vs . ± . ) and e . ( . ± . vs . ± . ), respectively. significant elevation of adc and reduction of fa was seen in absolute vertebrostenotic segments. significant elevation of e and e . were seen in vertebrostenotic segments compared with normal. conclusion: our results suggest a high sensitivity of dti metrics in the assessment of csm. significant increases in longitudinal and transverse diffusion were seen in our results which might represent a novel biomarker of csm. molli was performed at a mid-ventricular slice location pre-and - min ( min intervals) post-contrast administration. t values of the blood pool and the myocardium were measured for each time point and ecv assessment was based on myocardial Δr assessment (pre and post) in relation to Δr blood pool and incorporation of the haematocrit. results: while pre-contrast t values were similar (p= . ), post-contrast t values were significantly shorter at any measured time point post-injection after gadobutrol application (p < . ). myocardial ecv data though calculated for both agents did not show significant differences (p> . ). in addition, ecv data related to both agents did not show any significant differences over the assessed time course of - min p.i. (p> . , gadobutrol; p> . , gadoterate meglumine). conclusion: gadobutrol leads to a significantly higher shortening of myocardial t values as compared to gadoterate meglumine. the ecv assessment which is independent of the ca properties can be adequately evaluated as early as min p.i. in normal myocardium. purpose: existence of vortical blood flow in the main pulmonary artery as diagnostic criterion for diagnosis of pulmonary hypertension was analysed in -dimensional ( d) vector field and streamline representations. methods and materials: subjects with known or suspected pulmonary hypertension ( patients with and without pulmonary hypertension, age ± years) underwent right heart catheterisation and time-resolved, d phase contrast imaging of the main pulmonary artery. blood flow patterns were visualised as d velocity vector fields projected on -dimensional anatomical images ( d-vectors) and as d streamlines using d-flow software (siemens). relative period of existence of vortical blood flow within the cardiac cycle (tvortex) was evaluated. comparison of methods for using tvortex as diagnostic criterion for pulmonary hypertension was performed by receiver operating characteristic analysis. results: areas under the curve for diagnosis of pulmonary hypertension did not differ significantly (p= . ) and were . ( %-confidence interval . to . ) in case d-vector vortex detection and . ( %-confidence interval . to . ) in case of streamline vortex detection. the optimal tvortex cut-off value maximising sum of sensitivity and specificity was tvortex= . for both visualisations. resulting %-confidence intervals for sensitivity and specificity were . to . and . to . in case d-vector vortex detection and . to . and . to . in case d streamline vortex detection. conclusion: main pulmonary artery blood flow patterns provide an accurate tool for the diagnosis of pulmonary hypertension with the optimal tvortex cut-off value . . s a c d e f g b conclusion: using mbir significantly reduced the need for vessel-wall boundary corrections compared to other reconstruction algorithms, particularly at the side of calcifications. thus, mbir improves the feasibility of automated plaque assessment in ccta and potentially its clinical applicability. calcium score of small coronary calcifications on multi detector computed tomography: a phantom study j.m. groen , k.f. kofoed , m. zacho , r. vliegenthart , t.p. willems , m.j.w. greuter ; groningen/nl, copenhagen/dk (m.j.w.greuter@umcg.nl) purpose: to assess the feasibility of a new phantom which enables establishment of a calcium scoring protocol for multidetector computed tomography (mdct) that yields calcium scores comparable to electron beam tomography (ebt) values and to physical mass. methods and materials: a phantom containing small calcifications ranging . - . mm was scanned on ebt using a standard coronary calcium protocol, and on a -row mdct scanner using different scanning, reconstruction and scoring parameters (tube voltage - kv, slice thickness . - . mm, reconstruction kernel fc -fc and scoring threshold - hu). the agatston and mass score were compared and the influence of the parameters was assessed. results: on ebt, the agatston and mass scores were - , and - mg, respectively. on mdct, the agatston and mass scores were - , and - mg, respectively. the agatston score on mdct differed % between and kv, % between . and . mm and % between fc and fc . more calcifications were detected with a lower tube voltage, a smaller slice thickness, a sharper kernel and a lower threshold. an acquisition protocol with kv and two reconstructions protocols could be defined. this protocol yielded agatston scores as close to ebt as possible, as well as mass scores as close to physical mass as possible. purpose: Τo report -year results of a prospective randomised controlled trial investigating angioplasty with paclitaxel-coated balloons (pcb) versus plain balloon angioplasty for the treatment of failing arteriovenous dialysis access either a fistula (avf) or a graft (avg). this was a non-inferiority hypothesis trial registered in clinicaltrials.gov (nct ). enrollment criteria included an angiographic and clinical diagnosis of dysfunctional dialysis access due to at least one stenotic lesion in patients with avf or avg circuits. forty patients were randomised to undergo either pcb dilatation (n= ) or standard pta (n= ) of a venous outflow stenotic lesion. regular angiographic follow-up was scheduled every months. study primary endpoints included technical success (defined as residual stenosis of the treated lesion > % without any significant dissection) and -year primary patency of the treated site (defined as angiographic visualisation of a patent lesion with < % restenosis and no need for any additional repeat procedure within the previously treated lesion due to failing access). results: baseline variables were comparably distributed among the two groups. technical success was % for both groups. additional post-dilation with a highpressure balloon was necessary in / ( %) of the pcb-treated cases. at year, cumulative target lesion primary patency was significantly higher after pcb application ( % in pcb group versus % in pba group, p < . , hr ( %ci) = . ( . - . )). conclusion: pcb angioplasty might have a place in our quiver for the treatment of stenotic venous outflow lesions of failing dialysis access. for better trade-off of high temporal resolution, less noise and streak artefacts. this is combined with an automatic segmentation and suppression of catheter-induced streaks. this preliminary study included in vivo porcine models. images were evaluated by experienced cardiologists with respect to noise, temporal resolution and artefact susceptibility. results: an enhancement of temporal resolution was shown by a decreased fullwidth at half maximum of catheter cross sections using sr d-fd-ct as compared to static reconstructions. motion-map-processing of individual phases increased the contrast-to-noise ratio for each heart phase, e.g. in the left ventricle by an average of %. visual impression confirmed a significant streak reduction. conclusion: first results show the potential of sr d-fd-ct for pragmatic dinterventional imaging. sr d-fd-ct allows for dynamic segmentation of cardiac chambers and valves. purpose: for quantitative measurement of left ventricular myocardial perfusion, stability of hu-values in dynamic ct-scans is essential. a phantom study is used to evaluate this stability over slices and time using the philips ict -slice scanner. methods and materials: seven time series of ct-images with slices ( mm) over seconds of a catphan phantom were acquired using the ict at kvp/ mas. six different regions of interest (roi) were placed into the water regions of the phantom for all slices and time steps. five rois were arranged in a star-like pattern in order to enable evaluation of intra slice variability. one roi covered the entire water-region. stability over time and slices as well as within each slice was statistically examined. the absolute difference in the mean values of the entire water roi in all seven phantom studies was maximum . hu. the examination of the inter-slice variability revealed a drift of maximal . hu/slice. over time, a maximal drift of . hu/s could be observed. the maximum intra-slice difference of the mean values was at hu. this slightly higher value is due to beam hardening artefacts in the rois close to the high-density /bone simulating/ structure in the phantom. purpose: to evaluate the impact of iterative image reconstruction algorithms including adaptive statistical (asir) and model based (mbir) on the feasibility of automated plaque assessment in coronary computed tomography angiography (ccta) as compared to filtered-back-projection (fbp) reconstructed algorithm. methods and materials: three ex-vivo human hearts were imaged by ccta and reconstructed with fbp, asir and mbir. an automated plaque quantification software (vitrea cardiac solutions, mn) was applied for each of the algorithms to fit the outer and inner vessel-wall boundaries. each coronary cross section, in which the automated software detected wrongly the boundaries, was corrected in a random and blinded fashion. the percentages of corrections were compared between the reconstruction algorithms using chi-square-test. results: a total of ccta cross sections with . mm increments were assessed which equals to co-registered triplets (fbp/asir/mbir). any boundary corrections were performed in a total of cross sections ( . %), including outer (n= ) and inner (n= ) vessel-wall. the percentage of corrected cross sections was lower for mbir ( . %) as compared to asir ( . %, p= . ) and fbp ( . %, p < . ), and marginal between asir and fbp (p= . ). regional agreement of performed corrections existed between reconstruction algorithms (kappa= . ). the benefit of mbir above fbp was associated to the presence of moderate and severe calcification (or: . and . , p < . , respectively). were reviewed to classify arterial involvement according to: ) tasc ii, ) graziani's morphological classification, ) joint vascular society council calf and foot scores. clinical results (healing, non-healing, major amputation) were compared to baseline clinical data and angiographic results. results: percutaneous procedures were performed; the immediate technical success rate was . %. preprocedurally, the mean±sd calf and foot scores were . ± . and . ± . , respectively; patients ( . %) were in graziani's morphological classes to ; in ( . %) cases tasc ii was inapplicable, for the absence of femoro-popliteal lesions. post-procedurally, mean calf and foot scores were . ± . and . ± . , respectively, and . % of cases were into the graziani's classes and , whereas tasc ii was inapplicable in all cases. healing and major amputation rates were . % and . %, respectively; only pre-and post-procedural foot scores were significantly associated with the clinical outcome (p <. ). conclusion: endoluminal revascularization represents a valuable treatment option in diabetic patients with cli. in this population, tasc ii is inadequate to describe peripheral arterial involvement. pre-and post-procedural foot scores represent the most significant angiographic parameter to evaluate treatment success, thus aggressive treatment of foot arteries should be attempted whenever possible. months results of a randomised trial comparing mono-or dual-antiplatelet therapy in interventionally treated patients with peripheral arterial disease f.f. strobl , j. schmehl , k. brechtel , t. zeller , c.d. claussen , g. purpose: in this trial, peri-and postinterventional dual antiplatelet therapy significantly reduced rate of target lesion revascularisation after months. it is not known whether this effect persists after stopping clopidogrel. thus, we conducted an additional follow-up after months. in this double-blinded, randomised trial, we enrolled patients who were treated with pta or stenting in the upper leg. patients received pre-and postinterventional dual therapy with aspirin and clopidogrel. the other patients received same doses of aspirin and placebo instead of clopidogrel. clopidogrel/placebo was stopped after months and patients remained on aspirin only. tlr and mortality rate were reevaluated months after the intervention. results: we initially enrolled patients ( male, ± y), in each group in the study. months after the intervention, clopidogrel and placebo patients could be reevaluated. at months, clopidogrel patients had significantly lower rates of tlr compared to placebo patients: ( %) vs. ( %), p= . . after stopping clopidogrel/placebo, there was no more significant difference in tlr months after study inclusion with ( %) clopidogrel vs. ( . %) placebo patients (p= . ). mortality was vs. at months (p= . ) and vs. at months (p= . ). conclusion: in contrast to the first follow-up months after the intervention according reduction of tlr, this advantage of dual antiplatelet therapy does not persist after stopping clopidogrel. prolonged dual therapy (> months) should be evaluated and considered in patients with high risk for restenosis. comparing d angiography, d rotational angiography, and preprocedural ct image fusion with d fluoroscopy for endovascular repair of thoraco-abdominal aortic aneurysm v. tacher , m. lin , p. desgranges , t. grünhagen , a. luciani , j.-p. becquemin , j.-f. deux , a. rahmouni ; creteil/fr, briarcliff manor, ny/us, best/nl purpose: to evaluate the feasibility of pre-procedural arterial phase computed tomography image fusion with intra-procedural fluoroscopy (or image fusion: if) road-mapping in endovascular repair of thoraco-abdominal aortic aneurysm (evr-taaa) compared to current road-mapping methods ( d and d angiographies) in terms of x-ray exposure, injected contrast volume, and procedure time. methods and materials: single-institution prospective study (internal institute approved), on patients, informed written consent provided, and treated for evrtaaa. all interventions were performed on the same angiographic system. patients were consecutively placed in three groups in a seven-month period: " d angiography" ( da) ( patients), " d rotational angiography" ( da) ( patients) and "image fusion" (if) ( patients). injected contrast volume, x-ray exposure (dose-area-product: dap) and procedure time were recorded. to compare the groups in terms of the above measures and general patient characteristics, statistical tests using fisher's exact, kruskal-wallis and mann-whitney were performed. results: patient characteristics and stenting types were similar between all three groups with no statistically significant differences (p-value> . ). the if lower limb multilevel treatment with drug eluting balloon: -month results from the "debellum" trial f. fanelli, a. cannavale, p. lucatelli, a. wlderk, c. cirelli, f.m. salvatori; rome/it (fabrizio.fanelli@uniroma .it) purpose: to report -month results of the "debellum"-drug-eluting balloon evaluation for lower limb multilevel treatment-trial performed to evaluate the efficacy of drug-eluting balloon-deb versus conventional balloon catheter-ncb in the treatment of peripheral arterial disease. methods and materials: fifty consecutive patients (mean age ± years) with symptomatic peripheral arterial disease were randomised between deb ( patients- lesions) (inpact®-medtronic) and ncb ( patients- lesions). inclusion criteria were native single or multiple stenosis or occlusion (mean lesion length . ± . cm) in the femoro-popliteal or below the knee (btk) regions. dilatation was performed in each group either for native lesions ( deb; ncb) or post-stent implantation ( deb; ncb). primary end points were late lumen loss (lll) at and months. secondary end-points were target lesion revascularisation (tlr), amputation and thrombosis rate. results: one-hundred-twenty-two lesions were treated: . % in the femoropopliteal area; . % btk; . % total occlusions. lll was . ± . mm (deb) vs. . ± . mm (ncb) (p < . ) at months and . ± . mm (deb) vs. purpose: this study aimed at assessing retrospectively the middle-term clinical outcome of the femoropopliteal chronic total occlusion (ctos) treatment by means of directional atherectomy (da). methods and materials: between january and march , patients ( limbs, patient age ± years) were included in the study with mean follow-up of months ( - ). femoro-popliteal cto in patients with severe intermittent claudication (n= ; . %) or critical limb ischaemia (cli) (n= ; . %) were treated with silverhawk or turbohawk atherectomy followed by angioplasty in ( . %) cases. clinical and uscd follow-up was set at , and months and yearly thereafter. immediate technical success, disease-free patient survival and target lesion revascularisation (tlr) rates were assessed with kaplan-meier analysis. results: technical success rate was % with a lesion length of ± mm. limbsalvage and survival rates were . and . % at years, respectively. at , and months disease-free patient survival was . , . and . %. whereas adjunctive pta was performed in % cases to improve the angiographic result, % required an associated tibial vessel treatment. no perioperative mortality was observed. one complication ( %) occurred. conclusion: percutaneous directional atherectomy is a safe and effective technique in lower limb revascularisation. preliminary results supported by short-mid term data encourage use of da with silverhawk and turbohawk catheter in the femoro-popliteal obstructive lesions also in traditionally "forbidden districts". longterm data are missing. predictive value of angiographic scores for the integrated management of the ischaemic diabetic foot purpose: treatment of lumbar artery fed type endoleaks (laft e) after abdominal endovascular aneurysm repair (aevar) exhibits high failure and recurrency rates. we report our preliminary results of ct-guided direct sac puncture, followed by embolisation with the liquid embolic agent ethylene vinyl alcohol copolymer (onyx®). methods and materials: male patients (mean age ± yrs) with laft e were included after failure of conservative treatment. all received ct guided direct sac puncture under local anaesthesia, followed by ct fluoroscopic embolisation with onyx ® or ®. follow-up examination included contrast-enhanced ultrasound (ceus) and dual-phase ct angiography every months for at least years (ongoing). results: technical success was achieved in all cases, requiring dual puncture of the aneurysm sac in cases ( . %). average duration of the procedure was ± min. in mean . ml of onyx ® were used per procedure. in cases onyx ® was additionally used for complete filling of the endoleak. repeat intervention was necessary in cases ( . %) due to new endoleak development in the follow-up period of ± months. the procedure failed permanently in case. complications such as major bleeding, spinal ischaemia or non-target embolisations were not observed. conclusion: completely ct-guided treatment of laft e is a feasible and safe treatment alternative. difficulties lay in the determination of the necessary amount of onyx and the end point of the intervention. several punctures as well as repeat intervention might be necessary to achieve permanent endoleak occlusion. purpose: treatment of type endoleaks after endovascular aneurysm repair (evar) can be challenging. we describe a technique for direct embolisation with the liquid embolic agent ethylene vinyl alcohol copolymer onyx by direct catheter access to the endoleak, and present first results. methods and materials: patients ( male, female, mean age +- yrs) with a type a (n = ) or a type b (n = ) endoleak were treated. in cases, it was applied as stand-alone procedure, and in cases in combination with stent graft extension. access was trans-brachial for type a endoleaks, and trans-inguinal for type b endoleaks. a multi-purpose catheter was placed between the aortic wall and the stent graft to access the endoleak, followed by coaxial introduction of a dimethyl sulfoxide (dmso) compatible micro-catheter into the endoleak, and consecutive onyx embolisation. results: technical success was achieved in all cases. a mean volume of ml +- ml of onyx was used. in cases, additional coils were used as an anchor for onyx. patient developed reperfusion of the endoleak during follow-up of +- months, which was successfully treated with the same technique. non-target embolisation, catheter encasement, or anaphylactic reactions to dmso were not observed. the described technique is feasible, safe, and effective for treatment of type a and b endoleaks with excellent technical success rates, and low relapse rates. it can be used as stand-alone procedure or easily be combined with stent graft extension. conclusion: image fusion road-mapping for evrtaaa is feasible and is associated to a statistically significant reduction in contrast volume and a trend towards dap reduction while maintaining similar procedure time. the medium term follow-up was months. cross-tabulations were checked with chi-squared test, or by fisher's exact test. survivorships were analysed by kaplan-meyer product limit method and by cox semiparametric regression. results: technical success was achieved in . %. / presented endoleaks during the follow-up (type = , type = and type = ). during the follow-up there were mortalities, mean time . months (range - ). in survival rates there was no difference between hybrid procedures group (p= . ) and elective or emergency group (p= . ). there was a statistical difference on survival between the group that had endoleaks during the follow-up (p= . ) and who had had necessity of a second endovascular interventional (p= . ). statistical difference on survival was also seen between patients who developed type and endoleaks (p= . ). conclusion: tevar is a safe and effective treatment. the presence of endoleak, special type and the necessity of a second endovascular intervention reduces significantly the survival. selective coverage of the left subclavian artery without recanalization in patients with patent vertebro-vertebral arterial communications during tevar: a single centre study m. lee; seoul/kr (eterna @yuhs.ac) purpose: to evaluate the safety and effectiveness of selective coverage of the left subclavian artery (lsca) without recanalization during tevar in patients with patent vertebro-vertebral arterial communications and to assess morphologic change of the vertebral artery (va) after the procedure. methods and materials: among patients who underwent tevar, patients requiring lsca coverage without pre-emptive recanalization were retrospectively analysed. the patients' ages ranged from to years. vertebro-vertebral arterial communications in all patients were evaluated by contrast-enhanced computed tomography (cect), time-of flight magnetic resonance angiography, or conventional angiography. neurologic complications such as spinal cord ischaemia (sci) or cerebrovascular accidents (cva) were analysed. pre-and post-procedural changes in vas were evaluated on follow-up cect. the overall -day mortality was . % ( / ). none of the patients had an sci or stroke of posterior circulation alone. cva from embolic infarctions occurred in two patients ( . %). transient left arm ischaemic symptoms were present in patients ( . %), but none required secondary interventions. delayed development of type i endoleak occurred due to stent deformity in one patient, who underwent surgery. one patient required re-intervention after a pseudoaneurysm developed at the distal margin of the previously placed stent-graft at ten-month follow-up cect. hypertrophy of the right va after tevar was seen in of patients ( . %); two patients showed bilateral hypertrophy of vas. conclusion: lsca coverage without recanalization can be safely performed during tevar in patients with patent vertebro-vertebral communications. hypertrophy of the right va was noted in . % of patients after lsca coverage. purpose: double-bundle reconstruction with stump preservation has revolutionised the surgical treatment for anterior cruciate ligament (acl) injury. however, poor revascularization at the osteoligamentous interface (oi) of the tibia tunnel remains a major cause of graft complications. in this study, we applied dynamic contrastenhanced (ce) magnetic resonance imaging (mri) to quantify the oi enhancement values of the tibia tunnels and acl stump. we aimed to determine the relationship between graft complications and oi and stump enhancements. methods and materials: from october to april , patients were enrolled in our study (mean postoperative duration, . months). all patients underwent one . -t mri study with the imaging pulse-sequence protocol of proton density-weighted imaging (wi), t wi, pre-enhanced and post-enhanced t wi, and dynamic ce mri. graft complications, including cystic degeneration and tear, were evaluated using pre-enhanced mri, and peak enhancement (epeak) values were acquired from a dynamic ce study. the receiver operating characteristic (roc) analysis was used to obtain optimal cut-off values for complicated grafts. results: our study included patients (mean age, . years). nine patients ( . %) had cystic degeneration and ( . %) had complete posterolateral (pl) bundle tear. mean epeak percentages for graft with or without complications were . %/ . % for anterior--medial (am) bundle, . %/ . % for pl bundle, and %/ . % for stump, respectively. roc analysis yielded the optimal epeak cut-off values of %, %, and % for am bundle, pl bundle, and stump, respectively. conclusion: graft complications were directly associated with higher tibial oi values but inversely associated with higher stump values. purpose: to test if the posterior cruciate ligament (pcl) index is predictive of rotational knee kinematics during pivoting activities and anterior tibial translation (att) in patients after anatomic single-bundle (sb) anterior cruciate ligament reconstruction (aclr). sixteen patients with sb-aclr were prospectively evaluated with d-motion analysis during ( ) descending and pivoting, and ( ) landing and pivoting. the side-to-side difference of tibial rotation range of motion (ssdtr) between the aclr and the contralateral intact knee was calculated. att ssd was measured with a kt- arthrometer. mri was used to measure the pcl index for the study group and a control group. linear regression models were used with pcl index as predictor of ssdtr for each task and side to side anterior translation differences. unpaired sample t-test was used to compare pcl index group means between the study and control group. the level of significance was set at α= . . results: pcl index of the aclr knee was significantly lower compared to the healthy control knee (p < . ). the pcl index was predictive of low ssdtr during pivoting after descending and landing tasks (r = . , p= . and r = . , p= . respectively). pcl index was not predictive of att with n or maximum manual force (r = . , p= . and r = . , p= . respectively). the pcl index after anatomic sb aclr is predictive of rotational kinematics during dynamic pivoting activities. these results suggest that after anatomical aclr the pcl index can serve as an indicator of tibial-femoral position and may predict dynamic tibial rotation. microstructural evaluation of the cruciate ligaments with mr diffusion tensor imaging (dti): correlations with knee stability l. di clemente , d. tortora , v. panara , m. savastano , v. calvisi , p. palumbo , a. tartaro , a.r. cotroneo , m. caulo ; chieti/it, l'aquila/ it (lorisdiclemente@gmail.com) purpose: the evaluation of knee stability is currently based on tibio-femoral sagittal plane motion measurement as evaluated using the kt- arthrometer. conventional mri cannot evaluate knee stability. the aim of the study was to assess the use of mr-diffusion tensor imaging (dti) as a tool for a microstructural examination of the anterior and posterior cruciate ligaments and to correlate dti finding with clinically evaluated stability. methods and materials: subjects ( females) without previous history of knee injuries underwent mri using conventional and dti sequences. fractional anisotropy (fa) values were calculated in each anterior and posterior cruciate ligament within different rois placed in the lower, middle and upper portion of the ligaments. knee stability was assessed using kt- arthrometer in progressive active displacements: lbs, lbs, manual maximum displacement and under quadricipital muscle contraction. statistical analysis was performed using independent t-test and kendall tau rank correlation test, where appropriate (p < . ). results: fas of the acl (mean: . ± . ) were significantly lower compared with the pcl (mean: . ± . ) (p < . ), whereas no side differences were noted. a significant negative correlation between fa and kt- arthrometer values at lbs was present in the pcl (r=- . ; p= . ). no correlations were observed between the fa and kt- values in the acl. conclusion: functional assessment of the microstructural organisation of the cruciate ligaments with dti expands mri applications beyond simple morphological studies and could help bridge the gap between imaging and clinical evaluation of knee stability. the schatzker classification for tibial plateau fractures and the amount of articular depression were assessed using mdct. magnetic resonance images were evaluated for crucial and collateral ligament injury, meniscal tears and patellar retinaculum lesions. statistics included logistic regression and analysis of covariance. results: associated soft-tissue injuries were identified in % of the patients. logistic regressions revealed a significant impact of increasing amounts of tibial plateau fracture depression on the incidence of meniscus lateralis tears (p = . ) and lesions of the anterior cruciate ligament (p = . ). analysis of covariance demonstrated a significant correlation between the amount of articular depression and the absolute number of soft-tissue injuries (p = . ). conclusion: articular depression is a potential predictor of specific meniscal and ligamentous injuries in acute tibial plateau fracture. due to the high incidence of associated soft-tissue lesions, magnetic resonance imaging is generally recommended, especially in cases with distinct tibial plateau fracture depression at mdct imaging. anatomical risk factors in patients after patellar dislocation: a casecontrol study using mri t. köhlitz, s. scheffler, t. jung, e. wiener, b. vollnberg, g. diederichs; berlin/ de (bernd.vollnberg@charite.de) purpose: to assess anatomical risk factors in patients after lateral patellar dislocation (lpd) and controls using mri. methods and materials: mr images of knees after lpd and of age-and gender-matched controls were analysed. the presence of trochlear dysplasia was assessed by evaluation of trochlear inclination, facet asymmetry, and trochlear depth; patella alta was evaluated by insall-salvati-index and caton-deschampsindex; and lateralized force vector was measured by the tibial tuberosity-trochlear groove (tt-tg) distance. results: compared with controls, dislocators had significantly lower values for all three parameters of trochlear dysplasia (- %, - %, - %) and significantly higher values for patella alta (+ %, + %) and tt-tg (+ %) (all p < . ). trochlear dysplasia was observed in dislocators ( %), of whom ( %) additionally had patella alta and ( %) an abnormal tt-tg. as isolated risk factors, patella alta ( %) and abnormal tt-tg ( %) were rare. only dislocators ( %) had no anatomical risk factor. trochlear dysplasia in conjunction with abnormal tt-tg or patella alta is associated with a -fold and -fold higher risk. conclusion: most dislocators have anatomical risk factors, varying in severity and constellation. trochlear dysplasia is the main risk factor for lpd, while patellar alta and abnormal tibial tuberosity-trochlear groove distance may be additional factors. patient-specific evaluation of risk factors following lpd may help future management. early changes of trabecular bone structure in asymptomatic subjects with knee malalignment t. baum, j. penzel, m. sauerschnig, e.j. rummeny, k. wörtler, j.s. bauer; munich/ de (thbaum@gmx.de) purpose: knee malalignment is a risk factor for knee osteoarthritis (oa). the purpose of this study was to investigate whether alterations of trabecular bone structure can already be found in young, asymptomatic subjects with knee malalignment. methods and materials: forty-eight asymptomatic subjects ( females, males; age: ± years) without history of knee injury or surgery were included in this study. based on mr measurements, knee joint alignment of both lower extremities was assessed and subjects were divided into four groups (each including subjects, i.e. knees): neutral (up to ° varus/valgus), mild varus ( °- °), severe varus (greater °), and valgus ( °- °). a t -weighted d-flash sequence (spatial resolution: . x . x . mm³) was obtained of each knee at . t to determine histomorphometric and texture parameters of the trabecular bone in the medial/ lateral femur/tibia (mf,lf,mt,lt). the calculated parameters were compared between the four groups in each compartment using anova including bonferroni correction for multiple comparisons. purpose: we performed a randomised, double blinded, placebo controlled study to assess the effectiveness of lllt in patients with knee pain related to meniscal pathology. the study trial number is isrctn . we only included symptomatic patients with tiny focus of grade attenuation (seen only on . thickness sequences) or intrasubstance tears with spot of grade signal intensity approaching the articular surface. none of the patients in the study group underwent arthroscopy or new mri investigation. a paired samples t-test was used to detect significant changes in subjective knee pain over the experimental period within groups, and anova was used to detect any significant differences between the two groups. results: pain was significantly improved for the lllt group than for the placebo group (f= , p < . ). pain scores were significantly better after lllt. four ( . %) patients did not respond to lllt. at baseline, the average lysholm score was ± . for the lllt group, and . ± . for the placebo group [p> . ]. four weeks after lllt or placebo therapy, the laser group reported an average lysholm score of . ± . , the placebo group scored . ± . . at months, the laser group had an average lysholm score of . ± . , an after one year they scored . ± . (f= . , p= . ). treatment with lllt was associated with a significant decrease of symptoms compared to placebo. in patients with small meniscal tears who do not wish to undergo surgery, lllt should be considered as a non-invasive alternative. is not clear, i.e. whether meniscal injury leads to cartilage degeneration or vice versa. therefore, we aimed to evaluate the impact of meniscal tears on adjacent, morphologically intact knee cartilage using t relaxation time, a sensitive biomarker for early cartilage degeneration, and compare with healthy controls. methods and materials: sixty-nine subjects without evidence of oa were recruited from the osteoarthritis initiative. thirty-five subjects ( -women) with a normal medial meniscus were used as controls (age ± , bmi ± ). thirty-four subjects ( -women) had either a simple (non-displaced tear; n= , age ± , bmi ± ) or complex tear (displaced tear; n= , age ± , bmi ± ) of the posterior horn of the medial meniscus. none of the tear-subjects had morphological lesions of the medial tibio-femoral cartilage. t -measurements were performed in the whole medial tibia (mt) and the medial femur compartments (mf), and in tibio-femoral subregions adjacent to the torn meniscus (smt & smf). multiple linear-regression models were used to compare mean t -values of individuals with meniscal tears with normal controls. purpose: patients with good or complete response after neoadjuvant chemoradiation have excellent long-term outcome. minimal invasive treatment (i.e. transanal endoscopic microsurgery (tem) and wait-and-see policy) are increasingly considered as an alternative to major surgery. with this prospective cohort study we aimed to evaluate long-term outcome of strictly mr-based selected patients who have been treated with minimal invasive treatment. methods and materials: eight weeks after chemoradiation, endoscopy and restaging mri were performed (including diffusion-weighted mri for yt-staging and gadofosveset-enhanced mri for yn-staging). complete responders were selected for wait-and-see policy and good responders with small tumour remnant for tem. both treatment groups underwent intensive -to- monthly follow-up, using mr imaging (dwi+gadofosveset), cea, ct of thorax and abdomen and endoscopy was performed. long-term outcome was estimated with kaplan-meier curves. results: forty-one patients were included, thirty-three in the wait-and-see group and eight in the tem-group. mean follow-up was months (range - ). for the tem-group, patients had ypt and had ypt . two patients, both in the wait-and-see group, developed a local recurrence within two years and underwent surgery, leading to a -year local recurrence rate of %. both recurrences were detected on (dwi-)mri in an early stage. the cumulative probabilities of -year disease-free survival and overall survival were % and %, respectively. no recurrences occurred in the tem-group. conclusion: both selection and follow-up of good and complete responders after chemoradiation for rectal cancer with mri is feasible. long-term outcome so far is excellent. (dwi-)mri seems to be a reliable tool for early recurrence detection. diffusion-weighted-based volumetry in the assessment of response in patients with rectal cancer treated with neo-adjuvant therapy: feasibility study s.f. carbone, m. palumbo, v. ricci, l. pelliccia, e. cacchiarelli, l. volterrani; siena/it (fracarb@gmail.com) purpose: to establish the reproducibility of volumetric magnetic resonance diffusion (vdwi) and compare it with the conventional volume (vc) in the assessment of response in patients with rectal cancer treated with chemoradiotherapy (crt). we retrospectively examined patients (mean age . years) with rectal cancer who have performed mri before and after ± days of the crt after undergoing anterior resection of the rectum. after surgery, yptn and trg (tumour regression grading) according to mandard classification were obtained. we considered patients with trg - responder and non-responder patients with trg - . two radiologists, blinded, have extrapolated the volume vc and vdwi lesions pre-and post-crt. the inter-observer agreement and the agreement between vc and vdwi pre-and post-crt were calculated by intraclasscorrelation coefficient (icc). the inter-observer agreement for vc and vdwi was . and . respectively, while the correlation between vc and vdwi investigating pre-crt was . and in the post-crt in . . after crt, vc shows a correlation with the trg of rho = . (p < ), while a significant linear relationship was evident between vdwi and trg with rho = (p < . ). post-crt the vdwi shows a significant difference between responders and nonresponders (p = . ). the vdwi is a reproducible quantitative technique in assessing the response to crt in patients with rectal cancer and shows a better correlation with the residue of the disease compared with the vc. therapy response assessment in locally advanced rectal cancer: comparison between functional dynamic and diffusion parameters in mri r. fusco, v. granata, m. petrillo, m. sansone, a. petrillo; naples/it (roberta.fusco@unina.it) purpose: we investigated the diagnostic performance of dce-mri and dw-mri in evaluating neoadjuvant chemo-radiotherapy (crt) response in larc. we compared a semiquantitative dynamic feature, the standardised index of shape (sis) and the diffusion parameters obtained using intravoxel incoherent method. purpose: to compare image quality and detection of clinical findings of the new warp sequence versus conventional optimised mr sequences in patients with total knee arthroplasty (tka). methods and materials: forty-two patients with tka underwent . t mri in this prospective study. slice-encoding metal artefact correction (semac), view-angle tilting (vat), and increased bandwidth were combined by the "warp"-turbo spin echo sequence. twenty-four patients underwent ct as a reference standard. coronal stir-warp and sagittal intermediate-weighted (pd) warp-sequences were compared to standard sequences optimised with high readout bandwidth (stir-hibw/pd-hibw). signal void was quantified. qualitative criteria (depiction of anatomy, distortion, blurring, noise) were assessed on a five-point scale ( , no artefacts; , severe artefacts) by two readers. clinical findings (e.g. periprosthetic osteolysis) were noted. a t-test (quantitative data) and a wilcoxon signed rank test (qualitative data) served for statistics. results: signal void areas were smaller for stir-warp than stir-hibw (mean; . cm / . cm ), and for pd-warp than pd-hibw ( . cm / . cm ; p <. for all comparisons). depiction of anatomic structures was better on stir-warp versus stir-hibw ( . - . vs. . - . ; p <. ), and on pd-warp versus pd-hibw ( . - . vs. . - . ; p <. ). distortion and image noise were lower for warp than for the standard sequences (p <. ), while blurring was similar for both techniques. there was a statistically significant advantage for detection of clinical findings for stir-warp versus stir-hibw ( and findings; p <. ) and for pd-warp versus pd-hibw ( and findings; p <. ). the warp sequences showed a statistically significant improvement for most image criteria. detection of clinically relevant findings was markedly increased. : purpose: to determine the diagnostic accuracy of mr in patients with rectal carcinoma by comparing post-chemoradiation mr imaging with pathological specimens. we enrolled patients with a locally advanced rectal cancer. all patients received chemoradiation therapy before surgery. those patients underwent a neoadjuvant chemoradiation therapy followed by mr scans. the mr images were analysed by a team of two expert radiologists to whom clinical and histo-pathological findings were unknown. results: following neoadjuvant chemoradiation therapy, we observed ( %) patients with a rectum disease staged ² t and ( %) patients with a disease staged > t , after mr images analysis. post-treatment histological staging (tnm) analysis revealed patients with a disease > t and patients with a disease ² t . by arranging the kappa cohen test to find the agreement value between post-chemoradiation mr staging and histological response, we found that with a disease confined to the sierosa (² t ) the agreement was . %. we found an agreement of . % between mr and histology for a disease ² n and an accord of . % for a disease more advanced than n (> n ). conclusion: mr is critical in discovering a t disease; moreover, with morphologic mr imaging we do not have always the opportunity to discern a few residual cancer cells hidden in the fibrotic tissue that could cause a crm involvement on histology. monday fascia infiltration was present on the surgical specimen. in patients reticular (n= ) or linear-shaped (n= ) mesorectal enhancing strands were observed. reticular-shaped mesorectal enhancing strands were predictors of mesorectal fat infiltration (odds ratio, . ; % confidence intervals, . - . ; p < . ) but not of mesorectal fascia infiltration ( . ; . - . ; p= . ). the enhancing strands reaching the mesorectal fascia represent a predictors of mesorectal fascia infiltration ( . , . - . ; p < . ). the evidence of enhancing strands reaching the mesorectal fascia represents a predictor of mesorectal fascia infiltration and should suggest to intensify the crt. purpose: to show the utility of mdct assessing the tumour response in locally advanced colon cancer treated with neoadjuvant chemotherapy. methods and materials: consecutive patients who underwent this therapy during a -month period were included. all tumours were staged before treatment using mdct or pet-ct scan, and after neoadjuvant treatment other scan was performed by calculating the differences in tumour volumes making use of a dedicated software for semiautomatic volume segmentation, to assess tumour response before surgery. maximum standard uptake value (suv max) by pet-ct between the time of initial diagnosis and after neoadjuvant chemotherapy was also measured. surgical-related complications and oncological outcomes were obtained. results: tolerance to chemotherapy was excellent in . % of patients and . % completed the entire chemotherapy initially planned. after neoadjuvant treatment, . % reduction of tumour volume was observed by ct-scan and up to . % decrease of suvmax (standard uptake value) was achieved by pet/ mdct. none of the patients showed tumour progression during the preoperative treatment, and all of them underwent the previously planned surgical procedure. four patients developed postoperative complications. median time between the end of chemotherapy and surgery was days. conclusion: preoperative chemotherapy induces a tumour response that can be measured by imaging methods (mdct). assessment of the variation in the contrast-to-noise ratio across a range of ct scanners in a multicentre perfusion ct study of colorectal cancer (prospect): a phantom study m. lewis, v.j. goh; london/uk purpose: to determine the effect of ct scanner models, iterative reconstruction (ir) and phantom size on cnr of perfusion ct scans. methods and materials: a -cm diameter water phantom containing different iodine contrast inserts from . mg/ml to mg/ml was scanned on seven ct scanners from four manufacturers using the perfusion ct acquisition protocols of a multi-centre clinical trial in colorectal cancer (prospect). all acquisition protocols employed kv and ~ mm reconstructed slice. images were reconstructed with filtered back projection and iterative reconstruction, where available. ct numbers and background noise levels were measured and displayed ctdivol values noted. a sub-set of measurements was obtained on a -cm diameter phantom. the relationship between ct number and iodine density was determined for all datasets and cnr values calculated. results: a linear relationship between ct number and iodine density was observed, with small variations between ct scanners. no change in linearity was observed with ir of different 'strengths'. ctdivolvalues varied by a factor > . for the lowest density insert, cnr varied from . to . . with ir, cnr increased by a factor of . to . depending on ir'strength'. cnr decreased by ~ % in the cm phantom. the cnr varied by a factor of . across the range of scanners utilised in this mutlicentre study. the variation was largely due to image noise differences. ir does not affect contrast enhancement and can be used to achieve a given cnr at a reduced dose. author disclosures: v.j. goh: equipment support recipient; siemens healthcare, ge healthcare, texrad. research/grant support; nihr hta grant. methods and materials: consecutive patients with larc were enrolled. patients underwent dce-mri and dw-mri ( . t, magnetom simphony tim, siemens, erlangen). an expert radiologist performed a manual segmentation of the whole lesion on a derived series obtained subtracting the basal and the th post-contrastographic series and on dwi with b value= . sis and pure diffusion coefficient, pseudo-diffusion coefficient and perfusion fraction were calculated pixel by pixel. after surgery, tumour regression grade (trg) was obtained. patients with trg - were considered responders and patients with trg - - were considered non-responders. the value changes of each parameters from baseline to presurgical scan were assessed and correlated with the trg. sensitivity, specificity, roc analysis were applied. youden index was used to obtain the optimal cut-off value. mc-nemar test was performed to underline statistical difference. results: seven patients were classified as responders and as non-responders at histology. the diffusion parameter (fraction perfusion) showed a sensitivity of %, specificity of % and area under roc . (optimal cut-off value . %); sis showed a sensitivity of %, a specificity of % and area under roc . (optimal cut-off value . %). a p value of < . was obtained comparing sis vs diffusion parameter. conclusion: sis can achieve the best results in discriminating patients responders from non-responders. reproducibility of mri texture analysis in primary rectal cancer s. gourtsoyianni , g. ljungqvist , a. khan , r. glynne-jones , b. ganeshan , k. miles , v. goh ; london/uk, northwood/uk, falmer/uk (sgty @gmail.com) purpose: this study aimed at assessing the feasibility and reproducibility of mri texture analysis in rectal cancer. methods and materials: following irb approval, patients ( male, mean . years) with primary rectal cancer underwent two baseline mris. t -w axial sequences were exported for texture analysis (texrad, university of sussex). a laplacian of gaussian band-pass filter was applied to highlight different spatial scales (fine ( . ), medium ( . - . ) and coarse ( . ) texture). texture was quantified as entropy (e), uniformity (u), kurtosis (k), skewness (s) and standard deviation of the histogram (sdh) and recorded as for absolute scale values for each tumour. greater heterogeneity is represented by higher e, greater k, s and sdh and lower uniformity. overall group median values were recorded and reproducibility (testretest agreement) was assessed using bland-altman statistics. results: all tumours were greater than stage ii; mean length . cm. good reproducibility was achieved across all filters ( . - . ) for e, u and sdh with mean differences ranging from - . to + . for e; - . x - to + . x - for u; and + . to + . for sdh; and within subject coefficients of variation from . - . % for e, . - . % for u, and . - . % for sdh. there was greater variability for k and s: mean differences ranged from + . to + . for k; and + . to + . for s; within subject coefficients of variation from . - . % for k, and . - . % for s. conclusion: mri texture analysis is feasible in rectal cancer and a reproducible technique in the trial setting. predictors of mesorectal fascia infiltration on spectral pre-saturation inversion-recovery (spir) mr imaging sequence after gadolinium injection in patients with rectal carcinoma after neoadjuvant chemoand radiation therapy e. quaia, l. de paoli, a. gennari, b. cabibbo, m. cova; trieste/it (quaia@units.it) purpose: to retrospectively assess the value of spectral pre-saturation inversionrecovery (spir) mr imaging sequence after gadolinium injection to identify predictors of mesorectal fat and mesorectal fascia infiltration in patients with locally advanced rectal carcinoma after neoadjuvant chemo-and radiation therapy (crt). methods and materials: sixty-five consecutive patients (mean age: . years, range: - years, m:f : ) with locally advanced rectal carcinoma underwent crt followed by surgery. mr imaging was performed before and after completion of crt using t -weighted fast spin-echo and t -weighted spir sequences before and after gadolinium injection. mr images were assessed by two radiologists in consensus. the evidence of reticular (interwoven strands within the mesorectal fat creating a meshwork) or linear-shaped enhancing strands (strands travelling separately through the mesorectal fat) on mr images were retrospectively correlated to the histopathological findings. results: after crt the disease was either limited to the rectal wall (n= patients) or presented mesorectal fat infiltration (n= conclusion: cedm has a potential impact on the characterisation of breast lesions. intensely enhancing lesions are strongly indicative of a malignant nature, yet, overlap of enhancement patterns still exists and therefore further studies with a larger number of studied population are recommended. clinical feasibility of contrast-enhanced dual-energy mammography (cedem) with a tungsten (w)/titanium (ti) anode/filter combination: a prototype report t. knogler , r. leithner , m. hörnig , f. semturs , m. waitzbauer , g. langs , p. homolka , k. pinker-domenig , t.h. helbich ; vienna/at, erlangen/ de (thomas.knogler@meduniwien.ac.at) purpose: to test the feasibility of cedem with a w/ti anode/filter combination for high energy images in a clinical setting. methods and materials: fifteen female patients with breast lesions were included in this study. cedem was performed with a mammomat inspiration prototype (siemens, germany) before and after i.v. administration of -ml iomeron® (bracco, italy) per kg b.w. at a rate of . ml/sec. dual-energy images were acquired with - kvp and a w/rhodium (rh) anode/filter combination for lowenergy and kvp and a w/ti anode filter combination for high energy. weighted subtraction images were computed for diagnostic work-up. images were assessed by two readers with respect to lesion-enhancement and image quality. a histological work-up was performed in all lesions. results: histopathology revealed eight malignant lesions and seven benign lesions (size range from to mm). all malignant lesions enhanced and were seen from both readers on weighted subtraction images. benign lesions did not enhance thus they were not visualised on weighted subtraction images. image quality was rated excellent from both readers. based on the visibility of the lesion cedem allowed an accurate differentiation of benign and malignant breast lesions. conclusion: cedem with a w/ti anode/filter combination is suitable and feasible. lesion visibility and image quality were excellent. further research is needed to determine the value of cedem in a clinical setting. diffusion-weighted-based mri: volumetry and apparent diffusion coefficient s.f. carbone, m. palumbo, t. carfagno, v. ricci, l. pirtoli, l. volterrani; siena/it (fracarb@gmail.com) purpose: to assess the diagnostic accuracy of volumetric magnetic resonance diffusion (vdwi) and apparent diffusion coefficient (adc) in the assessment of response in patients with rectal cancer treated with chemoradiotherapy (crt). we retrospectively examined patients (mean age . years) with rectal cancer, who have performed mri before and after ± days of the crt after undergoing to anterior resection of the rectum. after surgery, yptn and trg (tumour regression grading) according to mandard classification were obtained. we considered responders patients with trg - or with a negative follow-up recurrence in the next months (only three cases). two radiologists, in consensus and using commercial software, have extrapolated pre-and post-crt vdwi of the lesions and calculated the adc. results: the adc did not show significant differences between responders and not-responders (p = . pre-crt, p = . post-crt); the vdwi of responders was significantly lower in both pre-crt (p = . ) and in post-crt (p = . ) compared with not-responders vdwi. the accuracy in the evaluation of response was of and %, respectively, for the adc and vdwi. the vdwi is more reliable than adc to assess the response to crt in patients with rectal cancer. computed tomography of the bowel: a prospective comparison study between four techniques m. revelli, f. paparo, l. bacigalupo, a. garlaschi, l. cevasco, e. biscaldi, g. rollandi; genoa/it purpose: our purposes were to compare the grade of bowel distension obtained with four different ct techniques dedicated for examination of small intestine (ct-enteroclysis and ct-enterography), colon (ct with water enema), or both (ct-enterography with water enema) and to assess patient tolerance towards each protocol. we recruited four groups of patients. each group corresponded to a specific ct technique, for a total of consecutive patients ( male, female; mean age . ± . years). ct studies were evaluated in consensus by two gastrointestinal-dedicated radiologists who performed quantitative and qualitative analysis of bowel distension. presence and type of adverse effects were recorded. results: ct-enteroclysis provided the best distension of jejunal loops (median diameter mm; range - mm) compared with all other techniques (p < . ). frequency of patients with an adequate distension of the terminal ileum was not significantly different among the four groups (p= . ). at both quantitative and qualitative analysis ct with water enema and ct-enterography with water enema determined a greater and more consistent luminal filling of the large intestine compared with the one provided by both ct-enteroclysis and ct-enterography (p < . for all colonic segments). adverse effects were more frequent in patients from the ct-enteroclysis group (p < . ). conclusion: ct-enteroclysis allows an optimal distension of jejunal loops, but it is the most uncomfortable ct protocol. when performing ct with water enema, an adequate retrograde distension of the terminal ileum was provided in a high percentage of patients. ct-enterography with water enema provides a simultaneous optimal distension of both small and large bowel. s c a d e f g b excellent ( . / . ), but worse for vee ( . / . ). correlations of small arbitrary rois were lower for all parameters. conclusion: perfusion and permeability parameters of dce-mri of rcc are influenced by roi-size and positioning. the best inter-and intraobserver correlation showed definition of whole tumour roi with morphological sequences or plasma flow maps. evaluating tumours or monitoring antiangiogenic therapy, perfusion parameters are more reliable, while permeability parameters are more susceptible to interobserver variability. can a contrast-enhanced ultrasound nephrostogram be used instead of a fluoroscopic nephrostogram: preliminary findings m. daneshi, k. patel, d. huang, m. sellars, p. sidhu; london/uk purpose: the use of contrast-enhanced ultrasound (ceus) has extended beyond traditional uses, and the possibility to delineate percutaneous tubes and drains is achievable. we have compared the traditional fluoroscopic nephrostogram using iodinated contrast agents with ceus nephrostogram to ascertain the accuracy, utility and convenience of the ceus nephrostogram. the standard conventional nephrostogram was performed immediately prior to the ceus nephrostogram. the ceus nephrostogram technique involved diluting . ml of sonovue with ml of normal saline and introduced into the renal collecting system via the nephrostomy tube. digital cineclips and still images were recorded to allow accurate retrospective comparison by two independent reviewers to the reference standard. results: twelve nephrostomies in patients (median age yrs, range - yrs, females and males) were performed and reviewed. the renal pelvicalyceal system was visualised in both ceus and fluoroscopic nephrostograms in / ( %) with one nephrostomy tube identified as being misplaced. the entire ureter was visualised in / ( %) with a ceus nephrostogram compared with / ( %) using traditional nephrostogram. fluoroscopic nephrostogram showed drainage of contrast into the bladder in / ( %) cases compared with / ( %) using ceus. conclusion: preliminary results suggest that ceus nephrostogram is a feasible method to confirm the correct positioning of the nephrostomy tube, image the ureters and determine if there is satisfactory drainage into the bladder. ceus nephrostogram is a suitable alternative for the traditional nephrostogram in patients with contraindications to iodinated contrast agents or if the procedure needs to be performed at the bedside. vena cava anomalies associated with horseshoe kidney on mdct t. ichikawa, j. koizumi, s. kawada, y. imai; isehara/jp (tamaki-i@mars.sannet.ne.jp) purpose: the incidence of vena cava (vc) anomalies in horseshoe kidney (hsk) patients is relatively high because of embryogenesis. we evaluated prevalence and variation of anomalous inferior vena cava (ivc) and superior vena cava (svc) in hsk patients detected using ct. methods and materials: seventy-one patients with hsk and patients with normal kidney (nk) who underwent chest ct were evaluated of prevalence and variation of anomalous svc and patients with hsk and patients with nk who underwent abdominal ct were evaluated of prevalence and variation of anomalous ivc. we reviewed axial ct images with -mm reconstruction interval and compared prevalence of anomalous vc between hsk and nk patients using chi-square test. results: anomalous svc was identified in patients ( . %) in hsk patients: double svcs and persistent left svc without right svc and patients ( . %) in nk patients: double svcs and persistent left svc without right svc. anomalous ivc was identified in patients ( . %) in hsk patients: preisthmic ivc with retrocaval ureter, double ivcs, left ivc, and ivc with azygos continuation and patients ( . %) in nk patients: double ivcs, left ivc, and one ivc with azygos continuation. there was a significantly higher prevalence of anomalous vc in patients with hsk than in those nk on mdct (p < . ). conclusion: hsk patients were frequently found anomalous vc and detection of those anomalies in hsk patients is important during central venous catheter procedures and operation. or excision biopsy. qualitative analysis of cine loops was assessed for each ceus examination by two observers and consensus reached on the pattern and timing of tumour enhancement. perfusion quantification of the lesions was performed where possible, with time-intensity curves were analysed. results: distinct differentiation on enhancement patterns was observed between leydig cell and germ cell tumours. all leydig cell tumours displayed intense early enhancement which persisted for longer than the normal testicular parenchymal enhancement. the germ cell tumours showed loss of the normal linear vascular pattern, but with a more rapid washout of contrast. quantitative analysis confirms the observation, with longer full width at maximum (fwhm) and slower contrast outflow on the time-intensity curves observed in leydig cell tumours comparing to germ cell tumours. with improved diagnostic confidence, testicular-sparing excisions were performed for lesions following pre-operative ceus analysis and unnecessary orchidectomies avoided. we describe, to date the first, consistent differentiating characteristic ceus enhancement pattern in rare benign leydig cell tumours. this observation increases diagnostic confidence, thus allows for testicular-preserving options to be considered. purpose: to describe us and colour-doppler findings in testicular lymphoma and their mimics. we reviewed the us and colour-doppler findings in pts with pathology-proven lymphoma of the testis and compared them with those in patients in whom lymphoproliferative disease was suspected on clinical and us grounds and pathology showed only inflammatory changes. results: lymphoma patients' age range was - years. six had testicular involvement in systemic disease or recurrence; four had primary disease. one had bilateral involvement. seven testes in patients were diffusely involved ( homogeneously; heterogeneously); four had nodular hypoechoic lesions which, in testis, were multiple. all lesions, either focal or diffuse, were hypervascular, with vessels of normal rectilinear shape. in patients with nodular lesions, there was no distorsion of vascular course at the point where vessels entered the mass. findings suggested an infiltrative process, and were confirmed at pathology. the remaining seven patients had history and us features suggesting testicular lymphoproliferative disease. all had hypoechoic focal hypervascular lesions containing vessels with rectilinear course that were eventually proved inflammatory changes ( chronic focal orchitis, idiopathic granulomatous orchitis, brucellosis, tuberculosis). conclusion: in patients over and/or with known lymphoproliferative disease, the presence of hypoechoic, hypervascular testicular lesion with absence of vascular distorsion must suggest lymphoma. care must be taken since, albeit rarely, inflammatory lesions may present the same imaging pattern in the absence of clinical signs and symptoms of inflammation. purpose: to assess the influence of region of interest (roi) size and positioning on parameters of perfusion and permeability and inter-and intraobserver variability of dce-mri of renal cell carcinoma (rcc) and metastases. methods and materials: patients with rcc and patients with metastases were examined with dynamic contrast-enhanced (dce) mri at . t with a half body weight-adapted dose of gadobutrol. analysis with a two-compartment exchange model provided four parameters: plasma flow (fp), plasma volume (vp), permeability-surface-product (ps) and interstitial volume (vee). arterial input function and retrospective respiratory triggering were applied. rois of the whole tumour, circular edge and an arbitrary vital region were defined on morphological sequences and on parametric plasma flow maps. consider tube current modulation (tcm). the aim of this study was to include tcm effects in mc dose simulations and to validate this approach. methods and materials: all measurements were performed on a somatom definition flash scanner (siemens healthcare, forchheim, germany) using three anthropomorphic phantoms: adult alderson-rando, -year-old child and -yearold child. the phantoms were scanned with a trunk protocol using an online tcm system (caredose , siemens healthcare, forchheim, germany). organ dose values were measured using calibrated thermoluminescent dosimeters (tld) for each phantom. mc simulations were performed using impactmc software (ct imaging gmbh, erlangen, germany) based on the d voxelised data derived from acquired ct images. the tool was modified to take tcm curves into account. the current values for different tube positions were extracted from the raw data using manufacturer software. simulated dose values were compared with tld measurements on a chip-by-chip basis. results: for mc calculations without taking tcm data into account the mean differences between measured and simulated dose values amounted to %, %, % for adult, -year-old child and -year-old phantoms, while modelling with tcm reduced the mean differences to . %, . % and . %, respectively. conclusion: mc dose estimates including tcm data were in good agreement with measurements. this technique can significantly improve the accuracy of d-dose assessment. monday kev; pixel size . µm), or at a laboratory set-up with a conventional x-ray tube (n= , kvp, ma, pixel size µm). tomographic images were reconstructed and compared to histopathology. independent readers determined vessel dimensions and signal-to-noise ratios (snr) between gb-pci and absorption images. results: in total, sections were included in the analysis. images from both setups provided sufficient contrast to differentiate vessel layers. there was a strong positive correlation between pci and histology with respect for lumen, intima and vessel wall area for both synchrotron and laboratory-based measurements (pearson's r > . and p < . for all). synchrotron-based images were characterised by significantly higher snrs than laboratory-based images (p < . ). both gb-pci set-ups had superior snrs compared to corresponding absorption-based images (p < . ). inter-reader reproducibility was excellent, with iccs > . for synchrotron and > . for laboratory-based measurements. conclusion: our results demonstrate the feasibility of gb-pci for carotid atherosclerotic plaque imaging using both synchrotron and laboratory-based experimental set-ups. the technique holds promise for accurate vessel wall characterisation. single contrast medium dose peripheral mr angiography is feasible without subtraction using two-point dixon fat saturation purpose: to investigate the feasibility and image quality of subtractionless firstpass single contrast medium dose ( . mmol/kg) peripheral contrast-enhanced magnetic resonance angiography (mra) using two-point dixon fat-saturation ( dixfs) compared with conventional subtraction-based mra with regard to vesselto-background contrast, signal-to-noise ratio (snr) and subjective image quality. methods and materials: patients ( m, f; mean age±sd, ± ) with known or suspected peripheral arterial disease underwent single contrast medium dose ( . mmol/kg body weight) . -t mra using dixfs during first arterial passage of contrast material. results were compared with data obtained using a conventional, subtraction-based approach. a phantom study was performed to assess signal-to-noise ratio (snr) of both mra techniques. vessel-to-background (vtb) contrast and snr were measured and compared with the paired samples t-test. two experienced observers scored subjective image quality. fisher's exact test was used to compare subjective image quality. agreement regarding subjective image quality was expressed in quadratic weighted κ values. results: patient data showed improved vtb contrast in all anatomical locations with dixfs versus the conventional, subtraction-based mra method (all p < . ). subjective image quality was uniformly higher with dixfs when compared with subtracted images. in all cases this was significant (p < . ), except the aortoiliac arteries for observer (p= . ). phantom studies indicated a % higher snr with the dixon technique ( . vs . ). conclusion: this study demonstrates the feasibility of single contrast medium dose subtractionless lower extremity mra using dixfs method. both objective and subjective image quality are better compared with subtraction based mra of the peripheral vascular tree. correlation of cardiovascular risk factors and occult atherosclerotic findings using whole body magnetic resonance imaging of the vascular system in an asymptomatic patient collective: initial results s. mangold, e. randrianarisoa, p. krumm, c. bretschneider, a. seeger, k. rittig, b. balletshofer, c.d. claussen, u. kramer; tübingen/ de (stefanie.mangold@med.uni-tuebingen.de) purpose: to evaluate the prevalence of atherosclerotic disease, myocardial infarction and cerebrovascular disease in asymptomatic patients with cardiovascular risk profile including whole body magnetic resonance imaging (wb-mri) of the cardiovascular system into the framework of a comprehensive prevention concept. methods and materials: prospectively, patients without any known cardiovascular disease ( men, woman, mean age . ± . years) but suffering from cardiovascular risk factors such as arterial hypertension [aht], impaired glucose tolerance, hyperlipidaemia and obesity, were clinically assessed including family history, blood collection, blood pressure assessment and oral glucose tolerance test. furthermore, the carotid intima-media thickness [cimt], potentially indicative for atherosclerotic disease was assessed by ultrasound and a wb-mr angiography ( . t, avanto, siemens medical solutions) containing an examination of the of renal artery using respiratory triggered (rt) or breath held (bh) in reference to dynamic contrast mra (cmra). methods and materials: patients were involved (median age years). rt and bh nc mras using pg were obtained at t (discovery mr , gehc) using inflow inversion recovery (ifir) d fiesta with fan beam k-space view ordering in a coronal plane. cmra with d efgre was obtained as reference [ . mmol/kg gd-chelate, injection ml/sec]. evaluation, image quality, artefacts ( undiagnostic- excellent) and visualisation of aorta and renal arteries were ranked with -point scale. contrast was calculated (si artery/surrounding tissue). wilcoxon signed rank test and student's t test with bonferroni correction was used for statistical evaluation. results: all ncmras were diagnostic ( . - . ). scores for image quality and artefacts of rt ncmra were better than those of bh ncmra (ns) although visualisation of aorta was slightly better with bh than rt ncmra. rt ncmra provided better visualisation of distal renal arteries and better contrast than those with cmra (p < . ). contrasts of aorta and proximal renal arteries were slightly better in cmra than those in ncmras (ns). conclusion: with pg, homogenous si in aorta was obtained in ncmra. when image quality of rt ncmra is not enough to evaluate arteries, bh ncmra can be used as substitute. purpose: to evaluate the quality, the diagnostic performance and the radiation exposure of low-kv ct angiography protocol ( kv) with ultra low-contrast medium volume ( ml) in the assessment of the aorta disease. methods and materials: seventy patients with thoracic or abdominal aortic disease were prospectively examined with mdct scan (brilliance ict, philips) using ultra low-dose radiation protocol ( kv; automated tube current modulation) and ultra low-contrast volume ( ml; ml/s; mgi/ml). in the thoracic aorta assessment we performed ecg-gated retrospective protocol, necessary for the evaluation of ascending aorta. density measurements were performed on ascending, arch, descending, abdominal aorta, renal arteries and common iliac arteries. a control groups of patients who underwent standard ct-angiography protocol ( kv; mas) and standard contrast volume ( ml) were also evaluated. the obtained data in terms of radiation dose exposure (dose-length product, dlp), administered contrast and intravessels density were compared and statistically analysed. results: in every ct-exam we could correctly visualise and evaluate main branch of thoracic and abdominal aorta. no significant difference of density measurements was achieved between the low-kv protocol: mean attenuation value of thoracic aorta hu, abdominal aorta hu and renal arteries hu; and control group: mean value of thoracic aorta hu, abdominal aorta hu and renal arteries hu. the radiation dose exposure in low-kv protocol was significantly reduced (p < . ) in comparison with control group, obtaining the following value for thoracic scan: dlp and abdominal scan: dlp, while in control group we obtained for the thoracic scan: dlp and for the abdominal scan: dlp , respectively. conclusion: low-kv protocol provides a comparable diagnostic performance with standard protocol, decreasing significantly the radiation dose exposure (over %) and allowing also a significant reduction of contrast material volume ( ml), preserving renal function. x-ray phase-contrast imaging of arterial vessel wall: translation from synchrotron radiation to a conventional lab-based x-ray source h. hetterich , m. willner , s. fill , f. bamberg , j. herzen , m. stockmar , f. pfeiffer , m.f. reiser , t. saam ; munich/de, garching/ de (holger.hetterich@med.uni-muenchen.de) purpose: phase-contrast imaging (pci) is a novel x-ray-based technique that provides excellent soft tissue contrast but so far was depending on synchrotron radiation. the aim of this study was to evaluate the feasibility of visualising human carotid arteries by grating-based pci (gb-pci) at two different experimental setups: ( ) applying synchrotron radiation and ( ) using a conventional x-ray tube. methods and materials: five ex-vivo carotid artery specimens were examined with gb-pci either at a synchrotron facility using a monochromatic x-ray beam (n= ; developed for adult trauma patients in and a novel approach based on recent literature and our additional observations. results: of the years considered, cases met the inclusion criteria. in cases a nahi was assumed. cases showed sdhy. only one sdhy case was assumed to be related to an accident. the new classification system for traumatic sdhy in children will be introduced and discussed. conclusion: as demonstrated for different sdhy appearances, neuroradiologists should be aware of the possible presentations of nahi. in addition, investigation of sdhy's may allow for new insights into the pathogenesis of phenomena such as the shaken baby syndrome. apparent kurtosis coefficient (akc) in brain: a feasibility study in paediatric populations i. d'errico, a. ciccarone, m. esposito, m. mortilla, c. fonda; florence/it (igni @hotmail.it) purpose: diffusion-weighted imaging (dwi) depends on the b-values employed in acquisition. at low b values (lower than s/mm ) the signal attenuation is bi-exponential and is influenced both by diffusion and perfusion. at high b values (higher than s/mm ) the signal attenuation is influenced by restricted water diffusion and hence follows a non-gaussian distribution. diffusion kurtosis imaging (dki) provides quantifiable information about the deviation from gaussian distribution in water diffusion process. our purpose was to apply dki method to paediatric patients with different pathologies (tumours, ischaemia) and to establish its feasibility in detecting brain diseases. we examined patients from newborn to -year-old. diffusion weighted imaging was performed with b values from to with step s/mm . fitting all b values we were able to discriminate diffusion and kurtosis parameters. a home-made software performed all fitting and dwi, adc, akc maps. results: akc maps revealed additional information for tissue characterisation. in ischaemia, akc demonstrated more details of pathologic tissue changes and provided information about prognosis. in tumours, akc maps were used for discriminating low-grade from high-grade lesions revealing a better accuracy than conventional diffusion parameters. conclusion: akc maps are non-invasive methods that are well tolerated by paediatric patients and that provide a more detailed characterisation of neural tissue in the clinical context. their application in pathological conditions such as ischaemia and tumours provides additional information about microstructural tissue changes, differential diagnosis and prognosis. which t pulse should be used to study the preterm brain with a tesla scanner? d. tortora, v. panara, p.a. mattei, s. salice, m. tagliamonte, c. briganti, a.r. cotroneo, a. tartaro, m. caulo; chieti/it (domenicotortora@hotmail.it) purpose: the loss of contrast on mr t -weighted images obtained at tesla ( t) may negatively influence the detection of punctate hyperintense lesions, which are indicative of periventricular leukomalacia (pvl) in preterm neonates. in this t mr study we compared the sensitivity of different t -weighted sequences in identifying pvl. the presence of non cystic-pvl was retrospectively evaluated in tesla ( t) mr brain studies of preterm neonates acquired at term-corrected age. in neonates with pvl, t hyperintense punctate lesions were counted by two neuroradiologists in consensus on different axial t -weighted sequences: mm inversion recovery (ir), spin echo (se), reformatted d-fast field echo (ffe) and mm reformatted d-ffe. sequences were presented randomly. statistical differences of the number of hyperintense lesions detected by the different sequences were evaluated using the student's paired t test (p < . ). results: the greater number of t hyperintense punctate lesion was identified using the mm axial reformatted d-ffe sequence ( lesions), which resulted to be the most sensitive sequence in identifying pvl lesions (p < . ). axial mm ffe, ir and se sequences identified , and hyperintense punctate lesions, respectively. no statistical differences were found between mm-t sequences (p> . ). conclusion: when using a tesla mr scanner mm axial reformatted t - d-ffe is the most sensitive t -weighted sequence for detecting punctate hyperintense lesions which may affect the brain of preterm neonates. brain and the heart was performed. a vessel score, determined from the sum of arteriosclerotic changes of all evaluated vessel divided by the number of vessels with a range from , normal to , stenosis > %, was introduced and score's association with risk factors was assessed. results: the mean mri score was . ± . .the wb-mr angiography-based score was significantly associated with the body mass index [bmi] (p= . ) and aht in combination with an elevated bmi (p= . ). no significant associations were found for age (p= . ), sex (p= . ), impaired fasting glucose (p= . ), hyperlipidaemia (p= . ) and cimt (p= . ) . no patients with myocardial infarction and patients with cerebrovascular disease were found. conclusion: wb-mr angiography allows the detection of occult atherosclerotic disease in asymptomatic patients with cardiovascular risk profile especially in cases of aht and/or obesity. : purpose: to evaluate image quality and radiation dose of ultra-low-dose ct examinations of the inner ear performed using adaptive statistical image reconstruction (asir) in infants candidate to cochlear prosthesis implantation. we evaluated infants ( males, females, age - months, mean months) with sensorineural deafness who underwent ct of the inner ear before cochlear prosthesis implantation. out of them, were imaged on a -row ct scanner (discovery ct hd, general electric, milwaukee, wi) using an ultra-low dose protocol ( kv, ma, . s gantry rotation time) and a model-based iterative reconstruction algorithm (asir™), while in the remaining ct had been performed on a -row scanner before the introduction of the -row ct equipment at our institution, using a regular paediatric protocol ( kv, ma, . s gantry rotation time) with conventional filtered backprojection. dose-length product (dlp) values were obtained from dose reports generated from the scanner at the end of each examination. image quality was rated in blind by two radiologists using a likert scale ( =non-diagnostic through =excellent). results: none of the examinations were rated as non-diagnostic. image quality was comparable between the -and the -row ct group ( . ± . vs . ± . , respectively; p= . ). dlp was significantly lower in the -row ct group ( . ± . vs . ± . mgy*cm, respectively; p < . ). conclusion: compared with a regular paediatric protocol, ultra-low-dose ct of the inner ear with asir allows for markedly reduced radiation dose with preserved image quality. traumatic subdural hygromas in children between and years: a retrospective ct and mri study m.l. hahnemann , a. schmeling , m. schlamann , m. forsting , h. pfeiffer , d. wittschieber ; essen/de, münster/de purpose: non-accidental head injuries (nahi) represent a leading cause of death in infants. in this context, the role of traumatic subdural hygromas (sdhy) as possible acute or chronic finding in child abuse, especially in shaken-baby-syndrome, is not well understood and still a matter of debate. by modern imaging techniques, the present study aimed to investigate the characteristics of sdhy. methods and materials: from the years - , we retrospectively analysed the images of all children between and years who were suspected to have a craniocerebral injury and got an initial cranial computer tomography at the university hospital essen. in cases where additional mr examinations existed these mr images were also analysed. all skeletal and cerebral pathologies, demographic data, and, if existing, related clinical anamneses and findings were recorded. all sdhy cases were classified according to both a classification system originally s c a d e f g b is a major cause too (n= ). spearman rho correlations between radiographer's time of experience and frequency of mri exams repetitions were poor and not significant (r= . ; p= . ). the correlations between radiographer's tiredness and frequency of mri exams repetitions were negative, weak and not significant (r= - . ; p= . ). the patients' movement may disrupt the examination or degrade the images with artefacts. the level of experience does not influence the repetitions of mri exams, it seems that senior radiographers do not have improvements in performance as it should be expected. it is recommendable to do training courses regularly to improve the performance and systematically evaluate. several features will need to be identified which would decrease the mri exams repetitions. functional mapping of the visual word form area with frequent words of the portuguese lexicon: an fmri study c. ferreira , p. martins , g. cunha , n. canário , c. nunes , a.c. miranda , j. ribeiro , s. afonso , m. castelo-branco ; coimbra/pt, aveiro/pt (c_dferreira@yahoo.com) purpose: the visual word form area (vwfa), part of the fusiform gyrus in the temporal lobe underlies word form encoding. impairment of this region causes reading deficits, including alexia. the aim of this study is to functionally map vwfa at the individual subject level using frequent words of the portuguese lexicon, to develop a paradigm potentially useful for clinical patients. methods and materials: functional magnetic resonance images (fmri) were acquired in from nine subjects. the visual paradigm used consisted of blocks ( seconds block duration): baseline (checkerboard stimuli), blocks of frequent words and of pseudo-words ( words/pseudowords per block). general linear model analysis was performed using brainvoyager qx to identify brain regions encoding word form. results: an area corresponding to vwfa could be mapped in both hemispheres in all subjects at a statistical threshold of . , corrected for multiple comparisons. seven of the cases had predominant activation in the left hemisphere, one has equivalent activations bilaterally and one subject has predominant activation in the right hemisphere. the number of activated clusters was significantly larger in the left hemisphere at the group level (p = . , wilcoxon signed rank test). conclusion: bilateral activation was replicated in vwfa in all subjects, with a clear left hemispheric dominance demonstrating the robustness of the paradigm, making it potentially useful in a clinical setting, e.g. pre-surgical mapping. a survey of the various methods and techniques employed in myocardial stress testing k. borg grima , l. rainford , p. bezzina , d. o'leary ; msida/mt, dublin/ie (karen.borg-grima@um.edu.mt) purpose: literature suggests a range of pharmacological stress agents and radioactive tracers, together with a variety of defined protocols that may be used in conducting myocardial stress testing prior to cardiac scintigraphy imaging. an online survey was performed to evaluate current practice. methods and materials: a survey was developed comprising of twelve questions, by using 'survey monkey', which aimed to identify the variances present in conducting myocardial stress testing and in clinical protocol details if available. professional groups working in nuclear medicine, such as the medical-physicsengineering community and virtual radiopharmacy, were targeted. access to the survey remained open for eight months. forty-three members, including both radiographers and medical physicists responded from across europe and australasia. spss was used to evaluate the results obtained, based on chi-square tests and comparisons between multiple responses. results: the majority ( %) of the participants were from united kingdom, % from other european countries and % from australasia. in centres pharmacological stress testing was performed either alone or in conjunction with exercise stress testing. the results indicated that % of the participants were aware of local stress test protocols; however, guidelines indicating which patients were not suitable for pharmacological stress tests may require clarification. conclusion: results suggest that for pharmacological stress testing there is a need for increased awareness of protocols, and across all responders the need for improved knowledge and understanding of local protocols was identified. this initial survey justifies further research towards increase protocol compliance and standardisation of practice during myocardial stress testing. templates were built taking into account the age of patients. artefact movements and eddy current distortions were removed. mean diffusivity (md) and fractional anisotropy (fa) were quantified together to the three principal directions of diffusion (eigenvectors) with their own eigenvalues (tensor diagonalization). so analysis of single fibre orientation for each voxel with a bayesian algorithm was executed. voxelwise statistical analysis of the fa, md and axial diffusivity data was carried out using tbss between focal cortical abnormalities sites and normal ones. results: different pattern of cortical organization and white matter projections are evidenced depending of lesional load and extension, site and age. in focal cortical abnormalities the tbss analysis revealed significant differences (p < . ) between affected cortical sites and normal ones. conclusion: different fa data were collected. the reductions of fa, the associated elevation of diffusivity in altered contiguous or distal area are evidenced. : purpose: the magnetic resonance imaging (mri) uses the magnetic field effects to its functioning. this study aimed to clarify the emf directive / /ec discussion which imposes limits to electromagnetic fields (emf) regarding the occupational exposure. methods and materials: it was explored policy documents, regulations, guidelines, laws and other official documents on this subject. to understand the reason of this controversy, the evidence of consequences from the emf exposure over professionals was analysed. from the information obtained an online survey was developed, with national and international coverage, towards professional groups considered involved in the controversy. the opinions were analysed by the force field analysis diagram, through the policymaker k -health™ application to speculate the influences, forces, power and strategies developed in this process. results and conclusion: from respondents % do not know the esr's position, the directive and its contents. % know the safety measures to apply in the mr room and report adverse events for lack of compliance with safety standards, being the levels of sar, the most topic referred. they do not know the limits imposed and have no opinion about the directive's controversy ( %). the political impact is considered neutral ( %) against the negative clinical and economic impacts ( %) that falls over the equipment manufacturers ( %). the professional societies have most decision, followed by physicists, doctors, manufacturers, government decision-makers and health-managers. the manufacturers, radiographers and supervisors have median influence, and the patients have weak influence over this process. on this matter influences and pressure strategies over the european commission and council were recognised. radiographers perceptions of magnetic resonance imaging: a study of the causes that lead to the repetition of exams t.r. filipe , l.p.v. ribeiro , r.p.p. almeida , s.i. rodrigues , k.b. azevedo , c.a. silva , a.f.l. abrantes ; faro/pt, Évora/pt (tiagofilipe__@hotmail.com) purpose: to know how often repetitions of mri exams and sequences occur in radiology departments. a self-applied questionnaire was used as instrument and assigned to radiographers who performed mri exams to determine which were the causes that lead to the repetition. the questionnaires were interpreted and statistically analysed through descriptive statistics and spearman's rho correlation. results: at a % confidence interval, the major results suggest that the patient's movement during the mri exams is the main cause to repeat this exams (mean of . on a -point likert scale). however, there are causes related to the radiographer's and the results showed that the introduction of wrong imaging parameters s a c d e f g results: the percentage of depression among mri technologists included in our sample was found to be % which is considered to be much more than the percentage ( %) found among the dentists in usa ( . %) and among community population in saudi arabia. conclusion: it was found that there is a strong relationship between the incident of depression among mri technologists and the incident is higher among technologists working for more than years. development and implementation of a synthetic data evaluation scenario for image fusion algorithms based on discrete wavelet transform and principal component analysis v. weiss; wiener neustadt/ at (volker.weiss@hotmail.com) purpose: successful image fusion reduces the amount of data without significantly reducing the amount of relevant information. this study aims to answer the question whether the image fusion results were calculated successfully and what successful image fusion actually means. the study presents two new approaches for the quantitative evaluation of image fusion schemes. it provides the development and implementation of a synthetic data evaluation scenario for image fusion algorithms based on discrete wavelet transform (dwt) and principal component analysis (pca). furthermore, it presents a medical application visualising and comparing fused axial ct slices, reconstructed from a ct volume data set with identical position but calculated with different convolution kernels. the study provides a ground truth data-based performance evaluation, as well as a comparison of the dwt and pca to each other by computing and visualising significant differences in their performance. results: in the present study, the dwt, compared to the pca, turns out to be the more powerful and therefore more suitable image fusion method, both qualitatively and quantitatively. conclusion: according to estimates of certain surveyed medical specialists, to whom the results have been shown, a serious diagnosis solely on the basis of fused images is conceivable. the fused images would also be conceivable for documentation purposes and printouts for the referring physicians. finally, storing fused image series instead of individual series would reduce the amount of memory required in long-term archives by half. image registration and fusion of ct and micro-ct of a sheep's cochlea s. leitner; berndorf/at purpose: the sheep's cochlea seems to be most similar to human ones. hence, it is of great interest in the fields of developing cochlea implants and improving operation techniques of electrode implantation in ent-(ear-nose-throat) surgery. methods and materials: for investigating the sheep as a suitable large animal model, data sets of high resolution micro-ct and ct of its cochlea were acquired. the research on inner-ear diseases and ent-surgery methods require image processing methods, such as image registration and image fusion. in this thesis, the micro-ct data set was registered with the ct data set in a common coordinate system using two different software packages. the registration was successful with both types of software. in order to evaluate the results visually, the fused multimodal data were represented by means of colour overlay as well as d rendering techniques. the basis of image-registration of these two modalities was laid and serves as comparison between the image information of the high resolution micro-ct and the conventional ct in order to overcome an interpretation gap between these two modalities. the appropriate d visualisation of the vestibule-cochlea system by means of the highest resolution image devices and medical image processing methods support fundamental research on macro-and micro-mechanical processes of hearing and basic understanding for developing therapeutic and preventive methods for ear diseases. purpose: scout images are essential in neuroradiology. though these images may have limited diagnostic quality, they visualise larger parts of the body. therefore, certain radiologic findings may be visualised only or largely in the scout images and truly constitute unexpected radiologic findings (uf). impact related to spinal location and imaging modality on to the incidence and distribution of uf remains unknown. methods and materials: patients undergoing ct and patients undergoing mri of spinal column between / / and / / are included. uf reported in the original dictations are separated into groups: scout only (i), scout+diagnostic images (ii) and diagnostic images (iii) only. in addition to type of imaging and spinal location, locations and organ system of these findings are recorded. results: there were uf in ct and in mri group. in both groups, patients with uf were significantly older than the ones without uf, with a slight female preponderance. majority of uf in ct were seen in diagnostic images. uf seen only in scout images of ct were exception although these were significant findings. uf distribution in mri was more even. equal numbers of uf were seen in groups ii and iii. approximately % of uf seen in mri were present in group i. conclusion: scout images of neuroradiologic studies may harbour significant number uf. this is especially true in mri where % of uf seen only in scout images. although uf seen solely in scout images of ct is rare, these are predominantly significant findings. comparison of a -channel-with a -channel head coil using snr measurements c. vandulek, d. kaczur, e. vinczen, i. repa; kaposvár/hu (cvandulek@gmail.com) purpose: one of the key attributes characterising the quality of an mri head coil is the signal-to-noise ratio (snr). the purpose of this study was to compare a -channel-with -channel head coil using standardised snr measurements. the measurements were performed on a . t mri scanner. the snr measurements were performed on the coils' phantoms and on volunteers. the snr protocol consisted of axial t fse and t fse measurements. analysis of the snr calculations was performed using roi's positioned in the phantoms and the brain tissue of the volunteers. the results of the snr measurements of the phantoms show that the snr of the -channel coil is double that of the -channel head coil. however, the snr of the volunteers showed only a % increase of snr with the t fse measurement, and a % increase with the t fse on the -channel coil. there were no artefacts observed on either measurements of the phantoms and human volunteers. conclusion: this study confirmed a difference of the snr between the -and -channel head coil. while the phantom measurements showed a twofold increase of snr between the two coils, this rate was not confirmed on the human volunteers. the results of this study amplify the advantage of using the -channel coil for neuroradiological examinations (e.g. fmri, mrs), whereas the -channel coil is sufficient for routine brain examinations. psychological effect of chronic exposure to high magnetic field on mri technologists n.m. mishah, w. hamed; jeddah/sa (nabeel @hotmail.com) purpose: the purpose of this study is to measure the incident of depression among mri technologists since they are chronically exposed to high magnetic fields that may carry occupational hazard on central nervous system and on their brain chemicals. this may cause a long-term psychological side effects such as depression. the data and the statistical information of this project were based on beck depression inventory bdi, version which is used by healthcare professionals as depression screening tool. the questionnaire of depression screening tool was delivered to all mri technologists working in major hospitals within large cities in makkah region. the total completed questionnaire received was and only was accepted with a rejection rate of . %. the received data were analysed using a computer-aided statistical tool then the percentage of depression found among mri technologists included in our study will be compared to previous study conducted on dentists in usa and among community population in saudi arabia. s c a d e f g b conclusion: regorafenib significantly suppressed tumour perfusion and vascularity quantified by dce-ct in experimental colon carcinomas in rats with good to moderate correlations to an immunohistochemical gold standard. tumour response biomarkers assessed by dce-ct might be a promising future approach to a more personalised and targeted cancer therapy. author disclosures: k. nikolaou: research/grant support; bayer healthcare, germany. c.c. cyran: research/grant support; bayer healthcare, germany. contrast-induced nephropathy in patients undergoing intravenous contrast-enhanced computed tomography and the relationship with risk factors: a meta-analysis s.i. moos, j. stoker, s. bipat; amsterdam/nl (s.i.moos@amc.uva.nl) purpose: to summarise the incidence of contrast-induced nephropathy (cin) and to study associations between cin and risk factors in patients undergoing intravenous contrast-enhanced computed tomography (cect). we searched the medline, embase and cochrane databases from till july . two reviewers checked inclusion criteria and extracted data. mean cin incidence and associations between risk factors and cin were pooled by random-effect approach. results: twenty-three articles with , patients (mean age . years, mean egfr at baseline . ml/min) were included. cin was defined as absolute or relative ( . µmol/l/> %) serum creatinine increase, mostly within hours. all studies included a high proportion of patients with risk factors; chronic kidney disease (ckd) in % of all patients, diabetes mellitus (dm) in %, hypertension (ht) in % and congestive heart failure (chf) in %. the mean incidence of cin was . % ( % ci: . %- . %). data analysis showed an increased risk for cin in the presence of dm ((odds ratio . ( % ci: . - . ), p= . )) and ckd ( . ( % ci: . - . ), p= . ). ht and chf were not associated with an increased risk (p= . , p= . ). the mean incidence of cin after cect was . % and is associated with dm and ckd. the incidence of cin is mostly reported in studies with a high proportion of patients with risk factors. therefore, the reported cin incidence and associated risk factors for cect might be overestimated compared to the cin incidence in a general population undergoing cect. purpose: to determine whether contrast agent (ca) dose reduction to one-half and one-quarter of the standardised dosage allows for preserved image quality of renal mr angiography at t. methods and materials: mr examinations were performed in healthy subjects on a t mr system (magnetom t), utilising a custom-built -channel rf body coil. dynamic d flash data sets were obtained pre contrast and sec after the application of contrast agent. examinations were performed at three different time points for injection of three dosages of ca (gadobutrol, bayer healthcare): ( ) . mmol/kg body weight (bw), ( ) . mmol/kg bw and ( ) . mmol/kg bw. contrast ratios (cr) were measured pre and post contrast in the aorta and both renal arteries in correlation to adjacent psoas major muscle. qualitative analysis with regard to delineation of the pre-contrast and post-contrast renal arterial vasculature was performed by two radiologists using a five-point-scale ( =excellent to = non diagnostic). results: non-enhanced t w mri provided an inherently high signal intensity of vasculature, yielding a good overall pre-contrast arterial delineation (mean . ). the application of contrast agent showed improved vessel delineation in qualitative and quantitative analysis for all three dosages, yielding comparable results in subjective ratings of qualitative analysis (mean . gd . ; mean . gd . ; mean . gd mean . ). quantitative analysis of contrast ratios showed only minor increase of mean values with increasing gadolinium dosage (mean . gd . ; mean . gd . ; mean . gd mean . ). conclusion: t ce-mra allows for a significant dose reduction to one-quarter while maintaining high image quality. diagnostic accuracy of dynamic gadoxetic-acid-enhanced mri and pet-ct in patients with liver metastases from neuroendocrine neoplasms purpose: to evaluate the diagnostic accuracy of dynamic gadoxetic-acid-enhanced mri parameters in comparison to standardised uptake values (suv) from both patients with proven liver metastases of neuroendocrine neoplasms (nen) up to three regions of interest (rois) were defined in metastases (> cm) and liver tissue in morphological images. corresponding rois were defined in the dce-mri dataset and in the pet-ct dataset. diagnostic accuracy for all perfusion parameters were evaluated for the differentiation between metastases and liver tissue: arterial and venous plasma flow (apf and vpf), extracellular mean transit time (exmtt), extracellular volume (exvol), intracellular uptake rate (ur) of gd-eob-dtpa and arterial flow fraction (aff) as well as suvs derived either from f-fdg or from ga-dotatate-pet-ct. results: area under the curve for different dce-mri parameters was between auc= . (extracellular mean transit time) and . (arterial plasma flow -sensitivity: . %, specificity: . %, cut-off value: . ml/min/ ml). sensitivity and specificity of suvmean derived from ga-dotatate were . % and . %, respectively (auc = . ). suvmean derived from f-fdg-pet-ct showed a sensitivity and specificity of . % and cp class liver damage groups. chi square test was used for statistics and p < . was considered statistical significant. results: in poor hbp cases (n= ), er of hbp and sdp were . ± . and . ± . . in control cases (n= ), er of hbp and sdp were . ± . and . ± . . er of hbp and sdp in cp-a poor hbp (n= ), cp-b poor hbp (n= ), cp-c poor hbp conclusion: in most of the poor hbp image cases, sdp image improve parenchymal and vascular contrast except cp-c liver damage cases results: we found characteristic signal criteria in all analysed plaque components. applying these criteria gb-pci had a good sensitivity for the detection of fc/nc, iph and ca (all > %) and excellent specificity and accuracy (all > %) with good inter-reader agreement ([[unable to display character: &# ;]]³ . , p < . ). there were excellent correlations for quantitative measurements of fc, nc and ca between gb-pci and histopathology (r³ . ). inter-reader reproducibility was excellent with icc³ . for all measurements. conclusion: gb-pci can identify and quantify atherosclerotic plaque components in a lab-based set-up with excellent correlation to histopathology. imaging of the therapeutic efficiency of photodynamic therapy with a new designed fluorescence optical annexin probe k. haedicke, s. gräfe, f. lehmann, w.a. kaiser, i. hilger; jena/ de (katja.haedicke@med.uni-jena.de) purpose: photodynamic therapy (pdt) destroys tumour tissue via generating reactive oxygen species after administration of a photosensitizer and illuminating the tumour with light. next to many other molecular processes, apoptosis occurs in the tumour after this therapy. we designed a new fluorescence optical probe based on annexin v to detect this therapeutic effect after pdt in vivo via non-invasive near-infrared fluorescence optical imaging. methods and materials: annexin v was labelled with the near-infrared dye dy- -nhs and characterised spectroscopically. binding affinity of the probe to apoptotic tongue-squamous epithelium carcinoma (cal- ) cells was analysed by purpose: to evaluate the potential of the reconstruction algorithm idose to preserve image quality in brain-ct acquired with % reduced radiation dose and to evaluate image quality assessment methods. interaction of magnetically labelled multipotent mesenchymal stromal cells and e-/p-selectins monitored by magnetic resonance imaging in mice j. salamon, k. peldschus, d. wicklein, c. lange, h. ittrich, u. schumacher, g. adam; hamburg/ de (j.salamon@uke.de) purpose: this study's purpose was to analyse the influence of e-and p-selectins on the migratory pattern of magnetically labelled multipotent mesenchymal stromal cells (msc) in e-/p-selectin deficient (ko) and wildtype (wt) mice using mri and fluorescence microscopy. methods and materials: murine msc were labelled with fluorescent iron-oxide micro-particles and carboxyfluorescein succinidylester. the ability to bind selectins and the expression of typical msc markers were assessed by flow cytometry. labelled msc were injected into ko-and wt-mice applying doses of × cells intracardially, × cells intravenously and × cells intraperitoneally. mice underwent sequential mri at . t using high-resolution t * d and d coherent gradient-echo sequences and histological evaluation after days. results: expression of typical msc markers and binding abilities to e-/p-selectins were found similar after labelling. after intravenous cell injection in ko-mice significant snr decrease was assessed solely in the liver from day to ; wt-mice revealed an increasing snr decrease of liver, spleen and bone marrow within days. after intraperitoneal injection no significant snr changes were observed in ko-mice; wt-mice showed an increasing snr decrease of liver, spleen and bone marrow within days. after intracardiac injection multiple susceptibility artefacts could be detected no longer then day in ko mice but persisted up to day in wt-mice. fluorescence microscopy confirmed mri findings. conclusion: this study demonstrates that msc retain their binding ability to e-/p-selectins after magnetic labelling. e-/p-selectin deficiency in mice significantly alters the distribution of magnetically labelled msc. de (holger.haubenreisser@medma.uni-heidelberg.de) purpose: to prospectively compare the image quality of cranial computed tomography (cct) with thin slice widths using traditional filtered back projection (fbp) and sinogram-affirmed iterative image reconstruction (safire). methods and materials: consecutive studies ( men; . ± . years) referred for cct were prospectively included. each cranial ct raw data set was reconstructed with fbp and safire with decreasing slice widths ( mm- mm). objective image quality was assessed by measuring image noise in three predefined regions of the brain (white matter, thalamus, cerebellum) using identical regions of interest (rois). subjective image quality was assessed by experienced radiologists by ranking the reconstructed data sets with respect to overall image quality. the mann-whitney u-test and cohen's kappa were used for statistical analysis. results: image noise was statistically significantly reduced in all safire images at identical slice widths when compared to the images reconstructed with fbp ( . ± . hu vs. . ± . hu at mm slice width) (p < . ). mean signal attenuation for each region and slice width remained constant between the two reconstruction methods (p> . ). snr was comparable between mm safire images and mm fbp images. subjective image quality of safire images was rated consistently higher than that of the fbp images (p < . ). interobserver agreement was excellent between both radiologists (cohen's k = . - . ). conclusion: iterative image reconstruction significantly reduces image noise, while increasing image quality. in cct this may be used to decrease slice width and thus reduce partial volume effects, which may lead to increased diagnostic accuracy. purpose: the aim of our study is to demonstrate the effectiveness of d mri in the diagnosis of lumbar radiculopathy in comparison with clinical and neurophysiological data. methods and materials: patients with l or s monoradiculopathy caused by a posterolateral or intraforaminal disk herniation underwent mri examination after preliminary clinical assessment and electromyography (emg). we performed conventional spin-echo and d coronal ffe sequences with selective water excitation (proset imaging). using d coronal ffe sequences indentation, swelling and tilting angle of the nerve root were evaluated. the tilting angle was compared with the asymptomatic contralateral side of the nerve root. all the data were processed using epi info . software (cdc, atlanta, ga, usa) and were compared by means of fisher exact test. results: proset sequence revealed abnormal tilting angle in patients ( . %; p < . ), monolateral swelling or indentation of roots and spinal nerves in patients ( . %; p < . ). in patients emg demonstrated an involvement of more than one nerve roots, whereas the proset revealed only one involved root. in patients the nerve alterations were revealed only by emg. conclusion: emg has an improved ability to highlight the early changes of the roots caused by mechanical and biochemical alterations due to compression. proset imaging demonstrates high sensitivity in identifying the exact level of the involved root and can provide a useful tool to plan surgical treatments. purpose: to investigate the utility of dti in detecting nerve injury or neuropathic changes in proximal nerve segments in patients with peripheral neuropathy. methods and materials: twenty-four age-matched individuals with (n= ) and without (n= ) peripheral neuropathy underwent dti of a defined sciatic nerve segment. patients and controls were evaluated by clinical examination and nerve conduction studies at baseline and six months after the initial dti scan. four patients were scheduled for a second scan six months after the initial mri. results: the mean fa value was significantly lower in sciatic nerves from patients with peripheral neuropathy as compared to controls. sciatic nerve fa values positively correlated with clinical disability scores and electrophysiological parameters of axonal damage, i.e. the compound muscle action potential amplitudes of the peroneal and tibial nerve at baseline and six months after mri scan. no correlation was found with axial and radial diffusivities. conclusion: dti-derived fa values are a sensitive measure to discriminate healthy from functionally impaired human sciatic nerve segments. this technique might be potentially useful in estimating the proximal axonal degeneration burden in patients with peripheral neuropathies. purpose: the purpose is to describe the imaging features of the involved brainstem and spinal cord tracts in cases of leukodystrophy with brainstem and spinal cord involvement and brain lactate elevation (lbsl). the importance of craniovertebral and cervicomedullary angle on cervicogenic headache g. Çoban , i. Çöven , e.b. Çifçi , e. yıldırım , c.a. yazıcı , b. horasanlı ; konya/tr, ankara/tr (drgokcencoban@gmail.com) purpose: many studies indicated that cervicogenic headache (ch) may originate from cervical structures innervated by the upper cervical spinal nerves and the trigeminal nerve branches. studies to date have not investigated whether the narrowing of the craniovertebral angle (cva) and cervicomedullary angle (cma) affects the nerve branches and causes pain. the aim of this study was to investigate the effect of the narrowing of the cva and cma values on the occurrence ch. methods and materials: between january and may , patients with the diagnosis of ch were included in the study. the pain scores in patients were carried out using a visual analogue scale from to (pain groups purpose: to assess the image quality after image-based processing of low-dose single-rotation intra-procedural d-fd-ct (sr d-fd-ct). multiple rotation contrast-enhanced d-fd-ct is associated with many c-arm projections (~ projections) and a high amount of contrast agent (ca). in this feasibility study, we used a single-rotation of the c-arm (artis zee biplane, siemens ag, healthcare sector, germany) accompanied by cardiac pacing acquiring a reduced number of low-dose projections (~ - purpose: to demonstrate that myocardial microvessels detection is feasible at high-resolution susceptibility-weighted mr imaging (swi). methods and materials: fourteen wistar rats underwent ex vivo cardiac mr imaging on a . tesla scanner using a cryogenic device. thin, tubular hypointensities within the myocardium of normal rat hearts at high-resolution susceptibility-weighted mr imaging (group , n= ) were presumed to be intramyocardial microvessels.to prove that these "strand-like" structures were microvessels, a reference map of the myocardial macrovessels (group , n= ) after direct intracoronary injection of barium sulphate, a viscous contrast media was defined. then, a superparamagnetic contrast agent (ferumoxsil, lumirem ®), an intravascular contrast agent, was injected to stack up the distribution of intramyocardial microvessels (group , n= ). for groups and , d fast imaging with steady state in precession ( d fisp) sequences was performed. the results of images in group (spatial resolution: μm) and group (spatial resolution: x x μm ) were qualitatively compared. results: after intracoronary artery injection of barium sulphate, the main coronary arteries were visible up to the third-order branches (group ). beyond this level, the coronary microvasculature was opacified with ferumoxsil (group ) as demonstrated by the presence of ferumoxsil inside the microvessels on mr-matched histological sections. the regional distribution of microvessels was similar between groups and . conclusion: myocardial microvessels appear as "strand-like" structures on highresolution mri without injection of contrast media. this provides new methods for evaluation of neovascularization in preclinical models of myocardial infarction. purpose: to prospectively compare the image quality and homogeneity of cardiac t -weighted dark blood images using a dual-source parallel radiofrequency (rf) transmission mr system with rf shimming at . t and conventional mr imaging at . t. methods and materials: dual-source parallel rf transmission . t mr system with local rf shimming was used to obtain t -weighted dark blood images in patients and compared with standard mri at . t. snr was determined in the interventricular septum (is), the lateral wall (lw), the right ventricular cavity (rv) and left ventricular cavity (lv) in the anterior wall (aw), posterior wall (pw) and in the left ventricular cavity (lv) in two-chamber orientation. (kerstin.bauner@med.uni-muenchen.de) purpose: to assess dynamic t shortening effects of equimolar doses of gadobutrol and gadoterate meglumine in myocardium and the effect on extracellular volume fractions (ecv) in an animal model. methods and materials: rabbits underwent cardiac mri under general anaesthesia on a . tesla scanner using an -element knee coil. exams included ssfp cine imaging as well as pre-and post-contrast myocardial t -mapping using a modified look locker inversion recovery (molli) technique. each animal was scanned twice with a -h interval after receiving either . mmol/kg gadobutrol methods and materials: twenty-five breast lesions classified suspicious in mammography or ultrasound (birads / ) were included in this prospective irb-approved study. all patients underwent t mri (siemens magnetom, erlangen, germany) using a dedicated -channel breast coil and a high temporal and spatial resolution d t -weighted sequence (twist, fat-sat, . mm isotropic, temporal resolution sec, examination time min) with a single dose of contrast agent (dotarem, guerbet). one patient had to be excluded due to insufficient data quality. two readers trained in different institutions independently assessed lesion morphology and enhancement kinetics and classified them according to bi-rads. lesion size, localisation and image quality were assessed. sensitivity, specificity, diagnostic accuracy and interrater agreement (kappa statistics) were calculated for both observers. the histopathological diagnoses were used as the standard of reference. results: there were three benign and malignant lesions. mean histopathological size was mm (range - mm). on the basis of lesion morphology and enhancement patterns, all lesions were correctly classified as benign (n= ) and malignant (n= ) by t ce-mri. sensitivity, specificity and diagnostic accuracy were %. interrater agreement for bi-rads ratings was excellent ( . ). kappa agreement for single bi-rads descriptors ranged between . and . conclusion: high spatial and temporal resolution imaging in clinical practice is feasible using t mri, revealing excellent diagnostic accuracy and interrater agreement. purpose: to study a potential role of quantitative mri (qmri) using t /t ratios to differentiate benign from malignant breast lesions, assess contralateral breast involvement and monitor response to treatment. a cross sectional study of women with breast lesions were scanned with the mixed-tse pulse sequence, which is multispectral in t and t , therefore, affords maps of t /t . patients were grouped according to histopathological stage of disease: untreated malignant tumor, treated malignancy and benign disease. qmri assessment of the same quadrant of contralateral breast that did not have cancerous lesion was performed and compared to the breast that was subjected to chemotherapy and/or radiation therapy in order to monitor response to treatment. results: elevated t /t means of . ± . (n= ) were observed for biopsy proven malignant lesions and . ± . (n= ) for malignant lesions that were treated prior to qmri with chemotherapy and/or radiation as compared to . ± . (n= ) for benign lesions. the higher stage of cancer determined by histopathology analysis was also strongly associated with higher t /t ratio (p= . ). estrogen and progesterone receptors negative status was strongly correlated with higher t /t ratio p= . and p= . , respectively. her /neu receptor status showed no significant correlation with t /t ratio (p= . ). the t /t ratios provide measures that strongly correlate with histopathological findings. this quantitative information of tissue properties can provide basis for improving the specificity of diagnostic breast imaging and serve as a tool to assess response to treatment and contralateral breast involvement. improved differentiation of breast tumours using novel imaging system based on co-registered opto-acoustic tomography and ultrasound p. otto , k. kist , n.c. dornbluth , t. stavros , d. herzog , b. clingman , j. zalev , p. lavin , a. oraevsky ; san antonio, tx/us, southborough, ma/us, houston, tx/us (ottop@uthscsa.edu)purpose: a novel system called imagio combines ultrasound and opto-acoustics (oa) to more accurately distinguish malignant from benign tumours. we analysed readers' ability to assess probability of malignancy (pom) using oa versus conventional diagnostic ultrasound (dus) alone. methods and materials: patients with breast masses were assessed with oa and dus. all the masses were biopsied. histology was the gold standard. oa employs near-infrared laser pulses at two different wavelengths (to provide contrast between oxygenated haemoglobin in benign lesions and de-oxygenated haemoglobin in malignant lesions) to illuminate tissues through a fibreoptic bundle incorporated into a prototype duplex hand-held ultrasound probe. it detects the laser-generated ultrasonic pressure waves that are then used for reconstruction of two-dimensional oa images. oa maps of total haemoglobin and blood oxygen purpose: to assess metabolic imaging of breast tumours with breast f-fdg pet-ct and compare it with t ce-mri. methods and materials: suspicious breast lesions were included in this irb-approved prospective study. all patients were examined with f-fdg pet-ct and t ce-mri of the breast. the mri protocol consisted of a t -w and a contrast-enhanced high-resolution d-t -w sequence with a single dose of contrast agent (dotarem®, guerbet). all patients were subjected to prone f-fdg pet-ct scanning. ct data were used for attenuation correction. breast pet-ct was assessed for f-fdg-avidity of lesions. tumours were classified as positive when f-fdg-uptake was greater than blood-pool activity. lesions within tissues demonstrating moderate/high physiologic background activity were considered positive if the activity was greater than the adjacent physiologic activity. t ce-mri was assessed for lesion morphology and enhancement kinetics and classified according to bi-rads®. all lesions were histopathologically verified. results: pet-ct had a sensitivity of %, a specificity of % and diagnostic accuracy of %. ce-mri had a sensitivity of %, a specificity of % and a diagnostic accuracy of %. there were benign and malignant lesions (mean lesion size . mm; range - mm). the false-negative lesions in pet-ct were small lesions (mean . mm), had a very low suv (mean suvmax . ) or were adjacent to tissue with high physiologic activity or low grade idcs. conclusion: t ce-mri is superior to pet-ct for assessment of breast lesions, but dedicated breast pet-ct is a valid alternative in patients, who are unsuitable for mri. high spatial and temporal resolution breast imaging at purpose: to validate a contrast-enhanced (ce) combined high spatial and temporal resolution imaging protocol for the assessment of breast tumours at tesla in clinical practice. the aim was to evaluate the safety and efficacy of cra as local therapy for breast carcinomas with bone metastases. methods and materials: sixteen cra breast lesions, mean size . (range . - . cm) in thirteen consecutive patients, mean age ( - ) with core-needle biopsy-proven breast carcinoma and bone metastases were enrolled in this study. patients had one lesion and three patients had lesions. under local anaesthesia and mild conscious sedation, the tumour and surrounding breast tissue were ablated with percutaneous ct-guided cra. cryoablation consisted of cycles each of minutes of freezing followed by a -min active thawing phase and a -min passive thawing phase for each one. ten patients underwent one cra session and two patients cra sessions. one patient is treated with two sessions for the same lesion. results: all cra sessions were successfully completed and all breast tumours were ablated. morbidity consists in transient and mild ecchymotic changes and post-procedural oedema seen in two cases and alteration in skin pigmentation seen in the point of insertion of the cryoprobes in other two cases. the therapeutic outcomes were evaluated by contrast-enhanced tc or mri at -, -and -month interval. purpose: stereotactic vacuum-assisted biopsy (vabb) is the first choice technique to characterise suspicious microcalcification clusters; however, considerable proportion of understaged invasive cancer (idc) at subsequent surgical histology has been reported. bles, thanks to a radiofrequency excisional system, remove a larger not fragmented histological sample ( x mm, weight g). our aim was to prospectively assess bles diagnostic and eventually therapeutic efficiency in a selected cohort of patients with suspicious microcalcification cluster. methods and materials: from september , patients with small microcalcification cluster, < cm, staged a- b according to bi-rads classification system, were proposed for excisional biopsy with bles. written informed consent was obtained.results: up to now, patients underwent bles at our centre; of them ( %) had malignant lesion, were idc and ( %) in-situ (dcis) carcinoma. rationale of the study was to completely remove microcalcification clusters, obtaining enough surrounding tissue for histological margins' evaluation. complete histological concordance was obtained in % of atypical hyperplasia. all patients with dcis underwent surgical excision: upgrading to idc resulted in only / ( % underestimation proportion); among dcis cases, surgical excision demonstrated complete removal of the lesion by bles in / patients ( %). conclusion: in our experience, bles is a valid, simple and safe alternative to vabb, providing better diagnostic performance evaluated as histologic accuracy with lower underestimation rate compared to previously reported for vabb. in selected cases, particularly in small microcalcification clusters, bles may represent an interesting new therapeutic strategy considering the high rate of complete lesion removal. purpose: the objective of the study is to assess the use of "intact" breast lesion excision system as the primary method for histopathology diagnosis in suspicious small and borderline lesions as well as the unclassified microcalcifications. methods and materials: cases were included (feb-august ). inclusion criteria: small lesion less than mm, unclassified microcalcifications, asymmetric densities, focal distortion. results: cases were successfully done, . % ( / ) cases were done under ultrasound guidance and . % ( / ) cases were done under stereotactic guidance. . % ( / ) lesions were removed using the mm probe and . % ( / ) lesions were removed using the mm probe size. the main indication was complete removal of a small mass ( / ) followed by biopsy of unclassified microcalcifications, either without mass ( / ) or associated with a mass ( / ). asymmetry and distortion were the indications in ( / ) and finally clustered micro cysts ( / ). as regards the histopathology after total excision; . % ( / ) of lesions were benign and only . % ( / ) of lesions were malignant. fibroadenoma was the commonly encountered benign lesion in the study group, it was encountered in . % ( / ), followed by papilloma found in . % ( / ), followed first experiences with a self-test for dutch breast screening radiologists as a quality assurance tool j. timmers , a. verbeek , r. pijnappel , m. broeders , g. den heeten ; nijmegen/nl, utrecht/nl, amsterdam/nl (j.timmers@lrcb.nl)purpose: to evaluate the use of a self-test as a quality assurance tool for screening radiologists in the dutch breast cancer screening programme. methods and materials: screening radiologists were invited to voluntarily complete a test set of screening mammograms. the following grading criteria were assigned regarding the most suspicious lesion: location, level of suspicion, bi-rads, laterality, type (well defined mass, ill defined mass, spiculated mass, microcalcification clusters, architectural distortion and asymmetric density) and mammographic density are assigned. also, several reader characteristics, such as years of experience and number of cases read per year, were to be completed. case and lesion sensitivity and specificity were determined for all readers. the spearman correlation coefficient was used to determine correlation between reader characteristics and performance measured by the area under the receiver operator characteristics (roc) curve (auc). results: radiologists completed the test set ( %). the mean age was (range - ) and on radiologists read on average , (range - , ) screening mammograms per year. the median auc value was . , case sensitivity %, lesion sensitivity was % and specificity %. the auc was not correlated to reader characteristics. the test-set revealed interobserver variation in assigning lesion types. conclusion: overall, a good performance was seen among all screening radiologists. readers are able to determine their educational needs and compare it with peers during training or audits. it is therefore a useful quality assurance tool. medical education should be dedicated to reducing interobserver variation. transition from analogue to digital screening mammography significantly increases the proportion of women referred twice for the same lesion l.e.m. duijm, h. wiersma; eindhoven/nl (lemduijm@hotmail.com) to determine the effect of transition from analogue to digital screening on the proportion of women referred twice for the same lesion and to assess screening outcome. we included , consecutive analogue screens (obtained between january and april ) and , consecutive digital screens (obtained between july and july ). review of the screening mammograms of women who had been referred twice was performed to determine whether their initial and second referral comprised the same lesion. during -year follow-up, radiology reports, surgical correspondence and pathology reports of each referred woman were collected. results: the overall positive predictive value (ppv) of referral was . % at analogue screening and . % at digital screening (p < . ). among women who had only been assessed by analogue screens, ( . % of referrals) had been referred twice for the same lesion. these referrals included malignancies (ppv . %). among the , women who received their first digital screen following one or several previous analogue screens, ( . % of digital referrals, p < . ) were referred again for a lesion for which she had been referred previously at analogue screening. these second referrals included malignancies (ppv . %, p= . ). conclusion: implementation of digital screening significantly increased the proportion of women referred twice for the same lesion. their ppv was significantly lower than the one found in women who had been referred repeatedly for the same lesion during analogue screening. purpose: to determine the impact of audits as a quality assurance tool to improve breast cancer screening performance. the dutch centrally organised breast cancer screening programme offers biennial mammography to women aged - years. a team of the national expert and training centre for breast cancer screening with peer radiologists conducts audits of all reading units every years as part of the quality assurance programme. data on screening outcomes are assessed and a on statistical significance and clinical relevance are: age, mass, calcifications, parenchymal deformity and asymmetric density. conclusion: with our nomogram we developed a tool to assist screening radiologists in determining the chance of malignancy based on mammographic findings. we propose cut-off values for assigning bi-rads categories in the dutch screening setting based on our nomogram which will need to be validated in future research. these values can easily be adapted for use in other screening programmes. purpose: automated d-breast ultrasound (abvs) is investigated as a six-monthly addition to annual breast cancer screening with mri+mammography (mm) in highrisk women (ltr> %). abvs, an inexpensive radiation-free technique, allows more frequent screening and temporal comparison. this study assesses effects of additional abvs examinations at baseline. the study population consists of women in whom abvs and mm were performed on the same day. all abvs and mm examinations were read by one of breast radiologist. the recall rate (rr), biopsy rate (br), cancer detection rate (cdr), sensitivity and specificity of abvs and mm screening were analysed. results: based upon mm, patients were recalled for further examination (rr= %). with abvs of these patients were also recalled, as well as other women. consequently, the rr increased to / . biopsies were deemed necessary in patients after mm and increased to with abvs added, an increase from %- %. additional abvs findings were resolved with targeted ultrasound. in total cancers were found by mm (cdr . %, sensitivity %, specificity %). two of these cancers were also detected by abvs (cdr . %, sensitivity % specificity %). the two missed cancers were retrospectively visible, but misinterpreted due to post-operative scarring. conclusion: adding abvs to high-risk mm screening increased rr and br at baseline. whether these negative effects are reduced when radiologists gain more experience and whether they are balanced by earlier detection of breast cancer due to the six-month interval of abvs remain to be determined.radiological review is performed ( interval cancers, screen detected stage-ii cancers and consecutive recalled cases). the audit is completed with a report, summarising the results and giving recommendations. this study compares four audit series ( - / - / - / - ) . results: recall rates (subsequent screens) increased from , , to per , respectively, in the four series. detection rates also increased from . , . , . to . per . distribution of tumour size and lymph-node status of invasive tumours remained stable (p= . ). the percentage interval and screen-detected stage ii cancers classified as "missed" during the review did not change ( % to %, p= . ). review of consecutive recalled cases showed an increasing number of cases the audit team would not have recalled with a higher recall rate of the screening radiologists. conclusion: we found audits are helpful in controlling the balance between (false positive) recalls and detected breast cancers. it also serves as a learning and feedback tool as it triggers discussion between screening radiologists. overall, it can be seen as an important quality assurance tool. purpose: according to current dutch guidelines, all women following a positive screening mammogram are referred for a full hospital assessment including surgical outpatient clinic and radiology department. till , all women with a positive screening mammogram in our screening region were only referred for further assessment to our radiology department. purpose of this study was to determine how often surgical consultation in women with a positive screening mammogram could be avoided by a radiological pre-assessment. methods and materials: all women with a positive screening mammogram, n= , referred to our radiology department from to were included. data were prospectively collected by a senior breast radiologist. in-hospital follow-up data were available till september . descriptive statistics were used. percentage of patients only assessed by a radiologist was determined. negative predictive value for malignancy was calculated from the in-hospital follow-up. results: of women ( %) were only assessed at the radiology department without further surgical consultation. during follow-up, of these women ( %) developed a malignancy in the same breast. at least of these malignancies were located at a different location than the original screening findings which led to the initial referral. the estimated negative predictive value for malignancy was . %. conclusion: by referring women with a positive screening mammogram to the radiology department for a pre-assessment, a surgical consultation was avoided in %, with an estimated negative predictive value for malignancy of . %. purpose: to determine the ability of t mapping of liver on gd-eob-dtpaenhanced mr imaging (mri) for estimating liver function and to compare the estimated liver function to the model for end-stage liver disease (meld) score. methods and materials: patients underwent gd-eob-dtpa-enhanced mri on a t system. patients were classified into two groups: meld score < (n= ) and meld score ³ (n= ). two turboflash sequences (ti = ms, ms) were acquired before and minutes after gd-eob-dtpa administration to obtain t maps. t relaxation times were determined indicating gd-eob-dtpa liver-uptake and correlated to the meld score. results: significant changes between t relaxation times of non-enhanced mri ( ms ± ms) and gd-eob-dtpa-enhanced mri ( ms ± ms) were observed (p < . ). t relaxation time for non-enhanced mri showed no significant differences (p= . ) between the group with meld score < ( ms ± ms) and the group with meld score ³ ( ms ± ms). after administration of gd-eob-dtpa t relaxation time of patients with meld score < ( ms ± ms) and patients with meld score ³ ( ms ± ms) shows a significant difference (p= . ). the shortening of t relaxation time was significantly lower for patients with a higher meld score (p= . ). conclusion: patients with advanced liver disease showed significantly lower changes in t mapping. therefore, evaluation of changes in t mapping of the liver parenchyma may serve as a useful method to determine whole liver function, to improve the estimation of segmental liver function and finally to define the grade of liver disease. liver dysfunction induced by amiodarone therapy: evaluation by sequential ct studies y. sonoyama, t. tajima, t. shiga, n. hagiwara, s. sakai; tokyo/jp (y-sonoyama@rad.twmu.ac.jp)purpose: to evaluate the relationship between the sequential changes of ct attenuation of the liver (ctl) and liver damage after administration of amiodarone (amd) for treatment of refractory ventricular arrhythmias. this was a retrospective study of patients ( men, women: age range - , mean ) with amd administration. serum level of drugs (amd and desethylamiodarone (d-amd), a metabolic product of amd), the percentage of rises in serum alanine transaminase (alt) level (alt%) and total administered dose of amd at evaluation ct were evaluated and compared with the ctl. as regards to patients who underwent ct before the initiation of amd administration, the medication periods and total administered doses of amd were compared with changes in ctl.results: there was a mild correlation between ctl and mean medication period (p= . , r= . ). there was a strong correlation between ctl and serum level of amd (p < . , r= . ), whereas there was a moderate correlation between ctl and serum level of drugs (amd) (p < . , r= . ). there were significant correlations between total doses of administered drug and the ctl (p= . , r= . ) and between alt% and the ctl (p= . , r= . ). conclusion: ctl was demonstrated to correlate with total administered doses of amd, alt%, medication periods and serum level of drugs, especially of d-amd. serial changes in ctl can be a sensitive less-invasive biomarker in patients treated with amd. the estimated population dose per caput is msv, which is lower than corresponding dose in usa ( msv) or in australia ( . msv). the highest average contribution is from ct, %. from plain radiography, fluoroscopy and interventional radiology the proportional fractions are %, % and . % respectively. from diagnostic nuclear medicine procedures, the estimated mean effective dose per caput is . msv. heart and bone examinations contribute % and %, respectively. conclusion: there were high variations between countries in frequencies (for example, in thorax radiography about ten-fold between spain or portugal and germany) and typical effective doses (for example, in ct head four-fold between denmark and luxembourg). this presentation will review the available data in europe using graphs in which countries can be identified. furthermore, the procedures contributing most to the population dose are highlighted. purpose: to assess the feasibility of the volumetric estimation of the left liver lobe, with d ultrasound, with mri comparison and surgical specimen. methods and materials: the data of consecutive patients referred for giving their left liver lobe to a child were reviewed (living donor transplantation program). the measurements of the d volumes of the segments ii and iii were performed retrospectively with comparison of the same evaluation performed with mri (the reference and routine technique for the preoperative assessment of the liver size). all the examinations were done twice by experts radiologists and radiologists in training. the results were statistically analysed (variance test, gage r&r and bland-altman). d and mri measurements were compared and related to surgically proved volume quantification. results: intra-and inter-observators reproducibility was poorly conclusive (for us and mri): gage r&r analysis is related to a prr of % for us and % for mri. bland-altman analysis was giving an underestimation of volume measurements with us (bias from - ml to - ml). agreement limits (- . sd to + . sd) for the observators were included between - . ml and + ml (from - . % to + . %). conclusion: correct estimation of the left liver lobe volume performed with d or mri is related to a low repeatability and a low reproducibility for both techniques. bland-altman analysis is also related to significative differences of volume measurement in both techniques. an accurate formula for a quick estimate of liver volume in polycystic liver disease m. chrispijn, t.j.g. gevers, j.p.h. drenth; nijmegen/nl (melissachrispijn@gmail.com)purpose: polycystic liver disease (pld) patients have severe hepatomegaly. primary aim of treatment is total liver volume (tlv) reduction. the gold standard to assess tlv is ct volumetry which involves manual delineating of the liver outline. this is time consuming and requires expertise. there is a clear need for an easy and fast approach to estimate tlv in routine practice. methods and materials: all pld patients with ³ ct scan were considered for inclusion. we measured the liver in transverse (t), anterioposterior (ap) and craniocaudal (cc) directions and performed ct liver volumetry. we had access to an inception and a replication cohort. we performed multiple linear regression to predict tlv using the three dimensions in the inception cohort. liver volumes were transformed logarithmically. the goodness of fit of the prediction model was assessed and stated as r . finally, we validated the prediction model in our replication cohort. results: the inception cohort included pld patients (median tlv ml (range - ml)). all three diameters were significantly correlated with tlv (p < . ). the linear regression model resulted in the following formula: predicted tlv = , +( . *t)+( . *ap)+( . *cc). our model predicted tlv accurately in the inception cohort (r = . adjusting and measuring ct dose in severely obese patients r. marcus, f. bamberg, k. neumaier, m.f. reiser, t.r.c. johnson; munich/ de (roy.marcus@med.uni-muenchen.de) purpose: ct in morbidly obese patients remains a challenge with respect to dose and image quality. automatic adaptation of parameters results in high dose length products which do not reflect the actual dose due to the shielding by the fat. aim of this study was to determine the actual dose and image quality. methods and materials: an alderson phantom was equipped with thermoluminiscent detectors. scans were performed using three set-ups: (i) 'obese' phantom in -cm circumferential fat (simulating cm/ kg patient) with a dual--source protocol at x kvp with current modulation; (ii) obese phantom with automatic potential and current modulation; (iii) slim phantom with automatic potential and current modulation; dose was calculated according to ircp- and based on dlp. image quality was assessed subjectively and by image noise. patient-specific whole body voxel model for accurate monte carlo ct dose estimation n. saltybaeva, y. smal, d. kolditz, w. kalender; erlangen/ de (natalia.saltybaeva@imp.uni-erlangen.de) purpose: the accuracy of ct dose estimates based on monte carlo (mc) techniques is limited as data is only available for the scanned volume. the purpose of this study was to generate and to validate whole body voxel models using the patient ct images extended by established voxel phantoms. methods and materials: measurements were performed on a somatom definition flash scanner (siemens, forchheim, germany) using the anthropomorphic rando-alderson phantom. the absorbed dose was measured using a set of calibrated thermoluminescent dosimeter (tld) chips for thorax protocols with tube voltage of , and kv. whole body voxel models were built as a combination of the patient ct images and the icrp adult male reference voxel phantom. mc simulations were performed using the impactmc software (ct imaging gmbh, erlangen, germany) for only the scanned volume and for the combined whole body model. measured and simulated dose values were compared for each tld chip. results: at kv, the dose values obtained by mc simulations based on only ct images differed from tld measurements by % on average with a maximum difference of % for the border slices, while the whole body model allowed for a mean difference of %. the difference between measured and calculated results was reduced by %, % and % for , and kv, respectively, when using the whole body voxel model instead of the ct-scanned volume only. the proposed whole body voxel model for monte carlo simulations significantly improves the accuracy of patient-specific ct dose estimates. purpose: accurate patient dose estimation using ct imaging is important particularly as the modality is being increasingly used. body habitus varies and the use of monte carlo simulations for "standard man" phantoms does not provide accurate dose estimation for non-standard patient sizes. the study proposes an algorithm for dose estimation for an individual patient from simulated data from mathematical phantoms. the algorithm interpolates doses simulated for ornl mathematical phantoms accounting for differences on patient and phantom sizes. four patient models were produced using anthropomorphic phantoms (representing -and -year-old children) with and without an additional fat-equivalent layer. all phantoms were scanned at and kv (trunk protocol). doses were measured with tld dosimeters. additionally, dicom images were segmented for organs and data were used as input for dose simulation. all simulations were performed with validated tool (impactmc). doses for phantoms and patients were estimated from the mc simulations using the proposed algorithm. calculated and measured doses were compared. the algorithm improved accuracy in dose estimation by , , , and % for small thin, small thick, large thin and large thick phantom sizes, respectively, compared with estimates based on ornl phantoms only. for patient data the accuracy in lung dose estimates improved from to %, and from to %, for -and -year-old patients, respectively. conclusion: the proposed algorithm improves dose estimation accuracy for individual paediatric patients. it is simple and suitable for implementation in software tool for dose calculation. purpose: the combined availability of dicom radiation dose structured report and active personal dosimeters in interventional radiology (ir) can support the optimisation of radiation protection, both of patient and staff. methods and materials: for nine months, interventionalists performing interventional cardiology procedures have used a personal active dosimeter (doseaware, philips) worn over the apron. information is displayed in real-time and transmitted to a database. the patient dosimetry report (allura fd , philips) has been also automatically collected for all procedures. a matlab routine integrates both information on procedure data and patient and staff exposures, providing a tool aiming to identify high and/or non-optimised exposures.results: on a sample of coronary angiography and percutaneous angioplasty procedures the derived mean kap (sd, maximum) per procedure was . ( . , . ) gycm . the first operator mean (range) personal equivalent dose was ( . ÷ . ) µsv/procedure. the mean (sd) scatter equivalent dose measured on the c-arm at the machine isocentre level per unit of kap was . ( . ) µsv/gycm . the availability of the dicom structured patient dosimetry report and the technology advancement of personal dosimetry can conveniently support the optimisation radiation protection process in ir. the described experience supports the initiative of isemir project (iaea, austria) that recommends the development of active dosimetry technology for a better monitoring of operators in ir and the development of a dicom operator structured dosimetry report as prerequisite to define and develop software platforms aiming to combine patient and staff exposure information. : purpose: the purpose of this study was to evaluate the additional diagnostic benefit of high-resolution steady state vibe imaging in peripheral mra. in this retrospective irb-approved study patients ( women, men, age . ± . ) were included who had undergone a peripheral mra exam after injection of . mmol/kg gadobutrol including a large field of view mra, time-resolved mra of the calf station and steady state d vibe sequence ( t siemens timtrio, . mm isotropic spatial resolution, pat , : min tacq per station) prior to the time-resolved mra. one board-certified radiologist rated image quality of the vibe sequences on an ordinal three-point scale and analysed the images for additional diagnostic findings. descriptive statistics and demographic patient data were used for further evaluation. the image quality of the vibe sequences of the pelvis, upper and lower leg was excellent in up to %, % and %, respectively. poor image quality was only detected in the upper ( %) and lower leg ( %). the vibe sequence yielded an additional diagnostic benefit in % of the patients overall. there was no significant difference in terms of additional findings between men and women ( % and %, p= . ). the patient sample revealed a distribution of % inpatients and % outpatients with additional pathology found in approximately % for each group. conclusion: steady-state d vibe sequences in peripheral mra yield additional relevant diagnostic findings in % and above in patients older than years irrespective of gender and patient status.author disclosures: h.j. michaely: consultant; bayer healthcare. in set-up iii, measured and calculated dose agreed well ( . vs. . msv). set-ups i and ii showed a discrepancy of % between measured and calculated dose ( . vs. . msv and . vs. . msv). image quality in set-ups i and ii was rated sufficient, compared to the excellent image quality in set-up iii. set-up.i. showed a lower image noise ( vs. hu) and lower dose ( %) than set-up ii. conclusion: morbidly obese patients receive higher dose in ct examinations, which is required to achieve diagnostic image quality. calculations based on dlp and standard conversion factors overestimate the dose by approx. % in kg patients, while the actual equivalent dose remains within the reference limits. the effects of head size/shape, head positioning, and bow-tie filter selection on peak tissue doses from brain perfusion -slice ct k. perisinakis , i. seimenis , a. tzedakis , a.e. papadakis , j. damilakis ; iraklion/gr, alexandroupolis/gr (kostas.perisinakis@med.uoc.gr) purpose: to determine peak doses to skin, eye lens, brain parenchyma and cranial red bone marrow (rbm) of adult individuals subjected to low-dose brain perfusion -slice ct studies, and investigate the effects of patient head size/shape, head position and bow-tie filter selection. methods and materials: peak doses to radiosensitive tissues were measured in individual-specific head phantoms subjected to the standard low dose brain perfusion ct on a -slice ct scanner using a novel monte carlo simulation software. the effects of head size/shape, head position during acquisition and bow-tie filter on resulting peak doses were investigated. the effects of head mis-centering and use of narrow bow-tie filter on image quality were assessed. the mean peak doses to eye lens, skin, brain and rbm were found to be , , and mgy, respectively. patient head size/shape was found to have minimal effect on peak doses, since maximum differences were less than %. bow-tie filter selection and head mis-centering were found to have a considerable effect on peak tissue doses with minimal image quality deterioration. the use of the narrower bow-tie filter available resulted in % reduction of peak tissue doses. conclusion: typical peak doses to skin, eye lens, brain and rbm from the standard low dose brain perfusion -slice ct exposure are well below the corresponding thresholds for induction of deterministic effects. the use of narrow bow-tie filters may considerably reduce peak absorbed dose to all above radiosensitive tissues with minimal degradation of image quality. detector dose vs image quality in radiography with digital detectors: a visual grading analysis r. decoster, h. mol, d. smits; brussels/be (robin.decoster@hubrussel.be)purpose: the introduction of digital detectors in the radiology predicted a dose reduction. due to the dynamic range, radiographs of sufficient quality can be produced with a lower detector air kerma (dak). however, this reduction was not observed. some authors indicate a creep toward higher dak, explained by better appreciation of the radiographs due to a higher contrast-to-noise ratio. to investigate the relation between the dak and the appreciation of image quality by radiologists, anterior-posterior (ap) radiographs of the knee and radiographs of the pelvis where collected randomly in radiologic centres. a visual grading analysis (vga) with a five-point scale was used to judge the image quality of seven anatomic structures. the mid-point of the scale was equalised to diagnostic image quality. six radiologists scored both datasets, in a controlled environment, with viewdex®. every observer received an instruction and a training dataset. to determine intra-observer variability twenty radiographs were repeated. results: the intra-observer variability was not significant (p> . ) in both datasets. the knee ap obtained a vga score of . , the pelvis obtained vga score of . . in both cases, the inter-observer correlations are high and significant. the correlation between the vgas and the dak (cr . µgy- . µgy; dr . µgy- µgy) was not significant in either dataset. neither were other analyses based on technical parameters. the vga revealed a mean image quality higher than diagnostic necessary. based on the dak, an overexposure is suspected. the relation between the dak range and the appreciation of the radiograph needs further investigation. (m.a.m.dekker@rad.umcg.nl) purpose: skin autofluorescence (af) is a non-invasive marker for advanced glycation endproducts (ages) and predicts cardiovascular disease (mortality) in diabetes and renal disease. we examined whether skin af is increased in subclinical atherosclerosis and whether it is associated with the degree of atherosclerosis independent of diabetes and renal function. methods and materials: cross-sectional study of patients referred for primary (pp;n= ) or secondary (sp;n= ) prevention. skin af was measured using the age-reader and the degree of atherosclerosis was assessed based on ultrasonographically detected plaques in carotid and femoral arteries (in pp only), and computed tomography-derived coronary artery calcium score (cacs . ], respectively; p = . and < . ). in controls and pad, skin af was higher in those with crp above median compared with below. in a multiple regression analysis, the association of skin af with the atherosclerosis categories was independent of age, gender, diabetes, framingham risk score, and kidney function. conclusion: skin af is increased in subjects with subclinical and clinical atherosclerosis, independently of known confounders. these data suggest that ages are associated with the burden of atherosclerosis. author disclosures: a.j. smit: founder; diagnoptics. evaluation of metabolic changes within the normal appearing grey and white matters in children with growth hormone deficiency: magnetic resonance spectroscopy and hormonal correlation j. bladowska, a. zimny, a. zacharzewska, t.m. gondek, a. banaszek, t. Żak, a. noczyńska, m. sąsiadek; wroclaw/pl (asia.bladowska@gmail.com) purpose: the pathogenesis of idiopathic growth hormone deficiency (ghd) in children, including possible cerebral metabolic alterations, remains unclear. the aim of the study was to evaluate the metabolic changes within the normal appearing brain in children with ghd using mr spectroscopy (mrs) and to correlate mrs measurements with hormonal concentrations. methods and materials: seventy-one children with ghd (mean age . yrs) and healthy controls (mean age . yrs) were enrolled in the study. the mrs examinations were performed on . t scanner. voxels were located in the posterior cingulate gyrus (pcg) and the left parietal white matter (pwm). the naa/cr, cho/cr and mi/cr ratios were analysed in both groups. there were also evaluated correlations between the metabolite ratios and hormonal concentrations: growth hormone (gh) in two stimulation tests and gh during the night, as well as igf- (insulinlike growth factor) and igfbp (insulin-like growth factor-binding protein) levels.results: there was statistically significant (p < . ) decrease of the naa/cr ratios in pcg and pwm in children with ghd compared to the normal subjects. other metabolite ratios showed no significant differences. we found also statistically significant positive correlations between naa/cr ratio in pwm and igfbp level, as well as gh concentration in stimulation test with glucagon. the reduction of naa/cr ratios may suggest loss of neuronal activity within normal appearing grey and white matters in children with ghd, thus mrs could be sensitive marker of cerebral metabolic disturbances associated with ghd and additional indicator for therapy with recombinant gh. purpose: the microstructure of tissues and white matter tracts in vivo may be studied with dti. the alterations involving the cerebral cortex associated in various degrees with subcortical white matter abnormalities often affect the projection white matter tracts. the white matter in cortical brain abnormalities is evaluated with diffusion tensor imaging (dti) and tract-based spatial statistics (tbss). methods and materials: patients ( year- year range) males and females) with different pattern of cortical alterations were studied. the dti data was processed in fsl. for each dti exam, brain extraction only of images with b value equal to zero was performed so that a mask of entire brain was created. gadoxetic acid-enhanced hepatobiliary phase mri and high b-value diffusion-weighted imaging (dwi) in the differential diagnosis between benign to malignant liver lesions p. arcuri, g. fodero, s. roccia, s. molica, v. arcuri; catanzaro/it (arppaolo@alice.it)purpose: the aim of our experience was to evaluate the value of gadoxetic acidenhanced hepatobiliary phase imaging and high b-value dwi in the differential diagnosis between benign and malignant liver lesions. methods and materials: twenty-four malignant liver lesions (fourteen small hcc and ten metastatic lesions) and twelve benign lesions (five fnh, four adenomas and three regenerative nodules in cirrhotic liver) were studied. a retrospective evaluation was made. the qualitative analysis was obtained by the evaluation of two radiologists of the lesions's signal intensity compared with that of the surrounding liver parenchyma on hepatobiliary phase images and dwi (b-value= s/mm ). the contrast-to-noise ratio (cnr) and relative contrast enhancement of lesions on hepatobiliary phase images and the apparent diffusion coefficient (adc) values were assessed (by rois) for quantitative analysis. statistical analysis was performed by the mann-whitney u test. p value less than . was considered statistically significant. in the qualitative analysis, nineteen malignant lesions ( %) and three benign lesions ( %) were hypointense on hepatobiliary phase images; five malignant lesions ( %) and nine benign lesions ( %) were iso-or hyperintense in the same phase. twenty malignant lesions ( %) and four benign lesions ( %) were hyperintense in dwi; four malignant lesions ( %) and nine benign lesions ( %) were iso-hypointense in dwi. in the quantitative analysis the mean relative contrast enhancement ratio of the malignant lesions was higher than that of benign lesions. conclusion: hypointensity on gadoxetic acid-enhanced hepatobiliary phase images and hyperintensity on dwi (b-factor= s/mm ) suggest malignant lesions rather than benign hepatocellular nodules. gadoxetic acid-enhanced mri of the liver: correlation between gadoxetic acid uptake and serum hepatic enzymes levels e. talakic purpose: to evaluate observer performance involving absolute visual grading analysis of image criteria using visual grading characteristic curves (vgc) and ordinal regression analysis during ct examination optimisation. methods and materials: images obtained from current and optimised head ct protocols (n= ) from suites were presented using viewdex on advantage workstations for evaluation by radiologists (n= ), grading the visibility of anatomical structures sourced from the european guidelines on quality criteria for ct. results: vgc analysis in terms of the area under the curve showed no significant differences (p> . ) from the . threshold value, indicating similar image quality between data sets. ordinal regression analysis indicated no significant (p> . ) change in image quality in suites and but discriminated between the data sets for suite and (p < . ). analysis on individual criteria indicated a difference (p < . ) in image quality between the protocols for all criteria in suite but no difference (p> . ) in suite . discussion: vgc curves demonstrated general trends between protocols. findings of ordinal regression analysis not only indicate significant differences in image quality but also identify specific anatomical criteria contributing to those differences. the importance of selecting the most appropriate method of analysis in optimisation techniques is highlighted as findings influence protocol implementation based on clinical requirements. conclusion: an overall % radiation dose saving was achieved as a result of optimisation of the head ct protocols. optimised protocols were implemented for initial diagnosis for three suites and only for follow-up cases excluding initial diagnosis for the remaining suite. : measuring hepatic functional reserve using low temporal resolution gd-eob-dtpa dynamic contrast-enhanced mri: a comparison study with galactosyl-human serum albumin scintigraphy and indocyanine green retention k. saito , j.r. ledsam , s.p. sourbron , t. hashimoto , y. araki , s. akata , k. tokuuye ; tokyo/jp, leeds/ uk (um jrl@leeds.ac.uk) purpose: to investigate if tracer kinetic modelling of low temporal resolution dynamic contrast-enhanced (dce) mri with gadoxetic acid (gd-eob-dtpa) has the potential to replace technetium m galactosyl human serum albumin (gsa) scintigraphy and indocyanine green (icg) retention for the measurement of liver functional reserve. methods and methods: patients ( males, females; mean age y) awaiting liver resection for various cancers underwent dcemri, gsa-scintigraphy and icg as part of routine pre-operative evaluation. examinations were conducted within a single month. underlying liver disease was present in patients. the gd-eob-dtpa mri sequence acquired images: pre-contrast, double arterial phase, portal phase, and minutes after injection. gsa-scintigraphy images were acquired every s following contrast injection. contrast uptake rate (ur) and extracellular volume (ve) were calculated from dce-mri, and the ratio of gsa radioactivity of liver to heart-plus-liver and percent of contrast uptake at minutes (lhl and lu , respectively) from gsa-scintigraphy. icg retention at minutes, child-pugh cirrhosis score (cps) and post-operative inuyama fibrosis biopsy criteria were also recorded. statistical analysis was with spss . purpose: to investigate dynamic contrast-enhanced computed tomography (dce-ct) for monitoring the effects of regorafenib on experimental colon carcinomas in rats by quantitative assessments of tumour microcirculation parameters with immunohistochemical validation. methods and materials: colon carcinoma xenografts (ht- ) implanted subcutaneously in female athymic rats (n= ) were imaged at baseline and after a one-week treatment with regorafenib by dce-ct ( slice dual source ct). the therapy group (n= ) received regorafenib daily ( mg/kg bodyweight) via gavage. quantitative parameters of tumour microcirculation (plasma flow, ml/ ml/min), endothelial permeability (ps, ml/ ml/min), and tumour vascularity (plasma volume, %) were calculated using a -compartment uptake model. dce-ct parameters were validated with immunohistochemical assessments of tumour microvascular density (cd- ), tumour cell apoptosis (tunel), and proliferation (ki- ). results: regorafenib significantly (p < . ) suppressed tumour perfusion ( . ± . to . ± . ml/ ml/min) and tumour vascularity ( . ± . to . ± . ml/ ml/min). significantly lower microvascular density was observed in the therapy group (cd- ; ± vs. ± , p < . ). in regorafenib-treated tumors, significantly more apoptotic cells (tunel; , ± , vs. , ± , , p < . ) and significantly less proliferating cells (ki- ; , ± vs. , ± , , p < . ) were observed. dce-ct tumour perfusion and tumour vascularity correlated significantly (p < . ) with microvascular density (cd- ; r= . and . ) and inversely with apoptosis (tunel; r=- . and - . ). arterial phase, portal venous phase, hepatovenous phase, equilibrium phase, and hepatobiliary phase which was minutes after gadoxetic administration. a test bolus was used to optimise the contrast injection protocol. signal intensity of the liver parenchyma in all phases was defined using region-of-interest (roi) measurements for enhancement calculation. serum hepatic enzyme levels (bilirubin; cholinesterase, che; aspartat-aminotransferase, ast; alanine-aminotransferase, alt; gamma-glutamyl-transpeptidase, ggt; alkaline phosphatase, ap) were available in all patients. spearman correlation test was used to test the correlation between liver enhancement during the different phases and serum hepatic enzyme levels.results: at late time points after contrast injection all serum hepatic enzymes were correlated with liver enhancement. bilirubin and che showed stronger correlations than the other serum hepatic enzymes and they became correlated at earlier time points. the strongest correlation was observed between bilirubin and enhancement during the hepatobiliary phase and between che and enhancement during the hepatobiliary phase. bilirubin showed negative and che showed positive correlation. the spearman correlation coefficient was - . for bilirubin and . for che. conclusion: in gadoxetic acid-enhanced mri of the liver gadoxetic uptake during the hepatobiliary phase is strongest correlated with bilirubin and che serum levels, whereas the other serum hepatic enzymes show weak or moderate correlations. purpose: aim of the study is to evaluate the use of mrcp using hepatospecific contrast media (gd-eob-dtba) to confirm biliary leak suspect and treatment planning. methods and materials: consecutive patients ( males, females -average age years), during months (april to may ) underwent mrcp study using gd-eob-dtba due to clinical suspect of biliary leak. using an . t mri scanner, t -weighted d gre pulse sequences before and in hepatospecific phase, after gd-eob-dtba injection, were performed. all patients with biliary leak underwent endoscopic, interventional radiology (ir) or surgical approach for treatment. results: biliary leak was clinically suspected in patients and underwent abdominal surgery ( laparoscopic cholecystectomy, various hepatic resections, resection of a pancreatic-duodenal mass) after days (av; range to ). in / biliary leak was found at minutes (av; range to minutes) from gd-eob-dtba injection, from intrahepatic ducts ( / ) site, cystic duct stump ( / ), both intrahepatic and principal biliary duct ( / ) and from a biliodigestive anastomosis ( / ). biliary leak was confirmed and successfully treated by percutaneous transhepatic cholangiography ( / ), endoscopic approach ( / ), ir and endoscopic "rendez-vouz" technique ( / ) and by surgical laparotomy ( / ). in / patients, no biliary leak was found and only clinical monitoring was performed, with good outcome. any adverse reaction or technical problem occurred during the mrcp examination. conclusion: mrcp with gd-eob-dtba is an high sensitivity, safe and fast examination to confirm the suspect and to locate precisely a biliary leak, concurring best planning for treatment. n-acetylcysteine for the prevention of contrast-induced nephropathy in rats m.f. İnci , i. Şalk , o. solak , Ü. vurdem , r. İnci ; kahramanmaraş/tr, sivas/tr, kayseri/tr (drfatihinci@gmail.com)purpose: to date, there is no effective treatment of contrast-induced nephropathy (cin). n-acetylcystein (nac) has yielded some promising results recently in the prevention of cin. in this study, the structural effects of nac on cin were analysed. methods and materials: forty adult wistar albino male rats were randomly allocated to four groups. the first group was the control group (n= ) which received only distilled water; second group was the contrast group (n= ) which received cm; the third group was the contrast plus nac group (n= ) which received cm and was treated with nac; and the last group was nac group (n= ) which received only nac. at the end of the rd day, the right and left kidneys were removed and reserved for histopathological examination. all tissue sections were examined with light microscope looking for histopathological changes by the same experienced pathologist, without knowledge of the prior treatment. histopathological examination was conducted in a blinded fashion, and glomerular injury scores, arteriolar injury scores and tubulointerstitial injury scores were calculated. results: there was a significant difference among the scores of glomerular injury, arteriolar injury and tubulointerstitial injury in all groups (p < . ).the scores of glomerular, arteriolar and tubulointerstitial injury of the group- and group- were not significantly different from each other (p < . ). renal injury scores in group- key: cord- - eo ityc authors: anzalone, nicoletta; castellano, antonella; scotti, roberta; scandroglio, anna mara; filippi, massimo; ciceri, fabio; tresoldi, moreno; falini, andrea title: multifocal laminar cortical brain lesions: a consistent mri finding in neuro-covid- patients date: - - journal: j neurol doi: . /s - - - sha: doc_id: cord_uid: eo ityc nan neurologic manifestations of severe acute respiratory syndrome coronavirus (sars-cov- ) have been recently reported [ , ] , with relevance to vascular aetiology [ , ] . the neuroinvasive potential of sars-cov- has also been advocated, by infecting the cns through hematogenous or neuronal retrograde route [ ] . here we report four cases of subacute encephalopathy occurring in patients with sars-cov- infection. they are part of a series of patients presenting with neurological symptoms studied with brain mri with otherwise no significant imaging findings. a multifocal involvement of the cortex was evident in all cases (figs. , ) . the multiple areas, from punctiform to some millimeters in extension, appeared hyperintense on t -weighted and flair images and were located in the parietal, occipital and frontal regions. on diffusion mri, all but two of the lesions were characterized by the absence of apparent diffusion coefficient (adc) changes (figs. c, c). a minimum involvement of the adjacent subcortical white matter was evident in only a few lesions. susceptibility-weighted imaging (swi) sequences were acquired in all patients and did not show any alteration. very subtle contrast enhancement was detected only in a cortical lesion. in one patient a follow-up mri scan was obtained after one month, demonstrating a complete resolution of all the lesions (fig. f-l) . all patients ( men, women; age range - years) have been intubated in the first week from onset of ards and presented neurological signs of agitation and spatial disorientation after weaning from mechanical ventilation. one patient had a generalized seizure. the time interval from onset of neurological symptoms to mri was - days. diagnosis of covid- was made by detection of sars-cov- viral nucleic acid in a nasopharyngeal swab specimen. all patients received the same treatment for sars-cov- infection. none of the patients had a relevant clinical history or previous treatment or hypertension. laboratory findings revealed in all cases a second smaller c-reactive protein peak from the initial one and raise of serum level of aspartate and alanine transaminase before the onset of neurological symptoms. d-dimer elevation was present and stable during the disease course. mri lesions' characteristics are unusual but demonstrate a highly consistent pattern through all the four patients with similar neurological symptoms. they do not fulfill any typical criteria for a definite neuroradiological entity. we speculate that this pattern may be related to a possible transient dysregulation of vasomotor reactivity. in particular, the cortical involvement may suggest a possible vascular mechanism more shifted toward transient vasoconstriction. although the predominantly parieto-occipital distribution of the lesions recalls posterior reversible encephalopathy syndrome (pres) [ ] , the prevalent cortical involvement and diffusion mri pattern are not typical of pres. at the same time, an alternative hypothesis of embolic cortical infarctions is unlikely due to the absence of diffusion restriction. it is currently known that sars-cov- might dysregulate the renin-angiotensin system (ras) system by acting on ace receptors, causing microcirculation impairment possibly impacting on blood flow regulation. more recently, evidence of direct viral infection of the endothelial cell and diffuse endothelial inflammation has been reported, resulting fig. forty-seven-year-old man diagnosed with covid- and presenting neurological signs of agitation and spatial disorientation after weaning from mechanical ventilation. before the onset of neurological symptoms, laboratory findings revealed a c-reactive protein peak ( . mg/l, normal range - mg/l). a axial flair, b diffusion-weighted image (dwi), c apparent diffusion coefficient (adc) map and (d, e) sagittal flair mr images. multiple, cortical areas of punctiform and gyriform flair and dwi hyperintensity (arrows) in both parietal lobes, with no adc changes fig. fifty-four-year-old woman diagnosed with covid- and presenting neurological signs of agitation and spatial disorientation after weaning from mechanical ventilation. before the onset of neurological symptoms, laboratory findings revealed a small c-reactive protein peak ( . mg/l, normal range - mg/l) and raise of total white blood cell count ( . × /l, normal range . - . × /l). cerebrospinal fluid (csf) analysis performed on the same day was negative for the presence of sars-cov- viral nucleic acid. a-e initial mri scan. f-l follow-up mri after one month. a, d, f, i axial flair, b, g diffusionweighted image (dwi), c, h apparent diffusion coefficient (adc) map and e, l sagittal flair mr images. multifocal linear and punctiform cortical flair and dwi hyperintensities in the left parietal lobe, bilateral precentral gyri and left middle frontal gyrus (a-c), with no adc changes. bilateral occipital involvement is shown in d, e, with a cortical/subcortical flair hyperintense lesion at the level of the left occipital pole. f-l follow-up mri demonstrates a complete resolution of all the lesions in endothelial dysfunction and impaired microcirculatory function [ ] . along with inflammation, there is a tendency to thrombosis in more severe cases [ ] . nonetheless, other vasculo-mediated mechanisms including altered vasomotor reactivity may play a role and cause neurological symptoms in covid- patients [ ] . in this regard, normalization of mri findings in one patient (fig. f-l) may corroborate the hypothesis of a transient functional nature of the impaired cerebral microcirculatory function. we believe that, due to the peculiarity and subtle appearance of the mri findings, our report may alert neurologists and radiologists to the existence of this subacute neuroimaging picture in sars-cov- patients, clearly different from cortical ischemia, and also to inform clinicians about the possible spontaneous reversibility of the picture. neurologic manifestations of hospitalized patients with coronavirus disease in wuhan, china neurologic features in severe sars-cov- infection large-vessel stroke as a presenting feature of covid- in the young neuroradiologists, be mindful of the neuroinvasive potential of covid- posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions endothelial cell infection and endotheliitis in covid- microvascular covid- lung vessels obstructive thromboinflammatory syndrome (microclots): an atypical acute respiratory distress syndrome working hypothesis informed consent all patients provided signed informed consent prior to mr imaging. informed consent was collected from the patients for the inclusion of deidentified clinical data in a scientific publication, in accordance with the declaration of helsinki. key: cord- -qtasvgtd authors: zhang, yu-dong; dong, zhengchao; wang, shui-hua; yu, xiang; yao, xujing; zhou, qinghua; hu, hua; li, min; jiménez-mesa, carmen; ramirez, javier; martinez, francisco j.; gorriz, juan manuel title: advances in multimodal data fusion in neuroimaging: overview, challenges, and novel orientation date: - - journal: inf fusion doi: . /j.inffus. . . sha: doc_id: cord_uid: qtasvgtd multimodal fusion in neuroimaging combines data from multiple imaging modalities to overcome the fundamental limitations of individual modalities. neuroimaging fusion can achieve higher temporal and spatial resolution, enhance contrast, correct imaging distortions, and bridge physiological and cognitive information. in this study, we analyzed over references from pubmed, google scholar, ieee, sciencedirect, web of science, and various sources published from to . we provide a review that encompasses ( ) an overview of current challenges in multimodal fusion ( ) the current medical applications of fusion for specific neurological diseases, ( ) strengths and limitations of available imaging modalities, ( ) fundamental fusion rules, ( ) fusion quality assessment methods, and ( ) the applications of fusion for atlas-based segmentation and quantification. overall, multimodal fusion shows significant benefits in clinical diagnosis and neuroscience research. widespread education and further research amongst engineers, researchers and clinicians will benefit the field of multimodal neuroimaging. neuroimaging has been playing pivotal roles in clinical diagnosis and basic biomedical research in the past decades. as described in the following section, the most widely used imaging modalities are magnetic resonance imaging (mri), computerized tomography (ct), positron emission tomography (pet), and single-photon emission computed tomography (spect). among them, mri itself is a non-radioactive, non-invasive, and versatile technique that has derived many unique imaging modalities, such as diffusion-weighted imaging, diffusion tensor imaging, susceptibility-weighted imaging, and spectroscopic imaging. pet is also versatile, as it may use different radiotracers to target different molecules or to trace different biologic pathways of the receptors in the body. therefore, these individual imaging modalities (the use of one imaging modality), with their characteristics in signal sources, energy levels, spatial resolutions, and temporal resolutions, provide complementary information on anatomical structure, pathophysiology, metabolism, structural connectivity, functional connectivity, etc. over the past decades, everlasting efforts have been made in developing individual modalities and improving their technical performance. directions of improvements include data acquisition and data processing aspects to increase spatial and/or temporal resolutions, improve signal-to-noise ratio and contrast to noise ratio, and reduce scan time. on application aspects, individual modalities have been widely used to meet clinical and scientific challenges. at the same time, technical developments and biomedical applications of the concert, integrated use of multiple neuroimaging modalities are trending up in both research and clinical institutions. the driving force of this trend is twofold. first, all individual modalities have their limitations. for example, some lesions in ms can appear normal in t -weighted or t -weighted mr images but show pathological changes in dwi or swi images [ ] . second, a disease, disorder, or lesion may manifest itself in different forms, symptoms, or etiology; or on the other hand, different diseases may share some common symptoms or appearances [ , ] . therefore, an individual image modality may not be able to reveal a complete picture of the disease; and multimodal imaging modality (the use of multiple imaging modalities) may lead to a more comprehensive understanding, identify factors, and develop biomarkers of the disease. in the narrow sense, a multimodal imaging study would mean the use of multiple imaging devices such as pet and mri scanners, different imaging modes such as structural mri, diffusion-weighted imaging, and magnetic resonance spectroscopy, or even different contract mechanism such as with or without contract agents in a single examination or experiment of a subject. this practice has been widely used in clinical diagnosis and medical research. for example, a routine protocol of mri examination of a stroke patient may include t -weighted, t -weighted high-resolution structural mri scans, diffusion-weighted imaging, swi, etc [ , ] . a protocol of an mri study of a psychiatric disorder may contain a combination of structural mri, functional mri, mr spectroscopic imaging, etc [ , ] . in the broad sense, a multimodal imaging study may mean the use of multimodal imaging data obtained separately, from different subjects, and/or from different clinical or research sites. this practice offers the advantages of large and diverse datasets. however, it also comes with challenges of sophisticated models, complicated data normalization (that includes correction of errors and variations imbedded in data from different institutions), data fusion, and data integration [ , ] . in recent years, the quantity of peer-reviewed journal articles on neuroimaging has been increasing steadily. a database (pubmed) query using the keywords in titles of "neuroimaging" or "brain imaging" returned more than , articles from to the present time when this paper was drafted in feb ( figure ). these publications include not only applications of multimodal neuroimaging in clinical examinations and biomedical research but also methodological studies in imaging processing and fusion of multimodal neuroimaging. therefore, this present paper will focus on the following two main aspects: ( ) we will review some of the recent, typical papers that exhibit the strength and limitations of the neuroimaging modalities and the corresponding analysis methods, and in particular, the needs for improved image fusion methods and ( ) we will review recent methodological development in data preprocessing and data fusion in multimodal neuroimaging. we note that although we tried to cover all neuroimaging modalities, we inevitably paid more attention to mri modalities. this is not only due to the most practical application and versatility of the mri but also due to the limitations of our expertise. figure shows the taxonomy of this review. the main contents of the paper are organized as follows. chapter will give a brief introduction to neuroimaging, and challenges of multimodal imaging; chapter introduces the commonly used neuroimaging modalities, which include computerized tomography, positron emission tomography, single-proton emission computed tomography, and magnetic resonance imaging, which has many modalities in its own right. for each modality, we will concisely describe its signal source, energy level, spatial resolution, temporal resolution, and major applications; chapter describe applications of neuroimaging in three major areas: the developing brains, the degenerative brains, and mental disorders. in each part, we will first briefly describe what the clinical and/or biomedical problems are, we then review recent papers on how neuroimaging has been used to address these problems, and we point out what the unmet needs and challenges; chapters to are devoted to the multimodal neuroimaging fusion, covering some important procedures in data fusion. the topics are not necessarily complete and their order of presentation is not necessarily coherent with the pipeline of fusion processing. chapter reviews the fundamental methods, which covers types, rules, atlas-based segmentation, decomposition, reconstruction, and quantification; chapter reviews subjective and objective assessment of data fusion in multimodal neuroimaging; chapter reviews the advantages of data fusion in improving the spatial/temporal resolution, distortion correction, and contrast; it also reviews the benefits of these advantages in fusing structural and functional images; chapter reviews atlas-based segmentations in multimodal imaging fusion; chapter reviews the quantification in multimodal neuroimaging fusion. while the focus of this part is given to pet and spect, some of the approaches and principles discussed here, such as partial volume correction and attenuation (relaxation), can be applied to quantitative mri modalities, such as dti, asl, quantitative susceptibility mapping (qsm), etc. chapter concludes the paper. figure numbers of peer-reviewed papers with the keywords of "neuroimaging" or "brain imaging" in titles (the numbers and the bar graph were generated by pubmed in feb ). in this part, we will review the current challenges of neuroimaging, including limited spatial/temporal resolution, lack of quantification, and imaging distortions. these challenges often create fundamental limitations on individual modalities of neuroimaging, while some challenges also exist in current multi-modal neuroimaging. this part will mainly cover the challenges of individual neuroimaging modalities that led to the development and ongoing research of multimodal neuroimaging methods. neuroimaging can be divided into structural imaging and functional imaging according to the imaging mode. structural imaging is used to show the structure of the brain to aid the diagnosis of some brain diseases, such as brain tumors or brain trauma. functional imaging is used to show how the brain metabolizes while carrying out certain tasks, including sensory, motor, and cognitive functions. functional imaging is mainly used in neuroscience and psychological research, but it is gradually becoming a new way of clinical-neurological diagnosis [ ] . the amount of information obtainable through single-mode imaging is limited and often cannot reflect the complex specificity of organisms. for instance, although ct imaging is effective in identifying normal structures and abnormal diseased tissues according to their density and thus can provide clear anatomical structure information, it cannot image soft tissue well. generally speaking, mri imaging has good soft-tissue contrast resolution for most sequences, but its display of bone structure is relatively poor. pet imaging and spect imaging are not limited by the detection depth, with high imaging sensitivity, and are easy to quantify, but their spatial resolutions are low [ ] . optical imaging refers to the detection of fluorescence or bioluminescent dyes using the principle of light emission. this technique has high sensitivity, no radioactivity, good specificity, and low cost. optical imaging allows dynamical monitoring of the replication process of virus bacteria in organisms. however, it has low spatial resolution and limited imaging depth [ , ] . therefore, it can be observed that various imaging technologies all have both benefits and drawbacks, as shown in figure , and it is difficult to provide comprehensive and accurate information through utilizing individual modality imaging. the nowadays most commonly used noninvasive functional imaging methods and their spatial and temporal range are illustrated in figure . it can be distinctly observed that among these most advanced methods, functional mri (fmri) reaches the highest range of spatial resolution. fmri can assess the whole brain and image the microscopic level hemodynamic processes at the layered and columnar levels of the human cortex, under the condition of a high-intensity magnetic field (i.e., submillimeter level) [ ] . however, it has a relatively lower temporal resolution in terms of imaging the neuronal population dynamics. electroencephalogram (eeg) and magnetoencephalography (meg) can both measure electromagnetic changes in the scale of milliseconds. however, their spatial resolution/uncertainty is more than several millimeters [ , ] . the microscopic level of neuroscience is often beyond the reach of noninvasive imaging techniques due to the requirement of high spatial or temporal resolution. the majority of imaging modalities are non-quantitative and have to gain complement information from other data. this additional information allows the normalization of signals, acquirement of absolute units, and inter-subject comparison. as an example, the fmri signal is a measure of neuronal activity incited hemodynamic changes caused by a combination of complex physical and physiological processes. in different subjects or brain areas, the same level of neuronal activity can evoke different corresponding fmri signals. as a consequence, fmri signals can only be considered as roughly proportional to the activity of neurons. four years later, in , the studies from ances have found that the cerebral blood flow (cbf) is relevant to fmri signal variations in individual's brain regions, patients' age groups, and health conditions. this broad relevance brings fmri signal high sensitivity [ ] . various approaches have been proposed to explain the ensuing sensitivity differences. amongst these approaches, the so-called calibrated bold approach proposed and improved by blockley, chiarelli and hoge over the years has been the most widely used [ ] [ ] [ ] . however, the more reliable absolute quantitative results of cbf with improved spatial and temporal resolutions are provided by the arterial spin labeling (asl) technique by the umich fmri lab. [ ] some neuroimaging modalities are prone to geometric distortions. echo-planar imaging (epi) is a fast imaging approach that could obtain the completespace data set just in a single acquisition. due to its unmatched acquisition speed, it has revolutionized the field of neuroimaging and has served as the standard readout module for most fmri and dmri acquisition. nevertheless, epi suffers from distortion and intensity loss mainly caused by field inhomogeneities, leading to relatively poor image quality [ ] . in general, the imperfection of equipment may result in information loss, noise amplification and artifacts, resulting in the distortion of images. to conclude, in practical application, utilizing individual modality imaging often has limitations, such as low sensitivity and specificity, low spatial/temporal/contrast resolution, distortion and so on. because of these deficiencies, we need to introduce the usage of multimodal neuroimaging to eliminate those shortcomings in some degree. positron emission tomography, shortened as pet, is a combination of nuclear medicine and biochemical analysis that is mostly used for the diagnosis of brain or heart conditions and cancer. instead of detecting the amount of a radioactive substance existing in body tissues of a specific location to check the tissue's function, pet detects the biochemical changes within body tissues. the biochemical changes can reveal the onset of a disease process before other imaging processes can visualize the anatomical changes related to the disease. during pet studies, only a tiny amount of radioactive substance is needed for the examination of targeted tissues. pet scans not only can be used to detect the presence of disease or other conditions of organs or tissues but can also be used to evaluate the function of organs, like the heart or the brain. the most common application of pet scan is cancer detection and treatment. figure (a) shows a pet image of the brain, and figure (b) shows a pet scan of the kidney [ ] . (a) brain scan via pet scan (b) kidney scan via pet scan (c) brain scan via spect (d) brain scan via mri figure common scan modalities single-photon emission computed tomography, commonly known as spect, uses gamma rays as the tracer to detect blood flow in organs or tissue. therefore, a gamma-emitting radioisotope, such as isotope gallium, should be injected into the bloodstream of the patient for spect. the computer collects the gamma rays from the tracer and shows it on the ct cross-section. it bears similarity with the traditional nuclear medicine planar imaging but provides d information as multiple images of cross-sectional slices through the patient. the information can be manipulated or reformatted freely according to diagnostic or research requirements. besides detecting blood flow, spect scanning is also applied for the presurgical evaluation of medically controlled seizures. figure (c) [ ] shows a spect scan of the brain magnetic resonance imaging (mri) utilizes strong magnetic field, magnetic field gradients, and radio waves to generate pictures of the anatomy and the physiological processes of the body [ ] . different from pet or ct, mri does not need the injection of ionizing radioisotopes or involve x-rays. as all radiation instances can cause ionization that leads to cancer, mri, without exposing the body to radiation, becomes a better choice than ct and one of the safest medical procedures. mri is widely used in hospitals and clinics for the medical diagnosis of different body regions, including the brain, spinal cord, bones and joints, breasts, heart and blood vessels, and other internal organs, such as the liver, womb or prostate gland [ ] [ ] [ ] . besides, mri can also be used for non-living objects [ ] . figure (d) shows an mri brain image [ ] . t , t and proton density (pd) are three basic types of mri imaging. t , t and pd, which all vary with sequence parameters, can simultaneously determine the contrast of the mr images [ ] . via selecting different pulse sequences with different timings, we can decide the contrast in the region being imaged. there are also other types of sequences, such as fluid attenuates inversion recovery (flair) and short tau inversion recovery (stir). in this section, we will only mention the three main types. figure shows the relationship between and , of which refers to plane [ ] . different from t and t , which mainly focuses on the magnetic characteristics of the hydrogen nuclei, pd is more related to the number of nuclei in the region being imaged. pd weighted images are obtained by a short echo time and a long repetition time, which can provide a more apparent distinction between the gray matter and white matter. pd weighted imaging is specifically useful for detecting joint disease and injury. figure (a) and (b) show a t weighted brain image and t weighted brain image, respectively [ ] . (a) t weighted brain image (b) t weighted brain image figure two types of weighted images of the same brain functional magnetic resonance imaging or functional mri (fmri) measures brain activity by detecting changes associated with blood flow. as it has been proved that when an area of the brain is in use, the blood flow to that area increases, which means that the neuronal activation and cerebral blood flow are matched. fmri is a particular type of imaging technology used to map the neuron activities in the spinal cord and brain of humans or animals by visualizing the change in blood flow, which is related to the energy use by brain cells. fmri also includes resting-state fmri [ ] or task-less fmri, which can provide subjects' baseline bold service [ ] . diffusion weighted/tensor imaging (dwi) generates image contrast from the differences in the magnitude of diffusion of water molecules within the brain. diffusion in biology is defined as the passive movement of molecules from a higher concentration region to a lower concentration region, which is also known as brownian motion [ ] . diffusion within the brain is affected by many factors, such as temperature, type of molecule under investigation, and the microenvironmental architecture in which the diffusion takes place. based on the mri sequences of which diffusion is sensitive to, the image contrast can be generated according to the difference in diffusion rates. dwi is highly effective for the early diagnosis of ischemic tissue injury, even before the pathology can be shown by the traditional mr sequence. therefore, dwi provides the time window for tissue salvaging interventions. perfusion weight imaging (pwi) is defined as a variety of mri techniques that are able to provide insights into the perfusion of tissues by blood [ ] . pwi can be used for the evaluation of ischaemic conditions, neoplasms, and neurodegenerative diseases. perfusion mri mainly has three main techniques: dynamic susceptibility contrast (dsc), dynamic contrast-enhanced (dce), and arterial spin labeling (asl). susceptibility weighted imaging (swi), previously known as bold venographic imaging, is a type of mri sequence that is extremely sensitive to venous blood, hemorrhage, and iron storage. as an fmri technique, swi can explore the susceptibility differences between tissues and detect differences based on the phase image. an enhanced contrast magnitude image can be obtained by combing the magnitude and phase data. swi is commonly used in traumatic brain injuries (tbi) and high-resolution brain venographies as it is sensitive to venous blood. magnetic resonance fingerprinting (mrf) [ ] is new mri technique that integrates mr physics theory and computer pattern recognition technology and realizes fast and multi-parameter parallel quantization imaging. the technique consists of three modules. first, the fingerprinting signals are excited and acquired from the subject in the mr scanner by the pseudorandom temporal varied pulse sequence to reflect the physiological property of tissue. second, the evolution of fingerprinting signals with different physiological parameter combinations are predicted by the computer simulation using the bloch equation; and a fingerprint dictionary indexed by the quantized parameters is constructed. finally, the pattern recognition technology is applied to find the matched fingerprinting entries for the measured fingerprinting signals, so as to obtain the corresponding quantization parameters and realize quantization mr imaging. different from most of the conventional mri modalities, which provide qualitative contrast-based images that are determined not only by the tissue properties but also by experimental conditions, mrf provides quantitative images of tissue properties that reflects pathological conditions of the subject. figure shows currently, the applications of mrf have been limited to biomedical research and the fusion of mrf with other neuroimaging modalities has not been reported. given its parametric and quantitative features, the mrf technique will play an important role not only in neuroimaging but also in fusion of multimodal neuroimaging. figure digital phantom experiments of conventional t weighted and t weighted mris, and mrf table lists the main advantages, disadvantages and applications of each neuroimaging technology. in this section, we listed some public databases, as shown in in this part, we will review recent advancements in the application of multimodal neuroimaging in some clinical and research areas such as early brain development, neurodegenerative diseases, psychiatric disorders, and neurological diseases. it is not our intention to cover all aspects or provide a complete review of these areas. instead, we focus on the aspects related to the development and applications of the multimodal neuroimaging techniques that meet the expectations and challenges of biomedicine. as such, each of the areas will begin with a brief description of background information such as clinical features, pathology, diagnosis, treatment of the diseases; then a general introduction of the roles, applications, and current status of the medical imaging techniques to the disease; the major part will be a review of recent papers that used one or more imaging modalities and used image fusion in multiple imaging modalities. recent studies show that the human brain experiences a rapid development in the first eight years and continues to develop and change into adulthood. during this long period, the brain develops in size, neuroanatomy, and functions. this period is significant for a person's physical and mental health, intellectual and emotional development, and learning, working, and life success [ ] [ ] [ ] . many factors have influences on the brain development of young children, which will have an impact on cognitive abilities and mental health in later life. these influencing factors include genes, maternal stress, and drug abuse, exposure to toxic environments, infectious diseases, socioeconomic status of the family, etc. approximately one-third of genes in the human genome are expressed primarily in the brain and will affect brain development. many psychiatric and mental disorders, such as autism, adhd, bipolar, and schizophrenia, are highly heritable or have genetic risk factors. maternal stress and drug abuse are associated with preterm birth and low birth weight and increased risk of neurodevelopmental disorders and mental disorders in children [ ] . the nutritional status of a child, which is affected by the socioeconomic status of the family, has a significant impact on neurocognitive development [ ] . neuroimaging techniques have been used to study normal and/or abnormal development of the brain, enhancing our understanding of neuroanatomy, connectivity, and functionality of the brain. these techniques also reveal the etiological associations of abnormal brain development with risk factors and contribute to the development of intervention procedures for diseased children [ ] . young children are more sensitive to radiation than adults are, so the use of pet and ct is limited. thanks to the in vivo nature and versatility of mri, not only young children but also newborn babies can be imaged, offering the opportunity to study white matter development and cognition in babies [ ] [ ] [ ] . mri has become the most important pediatric neuroimaging modality and has been widely used to study normal and abnormal brain development, allowing repeated longitudinal observation of the changes of brains of the same individuals before and after birth [ ] . in the following, our review will focus on the major mri modalities in pediatric imaging, which include structural, functional, and diffusion tensor imaging. early pediatric brain mri studies focused on the anatomical aspects using t -weighted and t -weighted images. qualitative studies provided information about changing patterns of gray matter and white matter differentiation and myelination in the first months of birth [ ] and early childhood [ ] . quantitative studies also revealed the changes in water contents, t , and t relaxation times in both gray matter and white matter; age-related changes in gray matter, white matter, and csf volumes. all these reflect ongoing maturation and remodeling of the central nervous system [ , ] . compared with adult cohorts, brain mr imaging of young children is challenging because of several factors. young children are less cooperative than adults with scanning procedures, which can be long, noisy, and uncomfortable when lying still for long; the images are often plagued with motion artifacts. the brain changes rapidly with age in early life after birth; the brain is not well myelinated; the contrast between gray matter and white matter is low. these pose difficulties to the optimized parameters for data acquisition protocol and also the standard parameters or criteria for the postprocessing procedures, such as the segmentation of the brain to determine cortical thickness [ ] . as a result, the physical properties, such as relaxation times, water content, diffusion coefficients, of the developing brain are not very well characterized. other technical challenges exist to scan young children [ ] . knowledge of the variations of biophysical properties, such as t and t relaxation times, water contents in gm and wm during the early life of children, is of critical importance to the understanding of neurodevelopment of young children and also to the development of diagnostic protocols of abnormal brain development. the measurement of these biophysical properties is challenging due to the prolonged scan time. recent technical development of magnetic resonance fingerprinting (mrf) allows rapid and quantitative analysis of multiple tissue properties [ ] . for example, mrf can provide t , t , and proton density maps of the brain in contrast to the conventional t -weighted, t -weighted, or proton density-weighted images. a recent paper reported an application of the mrf to study the t , t , and mwf of children aged from to years old [ ] . this study was able to record different patterns of variations of tissue biophysical parameters over different age stages. mrf techniques were also used to parametrically characterize brain tumors in children and young adults [ ] . in a broad sense, the parametric information in mrf opened doors to studies of the correlations between brain tissue properties and brain development, impairment, and physiopathology. techniques of image fusion can play an essential role in the processing, interpretation, and application of mrf data. degenerative brain diseases are caused by the decline of neuronal function and the reduction of numbers of neurons in the central nervous system (cns). known degenerative brain diseases include mild cognition impairment, alzheimer's disease (ad), parkinson's disease, etc. the patients of these diseases suffer from losses of functions in memory, speech, movement, etc. most of these diseases (except for some mild cognitive impairment subtypes) are progressive, i.e. the symptoms deteriorate as the brains age. as the population is rapidly aging, degenerative brain diseases post enormous impacts on individuals, families, and society. the etiology of these diseases is still unknown, and there is currently no cure. in the following sessions, we will review advances of neuroimaging on mci, ads, and pds. mild cognitive impairment (mci) is a clinical transition between normal aging and dementia or alzheimer's disease (ad), in which individuals have memory or other cognitive impairments beyond their age, but not to the extent of dementia. patients with mci often only have minor difficulties in functional ability. in studies based on people older than years of age, the incidence of mci is estimated to be at - % [ ] , and the mayo clinical study on aging shows an . % incidence of amnestic mci (amci) and . % incidence of non-amnestic mci (namci) in undiagnosed patients aged - years [ ] . several longitudinal studies have shown that most mci patients have a significantly higher risk of developing to dementia compared to the general u.s. population ( - %/ year) [ ] , the community population ( - %/ year), and the clinical patients ( - %/ year) [ ] [ ] [ ] . the latter data suggest that cognitive impairment tends to develop more rapidly for the patients that display serious symptoms. although some studies have shown that the incidence of mci reversals to normal cognitive function is as high as - %, recent studies suggest that the incidence may be lower. in addition, cognitive reversals over a short period of follow-up study showed that they did not prevent subsequent disease progression. magnetic resonance imaging magnetic resonance imaging (mri) techniques have been used in the clinical identification of mci and various types of dementia to predict the progression of mci to dementia. for mri measurements of brain structure, linear, area, or volume measurements can be used. the results showed that the area of mci brain atrophy was consistent with ad, but to a lesser extent, between the normal elderly (control group) and ad patients [ ] [ ] [ ] [ ] . similar results were found using voxel-based measurement and analysis, with abnormal changes in not only gray matter but also white matter [ , ] . the previous diagnosis of ad by structural mri was mainly based on the degree of brain atrophy, especially in the medial temporal lobe. the structural mri studies showed the atrophy along the hippocampal pathway (entorhinal cortex, hippocampus and posterior cingulate cortex), which was consistent with the loss of early memory. as the disease progresses, the temporal, frontal, and apical lobes shrink with neuronal loss, causing abnormalities in language, practice, vision, and behavior [ , ] . however, no definitive biomarkers have been identified by structural mri alone to distinguish mci and ad, to stage mci, and to predict mci conversion to ad or not [ , ] . mri-based functional imaging has been applied to the understanding of and to the discrimination between ad and mci. these techniques include perfusion-weighted imaging (pwi), diffusion-weighted imaging (dwi), diffusion tensor imaging (dti), and blood oxygen-dependent fmri (including task execution and resting state) [ ] . functional mri allows the delineation of microstructural brain changes, which is complementary to structural mri that can depict the global changes of the brain in mci. an mri-based functional imaging study that employed pwi, dti and proton mrs showed significant abnormalities in parameters derived from the three imaging modalities for ad patients. pwi and dti parameters showed a significant, but a lower degree of abnormalities in some areas for mci patients. fmri has also been used to distinguish ad and mci and to predict the transition from cognitive normal to mci and from mci to ad. recent studies show that bold-fmri can detect changes in brain function before mci progresses to ad, making it an important technique to study the neural mechanism of mci [ , ] . proton magnetic resonance spectroscopy ( hmrs) is a noninvasive imaging method that can detect biochemical and metabolic changes in brain tissue in vivo and conduct quantitative analysis. early mrs studies show abnormal concentrations of n-acetylaspartate (naa), creatine, and choline are associated with the status of memory and cognition impairment and have a promise for assessing cognitive status, evaluating response to medicine, and monitoring progression during treatment [ ] [ ] [ ] . in recent years, with advances in the technical development of mr hardware and pulse sequences, the roles of glutamate, the excitatory neurotransmitter, and gaba, the inhibitory neurotransmitter, in mci patients became the main focus [ ] [ ] [ ] . for example, with ultra-high field tesla mr scanner, abnormal concentrations of gaba, glutamate, naa, glutathione, and myo-inositol (mi) in different brain regions were detected [ ] . the manifestations of hmrs in mci patients were mainly shown in decreased naa/cr ratio and increased mi/cr ratio. the pathological results showed neuronal deletion and glial proliferation, and the changes in metabolite concentration were consistent with the pathological results [ , ] . multimodal imaging pet and spect provide insight into blood perfusion and metabolism in tissues and organs, as well as explore changes in function. the nuclear medical images of amci patients showed decreased perfusion and metabolism in the hippocampus, temporoparietal lobe, and posterior cingulate gyrus. studies using pet, spect, and mri have shown that glucose metabolism in the hippocampus, glucose metabolism rate in the bilateral temporal-parietal lobe, and blood perfusion in patients with amci are lower than those in normal elderly. these studies have also shown that low glucose metabolism in the temporal-parietal lobe is a reliable indicator of conversion to ad [ ] [ ] [ ] . excessive deposition of β-amyloid peptide in the brain and the cascade reaction caused by it are the early onset of ad. therefore, early detection of β-amyloid peptide in the brain can help identify patients with amci, and monitor the progression of the disease and treatment effect. it was found that the c-pib-pet could attach to aβ in the brain. pet imaging showed the amount and location of aβ deposition in the brain, which was expected to be an early diagnostic method for ad [ ] [ ] [ ] . multimodal imaging techniques involving mri-based imaging and pet-based imaging have been frequently used for prediction, characterization, and classification of mci [ , ] . in facilitating these complex tasks, imaging fusion methods based on artificial intelligence, neural network, deep learning and graph theory have been used [ ] [ ] [ ] . brain network studies based on multimodal mri and graph theory analysis have found that the topological properties of ad and amci affected brain networks have undergone abnormal changes, which mainly manifested as the imbalance between functional differentiation and integration. this approach provided a new way to reveal topological mechanisms and pathophysiological mechanisms of brain networks [ , ] . in addition, the combination of graph theory analysis and classification analysis suggests that the brain network topology attribute can be used as an imaging marker of ad and has a good clinical application prospect. alzheimer's disease (ad) is a neurodegenerative disorder and the most common cause of dementia. ad is characterized by progressive memory loss, aphasia, loss of use, loss of recognition, impairment of visual-spatial skills, executive dysfunction, and personality and behavior changes [ , ] . it has become one of the major diseases that seriously threaten the health and quality of life of the elderly [ ] . the onset of ad is slow or insidious, with patients and their families often unable to tell when it starts. it is more common in the elderly over the age of (the average male is , and the average female is years old), with more females than males (female to male ratio of : ) [ ] . there is currently no cure for ad, but large numbers of novel compounds are currently under development that have the potential to modify the course of the disease and to assess the efficacy of these proposed treatments. there is a pressing need for imaging biomarkers to improve understanding of the disease and to assess the efficacy of these proposed treatments. magnetic resonance imaging structural mri (smri) is the most widely used imaging modality for the study of ad. the techniques for analyzing smri are classified into volume-based and surface-based methods [ ] . previous studies have shown that hippocampal volume atrophy and whole-brain atrophy independently predicted the progression of ad [ ] . hippocampal damage or atrophy occurs in the early stage of ad, which is an important structural basis for the clinical manifestations of ad. although global hippocampal atrophy in ad was well accepted, the differences were often detected large sample-size studies [ ] . de winter et al. studied elderly ad patients with depression and healthy control elderly people and examined all the subjects with smri and neuropsychology [ ] . they found that there was no significant difference in the positive rate of aβ between the depression group and the healthy control group. however, the hippocampal volume in the depression group was significantly smaller than that in the healthy control group. there is significant hippocampal atrophy in elderly depression patients, and hippocampal atrophy has nothing to do with aβ, which challenges the reliability of hippocampal atrophy in the clinical diagnosis of ad. it is suggested that hippocampal atrophy not only occurs in ad but also in senile depression. the study of smri indicates that the brain atrophy shown by brain morphology and structure has reference value for the diagnosis of ad. however, the diagnosis of ad still needs to be confirmed by combining clinical manifestations, neuropsychological assessments, and other examination methods. it also indicates that follow-up is needed for suspected depression in patients with ad. the above studies showed the limitations of structural mri and the necessity of the multimodal approach in the study of ad [ ] . other mri modalities, including functional mri, dwi, pwi, have also been widely used in the study of neurodegenerative diseases. we will review recent advances of the resting-state functional magnetic resonance imaging (rs-fmri) as an example. as opposed to the conventional task-based fmri, rs-fmri does not require the subject to perform any task or be subjected to any external excitation. the rs-fmri captures the low-frequency oscillations signals that are related to the spontaneous neural activity of the brain by analyzing the brain blood oxygen level dependent (bold) signal. sophisticated methods of analysis of the rs-fmri data depict the functional connectivity of the brain. the rs-fmri has been used to reveal how the networks of the functional connectivity are correlated to the brain functions of individuals with cognitive impairment. zamboni et al. found that the recognition task of ad patients was related to the increased activation of the lateral prefrontal area, which also overlapped with the functional connection enhancement area indicated by the rs-fmri [ ] . zhou et al. predicted the pathological changes of ad by using the calculation model of resting brain function network and studied five different brain regions vulnerable to neurodegenerative diseases through the use of task state fmri [ ] . they found that the brain network of ad patients may have the phenomenon of weak functional connectivity and their ability to transmit information of functional brain network decline. wang et al. found that the functional brain network of mci patients had different degrees of functional connectivity disorder. the evaluation of overall functional brain connectivity of patients plays an important role in the early diagnosis and treatment of ad [ ] . abnormal brain connectivity can be a biomarker of the disease. many neuropsychiatric diseases and dementia can change the default mode network (dmn) of the brain. identification of the change in the connectivity of dmn is constructive for the early recognition of ad. jin et al. collected patients with amci and healthy people to analyze rs-fmri data by independent component analysis (ica) [ ] . they found that the functional activities of the lateral prefrontal cortex, left medial temporal lobe, left middle temporal gyrus and right angular gyrus in amci patients decreased, while the activity of the middle and medial prefrontal cortex and the left parietal cortex increased. further studies found that the functional activities of the left lateral prefrontal cortex, left middle temporal gyrus and right angular gyrus were positively correlated with memory, especially delayed memory [ ] . although there was no significant difference between the two groups in the degree of medial temporal lobe atrophy, the functional activities of the left medial temporal lobe decreased. this decrease suggests that the functional changes of dmn may occur in the early stage of ad, i.e. amci, and the functional changes may occur before the obvious change of brain structure. multimodal imaging due to severe overlap in symptoms and findings of individual imaging modalities of the neurodegenerative diseases, it is difficult to identify the biomarkers that could be used to differentiate the types of these diseases and/or to stage the progress of a disease. therefore, multimodal neuroimaging techniques are used to overcome the challenges [ ] . as pointed out in [ ] , individual modalities of mri and eeg lack precision in ad diagnosis and staging. by employing both imaging modalities, with the mri measuring the cortical thickness and the eeg measuring the rhythmic activities, the authors found joint markers that identified the subjects of alzheimer's disease with an accuracy of . %, a significant increase from those of individual modalities. while some studies of multimodal imaging confirmed correlations of findings among individual modalities as in a study of smri and fmri [ ] , multimodal imaging studies can also be used to dissociate the tau deposition and brain atrophy in early ads using pet and mri. the study found that the tau load had little effect on the gray matter atrophy, and this might imply that tau protein deposit precedes and predicts brain atrophy. the multimodal imaging studies require statistical and analytical models, advanced computing algorithms, and especially, novel data fusion methods [ ] [ ] [ ] [ ] , which will be reviewed in detail in the following sections. parkinson's disease (pd) is a chronic progressive degenerative disease of the central nervous system, which is commonly seen in elderly patients. typical clinical manifestations of pd include static tremor, myotonia, bradykinesia, and abnormal posture and pace [ ] . with the continuous increase of the aging population, the incidence and disability rates of the population are also increasing year by year. the results of epidemiological surveys indicate that the prevalence of pd in people over is about . %, and the prevalence of pd in people over is as high as % [ ] [ ] [ ] . pd is more and more harmful to the health of the middle-aged and elderly, especially involving the central nervous system. due to the lack of objective basis and diagnostic criteria for the diagnosis of pd, the previous clinical diagnosis of pd was mainly based on the clinical symptoms, resulting in a low coincidence rate between the clinical diagnosis and pathology of pd and in a significant lag behind the pathological changes of brain microstructure. with the increasingly standardized diagnosis and treatment of pd, neuroimaging examination has become an indispensable part of the diagnosis. this differential diagnosis of pd can help identify different movement disorders, locate anatomical dysfunction sites, and determine the causes of the lesion, which will improve clinical evaluation and prognosis [ , ] . magnetic resonance imaging structural cranial mri can distinguish white matter from gray matter by setting different imaging parameters while avoiding radiation. it is better than cranial ct in revealing white matter lesions, small infarcts, subacute intracerebral hemorrhage, and lesions in the brain stem, subcortical regions, and posterior fossa. on structural mri such as t , t -weighted, and fluid-attenuated inversion recovery (flair) images, pd patients usually exhibit broadening of the ventricles (caused by extrapyramidal atrophy) and widened sulci (diffuse brain cortical atrophy) [ ] . the quantitative measurements of cortical atrophy can be measured based on voxel morphometric assessment. when the compact belt of the substantia nigra shrinks and the short t signal of the substantia nigra disappears, the width of the dense belt of the substantia nigra, the ratio of the width of the dense belt of the substantia nigra to the diameter of the midbrain, the caudex nucleus, the putamen nucleus, the thalamus and other areas of interest are measured. in evaluating the extent of atrophy, physiological changes such as age increase and relevant clinical supporting evidence should be taken into account [ ] . neuromelanin-sensitive mri is used to detect neuromelanin, a surrogate biomarker for the pd. neuromelanin is a dark pigment found in neurons in the substantia nigra pars compacta. the concentration of neuromelanin increases with age but is found to be around % higher in pd patients compared with age-matched non-pd subjects, due to the death of cells in the substantia nigra. neuromelanin-sensitive mri allows the visualization of the neuromelanin-containing neurons in the substantia nigra, pars compacta. with the use of morphological analysis and signal intensity (contrast to noise ratio), the width and cnr of the lateral and central substantia nigra were found to be significantly lower in the pd subjects than in the control group and untreated essential tremor (et) group [ , ] . therefore, this imaging technique can be potentially used as a biomarker to differentiate et from the de novo tremor-dominant pd subtype. the neuromelanin levels were quantitatively assessed using neuromelanin-sensitive mri and quantitative susceptibility mapping (qsm) [ ] , an mri modality for measuring the absolute concentrations of iron, calcium, and other substances in tissues based on changes of local susceptibility [ ] . while the neuromelanin imaging found significantly lower neuromelanin levels in the pd group than the health controls (hc), which is in agreement with the neuromelanin mri only study, the qsm values were significantly higher in the ps group than in the hc group. this result suggested the usefulness of qsm in detecting pd [ ] . resting functional magnetic resonance imaging (fmri) is a technique that collects the blood oxygen level dependent signal changes of patients in the awake and resting states to obtain the functional activity level of the brain in the baseline state. in recent years, fmri has been widely used in clinical studies of all motor disorders or neurodegenerative diseases, including pd [ ] [ ] [ ] . resting-state functional mri (rs-fmri) can calculate a variety of brain activity attributes, such as local consistency, range of low-frequency fluctuation, and amplitude of low-frequency fluctuation etc. by observing the correlation between time-dependent signals of blood oxygen levels in different voxels or areas of interest, we can further evaluate the synchronization of functional activity in different brain areas, i.e. functional connectivity [ , , ] . in recent years, calculation methods based on independent component analysis, granger causality analysis and graph theory can help to find complex pattern changes in the brain network of pd patients. other imaging modalities and multimodal imaging other imaging modalities, including pet, spect, eeg, ct, have been applied to study the functional and structural abnormalities and changes of pd patients, and they provide much complementary information to mr-based imaging modalities mentioned earlier. pet studies investigated cerebral glucose metabolism with or without medications, with or without brain stimulations [ ] [ ] [ ] . metabolic and brain chemical changes related to dopamine neurons in pd patients were also studied using spect, which cannot be assessed by other mri modalities including proton magnetic resonance spectroscopy (mrs) [ ] . by jointly applying spect and dti, this study identified regions and connections of the brain that differentiate pd patients and healthy controls. different from the imaging modalities in that study, a recent study employed pet scans with two different tracers and rs-fmri to investigate variations of metabolism and functional connectivity of the pd patients [ ] . it identified correlations between motor impairments with hypometabolism and hypoconnectivity in multiple brain regions. with the use of different modalities under similar aims, results from these studies can provide complementary information for the impaired regions. the data from them can be integrated and analyzed using data fusion like the work in [ ] , in which data of anatomical mri, rs-fmri, and dti were analyzed for more accurate and reliable biomarkers of pd. mental disorders are conditions that affect a person's thinking, mode, behavior, relationship with others, and depression is a common mood disorder, which can be caused by a variety of reasons. the main clinical feature is marked with persistent depression of mood, which is incompatible with the situation. in severe cases, suicidal thoughts and behaviors may occur. most cases tend to show recurrence; and most can be relieved each time, while some may have residual symptoms or progress to chronic depression. at least % of clinical depression patients also show manic episodes and should be diagnosed as bipolar disorder [ , ] . what we commonly call depression is clinical or major depression, which affects % of the population at some point in their lives [ ] . in addition to the severe emotional and social costs of depression, the economic costs are also enormous. according to the world health organization, depression has become the fourth most serious disease in the world and is expected to become the second most serious disease after coronary heart disease by [ ] . so far, the etiology and pathogenesis of depression are not clear, and there are no obvious signs or laboratory indicators of abnormality. although there have been many basic and clinical studies on depression, no critical breakthrough has been made in the three most important clinical problems: pathogenesis, objective diagnosis, and efficient treatment. a key breakthrough in these issues is to find and establish a stable biological marker from gene to clinical phenotype and then further study its pathogenesis, establish objective diagnostic methods and develop efficient clinical therapy. magnetic resonance imaging up to now, in the clinical research field of mental illness, especially depression, the most sought after biological markers may potentially be provided by the study of neuroimaging, especially brain mri. brain mri examination have characteristics of good clinical applicability, non-invasive, simple operation, universal, relatively stable results and easy to repeat, but its sensitivity and specificity need to be improved. brain mri research has become an intermediate mechanism from molecular research to clinical phenotype. through this mechanism research, we can not only explore how genes, molecules, and proteins affect the brain structure and function of patients with depression but also use mri as an objective diagnostic tool for the most urgent clinical needs. over the past years, the application of multi-mode mri technology to study the brain structural and functional characteristics of depression, especially to establish clear biological marker targets around the characteristics of emotional circuits, has become one of the major scientific frontiers in the basic and clinical research of neuroscience. many studies have found that patients with depression have abnormalities in brain structure and function of emotional circuits, as well as in neurotransmitters associated with these circuits [ , ] . mri studies in recent years found that the depressive mood is associated with three brain regions, namely in the amygdala and the ventral striatum as the primary mood areas, the orbital gyrus, medial prefrontal cortex and cingulate gyrus as the emotional auto-regulation areas, and the dorsolateral and ventrolateral prefrontal cortex as the center of the active emotional regulation area [ ] [ ] [ ] . multimodal mri techniques used in mental disorders seek to find correlated, complementary, and/or converging image features from multiple image modalities and applied sophisticated analytical methods to identify robust biomarkers for the types of depression. a study employed dti, magnetic resonance spectroscopy (mrs), rs-fmri, and magnetoencephalography (meg) and revealed patterns of abnormalities of patients with major depressive disorders. these patterns included factors in the neurotransmitters (glutamate concentration), white matter fibers (fractional anisotropy), and functional excitations (fmri) [ ] . a multimodal mri study involves structural mri and asl to assess grey matter volume and regional cerebral blood flow in mdd patients. this multimodal study revealed negative correlations between the extent of depressive symptoms and cbf in the bilateral para-hippocampus and between depressive symptoms and cbf in the right middle frontal cortex [ ] . in addition to confirming the correlations among findings of individual modalities, some multimodal mri studies, however, found disrelations among individual findings in the mdd group [ ] . further multimodal data analysis involving mri imaging data and clinical, neurobiological metrics of the patients may resolve the disparities. among the methods of the multimodal mri image fusion in depressive disorders, support vector machine (svm) [ ] and linked independent component analysis [ ] was recently used, respectively, to identify biomarkers for the classification and prediction of symptom loads of heterogeneous mdd cohorts. imaging data and neurobiological data were included in the data fusion. in both studies, the results did not show strong support for the hypothesis and did not provide sufficient evidence for the sought biomarkers [ , ] . obsessive-compulsive disorder (ocd) is a group of neuropsychiatric disorders with obsessive thinking and compulsive behavior as the main clinical manifestations. it is characterized by the co-existence of conscious compulsion and anti-compulsion, and the repeated intrusion of thoughts or impulses into the daily life of patients that are often meaningless and involuntary. although patient perceives that these thoughts or impulses are their own and resist them to the utmost degree, he or she is still unable to control them. the intense conflict between the two causes the patient great anxiety and pain, which affects his other study, work, interpersonal communication, and even daily life. magnetic resonance imaging voxel-based morphometry was widely used in the smri studies of ocd. these studies measure the structures and volumes of regions of interest in various ocd groups and healthy control groups. ocd patients were found to have lower grey matter volumes in specific regions of the brain. for children with ocd, these regions include the bilateral frontal lobe, cingulate cortex, and temporal-parietal junction [ ] . for adults with ocd, these regions are the left and right orbitofrontal cortex [ ] . lower volumes were also seen in white matter in the cingulate and occipital cortex, right frontal and parietal and left temporal regions [ ] and in a small area of the parietal cortex for patients with ocd [ ] . fmri studies can provide information about the pathophysiology of ocd [ , ] . however, whether this information from single fmri modality alone could be of clinical value in the diagnosis of individual patients is not clear [ ] . the pathophysiological feature of ocd, as revealed by fmri studies, suggest that abnormal brain metabolites may be implied in ocds. abnormalities in brain metabolite concentrations in patients with ocd were investigated using proton mrs [ ] [ ] [ ] [ ] . among about ten detectable metabolites, glutamate, glutamine, and gaba are of particular interest, as they are involved in neurotransmission. recent studies show that ocd patients had an elevated gaba level and a higher gaba/glutamate ratio in the anterior cingulate cortex [ ] , and they had lower gaba concentration in the prefrontal lobe, as compared to healthy control groups [ ] . the roles of glutamate and glutamine in ocd are in the focus of research interest, but the findings lacked reasonable consistency [ ] [ ] [ ] . the heterogeneity of structural neuroimaging findings of ocd may reflect the heterogeneity of the disease itself. multimodal mri multimodal mri studies in ocd provide complementary, correlated and/or integrated information of findings from individual modalities [ , ] . early structural mri study suggested that the volume reduction of superior temporal gyrus (stg) is associated with the pathophysiology of ocd [ ] . a functional mri study found increased low-frequency fluctuations in neural activities in stg [ ] . a correlation between these findings was found in a combined structural mri and fmri study, which shows that the volume of the superior temporal sulcus is strongly correlated with functional connectivity between several brain regions that may form a neuro-network [ , ] . the simultaneous h-mrs and dti study, to investigate metabolic and white matter integrity alterations in ocd, found that the level of glx to cr ratio in the anterior cingulate cortex was higher in the ocd group than the healthy control group [ ] . the study also found from dti analysis that the fa values in the left cingulate bundle of the ocd group were significantly higher than the healthy controls. a limitation of this study is that the glx level, which is a combination of glutamate and glutamine, was measured instead of measuring glutamate and glutamine individually. it has been recognized that it is difficult to distinguish these two structurally similar metabolites using tesla scanners and ultra-high magnetic field (e.g. t) scanners are required. schizophrenia is a group of serious psychosis with unknown etiology, which usually starts slowly or sub-acute in the young and middle-aged individuals [ ] . clinically, it often manifests as a syndrome with different symptoms, including abnormalities in sensory perception, thinking, emotion, and behavior, as well as uncoordinated mental activities [ ] . schizophrenia is a multifactor disease [ ] . deterioration. some patients eventually show recession and mental disability, but some patients can maintain recovery or basic recovery after treatment [ ] . magnetic resonance imaging structural mri was widely used to study the morphology and volumetry of the brains of schizophrenia patients. studies found that the average brain volume of schizophrenia patients was smaller than that of healthy people [ , ] . the abnormal volume and structure of white matter usually appear before the onset of the disease, and these abnormalities tend to be stable during the development of the disease [ ] ; the change of gray matter volume is more evident after the onset of the disease and decreases progressively over time [ ] . according to a longitudinal study, gray matter deficiency in schizophrenia mainly occurs in the first five years [ ] . quiet complement to the structural mri, dti reveals the abnormalities of white matter microstructure of schizophrenia patients [ ] . decreased fractional anisotropy in white matter tracts, different cortical regions, and subcortical regions was found in schizophrenia patients in some studies. however, controversial findings were also reported [ , ] . these inconsistencies might be attributed, in part, to small sample sizes. a large-scale dti study involving more , subjects found widespread white matter microstructural differences between schizophrenia patients and healthy controls [ ] . significantly reduced fractional anisotropy values were found in of the investigated regions within the white matter. furthermore, significantly higher mean diffusivity and radial diffusivity were also observed in schizophrenia patients than in healthy controls. functional mri techniques are used to detect the deficits in neural networks of patients with schizophrenia [ ] . brain network studies show that the functional connectivity of the default mode network (dmn) in schizophrenic patients has changed. although the research structures are inconsistent, most studies show that dmn functional connectivity is enhanced in schizophrenia, and functional connectivity in the prefrontal cortex is weakened (especially in the prefrontal cortex) [ ] . in addition, the functional connections of auditory/linguistic networks and basal nuclei are related to auditory hallucinations and delusional symptoms. the study of brain structure networks found that the number of frontal and temporal core nodes decreased and the average shortest path increased, indicating decrease in global efficiency. wang et al constructed a network of dti images of schizophrenia patients and age-matched normal subjects [ ] . they found that: compared with the normal subjects, the global efficiency of the schizophrenic group decreased; the local efficiency of the core nodes distributed in the frontal cortex, the paralimbic system, the limbic system and the left putamen decreased; and the global efficiency of the network was negatively correlated with the panss score. research shows that the change in brain structure network started at the beginning of the disease. more severe symptoms indicate lower the global or local efficiency of the network, and the slower the speed of information integration. magnetic resonance spectroscopy studies found that the brain metabolism of schizophrenia patients was abnormal [ ] [ ] [ ] . the levels of n-acetyl-aspartic acid (naa) in the hippocampus, frontal lobe, temporal lobe, and thalamus of schizophrenic patients decreased; the levels of naa in the thalamus of high-risk groups also decreased, while the level of naa in temporal lobe decreased. it was also found that the increase of glutamate level in the hippocampus and medial temporal lobe was related to the decrease of executive function. multimodal imaging the heterogeneities of findings of individual imaging modalities have been driving the multimodal neuroimaging approach to the search of the more consistent and precise biomarkers for the deficits, abnormalities in functions of schizophrenia patients. a concerted use of three mri modalities, namely, resting-state of fmri, structural mri, and diffusion mri, was able to simultaneously reveal abnormalities from these three kinds of mri images and, thereby, identify the cortico-striato-thalamic circuits that might be related the cognitive impairments in schizophrenia [ ] . in addition to the multimodal imaging investigation of structural and functional brain abnormalities in schizophrenia, proton mrs has also been used in combination with fmri to investigate cognitive impairment in schizophrenia at both neurometabolic and functional levels [ ] . the combined proton mrs and fmri study are particularly useful for short-term longitudinal studies on the effects of medication, which is invariant to brain structural change. in this study [ ] , the relationship between glx/cr levels and bold response significantly changed after six weeks of medication for schizophrenia patients, although factors that confound interpretations of the results remain. more examples of multimodal imaging studies on schizophrenia are given in recent review articles [ , ] . multimodal fusion has gradually entered the center of research interest as an approach to tackle the challenges of neuroimaging. the first main reason is that there exists a great complementarity between different imaging modes. for instance, the images obtained by positron emission tomography imaging (pet) or single-photon emission tomography imaging (spect) do not contain high resolution, three-dimensional anatomical information. on the other hand, high-resolution structural images can be obtained via the use of ct and/or mri. these images complement each other to provide a complete picture of the targeted organs' anatomy, physiology, and pathology. the fusion of these images is of great significance for the relevant clinical and pre-clinical studies. another outstanding merit of utilizing multimodal fusion is that it efficiently enhances the spatial and temporal resolution in the characterization of brain processes. in other words, multimodal imaging may allow the combination of the hyper-temporal resolution of one imaging mode with the hyper-spatial resolution of another, taking advantage of the spatial-temporal complementarity. take a study in as an example, ke zhang et al have successfully measured the cerebral blood flow with a combination of arterial spin labeling (asl), mri and pet [ ] . apart from this, utilizing eeg together with fmri to improve spatial and temporal resolution has also been studied by many scientists in neuroscience [ ] [ ] [ ] [ ] it is worth mentioning that, in both narrow and wide senses, multimodal data fusion has a high capacity of generalization. a typical instance is the alignment of functional mri, eeg, and fnirs images to an anatomical coordinate system. the coordinate system can act as a template to standardize reported results. the alignment of the images to a single coordinate system not only allows comparison with other studies but also allows the combination of functional and structural information [ ] . pet/ct combination is a multimodal absolute quantification approach where ct provides structural data information on bones, which also serves as the main absorber for the γ-rays in pet. this combination allows decay correction, in which the accumulation of radioactive isotopes in human tissues becomes apparent, and the amount of radioactive decay can be absolutely quantified [ , ] . multimodal imaging also has the benefit of utilizing data from one modality to improve the data quality of another modality, such as correcting the geometric distortions of epi images by acquiring a b field map or obtaining epi with different parameters [ , ] . another classic case is in a combined mr-pet study, where the motion information provided by high-temporal resolution mri data was used to help the reconstruction of the pet data [ ] . the long history of neuroimaging has led to the development of an assortment of imaging technologies and modalities, as seen in section . the existing research and apparatus provided a solid foundation for multimodal fusion, leading to the rapid development of many fusion techniques. in this part, we classify reviewed methodologies into four primary forms: multimodal, multi-focus, multi-temporal, and multi-view. modern medical imaging methods aim at revealing possible dysfunctions in patients. for example, neuroimaging methods are often used to image the structure of nervous system on a macroscopic level, which in turn helps explore the neuroglial basis of behavior and cognition of patients. however, how to combine different medical imaging methods to provide images with better quality or clearer structures remains to be the heated research interest in the field. therefore, multimodal image fusion is proposed to minimize the gap. in a narrow sense, multimodal image fusion, a technique to improve the interpretation of the structure and functions of target organ or region, generally combines two or even more images collected from different imaging instruments. in order to achieve the goal of simultaneous acquisition, researchers have developed particular instrumentations to allow data of one modality to be acquired with low or neglectable inference from another modality. for instance, the eeg-fmri combination fuses data acquired from eeg instruments like amplifiers and mri scanners. also, the novel instrumentations range from simple arrangements to relatively complex technological innovations. however, in some combinations, simultaneous acquisition of data was impossible due to the physical interactions of the imaging devices. multimodal image fusion, in a broader sense, also combines data but collected with the same instrument. in this case, mri is widely used due to its versatility in the generation of different tissue contrasts with the well-studied phenomenon of magnetic resonance. there is also research that combines two and more contrasts in the same acquisition, which has been routinely used for many years. multiple contrasts can also be acquired by pet (positron emission tomography) when radioactive compounds injected are different. a region-based method, which incorporated segmentation into the fusion process, was proposed by s. li in and local focus measure comparison. it was pointed out that local features such as dense sift can also be used to match pixels that were misregistered between multiple source images. in methods based on frequency, images are transformed into the frequency-domain for fusion. wavelet-based methods, including discrete wavelet transform (dwt) [ ] , haar wavelet [ ] and pyramid-based methods such as the laplacian pyramid [ ] , fall under the category of frequency-domain methods. a dwt based method was proposed in [ ] . principal component analysis (pca) was used for approximating coefficients of input images. the principal components were evaluated to obtain multiscale coefficients. the weights for the fusion rule were then acquired by averaging those components. besides the promising performance, the proposed method was widely applied in medical image fusion for ct and mri images. in [ ] , the authors proposed the daubechies complex wavelet transform (dcxwt) to fuse multimodal medical image. by using the maximum selection rule, the complex wavelet coefficients of source images are fused. source images at different levels are decomposed by dcxwt, followed by inverse dcxwt to form the fused image. compared to the other five methods, including dual tree complex wavelet transform (dtcwt) based fusion and pca based fusion, the proposed method achieved the best performance in terms of five measurements, including standard deviation, entropy, edge strength, fusion symmetry, and fusion factor. it was proved that the proposed method was robust to noises, including speckle, salt and pepper, while maintaining the property of shift-invariance. multi-temporal fusion is to fuse images taken at different times but of the same modality. multi-temporal fusion enables easy detection of changes in images by subtracting one or multiple images from another. data acquisition consists of separate recording and simultaneous recording. the choice between separate or simultaneous acquisition should be cautiously considered. compared to separate recordings, where an image from each modality is acquired individually, simultaneous acquisitions have relatively lower data quality and more artifacts. for example, eeg-fmri simultaneously acquires cardio-ballistic artifacts and mri gradients. data acquisition consists of separate recording and simultaneous recording [ ] . in the mr-pet scenario, components of the mri scanner would trigger degradation in pet scanning results. therefore, the costs of simultaneous acquisition are higher than separate acquisition due to subject discomfort and long set-up time. however, there are also many cases in which costs are of less concern, given the benefits of simultaneous acquisitions. in multi-view fusion, images of the same modality are taken under different conditions at the same time. this fusion technique is applied to increase the amount of information for the fused images, while source images are taken under different conditions. the choice between asymmetric and symmetric data fusion makes a significant difference in the integration and joint analysis of multimodal data. for integration methods falling under the asymmetric category, information from different modalities is assigned with different weights so that information from one modality could be treated as a constraint on the other modality. for instance, fmri contrast maps limit the source localization of eeg/meg. modalities in symmetric data fusion, however, are treated equally in terms of spatial and temporal resolution as well as the uncertainty in the possible indirect relation to neural activity. hypothesis-driven approaches and data-driven approaches are the two main categories of symmetric fusion approaches. hypothesis-driven approaches, also called model-driven approaches, are usually in model-based setting, while data-driven approaches belong to blind source separation methods [ ] . examples of different fusion methods are shown in table . image fusion rules are applied to highlight the features of interest in images while suppressing the unimportant features. generally, fusion rules are mainly comprised of four components: activity-level measurement, coefficient grouping, coefficient combination, and consistency verification [ ] . the activity-level measurement rule, as can be subdivided into window-based activity (wba), coefficient-based activity (cba) and region-based activity (rba), characterizes coefficients at different scales. in the coefficient grouping component, there are mainly three typical groupings, including single-scale grouping (sg), multi-scale grouping (mg), and no-grouping (ng). sg indicates that the same strategy is applied to fuse different coefficients between sub-images on the same scale. the coefficient combination component mainly comprises of maximum rules (mr), weighted rules (war), and average rules (ar). mr can be given as: where c f indicates the combined coefficient, and are the coefficients of two input images at the level of . for war, and are combined by multiplying different weights and , that is ar, which has the coefficient of input images averaged, is a special case of war. the consistency verification component ensures that the same rules are applied to fuse the coefficients in the neighborhood. there are three different levels of image fusion: pixel level, feature level, and decision level. this categorization can be seen in table and figure . pixel level rules directly deal with the information acquired from each pixel of source images and then generates pixel values for the fused image correspondingly. feature level rules focus on regional information and features such as texture and salient features. the fused image in the decision level is acquired through rules of fuzzy logic and statistics. before rules in feature level and decision level apply to the source images, segmentation of the source images is needed. compared to the pixel level fusion, feature and decision level fusion shows more advantages are less affected by noises and misregistration. feature and decision level fusion also shows better contrast and lower complexity [ ] . in the following sections, we will introduce fusion rules for multi-model image fusion, followed by validation metrics. figure pixel-based and window-based fusion fuzzy logic-based rules belong to decision level fusion. these rules are usually used to solve challenges in blurry fused images. mamdani and t-s models are two fuzzy logic models. the difference between them lies in the consequence parts. t-s models linearly mapped input variables into functions to form the consequence parts, while mamdani models used fuzzy sets. the t-s model is more advantageous than the mamdani model in regard to number of rules and accuracy. in general, feature extraction through fuzzy logic algorithms is performed prior to fusion, which generates pixel-wise features and from two input images. the fusion procedure can be divided into three steps. in the first step, the fuzzy logic, which is usually comprised of four conditional rules, is used to label the individual pixels as following. = { , both of and are high (rule ) , is low but is high (rule ) or is high but is low (rule ) , both of and are low (rule ) then the new pixel-wise feature values can be calculated through: where , , corresponds to low, medium and high components, respectively. and are the mean and variance of each component. by incorporating the center average defuzzifier to process fuzzy outputs, the weight of fuzzy logic can be obtained. the essence in statistics-based methods lies in the data-driven technique and high order statistics that can reveal the underlying pattern across multiple modes of data. principal component analysis (pca) [ ] [ ] [ ] [ ] together with hidden markow tree (hmt) [ ] [ ] [ ] are two typical examples of statistic methods in the field of multi-modal medical image fusion. pca is an orthogonal linear transformation that reveals the most valuable components of the input images. let and be the two coefficients of the input images that can be denoted as: where and ( ≤ ≤ ) are column vectors of two coefficients and . the importance of components is related to the eigenvalues in the covariance matrix between and . the covariance matrix can be computed through: where is the expectation of vectors, ̅̅̅ and ̅̅̅ corresponds to the average of and respectively, that is given the eigenvalues obtained from the covariance matrix as , the normalized weights and for and can be denoted as: therefore, the fused coefficient can be the combination of two input images: the two-state hmt method, unlike pca methods, can be deployed to model the coefficients. two mixed gaussian random distributions, as well as the hidden states, depict intra-coefficients. the hidden states here refer to the one parent and four children coefficients. given each coefficient denoted as , the coefficient is obtained by probability density function: when the coefficient in the state n (n= , ), ( | = ) is the probability density function correspondingly. the fused coefficient is then given by: methods based on the human visual system (hvs) aim at solving the fusion problem in the way of image recognition and comprehension. the system includes components such as visibility, smallest univalve segment assimilating nucleus (susan) [ ] , and retina-inspired model (rim) [ , ] . the sharpness of an image can be quantified by visibility. therefore, the images with higher visibility show lower blurriness. given an image of size × , then the visibility of the can be mathematically expressed as : where µ is acquired by calculating the mean grey value of the image and , the visual constant varying from . to . . susan, proposed in [ ] , is a feature extraction algorithm inspired by hvs. susan computes the feature of a pixel by considering a circular mask around the pixel. in the mask, the area consisting of pixels that have similar brightness to the nucleus, or the central pixel, is selected and is called univalue segment assimilating nucleus (usan). let the input image to be and the circular mask with the radius , then simplest usan can be given as : where is the central pixel, is a nominal depicting surrounding pixels. ( )is the pixel value at and is the brightness difference threshold. the value of , which specifies the range of pixel values to be considered, must be carefully chosen because extracted features are sensitive to it. in order to lower the sensitiveness, the distance between pixels is also taken into consideration, and the extended usan function is: where is the distance scaling factor. for components in intensity-hue saturation (ihs) decomposition methods, the rim model can be used as the fusion rules. there are five layers in rim. the first cone layer outputs an array of high-resolution cone photoreceptors with high resolution. the second layer is the extractor for spatial feature, while the third layers are horizontal cells. the fourth and fifth layers, which combine features, are bipolar and ganglion cells the rim based image fusion rule can be demonstrated as: where and stand for intensity components of two source images. and are the filters of feature extractors. the filter , a high-scale spatial feature extractor, calculates the spatial difference between high-resolution and low-resolution. filter combines the output of horizontal cells. objective evaluation metrics are used to evaluate the efficacy of image fusion rules on improving the quality of the fused image. widely used metrics includes spatial frequency (sf) [ ] , the ratio of spatial frequency error (rsfe) [ ] , wavelet entropy (we) [ ] , signal noise ratio (snr) [ ] , mutual information (mi) [ ] and directive contrast (dc) [ ] . sf metric, which measures images' activity, is generally used for pca integrated his methods in multimodal image fusion. sf can be defined as where and stand for column frequency and row frequency, respectively. based on sf, rsfe compares the sf f ′ of the fused image with ′ and ′ of the input images where sf' can be extended as: where and are the main diagonal sf and the secondary diagonal sf. rsfe can then be formulated as: calculated by multi-scale entropy, we can be given by: where i is the resolution level, is the density distribution derived from the energy of the detail signal and the total energy = in [ ] , the authors proposed snr-based image fusion rules. the proposed fusion method can be formulated in the following form. for a specific region . ( ) is the activity level of that, while is the total number of pixels. the probability of pixel activity can be calculated through: where is the weight of snr from the image, is the number of decomposition levels and ( , ) is the detailed wavelet coefficient. mi is deployed as the fusion rule for wt-based multi-modal medical image fusion. mi between the input images , and the fused image , is maximized to give , which is acquired by: dc measures the difference between the pixel and its neighbors. the ratio between the high-frequency intensity and the low-frequency intensity is the intensity contrast dc. for the multi-modal image fusion of neuroimaging, the selection of various decomposition and reconstruction methods influence the fusion procedure and outcomes. in this survey, we shall discuss seven popular methods: (i) rgb-ihs; (ii) pyramid representation; (iii) wavelet-based approach and its variants; (iv) multi-resolution analysis; (v) sparse representation; and (vi) salient features. the intensity-hue-saturation (ihs) model [ ] helps transform the original image in rgb color space to hue, saturation, and intensity channels. this rgb to ihs procedure is calculated by simple equations. besides, the reconstruction is carried out by inversed transformation (ihs to rgb). for the rgb->ihs procedure, the intensity of each input image was estimated by the following equations: then, we consider three conditions: c : b